chlamydia trachomatis research paper

Research article
Open access
Published: 08 August 2020

Prevalence of genital Chlamydia trachomatis infection in the general population: a meta-analysis

Pengcheng Huai 1 , 2 ,
Furong Li 1 , 2 ,
Tongsheng Chu 1 , 2 ,
Dianchang Liu 1 , 2 ,
Jian Liu 1 , 2 &
Furen Zhang 1 , 2

BMC Infectious Diseases volume 20 , Article number: 589 ( 2020 ) Cite this article

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Metrics details

Estimating prevalence of Chlamydia trachomatis (CT) worldwide is necessary in designing control programs and allocating health resources. We performed a meta-analysis to calculate the prevalence of CT in the general population.

The Pubmed and Embase databases were searched for eligible population-based studies from its inception through June 5, 2019. Q test and I 2 statistic were used to calculate the heterogeneity between studies. Random effects models were used to pool the prevalence of CT. Meta regression was performed to explore the possible sources of heterogeneity. Publication bias was evaluated using a funnel plot and “trim and fill” method.

Twenty nine studies that reported prevalence of CT infection from 24 countries were identified, including a total population of 89,886 persons. The pooled prevalence of CT among the general population was 2.9% (95% CI, 2.4–3.5%), and females had a higher CT prevalence (3.1, 95% CI, 2.5–3.8%) than males (2.6, 95% CI, 2.0–3.2%) ( χ 2 = 10.38, P < 0.01). Prevalence of CT was highest in region of America (4.5, 95% CI, 3.1–5.9%), especially in Latin America (6.7, 95% CI, 5.0–8.4%), followed by females in region of Africa (3.8, 95% CI, 0.7–6.9%), while South-East Asia had a lowest CT prevalence 0.8% (95% CI, 0.3–1.3%).

Conclusions

This study provided the updated prevalence of CT among general population worldwide. General population from Latin America, especially females, and women in Africa should be given priority by WHO when design and delivery CT control programs.

Peer Review reports

Chlamydia trachomatis (CT) causes the most prevalent bacterial sexual transmitted infection (STI) in the world [ 1 ]. Based on the 2018 global STI surveillance from World Health Organization (WHO), global estimation of new CT cases in 2016 was 127 million [ 2 ]. Chlamydia infections are asymptomatic in 61% of women and 68% of men, and as a consequence often go undiagnosed, untreated, resulting in onward transmission [ 3 ]. Left timely untreated, CT infection can lead to pelvic inflammatory disease (PID), infertility, ectopic pregnancy, and chronic pelvic pain in women [ 4 ], and urethritis, epididymitis in men [ 5 ]. Thus, early detection and treatment is necessary to reduce the burden of CT infections and associated sequelae.

Estimation of CT prevalence in the general population is essential in designing a specific control program [ 3 ]. Population-based studies have been conducted in several countries to estimate prevalence of CT infection [ 6 , 7 , 8 , 9 ]. However, sample size of many studies was too small to obtain the precise estimation considering the low CT prevalence in general population [ 10 , 11 , 12 ]. Meta-analysis can obtain large sample size and provide robust and reliable estimation of CT prevalence. In 2015, a meta-analysis conducted by WHO found the global prevalence of CT was 4.2% for women and 2.7% for men [ 13 ]. In the same year, Redmond et al. calculated the genital CT prevalence in Europe and non-European high income countries using meta-analysis [ 14 ]. In addition, Rowley et al. performed a systematic review to estimate global prevalence of CT in 2016, and the prevalence of CT for women and men was 3.8 and 2.7%, respectively [ 15 ]. However, the included population-based studies of these three meta-analyses were all published before 2016. Another 5 eligible studies were published in succession since 2016 [ 3 , 16 , 17 , 18 , 19 ]. In addition, studies estimating prevalence of CT for selective populations such as high school students, military recruits, clinic based individuals were also included in these meta-analyses, which introduced potential heterogeneity for the pooled results [ 13 , 20 , 21 , 22 ]. Thus, we preformed this meta-analysis to update global and regional prevalence estimates for CT infection in the general population and provide convincing information for design and delivery CT control programs.

This study was conducted according to the meta-analysis of observational studies in epidemiology (MOOSE) guidelines [ 23 ].

Search strategy

The Pubmed and Embase databases were searched for population-based studies reported prevalence of CT from its inception through June 5, 2019. The following search strategy was used to identify all relevant articles: “ Chlamydia trachomatis ” AND “prevalence” AND “population based study”. The languages of studies were limited to English and Chinese, and the subjects were defined as humans. The reference lists of included articles were also screened for further studies.

Inclusion and exclusion criteria

Studies included in this meta-analysis met all the following inclusion criteria: (1) cross-sectional studies or baseline study of cohort studies; (2) reported data from a general population; (3) explicitly reported prevalence (or weighted prevalence) of CT infection, or number of infected cases; (4) used nucleic acid amplification test (NAAT) or cell culture for diagnostic testing. (5) Articles were published between January 1, 2000 and June 5, 2019. If multiple cross-sectional studies for the same subjects and areas were published, the most updated report was included. We excluded studies that (1) reported data from subsample or followed-up individuals; (2) reported on selective populations such as outpatients, pregnant women, military recruits, students, aborigines, or convicts; (3) used serologic test for CT diagnosis.

Data extraction and quality assessment

Data were extracted from included studies on first author, year of publication, study area or country, gender of subjects, sample size, detection methods, prevalence (or weighted prevalence) of CT infection, number of infected cases. In addition, studies were divided into the following 6 subgroups based on WHO regions: African group, American group, South-East Asian group, European group, Eastern Mediterranean group and Western Pacific group. Quality assessment for included studies using the assessment criterion for cross-sectional/prevalence studies (11 items), which was recommended by the Agency for Healthcare Research and Quality (AHRQ) in U.S. [ 24 ]. We chose “yes”, “no” or “unclear” for each item based on the contents of the articles. Item answered with “yes” was scored 1, otherwise, it was scored with 0. Articles scored “8–11”, “4–7”, “0–3” were defined as high quality, medium quality and low quality articles, respectively. Data extraction and quality assessment were performed by 2 authors independently. Any disagreements were resolved through discussion.

Statistical analysis

The pooled prevalence of CT infection and 95% confidence interval (CI) was calculated with STATA version 11 (StataCorp LP, College Station, TX, USA). Q test and I 2 statistic were used to calculate the heterogeneity between studies. I 2 describes the percentage of total variation because of between-study heterogeneity rather than chance, and it ranged from 0 to 100% [ 25 ]. Random (Dersimonian Laird method) effects models were used to calculate pooled prevalence of CT infection when heterogeneity was present ( I 2 > 50%), otherwise, fixed (Mantel Haenszel method) effects models were used [ 26 ]. Subgroup analysis was conducted according to WHO regions. Meta regression was performed to explore the possible sources of heterogeneity. Publication bias was evaluated using a funnel plot and “trim and fill” method. A P value < 0.05 was considered to be statistically significant.

Search results and study characteristics

In brief, a total of 29 eligible studies were identified and included into meta-analysis from 376 potentially relevant articles [ 3 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 16 , 17 , 18 , 19 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. A flow chart for inclusion and exclusion of articles was presented as Fig. 1 . The included 29 studies, with a total population of 89,886 persons, reported prevalence of CT infection from 24 countries. Ten studies were conducted in Americas [ 6 , 8 , 27 , 29 , 33 , 34 , 35 , 38 , 40 , 41 ], 9 in Europe [ 7 , 10 , 12 , 28 , 30 , 31 , 35 , 36 , 37 ], 7 in Western Pacific region [ 3 , 9 , 11 , 18 , 19 , 32 , 35 ], 4 in South-East Asia [ 16 , 17 , 35 , 39 ] and 3 in Africa [ 35 , 42 , 43 ]. No eligible studies were retrieved from Eastern Mediterranean region. One study involved men only [ 43 ], 9 studies involved women only [ 11 , 16 , 17 , 18 , 32 , 34 , 35 , 38 , 41 ], 17 studies involved both men and women and reported sex-specific results [ 3 , 6 , 7 , 8 , 9 , 10 , 12 , 19 , 28 , 29 , 30 , 31 , 33 , 36 , 37 , 39 , 42 ] and 2 studies involved both men and women but did not report sex-specific data [ 27 , 40 ]. One article reported results from both cross-sectional study and baseline of cohort study [ 35 ], the other studies were all cross-sectional studies [ 3 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 16 , 17 , 18 , 19 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. Based on assessment criterion, fifteen studies were defined as high quality articles [ 3 , 6 , 7 , 8 , 9 , 11 , 12 , 16 , 27 , 29 , 31 , 36 , 40 , 41 , 43 ], 14 studies were medium quality articles [ 10 , 17 , 18 , 19 , 28 , 30 , 32 , 33 , 34 , 35 , 37 , 38 , 39 , 42 ], and no low quality articles were defined. The above characteristics of included studies were extracted in Table S1 .

A flow chart of articles selection

Prevalence of CT infection

Prevalence of CT infection ranged from 0.2 to 12.2% for the included studies. Q test indicated that there was significant heterogeneity between 29 studies ( P Q < 0.01; I 2 = 96.7%), and a random effects model was used. The pooled prevalence of CT among the general population was 2.9% (95% CI, 2.4–3.5%) (Fig. 2 ). Prevalence of CT infection for men ranged from 1.0 to 12.1% for the 18 studies. A random effect model was used to pool the results because of the heterogeneity between studies ( P Q < 0.01; I 2 = 92.2%). The pooled prevalence of CT infection for men was 2.6% (95% CI, 2.0–3.2%). Prevalence of CT infection for women ranged from 0.2 to 12.2% for the 26 studies. There was significant heterogeneity between studies ( P Q < 0.01; I 2 = 96.0%), and a random effects model was used. The pooled prevalence of CT infection for women was 3.1% (95% CI, 2.5–3.8%). Result of Chi-square test indicated that prevalence of CT infection for women was significantly higher than that for men ( χ 2 = 10.38, P < 0.01).

Random effects meta-analysis of the prevalence of CT infection among general population

Subgroup analysis

The pooled prevalence of CT infection in the general population in Americas was 4.5% (95% CI, 3.1–5.9%), which was calculated with a random effects model ( P Q < 0.01; I 2 = 98.1%). Females (5.3, 95% CI, 3.6–7.1%) had a higher prevalence of CT than males (4.5, 95% CI, 2.2–6.7%) in the Americas ( χ 2 = 9.06, P < 0.01). Prevalence of CT in the population in Latin America (6.7, 95% CI, 5.0–8.4%) was higher than the prevalence in people from other countries in Americas (2.4, 95% CI, 1.4–3.4%) ( χ 2 = 333.2, P < 0.01). The pooled prevalence of CT in Europe, pooled with a random effects model ( P Q < 0.01; I 2 = 94.2%), was 2.7% (95% CI, 1.9–3.6%). No significant difference was detected for the prevalence of CT between males and females in Europe ( χ 2 = 0.20, P = 0.68). The pooled prevalence of CT in Africa was 2.6% (95% CI, 1.4–3.9%), which was similar to that in the Western Pacific (2.6, 95% CI, 1.8–3.5%). Both subgroup meta-analyses were performed with random effects models. The prevalence of CT for females (3.8, 95% CI, 0.7–6.9%) was significantly higher than that for males (1.4, 95% CI, 0.4–2.4%) in Africa ( χ 2 = 63.44, P < 0.01). The difference of CT prevalence between males and females was not significant in the Western Pacific region ( χ 2 = 1.46, P = 0.23). Prevalence of CT in South-East Asia, pooled with a random effects model ( P Q < 0.01; I 2 = 77.7%), was 0.8% (95% CI, 0.3–1.3%). The difference in prevalence of CT between males and females in South-East Asia was not significant ( χ 2 = 0.82, P = 0.47). Chi-square test indicated that the prevalence of CT infection among the 5 WHO regions was significantly different ( χ 2 = 413.5, P < 0.01). Detailed results of subgroup analysis were shown in Table 1 and Fig. 3 .

Pooled prevalence of CT infection among general population in 5 WHO regions

Exploration of the heterogeneity source

Exploratory univariate meta-regression was conducted with the introduction of sample size, number of cases, year of publication, country, WHO regions and scores in quality assessment, response rate and national/subnational studies. The meta-regression coefficients, 95% CI and P value for these variables were − 8.68e − 7 (95% CI, − 3.65e − 6 -1.92e − 6 , P = 0.53), − 1.40e − 6 (95% CI, − 7.26e − 5 -6.98e − 5 , P = 0.97), − 6.21e − 4 (95% CI, − 2.32e − 3 -1.08e − 3 , P = 0.46), − 7.26e − 4 (95% CI, − 2.18e − 3 -7.33e − 4 , P = 0.32), − 3.85e − 3 (95% CI, − 1.08e − 2 -3.11e − 3 , P = 0.27), − 1.91e − 3 (95% CI, − 9.16e − 3 -5.35e − 3 , P = 0.59), − 1.84e − 4 (95% CI, − 3.04e − 4 -6.72e − 4 , P = 0.45), − 4.81e − 3 (95% CI, − 2.51e − 2 -1.55e − 2 , P = 0.63). Thus, no variable was identified to be the main source of heterogeneity in this meta-analysis of the whole 29 studies.

Publication bias evaluation

The shape of the funnel plot was not symmetrical, which indicates the existence of publication bias for the included studies. Trim and fill method was used to adjust the pooled prevalence of CT infection. After adjustment, the pooled prevalence of CT infection among general population was 2.6% (95% CI, 2.0–3.1%).

This meta-analysis provided the updated estimation of prevalence of CT infection among the general population worldwide. This study included 29 studies with a total population of 89,886, which covered 24 countries from 5 WHO regions. The results of this study showed that prevalence of CT infection among general population was 2.9% (95% CI, 2.4–3.5%), and females had a higher CT prevalence than that for males. Prevalence of CT infection among the 5 WHO regions varied significantly. The general population in the Americas had the highest CT prevalence, followed by those in Europe, Africa, and the Western Pacific regions, while those in South-East Asia had the lowest CT prevalence.

The prevalence of CT infection in males was 2.6% (95% CI, 2.0–3.2%) in this study, which was very similar to the estimation (2.7, 95% uncertainty interval, UI, 1.9–3.7%) by Rowley et al. in 2016 [ 15 ]. However, the CT prevalence for females (3.1, 95% CI, 2.5–3.8%) was lower than the estimation (3.8, 95% UI, 3.3–4.5%) by Rowley [ 15 ], which may be due to the difference in inclusion criteria between two studies. Pregnant women, women at delivery, and women attending family planning clinics were recruited in the systematic review by Rowley, but those were excluded in our study. Pregnancy is a time of many changes in a woman’s life, including hormonal and physiological changes and reduced immune activity, making her vulnerable to infections [ 44 ]. Thus, females are more likely to acquire CT infections during pregnancy, which may result in the higher prevalence of CT estimated by Rowley et al. The pooled CT prevalence in Europe was in line with the meta-analysis by Redmond et al. in European Union/European Economic Area (EU/EEA) Member States, and the 95% CI were overlapped between two studies [ 14 ].

Our study found significant differences in the prevalence of CT infection between males and females in the general population. The higher CT prevalence in females may be due to several reasons. First, the anatomy of reproductive tract makes the females vulnerable to CT infection. Genital secretions and pathogen CT tend to pool in the vaginal vault, where they typically bathe the uterine cervix in the secretions, resulting in transmission of CT [ 45 ]. Second, cervical ectopy, which is a common physiological process in young women, was thought to increase risk of CT infection by exposing columnar epithelium to a potential infectious inoculum [ 46 ]. Third, Non-monogamous partnerships are more common among men than women [ 47 ]. As a consequence, men may transmit CT to multiple female partners, resulting in this increased CT prevalence. Considering cost-effective, females should be given priority when conduct CT control programs such as screening. In addition, contact tracing around an infected woman is also necessary to find out the men who might be responsible for several other infections. Therefore, CT screening, contact tracing, and cases treatment should be combined to prevent CT transmission.

The results of this study indicated regional variations of CT prevalence. Pooled CT prevalence was highest in the region of Americas and lowest in the South-East Asia. We further explored the heterogeneity between Latin America and U.S., Canada, and found a significant higher CT prevalence in population from Latin America. In U.S., all sexually active females ≤25 years of age were recommended to be screened for CT infections routinely since 2001 [ 48 ]. In Canada, sexually active young adult ≤25 years of age as well as pregnant women were recommended to be screened for CT infections [ 49 ]. Compared with Latin America, those CT control programs in U.S. and Canada may contribute to the lower CT prevalence. The results about spatial heterogeneity of CT prevalence provide information for WHO to design a CT control policy. The limited health resources, such as funding or human resources, should lean to the regions with high CT prevalence. Previous publications indicated that CT screening was cost effective for females at prevalence of 3.1–10% [ 50 , 51 , 52 ]. Thus, whether to conduct CT screening programs for females in Africa and Latin America should be evaluated by WHO. Regional variations may be associated with social, cultural and economic conditions, differences in control policy and gender inequality, but those need to be examined in further studies [ 53 ].

In this study, only general population were included into analysis, selective populations such as outpatients, military recruits or convicts were excluded from this study, which minimized the selection bias of this meta-analysis. There are also several limitations in this study. First, heterogeneity was found between studies through Q test. We used meta-regression to explore potential source of heterogeneity, but no variable was identified to be the main source of heterogeneity. Random effect models were used to pool the prevalence of CT, but the results may be not stable enough due to heterogeneity. Second, publication bias was identified for the included studies. Thus, trim and fill method was used to adjust the results and reduce the influence of publication bias. Third, only English and Chinese language articles were included in this meta-anlysis because the authors are fluent of these two languages. Eligible studies with other languages were not included, which may affect the results [ 26 ].

In conclusion, our study provides the updated prevalence of CT among general population worldwide. Pooled prevalence of CT was calculated for males and females from different regions, and high-prevalence areas and populations were identified. Based on the results, the general population from Latin America, especially females, and women in Africa should be given priority by WHO when design and delivery CT control programs.

Availability of data and materials

The dataset of this meta-analysis is included within the article’s additional file (Additional file 1 ).

Abbreviations

Agency for healthcare research and quality

Confidence interval

Chlamydia trachomatis

European economic area

European union

Meta-analysis of observational studies in epidemiology

Nucleic acid amplification test

Pelvic inflammatory disease

Sexual transmitted infection

World health organization

Kiguen AX, Marrama M, Ruiz S, Estofan P, Venezuela RF, Mosmann JP, et al. Prevalence, risk factors and molecular characterization of chlamydia trachomatis in pregnant women from Cordoba, Argentina: a prospective study. PLoS One. 2019;14(5):e217245.

Google Scholar

World Health Organization. Report on global sexually transmitted infection surveillance 2018. Available at: https://apps.who.int/iris/bitstream/handle/10665/277258/9789241565691-eng.pdf?sequence=5&isAllowed=y . (accessed 10 June 2019).

Huai P, Li F, Li Z, Sun L, Fu X, Pan Q, et al. Prevalence, risk factors, and medical costs of chlamydia trachomatis infections in Shandong Province, China: a population-based, cross-sectional study. BMC Infect Dis. 2018;18(1):534.

PubMed PubMed Central Google Scholar

Haggerty CL, Gottlieb SL, Taylor BD, Low N, Xu F, Ness RB. Risk of sequelae after chlamydia trachomatis genital infection in women. J Infect Dis. 2010;201(Suppl 2):S134–55.

PubMed Google Scholar

Lee YS, Lee KS. Chlamydia and male lower urinary tract diseases. Korean J Urol. 2013;54(2):73–7.

Torrone E, Papp J, Weinstock H. Prevalence of chlamydia trachomatis genital infection among persons aged 14-39 years-United States, 2007-2012. MMWR Morb Mortal Wkly Rep. 2014;63(38):834–8.

Sonnenberg P, Clifton S, Beddows S, Field N, Soldan K, Tanton C, et al. Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of sexual attitudes and lifestyles (Natsal). Lancet. 2013;382(9907):1795–806.

Carcamo CP, Campos PE, Garcia PJ, Hughes JP, Garnett GP, Holmes KK, et al. Prevalences of sexually transmitted infections in young adults and female sex workers in Peru: a national population-based survey. Lancet Infect Dis. 2012;12(10):765–73.

Parish WL, Laumann EO, Cohen MS, Pan S, Zheng H, Hoffman I, et al. Population-based study of chlamydial infection in China: a hidden epidemic. JAMA. 2003;289(10):1265–73.

Božičević I, Grgić I, Židovec-Lepej S, Čakalo JI, Belak-Kovačević S, Štulhofer A, et al. Urine-based testing for chlamydia trachomatis among young adults in a population-based survey in Croatia: feasibility and prevalence. BMC Public Health. 2011;11:230.

Hocking JS, Willis J, Tabrizi S, Fairley CK, Garland SM, Hellard M. A chlamydia prevalence survey of young women living in Melbourne, Victoria. Sex Health. 2006;3(4):235–40.

Fernández-Benítez C, Mejuto-López P, Otero-Guerra L, Margolles-Martins MJ, Suárez-Leiva P, Vazquez F. Prevalence of genital chlamydia trachomatis infection among young men and women in Spain. BMC Infect Dis. 2013;13:388.

Newman L, Rowley J, Vander HS, Wijesooriya NS, Unemo M, Low N, et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One. 2015;10(12):e143304.

Redmond SM, Alexander-Kisslig K, Woodhall SC, van den Broek IV, van Bergen J, Ward H, et al. Genital chlamydia prevalence in Europe and non-European high income countries: systematic review and meta-analysis. PLoS One. 2015;10(1):e115753.

Rowley J, Vander HS, Korenromp E, Low N, Unemo M, Abu-Raddad LJ, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97(8):548–62.

Shakya S, Thingulstad S, Syversen U, Nordbø SA, Madhup S, Vaidya K, et al. Prevalence of sexually transmitted infections among married women in rural Nepal. Infect Dis Obstet Gynecol. 2018;2018:4980396.

