introduction essay about malaria

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Malaria status & challenges of the epidemic

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1. Introduction

Anopheles mosquito, the vector for malaria

Malaria is one of the most common infectious diseases and a great public health problem worldwide, particularly in Africa and south Asia. About three billion people are at risk of infection in 109 countries. Each year, there are an estimated 250 million cases of malaria leading to approximately one million deaths, mostly in children under five years of age. The organism that causes the most dangerous form of malaria is a microscopic parasite called Plasmodium falciparum .

This parasite is transmitted by mosquito species belonging to the Anopheles genus and only by females of those species.

There is growing international agreement on how best to use prevention and treatment methods that are available. The most effective prevention measures include the use of mosquito bed nets treated with long-lasting insecticides – to avoid the mosquito bites and to kill the mosquitoes – and spraying the inside walls of houses with similar insecticides to kill malaria-carrying mosquitoes. The most effective treatment for malaria consists in using a combination of several anti-malarial drugs, one of which is a derivative of artemisinin . Preventive treatment of pregnant women with anti-malarial drugs can also reduce the harmful effects of malaria both on the mother and on the unborn child.

Several international organisations have set up ambitious objectives for large-scale malaria control. The target set by the Word Health Organization ( WHO ) in 2005 is to offer malaria prevention and treatment services by 2010 to at least 80% of the people who need them. By doing so, it aims to reduce at least by half the proportion of people who become ill or die from malaria by 2010 and at least by three quarters by 2015 compared to 2005.

It is vital to monitor malaria trends to see if malaria control campaigns are being effective, and to make improvements.

The WHO World Malaria Report 2008 estimates the number of malaria cases and deaths for the period 2001-2006 in affected countries and investigates whether or not WHO recommendations are being implemented. It evaluates progress made against the disease it also describes the sources of funding and reviews the impact of malaria control programmes. The aim of the report is to support the development of effective national malaria control programmes.

2. Which strategies were adopted to prevent and treat malaria?
3. How many people were affected by malaria in 2006?
4. What is being done to prevent and treat malaria?
5. How much funding is allocated to malaria control?
6. How effective is malaria control?
7. Can malaria be completely eradicated?
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Malaria: One of the leading causes of child deaths, but progress is possible and you can contribute to it

We do not have to live in a world in which 1320 children die from a preventable disease every day.

Malaria is a disease that is transmitted by infected mosquitoes. The bite of an infected Anopheles mosquito transmits a parasite that enters the victim’s blood stream and travels into the person’s liver where the parasite reproduces. The parasite, called plasmodium, causes a high fever that involves shaking chills and pain. In the worst cases malaria leads to coma and death.

The World Health Organization estimates that 241 million people contract the disease every year. 1 Only a small fraction of malaria victims die from it, but those who die are the very weakest – about three out of four malaria victims are children. 2 Malaria is one of the leading causes of child mortality; it kills about half a million children every year. 3 That’s 1320 dead children on any average day.

How can the world make progress against malaria?

In the history of health, the most important progress is often made in the prevention – rather than the treatment – of disease. For infectious diseases, prevention means interrupting its transmission.

Humanity’s most ingenious way of preventing infections is to achieve immunization through vaccines. The work on malaria vaccines goes back many decades, but unfortunately these vaccines have not been as successful as the vaccines against other diseases. 4

There is however the hope that this will change. The mRNA technology – spurred by the COVID pandemic – seems promising also for the prospect of a vaccine against malaria. But it will certainly still take some time until a highly efficacious malaria vaccine is widely available.

In the meantime the world has to protect itself from malaria in other ways. This is something the world has been getting increasingly successful at.

Malaria was common across half the world – since then it has been eliminated in many regions

One line of humanity’s attack is to progressively reduce the area where malaria is prevalent.

Malaria is not a tropical disease. Rather, it is a disease that was eliminated everywhere but the tropics. Historically, malaria was prevalent in Europe and North America – Oliver Cromwell contracted the disease in Ireland, Friedrich Schiller in Mannheim, and Abraham Lincoln in Illinois. 5

The map shows that in modern times the disease has been eliminated not only there, but also in East Asia and Australia and in many parts of the Caribbean, South America, and Africa. Researchers estimate that historically – and up to around the year 1900 – our ancestors were at risk from malaria across about half of the world’s land surface. Since then the area where humans are at risk of malaria contracted to a quarter. 6

This was achieved through the use of insecticides, the drainage of swampland, and better housing conditions. Economic growth was crucial for these developments so that the disease is today mostly prevalent in the world’s poorest regions.

The often-repeated claim that malaria killed half of all humans who ever lived is very likely an overstatement, but it is certainly the case that the mosquito-borne fever was one of the most common causes of death in human history. 7 In the last few generations humanity gained ground in this long-lasting battle against the disease. The WHO reports that the global mortality rate has declined by 90% in the 20th century. 8

→ More detail in my text Malaria was common across half the world – since then it has been eliminated in many regions

Net Results: how the world is achieving progress where malaria is still prevalent

Economic development is a slow process. Are there opportunities to protect people from malaria right now?

Yes. A surprisingly simple and cheap technology has saved the lives of millions of people in the last few years: insecticide-treated bed nets.

The nets protect those who sleep under them and the insecticide, with which they are impregnated, kills the mosquitoes – in this way the bed nets also protect their larger community, very similar to the way vaccinations do not only protect those who receive the vaccine, but also those around them. Such public health measures which protect the individual and the people they are in contact with are particularly successful ways to fight global problems.

The progress against malaria since the turn of the century is shown in the two visualizations below. The map shows us the change in child mortality due to malaria on the local-level across Africa (for which 2019 is the latest data). The global annual death toll – across all ages – declined from 900,000 to 630,000 per year. It also shows that the disruptions due to the pandemic led to an increase in malaria deaths.

How was this progress possible? The study by Samir Bhatt and colleagues 9 in Nature found that three health measures were particularly important for progress against malaria in Africa. By far the most important measure was the just-mentioned distribution of insecticide-treated bed nets; about two-thirds of the averted cases can be attributed to bed nets. The rest was achieved thanks to indoor residual spraying and the treatment of malaria cases with artemisinin, a drug discovered by Tu Youyou. She was awarded the Nobel Prize in Medicine in 2015 for this achievement.

Malaria mortality rate of children in 2000 and 2019 10

We can achieve more and you can help

Progress never happens by itself. For millennia our ancestors were exposed to the malaria parasite without defense; the fact that this changed is the achievement of the scientific, political, and economic achievements of the last few generations.

Today we are in the fortunate situation that we have several decades of progress behind us: We can look back and study what worked to use this knowledge to go further.

Some of the most important research in global development asks the question of where additional efforts can do the most good. A charity evaluator that is doing very rigorous work on this is ‘GiveWell’. Their research tells you where your donation can have the largest positive impact. It finds that donations to support the fight against malaria are one of the very most impactful ways for you to donate. At the top of GiveWell’s recommended charities are two organizations that work towards that goal: the Against Malaria Foundation and the Malaria Consortium .

Continuing the successful fight against malaria requires commitment from governments around the world. It is a problem that we might be able to solve with better technology in the future – most likely with a vaccine – if we choose to support scientific research.

But it is also a problem where each of us can individually contribute to progress right now. You can read the research about how your donation can contribute to progress against malaria here: GiveWell.org . If you want to contribute to this progress it is possible to make a donation right there.

Figures for 2020 according to the WHO: http://www.who.int/malaria/en/

The WHO estimates that in 2020 (latest data, as of writing) 77% of all deaths were in children younger than 5 years old. The IHME’s Global Burden of Disease also estimates that the majority of malaria deaths are in children younger than 5 years. According to their research the share of children younger than 5 among malaria victims fell slightly over the course of the last generation, from 66% in 1990 to 55% in 2019. Here is their data: https://ourworldindata.org/grapher/malaria-deaths-by-age

These are the WHO estimates and are calculated based on the two previously cited statistics: 627,000*0.77=482,790.

To not suggest that we have a very precise knowledge of the number of children that die from malaria I have rounded the number from 482,790 to ‘about half a million’.The estimates of the Institute of Health Metrics and Evaluation (IHME) – published in their Global Burden of Disease (GBD) study – are different: 643,000 malaria deaths in 2019; 356,000 of them are children younger than five. We have followed up with researchers in this field, but were not able to fully understand why the estimates from the IHME differ in their age-composition from the WHO estimates. To be on the conservative side I am relying on the estimates from the WHO throughout this text, but to provide perspective I also reference the IHME wherever relevant.

For more detail on this data see our entry on malaria .

Alphonse Laveran discovered already in 1880 that the Plasmodium parasite is the cause for malaria. But many attempts to develop vaccines were unsuccessful. Malaria vaccines such as SPf66 were insufficiently effective and until recently none of the scientific efforts led to a licensed vaccine. For an overview see Adrian V. S. Hill (2011) – Vaccines against malaria. In Philos Trans R Soc Lond B Biol Sci. 2011 Oct 12; 366(1579): 2806–2814. doi: 10.1098/rstb.2011.0091.

This has changed somewhat with the malaria vaccine RTS,S, the world's first licensed malaria vaccine, which has been approved by European regulators in 2015. See RTS,S Clinical Trials Partnership (2015) – Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. In The Lancet, Volume 386, ISSUE 9988, P31-45, July 04, 2015. Its efficacy is however not as high as that of other vaccines.

On the cause of Oliver Cromwell’s death see the FAQs at OliverCromwell.org , on Friedrich Schiller see Bayerischer Rundfunk here , on Abraham Lincoln see ‘The Physical Lincoln ’. Several popes also died of the disease as malaria was very prevalent in Italy until recently.

It should however be noted that it is not always possible to diagnose the causes of death of historical figures. The claim that the German renaissance painter Albrecht Dürer died from malaria is for example disputed by Seitz, H. (2010) – "Do der gelb fleck ist … " Dürers Malaria, eine Fehldiagnose. Wien Klin Wochenschr 122, 10–13 (2010). https://doi.org/10.1007/s00508-010-1432-z

See the publication Simon I Hay, Carlos A Guerra, Andrew J Tatem, Abdisalan M Noor, and Robert W Snow (2004) – The global distribution and population at risk of malaria: past, present, and future . In The Lancet Infectious Diseases 2004 June; 4(6): 327–336. DOI: 10.1016/S1473-3099(04)01043-6.

The historical mapping of the prevalence of malaria is based on the pioneering work of Lysenko in the 1960s: Lysenko AJ, Semashko IN. Geography of malaria (1968) – A medico-geographic profile of an ancient disease. In: Lebedew AW, editor. Itogi Nauki: Medicinskaja Geografija. Academy of Sciences, USSR; Moscow: 1968. pp. 25–146. Lysenko AJ, Beljaev AE (1969) – An analysis of the geographical distribution of Plasmodium ovale. Bull. World Health Organization; 40:383–94.

I have recreated that map and written about this research in Roser (2019) – Malaria was common across half the world – since then it has been eliminated in many regions . In Our World in Data.

That malaria was the most common cause of death was even suggested in a Nature article: Whitfield (2002) wrote “Malaria may have killed half of all the people that ever lived”.

Whitfield, J. Portrait of a serial killer. Nature (2002). https://doi.org/10.1038/news021001-6

But while there is obviously no hard evidence to establish or refute this claim other epidemiologists were skeptical that this is true. Tim Harford investigated the claim in an episode of the BBC’s “More or Less”: Have Mosquitoes Killed Half the World?

See “Box 4.1 Malaria-related mortality in the 20th century” in the World Health Organization’s World Health Report (1999) .

Bhatt et al. (2015) – The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015. Nature 526, 207–211 (08 October 2015) doi:10.1038/nature15535

The focus of the study was Africa, where – as the chart shows – most of the recent reduction was achieved.

Institute for Health Metrics and Evaluation (IHME), Malaria Atlas Project. Global Malaria Incidence, Prevalence, and Mortality Geospatial Estimates 2000-2019. Seattle, United States of America: Institute for Health Metrics and Evaluation (IHME), 2020. https://doi.org/10.6069/CG0J-2R97

Shown is the mortality rate due to plasmodium falciparum – direct link to the interactive maps as published by the IHME http://ihmeuw.org/5dhp

For the background see: Weiss, D. J., Lucas, T. C. D., Nguyen, M., Nandi, A. K., Bisanzio, D., Battle, K. E., Cameron, E., Twohig, K. A., Pfeffer, D. A., Rozier, J. A., Gibson, H. S., Rao, P. C., Casey, D., Bertozzi-Villa, A., Collins, E. L., Dalrymple, U., Gray, N., Harris, J. R., Howes, R. E., … Gething, P. W. (2019) – Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum, 2000–17: A spatial and temporal modelling study. In The Lancet, 394(10195), 322–331. https://doi.org/10.1016/S0140-6736(19)31097-9

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Essay on Malaria Awareness

Introduction.

Malaria is a common disease in tropical countries where children and pregnant women are the main victims. It is a parasitic infection caused by plasmodium, which can be deadly to these vulnerable sections. As children are more prone to this disease, it is important to create awareness in them. So, this essay on malaria awareness will be beneficial for them to know more about it.

The main symptom of malaria is high fever with chills. So, it is possible that people confuse it with a viral fever, and malaria gets untreated, leading to other serious consequences. Since it is the life of our children that is at stake, we must take necessary measures to prevent and treat malaria. This short essay on malaria awareness will alert both children and elders on how to tackle this life-threatening disease.

Importance of Malaria Awareness

Malaria is spread from one individual to another by female Anopheles mosquitoes, and the symptoms in affected individuals resemble that of any viral fever. This is why knowledge about the disease is given due importance in this essay on malaria awareness. While high temperature and headache are the most common signs of malaria, nausea and drowsiness are also found in sick people. By detecting the disease early, we will be able to start the treatment soon, thus reducing the risk in children.

As we mentioned earlier in the short essay on malaria awareness that malaria is more prevalent in tropical countries, travelling to such places with little awareness about the disease could be dangerous. Children could fall ill at the end of the trip, which will ruin all the fun they had. So, this malaria awareness essay will be useful to know that it is risky to travel in the wet season to places that have humid climates.

All these points emphasise that it is important to have knowledge about malaria to prevent infections in children as well as make their journeys memorable. They will also be able to write about a memorable day of my life .

Ways to Raise Malaria Awareness

Just like how crucial it is to bring attention to the spread of malaria, it is equally important to understand that prevention is better than cure. Since we know that malaria is transmitted through mosquitoes, the first and foremost step in raising awareness of the disease is by spreading messages about mosquito breeding and destroying its breeding places. In this section of the essay on malaria awareness, we will see effective methods to create awareness among children.

While elders can understand the gravity of the disease, it is a struggle to teach our children about the same. Malaria is a disease that must be feared but let us not induce this threat in our kids. Instead, let us focus on imparting knowledge about malaria, its symptoms, and treatment to them in a fun way. By asking them to do simple tasks like cleaning their houses and surroundings and emptying the stagnant water from broken cups and bottles, we can build their awareness about the disease.

This short essay on malaria awareness concludes that however much of the threat is malaria, we can control it with proper awareness. So, let us nurture our children to grow in health and happiness with BYJU’S amazing essays on various topics.

Frequently Asked Questions on Essay on Malaria Awareness

Why should we raise awareness about malaria.

Malaria is a dangerous disease that has the potential to threaten one’s life. So, it is essential to create awareness about it to understand the symptoms and thereby treat it without any delay.

What is the importance of the malaria awareness essay?

The essay on malaria awareness can be useful for children to know more about the disease and the ways to prevent it.

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Malaria: Obstacles and Opportunities (1991)

Chapter: 1. conclusions and recommendations, conclusions and recommendations, defining the problem.

The outlook for malaria control is grim. The disease, caused by mosquito-borne parasites, is present in 102 countries and is responsible for over 100 million clinical cases and 1 to 2 million deaths each year. Over the past two decades, efforts to control malaria have met with less and less success. In many regions where malaria transmission had been almost eliminated, the disease has made a comeback, sometimes surpassing earlier recorded levels. The dream of completely eliminating malaria from many parts of the world, pursued with vigor during the 1950s and 1960s, has gradually faded. Few believe today that a global eradication of malaria will be possible in the foreseeable future.

Worldwide, the number of cases of malaria caused by Plasmodium falciparum , the most dangerous species of the parasite, is on the rise. Drug-resistant strains of P. falciparum are spreading rapidly, and there have been recent reports of drug resistance in people infected with P. vivax , a less virulent form of the parasite. Furthermore, mosquitoes are becoming increasingly resistant to insecticides, and in many cases, have adapted so as to avoid insecticide-treated surfaces altogether.

plied inappropriately. The situation in many African nations is particularly dismal, exacerbated by a crumbling health infrastructure that has made the implementation of any disease control program difficult.

Malaria cases among tourists, business travelers, military personnel, and migrant workers in malarious areas have been increasing steadily in the last several years, posing new concerns that the disease will be introduced to currently nonmalarious areas. Recent epidemics have claimed tens of thousands of lives in Africa, and there is an increasing realization that malaria is a major impediment to socioeconomic development in many countries. Unless practical, cost-effective strategies can be developed and successfully implemented, malaria will continue to exact a heavy toll on human life and health around the world.

Although often considered a single disease, malaria is more accurately viewed as many diseases, each shaped by subtle interactions of biologic, ecologic, social, and economic factors. The species of parasite, the behavior of the mosquito host, the individual's immune status, the climate, human activities, and access to health services all play important roles in determining the intensity of disease transmission, who will become infected, who will get sick, and who will die.

Gem miners along the Thailand-Cambodia border, American tourists on a wildlife safari in East Africa, villagers living on the central highlands in Madagascar, residents of San Diego County, California, a young pregnant woman in Malawi, Swiss citizens living near Geneva International Airport, children in Africa south of the Sahara, and a U.S. State Department secretary in Tanzania seem to have little in common, yet they are all at risk of contracting malaria. Because of the disease's variable presentations, each will be affected differently, as illustrated below.

For the hundreds of thousands of Thai seasonal agricultural workers who travel deep into the forest along the Thailand-Cambodia border to mine for gems, malaria is the cost of doing business. These young men are exposed to aggressive forest mosquitoes, and within two to three weeks after arriving, almost every miner will get malaria. Many gem miners seek medications to prevent and self-treat mild cases of the disease. But because malaria in this part of the world is resistant to most antimalarial drugs, the few effective drugs are reserved for the treatment of confirmed cases of malaria. To complicate matters, there are no health services in the forest to treat patients, and the health clinics in Thailand are overburdened by the high demand for treating those with severe malaria, most of whom are returning gem miners. A similar scenario involving over 400,000 people exists among gold miners in Rondonia, Brazil.

Each year, over seven million U.S. citizens visit parts of the world

where malaria is present. Many, at the recommendation of their travel agent or physician, take antimalarial medications as a preventive measure, but a significant number do not. Tourists and other travelers who have never been exposed to malaria, and therefore have never developed protective immunity, are at great risk for contracting severe disease. Ironically, it is not the infection itself that poses the biggest danger, but the chance that treatment will be delayed because of misdiagnosis upon the individual's return to the United States. Most U.S. doctors have never seen a patient with malaria, are often confused by the wide array of symptoms, and are largely unaware that malaria in a nonimmune person can be a medical emergency, sometimes rapidly fatal.

Prior to 1950, malaria was the major cause of death in the central highlands of the African island nation of Madagascar. In the late 1950s, an aggressive program of indoor insecticide spraying rid the area of malaria-carrying mosquitoes, and malaria virtually disappeared. By the 1970s, confident of a victory in the battle against malaria, Madagascar began to phase out its spraying program; in some areas spraying was halted altogether. In the early 1980s, the vector mosquitoes reinvaded the central highlands, and in 1986 a series of devastating epidemics began. The older members of the population had long since lost the partial immunity they once had, and the younger island residents had no immunity at all. During the worst of the epidemics, tens of thousands of people died in one three-month period. The tragedy of this story is that it could have been prevented. A cheap antimalarial drug, chloroquine, could have been a powerful weapon in Madagascar, where drug resistance was not a significant concern. Because of problems in international and domestic drug supply and delivery, however, many people did not receive treatment and many died. In the last 18 months, surveillance has improved, spraying against the mosquito has resumed, and more effective drug distribution networks have been established. Malaria-related mortality has declined sharply as a result.

Malaria, once endemic in the southern United States, occurs relatively infrequently. Indeed, there have been only 23 outbreaks of malaria since 1950, and the majority of these occurred in California. But for each of the past three years, the San Diego County Department of Health Services has had to conduct an epidemiologic investigation into local transmission of malaria. An outbreak in the late summer of 1988 involved 30 persons, the largest such outbreak in the United States since 1952. In the summer of 1989, three residents of San Diego County—a migrant worker and two permanent residents—were diagnosed with malaria; in 1990, a teenager living in a suburb of San Diego County fell ill with malaria. All of the cases were treated successfully, but these incidents raise questions about the possibility of new and larger outbreaks in the future. Malaria

transmission in San Diego County (and in much of California) is attributed to the presence of individuals from malaria-endemic regions who lack access to medical care, the poor shelter and sanitation facilities of migrant workers, and the ubiquitous presence of Anopheles mosquitoes in California.

A 24-year-old pregnant Yao woman from the Mangochi District in Malawi visited the village health clinic monthly to receive prenatal care. While waiting to be seen by the health provider, she and other women present listened to health education talks which were often about the dangers of malaria during pregnancy, and the need to install screens around the house to keep the mosquitoes away, to sleep under a bednet, and to take a chloroquine tablet once a week. Toward the end of her second trimester of pregnancy, the woman returned home from her prenatal visit with her eight tablets of chloroquine wrapped in a small packet of brown paper. She promptly gave the medicine to her husband to save for the next time he or one of their children fell ill. The next week she developed a very high malarial fever and went into labor prematurely. The six-month-old fetus was born dead.

Over a two-week period in the summer of 1989, five Swiss citizens living within a mile of Geneva International Airport presented at several hospitals with acute fever and chills. All had malaria. Four of the five had no history of travel to a malarious region; none had a history of intravenous drug use or blood transfusion. Apart from their symptoms, the only thing linking the five was their proximity to the airport. A subsequent epidemiologic investigation suggested that the malaria miniepidemic was caused by the bite of stowaway mosquitoes en route from a malaria-endemic country. The warm weather, lack of systematic spraying of aircraft, and the close proximity of residential areas to the airport facilitated the transmission of the disease.

Malaria is a part of everyday life in Africa south of the Sahara. Its impact on children is particularly severe. Mothers who bring unconscious children to the hospital often report that the children were playing that morning, convulsed suddenly, and have been unconscious ever since. These children are suffering from the most frequently fatal complication of the disease, cerebral malaria. Other children succumb more slowly to malaria, becoming progressively more anemic with each subsequent infection. By the time they reach the hospital, they are too weak to sit and are literally gasping for breath. Many children are brought to hospitals as a last resort, after treatment given for “fever” at the local health center has proved ineffective. Overall, children with malaria account for a third of all hospital admissions. A third of all children hospitalized for malaria die. In most parts of Africa, there are no effective or affordable options to prevent the

disease, so children are at high risk until they have been infected enough times to develop a partial immunity.

A 52-year-old American woman, the secretary to the U.S. ambassador in Tanzania, had been taking a weekly dose of chloroquine to prevent malaria since her arrival in the country the year before. She arrived at work one morning complaining of exhaustion, a throbbing headache, and fever. A blood sample was taken and microscopically examined for malaria parasites. She was found to be infected with P. falciparum , and was treated immediately with high doses of chloroquine. That night, she developed severe diarrhea, and by morning she was found to be disoriented and irrational. She was diagnosed as having cerebral malaria, and intravenous quinine treatment was started. Her condition gradually deteriorated—she became semicomatose and anemic, and approximately 20 percent of her red blood cells were found to be infected with malaria parasites. After continued treatment for several days, no parasites were detected in her blood. Despite receiving optimal care, other malaria-related complications developed and she died just nine days after the illness began. The cause of death: chloroquine-resistant P. falciparum .

These brief scenarios give a sense of the diverse ways that malaria can affect people. So fundamental is this diversity with respect to impact, manifestation, and epidemiology that malaria experts themselves are not unanimous on how best to approach the disease. Malariologists recognize that malaria is essentially a local phenomenon that varies greatly from region to region and even from village to village in the same district. Consequently, a single global technology for malaria control is of little use for specific conditions, yet the task of tailoring strategies to each situation is daunting. More important, many malarious countries do not have the resources, either human or financial, to carry out even the most meager efforts to control malaria.

These scenarios also illustrate the dual nature of malaria as it affects U.S. policy. In one sense, it is a foreign aid issue; a devastating disease is currently raging out of control in vast, heavily populated areas of the world. In another sense, malaria is of domestic public health concern. The decay of global malaria control and the invasion of the parasite into previously disease-free areas, coupled with the increasing frequency of visits to such areas by American citizens, intensify the dangers of malaria for the U.S. population. Tourists, business travelers, Peace Corps volunteers, State Department employees, and military personnel are increasingly at risk, and our ability to protect and cure them is in jeopardy. What is desperately needed is a better application of existing malaria control tools and new methods of containing the disease.

In most malarious regions of the world, there is inadequate access to malaria treatment. Appropriate health facilities may not exist; those that do exist may be inaccessible to affected populations, may not be supplied with effective drugs, or may be staffed inappropriately. In many countries, the expansion of primary health care services has not proceeded according to expectations, particularly in the poorest (and most malarious) nations of the tropical world.

In some countries, antimalarial interventions are applied in broad swaths, without regard to underlying differences in the epidemiology of the disease. In other countries, there are no organized interventions at all. The malaria problem in many regions is compounded by migration, civil unrest, poorly planned exploitation of natural resources, and their frequent correlate, poverty.

During the past 15 years, much research has focused on developing vaccines for malaria. Malaria vaccines are thought to be possible in part because people who are naturally exposed to the malaria parasite acquire a partial immunity to the disease over time. In addition, immunization of animals and humans by the bites of irradiated mosquitoes infected with the malaria parasite can protect against malaria infection. Much progress has been made, but current data suggest that effective vaccines are not likely to be available for some time.

Compounding the difficulty of developing more effective malaria prevention, treatment, and control strategies is a worldwide decline in the pool of scientists and health professionals capable of conducting field research and organizing and managing malaria control programs at the country level. With the change in approach from malaria eradication to malaria control, many malaria programs “lost face,” admitting failure and losing the priority interest of their respective ministries of health. As external funding agencies lost interest in programs, they reduced their technical and financial support. As a consequence, there were fewer training opportunities, decreased contacts with international experts, and diminished prospects for improving the situation. Today, many young scientists and public health specialists, in both the developed and developing countries, prefer to seek higher-profile activities with better defined opportunities for career advancement.

dations to the U.S. government on promising and feasible strategies to address the problem. During the 18-month study, the committee reviewed the state of the science in the major areas of malariology, identified gaps in knowledge within each of the major disciplines, and developed recommendations for future action in malaria research and control.

Organization

Chapter 2 summarizes key aspects of the individual state-of-the-science chapters, and is intended to serve as a basic introduction to the medical and scientific aspects of malaria, including its clinical signs, diagnosis, treatment, and control. Chapter 3 provides a historical overview of malaria, from roughly 3000 B.C. to the present, with special emphasis on efforts in this century to eradicate and control the disease. The state-of-the-science reviews, which start in Chapter 4 , begin with a scenario titled “Where We Want To Be in the Year 2010.” Each scenario describes where the discipline would like to be in 20 years and how, given an ideal world, the discipline would have contributed to malaria control efforts. The middle section of each chapter contains a critical review of the current status of knowledge in the particular field. The final section lays out specific directions for future research based on a clear identification of the major gaps in scientific understanding for that discipline. The committee urges those agencies that fund malaria research to consult the end of each state-of-the-science chapter for suggestions on specific research opportunities in malaria.

Sponsorship

This study was sponsored by the U.S. Agency for International Development, the U.S. Army Medical Research and Development Command, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

CONCLUSIONS AND RECOMMENDATIONS

A major finding of the committee is the need to increase donor and public awareness of the growing risk presented by the resurgence of malaria. Overall, funding levels are not adequate to meet the problem. The committee believes that funding in the past focused too sharply on specific technologies and particular control strategies (e.g., indiscriminate use of insecticide spraying). Future support must be balanced among the needs outlined in this report. The issue for prioritization is not whether to select specific technologies or control strategies, but to raise the priority for solv-

ing the problem of malaria. This is best done by encouraging balanced research and control strategies and developing a mechanism for periodically adjusting support for promising approaches.

This report highlights those areas which the committee believes deserve the highest priority for research or which should be considered when U.S. support is provided to malaria control programs. These observations and suggestions for future action, presented below in four sections discussing policy, research, control, and training, represent the views of a multidisciplinary group of professionals from diverse backgrounds and with a variety of perspectives on the problem.

The U.S. government is the largest single source of funds for malaria research and control activities in the world. This investment is justified by the magnitude of the malaria problem, from both a foreign aid and a public health perspective. The increasing severity of the threat of malaria to residents of endemic regions, travelers, and military personnel, and our diminishing ability to counter it, should be addressed by a more comprehensive and better integrated approach to malaria research and control. However, overall U.S. support for malaria research and control has declined over the past five years. The committee believes that the amount of funding currently directed to malaria research and control activities is inadequate to address the problem.

Over the past 10 years, the majority of U.S. funds available for malaria research have been devoted to studies on immunity and vaccine development. Although the promise of vaccines remains to be realized, the committee believes that the potential benefits are enormous. At the same time, the relative paucity of funds available for research has prevented or slowed progress in other areas. Our incomplete knowledge about the basic biology of malaria parasites, how they interact with their mosquito and human hosts, and how human biology and behavior affect malaria transmission and control remains a serious impediment to the development and implementation of malaria control strategies. The committee believes that this situation must be addressed without reducing commitment to current research initiatives. The committee further believes that such research will pay long-term dividends in the better application of existing tools and the development of new drugs, vaccines, and methods for vector control.