Krishnan A, Sabeena S, Bhat PV, Kamath V, Hindol M, Zadeh VR, et al. Detection of genital chlamydial and gonococcal infection using urine samples: a community-based study from India. J Infect Public Health. 2018;11(1):75–9.

Luo ZZ, Li W, Wu QH, Zhang L, Tian LS, Liu LL, et al. Population-based study of chlamydial and gonococcal infections among women in Shenzhen, China: implications for programme planning. PLoS One. 2018;13(5):e196516.

Wong WC, Zhao Y, Wong NS, Parish WL, Miu HY, Yang LG, et al. Prevalence and risk factors of chlamydia infection in Hong Kong: a population-based geospatial household survey and testing. PLoS One. 2017;12(2):e172561.

Pierpoint T, Thomas B, Judd A, Brugha R, Taylor-Robinson D, Renton A. Prevalence of chlamydia trachomatis in young men in north West London. Sex Transm Infect. 2000;76(4):273–6.

CAS PubMed PubMed Central Google Scholar

Baud D, Jaton K, Bertelli C, Kulling JP, Greub G. Low prevalence of chlamydia trachomatis infection in asymptomatic young Swiss men. BMC Infect Dis. 2008;8:45.

Corwin P, Abel G, Wells JE, Coughlan E, Bagshaw S, Sutherland M, et al. Chlamydia trachomatis prevalence and sexual behaviour in Christchurch high school students. N Z Med J. 2002;115(1158):U107.

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.

CAS PubMed Google Scholar

Rostom A, Dubé C, Cranney A, et al. Celiac disease. Rockville (MD): Agency for Healthcare Research and Quality (US); 10 Sep 2004. (Evidence Reports/Technology Assessments, No. 104.) Appendix D. Quality Assessment Forms. Available from: https://www.ncbi.nlm.nih.gov/books/NBK35156/ . Accessed 10 June 2019.

Huai P, Xun H, Reilly KH, Wang Y, Ma W, Xi B. Physical activity and risk of hypertension: a meta-analysis of prospective cohort studies. Hypertension. 2013;62(6):1021–6.

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

Rotermann M, Langlois KA, Severini A, Totten S. Prevalence of chlamydia trachomatis and herpes simplex virus type 2: results from the 2009 to 2011 Canadian health measures survey. Health Rep. 2013;24(4):10–5.

Kløvstad H, Grjibovski A, Aavitsland P. Population based study of genital chlamydia trachomatis prevalence and associated factors in Norway: a cross sectional study. BMC Infect Dis. 2012;12:150.

Eggleston E, Rogers SM, Turner CF, Miller WC, Roman AM, Hobbs MM, et al. Chlamydia trachomatis infection among 15- to 35-year-olds in Baltimore, MD. Sex Transm Dis. 2011;38(8):743–9.

Goulet V, de Barbeyrac B, Raherison S, Prudhomme M, Semaille C, Warszawski J, et al. Prevalence of chlamydia trachomatis: results from the first national population-based survey in France. Sex Transm Infect. 2010;86(4):263–70.

Uusküla A, Kals M, Denks K, Nurm U, Kasesalu L, Dehovitz J, et al. The prevalence of chlamydial infection in Estonia: a population-based survey. Int J STD AIDS. 2008;19(7):455–8.

Lan PT, Lundborg CS, Phuc HD, Sihavong A, Unemo M, Chuc NT, et al. Reproductive tract infections including sexually transmitted infections: a population-based study of women of reproductive age in a rural district of Vietnam. Sex Transm Infect. 2008;84(2):126–32.

Adams OP, Carter AO, Prussia P, McIntyre G, Branch SL. Risk behaviour, healthcare access and prevalence of infection with chlamydia trachomatis and Neisseria gonorrhoeae in a population-based sample of adults in Barbados. Sex Transm Infect. 2008;84(3):192–4.

Oliveira FA, Pfleger V, Lang K, Heukelbach J, Miralles I, Fraga F, et al. Sexually transmitted infections, bacterial vaginosis, and candidiasis in women of reproductive age in rural Northeast Brazil: a population-based study. Mem Inst Oswaldo Cruz. 2007;102(6):751–6.

Franceschi S, Smith JS, van den Brule A, Herrero R, Arslan A, Anh PT, et al. Cervical infection with chlamydia trachomatis and Neisseria gonorrhoeae in women from ten areas in four continents. A cross-sectional study. Sex Transm Dis. 2007;34(8):563–9.

van Bergen J, Gotz HM, Richardus JH, Hoebe CJ, Broer J, Coenen AJ. Prevalence of urogenital chlamydia trachomatis increases significantly with level of urbanisation and suggests targeted screening approaches: results from the first national population based study in the Netherlands. Sex Transm Infect. 2005;81(1):17–23.

Klavs I, Rodrigues LC, Wellings K, Kese D, Hayes R. Prevalence of genital chlamydia trachomatis infection in the general population of Slovenia: serious gaps in control. Sex Transm Infect. 2004;80(2):121–3.

Miranda AE, Szwarcwald CL, Peres RL, Page-Shafer K. Prevalence and risk behaviors for chlamydial infection in a population-based study of female adolescents in Brazil. Sex Transm Dis. 2004;31(9):542–6.

Joyee AG, Thyagarajan SP, Rajendran P, Hari R, Balakrishnan P, Jeyaseelan L, et al. Chlamydia trachomatis genital infection in apparently healthy adult population of Tamil Nadu, India: a population-based study. Int J STD AIDS. 2004;15(1):51–5.

Rogers SM, Miller HG, Miller WC, Zenilman JM, Turner CF. NAAT-identified and self-reported gonorrhea and chlamydial infections: different at-risk population subgroups? Sex Transm Dis. 2002;29(10):588–96.

Klausner JD, Mcfarland W, Bolan G, Hernandez MT, Molitor F, Lemp GF, et al. Knock-knock: a population-based survey of risk behavior, health care access, and chlamydia trachomatis infection among low-income women in the San Francisco Bay area. J Infect Dis. 2001;183(7):1087–92.

Obasi AI, Balira R, Todd J, Ross DA, Changalucha J, Mosha F, et al. Prevalence of HIV and chlamydia trachomatis infection in 15-19-year olds in rural Tanzania. Tropical Med Int Health. 2001;6(7):517–25.

CAS Google Scholar

Watson-Jones D, Mugeye K, Mayaud P, Ndeki L, Todd J, Mosha F, et al. High prevalence of trichomoniasis in rural men in Mwanza, Tanzania: results from a population based study. Sex Transm Infect. 2000;76(5):355–62.

Azevedo M, Nunes S, Oliveira FG, Rocha DAP, et al. High prevalence of chlamydia trachomatis in pregnant women attended at primary health care services in Amazon, Brazil. Rev Inst Med Trop Sao Paulo. 2019;61:–e6.

Hook ER. Gender differences in risk for sexually transmitted diseases. Am J Med Sci. 2012;343(1):10–1.

Lee V, Tobin JM, Foley E. Relationship of cervical ectopy to chlamydia infection in young women. J Fam Plann Reprod Health Care. 2006;32(2):104–6.

Mosher WD, Chandra A, Jones J. Sexual behavior and selected health measures: men and women 15-44 years of age, United States, 2002. Adv Data. 2005;362:1–55.

U.S. Preventive Services Task Force. Screening for chlamydial infection: recommendations and rationale. Am J Prev Med. 2001;20(3 suppl):90–4.

Public Health Agency of Canada. Canadian guidelines on sexually transmitted infections. 2016. (Management and Treatment of Specific Infections/Chlamydia Infections/screening). Available at: https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexuallytransmitted-infections/canadian-guidelines/sexually-transmitted-infections.html. . Accessed 10 June 2019.

Honey E, Augood C, Templeton A, Russell I, Paavonen J, Mårdh PA, et al. Cost effectiveness of screening for chlamydia trachomatis: a review of published studies. Sex Transm Infect. 2002;78(6):406–12.

Scholes D, Stergachis A, Heidrich FE, Andrilla H, Holmes KK, Stamm WE. Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med. 1996;334(21):1362–6.

Ostergaard L, Andersen B, Moller JK, Olesen F. Home sampling versus conventional swab sampling for screening of chlamydia trachomatis in women: a cluster-randomized 1-year follow-up study. Clin Infect Dis. 2000;31(4):951–7.

Unemo M, Bradshaw CS, Hocking JS, de Vries HJC, Francis SC, Mabey D, et al. Sexually transmitted infections: challenges ahead. Lancet Infect Dis. 2017;17(8):e235–79.

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Acknowledgments

We thank the authors of the included 29 studies. Ethics approval and consent to participate

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This study was funded by the Innovation Project of Shandong Academy of Medical Sciences. The funder had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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Pengcheng Huai, Furong Li, Tongsheng Chu, Dianchang Liu, Jian Liu & Furen Zhang

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FZ conceived, designed the study, and revised the manuscript. PH searched for eligible studies, extracted the variables, analyzed the data and wrote the first draft of the manuscript. FL and TC searched for eligible studies and extracted the variables. DL and JL re-checked the extracted data and help with the analysis. All authors reviewed and approved the final version of the Article.

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. Characteristics of the 29 included studies in this meta-analysis.

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Huai, P., Li, F., Chu, T. et al. Prevalence of genital Chlamydia trachomatis infection in the general population: a meta-analysis. BMC Infect Dis 20 , 589 (2020). https://doi.org/10.1186/s12879-020-05307-w

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Towards a deeper understanding of chlamydia trachomatis pathogenetic mechanisms: editorial to the special issue “ chlamydia trachomatis pathogenicity and disease”.

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Rowley, J.; vander Hoorn, S.; Korenromp, E.; Low, N.; Unemo, M.; Abu-Raddad, L.J.; Chico, R.M.; Smolak, A.; Newman, L.; Gottlieb, S.; et al. Chlamydia, Gonorrhoea, Trichomoniasis and Syphilis: Global Prevalence and Incidence Estimates, 2016. Bull. World Health Organ. 2019 , 97 , 548. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Di Pietro, M.; Filardo, S.; Romano, S.; Sessa, R. Chlamydia Trachomatis and Chlamydia Pneumoniae Interaction with the Host: Latest Advances and Future Prospective. Microorganisms 2019 , 7 , 140. [ Google Scholar ] [ CrossRef ] [ PubMed ] [ Green Version ]
Filardo, S.; Di Pietro, M.; Frasca, F.; Diaco, F.; Scordio, M.; Antonelli, G.; Scagnolari, C.; Sessa, R. Potential IFNγ Modulation of Inflammasome Pathway in Chlamydia Trachomatis Infected Synovial Cells. Life 2021 , 11 , 1359. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Filardo, S.; Di Pietro, M.; Diaco, F.; Sessa, R. In Vitro Modelling of Chlamydia Trachomatis Infection in the Etiopathogenesis of Male Infertility and Reactive Arthritis. Front. Cell. Infect. Microbiol. 2022 , 12 , 840802. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Di Pietro, M.; Filardo, S.; Frasca, F.; Scagnolari, C.; Manera, M.; Sessa, V.; Antonelli, G.; Sessa, R. Interferon-γ Possesses Anti-Microbial and Immunomodulatory Activity on a Chlamydia Trachomatis Infection Model of Primary Human Synovial Fibroblasts. Microorganisms 2020 , 8 , 235. [ Google Scholar ] [ CrossRef ] [ PubMed ] [ Green Version ]
Finethy, R.; Coers, J. Sensing the Enemy, Containing the Threat: Cell-Autonomous Immunity to Chlamydia Trachomatis. FEMS Microbiol. Rev. 2016 , 40 , 875–893. [ Google Scholar ] [ CrossRef ] [ PubMed ] [ Green Version ]
Helble, J.D.; Starnbach, M.N. T Cell Responses to Chlamydia. Pathog. Dis. 2021 , 79 , ftab014. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Pekmezovic, M.; Mogavero, S.; Naglik, J.R.; Hube, B. Host-Pathogen Interactions during Female Genital Tract Infections. Trends Microbiol. 2019 , 27 , 982–996. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Filardo, S.; Di Pietro, M.; Tranquilli, G.; Latino, M.A.; Recine, N.; Porpora, M.G.; Sessa, R. Selected Immunological Mediators and Cervical Microbial Signatures in Women with Chlamydia Trachomatis Infection. mSystems 2019 , 4 , e00094-19. [ Google Scholar ] [ CrossRef ] [ PubMed ] [ Green Version ]
Tamarelle, J.; Ma, B.; Gajer, P.; Humphrys, M.S.; Terplan, M.; Mark, K.S.; Thiébaut, A.C.M.; Forney, L.J.; Brotman, R.M.; Delarocque-Astagneau, E.; et al. Nonoptimal Vaginal Microbiota After Azithromycin Treatment for Chlamydia Trachomatis Infection. J. Infect. Dis. 2020 , 221 , 627–635. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Masha, S.C.; Owuor, C.; Ngoi, J.M.; Cools, P.; Sanders, E.J.; Vaneechoutte, M.; Crucitti, T.; de Villiers, E.P. Comparative Analysis of the Vaginal Microbiome of Pregnant Women with Either Trichomonas Vaginalis or Chlamydia Trachomatis. PLoS ONE 2019 , 14 , e0225545. [ Google Scholar ] [ CrossRef ] [ PubMed ] [ Green Version ]
Yin, X.; Altman, T.; Rutherford, E.; West, K.A.; Wu, Y.; Choi, J.; Beck, P.L.; Kaplan, G.G.; Dabbagh, K.; DeSantis, T.Z.; et al. A Comparative Evaluation of Tools to Predict Metabolite Profiles From Microbiome Sequencing Data. Front. Microbiol. 2020 , 11 , 595910. [ Google Scholar ] [ CrossRef ] [ PubMed ]
Raimondi, S.; Candeliere, F.; Amaretti, A.; Foschi, C.; Morselli, S.; Gaspari, V.; Rossi, M.; Marangoni, A. Vaginal and Anal Microbiome during Chlamydia Trachomatis Infections. Pathogens 2021 , 10 , 1347. [ Google Scholar ] [ CrossRef ] [ PubMed ]

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Filardo, S.; Di Pietro, M.; Sessa, R. Towards a Deeper Understanding of Chlamydia trachomatis Pathogenetic Mechanisms: Editorial to the Special Issue “ Chlamydia trachomatis Pathogenicity and Disease”. Int. J. Mol. Sci. 2022 , 23 , 3943. https://doi.org/10.3390/ijms23073943

Filardo S, Di Pietro M, Sessa R. Towards a Deeper Understanding of Chlamydia trachomatis Pathogenetic Mechanisms: Editorial to the Special Issue “ Chlamydia trachomatis Pathogenicity and Disease”. International Journal of Molecular Sciences . 2022; 23(7):3943. https://doi.org/10.3390/ijms23073943

Filardo, Simone, Marisa Di Pietro, and Rosa Sessa. 2022. "Towards a Deeper Understanding of Chlamydia trachomatis Pathogenetic Mechanisms: Editorial to the Special Issue “ Chlamydia trachomatis Pathogenicity and Disease”" International Journal of Molecular Sciences 23, no. 7: 3943. https://doi.org/10.3390/ijms23073943

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Research Article

Knowledge about and prevalence of Chlamydia trachomatis in a population-based sample of emerging Croatian adults

Roles Conceptualization, Investigation, Methodology, Writing – original draft, Writing – review & editing

Affiliation World Health Organization Collaborating Centre for HIV Strategic Information, University of Zagreb School of Medicine, Zagreb, Croatia

Roles Conceptualization, Funding acquisition, Investigation, Methodology, Project administration, Writing – review & editing

* E-mail: [email protected]

Affiliation Division for Epidemiology of Communicable Diseases, Department for HIV, Sexual and Blood Transmitted Diseases, Croatian Institute of Public Health, Zagreb, Croatia

Roles Investigation, Writing – review & editing

Affiliation Division for Epidemiology, Department of Epidemiology of Infectious Diseases, Teaching Institute for Public Health “Andrija Stampar”, Zagreb, Croatia

Affiliation Division for Clinical Microbiology, Department of Molecular Microbiology, Teaching Institute for Public Health “Andrija Stampar”, Zagreb, Croatia

Roles Writing – review & editing

Affiliation University Centre Varazdin, University North, Varazdin, Croatia

Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing

Affiliation Department of Sociology Faculty of Humanities and Social Sciences, University of Zagreb, Zagreb, Croatia

Ivana Bozicevic,
Tatjana Nemeth Blazic,
Mirjana Lana Kosanovic Licina,
Tatjana Marijan,
Tomislav Mestrovic,
Tihana De Zan,
Aleksandar Stulhofer

Published: October 27, 2023
https://doi.org/10.1371/journal.pone.0293224
Reader Comments

To determine the prevalence of genital Chlamydia trachomatis (chlamydia) infection, knowledge about chlamydia and experience of previous testing for chlamydia, we carried out a national probability-based survey in emerging adults aged 18–25 years in Croatia in 2021–2022. Participants ( n = 1197), members of a national online panel, completed a web-based questionnaire that collected information on socio-demographics, sexual behaviours and knowledge about sexually transmitted infections (STIs). Urine specimens from a sample of sexually experienced participants were self-collected and tested for chlamydia using Cobas 4800 CT/NG test. To achieve broad representativeness of the emerging adult population in the country, we applied post-hoc weighting for gender and age. Multivariable ordinary least squares linear regression was used to determine correlates of knowledge about chlamydia infection and binomial logistic regression to assess correlates of the willingness to test for chlamydia. Among 448 participants who sent in their urine specimens chlamydia prevalence was 2.5% (95% CI 1.2–5.1) in women and 1.0% (0.3–3.2%) in men. A total of 8.0% of women and 4.7% men reported testing for chlamydia prior to the survey. About a quarter of the sample was characterized by not answering correctly any of the six questions related to knowledge about chlamydia, while only 9.6% had five or six correct answers. In the multivariable analysis, significantly higher odds of willingness to test for chlamydia were found in females compared to males ( OR = 1.34, p = 0.024), those with better knowledge about the infection ( OR = 1.11, p = 0.005), and those with lower religiosity ( OR = 0.91, p = 0.017). In conclusion, prevalence of chlamydia in emerging adults in Croatia is considerable. Efforts to control this infection should focus on primary prevention and targeted testing combined with effective case management strategies.

Citation: Bozicevic I, Blazic TN, Kosanovic Licina ML, Marijan T, Mestrovic T, De Zan T, et al. (2023) Knowledge about and prevalence of Chlamydia trachomatis in a population-based sample of emerging Croatian adults. PLoS ONE 18(10): e0293224. https://doi.org/10.1371/journal.pone.0293224

Editor: Stefan Grosek, University Medical Centre Ljubljana (UMCL) / Faculty of Medicine, University Ljubljana (FM,UL), SLOVENIA

Received: April 8, 2023; Accepted: October 4, 2023; Published: October 27, 2023

Copyright: © 2023 Bozicevic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting information files.

Funding: The study was funded by the Croatian Science Foundation, Research Project IP-2019-04 (grant # IP-2019-04-3609). Additional financial support for the biological part of the study (for the purpose of financial compensation for the coordination of sample collection, entering the results into the results application for participants and telephone counseling and informing respondents with positive findings) was provided by the Croatian institute of Public Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Chlamydia trachomatis (chlamydia) infection is one of the most frequent sexually transmitted infections (STIs) in young people and may cause complications such as pelvic inflammatory disease, ectopic pregnancy and infertility in women and epididymitis and epididymo-orchitis in men [ 1 ]. This infection is often asymptomatic, particularly in women, and can therefore remain undiagnosed and untreated. According to the World Health Organization (WHO) most recent estimates, prevalence of chlamydia among 15–49 years old population in the WHO European Region in 2016 was 2.7% (2.1–3.5%) [ 2 ].

In Croatia, the number of reported cases of chlamydia was declining in the 2011–2021 period, from the highest number of 386 cases in 2014 to 115 cases in 2021 while in this same time-period no new or enhanced chlamydia control activities were implemented at the national level [ 3 ]. According to the latest European Centre for Disease Prevention and Control (ECDC) data, chlamydia case notification rate in Croatia was 3.7 per 100,000 population in 2019 while the European Union and the European Economic Area (EU/EEA) average was 157.0 per 100,000 population [ 4 ]. Among 26 countries of the European Union and the EU/EEA that reported in the 2015–2019 period, the largest decline in the rate of reported cases was seen in Croatia (53%), compared to an average 6% decline in the EU/EEA countries. Differences in chlamydia reporting rates across Europe reflect availability of appropriate diagnostics, level of testing for chlamydia, data reporting practices of health care providers and intensity of chlamydia control activities [ 5 , 6 ].

Cross-sectional surveys carried on in a representative sample of the general population can provide estimates of the burden of chlamydia provided that participation bias is not substantial, which is often not the case with household-based surveys of sexual behaviours and prevalence of STIs [ 7 ]. Recently, Internet-based surveys on sexual behaviours have been successfully utilised to recruit large samples of young people as Internet provides a private, anonymous setting for participation in research, which is beneficial for studies that involve reporting private and sensitive sexual information [ 8 , 9 ].

The objective of our study was to determine the prevalence of chlamydia among 18–25 year old people in Croatia, assess the level of knowledge about chlamydia and experience of previous testing for chlamydia, and describe correlates of chlamydia-related knowledge and willingness to provide urine specimen to test for chamydial infection in the survey.

Participants

Data for this study were collected in a large-scale national sample of emerging Croatian adults. In the late 2021, 1,197 participants aged 18–25 years were surveyed using an online questionnaire. All participants were members of a commercial online panel maintained by an international research company. Such approach was deemed the most feasible and efficient considering the coronavirus disease 2019 (COVID-19) pandemic restrictions and widespread concerns that a household-based survey will yield a low response rate. Two-stage stratification (by region and settlement size) grid was used to randomly draw eligible participants from the panel database. Study response rate was 29%, which is comparable to the response of 32% observed in another national study of emerging adults’ sexual and reproductive health more than a decade ago [ 10 ]. To achieve broad representativeness of the emerging adult population in the country, we applied post-hoc weighting for gender and age.