The committee recommends that increased funds be made available so that U.S. research on malaria can be broadened according to the priorities addressed in this report, including laboratory and field research on the biology of malaria parasites, their mosquito vectors, and their interaction with humans.

The committee believes that the maximum return on investment of funds devoted to malaria research and control can be achieved only by rigorous review of project proposals. The committee further believes that the highest-quality review is essential to ensure that funding agencies spend their money wisely. The committee believes that all U.S.-supported malaria field activities, both research and control, should be of the highest scientific quality and relevance to the goals of malaria control.

The committee recommends decisions on funding of malaria research be based on scientific merit as determined by rigorous peer review, consistent with the guidelines of the National Institutes of Health or the United Nations Development Program/World Bank/ World Health Organization Special Programme for Research and Training in Tropical Diseases, and that all U.S.-supported malaria field projects be subject to similar rigorous review to ensure that projects are epidemiologically and scientifically sound.

Commitment and Sustainability

For malaria control, short-term interventions can be expected to produce only short-term results. The committee believes that short-term interventions are justified only for emergency situations. Longer-term interventions should be undertaken only when there is a national commitment to support sustained malaria surveillance and control.

The committee recommends that malaria control programs receive sustained international and local support, oriented toward the development of human resources, the improvement of management skills, the provision of supplies, and the integration of an operational research capability in support of an epidemiologically sound approach to malaria control.

Surveillance

During the major effort to eradicate malaria from many parts of the world that began in the late 1950s and ended in 1969, it was important to establish mechanisms to detect all malaria infections. As a result, systems were established in many countries to collect blood samples for later microscopic examination for the presence of parasites. Each year, the results from more than 140 million slides are reported to the World Health Organization, of which roughly 3 to 5 percent are positive for malaria. This approach seeks to answer the question posed 30 years ago: How many people are infected with the malaria parasite? It does not answer today's questions: Who is sick? Where? Why? The committee concludes that the mass collection of blood slides requires considerable resources, poses seri-

ous biosafety hazards, deflects attention from the treatment of ill individuals, and has little practical relevance for malaria control efforts today.

Instead of the mass collection of slides, the committee believes that the most effective surveillance networks are those that concurrently measure disease in human populations, antimalarial drug use, patterns of drug resistance, and the intensity of malaria transmission by vector populations. The committee believes that malaria surveillance practices have not received adequate recognition as an epidemiologic tool for designing, implementing, and evaluating malaria control programs.

The committee recommends that countries be given support to orient malaria surveillance away from the mass collection and screening of blood slides toward the collection and analysis of epidemiologically relevant information that can be used to monitor the current situation on an ongoing basis, to identify high-risk groups, and to detect potential epidemics early in their course.

Inter-Sectoral Cooperation

The committee believes that insufficient attention has been paid to the impact that activities in non-health-related sectors, such as construction, industry, irrigation, and agriculture, have on malaria transmission. Conversely, there are few assessments of the impact of malaria control projects on other public health initiatives, the environment, and the socioeconomic status of affected populations. Malaria transmission frequently occurs in areas where private and multinational businesses and corporations (e.g., hotel chains, mining operations, and industrial plants) have strong economic interests. Unfortunately and irresponsibly, some local and multinational businesses contribute few if any resources to malaria control in areas in which they operate.

The committee recommends greater cooperation and consultation between health and nonhealth sectors in the planning and implementation of major development projects and malaria activities. It also recommends that all proposed malaria control programs be analyzed for their potential impact on other public health programs, the environment, and social and economic welfare, and that local and multinational businesses be recruited by malaria control organizations to contribute substantially to local malaria control efforts.

New Tools for Malaria Control

The committee believes that, as a policy directive, it is important to support research activities to develop new tools for malaria control. The

greatest momentum for the development of new tools exists in vaccine and drug development, and the committee believes it essential that this momentum be maintained. The committee recognizes that commendable progress has been made in defining the characteristics of antigens and delivery systems needed for effective vaccines, but that the candidates so far tested fall short of the goal. Much has been learned which supports the hope that useful vaccines can be developed. To diminish activity in vaccine development at this stage would deal a severe blow to one of our best chances for a technological breakthrough in malaria control.

The committee recommends that vaccine development continue to be a priority of U.S.-funded malaria research.

Only a handful of drugs are available to prevent or treat malaria, and the spread of drug-resistant strains of the malaria parasite threatens to reduce further the limited pool of effective drugs. The committee recognizes that there is little economic incentive for U.S. pharmaceutical companies to undertake antimalarial drug discovery activities. The committee is concerned that U.S. government support of these activities, based almost entirely at the Walter Reed Army Institute of Research (WRAIR), has decreased and is threatened with further funding cuts. The committee concludes that the WRAIR program in antimalarial drug discovery, which is the largest and most successful in the world, is crucial to international efforts to develop new drugs for malaria. The benefits of this program in terms of worldwide prevention and treatment of malaria have been incalculable.

The committee strongly recommends that drug discovery and development activities at WRAIR receive increased and sustained support.

The next recommendation on policy directions reflects the committee 's concern about the lack of involvement in malaria research by the private sector. The committee believes that the production of candidate malaria vaccines and antimalarial drugs for clinical trials has been hampered by a lack of industry involvement. Greater cooperation and a clarification of the contractual relationships between the public and private sectors would greatly enhance the development of drugs and vaccines.

The committee recommends that mechanisms be established to promote the involvement of pharmaceutical and biotechnology firms in the development of malaria vaccines, antimalarial drugs, and new tools for vector control.

Coordination and Integration

The committee is concerned that there is inadequate joint planning and coordination among U.S.-based agencies that support malaria research and

control activities. Four government agencies and many nongovernmental organizations in the United States are actively involved in malaria-related activities. There are also numerous overseas organizations, governmental and nongovernmental, that actively support such activities worldwide.

The complexity and variability of malaria, the actual and potential scientific advances in several areas of malariology, and most important the worsening worldwide situation argue strongly for an ongoing mechanism to assess and influence current and future U.S. efforts in malaria research and control.

The committee strongly recommends the establishment of a national advisory body on malaria.

In addition to fulfilling a much needed coordinating function among U.S.-based agencies and between the U.S. and international efforts, the national advisory body could monitor the status of U.S. involvement in malaria research and control, assess the relevant application of knowledge, identify areas requiring further research, make recommendations to the major funding agencies, and provide a resource for legislators and others interested in scientific policy related to malaria. The national advisory body could convene specific task-oriented scientific working groups to review research and control activities and to make recommendations, when appropriate, for changes in priorities and new initiatives.

The committee believes that the national advisory body should be part of, and appointed by, a neutral and nationally respected scientific body and that it should actively encourage the participation of governmental and nongovernmental organizations, industry, and university scientists in advising on the direction of U.S. involvement in malaria research and control.

The increasing magnitude of the malaria problem during the past decade and the unpredictability of changes in human, parasite, and vector determinants of transmission and disease point strongly to the need for such a national advisory body, which can be responsive to rapidly changing problems, and advances in scientific research, relating to global efforts to control malaria.

Malaria Research Priorities

Malaria control is in crisis in many areas of the world. People are contracting and dying of severe malaria in unprecedented numbers. To address these problems, the committee strongly encourages a balanced research agenda. Two basic areas of research require high priority. Research that will lead to improved delivery of existing interventions for malaria, and the development of new tools for the control of malaria.

Research in Support of Available Control Measures

Risk Factors for Severe Malaria People who develop severe and complicated malaria lack adequate immunity, and many die from the disease. Groups at greatest risk include young children and pregnant women in malaria endemic regions; nonimmune migrants, laborers, and visitors to endemic regions; and residents of regions where malaria has been recently reintroduced. For reasons that are largely unknown, not all individuals within these groups appear to be at equal risk for severe disease. The committee believes that the determinants of severe disease, including risk factors associated with a population, the individual (biologic, immunologic, socioeconomic, and behavioral), the parasite, or exposure to mosquitoes, are likely to vary considerably in different areas.

The committee recommends that epidemiologic studies on the risk factors for severe and complicated malaria be supported.

Pathogenesis of Severe and Complicated Malaria Even with optimal care, 20 to 30 percent of children and adults with the most severe form of malaria—primarily cerebral malaria—die. The committee believes that a better understanding of the disease process will lead to improvements in preventing and treating severe forms of malaria. The committee further believes that determining the indications for treatment of severe malarial anemia is of special urgency given the risk of transmitting the AIDS virus through blood transfusions, the only currently available treatment for malarial anemia. Physicians need to know when it is appropriate to transfuse malaria patients.

The committee recommends greater support for research on the pathogenesis of severe and complicated malaria, on the mechanisms of malarial anemia, and on the development of specific criteria for blood transfusions in malaria.

into program design. In most countries, little is known about how the demand for and utilization of health services is influenced by such things as user fees, location of health clinics, and the existence and quality of referral services. The committee concludes that modern social science techniques have not been effectively applied to the design, implementation, and evaluation of malaria control programs.

The committee recommends that research be conducted on local perceptions of malaria as an illness, health-seeking behaviors (including the demand for health care services), and behaviors that affect malaria transmission, and that the results of this research be included in community-based malaria control interventions that promote the involvement of communities and their organizations in control efforts.

Innovative Approaches to Malaria Control Malaria control programs will require new ideas and approaches, and new malaria control strategies need to be developed and tested. There is also a need for consistent support of innovative combinations of control technologies and for the transfer of new technologies from the laboratory to the clinic and field for expeditious evaluation. Successful technology transfer requires the exchange of scientific research, but more importantly, must be prefaced by an improved understanding of the optimal means to deliver the technology to the people in need (see Chapter 11 ).

The committee recommends that donor agencies provide support for research on new or improved control strategies and into how new tools and technologies can be better implemented and integrated into on-going control efforts.

Development of New Tools

Antimalarial Immunity and Vaccine Development Many people are able to mount an effective immune response that can significantly mitigate symptoms of malaria and prevent death. The committee believes that the development of effective malaria vaccines is feasible, and that the potential benefits of such vaccines are enormous. Several different types of malaria vaccines need to be developed: vaccines to prevent infection (of particular use for tourists and other nonimmune visitors to endemic countries), prevent the progression of infection to disease (for partially immune residents living in endemic areas and for nonimmune visitors), and interrupt transmission of parasites by vector populations (to reduce the risk of new infections in humans). The committee believes that each of these directions should be pursued.

The committee recommends sustained support for research to identify mechanisms and targets of protective immunity and to exploit the

use of novel scientific technologies to construct vaccines that induce immunity against all relevant stages of the parasite life cycle.

Drug Discovery and Development Few drugs are available to prevent or treat malaria, and the spread of drug-resistant strains of malaria parasites is steadily reducing the limited pool of effective chemotherapeutic agents. The committee believes that an inadequate understanding of parasite biochemistry and biology impedes the process of drug discovery and slows studies on the mechanisms of drug resistance.

The committee recommends increased emphasis on screening compounds to identify new classes of potential antimalarial drugs, identifying and characterizing vulnerable targets within the parasite, understanding the mechanisms of drug resistance, and identifying and developing agents that can restore the therapeutic efficacy of currently available drugs.

Vector Control Malaria is transmitted to humans by the bites of infective mosquitoes. The objective of vector control is to reduce the contact between humans and infected mosquitoes. The committee believes that developments are needed in the areas of personal protection, environmental management, pesticide use and application, and biologic control, as well as in the largely unexplored areas of immunologic and genetic approaches for decreasing parasite transmission by vectors.

The committee recommends increased support for research on vector control that focuses on the development and field testing of methods for interrupting parasite transmission by vectors.

Malaria Control

Malaria is a complex disease that, even under the most optimistic scenario, will continue to be a major health threat for decades. The extent to which malaria affects human health depends on a large number of epidemiologic and ecologic factors. Depending on the particular combination of these and other variables, malaria may have different effects on neighboring villages and people living in a single village. All malaria control programs need to be designed with a view toward effectiveness and sustainability, taking into account the local perceptions, the availability of human and financial resources, and the multiple needs of the communities at risk. If community support for health sector initiatives is to be guaranteed, the public needs to know much more about malaria, its risks for epidemics and severe disease, and difficulties in control.

antimalarial tools, the committee suggests that donor agencies support four priority areas for malaria control in endemic countries.

The committee believes that the first and most basic priority in malaria control is to prevent infected individuals from becoming severely ill and dying. Reducing the incidence of severe morbidity and malaria-related mortality requires a two-pronged approach. First, diagnostic, treatment, and referral capabilities, including the provision of microscopes, training of technicians and other health providers, and drug supply, must be enhanced. Second, the committee believes that many malaria-related deaths could be averted if individuals and caretakers of young children knew when and how to seek appropriate treatment and if drug vendors, pharmacists, physicians, nurses, and other health care providers were provided with up-to-date and locally appropriate treatment and referral guidelines. The development and implementation of an efficient information system that provides rapid feedback to the originating clinic and area is key to monitoring the situation and preventing epidemics.

The committee believes that the second priority should be to promote personal protection measures (e.g., bednets, screens, and mosquito coils) to reduce or eliminate human-mosquito contact and thus to reduce the risk of infection for individuals living in endemic areas. At the present time, insecticide-treated bednets appear to be the most promising personal protection method.

In many environments, in addition to the treatment of individuals and use of personal protection measures, community-wide vector control is feasible. In such situations, the committee believes that the third priority should be low-cost vector control measures designed to reduce the prevalence of infective mosquitoes in the environment, thus reducing the transmission of malaria to populations. These measures include source reduction (e.g., draining or filling in small bodies of water where mosquito larvae develop) or the application of low-cost larval control measures. In certain environments, the use of insecticide-impregnated bednets by all or most members of a community may also reduce malaria transmission, but this approach to community-based malaria control remains experimental.

The committee believes that the fourth priority for malaria control should be higher cost vector control measures such as large-scale source reduction or widespread spraying of residual insecticides. In certain epidemiologic situations, the use of insecticides for adult mosquito control is appropriate and represents the method of choice for decreasing malaria transmission and preventing epidemics (see Chapter 7 and Chapter 10 ).

The committee recommends that support of malaria control programs include resources to improve local capacities to conduct prompt diagnosis, including both training and equipment, and to ensure the availability of antimalarial drugs.

The committee recommends that resources be allocated to develop and disseminate malaria treatment guidelines for physicians, drug vendors, pharmacists, village health workers, and other health care personnel in endemic and non-endemic countries. The guidelines should be based, where appropriate, on the results of local operational research and should include information on the management of severe and complicated disease. The guidelines should be consistent and compatible among international agencies involved in the control of malaria.

The committee recommends that support for malaria control initiatives include funds to develop and implement locally relevant communication programs that provide information about how to prevent and treat malaria appropriately (including when and how to seek treatment) and that foster a dialogue about prevention and control.

Organization of Malaria Control

One of the major criticisms of malaria control programs during the past 10 to 15 years has been that funds have been spent inappropriately without an integrated plan and without formal evaluation of the efficacy of control measures instituted. In many instances, this has led to diminished efforts to control malaria.

The committee strongly encourages renewed commitment by donor agencies to support national control programs in malaria-endemic countries.

The committee recommends that U.S. donor agencies develop, with the advice of the national advisory body, a core of expertise (either in-house or through an external advisory group) to plan assistance to malaria control activities in endemic countries.

The committee believes that the development, implementation, and evaluation of such programs must follow a rigorous set of guidelines. These guidelines should include the following steps:

Identification of the problem

Determine the extent and variety of malaria. The paradigm approach described in Chapter 10 should facilitate this step.

Analyze current efforts to solve malaria problems.

Identify and characterize available in-country resources and capabilities.

Development of a plan

Design and prioritize interventions based on the epidemiologic situation and the available resources.

Design a training program for decision makers, managers, and technical staff to support and sustain the interventions.

Define specific indicators of the success or failure of the interventions at specific time points.

Develop a specific plan for reporting on the outcomes of interventions.

Develop a process for adjusting the program in response to successes and/or failures of interventions.

Review of the comprehensive plan by a donor agency review board

Modification of the plan based on comments of the review board

Implementation of the program

Yearly report and analysis of outcome variables

To guide the implementation of the activities outlined above, the committee has provided specific advice on several components, including an approach to evaluating malaria problems and designing control strategies (the paradigm approach), program management, monitoring and evaluation, and operational research.

Paradigm Approach

Given the complex and variable nature of malaria, the committee believes that the epidemiologic paradigms (see Chapter 10 ), developed in conjunction with this study, may form the basis of a logical and reasoned approach for defining the malaria problems and improving the design and management of malaria control programs.

The committee recommends that the paradigm approach be field tested to determine its use in helping policymakers and malaria program managers design and implement epidemiologically appropriate and cost-effective control initiatives.

The committee recognizes that various factors, including the local ecology, the dynamics of mosquito transmission of malaria parasites, genetically determined resistance to malaria infection, and patterns of drug use, affect patterns of malaria endemicity in human populations and need to be considered when malaria control strategies are developed. In most endemic countries, efforts to understand malaria transmission through field studies of vector populations are either nonexistent or so limited in scope that they have minimal impact on subsequent malaria control efforts. The committee recognizes that current approaches to malaria control are clearly inadequate. The committee believes, however, that malaria control strategies are sometimes applied inappropriately, with little regard to the underlying differences in the epidemiology of the disease.

The committee recommends that support for malaria control programs include funds to permit a reassessment and optimization of antimalarial tools based on relevant analyses of local epidemiologic, parasitologic, entomologic, socioeconomic, and behavioral determinants of malaria and the costs of malaria control.

Poor management has contributed to the failure of many malaria control programs. Among the reasons are a chronic shortage of trained managers who can think innovatively about health care delivery and who can plan, implement, supervise, and evaluate malaria control programs. Lack of incentives, the absence of career advancement options, and designation of responsibility without authority often hinder the effectiveness of the small cadre of professional managers that does exist. The committee recognizes that management technology is a valuable resource that has yet to be effectively introduced into the planning, implementation, and evaluation of most malaria control programs.

The committee recommends that funding agencies utilize management experts to develop a comprehensive series of recommendations and guidelines as to how basic management skills and technology can be introduced into the planning, implementation, and evaluation of malaria control programs.

The committee recommends that U.S. funding of each malaria control program include support for a senior manager who has responsibility for planning and coordinating malaria control activities. Where such an individual does not exist, a priority of the control effort should be to identify and support a qualified candidate. The manager should be supported actively by a multidisciplinary core group with expertise in epidemiology, entomology, the social sciences, clinical medicine, environmental issues, and vector control operations.

Monitoring and Evaluation

Monitoring and evaluation are essential components of any control program. For malaria control, it is not acceptable to continue pursuing a specific control strategy without clear evidence that it is effective and reaching established objectives.

The committee recommends that support for malaria control programs include funds to evaluate the impact of control efforts on the magnitude of the problem and that each program be modified as necessary on the basis of periodic assessments of its costs and effectiveness.

Problem Solving (Operational Research) and Evaluation

At the outset of any malaria prevention or control initiative and during the course of implementation, gaps in knowledge will be identified and problems will arise. These matters should be addressed through clearly defined, short-term, focused studies. Perhaps the most difficult aspects of operational research are to identify the relevant problem, formulate the appropriate question, and design a study to answer that question.

The committee recommends that a problem-solving (operational research) component be built into all existing and future U.S.-funded malaria control initiatives and that support be given to enhance the capacity to perform such research. This effort will include consistent support in the design of focused projects that can provide applicable results, analysis of data, and dissemination of conclusions.

The committee concludes that there is a need for additional scientists actively involved in malaria-related research in the United States and abroad. To meet this need, both short- and long-term training at the doctoral and postdoctoral levels must be provided. This training will be of little value unless there is adequate long-term research funding to support the career development of professionals in the field of malaria.

The committee recommends support for research training in malaria.

Whereas the curricula for advanced degree training in basic science research and epidemiology are fairly well defined, two areas require attention, especially in the developing world: social sciences and health management and training.

The committee recommends that support be given for the development of advanced-degree curricula in the social sciences, and in health management and training, for use in universities in developing and developed countries.

The availability of well-trained managers, decision makers, and technical staff is critical to the implementation of any malaria prevention and control program. The development of such key personnel requires a long term combination of formal training, focused short courses, and a gradual progression of expertise.

between institutions in developed and developing countries; through the encouragement of both formal and informal linkages among malaria-endemic countries; through the use of existing training courses; and through the development of specific training courses.

The committee recommends further that malaria endemic countries be supported in the development of personnel programs that provide long-term career tracks for managers, decision makers, and technical staff, and that offer professional fulfillment, security, and competitive financial compensation.

Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death.

This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities.

The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the:

Nature, clinical manifestations, diagnosis, and epidemiology of malaria.
Biology of the malaria parasite and its vector.
Prospects for developing malaria vaccines and improved treatments.
Economic, social, and behavioral factors in malaria control.

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Open access
Published: 07 January 2021

Plasmodium —a brief introduction to the parasites causing human malaria and their basic biology

Shigeharu Sato ORCID: orcid.org/0000-0003-2738-430X 1 , 2

Journal of Physiological Anthropology volume 40 , Article number: 1 ( 2021 ) Cite this article

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A Correction to this article was published on 29 January 2021

This article has been updated

Malaria is one of the most devastating infectious diseases of humans. It is problematic clinically and economically as it prevails in poorer countries and regions, strongly hindering socioeconomic development. The causative agents of malaria are unicellular protozoan parasites belonging to the genus Plasmodium. These parasites infect not only humans but also other vertebrates, from reptiles and birds to mammals. To date, over 200 species of Plasmodium have been formally described, and each species infects a certain range of hosts. Plasmodium species that naturally infect humans and cause malaria in large areas of the world are limited to five— P. falciparum , P. vivax , P. malariae , P. ovale and P. knowlesi . The first four are specific for humans, while P. knowlesi is naturally maintained in macaque monkeys and causes zoonotic malaria widely in South East Asia. Transmission of Plasmodium species between vertebrate hosts depends on an insect vector, which is usually the mosquito. The vector is not just a carrier but the definitive host, where sexual reproduction of Plasmodium species occurs, and the parasite’s development in the insect is essential for transmission to the next vertebrate host. The range of insect species that can support the critical development of Plasmodium depends on the individual parasite species, but all five Plasmodium species causing malaria in humans are transmitted exclusively by anopheline mosquitoes. Plasmodium species have remarkable genetic flexibility which lets them adapt to alterations in the environment, giving them the potential to quickly develop resistance to therapeutics such as antimalarials and to change host specificity. In this article, selected topics involving the Plasmodium species that cause malaria in humans are reviewed.

Background: battle of humans against malaria—past and present

Malaria has been recognised as a serious health problem since the earliest historical times. This disease is caused by protozoan parasites belonging to the genus Plasmodium . The strong negative pressure of the disease has likely forced the evolution of human populations in malaria endemic regions and the selection of some unique genetic variants. For example, thalassemia and sickle-cell disease, each of which is a genetic disorder affecting red blood cells, are commonly found in malaria endemic areas [ 1 ], and people with these two disorders show resistance to malaria. Another well-known example is the Duffy-negative blood type that the majority of people living in Central and West Africa have [ 2 ]. This confers specific resistance to infection by one particular Plasmodium species, P. vivax [ 3 , 4 ]. The spread of this trait in the population is estimated to have begun around 42,000 years ago [ 5 ], and today P. vivax malaria is rare in these areas whereas P. falciparum malaria is prevalent [ 6 ].

Even in the modern world with effective antimalarials and insecticide-treated bed nets (ITNs), people in many countries remain at risk, and the number of malaria cases, particularly those resulting from P. falciparum that causes the most serious infection, remains high in economically poor countries, especially in Africa [ 7 ]. Rolling out adequate and continuous programmes to effectively control malaria has been difficult mainly due to lack of finance. In 2000, the health programme to “combat malaria” was selected as one of the critical global targets of the Millennium Development Goals set by the United Nations. This global effort was to achieve the targets that were set for measurable health indicators, such as disease prevalence, death rates and protection of children under 5-years of age with ITNs and appropriate antimalarial drugs. In 2005, the sum of global investments for malaria control was an estimated US$960 million, mostly from National Malaria Control Programmes (NMCPs) [ 7 ]. Whilst contributions from NMCPs remained at the same level, investments from other sources started to increase steadily since 2006. As a result, the sum of global investments surpassed US$2000 million in 2009 and has remained almost at this level thereafter [ 7 ]. With this extra financing, malaria control programs achieved a remarkable level of progress globally. For example, in 2000, the annual deaths caused by malaria in the entire world and in Africa were estimated to be 839,000 (between 653,000 and 1.1 million) and 694,000 (569,000–901,000), respectively. By 2015, these numbers had been reduced to 483,000 (236,000–635,000) and 292,000 (212,000–384,000) [ 7 ]. The number of countries estimated to have fewer than 1000 indigenous malaria cases increased from 13 in 2000 to 33 in 2015 [ 7 ], and six countries (United Arab Emirates, Morocco, Armenia, Turkmenistan, Kyrgyzstan and Sri Lanka) achieved at least 3 consecutive years of zero indigenous cases between 2000 and 2015 and were certified as malaria free by WHO [ 8 ].

Plasmodium species infecting humans share a similar life cycle with an initial development phase in the liver and subsequent further proliferation in the blood of the host. They also show a similar susceptibility to some antimalarial drugs such as quinine, chloroquine and artemisinin, as well as the development of resistance to these drugs [ 9 , 10 ]. Transmission is also mediated by the same group of anopheline mosquitoes [ 11 ]. P. vivax malaria can relapse after chemotherapy with drugs that kill the parasites only in the intraerythrocytic development stage [ 12 ], but 8-aminoquinolines such as primaquine are known to prevent this effectively [ 13 ]. Thus, systematic control programmes involving appropriate chemotherapy including administration of primaquine to patients with P. vivax malaria, as well as proper mosquito control, can simultaneously reduce the number of malaria incidents caused by any Plasmodium species.

There have been reports of malaria in humans caused by other Plasmodium species that naturally infect other primate hosts. But zoonotic malaria is rare, except for that caused by P. knowlesi , which naturally infects macaque monkeys such as the long-tailed and the pig-tailed macaques ( Macaca fascicularis and M. nemestrina , respectively). Human infection by P. knowlesi has been reported since the 1960s [ 14 , 15 ], but it had been long thought exceptional like other zoonotic malarias.

The NMCP rolled out in Malaysia in the 1960s had achieved a dramatic reduction of the number of human malaria cases caused by P. falciparum and P. vivax in Sarawak in Malaysian Borneo by the late 1990s–early 2000s. By contrast, the incidence of P. malariae which is rather rare in that state [ 16 ] showed an apparent increase [ 17 ]. At that time, the species of Plasmodium present in patients in Sarawak was identified solely by microscopical observation of parasites in blood films. However, a molecular diagnosis combining nested PCR and DNA sequencing revealed that most of the malaria cases attributed to P. malariae by microscopy were actually caused by P. knowlesi [ 18 ]. Following the identification of human cases of P. knowlesi in Sarawak, similar cases were identified in neighbouring Sabah state [ 19 ] and within the Peninsular Malaysia [ 20 ]. Human infections of P. knowlesi have also been reported in other South East Asian countries including Vietnam and Thailand [ 17 ], and P. knowlesi malaria is now recognised as the fifth human malaria [ 21 ]. It has been confirmed that P. knowlesi can produce gametocytes in patients who naturally acquire the infection [ 22 ], although transmission of P. knowlesi malaria between humans has not been reported yet. The clinical importance of P. knowlesi malaria is particularly high in Malaysia, where malaria caused by the other four human-infective species has been almost completely eliminated thanks to the successful NMCP [ 6 ]. Now, almost all malaria cases identified in the country are caused by P. knowlesi .

Like P. knowlesi , other Plasmodium species that naturally infect non-human primates have been considered as potential threats to human health through zoonosis [ 23 , 24 ]. Macaques in Sarawak in Malaysian Borneo are known to be the reservoir of six Plasmodium species— P. knowlesi , P. inui , P. cynomolgi , P. coatneyi , P. fieldi and P. simiovale [ 25 ]. Of these, P. cynomolgi has been proven to naturally cause human infection [ 26 ], and P. inui can establish an infection when experimentally introduced into humans [ 27 ]. Clinical cases of zoonotic malaria caused by these species are currently either extremely rare ( P. cynomolgi ) or unreported ( P. inui ), but they might become the next Plasmodium species to significantly affect human health in the future.

Zoonotic malaria has been reported in South America as well. The species of Plasmodium implicated there are P. simium [ 28 ] and P. brasilianum [ 29 ], parasites that naturally infect platyrrhine monkeys. The two species, P. simium and P. brasilianum , have been shown to be phylogenetically very close to P. vivax and P. malariae , respectively [ 30 ].

Malaria and Plasmodium biology

Life cycle of plasmodium.

All Plasmodium species share a similar life cycle [ 31 ]. It has two parts—in the first, the parasite infects a person (or a vertebrate host), and in the second, it is transmitted from the malaria patient (or infected vertebrate host) to another host by an insect vector. The vectors that transmit the five Plasmodium species naturally infecting humans are mosquitoes of the genus Anopheles . These mosquitoes also transmit other Plasmodium species parasitising other mammals whereas transmission of Plasmodium infecting birds and reptiles depends on mosquitoes of other genera or other blood-sucking insects [ 32 ].