Data collection, using computer-assisted web-survey, was carried out in from 19 November 2021 to 31 January 2022. Study design and procedures are in detail described elsewhere [ 11 ]. All participants were asked for informed consent before starting an online questionnaire and before participating in the biological part of the research. The questionnaire was originally developed in 2005 to assess knowledge about HIV and STIs, attitudes and beliefs about sexuality, and sexual behaviours of emerging adults [ 12 ]. The questionnaire was further validated in 2010, while a couple of recently developed measures were piloted in a sample of university students in 2020. The questionnaires took approximately 20 minutes to complete.

Following the completion of the questionnaire, for which they received a small token of appreciation (5 EUR voucher), participants were again contacted by the research company and offered to participate in a biological part of the study, which included provision of a urine sample for chlamydia testing. Participation in the biological arm of the study was rewarded with a voucher worth 20 EUR. Procedures in the process of sampling and communication with respondents (sending invitations to online questionnaire, testing kit, reminders to participate and view results) were carried out by the research company electronically using the usual way of communicating with panel members according to current regulations and existing standards in this area. The research was conducted in such a way that the anonymity of the participants towards the researchers and third parties was ensured. To preserve anonymity, randomly generated 4-digit codes were used to link biological and behavioral data. Testing kit was mailed via post along with a detailed photo-illustrated instructions and a link to a film about how to collect a urine specimen and check test results on-line. Participants were also provided with a specimen return package with the prepaid postage. Urine samples were mailed to the laboratory of the National Referent Center for the Diagnostics of STIs at the Zagreb Teaching Institute for Public Health “Dr. Andrija Stampar”. Specimens were analysed using Cobas 4800 CT/NG Test (Roche Diagnostics, Mannheim, Germany), which is a nucleic acid amplification test (NAAT) for detection of chlamydia.

Together with the testing kit, participants received a card with a unique code to be used for learning test result. Participant could obtain test results by typing in their personal code on a web page specifically designed for the purpose of the survey. Positive results were linked to information of health care specialists that were recommended to be contacted regarding start of the treatment.

All study procedures were approved by the Ethical Review Board of the Faculty of Humanities and Social Sciences, University of Zagreb (approval number 2019–14) and, for the biological arm, by the Institutional Review Board of the Croatian Institute of Public Health, (approval number 030-02/21-01/6 -381-15-20-3).

The questionnaire included questions on demographics, sexual behaviours (number of sexual partners and condom use), knowledge about HIV and STIs and previous testing for chlamydia. Knowledge about chlamydia infection was assessed by six questions such as: “A person can get infected by chlamydia only once”; “Most women who are infected with chlamydia have no symptoms”, “In men, genital chlamydia infection can be without symptoms”, “If untreated, genital chlamydia infection can have negative consequences on fertility in men”, “If untreated, genital chlamydia infection can have negative consequences on fertility in women” and “Urogenital chlamydial infection can be detected from urine”. Answers were coded as 0 = incorrect and 1 = correct, and summed to form an additive indicator ranging from 0–6. The composite had acceptable internal consistency (KR-20 = 0.65).

Socio-demographics controls were participant’s education (years of formal education divided by age), participant’s family socioeconomic standing (ranging from 1 = “much worse than average family in the country to 5 = “much better than average family”), participant’s religiosity (i.e., frequency of attending religious ceremonies ranging from 1 = “I am not religious” to 7 = “daily or almost daily”, education of participant’s mother and father (0 = less than college education, 1 = college or university education), and place of residence (0 = urban, 1 = rural/semi-urban).

Analytical strategy

Following descriptive analysis and t-testing for gender differences in key indicators, which were carried out on weighted data, two multivariable regression analysis were carried out: linear regression was used with knowledge about chlamydia infection as dependent variable and binomial logistic regression with willingness to test for chlamydia (non-tested vs. tested participants) as dependent variable. To check for potential underestimation of standard errors due to cluster-based sampling approaching, we first estimated intra-cluster correlation (ICC) in unconditional mixed models with sampling points as random effect. Considering that ICC for knowledge about chlamydia was 0.03 and ICC for testing for infection <0.01, the risk of false positives was judged highly unlikely. The proportion of missing data on indicators of interest was low (up to one percent), with the notable exception of the variable number of sexual partners in the past 12 months, which had 31% of missing responses. Following Little’s test of missing completely at random, which suggested that data were missing in non-systematic manner (χ 2 (20) = 27.19, p = 0.130), we applied multiple imputation ( m = 40) to check the robustness of regression findings [ 13 ].

To avoid potential biases associated with an overly liberal approach to the inclusion of control variable, only constructs that have been both conceptually and empirically linked to the outcomes (family socioeconomic background, parents’ education, religiosity, and rural vs. urban place of residence) were included in the regression models, together with the number of sexual partners in the past 12 months as an indicator of sexual risk taking, knowledge about chlamydia, as well as previous testing for the infection [ 14 , 15 ]. Finally, gender was controlled due to gender-specific sexual socialization of young people and higher levels of health concerns in women, especially in the context of reproductive health, compared to men.

Statistical analysis was carried out using IBM SPSS Statistics for Windows, version 29 (IBM Corp., Armonk, N.Y., USA) (descriptive, bivariate, and multivariable analyses with post-hoc weighting) and jamovi statistical software packages (ICC testing) [ 16 ].

Socio-demographic characteristics of the sample are presented in Table 1 . Mean age of participants was 21.7 years ( SD = 2.21) and 48.3% of participants were female. Reflecting national educational structure, most participants reported that their parents completed secondary education. The majority reported some level of religiosity. Regarding sexual behavior, most participants (74.6%) reported a single sexual partner in the past 12 months. Eight percent had no partners in the same period, while 10.8% reported two and 6.6% three or more sexual partners.

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https://doi.org/10.1371/journal.pone.0293224.t001

A total of 553 participants (46.3% of the sample) expressed interest to receive urine specimen collection device. The majority (81.0%) returned a urine sample. Of the 448 emerging adults who sent in their urine sample—40.4% (n = 245) of female and 34.3% (n = 203) of male participants -, positive result was obtained in nine participants–seven women (2.5%; 95% CI 1.2–5.1) and two men (1.0%; 0.3–3.2). All nine individuals who tested positive learned about their result. According to the weighted analysis, only 6.3% of participants (8.0% of female and 4.7% of male participants) tested for chlamydia prior to this survey while an additional 7.6% of females and 7.8% of males did not remember.

Knowledge about the infection, which ranged from 0 (no correct answers) to 6 (all sex questions correctly answered), was skewed toward lower knowledge ( M = 2.2 SD = 1.65; Median score = 2). About a quarter of the sample was characterized by not a single correct answer, while only 9.6% had five or six correct answers. Most emerging adults either reported no (21.6%) or only three correct answers (21.6%). We observed no substantial gender difference in knowledge about the infection ( t (1196 = -1.72, p = 0.086). While approximately one in two respondents knew that infection with chlamydia can have adverse consequences on female and male fertility, only 4.5% of men and 1.9% of women knew that this infection can be acquired more than once in a lifetime. A minority– 24.6% of male and 25.2% of female respondents—knew that the majority of women with chlamydia infection do not have any symptoms.

Correlates of knowledge about and testing for chlamydia

Tables 2 and 3 show correlates of knowledge about chlamydia and of providing urine specimens for testing, respectively, using weighted multivariable regression analysis. The results of multivariable regression analysis suggest that participants who self-reported being tested for chlamydia before this survey had significantly better knowledge about chlamydia ( B = 0.87, S.E. = 0.21; p<0.001) compared to those who did not test before.

https://doi.org/10.1371/journal.pone.0293224.t002

https://doi.org/10.1371/journal.pone.0293224.t003

Table 3 (the upper part) shows the results of testing for correlates of providing a urine sample. Somewhat unexpectedly, none of the independent variables significantly contributed to distinguishing between emerging adults who tested for chlamydia in the current study and those who did not.

In the final step, the two regression analyses were repeated using the dataset in which missing information was replaced by multiple imputation. In the case of knowledge about chlamydia (not shown in a table), ever being testing for the infection remained the sole significant predictor ( B = 0.74, S.E. = 0.18, p < 0.001). However, the second analysis resulted in a markedly different pattern of (non-)significant findings (see the lower half of Table 3 ). With missing data imputed, three significant predictors of testing for chlamydia emerged: gender ( OR = 1.34, p = 0.024), knowledge about the infection ( OR = 1.11, p = 0.005), and religiosity ( OR = 0.91, p = 0.017). While female gender and better knowledge about the infection significantly increased the odds of testing, higher religiosity worked in the opposite direction.

The prevalence of chlamydia infection in our study was relatively similar to the prevalence found in nationally representative surveys of sexually experienced adults aged 18–26 years in the EU/EEA countries (3.6%) in women, but lower in men (3.5% in the EU/EEA) [ 5 ]. The prevalence found in this survey was substantially lower compared to the last round of nationally representative survey among adults aged 18–25 years in Croatia, which found prevalence of chlamydia of 5.3% in women and 7.3% in men in 2010 [ 17 ]. However, that study was household-based, with a lower response rate for testing for chlamydia (32.5%) compared to this round of the survey (46.2%). Comparisons between these two surveys should be made with caution due to differences in the recruitment strategies (previous survey was household-based while this one was internet-based) and the fact that the surveys were not powered to detect a change in prevalence. There is evidence that estimates of chlamydia prevalence might be higher in surveys with lower response rates compared to surveys with higher response rates [ 5 ].

Prevalence of chlamydia in our study was similar to the prevalence of 2.99% among 1238 students in the city of Zagreb who were tested for chlamydia as part of a three-year screening conducted in in 2017–2019 [ 18 ].

Only a minority of respondents in our survey reported being tested for chlamydia before, which shows low availability of chlamydia testing in Croatia. A substantially higher proportion of respondents aged 16–24 years sampled in the nationally representative survey in Britain (Natsal-3) reported being tested for chlamydia in the year before the survey– 54.2% of women and 34.6% of men, reflecting longer-standing and extensive presence of screening for chlamydia in Britain [ 19 ]. Furthermore, in a study on randomly selected 377 women aged 18–25 from Washington State in the US, 53% self-reported chlamydia testing in the preceding year [ 20 ].

It is discouraging to observe that those with higher number of partners in the past 12 months were not significantly more likely to provide urine specimens for testing for chlamydia in the survey, which might indicate low perception of risk of infection or the possibility that the survey sampling method did not reach those at higher risk of infection.

In contrast to that, those with better knowledge about chlamydia were significantly more likely to provide urine samples for testing. This shows that interventions focused on increasing knowledge and awareness about chlamydia could lead to better uptake of testing.

There is no organized opportunistic testing for chlamydia in Croatia. ECDC recommends that widespread opportunistic testing or screening of sexually active men and women under 25 years in case of sufficient resources and existence of a monitoring and evaluation system, none of which is in place in Croatia [ 21 ]. However, effectiveness of chlamydia screening on lowering chlamydia prevalence, preventing pelvic inflammatory disease, ectopic pregnancy or female infertility has been questioned and is a subject of ongoing debates [ 22 , 23 ]. Targeted testing combined with effective case management strategies, which includes partner notification, and the emphasis on primary prevention of STIs might be a reasonable way forward for chlamydia control in Croatia [ 20 , 24 , 25 ]. It is also important to consider participation rates in such testing approaches, since de Wit and colleagues showed that they are crucial for reaching (or preserving) cost-effectiveness of nationwide chlamydia screening programs–emphasizing the need for extensive piloting prior to implementation decisions [ 26 ].

We found considerable gaps in knowledge about chlamydia among young people. Therefore, there is a need for raising awareness and knowledge in the general population of young people about asymptomatic nature of chlamydia infection and its consequences and the risks of re-infections, which might lead to higher demand for testing [ 27 ].

Establishment of online services for chlamydia testing should be also considered as this may address barriers to clinic attendance such as long waiting times, inconvenient opening hours, perceived stigma and travel time or cost. Availability of online services in the community alongside clinic services can increase uptake of STI testing in young people, and in particular those that have lower access to services [ 28 ], while the experience from Sweden emphasized behavioural risk profile and antecedent chlamydia test results in users of such services to demonstrate how it can indeed reach a relevant target group [ 29 ].

Study limitations

Our findings are impacted by accuracy of self-reporting on sexual behaviours. Although Internet recruitment into surveys has a number of advantages it is affected by the sampling and participation bias, which is especially relevant in research on sexual behaviours due to their private nature. Questions were answered via internet and by self-completion, which should have minimised social desirability bias. Since data collection was done on-line, the survey included population with access to internet via mobile or desktop devices. According to data of the Croatian Bureau of Statistics, 86% of households had access to Internet in 2021, while 97% of people aged 16–24 years used Internet [ 30 ].

Regarding chlamydia testing, first catch urine is an adequate specimen for screening high-risk groups such as emerging adults for chlamydia by NAAT [ 31 ]. COBAS 4800 test used in our study is validated for first catch urine testing in men and women, while transport media used in the testing procedure ensures cellular quality and improves the sensitivity.

Besides its limitations, the internet-based survey on sexual behaviours, which included self-collection of urine samples and testing for chlamydia in young people in Croatia has proven to be feasible and a lower-cost alternative to a household-based survey. It has also been a powerful tool to update and fill the gap of information concerning the prevalence of chlamydia among emerging adults and knowledge about chlamydia infection.

In conclusion, our study found a considerable prevalence of chlamydia among young people in Croatia and low reported prior testing, which implies a need to strengthen chlamydia control efforts by providing innovative targeted chlamydia screening strategies.

Supporting information

https://doi.org/10.1371/journal.pone.0293224.s001

Acknowledgments

The authors would like to express their gratitude to Goran Koletić, Ivan Landripet and Kristina Stepusin Seferovic for their help with data collection.

1. Progress report on HIV, viral hepatitis and sexually transmitted infections. Accountability for the global health sector strategies, 2016–2021. Geneva: World Health Organization, 2019.
2. Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2021. Accountability for the global health sector strategies 2016–2021: actions for impact. Web Annex 1. Key data at a glance. Geneva: World Health Organization, 2021.
3. Infectious disease in Croatia. Croatian health statistics for 2021. Zagreb: Croatian Institute for Public Health, 2022. In Croatian .
4. Chlamydia infection. Annual epidemiological report for 2019. Stockholm: European Center for Disease Prevention and Control, 2022.
View Article
PubMed/NCBI
Google Scholar
8. Roath OK, Chen X, Kolacz. Predictors of Participation for Sexuality Items in a U.S. Population-Based Online Survey. Arch Sex Behav 2023; Online ahead of print
15. Spector PE, Brannick MT. Methodological urban legends: The misuse of statistical control variables. In Boyle GJ, O’Gorman JG, Fogarty GJ (Eds.). Work and organisational psychology: Research methodology; Assessment and selection; Organisational change and development; Human resource and performance management; Emerging trends: Innovation/globalisation/technology (pp. 63–86). Sage Publications, Inc., 2016.
16. The jamovi project, 2021. jamovi . (Version 2.3.21) [Computer Software]. Feb. 2, 2023 https://www.jamovi.org .
18. De Zan T, Vranes J, Marijan T, Kvaternik Celjak M, Cesic S, Posavec M, et al. Results of a three-year screening for Chlamydia trachomatis and Mycoplasma genitalium in the student population in Zagreb, Croatia. Abstracts of the 13 th Croatian Congress on Clinical Microbiology and the 10 th Croatian Congress on Infectious Diseases. Sibenik, Croatia, 20–23 October 2022. In Croatian .
21. Guidance on chlamydia control in Europe. Scientific advice. Stockholm: European Centre for Disease Prevention and Control, 2005.
30. Usage of information and communication technologies in households and by individuals in 2021. Croatian Bureau of Statistics, 2021. https://podaci.dzs.hr/2021/hr/10262 Accessed on 3 March 2023. In Croatian .

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Paper-based molecular diagnostic for Chlamydia trachomatis

Affiliations.

1 Biomedical Engineering, Boston University, Boston, MA, 02215.
2 BioHelix Corporation, Beverly, MA, 01915.
PMID: 25309740
PMCID: PMC4188396
DOI: 10.1039/C4RA07911F

Herein we show the development of a minimally instrumented paper-based molecular diagnostic for point of care detection of sexually transmitted infections caused by Chlamydia trachomatis . This new diagnostic platform incorporates cell lysis, isothermal nucleic acid amplification, and lateral flow visual detection using only a pressure source and heat block, eliminating the need for expensive laboratory equipment. This paper-based test can be performed in less than one hour and has a clinically relevant limit of detection that is 100x more sensitive than current rapid immunoassays used for chlamydia diagnosis.

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RANIT MISHORI, MD, MHS, ERICA L. MCCLASKEY, MD, MS, AND VINCE J. WINKLERPRINS, MD

Am Fam Physician. 2012;86(12):1127-1132

A more recent article on chlamydial and gonococcal infections is available.

Patient information: A handout on this topic is available at https://familydoctor.org/familydoctor/en/diseases-conditions/chlamydia.html .

Author disclosure: No relevant financial affiliations to disclose.

Chlamydia trachomatis is a gram-negative bacterium that infects the columnar epithelium of the cervix, urethra, and rectum, as well as nongenital sites such as the lungs and eyes. The bacterium is the cause of the most frequently reported sexually transmitted disease in the United States, which is responsible for more than 1 million infections annually. Most persons with this infection are asymptomatic. Untreated infection can result in serious complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy in women, and epididymitis and orchitis in men. Men and women can experience chlamydia-induced reactive arthritis. Treatment of uncomplicated cases should include azithromycin or doxycycline. Screening is recommended in all women younger than 25 years, in all pregnant women, and in women who are at increased risk of infection. Screening is not currently recommended in men. In neonates and infants, the bacterium can cause conjunctivitis and pneumonia. Adults may also experience conjunctivitis caused by chlamydia. Trachoma is a recurrent ocular infection caused by chlamydia and is endemic in the developing world.

Chlamydia trachomatis is a gram-negative bacterium that infects the columnar epithelium of the cervix, urethra, and rectum, as well as nongenital sites. The bacterium is the cause of the most frequently reported sexually transmitted disease in the United States, 1 and is the leading cause of infectious blindness in the world. 2 According to the Centers for Disease Control and Prevention (CDC) in 2009, the rate of sexually transmitted chlamydia infections in the United States was 426 cases per population of 100,000, which represents a 24 percent increase in the rate of infection since 2006. 3 More recent data from 2010 indicates that 1,307,893 chlamydia infections were reported to the CDC from all 50 states and the District of Columbia. 4 The CDC estimates that there are 2.8 million chlamydia cases in the United States annually—more than twice the number actually reported. 5 This is an increase of 5 percent over the past year, and 27 percent from four years ago. 5 From 2000 to 2010, the chlamydia screening rate among young women nearly doubled, from 25 to 48 percent. 5


Nucleic acid amplification tests are the most sensitive tests for detecting chlamydia infection, and may be performed on endocervical, urethral, vaginal, pharyngeal, rectal, or urine samples.	C
Azithromycin (Zithromax) or doxycycline should be used for the treatment of uncomplicated genitourinary chlamydia infection in men and women.	A
Azithromycin or amoxicillin should be used as first-line treatment of genitourinary chlamydia infection in pregnant women.	A
The USPSTF recommends screening for chlamydia infection in all sexually active nonpregnant women 24 years and younger, and all nonpregnant women 25 years and older who are at increased risk.	A
The USPSTF concludes there is insufficient evidence to recommend for or against the screening of men for chlamydia infection.	C
Although the CDC recommends screening for chlamydia infection in all pregnant women, the USPSTF recommends routine screening only in all pregnant women 24 years and younger, and in pregnant women 25 years and older who are at increased risk.	B	,
Some experts recommend screening certain groups of high-risk men (e.g., men who have sex with men) for rectal chlamydia infection.	C	,

Genitourinary Infections

Genitourinary infection affects primarily young adults and persons with multiple sex partners. 6 Women carry a disproportionate burden: CDC statistics show that the overall rate of infection was almost three times higher among women than men, 7 although this may be because of existing screening programs for women. Approximately 79 percent of the U.S. health costs for chlamydia infections can be attributed to women. 8

Young women 15 to 19 years of age carry the highest incidence of disease, followed by women 20 to 24 years of age. Although chlamydia is common in all races, blacks, American Indians/Alaska Natives, and Hispanic women are disproportionately affected. Other groups at higher risk include adolescents and men who have sex with men. 8

According to the CDC, chlamydia infection rates in men are also increasing, and at a faster rate than in women. Between 2005 and 2009, the reported infection rate for men rose from 159.4 to 219.3 cases per 100,000 males, a 37.6 percent increase. 7 During the same period, the rate of infection among women increased 29.3 percent. 7

Prevalence rates among men vary depending on the subgroups screened. One study reported a prevalence of 3.7 percent in men 18 to 26 years of age. 9 Other studies report an overall prevalence among asymptomatic men in the United States of between 6 and 7 percent, and as much as 18 to 20 percent in men attending inner-city primary care clinics. 10 In select groups, such as men who have sex with men, rates of rectal infections were found to be high. 11 Risk factors for men and women include lack of condom use, lower socioeconomic status, living in an urban area, and having multiple sex partners.

PRESENTATION

Most persons who are infected with C. trachomatis are asymptomatic. However, when symptoms of infection are present, in women they most commonly include abnormal vaginal discharge, vaginal bleeding (including bleeding after intercourse), and dysuria. 12 On physical examination, mucopurulent or purulent discharge from the endocervical canal and cervical friability are common. In men, symptoms may include penile discharge, pruritus, and dysuria. However, in one study, only 2 to 4 percent of infected men reported any symptoms. 10

Persons who have receptive anal intercourse can acquire a rectal infection, which can present as pain, discharge, or bleeding. Those engaging in oral sex can acquire a pharyngeal infection from an infected partner.