The Plasmodium life cycle begins when parasites known as sporozoites produced in the insect vector enter the blood of the vertebrate host following a bite [ 33 ]. Sporozoites deposited in the dermis [ 34 ] rapidly migrate to the liver and invade hepatocytes where they multiply by thousands—a process known as schizogony [ 35 ]. The resulting parasites, now called merozoites, are released back into the blood [ 36 ] and infect erythrocytes. In an erythrocyte, one merozoite multiplies asexually by schizogony to generate between 8 and 64 new merozoites (the number depending on the species) [ 37 ]. These new merozoites are released back to the blood, and the parasites repeat this intraerythrocytic propagation cycle every 24 ( P. knowlesi ), 48 ( P. falciparum , P. ovale , P. vivax ) or 72 ( P. malariae ) hours. Some merozoites then differentiate into the next developmental stage called the gametocyte for sexual reproduction [ 38 , 39 ]. Just when gametocyte differentiation (gametocytogenesis) starts depends on the species. For example, P. falciparum needs to complete several cycles of intraerythrocytic propagation before it starts differentiation into gametocytes, whereas P. vivax continuously produces gametocytes even in its early intraerythrocytic propagation cycles (Table 1 ). While each gametocyte has a similar appearance during its early development, they are already programmed to differentiate into either male or female gametes (gametogenesis, sexually committed). This completes the part of the parasites’ life cycle that occurs inside the human body. Development beyond the gametocyte stage normally takes place following a blood meal, in the lumen of the mosquito midgut, where the male and the female gametes fuse [ 52 ]. However, there are sporadic reports of exflagellated forms (male gametes) of P. falciparum observed in the human body [ 53 ].

The second part of the life cycle in the insect vector begins when the insect ingests the blood containing gametocytes from an infected vertebrate host. The gametocytes are activated once exposed to the specific environment of the mosquito midgut lumen, and the male and the female gametocytes differentiate to produce microgametes and macrogametes, respectively [ 52 ]. The microgamete fertilises the macrogamete to produce a zygote, the only developmental stage of the parasite that has a diploid genome [ 54 ]. Genetic crossing experiments with gametocytes of two clones of P. falciparum with different allelic variants demonstrated that recombination can occur in zygotes [ 55 , 56 ]. Soon the zygote undergoes meiosis and differentiates into a motile form, the ookinete, that now contains four haploid genomes in its nucleus [ 54 ]. The ookinete penetrates the wall of the mosquito midgut and forms an oocyst on the outer side [ 57 ]. In the oocyst, several rounds of mitosis take place, and numerous sporozoites are produced by sporogony [ 58 , 59 ]. When the oocyst matures, it ruptures, and sporozoites released into the haemolymph migrate to the salivary glands, where they acquire the ability to infect human cells [ 60 ] when released into the body of a vertebrate host during a blood meal. Human-infecting Plasmodium species complete this second part of the life cycle (gametocytes to sporozoites ready to infect the next person) in around 10–18 days.

Besides the nucleus, the Plasmodium cell has two distinct organelles that contain their own genomic DNA, the mitochondrion and the apicoplast (see below). It has been shown that each oocyst of P. falciparum developing in the mosquito inherits the mitochondrial genomic DNA uniparentally from the female gamete [ 61 ]. A further study reported that both organellar genomic DNAs were detected in female gametes of P. gallinaceum (a species infecting chickens) but not in male gametes [ 62 ]. This suggests that Plasmodium inherits both the mitochondrion and the apicoplast only through the female gamete (macrogamete).

Recurrence of malaria and the hypnozoite

Malaria can recur after the parasites apparently have been cleared from the patient’s blood. Recurrence is due either to a recrudescence or a relapse (Table 1 ). Recrudescence originates from a minor population of parasites that survived undetected in the patient’s blood, whereas relapse is caused by cryptic, dormant cells called hypnozoites [ 43 ] that persist in the patient’s liver. Hypnozoites originate exclusively by differentiation from sporozoites and never from another form of the parasite, such as the merozoites circulating in the patient’s blood [ 63 ].

P. vivax is known to produce hypnozoites that cause relapses after the parasites have been cleared from the patient’s blood by treatment with antimalarial drugs such as chloroquine or quinine [ 12 ]. There is one report that, in the majority of relapse cases studied, the genotype of the parasites in the first relapse is different from those during the preceding acute episode [ 64 ]. This result was probably due to the following: (1) P. vivax sporozoites of two or more different genotypes infecting a person, (2) sporozoites other than the one that caused the acute episode differentiating into a hypnozoite in the liver, and (3) only one of those hypnozoites causing the relapse event. External stimuli such as other infections, including P. falciparum malaria, have been suggested to activate the hypnozoite and initiate a relapse of P. vivax malaria [ 65 ], although the mechanism has not been explained.

Of the other human malaria parasites, P. ovale has long been believed to develop hypnozoites because there are reports of recurrence without a second infection by the same species. However, this view has been questioned recently because of a lack of experimental and clinical data unequivocally supporting the presence of hypnozoites in the liver [ 49 , 50 ].

Neither P. falciparum nor P. malariae is thought to develop hypnozoites, and such cells have never been identified in either species [ 63 ]. Nevertheless, these two species can cause persistent infection without the development of any symptoms over long periods of time. For example, there is a case report of a P. falciparum infection that persisted asymptomatically in the human body for 13 years [ 66 ]. A P. malariae case that most likely developed after an asymptomatic infection lasted over 40 years has also been reported [ 47 ]. Plasmodium parasites can be maintained in the human blood over long periods of time at a very low number when their growth rate and the host’s immunity are able to maintain a subtle balance. Recurrence (recrudescence) is believed to begin when the balance is broken.

Whilst there is strong evidence that hypnozoites cause relapses in P. vivax malaria, some recurrences of P. vivax malaria might have originated from non-hypnozoite cells, as in other human malarias [ 67 , 68 , 69 ]. Recently, it was reported that recurrence of parasitaemia had been recorded in some neurosyphilis patients who had received a P. vivax malaria patient’s blood for malariotherapy [ 70 , 71 , 72 ]. Because P. vivax does not persist as sporozoites in human blood, no hypnozoite could have developed in the recipients. Thus, these records may suggest that P. vivax malaria can recur independent of hypnozoites.

Gametocytes

Throughout development in their vertebrate hosts, Plasmodium cells have a haploid genome. Nevertheless, a cloned line of Plasmodium originating from a single cell generates both male and female gametocytes in the vertebrate host. This indicates that the sex of Plasmodium gametocytes is not determined chromosomally but epigenetically, and evidence explaining the mechanism is being accumulated [ 38 ]. The gametocyte sex ratio is apparently affected by environmental factors [ 73 , 74 , 75 ], and this may optimise parasite transmission.

Gametocytes of the Plasmodium species that infect humans are known to be susceptible to 8-aminoquinolines such as primaquine, but not to other antimalarials such as artemisinin and chloroquine that kill the parasites in asexual intraerythrocytic development [ 76 ]. Thus, even after parasites in their asexual intraerythrocytic development cycle are removed by treatment with those antimalarials, transfer of gametocytes in the blood can cause malaria in other people. In addition, it has been reported that P. falciparum gametocytes can persist for several weeks after the clearance of asexual blood stage parasites by drug treatment such as artemisinin-combination therapy [ 77 ]. An in vitro study using culture of gametocytes from one clinical isolate and two laboratory strains of P. falciparum observed that gametocytes had a 50% survival rate of 2.6–6.5 days and that surviving cells were detectable until almost 2 months after the start of the experiment [ 78 ]. Both the rate of clearance of gametocytes from the patient’s body and the rate of decline of gametocyte infectivity for mosquitoes depend on multiple factors such as the kind of treatment and the way it is implemented [ 79 , 80 ], as well as host immunity [ 81 ]. People with asymptomatic infection can carry a high number of gametocytes in their blood, just like patients with symptoms of malaria [ 82 , 83 , 84 ]. Therefore, gametocytocidal treatment should be given not only to malaria patients with symptoms but also to asymptomatic Plasmodium carriers to prevent the parasites in them causing new malaria cases.

Asymptomatic carriers

In areas endemic for malaria, many people carry Plasmodium without developing symptoms because of acquired immunity [ 85 , 86 ]. Often, the presence of parasites in those carriers cannot be detected either by microscopy or rapid detection tests (RDTs), the two standard tests for detecting Plasmodium in malaria patients’ blood. However, infection can be detected with more sensitive methods, e.g., molecular detection by PCR and LAMP [ 87 ], or ultrasensitive variations of RDTs [ 88 ]. Asymptomatic carriers can supply infectious gametocytes to mosquitoes, though their impact on malaria in the community where they live may be low or negligible when the number of gametocytes in the blood is not high [ 89 ]. Asymptomatic Plasmodium carriers can develop an episode of malaria when their immunity against the parasite is compromised, for example, when they move to a malaria-free area where they no longer have new Plasmodium infections that sustain immunity against the parasite. As a result, asymptomatic carriers may cause imported malaria [ 90 , 91 ]. Even without developing any episodes of malaria, they can also cause transfusion malaria [ 92 ] or organ-transplantation malaria [ 93 ].

The importance of controlling asymptomatic carriers of malaria parasites in the modern world is higher than ever. It is mainly because people’s movements have become much easier than in earlier times, thanks to economic development and transportation. In addition, the number of refugees from regional conflicts, many of which occur in malaria endemic areas, has increased. Asymptomatic carriers within migrants from malaria endemic areas ought to be identified and adequately cared for, like patients with apparent malaria symptoms, in order to prevent the spread or re-introduction of malaria into malaria-free areas [ 94 , 95 ].

Apicoplast and plant-like metabolism

The genus Plasmodium belongs to a larger group of protozoans called the Apicomplexa, part of the superphylum Alveolata that also includes dinoflagellates and ciliates [ 96 ]. Like Plasmodium , almost all apicomplexans are obligate parasites [ 31 ], and many of them, including all Plasmodium species, have a vestigial, non-photosynthetic plastid called the apicoplast in the cell [ 97 , 98 , 99 ]. The apicoplast is a secondary plastid surrounded by four layers of membrane [ 100 , 101 ] and has a tiny genome, the smallest in size of all known plastid genomes [ 102 , 103 ]. Recently, exceptional apicomplexan species that have a photosynthetic plastid were also discovered [ 104 , 105 ]. These new species, grouped as chromerids, can grow phototrophically without parasitising other organisms. The plastids of chromerids contain chlorophyll a but lack chlorophyll c that is universally found in the plastids of other phototrophic alveolates. Like the apicoplast, the photosynthetic plastids of chromerids are secondary plastids [ 106 ]. Features of the organellar genome suggest that all apicomplexan plastids originated from the last common ancestor of present apicomplexans [ 107 ].

Unlike plastids of photosynthetic organisms, the apicoplast is non-photosynthetic, and almost all gene products encoded in the tiny organellar genome are predicted to be involved in either transcription or translation [ 108 ]. Therefore, the reason why parasitic apicomplexans such as Plasmodium carry a non-photosynthetic plastid was not clear when the organelle’s presence in the parasite was first recognised [ 109 ]. However, as the genomic information encoded in the nuclear genome of the parasites became available [ 110 ], it gradually became evident that the Plasmodium apicoplast is involved in plant-type metabolic pathways including isoprenoid biosynthesis [ 111 ], type II fatty acid biosynthesis [ 112 ] and haem biosynthesis [ 113 ]. These plant-type pathways involving the apicoplast have been suggested to be important for Plasmodium to complete its development, especially in mosquitoes [ 114 , 115 ] and in the liver [ 116 , 117 ]. However, it has been shown that Plasmodium in the intraerythrocytic cycle can keep growing in in vitro culture as long as a sufficient amount of isopentenyl pyrophosphate (IPP) is supplied in the culture medium, even when they have lost the apicoplast [ 118 ]. This suggests that the requirement of the apicoplast for this stage of the parasites is solely to obtain IPP. IPP is the precursor of various isoprenoids and is essential for eukaryotes including Plasmodium to survive, and the plant-type methylerythritol phosphate (MEP) pathway in the apicoplast is the only source of this critical molecule in the parasite [ 119 ]. One of the enzymes involved in the MEP pathway, 1-deoxy-D-xylulose-5-phosphate reductoisomerase, is inhibited by a specific inhibitor called fosmidomycin [ 120 ], and growth of P. falciparum is inhibited by fosmidomycin both in vitro and in vivo [ 121 , 122 ]. By contrast, fosmidomycin does not show a significant inhibitory effect on the growth of another distantly related apicomplexan Toxoplasma gondii , which also is supposed to depend on IPP supplied by the MEP pathway in the apicoplast [ 123 ]. The molecular basis of the resistance of T. gondii to fosmidomycin has been studied, and it was suggested that poor drug uptake through the parasite’s plasma membrane is the cause [ 124 ]. Another study suggested that the uptake of fosmidomycin into the erythrocyte which P. falciparum infects depends on a new permeability pathway induced by the parasite [ 125 ]. Although fosmidomycin has good properties as a novel antimalarial [ 126 ], Plasmodium may be able to develop resistance to the drug by mutation in unexpected genes.

Some apicomplexans such as Cryptosporidium and Gregarina do not have the apicoplast [ 127 ], while P. falciparum and T. gondii cannot survive if they lose the organelle [ 118 , 128 ]. The enzymes involved in the plant-like metabolism in the apicoplast are encoded in the nuclear genome, and apicomplexan species that do not have the apicoplast tend to lack all the genes specifying these enzymes [ 129 ]. By contrast, the genome of Cryptosporidium species encodes a remarkably large number of putative amino acid transporters compared to apicomplexans with an apicoplast [ 130 ]. These species without an apicoplast probably acquire the metabolites that ordinary apicomplexans synthesise in the apicoplast, from the host using some of those additional transporters.

Antimalarial drugs and resistance

From ancient times, various plant products have been used in folk medicine to treat malaria. In the seventeenth century, it was shown that the bark of South American quina-quina trees ( Cinchona spp.) contains an agent with antimalarial activity. This substance, quinine, has been used in the treatment of malaria since then [ 131 ]. In the nineteenth century, efforts began to chemically synthesise pure compounds with antimalarial activity, and some clinically useful synthetic antimalarials such as chloroquine became available in the 1930s. In 1972, another natural compound used traditionally in China, artemisinin, was reported to have antimalarial effect.

Antimalarial drugs currently used in the clinical treatment of human malaria come in five classes based on their structural backbone and apparent action [ 132 ]. Those classes are (1) endoperoxides (e.g. artemisinin and its derivatives), (2) 4-aminoquinolines (chloroquine), aryl-amino alcohols (quinine, mefloquine), (3) antifolates (pyrimethamine, proguanil, sulfadoxine), (4) naphthoquinones (atovaquone) and (5) 8-aminoquinolines (primaquine, tafenoquine). The main targets of inhibition by 4-aminoquinolines, anitifolates and naphthoquinones have been shown to be detoxification of haem released from digested haemoglobin, pyrimidine biosynthesis and mitochondrial cytochrome b involved in oxidoreduction, respectively. Aryl amino alcohol class inhibitors seem to inhibit the same metabolism as 4-aminoquinolines, whereas endoperoxides, such as artemisinin, act on multiple cellular processes involving reactive oxygen species in Plasmodium cells.