Nucleic acid amplification tests (NAATs) are the most sensitive tests for detecting chlamydia and gonococcal infections. 13 NAATs can be performed on endocervical, urethral, vaginal, pharyngeal, rectal, or urine samples (first-void is preferred). 13 The accuracy of NAATs on urine samples has been found to be nearly identical to that of samples obtained directly from the cervix or urethra. 13 On wet mount, a finding of leukorrhea (more than 10 white blood cells per high-power field on microscopic examination of vaginal fluid) has been associated with chlamydial and gonococcal infections of the cervix. 1 Oropharyngeal and rectal swabs may be obtained in persons who engage in receptive oral or anal intercourse. 13

Point-of-care testing at a physician's office is recommended, although increasingly, researchers have begun to evaluate commercially available mail-in kits. To date, commercial kits have not been shown to be reliable, and have lower sensitivity and specificity than NAATs. 14

Uncomplicated genitourinary chlamydia infection should be treated with azithromycin (Zithromax; 1 g, single dose) or doxycycline (100 mg twice daily for seven days; Table 1 1 , 15 – 22 ). Studies indicate that both treatments are equally effective. 15 Although dual therapy to cover gonorrhea and chlamydia is recommended when patients are diagnosed with gonorrhea, additional coverage for gonorrhea is not required with the diagnosis of chlamydia alone. 1


Uncomplicated genitourinary infection	Azithromycin (Zithromax), 1 g (single dose)

	Doxycycline, 100 mg twice daily for seven days
	Alternatives:
		Erythromycin, 500 mg four times daily for seven days
		Erythromycin ethylsuccinate, 800 mg four times daily for seven days
		Levofloxacin (Levaquin), 500 mg once daily for seven days
		Ofloxacin (Floxin), 300 mg twice daily (or 600 mg once daily) for seven days
Infection during pregnancy ,	Azithromycin, 1 g (single dose)

	Amoxicillin, 500 mg three times daily for seven days
	Alternatives:
		Erythromycin, 500 mg four times daily for seven days, or 250 mg four times daily for 14 days
		Erythromycin ethylsuccinate, 800 mg four times daily for seven days, or 400 mg four times daily for 14 days
Chronic reactive arthritis ,	Doxycycline, 100 mg twice daily, plus rifampin, 300 mg once daily for six months

	Azithromycin, 500 mg once daily for five days, then500 mg twice weekly, plus rifampin, 300 mg once daily for six months
Lymphogranuloma venereum	Doxycycline, 100 mg twice daily for 21 days
	Alternatives:
		Erythromycin, 500 mg four times daily for 21 days
	Azithromycin, 1 g once weekly for three weeks
Neonatal pulmonary infection	Erythromycin or erythromycin ethylsuccinate, 50 mg per kg daily in four divided doses for 14 days
Ocular infection: ophthalmia neonatorum	Erythromycin or erythromycin ethylsuccinate, 50 mg per kg daily in four divided doses for 14 days
Adult-inclusion conjunctivitis ,	Doxycycline, 100 mg twice daily for one to three weeks

	Erythromycin, 250 mg four times daily for one to three weeks
Trachoma	Azithromycin, 1 g (single dose)

	Doxycycline, 100 mg twice daily for 21 days

Alternative regimens for uncomplicated chlamydia infection include erythromycin (500 mg four times daily for seven days), erythromycin ethylsuccinate (800 mg four times daily for seven days), levofloxacin (Levaquin; 500 mg once daily for seven days), or ofloxacin (Floxin; 300 mg twice daily or 600 mg once daily for seven days). 1 Erythromycin is reported to have higher occurrences of gastrointestinal adverse effects. 15

Pregnant women may be treated with azithromycin (1 g, single dose) or amoxicillin (500 mg three times daily for seven days). Alternative regimens include erythromycin (500 mg four times daily for seven days or 250 mg four times daily for 14 days) and erythromycin ethylsuccinate (800 mg four times daily for seven days or 400 mg four times daily for 14 days). Although all three medications show similar effectiveness, a recent review indicates that azithromycin may have fewer adverse effects when compared with erythromycin or amoxicillin in pregnant women. 16

Test of cure is recommended three to four weeks after completion of treatment in pregnant women only. If chlamydia is detected during the first trimester, repeat testing for reinfection should also be performed within three to six months, or in the third trimester. 1 Men and nonpregnant women should be retested at three months. If this is not possible, clinicians should retest the patient to screen for reinfection when he or she next presents for medical care within 12 months after treatment. 1

Partners should be notified of infection and treated appropriately. Studies indicate that expedited partner therapy (partners treated without medical consultation) may improve clinical and behavioral outcomes pertaining to partner management among heterosexual men and women with chlamydia infection. 23 Partners should be referred for evaluation, testing, and treatment if they engaged in sexual contact within 60 days before a diagnosis was made or at the onset of symptoms. 1 Patients should also be instructed to abstain from sexual intercourse until seven days after a single-dose regimen or after completion of a multiple-dose regimen, and after their partner has also completed treatment. 1 Patients infected with human immunodeficiency virus (HIV) should be treated using the same regimens recommended for those who are HIV-negative ( Table 2 ) . 1 As of January 2000, all 50 states and the District of Columbia require chlamydia cases be reported to state or local health departments.

Make diagnosis via specimen collection (i.e., urine, urethra, endocervix, pharynx, rectum, or vagina), using a nucleic acid amplification test.

All pregnant women infected with chlamydia should be retested three to four weeks after completing treatment.

Test of cure is not advised for nonpregnant patients who finished one of the recommended courses of treatment.

Repeat testing for reinfection of men and women who were recently infected is recommended at three months after completion of treatment, or within the first year following treatment.

Sex partners should be referred for evaluation, testing, and treatment if they engaged in sexual contact within 60 days before a diagnosis was made or at the onset of symptoms.

Advise patients to abstain from sexual contact until they and their sex partners have finished one of the recommended treatments, and for seven days afterward.

SCREENING FOR GENITOURINARY CHLAMYDIA

Currently, the U.S. Preventive Services Task Force recommends routine screening in all sexually active women 24 years and younger, and in women 25 years and older who are at increased risk because of having multiple partners or a new sex partner. 24 Because of the high risk of intrauterine and postnatal complications if left untreated, all pregnant women at increased risk should be routinely screened for chlamydia during the first prenatal visit. 1 Additionally, any pregnant woman undergoing termination of pregnancy should be tested for chlamydia infection. 25

There is insufficient evidence to recommend screening in men, although a small number of studies suggest that screening high-risk groups may be useful and cost-effective. 24 , 26 – 29 Per the CDC, the screening of sexually active young men should be considered in clinical settings with a high prevalence of chlamydia (e.g., adolescent clinics, correctional facilities, sexually transmitted disease clinics), and in certain groups (e.g., men who have sex with men). In men who have sex with men, some experts recommend screening for rectal infections (a rectal swab in those who have had receptive anal intercourse during the preceding year). 1 , 11 The CDC includes chlamydia screening with a urine test among the list of annual tests for all men who have had insertive intercourse within the previous 12 months. 1 Testing for C. trachomatis pharyngeal infection is not recommended in men who have had receptive oral intercourse.

There are a number of ways to prevent, or at least significantly reduce, the incidence of genitourinary chlamydia infection. The most definitive methods of prevention are practicing abstinence and being in a long-term, mutually monogamous relationship. Patients should be encouraged to avoid high-risk behaviors such as having unprotected sex or multiple sex partners. In addition, the correct and consistent use of condoms has been shown to reduce the risk of transmission of sexually transmitted diseases. For adolescents who are considered high risk, specific education about the transmission of disease through unprotected vaginal, anal, or oral sex is warranted. 1

COMPLICATIONS

The health consequences for women who are infected with chlamydia may be substantial and life-threatening. Chlamydia infections put women at an increased risk of developing pelvic inflammatory disease, infertility, or perihepatitis (Fitz-Hugh-Curtis syndrome). Additional negative outcomes include chronic pelvic pain and ectopic pregnancy.

Infection during pregnancy increases the risk of poor outcomes for the fetus. Complications may include miscarriage, premature rupture of membranes, preterm labor, low birth weight, and infant death. 30

In men, consequences may include epididymoorchitis, resulting in infertility. 31 A chlamydia infection may also increase a person's susceptibility to HIV, if exposed. 32 For men and women who are already co-infected with HIV, a concurrent chlamydia infection may increase shedding of the virus. 31 Some studies have also documented an association between co-infection, human papillomavirus, and the subsequent development of cervical cancer, although the association is not definitive. 33

Reactive arthritis (Reiter syndrome), a triad of aseptic arthritis, nongonococcal urethritis, and conjunctivitis, can also occur. Chlamydia-induced reactive arthritis is believed to be underdiagnosed, and emerging data suggest that asymptomatic chlamydia infections may be a common cause. 17 Studies suggest that prolonged antimicrobial therapy, up to six months of combination antibiotics, may be effective. 18

LYMPHOGRANULOMA VENEREUM

Another sexually transmitted infection caused by C. trachomatis (a different serovar) is lymphogranuloma venereum (LGV). It generally presents as a unilateral, tender inguinal or femoral node, and may include a genital ulcer or papule. Anal exposure may result in proctocolitis, rectal discharge, pain, constipation, or tenesmus. 1 If left untreated, it may lead to chronic symptoms, including fistulas and strictures. Diagnosis is based on clinical symptoms and a genital lesion swab or lymph node sample, similar to those used to diagnose the more typical C. trachomatis genitourinary infection. Molecular identification may be needed to differentiate LGV from non-LGV C. trachomatis . Doxycycline (100 mg twice daily for 21 days) is the preferred treatment. An alternative treatment regimen includes erythromycin (500 mg four times daily for 21 days); azithromycin (1 g once weekly for three weeks) may also be used. 1

Pulmonary Infection

C. trachomatis is thought to cause about 12,000 cases of neonatal pneumonia per year in the United States. 34 , 35 Fewer than 10 percent of neonates born to women with active chlamydia infection during labor develop chlamydia pneumonia. 34 , 35 C. trachomatis pneumonia usually manifests one to three months following birth, and should be suspected in a child who has tachypnea and a staccato cough (short bursts of cough) without a fever. Chest radiography may reveal hyperinflation and bilateral diffuse infiltrates, and blood work frequently reveals eosinophilia (400 or more cells per mm 3 ). 19 In addition, specimens should be collected from the nasopharynx. For neonates who have a lung infection, erythromycin (base or ethylsuccinate, 50 mg per kg daily divided into four doses for 14 days) is the treatment of choice. Follow-up is recommended, and a second course of antibiotics may be required. 19

Ocular Infection

Ocular C. trachomatis infection occurs in three distinct disease patterns: ophthalmia neonatorum/neonatal conjunctivitis, adult inclusion conjunctivitis, and trachoma. Physicians treating immigrant and refugee populations, or those practicing internationally, may encounter chronic trachoma cases and should be familiar with its presentation and management.

OPHTHALMIA NEONATORUM/NEONATAL CONJUNCTIVITIS

This infection is transmitted vaginally from an infected mother, and can present within the first 15 days of life. One-third of neonates exposed to the pathogen during delivery may be affected. 19 Symptoms include conjunctival injection, various degrees of ocular discharge, and swollen eyelids. The diagnostic standard is to culture a conjunctival swab from an everted eyelid, using a Dacron swab or another swab specified for this culture. The culture must contain epithelial cells; exudates are not sufficient. 19

The recommended treatment is oral erythromycin base or ethylsuccinate (50 mg per kg daily in four divided doses for 14 days). 19 Prophylaxis with silver nitrate solution or antibiotic ointments does not prevent vertical perinatal transmission of C. trachomatis , but it will prevent ocular gonococcal infection and should therefore be administered. 1

ADULT INCLUSION CONJUNCTIVITIS

This acute mucopurulent conjunctival infection is associated with concomitant genitourinary tract chlamydia infection. If the diagnosis is suspected, a specimen from an everted lid collected using a Dacron swab should be sent for culture. Special culture media are required. Treatment consists of doxycycline (100 mg twice daily for one to three weeks) or erythromycin (250 mg four times daily for one to three weeks). 20 According to one study, a single 1-g dose of azithromycin may be just as effective. 21

Trachoma is a chronic or recurrent ocular infection that leads to scarring of the eyelids. This scarring often inverts the eyelids, causing abnormal positioning of the eyelashes that can scratch and damage the bulbar conjunctiva. Trachoma is the primary source of infectious blindness in the world, affecting primarily the rural poor in Asia and Africa. 36 The initial infection is usually contracted outside of the neonatal period. It is easily spread via direct contact, poor hygiene, and flies. Although it has been eradicated in the United States, physicians may encounter cases in immigrants from endemic areas or during global health work.

Treatment has focused primarily on antibiotics ( Table 1 1 , 15 – 22 ) . Although the World Health Organization has instituted its SAFE (surgery, antibiotics, facial cleanliness, and environmental improvement) program, the large heterogeneity of studies has not clearly identified which of these modalities are most effective at stemming the disease. 22 , 37 Topical treatment is not effective. Mass community treatment, in which all members of a community receive antibiotics, has been found to be effective for up to two years following treatment, but recurrence and scarring remain problematic. 38

Data Sources: We performed a Clinical Query PubMed search using the search terms Chlamydia trachomatis with limits including: humans, clinical trial, meta-analysis, practice guideline, randomized controlled trial, review, English, and being published within the past five years. The choice of authorship of this review also coincided with the publication of the Centers for Disease Control and Prevention's Sexually Transmitted Diseases: Treatment Guidelines, 2010. Articles referenced in this review were considered. We searched Dynamed, Essential Evidence Plus, the Cochrane Database of Systematic Reviews, the National Guideline Clearinghouse, the Institute for Clinical Systems Improvement, and the U.S. Preventive Services Task Force using the same search terms. Search date: December 16, 2010.

Workowski KA, Berman S Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010 [published correction appears in MMWR Recomm Rep . 2011;60(1):18]. MMWR Recomm Rep. 2010;59(RR-12):1-110.

Hu VH, Harding-Esch EM, Burton MJ, Bailey RL, Kadimpeul J, Mabey DC. Epidemiology and control of trachoma: systematic review. Trop Med Int Health. 2010;15(6):673-691.

Centers for Disease Control and Prevention. STD trends in the United States: 2010 national data for gonorrhea, chlamydia, and syphilis Snapshot sexually transmitted diseases in 2010. http://www.cdc.gov/std/stats10/tables/trends-snapshot.htm . Accessed May 21, 2012.

Centers for Disease Control and Prevention. Chlamydia – CDC fact sheet. http://www.cdc.gov/std/chlamydia/stdfact-chlamydia.htm . Accessed May 21, 2012.

Centers for Disease Control and Prevention. STD trends in the United States: 2010 national data for gonorrhea, chlamydia, and syphilis. Table. http://www.cdc.gov/std/stats10/tables/trends-table.htm . Accessed May 21, 2012.

Chesson HW, Sternberg M, Leichliter JS, Aral SO. The distribution of chlamydia, gonorrhoea and syphilis cases across states and counties in the USA, 2007. Sex Transm Infect. 2010;86(suppl 3):iii52-iii57.

Centers for Disease Control and Prevention. 2009 Sexually transmitted diseases surveillance. Chlamydia. http://www.cdc.gov/std/stats09/chlamydia.htm . Accessed March 6, 2011.

Mangione-Smith R, O'Leary J, McGlynn EA. Health and cost-benefits of chlamydia screening in young women. Sex Transm Dis. 1999;26(6):309-316.

Miller WC, Ford CA, Morris M, et al. Prevalence of chlamydial and gonococcal infections among young adults in the United States. JAMA. 2004;291(18):2229-2236.

Schillinger JA, Dunne EF, Chapin JB, et al. Prevalence of Chlamydia trachomatis infection among men screened in 4 U.S. cities. Sex Transm Dis. 2005;32(2):74-77.

Annan NT, Sullivan AK, Nori A, et al. Rectal chlamydia—a reservoir of undiagnosed infection in men who have sex with men. Sex Transm Infect. 2009;85(3):176-179.

Stamm WE, Holmes K. Chlamydia trachomatis infections of the adult. In: Holmes KK, Mardh PA, Sparling PF, et al., eds. Sexually Transmitted Diseases . 2nd ed. New York, NY: McGraw-Hill; 1990:181–193.

Cook RL, Hutchison SL, Østergaard L, Braithwaite RS, Ness RB. Systematic review: noninvasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae . Ann Intern Med. 2005;142(11):914-925.

van Dommelen L, van Tiel FH, Ouburg S, et al. Alarmingly poor performance in Chlamydia trachomatis point-of-care testing. Sex Transm Infect. 2010;86(5):355-359.

Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Sex Transm Dis. 2002;29(9):497-502.

Pitsouni E, Iavazzo C, Athanasiou S, Falagas ME. Single-dose azithromycin versus erythromycin or amoxicillin for Chlamydia trachomatis infection during pregnancy: a meta-analysis of randomised controlled trials. Int J Antimicrob Agents. 2007;30(3):213-221.

Carter JD, Hudson AP. The evolving story of chlamydia-induced reactive arthritis. Curr Opin Rheumatol. 2010;22(4):424-430.

Carter JD, Espinoza LR, Inman RD, et al. Combination antibiotics as a treatment for chronic chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial. Arthritis Rheum. 2010;62(5):1298-1307.

Darville T. Chlamydia trachomatis infections in neonates and young children. Semin Pediatr Infect Dis. 2005;16(4):235-244.

Gilbert DN, Moellering RC, Eliopoulos GM. The Sanford Guide to Antimicrobial Therapy 2010 . 40th ed. Sperryville, Va.: Antimicrobial Therapy; 2010.

Katusic D, Petricek I, Mandic Z, et al. Azithromycin vs doxycycline in the treatment of inclusion conjunctivitis. Am J Ophthalmol. 2003;135(4):447-451.

Mabey D, Fraser-Hurt N, Powell C. Antibiotics for trachoma. Cochrane Database Syst Rev. ;2005(2):CD001860.

Centers for Disease Control and Prevention Expedited partner therapy in the management of sexually transmitted diseases Atlanta, Ga:. U.S. Department of Health and Human Services; 2006. http://www.cdc.gov/std/treatment/eptfinalreport2006.pdf . Accessed March 21, 2012.

U. S. Preventive Services Task Force. Screening for chlamydia infection: recommendation statement. Ann Intern Med. 2007;147(2):128-134.

Scottish Intercollegiate Guidelines Network. Management of genital chlamydia trachomatis infection. March 2009. http://www.sign.ac.uk/guidelines/fulltext/109/index.html . Accessed November 26, 2012.

Gift TL, Blake DR, Gaydos CA, Marrazzo JM. The cost-effectiveness of screening men for Chlamydia trachomatis : a review of the literature. Sex Transm Dis. 2008;35(11 suppl):S51-S60.

Blake DR, Quinn TC, Gaydos CA. Should asymptomatic men be included in chlamydia screening programs? Cost-effectiveness of chlamydia screening among male and female entrants to a national job training program. Sex Transm Dis. 2008;35(1):91-101.

Scholes D, Heidrich FE, Yarbro P, Lindenbaum JE, Marrazzo JM. Population-based outreach for chlamydia screening in men: results from a randomized trial. Sex Transm Dis. 2007;34(11):837-839.

Chai SJ, Aumakhan B, Barnes M, et al. Internet-based screening for sexually transmitted infections to reach nonclinic populations in the community: risk factors for infection in men. Sex Transm Dis. 2010;37(12):756-763.

Horner PJ, Boag F. 2006 UK national guideline for the management of genital tract infection with Chlamydia trachomatis. London (UK): British Association of Sexual Health and HIV (BASHH); 2006. http://www.bashh.org/documents/61/61.pdf. Accessed March 22, 2012.

Shahmanesh M, Moi H, Lassau F, Janier M IUSTI/WHO. 2009 European guideline on the management of male nongonococcal urethritis. Int J STD AIDS. 2009;20(7):458-464.

Laga M, Manoka A, Kivuvu M, et al. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS. 1993;7(1):95-102.

Safaeian M, Quint K, Schiffman M, et al. Chlamydia trachomatis and risk of prevalent and incident cervical premalignancy in a population-based cohort. J Natl Cancer Inst. 2010;102(23):1794-1804.

Tipple MA, Beem MO, Saxon EM. Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than six months of age. Pediatrics. 1979;63(2):192-197.

Bell TA, Stamm WE, Kuo CC, Wang SP, Holmes KK, Grayston JT. Risk of perinatal transmission of Chlamydia trachomatis by mode of delivery. J Infect. 1994;29(2):165-169.

Global Network for Neglected Tropical Diseases. Trachoma interactive fact sheet. http://old.globalnetwork.org/sites/all/modules/globalnetwork/factsheetxml/disease.php?id=9. Accessed February 6, 2011.

Rabiu M, Alhassan MB, Ejere H. Environmental sanitary interventions for preventing active trachoma. Cochrane Database Syst Rev. ;2007(4):CD004003.

Solomon AW, Holland MJ, Alexander ND, et al. Mass treatment with single-dose azithromycin for trachoma. N Engl J Med. 2004;351(19):1962-1971.

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Review Article
Published: 20 March 2024

Antimicrobial treatment and resistance in sexually transmitted bacterial infections

Jorgen S. Jensen ORCID: orcid.org/0000-0002-7464-7435 1 &
Magnus Unemo ORCID: orcid.org/0000-0003-1710-2081 2 , 3

Nature Reviews Microbiology volume 22 , pages 435–450 ( 2024 ) Cite this article

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Bacterial infection
Urogenital diseases

Sexually transmitted infections (STIs) have been part of human life since ancient times, and their symptoms affect quality of life, and sequelae are common. Socioeconomic and behavioural trends affect the prevalence of STIs, but the discovery of antimicrobials gave hope for treatment, control of the spread of infection and lower rates of sequelae. This has to some extent been achieved, but increasing antimicrobial resistance and increasing transmission in high-risk sexual networks threaten this progress. For Neisseria gonorrhoeae , the only remaining first-line treatment (with ceftriaxone) is at risk of becoming ineffective, and for Mycoplasma genitalium , for which fewer alternative antimicrobial classes are available, incurable infections have already been reported. For Chlamydia trachomatis , in vitro resistance to first-line tetracyclines and macrolides has never been confirmed despite decades of treatment of this highly prevalent STI. Similarly, Treponema pallidum , the cause of syphilis, has remained susceptible to first-line penicillin.

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Sexually transmitted infections and female reproductive health

Cost-effectiveness of resistance-guided therapy for Mycoplasma genitalium in Australia

Li, Y. et al. The estimated lifetime quality-adjusted life-years lost due to chlamydia, gonorrhea, and trichomoniasis in the United States in 2018. J. Infect. Dis. 227 , 1007–1018 (2023).

Article PubMed PubMed Central Google Scholar

Tang, W. et al. Pregnancy and fertility-related adverse outcomes associated with Chlamydia trachomatis infection: a global systematic review and meta-analysis. Sex. Transm. Infect. 96 , 322–329 (2020).

Article PubMed Google Scholar

Hook, E. W., III & Handsfield, H. H. in Sexually Transmitted Diseases (eds Holmes, K. K. et al.) Ch. 35 (McGraw Hill, 2008).

Gomez, G. B. et al. Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis. Bull. World Health Organ. 91 , 217–226 (2013).

Malekinejad, M. et al. Risk of HIV acquisition among men who have sex with men infected with bacterial sexually transmitted infections: a systematic review and meta-analysis. Sex. Transm. Dis. 48 , e138–e148 (2021).

WHO. Global progress report on HIV, viral hepatitis and sexually transmitted infections. World Health Organization https://www.who.int/publications/i/item/9789240027077 (2021).

Furegato, M. et al. Examining the role of socioeconomic deprivation in ethnic differences in sexually transmitted infection diagnosis rates in England: evidence from surveillance data. Epidemiol. Infect. 144 , 3253–3262 (2016).

Article CAS PubMed Google Scholar

Traeger, M. W. et al. Association of HIV preexposure prophylaxis with incidence of sexually transmitted infections among individuals at high risk of HIV infection. JAMA 321 , 1380–1390 (2019).

Bjartling, C., Osser, S. & Persson, K. The frequency of salpingitis and ectopic pregnancy as epidemiologic markers of Chlamydia trachomatis . Acta Obstet. Gynecol. Scand. 79 , 123–128 (2000).

Unemo, M. et al. WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017-18: a retrospective observational study. Lancet Microbe 2 , e627–e636 (2021).

Machalek, D. A. et al. Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium : a systematic review and meta-analysis. Lancet Infect. Dis. 20 , 1302–1314 (2020).

Wang, S. A. et al. Evaluation of antimicrobial resistance and treatment failures for Chlamydia trachomatis : a meeting report. J. Infect. Dis. 191 , 917–923 (2005).

O’Neill, C. E. et al. Chlamydia trachomatis clinical isolates identified as tetracycline resistant do not exhibit resistance in vitro: whole-genome sequencing reveals a mutation in porB but no evidence for tetracycline resistance genes. Microbiology 159 , 748–756 (2013).

Kong, F. Y. S., Horner, P., Unemo, M. & Hocking, J. S. Pharmacokinetic considerations regarding the treatment of bacterial sexually transmitted infections with azithromycin: a review. J. Antimicrob. Chemother. 74 , 1157–1166 (2019).

Geisler, W. M. et al. Azithromycin versus doxycycline for urogenital Chlamydia trachomatis infection. N. Engl. J. Med. 373 , 2512–2521 (2015).

Article CAS PubMed PubMed Central Google Scholar

Sena, A. C. et al. Optimising treatments for sexually transmitted infections: surveillance, pharmacokinetics and pharmacodynamics, therapeutic strategies, and molecular resistance prediction. Lancet Infect. Dis. 20 , e181–e191 (2020).

Molini, B. J. et al. Macrolide resistance in Treponema pallidum correlates with 23S rDNA mutations in recently isolated clinical strains. Sex. Transm. Dis. 43 , 579–583 (2016).

Beale, M. A. et al. Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis. Nat. Microbiol. 6 , 1549–1560 (2021).

Janier, M. et al. 2020 European guideline on the management of syphilis. J. Eur. Acad. Dermatol. Venereol. 35 , 574–588 (2021).

Baumann, L. et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis. Sex. Transm. Infect. 94 , 255–262 (2018).

Sonnenberg, P. et al. Epidemiology of Mycoplasma genitalium in British men and women aged 16-44 years: evidence from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Int. J. Epidemiol. 44 , 1982–1994 (2015).

Manhart, L. E., Holmes, K. K., Hughes, J. P., Houston, L. S. & Totten, P. A. Mycoplasma genitalium among young adults in the United States: an emerging sexually transmitted infection. Am. J. Public Health 97 , 1118–1125 (2007).

Rowley, J. et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull. World Health Organ. 97 , 548–562P (2019).

Unemo, M. et al. Gonorrhoea. Nat. Rev. Dis. Prim. 5 , 79 (2019).

Whelan, J., Abbing-Karahagopian, V., Serino, L. & Unemo, M. Gonorrhoea: a systematic review of prevalence reporting globally. BMC Infect. Dis. 21 , 1152 (2021).

Surveillance atlas of infectious diseases. European Centre for Disease Prevention and Control https://www.ecdc.europa.eu/en/surveillance-atlas-infectious-diseases (2023).

Sonnenberg, P. et al. Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal). Lancet 382 , 1795–1806 (2013).

Unemo, M. et al. Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 2016. Clin. Microbiol. Infect. 24 , 533–539 (2018).

Frølund, M. et al. Urethritis-associated pathogens in urine from men with non-gonococcal urethritis: a case-control study. Acta Derm. Venereol. 96 , 689–694 (2016).

Salado-Rasmussen, K. et al. Clinical importance of superior sensitivity of the Aptima TMA-based assays for Mycoplasma genitalium detection. J. Clin. Microbiol. 60 , e0236921 (2022).

Taylor-Robinson, D. & Jensen, J. S. Mycoplasma genitalium : from chrysalis to multicolored butterfly. Clin. Microbiol. Rev. 24 , 498–514 (2011).

Jensen, J. S. & Bradshaw, C. Management of Mycoplasma genitalium infections — can we hit a moving target? BMC Infect. Dis. 15 , 343 (2015).

Lis, R., Rowhani-Rahbar, A. & Manhart, L. E. Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin. Infect. Dis. 61 , 418–426 (2015).

Clausen, H. F. et al. Serological investigation of Mycoplasma genitalium in infertile women. Hum. Reprod. 16 , 1866–1874 (2001).

Svenstrup, H. F. et al. Mycoplasma genitalium , Chlamydia trachomatis , and tubal factor infertility — a prospective study. Fertil. Steril. 90 , 513–520 (2008).

Lind, K., Lindhardt, B. Ø., Schütten, H. J., Blom, J. & Christiansen, C. Serological cross-reactions between Mycoplasma genitalium and Mycoplasma pneumoniae . J. Clin. Microbiol. 20 , 1036–1043 (1984).

Hocking, J. S., Geisler, W. M. & Kong, F. Y. S. Update on the epidemiology, screening, and management of Chlamydia trachomatis infection. Infect. Dis. Clin. North Am. 37 , 267–288 (2023).

Stamm, W. E. in Sexually Transmitted Diseases (eds Holmes, K. K. et al.) Ch. 32, (McGraw Hill, 2008).

Peeling, R. W., Mabey, D., Chen, X. S. & Garcia, P. J. Syphilis. Lancet 402 , 336–346 (2023).

Gilmour, L. S. & Walls, T. Congenital syphilis: a review of global epidemiology. Clin. Microbiol. Rev. 36 , e0012622 (2023).

Lanjouw, E. et al. 2015 European guideline on the management of Chlamydia trachomatis infections. Int. J. STD AIDS 27 , 333–348 (2016).

Article CAS Google Scholar

Day, M. J. et al. Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016. BMC Infect. Dis. 18 , 609 (2018).

Unemo, M. et al. World Health Organization Global Gonococcal Antimicrobial Surveillance Program (WHO GASP): review of new data and evidence to inform international collaborative actions and research efforts. Sex. Health 16 , 412–425 (2019).

Wi, T. et al. Antimicrobial resistance in Neisseria gonorrhoeae : global surveillance and a call for international collaborative action. PloS Med. 14 , e1002344 (2017).

Fifer, H., Saunders, J., Soni, S., Sadiq, S. T. & FitzGerald, M. 2018 UK national guideline for the management of infection with Neisseria gonorrhoeae . Int. J. STD AIDS 31 , 4–15 (2020).

Workowski, K. A. et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm. Rep. https://doi.org/10.15585/mmwr.rr7004a1 (2021).

Unemo, M. et al. 2020 European guideline for the diagnosis and treatment of gonorrhoea in adults. Int. J. STD AIDS https://doi.org/10.1177/0956462420949126 (2020).

Hamasuna, R. et al. The JAID/JSC guidelines to Clinical Management of Infectious Disease 2017 concerning male urethritis and related disorders. J. Infect. Chemother. 27 , 546–554 (2021).

Guidelines of Clinical Management of Sexually Transmitted Diseases [in Chinese]. (Shanghai Science and Technology Press, 2020).

WHO guidelines for the treatment of Neisseria gonorrhoeae . World Health Organization https://apps.who.int/iris/bitstream/handle/10665/246114/9789241549691-eng.pdf;jsessionid=7B95502B9A64B5FCDF3E7AE5F88087D6?sequence=1 (2016).

Public Health Agency of Canada . Gonorrhea guide: key information and resources. Government of Canada https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/gonorrhea.html#a2 (2023).

The Australasian STI management guidelines, gonorrhoea. The Australasian Sexual and Reproductive Health Alliance (ASHA) https://www.sti.guidelines.org.au/sexually-transmissible-infections/gonorrhoea (2021).

Chisholm, S. A. et al. Cephalosporin MIC creep among gonococci: time for a pharmacodynamic rethink? J. Antimicrob. Chemother. 65 , 2141–2148 (2010).

Theuretzbacher, U. et al. Pharmacokinetic/pharmacodynamic considerations for new and current therapeutic drugs for uncomplicated gonorrhoea — challenges and opportunities. Clin. Microbiol. Infect. 26 , 1630–1635 (2020).

Jacobsson, S. et al. Pharmacodynamics of zoliflodacin plus doxycycline combination therapy against Neisseria gonorrhoeae in a gonococcal hollow-fiber infection model. Front. Pharmacol. 14 , 1291885 (2023).

Jacobsson, S. et al. Pharmacodynamic evaluation of lefamulin in the treatment of gonorrhea using a hollow fiber infection model simulating Neisseria gonorrhoeae infections. Front. Pharmacol. 13 , 1035841 (2022).

Jacobsson, S. et al. Pharmacodynamic evaluation of zoliflodacin treatment of Neisseria gonorrhoeae strains with amino acid substitutions in the zoliflodacin target GyrB using a dynamic hollow fiber infection model. Front. Pharmacol. 13 , 874176 (2022).

Jacobsson, S. et al. Pharmacodynamic evaluation of dosing, bacterial kill, and resistance suppression for zoliflodacin against Neisseria gonorrhoeae in a dynamic hollow fiber infection model. Front. Pharmacol. 12 , 682135 (2021).

Bradshaw, C. S., Jensen, J. S. & Waites, K. B. New horizons in Mycoplasma genitalium treatment. J. Infect. Dis. 216 , S412–S419 (2017).

Horner, P. et al. Which azithromycin regimen should be used for treating Mycoplasma genitalium ? A meta-analysis. Sex. Transm. Infect. 94 , 14–20 (2018).

Waites, K. B., Crabb, D. M., Atkinson, T. P., Geisler, W. M. & Xiao, L. Omadacycline is highly active in vitro against Mycoplasma genitalium . Microbiol. Spectr. 10 , e0365422 (2022).

Falk, L., Fredlund, H. & Jensen, J. S. Tetracycline treatment does not eradicate Mycoplasma genitalium . Sex. Transm. Infect. 79 , 318–319 (2003).

Manhart, L. E. et al. Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial. Clin. Infect. Dis. 56 , 934–942 (2013).

Read, T. R. H. et al. Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: a prospective evaluation. Clin. Infect. Dis. 68 , 554–560 (2018).

Article PubMed Central Google Scholar

Jensen, J. S. et al. 2021 European guideline on the management of Mycoplasma genitalium infections. J. Eur. Acad. Dermatol. Venereol. 36 , 641–650 (2022).

The Australasian STI management guidelines, Mycoplasma genitalium . The Australasian Sexual and Reproductive Health Alliance (ASHA) http://www.sti.guidelines.org.au/sexually-transmissible-infections/mycoplasma-genitalium (2021).

Soni, S. et al. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int. J. STD AIDS 30 , 938–950 (2019).

Bradshaw, C. S., Chen, M. Y. & Fairley, C. K. Persistence of Mycoplasma genitalium following azithromycin therapy. PloS ONE 3 , e3618 (2008).

Read, T. R. H. et al. Use of pristinamycin for macrolide-resistant mycoplasma genitalium infection. Emerg. Infect. Dis. 24 , 328–335 (2018).

Doyle, M. et al. Nonquinolone options for the treatment of Mycoplasma genitalium in the era of increased resistance. Open Forum Infect. Dis. 7 , ofaa291 (2020).

Kong, F. Y. et al. The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis. J. Antimicrob. Chemother. 70 , 1290–1297 (2015).

Dukers-Muijrers, N. H., Schachter, J., van Liere, G. A., Wolffs, P. F. & Hoebe, C. J. What is needed to guide testing for anorectal and pharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae in women and men? Evidence and opinion. BMC Infect. Dis. 15 , 533 (2015).

Jensen, J. S., Bradshaw, C. S., Tabrizi, S. N., Fairley, C. K. & Hamasuna, R. Azithromycin treatment failure in Mycoplasma genitalium -positive patients with nongonococcal urethritis is associated with induced macrolide resistance. Clin. Infect. Dis. 47 , 1546–1553 (2008).

Unemo, M. & Shafer, W. M. Antimicrobial resistance in Neisseria gonorrhoeae in the 21st century: past, evolution, and future. Clin. Microbiol. Rev. 27 , 587–613 (2014).

Golparian, D. et al. Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928-2013): antimicrobial use/misuse selects for resistance and drives evolution. BMC Genom. 21 , 116 (2020).

Golparian, D. & Unemo, M. Antimicrobial resistance prediction in Neisseria gonorrhoeae : current status and future prospects. Expert Rev. Mol. Diagn. 22 , 29–48 (2022).

Sanchez-Buso, L. et al. A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch. Genome Med. 13 , 61 (2021).

Ohnishi, M. et al. Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob. Agents Chemother. 55 , 3538–3545 (2011).

Unemo, M. & Nicholas, R. A. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 7 , 1401–1422 (2012).

Bignell, C. & Unemo, M. European guideline on the diagnosis and treatment of gonorrhoea in adults. Int. J. STD AIDS 24 , 2013 (2012).

Google Scholar

Bignell, C., Fitzgerald, M., Guideline Development Group & British Association for Sexual Health & HIV UK., UK national guideline for the management of gonorrhoea in adults, 2011. Int. J. STD AIDS 22 , 541–547 (2011).

Fifer, H. et al. Failure of dual antimicrobial therapy in treatment of gonorrhea. N. Engl. J. Med. 374 , 2504–2506 (2016).

Nakayama, S. et al. New ceftriaxone- and multidrug-resistant Neisseria gonorrhoeae strain with a novel mosaic penA gene isolated in Japan. Antimicrob. Agents Chemother. 60 , 4339–4341 (2016).

Lahra, M. M. et al. Cooperative recognition of internationally disseminated ceftriaxone-resistant Neisseria gonorrhoeae strain. Emerg. Infect. Dis. 24 , 735–740 (2018).

Golparian, D. et al. Multidrug-resistant Neisseria gonorrhoeae isolate, belonging to the internationally spreading Japanese FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, Ireland, August 2018. Eur. Surveill. 23 , 1800617 (2018).

Article Google Scholar

Lefebvre, B. et al. Ceftriaxone-resistant Neisseria gonorrhoeae , Canada, 2017. Emerg. Infect. Dis. 24 , 381–383 (2018).

Terkelsen, D. et al. Multidrug-resistant Neisseria gonorrhoeae infection with ceftriaxone resistance and intermediate resistance to azithromycin, Denmark, 2017. Eur. Surveill. 22 , 17-00659 (2017).

Poncin, T. et al. Multidrug-resistant Neisseria gonorrhoeae failing treatment with ceftriaxone and doxycycline in France, November 2017. Eur. Surveill. 23 , 1800264 (2018).

Ko, K. K. K. et al. First case of ceftriaxone-resistant multidrug-resistant neisseria gonorrhoeae in Singapore. Antimicrob. Agents Chemother. 63 , e02624–e02718 (2019).

Eyre, D. W. et al. Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018. Eur. Surveill. 24 , 1900147 (2019).

Day, M. et al. Detection of 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae in the United Kingdom, December 2021 to June 2022. Eur. Surveill. 27 , 2200803 (2022).

Lin, X. et al. Dissemination and genome analysis of high-level ceftriaxone-resistant penA 60.001 Neisseria gonorrhoeae strains from the Guangdong Gonococcal Antibiotics Susceptibility Programme (GD-GASP), 2016-2019. Emerg. Microbes Infect. 11 , 344–350 (2022).

Lee, K. et al. Clonal expansion and spread of the ceftriaxone-resistant Neisseria gonorrhoeae strain FC428, identified in Japan in 2015, and closely related isolates. J. Antimicrob. Chemother. 74 , 1812–1819 (2019).

Ouk, V. et al. The enhanced gonococcal surveillance programme, Cambodia. Lancet Infect. Dis. 23 , e332–e333 (2023).

Jennison, A. V. et al. Genetic relatedness of ceftriaxone-resistant and high-level azithromycin resistant Neisseria gonorrhoeae cases, United Kingdom and Australia, February to April 2018. Eur. Surveill. 24 , 1900118 (2019).

Eyre, D. W. et al. Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018. Eur. Surveill. 23 , 1800323 (2018).

Pleininger, S. et al. Extensively drug-resistant (XDR) Neisseria gonorrhoeae causing possible gonorrhoea treatment failure with ceftriaxone plus azithromycin in Austria, April 2022. Eur. Surveill. 27 , 2200455 (2022).

van der Veen, S. Global transmission of the penA Allele 60.001-containing high-level ceftriaxone-resistant gonococcal FC428 clone and antimicrobial therapy of associated cases: a review. Infect. Microbes Dis. 5 , 13–20 (2023).

Golparian, D. et al. Multidrug-resistant Neisseria gonorrhoeae isolate SE690: mosaic penA-60.001 gene causing ceftriaxone resistance internationally has spread to the more antimicrobial-susceptible genomic lineage, Sweden, September 2022. Eur. Surveill. 28 , 2300125 (2023).

Al-Maslamani, M. et al. First characterisation of antimicrobial susceptibility and resistance of Neisseria gonorrhoeae isolates in Qatar, 2017-2020. PloS ONE 17 , e0264737 (2022).

Machado, H. M. et al. National surveillance of Neisseria gonorrhoeae antimicrobial susceptibility and epidemiological data of gonorrhoea patients across Brazil, 2018-20. JAC Antimicrob. Resist. 4 , dlac076 (2022).

Aniskevich, A. et al. Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009-2019. BMC Infect. Dis. 21 , 520 (2021).

Congo-Ouedraogo, M. et al. Genomic and antimicrobial resistance analyses of Neisseria gonorrhoeae isolates, Burkina Faso, 2018-2019. J. Eur. Acad. Dermatol. Venereol. 36 , e565–e568 (2022).

Lahra, M. M., Shoushtari, M. & Hogan, T. R. Australian Gonococcal Surveillance Programme 1 April to 30 June 2021. Commun. Dis. Intell . https://doi.org/10.33321/cdi.2021.45.68 (2021).

Thorington, R. S. et al. Antimicrobial susceptibilities of Neisseria gonorrhoeae in Canada, 2020. Can. Commun. Dis. Rep. 48 , 571–579 (2022).

UK Health Security Agency. Antimicrobial resistance in Neisseria gonorrhoeae in England and Wales: key findings from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2021). UK Health Security Agency https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1118837/GRASP_2021_report.pdf (2022).

Sexually Transmitted Disease Surveillance 2020: Gonococcal Isolate Surveillance Project (GISP). Centers for Disease Control and Prevention https://www.cdc.gov/std/gisp/default.htm (2022).

Sarenje, K. L. et al. Antimicrobial resistance of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Urban Hospitals, Lusaka, Zambia. BMC Infect. Dis. 22 , 688 (2022).

Harris, S. R. et al. Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey. Lancet Infect. Dis. 18 , 758–768 (2018).

Golparian, D. et al. Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015-16. J. Antimicrob. Chemother. 75 , 3163–3172 (2020).

Golparian, D. et al. Genomic surveillance and antimicrobial resistance in Neisseria gonorrhoeae isolates in Bangkok, Thailand in 2018. J. Antimicrob. Chemother. 77 , 2171–2182 (2022).

Gianecini, R. A. et al. Genome-based epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates with decreased susceptibility and resistance to extended-spectrum cephalosporins in Argentina in 2011-16. J. Antimicrob. Chemother. 74 , 1551–1559 (2019).

Lan, P. T. et al. Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015-16. J. Antimicrob. Chemother. 75 , 1432–1438 (2020).

Town, K. et al. Genomic and phenotypic variability in Neisseria gonorrhoeae antimicrobial susceptibility, England. Emerg. Infect. Dis. 26 , 505–515 (2020).

Yahara, K. et al. Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae . Genome Med. 13 , 51 (2021).

Peng, J. P. et al. A whole-genome sequencing analysis of Neisseria gonorrhoeae isolates in China: an observational study. EClinicalMedicine 7 , 47–54 (2019).