The parasites causing human malaria, especially P. falciparum , have acquired resistance to each of these antimalarials one by one, and today, drug-resistant parasites are prevalent in malaria endemic areas [ 133 ]. It has been well documented that point mutations causing amino acid substitutions in the active site of dihydrofolate reductase (the target enzyme of pyrimethamine and proguanil) make P. falciparum highly resistant to those antifolate drugs [ 134 , 135 ]. Another example includes specific point mutations occurring in pfcrt and pfmdr1 , which specify transporters CRT and MDR1, respectively, which promote the efflux of antimalarials such as 4-aminoquinolines and aryl amino alcohols from the digestive vacuoles of P. falciparum [ 136 ]. As a result, parasites with these mutated genes become resistant to antimalarials that block haem detoxification in the digestive vacuoles. Point mutations in a gene are not the only the way for the parasites to acquire resistance to antimalarials. For example, when expression of the affected gene product is elevated because of gene amplification or a change in regulatory mechanisms, antimalarials can reduce or lose their efficacy [ 137 , 138 ]. It is also potentially possible that Plasmodium species acquire new machinery with which the parasites can survive without the metabolism targeted by an antimalarial. For example, if Plasmodium acquires a new transporter with which they can acquire IPP from the host, as Cryptosporidium species can, the parasites become resistant to fosmidomycin.

It has been reported that clinical isolates of P. falciparum showing resistance to multiple antimalarial drugs tend to have defects in DNA mismatch repair [ 139 , 140 ]. Genetic changes are often harmful, so having defects in DNA mismatch repair, which causes a higher rate of genetic changes in the genome, can reduce the fitness of the parasites affected. However, parasites with such defects have a potential to generate a wider variety of genetic changes compared to those without such defects. This is presumably beneficial for the parasites in order to survive under strong drug pressure. The A + T content of the genome of Plasmodium species is generally high (> 60%); it is especially high in the genome of P. falciparum —nearly 80% in coding regions and approaching 90% in non-coding regions. The genome of P. falciparum has been shown to be prone to small genetic changes such as indel mutations [ 141 ]. The high A + T content of the genome may also contribute to Plasmodium developing drug resistance.

Host specificity

The natural host range of Plasmodium depends on the species. It can be extremely narrow as in P. falciparum , which infects humans but not African apes that are phylogenetically very close to humans [ 142 ]. The range can also be very wide as in P. relictum , which is known to infect more than 100 different species of birds around the world, classified into different families and orders [ 143 ]. Traditionally, Plasmodium species are sub-categorised into distinct subgenera based on their morphology and ranges of vertebrate hosts and vectors [ 32 ]. It has been pointed out that the genus Plasmodium as a whole is polyphyletic and that the taxonomy of the order Haemosporidia, which consists of Plasmodium and other related genera, has many conflicts [ 144 ]. Nevertheless, each subgenus of Plasmodium seems to be monophyletic. Plasmodium species that infect mammals generally belong to either one of three subgenera, Laverania , Plasmodium or Vinckeia , apart from some species recently identified from ungulate hosts [ 32 , 144 , 145 ]. The subgenera Laverania , Plasmodium and Vinckeia consist of parasite species that infect apes, monkeys and rodents, respectively.

Unlike Plasmodium species that infect birds, which are transmitted by a wide variety of mosquitoes including Culex and Aedes , mammalian malaria parasites belonging to subgenera Laverania , Plasmodium and Vinckeia are transmitted only by anopheline mosquitoes [ 32 ]. This is because mammalian Plasmodium species can complete their development from gametocytes to infectious sporozoites only in anopheline mosquitoes. However, this does not mean that these parasites cannot developmentally differentiate from gametocytes in non-anopheline mosquitoes [ 146 ]. There was an early report that oocysts formed on the midgut epithelium, and sporozoites were observed in the salivary gland when Culex bitaeniorhynchus was fed with human blood containing gametocytes of P. falciparum or other human malaria parasites [ 147 ]. However, another recent study reported that a laboratory strain of P. falciparum fed to C. quinquefasciatus developed ookinetes that soon lysed and never formed oocysts [ 148 ]. This suggests that P. falciparum is killed by the mosquito’s immune system when the ookinetes are exposed to the haemolymph of non-anopheline mosquitoes [ 149 ].

It is not true that all anopheline mosquitoes are equally important in transmitting Plasmodium between humans or animals; different Anopheles species have different habitats, feeding behaviour and preference for the animal species from which they suck blood [ 150 ]. These differences may promote species differentiation in the parasites they carry and provide a chance for the parasite to switch its host [ 151 ].

Of the four human Plasmodium species, P. falciparum belongs to subgenus Laverania , whereas all the others belong to subgenus Plasmodium . P. knowlesi that causes zoonotic malaria in humans also belongs to the subgenus Plasmodium . Generally, P. falciparum only infects humans in natural conditions [ 152 ], though it is possible to adapt the species to infect chimpanzees in the laboratory [ 153 ]. Krief et al. reported that they isolated P. falciparum from bonobos ( Pan paniscus ) kept at the Lola ya Bonobo Sanctuary in the Democratic Republic of the Congo, though the mitochondrial haplotype map they drew indicated that the isolates from bonobos were genetically distant from P. falciparum parasites infecting humans [ 154 ]. The non- P. falciparum Laverania species that is phylogenetically closest to P. falciparum is P. praefalciparum , which infects gorillas but not humans or chimpanzees [ 152 ]. As with these two species, all Plasmodium species of subgenus Laverania so far described show a strong host specificity in their natural transmission [ 152 , 155 ]. A longitudinal survey of anopheline mosquitoes carried out in two wildlife reserves in Gabon where different Laverania species coexist revealed that the three sylvan Anopheles species collected in the survey, An. vinckei , An. moucheti and An. marshallii , carried multiple Laverania species whose vertebrate host specificity varied [ 151 ]. This indicates that the strong host specificity of the Laverania species is not solely caused by specific association between anopheline vectors and vertebrate hosts. A recent comparative genomics study between Laverania species revealed that these parasites have striking copy number differences and structural variations in multiple gene families in their genomes [ 156 ]. Variations in the stevor family, which has been shown to be involved in host-parasite interactions in P. falciparum [ 157 ], showed a host-specific sequence pattern. Probably these variations are critically important for each Laverania species to determine their strong host specificity. Rh5 , a member of another gene family, has been shown to be important for Plasmodium species of subgenus Laverania to bind to erythrocytes of specific hosts [ 158 ]. EBA165 , a member of the erythrocyte binding-like (EBL) gene family, is pseudogenised in the genome of P. falciparum but not in other Laverania species’ genomes. A recent study showed that P. falciparum becomes capable of binding to ape erythrocytes but loses the ability to bind human erythrocytes when a functional EBA165 product is expressed [ 159 ]. This suggests that losing the functional EBA165 product was a key step in the emergence of the human-infecting P. falciparum from its P. praefalciparum -like ancestor that probably did not infect humans .

In the mosquito survey in Gabon described above, it was also found that the three sylvan species of Anopheles carried Plasmodium species which were extremely close to P. vivax or P. malariae [ 151 ]. In a phylogenetic analysis, these P. vivax -like isolates from mosquitoes collected in the survey in Gabon made a cluster with P. simium , one of the two South American zoonotic Plasmodium species [ 151 ]. Another study suggested that P. brasilianum , the other South American zoonotic Plasmodium , is probably an amphixenotic variant of P. malariae that acquired infectivity to the simian hosts while also keeping its original human infectivity [ 29 ]. All these suggest that both P. vivax and P. malariae can switch their host more easily than the species of subgenus Laverania [ 151 ]. However, the mechanisms behind host switching of species of subgenus Plasmodium including P. knowlesi and other simian species causing zoonotic malaria are not well understood.

Conclusions

Humans have long suffered from malaria, the disease caused by Plasmodium . Thanks to the discovery of natural and chemically synthesised antimalarials, malaria has become a disease curable by chemotherapy. Together with mosquito vector control using insecticides, treatment of malaria patients with synthetic antimalarials such as chloroquine and artemisinin has dramatically reduced the burden of malaria in the modern world compared to the past. Nevertheless, malaria is still prevalent, killing hundreds of thousands of people globally every year.

One of the problems that hinder control of malaria is the emergence and spread of chemotherapy-resistant parasites [ 160 , 161 , 162 ]. To solve this problem, novel antimalarial substances whose targets are different from those of existing antimalarials are sought. Using those inhibitors in combination with existing antimalarials largely reduces the risk that the parasites acquire resistance to each substance. For example, inhibitors of the plant-like metabolic pathways of the parasite are attracting attention.

Another problem is that Plasmodium can be easily carried from endemic areas to non-endemic areas in the modern world because of increased movement of people. Malaria-free countries and areas are steadily increasing, but imported malaria is a commonly shared threat against health in many countries and areas. Plasmodium species can be retained in the human body for a long time without causing any overt symptoms. Asymptomatic Plasmodium carriers can start developing malaria spontaneously and spread imported malaria in malaria non-endemic countries and areas. These people may also spread the parasite when they are involved in blood transfusions and organ transplantation as donors.

P. falciparum and other human-infecting Plasmodium species share a characteristic that lets them infect humans, which is the outcome of convergent evolution. Currently, Plasmodium species that naturally cause malaria in humans are limited, but other species may also acquire natural infectivity to humans and start causing new zoonotic malaria at any time. The physical distance between humans and non-human animals such as other primates can depend on the degree of local development, and this could affect the chance of non-human Plasmodium species becoming the cause of zoonotic malaria in humans.

Plasmodium species may change their insect hosts as well. Unlike the Plasmodium species that infect mammals, avian malaria parasites develop and produce infectious sporozoites in non-anopheline mosquitoes. This implies that mammalian Plasmodium species also could acquire resistance to the immune system of non-anopheline mosquitoes such as Culex and Aedes and use them as transmission vectors. Some non-anopheline mosquito species can breed even in harsh environments such as in tunnels, on the coast or in urbanised areas, and can be cosmopolitan [ 163 , 164 ]. If a Plasmodium species that can cause malaria in humans acquired the capability of completing its mosquito stage development in non-anopheline mosquitoes, its impact on human society could be substantial.

The relationship between humans and Plasmodium changes dynamically due to both the parasites’ nature and the activities of humans. Understanding the basic biology of the parasites that leads to these changes, and applying the knowledge to malaria control, should help to achieve a healthier global society.

Availability of data and materials

Not applicable.

Change history

29 january 2021.

An amendment to this paper has been published and can be accessed via the original article.

Abbreviations

Insecticide-treated bed net

National Malaria Control Programme

Rapid detection test

Isopentenyl pyrophosphate

Methylerythritol phosphate

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Sato, S. Plasmodium —a brief introduction to the parasites causing human malaria and their basic biology. J Physiol Anthropol 40 , 1 (2021). https://doi.org/10.1186/s40101-020-00251-9

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Factors associated with malaria vaccine uptake in Nsanje district, Malawi

Atusaye J. Simbeye 1 ,
Save Kumwenda 2 na1 ,
Lauren M. Cohee 3 , 4 na1 ,
Dickens Omondi 1 ,
Peninah K. Masibo 5 ,
Hesborn Wao 6 &
Shehu S. Awandu 1 na1

Malaria Journal volume 23 , Article number: 105 ( 2024 ) Cite this article

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Malaria remains a significant global health burden affecting millions of people, children under 5 years and pregnant women being most vulnerable. In 2019, the World Health Organization (WHO) endorsed the introduction of RTS,S/AS01 malaria vaccine as Phase IV implementation evaluation in three countries: Malawi, Kenya and Ghana. Acceptability and factors influencing vaccination coverage in implementing areas is relatively unknown. In Malawi, only 60% of children were fully immunized with malaria vaccine in Nsanje district in 2021, which is below 80% WHO target. This study aimed at exploring factors influencing uptake of malaria vaccine and identify approaches to increase vaccination.

In a cross-sectional study conducted in April–May, 2023, 410 mothers/caregivers with children aged 24–36 months were selected by stratified random sampling and interviewed using a structured questionnaire. Vaccination data was collected from health passports, for those without health passports, data was collected using recall history. Regression analyses were used to test association between independent variables and full uptake of malaria vaccine.

Uptake of malaria vaccine was 90.5% for dose 1, but reduced to 87.6%, 69.5% and 41.2% for dose 2, 3, and 4 respectively. Children of caregivers with secondary or upper education and those who attended antenatal clinic four times or more had increased odds of full uptake of malaria vaccine [OR: 2.43, 95%CI 1.08–6.51 and OR: 1.89, 95%CI 1.18–3.02], respectively. Children who ever suffered side-effects following immunization and those who travelled long distances to reach the vaccination centre had reduced odds of full uptake of malaria vaccine [OR: 0.35, 95%CI 0.06–0.25 and OR: 0.30, 95%CI 0.03–0.39] respectively. Only 17% (n = 65) of mothers/caregivers knew the correct schedule for vaccination and 38.5% (n = 158) knew the correct number of doses a child was to receive.

Only RTS,S dose 1 and 2 uptake met WHO coverage targets. Mothers/caregivers had low level of information regarding malaria vaccine, especially on numbers of doses to be received and dosing schedule. The primary modifiable factor influencing vaccine uptake was mother/caregiver knowledge about the vaccine. Thus, to increase the uptake Nsanje District Health Directorate should strengthen communities’ education about malaria vaccine. Programmes to strengthen mother/caregiver knowledge should be included in scale-up of the vaccine in Malawi and across sub-Saharan Africa.

Malaria continues to pose a significant global health challenge. Globally, an estimated 249 million cases of malaria occurred in year 2022 which was 2 million more cases than in 2021 [ 1 ]. Sub-Saharan African countries facing the hardest hit contributing 93.6% (233 million) of total malaria cases and 95.4% (580,000) of total malaria deaths [ 1 ]. In Africa, about 78.1% (453,000) of the total deaths in 2022 were children below 5 years [ 1 ]. Malawi is among the 15 countries with the highest burden of malaria reporting over 4 million estimated malaria cases were reported in 2022 [ 1 ].

To control malaria, the National Malaria Control Programme (NMCP) within the Malawi Ministry of Health (MOH) currently supports the following interventions: long-lasting insecticidal nets (LLINs), prompt diagnosis with effective treatment with artemisinin-based combination therapy (ACT), and indoor residual spraying (IRS). The RTS,S/AS01 malaria vaccine is a new addition to malaria control tools [ 2 ]. In 2021, the World Health Organization (WHO) recommended RTS,S/AS01 for children at risk of malaria in sub-Saharan African regions of moderate to high malaria transmission [ 3 ]. The successful deployment of a malaria vaccine could substantially reduce the burden of malaria-related morbidity and mortality in under five children 4 , 5 , 6 . However, vaccines cannot achieve their anticipated benefits if the uptake is low. It is estimated that 1 out of every 5 children do not receive basic vaccines which contributes to more than 30 million under five years children suffering from Vaccine Preventable Disease (VPDs) each year [ 5 ]. For instance, the 2023 measles outbreak in South Africa was caused due to low coverage of measles vaccine [ 7 ]. Similarly, there was an outbreak of Polio in Cameroon due to low coverage of Oral Polio Vaccine (OPV) [ 8 ], low vaccine coverage has contributed to infectious disease outbreaks in vulnerable population [ 9 ]. Vaccine hesitancy also contributes to low vaccination coverage in many Africa countries [ 10 ].

In 2019, a Phase IV implementation study of the RTS,S/AS01 vaccine delivered through routine EPI platforms was conducted in Malawi. The four required doses of malaria vaccine were delivered at 5, 6, 7, and 22 months. The implementation study took place in 11 districts, including Nsanje. The effectiveness and impact of malaria vaccine relies not only on its introduction to the country but also on its widespread acceptance and uptake. This research study aimed to quantify the uptake of malaria vaccine in Nsanje district and investigate the factors associated with malaria vaccine uptake, including sociodemographic, mother/caregiver-related factors, and health care system factors. Identification of these factors may help to develop approaches to accelerate high levels of uptake of malaria vaccines, thereby advancing the global agenda towards malaria eradication.

All the 4 contacts for malaria vaccine are new and are not given with any other EPI interventions (Table 1 ). The only other vaccine that is given in the second year of life is measles and rubella vaccine dose 2, which is given at 15 months.

According to the WHO, it is recommended that the first dose of RTS,S vaccine should be received at 5 months, with the successive doses being received at 1 month apart and the 4th dose to be received at 15–18 months after the third dose. However, the WHO also states that vaccination programmes may choose to give the first dose at a later or slightly earlier age based on operational considerations. At 11 months, is the latest month a child can receive the first dose of malaria vaccine and at 36 months is the latest month for a child to receive dose 4.

Nsanje district is located in the southern region of Malawi. It is situated at the tip of the country along latitude 16°45′00″S and longitude 35°10′00″E. The district is a flatland in the lower Shire valley covering 1,942 square kilometres with an estimated population of 299,168 11 , 12 .The district has 23 health facilities (3 hospitals, 12 health centres and 8 health posts) which are divided into five clusters for health administration purposes. The malaria vaccine was implemented in four out of the five clusters. This study was conducted in the catchment areas of health facilities within each implementation cluster: Mlolo cluster (Mlolo, Trinity, Masenjere, Makhanga, Sankhulani and Mchacha), Kalemba cluster (Kalemba, Phokera, Sorgin, Misamvu, Kanyimbi), Tengani cluster (Tengani, Nyamithuthu and Mkango) and Boma cluster (Nsanje district Hospital and Chididi) [ 12 ]. Cluster sampling was performed.

Study design

This was a cross-sectional study utilizing structured questionnaires together with checklists to collect data on the uptake of malaria vaccine and factors that influence uptake. Data on child vaccination status were obtained by reviewing their health passport. Mothers/caregivers were asked demographic questions about themselves and their children and also about factors that were associated with the uptake of the malaria vaccine.

Study population

In February 2023, names of the mothers/caregivers of children 24–36 months old were extracted from village registers with the help of Health Surveillance Assistants. Children in this age group were eligible to have received all four doses of the vaccine. After all the names were extracted from the village registers, the participants were selected using stratified random sampling. Mothers/caregivers of the selected children were contacted and eligibility assessment was conducted. The eligibility criteria were: a mother/caregiver responsible for the selected child aged 24–36 months by the time of data collection, and the child was a permanent resident of Nsanje district by birth.

Sample size calculation

Using Cochrane’s formula to estimate proportion of children receiving vaccine (prior estimate of dose 4 = 60%) with a margin of error of 5% assuming a normal distribution of the margin of error, the minimum sample was calculated to be 369 participants. After adjustment for a 10% non-response rate and rounding the target sample size was 410.

The total population in the four target clusters is 245,620 including an estimated 12,281 mothers/caregivers. Stratified sampling technique proportionate to size of the cluster population was used in selecting participants for the study. Table 2 shows the sample proportions.

Sampling individual participants

To sample individual respondents in this study, firstly, systematic sampling technique was used to selected respondents from each sub-cluster. The Village Health Registers were used as source of the names for mothers/caregivers. The names of all mothers/caregivers who met the eligibility criteria in each cluster were numbered and written down, thus forming the sampling frame. A formula was used to determine a sampling interval from each cluster. The formula that was used was i = N/n where i was the sampling interval, N was the total number of eligible mothers/caregivers in the sampling frame whereas n was sample size of the cluster. The names and the villages of the mothers/caregivers counting from one to the sampling frame were written on a piece of paper, folded, mixed thoroughly and put in a box then a simple random sampling technique was used to select the first sample. After the first sample was drawn, the initial list that was written down was used to select the subsequent participant. The subsequent participants were selected by adding the sampling interval to the number of the initial sample until the required samples were drawn for that cluster.

Data collection

Questionnaires were administered by research assistants to the study participants. Questions included mothers/caregiver socio-demographic characteristics, child factors (e.g. history of vaccine adverse reactions), community level factors and health care system factors. Information on vaccine uptake and timeliness was extracted from the health passport of the child. For mothers/caregivers who did not have health passports for the children, data was recorded using recall history. The questions were adopted from previous validated questionnaires used in Malaria Indicator surveys and Demographic and Health surveys. Mothers/caregivers were contacted in their homes depending on when they were available to respond to the questionnaire; interviews were not conducted at health facilities or at the vaccination point. Ethical approval was obtained from Jaramogi Oginga Odinga University of Science and Technology, approval number ERC 37/04/23-5/05 and from Malawi National Health Sciences Research Committee, protocol number 23/02/3167. Informed consent was sought from each study participant.

Data analysis

Data from paper-based questionnaires were entered in Microsoft Excel by a single study team member. A second team member double-checked data entry by comparing the questionnaires and the data entered in Microsoft Excel. The cleaned data set was imported to STATA version 16 for analysis. Descriptive statistics were calculated for binary, categorical, and continuous variables. Logistic regression was used to evaluate the association between the independent variables (for example socio-demographic) and the level of malaria vaccine uptake (dependent variable). Malaria vaccine uptake was divided into three categories: no uptake (child has not received any dose of malaria vaccine), partial uptake (child has received first, second or third dose) and full uptake (child has received all four doses). After the univariate analysis, a multivariate analysis was performed on those independent variables with significant p-values of 0.05 in the first stage. The binary regression involved the comparing between full malaria vaccine uptake against partial uptake and no uptake. Final model selection was based on having the lowest Akaike’s Information Criteria (AIC).

Socio-demographics characteristics of mothers/caregiver and their children

A total of 410 mothers/caregivers with children aged 24 to 36 months participated in this study. Participants were most commonly married females (79.8%, n = 327) who were 20–29 years old (54.2%, n = 222), self-employed (58.8%, n = 241), Christians (95.1%, n = 390), and were most often parents as opposed to caregivers (Table 3 ). Education level varied with more than half having no formal education (22%, n = 90) or only primary school (36%, n = 149). Most had at least four antenatal care visits during pregnancy (56.2%, n = 168). Out of the 410 participants, 82.4% (338) had their children’s health passports present whereas 17.6% (72) had no health passports for their children. The median age of the children whose data was collected was 29 months (IQR 26–33), half were male, and almost all were delivered at a health facility (98.8%, n = 405) (Table 4 ).

Uptake of malaria vaccine

The crude uptake was used for this study (vaccinations from health passport plus mothers/caregivers recall). Out of the 410 children, 9.5% of children did not receive any doses of the malaria vaccine. Among those who received the vaccine, coverage was relatively high for dose 1 and 2 (90.5% and 87.6%, respectively), but declined for dose 3 and 4 (69.5% and 41.2%, respectively) (Fig. 1 ). Thus, the levels of malaria vaccine uptake were 9.5% (n = 39) for no uptake , 49.3% (n = 202) for partial uptake and full uptake 41.2% (n = 169) (Table 5 ). Children of the 72 mothers/caregivers who had no health passports of their children had the following levels of uptake of malaria vaccine (no uptake, 33.3%, n = 24), while 40.3% (n = 29) had partial uptake, and 26.4% (n = 19) had taken all the doses of malaria vaccine (full uptake).

Uptake of malaria vaccine among children aged 24–36 months in Nsanje district. Blue bars: uptake (%), Orange bar: recommended target

Reasons for incomplete vaccination

Among the 39 participants whose child did not receive any dose of malaria vaccine, 26 (67%) did not know their child was eligible, nine (23%) said their religious belief prohibited them from taking the vaccine, and four (10.3%) made a personal decision to refuse the vaccine. Out of the 202 participants who had partial uptake of the vaccine, 70.4% did not know the next date when the vaccination was due and 15 (4%) were not comfortable with issues surrounding vaccines. In total 28 participants reported vaccine hesitancy with their reasons being complete refusal (n = 4), religious reasons (n = 9) and not comfortable with issues surrounding vaccine (n = 15) leading to no or partial uptake (Table 6 ).

Mother/caregiver and child characteristics associated with vaccine uptake

Mothers/caregivers who had secondary or higher education had increased odds of having full uptake of malaria vaccine compared to their counterparts (OR = 2.43, 95% CI 1.43–4.12, p = 0.001). Having attended four or more antenatal visits was associated with full uptake of malaria vaccine (OR = 1.89, 95% CI 1.18–3.02, p = 0.008). However, there was no statistically significant association between sex, religion, occupation of the mother/caregiver and full uptake of malaria vaccine. Children aged 32 to 36 months had increased odds of full malaria vaccine uptake compared to those aged 24 to 27 months (OR = 1.72, 95% CI 1.11–2.69, p = 0.008) whereas sex and place of delivery was not statistically associated.

General knowledge about the malaria vaccine was associated with increased vaccination rates; mothers/caregivers who had heard about malaria vaccine prior this study had increased odds of full malaria vaccine uptake compared to those who never heard about it (OR = 4.47, 95%CI 1.29–15.41). Those who received messaging about the malaria vaccine from under 5 clinic had increased odds to having full malaria vaccine uptake compare to those who learned about the vaccine from the radio (OR = 3.15, 95% CI 1.22–8.11, p = 0.018). However, detailed knowledge about the vaccine, for example, knowing the number of malaria doses to be received and the specific age at which those doses should be received, was not associated with full uptake of malaria vaccine.

Children who ever suffered side effects following immunization were associated with reduction in full uptake of malaria vaccine (OR = 0.36, 95% CI 0.24–0.54, p < 0.001).

Mode of transport was associated with full uptake of malaria vaccine. Those mothers/caregivers who used motorbikes/bikes to go the vaccination point had increased odds (OR = 2.79, 95% CI 1.50–5.18, p = 0.001).

Having heard negative rumours about the malaria vaccine, for example that children were being used for experiments or that the vaccine will affect child development, reduced the odds of full uptake by 25% (OR = 0.25, 95% CI 0.14–044, p ≤ 0.001). Mothers/caregiver who had no problem with the introduction of malaria vaccine had increased odds to full uptake of the vaccine (OR = 3.47, 95% CI 1.29–9.39, p = 0.014).

Multivariate analysis of associations between full uptake of malaria vaccine and mother/caregiver and child factors

Multivariate logistic regression showed that the odds of malaria vaccine uptake was 26.56 times to those who ever heard of malaria vaccine than those who did not. Further, it showered that distance to vaccination point reduced the odds of full uptake by 24% whereas child ever suffered side effects following immunization reduced the odds by 23%. Table 7 below shows the details of multivariate logistic regression.

This study found that only the uptake of the first and the second doses of the RTS,S malaria vaccine met target of coverage for childhood vaccines set by the WHO [ 13 ]. Coverage for the subsequent doses fell below the target with the 4th dose reaching few than half of eligible children. This result means that the malaria vaccine cannot meet its intended purpose of averting childhood malaria morbidity and mortality unless its uptake for full vaccination can be improved. Decreasing coverage after the first dose of a multi-dose vaccine is common and has been reported for RTS,S in Ghana [ 14 ] as well as other childhood vaccine studies on vaccine uptake 15 , 16 , 17 .

The high coverage of RTS,S doses 1 and 2 could have been achieved due to of the campaign conducted during the launch of the vaccine in the routine vaccination system in Nsanje district. This possibly created a lot of demand for the vaccine and it made the communities aware of the vaccine. The district health directorate created demand through risk communication during community engagement. Later after the launch campaigns, the demand could have been reducing which could lead to reduction of the subsequent doses.

The data for coverages of other vaccines offered in the district the same period when this study was conducted was high. Then coverage for BCG was at 99.5%, MR 1 was at 97%, MR 2 was at 92%, Rota 1 was at 98.6% and for Rota 2 was at 94.3%. No vaccine was below 80% whether it was administered once or had several numbers of doses. This showed that only the malaria vaccine had the lowest coverage for full uptake.

Knowledge of the mothers/caregivers on the childhood vaccines, ages at which those vaccines are received and the number of vaccines doses a child should receive to be fully vaccinated is important in order to increase the uptake levels of the vaccine. Although the majority of the mothers/caregivers had ever heard about malaria vaccine, only a few knew the vaccination schedule and number of doses to be received for a child to be fully vaccinated. This poor knowledge could have contributed to the reduction of subsequent doses observed in this study. This indicated that health education and promotion on malaria vaccine is not adequately done in Nsanje district. Similarly, a study conducted by Biset et al . [ 16 ] found that low knowledge about childhood vaccine was associated negatively with full vaccination coverage. Most mothers/caregivers relied on the community health volunteer or the Health Surveillance Assistant to remind them about the next day of vaccination hence there was no association between having knowledge on vaccine schedule and ages with full uptake of malaria vaccine. However, it is very important that the mothers/caregivers should know the ages and the vaccination schedule in cases whereby the community health volunteer or Health Surveillance Assistant did not remind them about the next visit day, they should be able to remember by themselves. In doing so, the coverages could be high. In a study conducted by Victoria et al . [ 18 ], in Ghana, concluded that health education is important because fears and concerns about malaria vaccine are addressed. Addressing the mothers/caregivers concerns through health education may enable the mothers/caregivers to encourage other mothers/caregivers in their communities to get their children vaccinated hence increasing the vaccine coverage. Additionally, some systematic reviews conducted in Africa on childhood vaccination also found that full uptake of childhood vaccines was influenced by mothers knowledge on vaccines 19 , 20 .

In this study, few children did not take any malaria dose. The main reason was that their mother/caregiver not knowing that their children were eligible while some did not take any dose of malaria vaccine because of religious beliefs. In Nsanje district there are certain religions that prohibits its member to go to the hospital or access any other health services. Since mothers/caregivers from these religions are likely not be found at under 5 clinic to learn the importance of malaria vaccines, even if they are willing to vaccinate their children, their religious leader will prevent them from accessing the health services. This was also evidenced in a study conducted by Adeyanju et al . [ 21 ] in Malawi, which reported that religious groupings, for example Zion and Apostolic faith, were prohibiting their members from visiting the hospital and accessing vaccines.

A majority of the children in this study had no or partial uptake of malaria vaccine. The main reason for no/partial uptake being low levels of knowledge and awareness on next visit date and knowing if their child was eligible. This finding is similar to reports by Price et al . [ 22 ] which reported that in first three implementing countries of malaria vaccine, information barrier contributed to no or partial uptake of malaria vaccine. Additionally, in Kenya, a recent study by Hoyt et al . [ 23 ] found that lack of awareness on malaria vaccine was a factor that led to lower coverage of malaria vaccine. Another study by Yeboah et al . [ 24 ] in Ghana recommended that mothers should understand the importance of their children getting the vaccine even during their second year of life, to help increase the uptake of dose 4 of malaria vaccine.