Grad, Y. H. et al. Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study. Lancet Infect. Dis. 14 , 220–226 (2014).

Demczuk, W. et al. Genomic epidemiology and molecular resistance mechanisms of azithromycin-resistant Neisseria gonorrhoeae in Canada from 1997 to 2014. J. Clin. Microbiol. 54 , 1304–1313 (2016).

Reimche, J. L. et al. Genomic analysis of the predominant strains and antimicrobial resistance determinants within 1479 Neisseria gonorrhoeae isolates from the US Gonococcal Isolate Surveillance Project in 2018. Sex. Transm. Dis. 48 , S78–S87 (2021).

Hadad, R. et al. First national genomic epidemiological study of Neisseria gonorrhoeae strains spreading across Sweden in 2016. Front. Microbiol. 12 , 820998 (2021).

Sanchez-Buso, L. et al. Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study. Lancet Microbe 3 , e452–e463 (2022).

Kakooza, F. et al. Genomic surveillance and antimicrobial resistance determinants in Neisseria gonorrhoeae isolates from Uganda, Malawi and South Africa, 2015-20. J. Antimicrob. Chemother. 78 , 1982–1991 (2023).

Jensen, J. S., Fernandes, P. & Unemo, M. In vitro activity of the new fluoroketolide solithromycin (CEM-101) against macrolide-resistant and -susceptible Mycoplasma genitalium strains. Antimicrob. Agents Chemother. 58 , 3151–3156 (2014).

Kenyon, C., Manoharan-Basil, S. S. & Van Dijck, C. Is there a resistance threshold for macrolide consumption? Positive evidence from an ecological analysis of resistance data from Streptococcus pneumoniae, Treponema pallidum , and Mycoplasma genitalium . Microb. Drug Resist. 27 , 1079–1086 (2021).

Read, T. R. et al. Azithromycin 1.5g over 5 days compared to 1g single dose in urethral mycoplasma genitalium: impact on treatment outcome and resistance. Clin. Infect. Dis. 64 , 250–256 (2017).

Shimada, Y. et al. Emergence of clinical strains of Mycoplasma genitalium harbouring alterations in ParC associated with fluoroquinolone resistance. Int. J. Antimicrob. Agents 36 , 255–258 (2010).

Hamasuna, R. et al. Mutations in ParC and GyrA of moxifloxacin-resistant and susceptible Mycoplasma genitalium strains. PloS ONE 13 , e0198355 (2018).

Li, Y. et al. Mycoplasma genitalium in symptomatic male urethritis: macrolide use is associated with increased resistance. Clin. Infect. Dis. 70 , 805–810 (2020).

Hamasuna, R. et al. Analysis of fluoroquinolone-resistance using MIC determination and homology modelling of ParC of contemporary Mycoplasma genitalium strains. J. Infect. Chemother. 28 , 377–383 (2022).

Murray, G. L. et al. parC variants in Mycoplasma genitalium : trends over time and association with moxifloxacin failure. Antimicrob. Agents Chemother. 66 , e0027822 (2022).

Sweeney, E. L., Bradshaw, C. S., Murray, G. L. & Whiley, D. M. Individualised treatment of Mycoplasma genitalium infection-incorporation of fluoroquinolone resistance testing into clinical care. Lancet Infect. Dis. 22 , e267–e270 (2022).

Murray, G. L. et al. gyrA mutations in Mycoplasma genitalium and their contribution to moxifloxacin failure: time for the next generation of resistance-guided therapy. Clin. Infect. Dis. 76 , 2187–2195 (2023).

Damiao Gouveia, A. C., Unemo, M. & Jensen, J. S. In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains. J. Antimicrob. Chemother. 73 , 1291–1294 (2018).

Jensen, J. S., Norgaard, C., Scangarella-Oman, N. & Unemo, M. In vitro activity of the first-in-class triazaacenaphthylene gepotidacin alone and in combination with doxycycline against drug-resistant and -susceptible Mycoplasma genitalium . Emerg. Microbes Infect. 9 , 1388–1392 (2020).

Wood, G. E. et al. Azithromycin and doxycycline resistance profiles of U.S. Mycoplasma genitalium strains and their association with treatment outcomes. J. Clin. Microbiol. 59 , e0081921 (2021).

Chopra, I. & Roberts, M. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 65 , 232–260 (2001).

Amram, E. et al. 16S rRNA gene mutations associated with decreased susceptibility to tetracycline in Mycoplasma bovis . Antimicrob. Agents Chemother. 59 , 796–802 (2015).

Chua, T. P. et al. Impact of 16S rRNA single nucleotide polymorphisms on Mycoplasma genitalium organism load with doxycycline treatment. Antimicrob. Agents Chemother. 66 , e0024322 (2022).

Le Roy, C. et al. Identification of 16S rRNA mutations in Mycoplasma genitalium potentially associated with tetracycline resistance in vivo but not selected in vitro in M. genitalium and Chlamydia trachomatis . J. Antimicrob. Chemother. 76 , 1150–1154 (2021).

Waites, K. B., Crabb, D. M., Xiao, L., Duffy, L. B. & Leal, S. M. Jr In vitro activities of eravacycline and other antimicrobial agents against human mycoplasmas and ureaplasmas. Antimicrob. Agents Chemother. 64 , e00698–e00720 (2020).

Fernandez-Huerta, M. et al. Single-locus-sequence-based typing of the mgpB gene reveals transmission dynamics in Mycoplasma genitalium . J. Clin. Microbiol. 58 , e01886–e01919 (2020).

Fookes, M. C. et al. Mycoplasma genitalium : whole genome sequence analysis, recombination and population structure. BMC Genom. 18 , 993 (2017).

McGowin, C. L. et al. Draft genome sequences of four axenic Mycoplasma genitalium strains isolated from Denmark, Japan, and Australia. J. Bacteriol. 194 , 6010–6011 (2012).

Jensen, J. S., Hansen, H. T. & Lind, K. Isolation of Mycoplasma genitalium strains from the male urethra. J. Clin. Microbiol. 34 , 286–291 (1996).

Molina, J. M. et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect. Dis. 18 , 308–317 (2018).

Luetkemeyer, A. F. et al. Postexposure doxycycline to prevent bacterial sexually transmitted infections. N. Engl. J. Med. 388 , 1296–1306 (2023).

Unemo, M. & Kong, F. Y. S. Doxycycline-PEP — novel and promising but needs monitoring. Nat. Rev. Urol. 20 , 522–523 (2023).

Kong, F. Y. S., Kenyon, C. & Unemo, M. Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections. J. Antimicrob. Chemother. 78 , 1561–1568 (2023).

Reichert, E. & Grad, Y. H. Resistance and prevalence implications of doxycycline post-exposure prophylaxis for gonorrhea prevention in men who have sex with men: a modeling study. Preprint at medRxiv https://doi.org/10.1101/2023.04.24.23289033 (2023).

Marti, H. et al. Tet(C) gene transfer between Chlamydia suis strains occurs by homologous recombination after co-infection: implications for spread of tetracycline-resistance among Chlamydiaceae . Front. Microbiol. 8 , 156 (2017).

Chen, M. Y. et al. Solithromycin versus ceftriaxone plus azithromycin for the treatment of uncomplicated genital gonorrhoea (SOLITAIRE-U): a randomised phase 3 non-inferiority trial. Lancet Infect. Dis. 19 , 833–842 (2019).

Hook, E. W. III et al. Efficacy and safety of single-dose oral delafloxacin compared with intramuscular ceftriaxone for uncomplicated gonorrhea treatment: an open-label, noninferiority, phase 3, multicenter, randomized study. Sex. Transm. Dis. 46 , 279–286 (2019).

Golparian, D. et al. GyrB in silico mining in 27 151 global gonococcal genomes from 1928-2021 combined with zoliflodacin in vitro testing of 71 international gonococcal isolates with different GyrB, ParC and ParE substitutions confirms high susceptibility. J. Antimicrob. Chemother. 78 , 150–154 (2022).

Unemo, M. et al. High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinical Neisseria gonorrhoeae isolates from 25 European countries, 2018. J. Antimicrob. Chemother. 76 , 1221–1228 (2021).

Taylor, S. N. et al. Single-dose zoliflodacin (ETX0914) for treatment of urogenital gonorrhea. N. Engl. J. Med. 379 , 1835–1845 (2018).

Jacobsson, S., Golparian, D., Scangarella-Oman, N. & Unemo, M. In vitro activity of the novel triazaacenaphthylene gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae . J. Antimicrob. Chemother. 73 , 2072–2077 (2018).

Article CAS PubMed Central Google Scholar

Taylor, S. N. et al. Gepotidacin for the treatment of uncomplicated urogenital gonorrhea: a phase 2, randomized, dose-ranging, single-oral dose evaluation. Clin. Infect. Dis. 67 , 504–512 (2018).

Scangarella-Oman, N. E. et al. Microbiological analysis from a phase 2 randomized study in adults evaluating single oral doses of gepotidacin in the treatment of uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae . Antimicrob. Agents Chemother. 62 , e01221–e01318 (2018).

Positive results announced in largest pivotal phase 3 trial of a first-in-class oral antibiotic to treat uncomplicated gonorrhoea. Global Antibiotic Research & Development Partnership (GARDP) https://gardp.org/positive-results-announced-in-largest-pivotal-phase-3-trial-of-a-first-in-class-oral-antibiotic-to-treat-uncomplicated-gonorrhoea/ (2023).

Bradford, P. A., Miller, A. A., O’Donnell, J. & Mueller, J. P. Zoliflodacin: an oral spiropyrimidinetrione antibiotic for the treatment of Neisseria gonorrheae , including multi-drug-resistant isolates. ACS Infect. Dis. 6 , 1332–1345 (2020).

Jacobsson, S., Paukner, S., Golparian, D., Jensen, J. S. & Unemo, M. In vitro activity of the novel pleuromutilin lefamulin (BC-3781) and effect of efflux pump inactivation on multidrug-resistant and extensively drug-resistant Neisseria gonorrhoeae . Antimicrob. Agents Chemother. 61 , e01497–e01517 (2017).

Jacobsson, S., Mason, C., Khan, N., Meo, P. & Unemo, M. In vitro activity of the novel oral antimicrobial SMT-571, with a new mechanism of action, against MDR and XDR Neisseria gonorrhoeae : future treatment option for gonorrhoea? J. Antimicrob. Chemother. 74 , 1591–1594 (2019).

Edwards, J. L. et al. Potent in vitro and ex vivo anti-gonococcal activity of the RpoB inhibitor corallopyronin A. mSphere 7 , e0036222 (2022).

Jonsson, A. et al. In vitro activity and time-kill curve analysis of sitafloxacin against a global panel of antimicrobial-resistant and multidrug-resistant Neisseria gonorrhoeae isolates. APMIS 126 , 29–37 (2018).

Unemo, M. et al. Sexually transmitted infections: challenges ahead. Lancet Infect. Dis. 17 , e235–e279 (2017).

Paukner, S., Gruss, A. & Jensen, J. S. In vitro activity of lefamulin against sexually transmitted bacterial pathogens. Antimicrob. Agents Chemother. 62 , e02380–e02417 (2018).

Manhart, L. E. et al. Effectiveness of lefamulin for Mycoplasma genitalium (MG) treatment failures in Australia and the United States (US). STI & HIV 2023 World Congress https://stihiv2023.eventscribe.net/fsPopup.asp?efp=Rk1IS0dYVEYxOTcxMA&PosterID=585522&rnd=0.679136&mode=posterInfo (2023).

Wood, G. E., Kim, C. M., Aguila, L. K. T. & Cichewicz, R. H. In vitro susceptibility and resistance of Mycoplasma genitalium to nitroimidazoles. Antimicrob. Agents Chemother. 67 , e0000623 (2023).

Wiesenfeld, H. C., Meyn, L. A., Darville, T., Macio, I. S. & Hillier, S. L. A randomized controlled trial of ceftriaxone and doxycycline, with or without metronidazole, for the treatment of acute pelvic inflammatory disease. Clin. Infect. Dis. 72 , 1181–1189 (2021).

Goodfellow, J. J. et al. Novel use of oral chloramphenicol for treatment-resistant Mycoplasma genitalium . Sex. Transm. Infect. 99 , 208–210 (2023).

PubMed Google Scholar

Saito, I. Clinical evaluation of thiamphenicol in treatment of nongonococcal urethritis. Sex. Transm. Dis. 11 , 460–462 (1984).

Ferreyra, C. et al. Developing target product profiles for Neisseria gonorrhoeae diagnostics in the context of antimicrobial resistance: an expert consensus. PloS ONE 15 , e0237424 (2020).

Wi, T. E. et al. Diagnosing sexually transmitted infections in resource-constrained settings: challenges and ways forward. J. Int. AIDS Soc. 22 , e25343 (2019).

Toskin, I. et al. Call to action for health systems integration of point-of-care testing to mitigate the transmission and burden of sexually transmitted infections. Sex. Transm. Infect. 96 , 342–347 (2020).

Public Health Agency of Canada. Mycoplasma genitalium guide: key information and resources. Government of Canada https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/mycoplasma-genitalium.html#Key_information (2023).

Wada, K., Hamasuna, R., Sadahira, T., Araki, M. & Yamamoto, S. UAA-AAUS guideline for M. genitalium and non-chlamydial non-gonococcal urethritis. J. Infect. Chemother. 27 , 1384–1388 (2021).

Pham, C. D. et al. Atypical mutation in Neisseria gonorrhoeae 23S rRNA associated with high-level azithromycin resistance. Antimicrob. Agents Chemother. 65 , e00885–e00920 (2021).

The Global Health Observatory. Proportion of isolates tested (WHO-GASP). World Health Organization https://www.who.int/data/gho/data/themes/topics/indicator-groups/indicator-group-details/GHO/proportion-of-isolates-tested-(who-gasp-amr) (2024).

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The authors are very grateful to the WHO and the WHO Global Gonococcal Antimicrobial Surveillance Program (GASP), especially T. Wi, M. Escher and I. Maatouk, for sharing antimicrobial resistance data for N. gonorrhoeae .

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Jensen, J.S., Unemo, M. Antimicrobial treatment and resistance in sexually transmitted bacterial infections. Nat Rev Microbiol 22 , 435–450 (2024). https://doi.org/10.1038/s41579-024-01023-3

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Indian J Med Res
v.138(3); 2013 Sep

Genital Chlamydia trachomatis : An update

Meenakshi malhotra.

* Regional STD Teaching, Training & Research Center, Vardhman Mahavir Medical College & Safdarjang Hospital, New Delhi, India

Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India

Anjan Mukherjee

Sumathi muralidhar.

Chlamydia trachomatis is the most common cause of curable bacterial sexually transmitted infection (STI) worldwide. It manifests primarily as urethritis in males and endocervicitis in females. Untreated chlamydial infection in man can cause epididymitis and proctitis. Though most women with Chlamydia infection are asymptomatic or have minimal symptoms, some develop salpingitis, endometritis, pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility. It is associated with an increased risk for the transmission or acquisition of HIV and is also attributed to be a risk factor for the development of cervical carcinoma. Early diagnosis and treatment of infected individuals is required to prevent the spread of the disease and severe sequelae. Traditionally, tissue culture was considered the gold standard for the diagnosis. However, with the availability of newer diagnostic techniques particularly molecular methods which are not only highly sensitive and specific but are cost-effective also, the diagnosis has became fast and easy. The purpose of this review is to study the various aspects of genital C. trachomatis infection. Also the advances related to the clinical picture, various diagnostic modalities, prevention, treatment, drug resistance and control measures will be dealt with.

Introduction

Chlamydia trachomatis is the most common bacterial sexually transmitted infections worldwide 1 , and women carry the major burden of the disease. These women are also a potential source of infection to their partners. It causes urethritis in men and mucopurulent cervicitis, urethritis, and endometritis in women. Mucopurulent cervicitis can lead to at least three types of complications 2 - ascending intraluminal spread of organism from cervix producing pelvic inflammatory disease (PID); ascending infection during pregnancy resulting in premature rupture of the membrane, chorioamnionitis, premature delivery and puerperal and neonatal infections (conjunctivitis and possibly intestitial pneumonia); and also an increased risk of the development of cervical carcinoma 2 . A 3- to 4-fold increased risk of transmission of HIV is an added cause of concern 3 . The incidence of chlamydial infections in women has increased dramatically from 79 to 467 per 100,000 between 1987 and 2003 4 . According to the World Health Organization (WHO) 1 , 101 million chlamydial infections are detected annually worldwide. The clinical presentation, course, complications and late sequelae of C. trachomatis closely resemble Neisseria gonorrhoeae infection.

C. trachomatis is also considered to be a leading cause of PID and female infertility worldwide. More than 13.5 per cent of women less than 25 yr old infected with C. trachomatis have lower genital tract infection, reducing to 4.4 per cent in women 25 yr and above 5 . In USA, approximately 20-30 per cent of PID cases have been attributed to C. trachomatis 6 . Recent studies from India have revealed the prevalence of C. trachomatis infection to be 23 per cent in gynaecology outpatient department (OPD) 7 and 19.9 per cent in STD patients 8 .

It has been recovered from 30-60 per cent cases of salpingitis and PID 9 patients in India, while sero-prevalance is shown to be higher in at least one recent study 10 . An estimated 15-40 per cent of women with cervical chlamydial infections develop PID 11 . Twenty per cent of women who develop PID become infertile, 18 per cent develop chronic pelvic pain, and nine per cent have a tubal pregnancy 12 .

Neonates are also at risk while passing through the contaminated birth canal during parturition. Screening young women for Chlamydia has been proven to be a cost-effective method of preventing PID. The US Preventive Services Task Force (USPSTF) 13 recommends that all women aged ≤24 yr receive routine screening for Chlamydia . However, insufficient evidence was found to recommend for or against routine screening for chlamydial infection in asymptomatic males 13 .

The challenge being faced in the control of chlamydial disease is that as many as 70-80 per cent of women and up to 50 per cent men have asymptomatic infection 14 . This results in a large reservoir of unrecognized, infected individuals who are capable of transmitting the infection to their sexual partners. Further, the sequelae of C. trachomatis infection in women, namely PID, infertility and ectopic pregnancy, is the most costly outcome of any STD except HIV or AIDS 15 . This review covers the various aspects of genital chlamydial infection as also the clinical picture, various diagnostic modalities, prevention, treatment and control measures.

Chlamydia trachomatis - the microorganism

Chlamydiae are spherical or ovoid obligate intracellular bacteria that are ubiquitous. Intracellular parasitism of Chlamydia differentiates it from other bacteria. Unlike viruses, Chlamydiae possess both DNA and RNA, multiply by binary fission rather than self-assembly, contain their own ribosome, have a peptidoglycan free cell wall and are susceptibile to various antimicrobial agents 16 .

Immunopathogenesis

C. trachomatis is a strong immunogen, which stimulates both humoral and cell mediated immune responses. In addition to the immunogenic antigens, the outcome of chlamydial infection depends on interaction and balance of cytokines secreted by the activated lymphocytes. Interferon gamma (IFN-γ) has been described as a single most important factor in host defense against Chlamydia , while disease susceptibility has been linked with enhanced expression of Interleukin- 10 (IL-10) 17 . Immune system changes or disturbances induced by C. trachomatis may favour its own survival in the infected host, and induce persistent infections.

C. trachomatis infection may be primary or a chronic recurrence/re-infection.

(i) Primary infection: A serial infection of the mucosal cells is seen during the primary infection. The damaging and infected epithelial cells secrete numerous pro-inflammatory chemokines and cytokines, including IL-1, IL-6, IL-8, granulocyte - macrophage colony stimulating factor (GM-CSF), growth regulated oncogene, and tumour necrosis factor alpha (TNF-α) 18 , 19 . The released cytokines cause vasodilatation, increased endothelial permeability, activation and influx of neutrophils, monocytes and T-lymphocytes, and elevated expression of adhesion molecules. In addition, it stimulates other cells to secrete cytokines. Neutrophils appear to play a role in reducing the initial amplification of C. trachomatis and possibly in limiting the spread within the female genital tract. IL-1 is secreted initially by the undamaged cells and stimulates the secretion of other cytokines from other non-infected cells, like TNF-α 20 . During the same period, Chlamydia passes via lymphatic vessels to local lymph nodes. The decaying epithelial cells release a few elementary bodies which are phagocytosed by neutrophills through phagolysosomes.

T lymphocytes mainly T helper cells (Th1) play an important role during early phase of infection, which, due to Chlamydia antigen-induced activation, secrete IFN-γ, necessary for infection regression. It increases the potential of various phagocytes to destroy Chlamydia and stimulates the secretion of other cytokines, including IL-1. IL-1, in turn, by stimulating the secretion of IL-2 by Th1 cells causes increased replication of cytotoxic lymphocytes and natural killer cells 21 . The role of secretory IgA has also been established in the neutralization of primary infection 22 .

An intimate relationship between chlamydia and the host immune system has been described by Paavoven 23 . It has been observed that a single acute episode of chlamydial infection cannot lead to serious sequelae associated with this infection, persistent infection may be responsible for the grave consequences.

(ii) Chronic infection - recurrence/reinfection: Chronic infection, associated with persistence of Chlamydia in the host cells, recurrent infection or reinfection are more dangerous. A delayed hypersensitivity reaction or rarely type 3 hypersensitivity reactions (Arthus reaction) is observed in long term or recurrent stimulatory action of chlamydial antigens 23 . Antibodies are not involved in the delayed type of reaction developing within 24-48 h due to antigen interaction with specifically sensitized Th1 lymphocytes. Processes which occur during these reactions lead to tissue damage, fibrosis and cicatrization within the affected organs. Irreversible consequences like PID leading to mechanical infertility, ectopic pregnancy, chronic pelvic pains and chronic urethritis may occur. After a single episode of salpingitis about one in 10 patients become infertile because of tubal occlusion. After 2-3 episodes, infertility ensues in about 35-70 per cent cases. In several studies, repeated chlamydial infection was associated with PID and other reproductive sequelae, although it was difficult to determine whether the risk per infection increased with recurrent episode 25 . Lack of treatment or improper therapeutic management may result in chronic infection. A significant role of dietary factors like insufficient supply of tryptophan, L-isoleucine, and cysteine in diet, as well as certain cytokines like INF-γ, TNF-α, transforming growth factor has been observed 26 .

Formation of atypical chlamydial forms in vitro has been demonstrated in INFγ treated cells. The atypical forms 26 are large, non-infectious, have reduced metabolic activity, and do not replicate, yet remain alive. Such atypical forms display decreased levels of chlamydial major outer membrane protein (MOMP) and lipopolysaccharide (LPS) antigens but continue with high production of chlamydial heat shock protein 60 (hsp60), which is capable of inducing chronic inflammation and scarring. Chronic and occult infections pose several diagnostic and therapeutic problems. Due to the variable antigenic structure of atypical forms, the routine diagnostic methods do not always identify them. Moreover, these forms have reduced MOMPs which lead to decreased transport of antibiotic across the cell. Therefore, in case of chronic infections, therapy frequently results in failure.

Reinfection is due to the repeated infection, while recurrence is caused by the presence of a Chlamydia reservoir in the lymph node and spleen 26 . Macrophages have been found to play an important role in the recurrence of infection as C. trachomatis circulates within the macrophages, finding a temporary shelter in the lymph nodes, spleen and serous cavities. It has been observed that recurrences were more frequent in young patients with prolongation of the active period in comparison with patients in older age group 27 . The less common spread of infection in the older age group has been attributed to low exposure to C. trachomatis and by physiological changes which reduce sensitivity to the acquisition 26 .

Risk factors and demographic factors for Chlamydia trachomatis infection

The most common demographic correlate 16 of infection with chlamydial infection in women is young age (<20 yr). This could be explained by the anatomic differences in the cervix of the younger women, wherein the squamo-columnar junction, a primary host target for C. trachomatis , is everted and thus more exposed. Other factors associated with chlamydial infection include unmarried status, nulliparity, black race and poor socio-economic condition 28 . A large number of sexual partners, a new sexual partner, lack of use of barrier contraceptive devices and concurrent gonococcal infection are also known to be associated with chlamydial infection 29 . Cervical chlamydial infections are also found to be associated with the use of oral contraceptives 29 .

Epidemiology

C. trachomatis was detected in 23.0 per cent of patients attending gynaecology OPD 7 and among 19.9 per cent patients attending STD clinic in a study from New Delhi 8 .

In Mumbai, in a study conducted in female sex workers (FSW) and married contacts, attending a STD clinic 23.2 per cent chlamydial positivity was found 30 . In a study from Aligarh 31 , C. trachomatis was detected in 28.1 per cent of infertile women. The prevalence of C. trachomatis in asymptomatic and symptomatic women attending a gynaecology clinic at Delhi was 4 and 30.4 per cent, respectively 32 .

Anti-chlamydial IgG antibodies were present in 68 per cent of women with infertility, 50 per cent with bad obstretic history (BOH) and 10 per cent of healthy pregnant women, in a study conducted in Amritsar district in Punjab, India 33 . Joyee et al 34 found the prevalence of Chlamydia in STD patients to be 30.8 per cent, while in another study, prevalence of C. trachomatis infection in male patients with urethritis was found to be 17.5 per cent 35 .

A study from UK 36 has shown that health care settings had higher prevalence estimates than population based studies. Among less than 20 years, prevalence estimates were 17.3 per cent in genitourinary clinics, 12.6 per cent in antenatal clinics, 12.3 per cent in termination of pregnancy clinics, 10.7 per cent in youth clinics, 10.0 per cent in family planning clinics compared to 5.0 per cent in population based studies. Vuylsteke et al 37 reported 7.3 per cent prevalence of C. trachomatis in females attending STD/genitourinary clinic in Belgium. In Europe 38 , C. trachomatis infection prevalence was estimated to be 5 to 12 per cent for women undergoing termination of pregnancy. Studies in Latin America show C. trachomatis prevalence rates of 1.9 to 4.5 per cent in Chile, Peru, Brazil, and Mexico 39 , 40 and 12.2 per cent 41 in women attending family planning clinics in Jamaica.

Clinical diagnosis : Clinical picture of the patients suffering from chlamydial infection could be misleading as up to 70-80 per cent of the infected women and 50 per cent of the infected men are asymptomatic. Typically, a female with uncomplicated chlamydial infection will present with odourless, mucoid vaginal discharge without pruritis. Dysuria without frequency or urgency will be complained of if urethra is involved. Further, in PID, history of severe abdominal pain with high fever, dyspareunia, prolonged menstrual cycles and intermenstural bleeding can be elicited. On examination, cervicitis with a yellow, cloudy, mucoid discharge can be seen from the os. The cervix tends to bleed easily when scraped with spatula or brush. Urinalysis will reveal the presence of >5 WBC/HPF (high power field), which is suggestive of urethritis 13 . Chlamydial infections cannot be distinguished from other urethral infections clinically. Amine test ( i.e. , significant odour release on addition of KOH to the vaginal secretion) can help differentiate chlamydial infections from other lower genital tract infections but has a low specificity.

Chlamydial infection in males manifests as urethritis in 15-55 per cent of the affected less than or equal to 35 yr, occasionally epididymitis may be seen 2 . Mild to moderate clear to white urethral discharge is seen in the morning before the patient voids. In epididymitis, history of unilateral testicular pain with scrotal erythema, tenderness or swelling over the epididymis may be elicited. The diagnosis can be established by the presence of mucopurulent discharge from penis which on Gram staining shows >5 WBC/HPF and absence of intracellular Gram negative diplococci. Reiter's syndrome may be a rare complication of untreated chlamydial infection. A reactive arthritis that includes triad of urethritis/cervicitis in females, conjuntivitis and painless mucopurulent eruption on palms and soles of feet is seen in Reiter's syndrome 29 . Female are more commonly affected than males. There is asymmetrical multiple joint involvements with predilection for lower extremities.

Laboratory diagnosis : Asymptomatic nature of the disease and the increasing spectrum of infections caused by C. trachomatis emphasize the need for the sensitive and reliable laboratory methods.

Proficiency in specimen collection and transport is paramount to accuracy in diagnostic testing. Both the sensitivity and specificity of diagnostic tests for C. trachomatis have been shown to be directly related to the adequacy of the specimen. The host cells that harbour the organism should be included in the specimen collection as the chlamydiae are obligate intracellular pathogens, especially in techniques involving direct visualization of the organism.

The choice of sampling sites can influence the likelihood of recovering the pathogen. A 10-20 per cent increase in the recovery of C. trachomatis from genital tract has been observed if both cervical and urethral specimens are taken in comparison to cervical sampling only 42 . Endocervical swab, vaginal/introital swab, vulval swab as well as urethral and rectal swab and first catch urine are the common samples taken from the female patients. Urethral and rectal swab and first catch urine sample can also be collected from male patients in addition to other specific samples like prostatic fluid.

Quality assurance of collection and transport of the specimen : Specimen adequacy can be determined by visualization of squamo-columnar cells during microscopy. A specimen is considered adequate if it contains one columnar/metaplastic cell per slide. The likelihood of isolation is optimized if the specimen is refrigerated immediately after collection at 2-8°C. The time between sample collection and processing should ideally be less than 48 h, if that is not possible these may be frozen at -70 °C until processed 16 . Foetal bovine serum (2-5%) helps to preserve the viability of chlamydiae in specimen, which is to be frozen. Two-molar sucrose phosphate (2-MSP) or sucrose glutamate phosphate are the most commonly used transport medium. Synthetic transport media for culture and some non- culture tests have been developed and approved for diagnostic use, i.e. M4 transport medium, Flex Trans medium and new M4 synthetic/universal medium.

The laboratory diagnosis of Chlamydia consists of the following methods:

(i) Specific tests

Cell culture : Isolation of the organism is the definitive method for the diagnosis of chlamydial infection. Chlamydia is an obligate intracellular pathogen and, therefore, requires embryonated hen's egg or animal cell lines for culture. Such culture methods are technically difficult, labour intensive, cumbersome and expensive, and have not been widely adopted as a routine test performed in general clinical laboratories. However, three in vitro systems have been used for culture of chlamydiae viz . mouse inoculation (intraperitoneal, intracranial and intravenous), yolk sac-inoculation (7-8 day old chick embryo yolk sac inoculation) and cell-culture lines 16 . The most commonly used cell lines include- HeLa 229 cells, McCoy cells, BHK21 and BGMK cells 24 .

The sensitivity of cell culture for isolation of chlamydiae is enhanced by the pre-treatment of cell by polycations, DEAE-dextrans, centrifugation of the inoculum on to the cell monolayer and incorporation of anti-metabolites such as cycloheximide or cytochalasin B into the cell culture medium 42 . Cell monolayer for culture of C. trachomatis is grown in drum or shell vials on glass coverslips or in the wells of multiwell cell culture dishes. The shell vial method is more sensitive for clinical specimen than multiwell cell culture due to less chances of cross-contamination 42 . Prior to inoculation, the specimen should be sonicated to disrupt the host cells and to separate chlamydial inclusions. To inoculate the cell cultures, the overlying culture medium should be removed and replaced with enough of specimen in the culture transport medium to cover the monolayer and prevent drying.

The most commonly used growth medium is Eagles Minimal Essential Medium (EMEM) supplemented with amino acids and vitamins, foetal calf serum (5-10), extra glucose (0.056 m) and 2-glutamine 42 . After inoculation, the cultures are incubated at 37 o C for 2-3 days. The chlamydial inclusions are then observed by immunofluorescent staining. The sensitivity of the isolation has been shown to range from 70-85 per cent depending on the laboratory and the culture system used. Traditionally, this is the “gold standard” for the diagnosis of C. trachomatis as it is 100 per cent specific 42 . Unfortunately, it is beyond the capabilities of most private and public laboratories due to its technical demand, labour intensity and high cost.

Direct fluorescent test (DFA) : The DFA test adds the considerable advantage of Chlamydia specific antibody staining to direct examination of specimen and remains one of the most useful diagnostic techniques. In this test, rapid identification of elementary bodies in smears with flourescein isothiocynate- conjugated monoclonal antibodies (FITC-Mab) against MOMP or genus specific LPS are used. Elementary bodies appear as distinct, sharply outlined, apple green, disk shaped (300 nm) particles and reticulate bodies appear about three times larger than elementary bodies having a fluorescing halo.

This procedure does not require stringent conditions for specimen transportation as a bed side smear is prepared and subsequently transported for processing. With the use of MOMP of C. trachomatis the sensitivity and specificity of DFA is found to be 80-90 per cent and 98-99 per cent, respectively in relation to culture 43 . The high specificity of DFA is attributed to its dependence on the visualization of distinctive morphology and staining characteristics of chlamydial inclusions. The DFA is the only diagnostic test available that permits simultaneous assessment of specimen adequacy by visualization of epithelial cells present in the smear. It is rapid and simple (turnaround time about 30 min) but microscopic examination and interpretation of results requires expertise. This method is, therefore, recommended for low volume laboratories. This test can also be applied to extragenital sites. It is reported to be more sensitive than culture for the detection of Chlamydia in endometrial or tubal specimen 42 .

ELISA (enzyme linked immunosorbant assay) : ELISA is available for the detection of C. trachomatis antigen. Several commercially available ELISA kits are available for the purpose. Most of these detect chlamydial LPS which is more soluble than MOMP. The enzyme immunoassay (EIA) tests have been reported to have a sensitivity of 62-96 per cent and a specificity of 86-99 per cent in comparison to cell culture 44 . This test is suitable for laboratories without access to cell culture. However, different large and small studies across the world including India have reported poor sensitivity of ELISA in comparison to DFA and PCR 45 , 46 , 47 .

Cytology : Cytology is an easily available, simple to use and cost-effective diagnostic test. It does not require precautions for specimen storage and transport, and non-viable/non-infectious particles can also be detected. The quality of the clinical specimen can be assessed by the microscopic technique and the technical procedures used in these tests are usually quicker and simpler to perform than culture. Giemsa, immunoflourescence and iodine staining methods are most commonly used. Other stains like immunoperoxidase, immunoferritin, May Grunwald, Giemenez, Macchiavello and acridine orange can also be used for detecting chlamydial inclusion in exfoliated cells. The presence of intracytoplasmic inclusions is pathogonomic for chlamydial ocular infections in neonates, however, this method is not recommended for diagnosing conjunctivitis or genital infection in adults due to the lack of sensitivity. Of the three methods, immunofluorescence offers the highest sensitivity followed by Giemsa and then iodine staining 42 .

Molecular methods : The traditional methods of diagnosis have several limitations which include low sensitivity, long testing time and high cost. Therefore, tests based on the direct recognition of DNA and RNA sequences are devised. The commercially available DNA probe for the detection of Chlamydia is PACE 2 test (Probe Assay Chemiluminescence Enhanced) 48 , capable of detecting Neisseria gonorrhoeae also, which is a non-isotopic DNA probe for the detection of specific parts of r-RNA of C. trachomatis in the endocervical and urethral specimen. Another DNA probe, PACE 2C test has also been developed which simultaneously detects both C. trachomatis and N. gonorrhoeae from a single specimen; however, further evaluation of PACE 2C is required before its use in diagnostics. These tests employ a chemiluminescent DNA probe that hybridizes to a species- specific sequence of chlamydial 16S rRNA. Once the DNA-rRNA hybrid is formed, it is adsorbed onto a magnetic bead and the chemiluminescent response is detected quantitatively with a luminometer. Since actively dividing chlamydiae contain up to 10 4 copies of 16S rRNA, the PACE 2 test should theoretically be more sensitive than antigen detection systems. The sensitivity of PACE 2 relative to a DNA amplification standard has not yet been well evaluated but has been reported to be 77 to 93 per cent 48 in one study.

The development of tests based on nucleic acid amplification technology (NAAT) has been the most important advancement in the field of chlamydial diagnosis since in vitro cell culture techniques replaced the yolk sac for culture and isolation of the organism from clinical specimens. NAAT is at least 20-30 per cent more sensitive (capable of detecting as little as a single gene copy) and 100 per cent specific 49 , 50 . It offers the opportunity to use non-invasive samples like urine to screen for infections in asymptomatic individuals who would not ordinarily seek clinical care. This is a critical advantage, since the majority of chlamydial infections in women and a significant proportion of infections in men are asymptomatic. The most widely known of the DNA amplification technologies is PCR. PCR can be genus, species, group, or strain specific depending on the primer design. Genes targeted for diagnosis of C. trachomatis are the MOMP gene, the endogeneous plasmid, the phospholipase gene and the 16S and 23S rRNA gene. Since all nucleic acid amplification technologies detect nucleic acid targets, these do not depend on either viability or an intact state of the target organism for a positive result. Hence, transportation of sample is not a critical issue 49 . Although it has not been well studied, the “window” for the culture-negative, PCR positive state following therapy with doxycycline appears to last up to 3 wk 29 . After this time, patient specimens become both culture and PCR negative.

The PCR test for detection of C. trachomatis developed by Roche Diagnostics, Basel Switzerland (Roche-Amplicor) was the first PCR test to be approved by the FDA in the United States 51 . Since 1993, Amplicor PCR has been relatively well evaluated for both urogenital and urine specimens, with an overall sensitivity and specificity of 90 and 99 to 100 per cent, respectively 51 . Amplicor PCR is approved for cervical, male urethral and male urine specimens.

With the explosion of molecular biology techniques newer assays like the m2000 system (Abbott) as well as strand-displacement amplification (SDA) (BD ProbeTec strand displacement amplification developed by Becton Dickinson and Company, Diagnostic Systems, Franklin Lakes, N.J.) and transcription-mediated amplification (TMA) (APTIMA system by Gen-Probe, Inc., San Diego) became available for C. trachomatis . Although popular in the developed countries, their high initial and maintenance cost prevent their use in resource-poor settings.

The burden of C. trachomatis organisms in the genital tract (chlamydial load) can be detected by quantitative real-time PCR and can vary from 10 to over a million organisms/ml of genital tract secretions 52 . This is likely to influence the performance of different nucleic acid amplification tests, which do not routinely distinguish between people with high and low chlamydial loads. Differences in chlamydial load have been reported to be associated with the presence of clinical symptoms, the transmissibility and persistence of infection, and the risk of developing chronic sequelae 53 . Hence, there is a critical role of quantification in the diagnosis and treatment of chlamydial infections.

The NAATs are the most sensitive tests for the screening and diagnosis of chlamydial and gonococcal infections of the genital tract 54 , 55 , 56 . However, doubts regarding their performance in low prevalence areas are reported 57 , 58 . In 2002, the CDC recommended to confirm all positive NAATs for C. trachomatis when the positive predictive value of the test is <90 per cent 59 . However, the true specificities of NAAT methods are found to be >99 per cent 54 , 55 .

The CDC has also suggested several possible strategies for confirmation 59 which include (i) testing a second specimen with a different NAAT having equal or higher sensitivity to the first test, (ii) performing a different NAAT having equal or higher sensitivity to the first test targeting a different nucleic acid sequence on the original specimen, (iii) repeating the original test on the original specimen, and (iv) bringing the patient back for a retest.

However, limitations described are that most clinicians will not collect two samples for the same evaluation, nor is it feasible to bring back the patient to collect another sample, and most laboratories do not have the facilities / capability to perform two different NAATs.

The concept of confirmatory testing is not new 57 . However; it complicates the handling of a NAAT positive sample and adds cost to an already expensive screening test. Also, there is still room for improving the sensitivity of NAATs, perhaps by better specimen preparation, automation, or target concentration.

(ii) Non-specific tests

Leukocyte esterase (LE) test is a rapid dipstick test for use with urine specimens. This test is designed to detect urinary tract infections by detecting the enzyme produced by the polymorphonuclear (PMN) cells. Positive LE test results occur with infections caused by a number of different agents including C. trachomatis and N. gonorrhoeae .

The sensitivity of the LE test for detection of C. trachomatis infection varies widely from 31 to 100 per cent, and specificities range from 83 to 100 per cent 60 . The LE test has been considered the best screening test for adolescent males and, according to most reports, should not be used for testing specimens from women or older men due to unsatisfactory performance.

(iii) Rapid point of care (POC) tests

Rapid tests, also called “point-of-care” tests for C. trachomatis employ EIA technology in formats based primarily on membrane capture or latex immunodiffusion. Rapid tests are performed in physician's offices, do not require sophisticated equipment, and can be completed in about 30 min. Results are read visually and are thus qualitative. Though several kits are commercially available, but none has been well evaluated. In general, the rapid tests are significantly less sensitive and specific than laboratory-performed EIAs. Compared with PCR, the sensitivity and specificity of the Clearview test (Unipath Ltd., UK) were 53.8 and 99.1 per cent, respectively, with endocervical swab specimens, and 31.1 and 95.2 per cent with vaginal swab specimens from Filipino women 61 . The rapid tests offer an advantage over conventional laboratory tests only when results are required immediately for patient management. Rapid tests should not be used in a low-prevalence population or for asymptomatic individuals due to the potential for false-positive results. The results of a rapid test should always be considered presumptive and, if positive, should be confirmed by a laboratory-performed test.

In conclusion, although culture is 100 per cent specific, its estimated sensitivity may be as low as 50 per cent. Majority of laboratories have moved away from culture due to the expense involved, time and technical difficulties. Thus, instead of culture as a diagnostic gold standard, the expanded gold standard/defined reference standard, i.e. , commonly consistent result with two non-culture techniques is considered to be useful as research tool 43 .

(iv) Serology

The serological tests are generally not useful in the diagnosis of genital tract infections caused by C. trachomatis . Antibodies elicited by C. trachomatis infection are long lived and a positive antibody test will not distinguish a previous from a current infection.

New variant of Chlamydia trachomatis

A new variant Chlamydia trachomatis (nvCT) strain has been recently isolated in Sweden (2006) 62 , which has a 377 bps deletion in a portion of the plasmid that is the target area for some of the NAATs. Consequently these tests often give false negative results when presented with this strain. Therefore, it is important to select primers for NAAT carefully particularly those targeting the endogenous plasmids. The symptoms and treatment of this strain do not differ from those for normal chlamydiae. So far, this strain has been found in Sweden and Norway. The clinicians and microbiologists should remain vigilant for suspicious negative results as well as unexplained fall in positive results. However, other commercially available NAAT systems that use a different sequence (Gene Probe Aptima Combo AC 2, Probe Tech, BD, etc .) accurately detect this agent.

Chlamydia trachomatis and pelvic inflammatory disease

Twenty per cent of the women with chlamydial lower genital tract infection will develop PID 63 and 4 per cent will develop chronic pelvic pain 2 . The clinical spectrum of chlamydial PID ranges from subclinical endometritis to frank salpingitis, tubo-ovarian masses, pelvic peritonitis, periappendicitis and perihepatitis. However, symptomatic chlamydial infections represent only the tip of the iceberg of all chlamydial infections as majority of genital chlamydial infections are asymptomatic.

Chlamydia trachomatis and pregnancy

The prevalence of C. trachomatis infection in pregnant women ranges from 2-35 per cent 42 . Pregnant women with chlamydial infection are at increased risk for adverse outcomes of pregnancy and post-partum PID. Sequelae like still birth, low birth weight, neonatal death, decrease gestational periods, preterm delivery and premature rupture of membranes (PROM) have been reported 16 . Nine per cent of the women with chlamydial infection who develop PID have tubal pregnancy 59 . Early pregnancy loss or recurrent pregnancy loss may be induced by asymptomatic chlamydial infection through the operation of immune mechanism.

Chlamydia trachomatis and infertility

Chlamydial PID is the single most important preventable cause of infertility. Approximately, 3 per cent women with chlamydial genital tract infection develop infertility. After a single episode of PID, the risk of tubal factor infertility is approximately 10 per cent, each repeat episode doubles the risk 64 . Although the majority of patients are asymptomatic but re-infection/persistent infection with C. trachomatis leads to more severe tubal damage than other agents.

The role of C. trachomatis in the development of urethritis, epididymitis and orchitis in men is widely accepted. Though the role of this organism in prostatitis is controversial, but up to 35- 50 per cent incidence has been reported in patients with prostatitis 65 . Infection of the testes and the prostrate is implicated in the deterioration of sperm (decrease sperm motility, increase proportion of sperm abnormalities, significant reduction in sperm density, sperm morphology and viability and increased likelihood of leucocytospermia) affecting fertility. Chlamydial infection may also affect the male fertility by directly damaging the sperm as sperm parameters, proportion of DNA fragmentation and acrosome reaction capacity are impaired. However, the role of C. trachomatis in male infertility is not yet proven.

Chlamydia trachomatis and HIV

Chlamydial infection of the genital tract facilitates the transmission of HIV. This is confirmed by various studies 12 , 15 , 23 . The combined epidemiology of these infections may partly be due to the fact that STDs including C. trachomatis and HIV have common sexual/behavioural risk factors. But, C. trachomatis and HIV have inter-relationship independent of the sexually transmissible risk factors 34 . The possible inter-relationship between HIV infection and C. trachomatis includes (i) the invasive intracellular pathogenesis of C. trachomatis can cause substantial damage to the genital epithelial layer that may facilitate HIV infection, and (ii) the immunological changes due to HIV infection may favour chlamydial infection.

On the other hand, immunosuppression due to HIV may lead to more aggressive chlamydial disease conditions like PID in those who are infected. Thus, early diagnosis and treatment of chlamydial infections are important to prevent HIV risk and devastating clinical consequence.

Chlamydia trachomatis and co-infection with other STI/ RTI/ infections

C. trachomatis and N. gonorrhoeae are the two most common bacterial causes of lower genital tract infection. Clinical findings need to be corroborated with the laboratory investigations as the signs and symptoms of both are indistinguishable. Therefore, in the syndromic approach used in resource-limited settings, urethral discharge (UD) is simultaneously treated for both. C. trachomatis is recovered more often from women who acquire gonorrhoea than from similarly exposed women who do not acquire gonorrhoea. In individuals with gonorrhoea, there exists a 15-40 per cent higher risk of acquiring Chlamydia. Further, individuals infected with both C. trachomatis and N. gonorrhoeae shed larger number of C. trachomatis than those infected with C. trachomatis alone. These data suggest that acquisition of a gonococcal infection either reactivates a persistent chlamydial infection or increases the susceptibility of the host to Chlamydia . Post-gonococcal urethritis is often due to C. trachomatis infection which is not cured by conventional therapy against gonorrhoea. Co-infection of C. trachomatis with N. gonorrheae has been reported to range between 1.1 to 67 per cent 66 , 67 , 68 , 69 , 70 .

In a study in STD patients in New Delhi, 19.9 per cent prevalence of C. trachomatis was observed 9 . The co-infection of C. trachomatis with bacterial vaginosis was found to be 12.7 per cent, candidiasis in 10.9 per cent cases, syphillis in 3.6 per cent cases and chancroid in 1.8 per cent cases. However, co-infection with N. gonorrheae was not found. Two cases with multiple infections were also reported ( i.e. one with C. trachomatis , Candida albicans , HIV and syphilis and the other with C. trachomatis , C. albicans , HIV and bacterial vaginosis). In another study, the prevalence of C. trachomatis in STD patients was found to be 30.8 per cent 34 . Thirty per cent of the Chlamydia infected cases had HIV infection, while the analysis revealed that 50 per cent of the HIV positive cases happened to be proven C. trachomatis positive cases.

Prevention of Chlamydia trachomatis infection

The control of STD is a public health priority and the importance of these infections has increased in salience over the past decade, with the growing evidence of co- transmission of HIV. The CDC guidelines 59 for the prevention and control of STDs are based on five major concepts: (i) Education and counselling on safer sexual behaviour in persons at risk. (ii) Identification of asymptomatic infected persons and of symptomatic persons unlikely to seek diagnostic and treatment services. (iii) Effective diagnosis and treatment of infected persons. (iv) Evaluation, treatment and counselling of sex partners of persons infected with a STD. (v) Pre-exposure immunization for vaccine preventable diseases.

The CDC strongly recommends that all sexually active women (≤25 yr) and women at increased risk of infection should be routinely screened for Chlamydia . However, screening for chlamydial infection is not recommended for men, including those who have sex with other men 71 . Prevention of C. trachomatis infection can be done at primary, secondary and tertiary levels. Primary prevention involves preventing both exposure to and acquisition of chlamydial infection through lifestyle counselling and health education. Clinicians play an important role by enquiring about the risk taking sexual behaviour, by encouraging screening tests for those at risk, by ensuring that partners are evaluated and treated and by counselling about safe sex practices. Effective school based health programmes should be implemented among adolescents. Unfortunately, primary prevention has not gained popularity especially in the developing world 72 . Secondary prevention means early detection of asymptomatic disease by screening in order to prevent the drastic sequelae of chlamydial infection. Chlamydial infection fills the general pre-requisite for disease prevention by screening, since these are highly prevalent, are associated with significant morbidity, can be diagnosed, and are treatable. Recent advances like testing non-invasive specimen, utilization of nucleic acid amplification tests and single dose therapy using azithromycin further enhance the efforts to prevent chlamydial infection. Tertiary prevention of acute and chronic chlamydial infection of the upper genital tract has largely failed because by the time patient becomes symptomatic substantial tubal damage already occurs.

Treatment of urogenital Chlamydia trachomatis infection

The treatment of chlamydial infection depends on the site of infection, the age of the patient, and whether the infection is complicated or not. Treatment also differs during pregnancy.

Uncomplicated infection : The CDC recommends 1 g azithromycin orally in a single dose, or 100 mg doxycycline orally twice a day (bd) for seven days for uncomplicated genito-urinary infection. Alternate regimens include erythromycin 500 mg orally four times a day (qid) or ofloxacin 300 mg orally (bd) for seven days.

Compared with the conventional therapy, azithromycin has advantage of having better compliance being administered in the physicians’ chamber. All the other regimens have similar cure rates and adverse effect profiles. Patients should be instructed to abstain from sexual intercourse for seven days after the treatment initiation. Both the partners should be treated simultaneously in order to prevent re-infection of the index patient. Patient need not be re-tested after completing the treatment, unless the symptoms persist or re-infection is suspected.

Chlamydial infection with PID : Recurrent chlamydial infection increases the risk for developing ectopic pregnancy and PID. PID can be treated on an outpatient basis unless indicated (accompanied by severe illness, nausea, vomiting, high-grade fever, tubo-ovarian abcess or intolerance or unresponsiveness to oral therapy). The CDC has recommended ofloxacin 400 mg orally (bd) or levofloxacin 500 mg orally once a day (od) with or without metronidazole 500 mg orally (bd) for two weeks. In case of intolerance to the above mentioned regimen, ceftriaxone 250 mg intramuscular (im) or cefoxitin 2 g (im) as a single dose with concurrent probenicid 1 g orally in single dose plus doxycycline 100 mg orally (bd) with or without metronidazole 500 mg orally (bd) for two weeks 13 .

Treatment during pregnancy : Levofloxacin, ofloxacin and doxycycline are contraindicated during pregnancy. Therefore, azithromycin 1 g orally in a single dose or amoxycillin 500 mg orally thrice a day (tds) is recommended. Amoxycillin is reported to be more effective and with fewer side effects than erythromycin in treating antenatal chlamydial infection. Alternatively, erythromycin base 500 mg orally (qid) is a safe and effective alternative 13 . Testing for cure is indicated in patients who are pregnant and should be performed three weeks after completion of treatment. If the risk of re-exposure is high, screening should be repeated throughout pregnancy.

Multidrug resistant and heterotypic resistant Chlamydia trachomatis

In 1980, Mourad et al 73 were the first to report the reduced sensitivity to erythromycin. Decreased sensitivity to tetracycline was first reported by Jones et al 74 in 1997. They identified five isolates from cases of tubal infertility which had minimum inhibitory concentration (MICs) to tetracycline of 4 to >8 mg/l, compared with control MICs of 0.125 to 0.25 mg/l. The isolates were also resistant to erythromycin, clindamycin and sulphonamide, but sensitive to ciprofloxacin and ofloxacin. Tetracycline resistance was also reported from France in 1997 75 . In 2000, Somani et al 76 reported multidrug resistant isolates of C. trachomatis associated with treatment failure with azithromycin.

The characteristics of antibiotic resistance of C. trachomatis differ significantly from those of other bacteria in several ways. First, because chlamydiae are intracellular pathogens, antimicrobial susceptibility must be determined by their ability to proliferate within a host cell in the presence of varying concentrations of antibiotic. Second, unlike the case for most bacteria, when C. trachomatis organisms are found to be resistant to typically effective antibiotics such as tetracycline, the resistance is not absolute. In fact, C. trachomatis displays what is known as “heterotypic resistance” in vitro ; that is, the chlamydial population contains both susceptible and resistant organisms. Thus, although it is possible that all organisms within a population may be capable of expressing resistance, only a small proportion does so at any one time. Testing for the MCC (defined as lowest concentration of drug that permitted no inclusions to be formed on passage on an antibiotic free medium) may allow the small percentage of organisms that were resistant to the first exposure to antibiotic (MIC) to then multiply and form inclusions 76 . Heterotypic resistance exhibited by some C. trachomatis strains, therefore, may be missed unless both MIC and MCC testing is done. In strains that exhibit heterotypic resistance, many aberrant inclusions are seen, and the proportion of atypical to typical inclusions gradually increases along with a decrease in the overall number of inclusions until all inclusions become aberrant or absent, which is reinforcing the fact that the resistance exhibited by individual organisms within the chlamydial population is heterogenous (defined as heterotypic resistance). The mechanisms underlying heterotypic resistance in C. trachomatis is not known. It is hypothesized that multidrug resistance in C. trachomatis is phenotypic in nature rather than genotypic 76 . Also, heterotypic resistance may be a byproduct of some undefined alteration of the growth rate or life cycle, resulting in a longer phase or intermediate stage that is more refractory to the antimicrobial agents. Alternatively, it may be mediated by some kind of mechanisms that exclude the drug from cell wall or chlamydial inclusion ( e.g. efflux pump) 76 . Further studies are required to prove these hypotheses.

There are no data regarding management of clinically resistant C. trachomatis infection. In vitro data suggest that resistance to ofloxacin imparts resistance to other fluoroquinolones, such as ciprofloxacin. Although many of the newer quinolones, including trovafloxacin, sparfloxacin, grepafloxacin and tosufloxacin have equal or greater MICs for C. trachomatis , these need to be tested against an ofloxacin-resistant strain 74 , 77 . Perhaps a prolonged course of therapy with a standard agent such as doxycycline or azithromycin would be effective against resistant C. trachomatis disease, because such therapy has been efficacious against C. pneumoniae infection in cases of relapse 78 .

Azithromycin 1 g immediately and doxycycline 100 mg twice daily have shown good antimicrobial activity against C. trachomatis and studies have demonstrated >95 per cent microbiological cure at 2-5 wk, with antimicrobial resistance being hardly reported 72 . However, there are evidences of multidrug resistance to C. trachomatis in women with high bacterial load but not in men who had been sexually inactive after treatment 72 .

Vaccination could be substantially more effective than other biomedical interventions in controlling epidemics of Chlamydia infection. Currently, the best public health intervention available is increasing the rate of screening and treating infected individuals. Administrating a protective vaccine to adolescents before their first sexual experience could induce a significant reduction in prevalence which could not be obtained by screening teenagers, even with a coverage of 100 per cent 79 . Unfortunately, no protective vaccines, either fully or partially, are available although there have been many attempts to develop one. The immunological characteristics of the genital tract and the tropism of Chlamydia for mucosal epithelial cells emphasize that a C. trachomatis vaccine must induce both mucosal and systemic protective responses 80 . The research goal for an efficacious human chlamydial vaccine has faced key challenges to define the elements of protective immunity to facilitate vaccine evaluation, the judicious selection of appropriate vaccine candidates that possess stable antigenic and immunologic properties and the development of effective delivery vehicles and adjuvants to boost immune effectors to achieve long term protective immunity. Progress in the functional immunobiology of Chlamydia has established the essential immunologic paradigms for vaccine selection and evaluation, including the obligatory requirement for a vaccine to induce T- helper type 1 immune response that controls Chlamydia . Major inroads are however, required in the construction and development of novel and effective delivery systems, such as vectors and adjuvants.

Role of C. trachomatis in serious genitourinary complications in women and men is widely accepted. Further, it has been found to facilitate the acquisition and transmission of HIV infection. Information is now available on cell biology, bacterium- host cell interactions, disease producing mechanisms, host defense evading factors, transmission sources and antimicrobials used for treatment. Despite these advances, there are many lacunae which need to be addressed. Asymptomatic infection in the majority coupled with re-infection, recurrent and latent infections are the major challenges to the control of this bacterial STI. The best available intervention today is the early detection by screening and treatment of infected cases and their sexual partners. However, the ultimate intervention - the development of an effective vaccine is still far away and further research is required.

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Chlamydia trachomatis as a Current Health Problem: Challenges and Opportunities
3. Chlamydia trachomatis Development and Immune Response. Chlamydia trachomatis has a particular development biphasic cycle, as shown in Figure 1.Briefly, this pathogen alternates between two distinct forms. Firstly, the infectious form, named the elementary body (EB), which when in contact with a host cell, can be internalized into the cell cytoplasm by cell adhesion through the major out ...
Chlamydia
Chlamydia is a sexually transmitted infectious disease caused by the bacterium Chlamydia trachomatis. In the United States, it is the most commonly reported bacterial infection. Globally, it is the most common sexually transmitted infection. It causes an ocular infection called "trachoma," which is the leading infectious cause of blindness worldwide.
Therapeutic Options for Chlamydia trachomatis Infection: Present and
1. Introduction. Sexually transmitted infections (STIs) have a huge impact on communities; they are associated with individuals' morbidity and mortality, and also with increased public health expenses through their direct effect on fertility, pregnancy process, and carcinogenesis [1,2].Chlamydial infection is among the most common curable STIs worldwide, caused by Chlamydia trachomatis (Ct) [].
Diagnosis and Management of Uncomplicated Chlamydia trachomatis
5 Vaccine Research Laboratory, University of British Columbia Centre for Disease Control, Vancouver, Canada. ... and management of sexually transmitted infections.This paper summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infections in adolescents and ...
Update on the Epidemiology, Screening, and Management of Chlamydia
Abstract. Chlamydia trachomatis infection ("chlamydia") is the most commonly diagnosed bacterial sexually transmitted infection globally, occurring in the genitals (urethra or vagina/cervix), rectum, or pharynx. If left untreated in women, genital chlamydia can ascend into the upper genital tract causing pelvic inflammatory disease, increasing ...
A Systematic Literature Review of Reviews on the Effectiveness of
Chlamydia trachomatis is the most common bacterial sexually transmitted infection, causing significant morbidity and economic burden. ... 8 University College London Centre for Clinical Research in Infection and Sexual Health, Institute for Global Health, London, United Kingdom. PMID: 31565737 DOI: 10.1093/epirev/mxz007 ...
Chlamydia cell biology and pathogenesis
Chlamydia trachomatis and Chlamydia pneumoniae, the major species that infect humans, are responsible for a wide range of diseases 2,4 and will be the focus of this Review.
Prevalence of genital Chlamydia trachomatis infection in the general
Background Estimating prevalence of Chlamydia trachomatis (CT) worldwide is necessary in designing control programs and allocating health resources. We performed a meta-analysis to calculate the prevalence of CT in the general population. Methods The Pubmed and Embase databases were searched for eligible population-based studies from its inception through June 5, 2019. Q test and I2 statistic ...
Diagnostics
Feature papers represent the most advanced research with significant potential for high impact in the field. A Feature Paper should be a substantial original Article that involves several techniques or approaches, provides an outlook for future research directions and describes possible research applications. ... D. Chlamydia trachomatis ...
Chlamydia trachomatis: the Persistent Pathogen
Chlamydia trachomatis is an obligate intracellular bacterium whose only natural host is humans. Although presenting as asymptomatic in most women, genital tract chlamydial infections are a leading cause of pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. C. trachomatis has evolved successful mechanisms to avoid ...
Chlamydia trachomatis : the Persistent Pathogen
Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium. Humans are its exclusive natural host. Different chlamydial serovars are the major etiological agents of preventable blindness (serovars A to C), the most common bacterial sexually transmitted infections worldwide (serovars D to K), and lymphatic system infections (serovars L1 to L3).
Towards a Deeper Understanding of Chlamydia trachomatis ...
Chlamydia trachomatis, an obligate intracellular Gram-negative bacterium, is characterized by a wide range of different serotypes responsible for several local or systemic human diseases, including genital tract manifestations (D-K), trachoma (A-C), and lymphogranuloma venereum (L1-3).Among them, C. trachomatis genital infections are the most common sexually transmitted diseases of ...
Chlamydia Trachomatis Infection: Epidemiology, Prevention, Clinical
Chlamydia trachomatis infection is the most frequently reported bacterial sexually transmitted infection (STI) globally, with an estimated 131 million new cases occurring annually. Chlamydia spreads through vaginal, anal, or oral sex with a partner with the infection. It is common among young people aged 15-24 years. However, as chlamydia infections are often asymptomatic, most infected are ...
PDF WHO GUIDELINES FOR THE
WHO guidelines for the treatment of Chlamydia trachomatis. &RQWHQWV :HE DQQH[ ' (YLGHQFH SUR ÌOHV DQG HYLGHQFH WR GHFLVLRQ framework -- Web annex E: Systematic reviews -- Web annex F: Summary RI FRQ ÍLFWV RI LQWHUHVW 1.Chlamydia trachomatis. 2.Chlamydia Infections - drug therapy. 3.Sexually Transmitted Diseases. 4.Guideline.
Chlamydia
Chlamydia is a sexually transmitted infectious disease caused by the bacterium Chlamydia trachomatis. In the United States, it is the most commonly reported bacterial infection. Globally, it is the most common sexually transmitted infection. It causes an ocular infection called "trachoma," which is the leading infectious cause of blindness ...
Knowledge about and prevalence of Chlamydia trachomatis in a population
To determine the prevalence of genital Chlamydia trachomatis (chlamydia) infection, knowledge about chlamydia and experience of previous testing for chlamydia, we carried out a national probability-based survey in emerging adults aged 18-25 years in Croatia in 2021-2022. Participants (n = 1197), members of a national online panel, completed a web-based questionnaire that collected ...
Chlamydia trachomatis Genital Infections
EPIDEMIOLOGY. C. trachomatis is the leading cause of bacterial sexually transmitted infection (STI) in the world. However, in endemic areas, mostly in Africa and the Middle East, C. trachomatis also causes trachoma, a leading cause of preventable blindness worldwide. The World Health Organization estimated a global prevalence of chlamydia at 4.2% (95% uncertainty interval: 3.7-4.7) among women ...
Chlamydia trachomatis infection in Cuban adolescent and young
In Cuba, little is known regarding the prevalence of Chlamydia trachomatis (CT) infection in adolescents and young people. We study the frequency of CT infection in these populations, and its association with clinical-epidemiological variables.
A review of current guidelines and research on the management of
A prospective cohort study evaluating women with rectal chlamydia found improved cure rates with doxycycline (95.5%) compared with azithromycin (78.5) (p < 0.001). 87 In a retrospective chart review of 526 men and women with rectal chlamydia, among those who presented for re-testing, the reinfection rate was 5.8% in those treated with ...
Editorial: Sexually transmitted infections during pregnancy
Search for more papers by this author. ... and to identify areas for future implementation research. Then, Drew and Eogan 2 review international guidelines on the recommendations for ... Pant et al. 9 search for an association between MMP2 and CD63 gene variants and risk of ectopic pregnancy during Chlamydia trachomatis infection in an ...
Diagnosis and Management of Uncomplicated Chlamydia trachomatis
Chlamydia trachomatis (CT) infection remains the most prevalent reportable bacterial sexually transmitted infection (STI) in the United States (US), with >1.8 million cases reported to the Centers for Disease Control and Prevention (CDC) in 2019 [].Young age remains a strong predictor of CT infection, with the highest CT infection rate in persons aged <25 years [].
Paper-based molecular diagnostic for Chlamydia trachomatis
Herein we show the development of a minimally instrumented paper-based molecular diagnostic for point of care detection of sexually transmitted infections caused by Chlamydia trachomatis.This new diagnostic platform incorporates cell lysis, isothermal nucleic acid amplification, and lateral flow visual detection using only a pressure source and heat block, eliminating the need for expensive ...
Chlamydia Trachomatis Infections: Screening, Diagnosis, and ...
Chlamydia trachomatis is a gram-negative bacterium that infects the columnar epithelium of the cervix, urethra, and rectum, as well as nongenital sites. The bacterium is the cause of the most ...
Antimicrobial treatment and resistance in sexually transmitted
In the Review, Jensen and Unemo examine the epidemiology and clinical features, treatment options, and antimicrobial resistance of Neisseria gonorrhoeae and Mycoplasma genitalium, while briefly ...
Genital Chlamydia trachomatis: An update
Risk factors and demographic factors for Chlamydia trachomatis infection. The most common demographic correlate 16 of infection with chlamydial infection in women is young age (<20 yr). This could be explained by the anatomic differences in the cervix of the younger women, wherein the squamo-columnar junction, a primary host target for C. trachomatis, is everted and thus more exposed.

Prevalence of genital Chlamydia trachomatis infection in the general population: a meta-analysis

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Chlamydia Trachomatis Infection: Epidemiology, Prevention, Clinical, and Basic Science Research

Knowledge about and prevalence of Chlamydia trachomatis in a population-based sample of emerging Croatian adults

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