Furthermore, this study showed that the education level of mothers/caregivers was associated with full uptake of malaria vaccine. Mothers/caregivers who had secondary education and above managed to fully vaccinate their children with malaria vaccine. The high uptake of malaria vaccine by those mothers/caregiver that are more educated is because as they can easily understand the importance of malaria vaccine to their children, but also they could have greater access to information regarding malaria vaccines and other vaccines in general. This finding is consistent with the findings from a study conducted in Malawi [ 25 ]. In additional, a study conducted in Burkina Faso reported that level of education was a determinant in the uptake of childhood vaccines [ 26 ]. A systematic review conducted in Sub-Saharan Africa by Tekle et al . [ 27 ] and another study conducted by Touray et al . [ 27 ] found that level of education of a mother/caregiver was associated with full uptake of childhood vaccine.

Number of antenatal visits was a factor affecting full uptake of malaria vaccine. The children whose mothers/caregivers went for ante natal clinic 4 times or more had increased odds of getting fully vaccinated. This could be due to their health seeking behavior but also because they could have heard about the introduction of malaria vaccine at ANC and being told the importance of vaccinating their children. Similar results were reported in studies conducted by in Malawi, Ghana and Kenya [ 23 , 24 , 25 ].

This study showed that mothers/caregivers whose children ever suffered side effects following immunization had decreased odds of completing all the four doses of malaria vaccine. These mothers/caregivers could have been afraid of taking their children for vaccination in fear of the side effects. Studies conducted in Nigeria, Burkina Faso and Ethiopia also reported side effects following immunization affected the uptake of childhood vaccines [ 21 , 25 , 26 ]. Since malaria vaccine was being newly introduced in Nsanje district mothers/caregivers could think that the vaccine may have worst adverse effects after immunization hence hesitating in the uptake. This could have contributed to the low coverage of fully vaccinated children with malaria vaccine.

Mothers/caregivers who were living near the vaccination point had increased odds in getting their children receiving all the doses than those mothers who were living far. Similar results were observed in studies conducted in Malawi . Three systematic reviews conducted in Ethiopia, Nigeria and in sub-Saharan African systematic also found that distance to the vaccination site was a determinant for full uptake of childhood vaccines 16 , 20 , 28 Furthermore, mode of transport was found to be a significant factor associated with full uptake of malaria vaccine. This study observed that those mothers/caregivers who used commercial motorbikes or bikes were finding it easy to reach the vaccination points hence most of them had their children full vaccinated. Similar findings were reported in a study conducted in Togo [ 29 ].

The study found that having attended vaccination site and failed to vaccinate the child was significantly associated with malaria vaccine uptake. The reasons for mothers/caregivers not vaccinating their child while already at the vaccination site could be vaccine stock-outs, cancellation of the vaccination clinic, arriving at the clinic late while it has already been closed. This could have made some mothers/caregivers not to go to the vaccination site again as they think they may just waste their time to go to the vaccination site and never vaccinate their children hence leading to low coverage of malaria vaccine. Similarly, Lee et al . [ 30 ] found that vaccine stock-outs were significantly associated with low coverage of vaccines. Additionally, a study conducted in Ethiopia in 2021 reported that mothers/caregivers unsatisfied with health care workers was a determinant for incomplete childhood vaccination [ 31 ].

Limitations of the study

Some of the mothers/caregivers had no health passports for their children and consequently the researcher only relied on the word of mouth to re-call some information. This study did not collect qualitative data using Focus Group Discussions (FGDs), this would have thrown more light on the health system factors affecting the uptake of malaria vaccine it could also have given more understanding on perceptions, experiences and challenges faced by mothers/caregivers getting their children to receive malaria vaccine.

In order to reach WHO vaccine targets and increase the effectiveness of the malaria vaccine, district and national level agencies, e.g. Nsanje Directorate of Health and Social Services and Malawi Ministry of Health, should intensify and sustain information, education and communication in the communities about the malaria vaccine. Engaging religious leaders may also enhance these messages.

Availability of data and materials

Relevant datasets for this study are availability from the corresponding author upon request.

Abbreviations

Adverse event following immunization

Ante-natal care

Expanded programme on immunization

Long lasting insecticidal nets

Ministry of Health

National Malaria Control Programme

Piperonyl butoxide

Malaria vaccine

Vaccine preventable diseases

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Acknowledgements

I would like to express my sincere gratitude to Nsanje Directorate of Health and Social Services for giving me clearance to conduct the study in their Health Catchment areas. We would also like to thank village heads who gave permission for us to interview the participants in their villages. We thank Mr. Jomo Sumani, Mr. Mphatso William, Mr. Ben Chilongo, Mr. Wilson Ntchembere, Mr. Doubtful Thete and Mrs. Edina Sadik who participated in data collection. I special thanks should also go to Mr. Jekiyala Kalonga (Nsanje District Malaria Coordinator), Mr. Willy Magwira (Nsanje Health Management Information System Officer), Mr. Fred Minyaliwa (Nsanje District Environmental Health Officer) for their logistical and technical assistance during the implementation of this study.

This work was supported by the Capacity Development of Applied Epidemiologists in Eastern Africa Region (CDAE), a project which is part of European and Developing Countries Clinical Trials Partnership II (EDCPT2) Programme supported by the European Union. CDAE is jointly implemented by the Africa Population and Health Research Center (APHRC), the Amref International University (AMIU) and the Jaramogi Oginga Odinga University of Science and Technology (JOOUST) and funded by the EDCPT2 (Grant: CSA2020E-3139) awarded to AJS.

Author information

Save Kumwenda, Lauren M. Cohee and Shehu S. Awandu shares the final authorship, having contributed equally to the study.

Authors and Affiliations

Department of Biomedical Sciences, School of Health Sciences, Jaramogi Oginga Odinga University of Science and Technology, P. O. Box 210-40601, Bondo, Kenya

Atusaye J. Simbeye, Dickens Omondi & Shehu S. Awandu

Department of Public and Environmental Health Sciences, School of Science and Technology, Malawi University of Business and Applied Sciences, Chichiri, Private Bag 303, Blantyre, Malawi

Save Kumwenda

Department of Pediatrics, Division of Infectious Disease and Tropical Pediatrics, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 655 B Baltimore St S, Baltimore, MD, 21201, USA

Lauren M. Cohee

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK

School of Public Health, Amref International University, P. O. Box 27691-00506, Nairobi, Kenya

Peninah K. Masibo

African Population and Health Research Centre (APHRC), P. O. Box 10787-00100, Nairobi, Kenya

Hesborn Wao

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AJS, SK, LMC and SSA conceived the study and developed study protocol. AJS conducted data collection supervision. AJS, LMC and SSA conducted data analysis. AJS wrote the first draft of the manuscript. SK, LMC, DO, PKM, HW and SSA revised the manuscript and all authors approved the final manuscript prior to submission. All authors approved the final manuscript.

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Permision to conduct this study was obtained from Jaramogi Oginga Odinga University of Science and Technology ethical review committee (JOOUST-ERC), reference number: JOOUST/DVC-RIO/E4, approval number: ERC 37/04/23-5/05 and from Malawi National Health Sciences Research Committee (NHSRC), protocol number: 23/02/3267, approval number: 3267. Clearance was obtained from Nsanje District Health Directorate before commencement of the study activities. Permission was also sought from local leaders verbally before entering in their villages. Before data collection, informed consent was sought from each study to ensure voluntary participation in the study. All necessary information about the study was explained to the participants. The purpose, risks, and benefits of the study was explained to each study participant. Further, the study participants were told that they have right to withdraw from the study at any point during the study period. Those participants who agreed to be interviewed were requested to either sign or thumbprint the informed consent form.

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Simbeye, A.J., Kumwenda, S., Cohee, L.M. et al. Factors associated with malaria vaccine uptake in Nsanje district, Malawi. Malar J 23 , 105 (2024). https://doi.org/10.1186/s12936-024-04938-7

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The Transformation Agenda »

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Speeches & Messages

World Malaria Day 2024

Message of the WHO Regional Director for Africa, Dr Matshidiso Moeti

Malaria has been a priority health problem in the African region over the past decades. It remains a leading cause of illness, hospital admissions, and deaths, especially in young children and pregnant women.

We appreciate the progress made over the last two decades.

Since 2000, the world has mobilized more than US$50 billion to support malaria control and elimination efforts, and as a result, 2.1 billion malaria cases and 11.7 million malaria deaths were averted in the period 2000–2022.

This investment reduced the malaria mortality rate by half, from about 29 deaths per 100 000 population at risk in 2000 to 14.3 in 2022—despite the COVID-19 pandemic. We’ve recorded milestones toward malaria elimination; Cabo Verde was recently certified in January 2024, after Algeria in 2017.

In 2023, WHO approved the second malaria vaccine, R21/MatrixM, after RTS,S in 2021. Both vaccines will be rolled out in 19 countries in the African region this year; they’ll provide new hope for hundreds of thousands of children at risk of dying from malaria.

As countries make progress, families are yielding dividends in terms of well-being.

Charity Damoah, a 36-year-old woman, lost count of the number of times she was admitted to hospital with malaria while growing up in Sunyani, in Ghana’s Bono region. But things are different now for her two-year-old son, John, who has never had malaria because he has been on preventive medicines, uses a treated bed net and has received vaccines.

However, the African region has reached a crossroad in controlling the disease: Twenty of the most affected countries3 - that contribute more than 85% of cases and deaths - are in our region. Multiple challenges account for this, such as extreme weather events, conflict and humanitarian crises, resource constraints, biological threats, and inequities.

With the international community, we commemorate this 17th World Malaria Day under the theme: “Advancing health equity, gender equality and human rights”, This year’s theme highlights the need to ensure continuous and equitable delivery of malaria services to all who need them despite funding constraints, ensuring adequate coverage of the most vulnerable and at-risk populations with effective interventions.

The last World Malaria Report demonstrates how malaria disproportionately affects vulnerable populations such as young children, pregnant women, rural communities, and displaced populations.

Infants and young children represent about 80% of the mortality, while studies show that children under the age of five from the poorest households in sub-Saharan Africa are five times more likely to be infected with malaria than those from the wealthiest households.

In addition to children and women, other high-risk groups have been identified in some areas, such as refugees, migrants, and internally displaced populations.

In 2019-2022, 41 malaria-endemic countries suffered humanitarian and health emergencies, and about 258 million people needed assistance because of health and humanitarian emergencies in 2022 alone. These populations have poor access to health services and require tailored interventions to fit their needs.

Empowering people to understand and exercise their rights to health through meaningful participation, accountability, and transparency in decision-making processes can improve the demand for quality health services and increase the impact of interventions.

The WHO African Region has been supporting strategic initiatives to maintain and sustain the equitable deployment of malaria control and elimination services.

First, in 2018, WHO and the RBM Partnership catalyzed the “High Burden High Impact” (HBHI) approach, a targeted, data-driven approach to sustainably and equitably address malaria in countries hardest hit by the disease. Through HBHI, malaria affected countries have been tackling the disease by identifying the people who suffer most and making a purposeful effort to reach them with customized packages of interventions and services based on local data and the local disease setting.

The Ministers of Health representing HBHI countries gathered in Yaounde in March 2024 to renew their commitment to the fundamental principle that no one should die from malaria, given the tools and systems available.

With our partners, we will support these countries and others in adapting national monitoring and evaluation frameworks to translate these commitments into concrete actions.

Second, with our partners, we have implemented proven interventions guided by evidence and their amenability to local settings. In 2022, 260 million insecticide treated nets (ITNs) were delivered to sub-Saharan Africa, resulting in 70% of households with at least one ITN and 56% percentage of children under five years and pregnant women sleeping under an ITN. IRS has also been implemented in a few countries in the region. To date, 35 African countries have adopted intermittent preventive treatment in pregnant women (IPTp), with an estimated 42% of pregnant women at risk of malaria receiving three doses of the preventive therapy.

Still, coverage remains well below the target of 80%. Seasonal Malaria Chemoprevention has been implemented in 17 of our Member States, with the average number of children treated per cycle reaching 49 million in 2022. The availability of rapid diagnostic tests (RDTs) and artemisinine based combination therapies (ACTs) increased in 2022, with 90% and 97% of global quantities distributed in sub-Saharan Africa.

Third, with our partners, we support innovation and research to ensure that new strategies and tools that target vulnerable groups can be developed, approved, and rapidly deployed for public health use. In this light, we will continue supporting the malaria vaccine roll out through our strategic initiative, the Accelerated Malaria Vaccine Introduction and Rollout in Africa (AMVIRA), a multi-partner platform designed to mobilize technical and financial assistance to countries to ensure optimal coverage for all eligible children. We will equally support our Member States in implementing two newly recommended classes of dual-ingredient ITNs and other vector control interventions to increase the effect against pyrethroid-resistant malaria vectors.

Finally, we made all this progress thanks to the leadership of governments, global solidarity, and essential resources mobilized by countries and their partners.

I thank the Global Fund, the US President’s Malaria Initiative, GAVI, the Bill and Melinda Gates Foundation, and other bilateral development partners that have mobilized financial and technical resources to support our Member States in continuing to deliver malaria services to affected communities. We will foster effective partnerships and strengthen coordination of the regional malaria response.

World Malaria Day allows us to renew political commitments and bolster malaria prevention and control investments.

I call on the governments of our Member States, affected communities, and partners to keep investing in malaria control and build resilient health systems while strengthening primary health care to ensure that quality services are available to all.

I urge countries to develop surveillance, monitoring and evaluation systems to generate reliable and sub-national data to target interventions and adapt services to the most at-risk groups, accelerating progress toward achieving the SDGs.

Together, we can accelerate our efforts to get back on track and achieve a malaria free Africa.

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Institute of Medicine (US) Committee for the Study on Malaria Prevention and Control; Oaks SC Jr., Mitchell VS, Pearson GW, et al., editors. Malaria: Obstacles and Opportunities. Washington (DC): National Academies Press (US); 1991.

Malaria: Obstacles and Opportunities.

Hardcopy Version at National Academies Press

1 Conclusions and Recommendations

DEFINING THE PROBLEM

In large part because of the spread of drug and insecticide resistance, there are fewer tools available today to control malaria than there were 20 years ago. In many countries, the few remaining methods are often applied inappropriately. The situation in many African nations is particularly dismal, exacerbated by a crumbling health infrastructure that has made the implementation of any disease control program difficult.

For the hundreds of thousands of Thai seasonal agricultural workers who travel deep into the forest along the Thailand-Cambodia border to mine for gems, malaria is the cost of doing business. These young men are exposed to aggressive forest mosquitoes, and within two to three weeks after arriving, almost every miner will get malaria. Many gem miners seek medications to prevent and self-treat mild cases of the disease. But because malaria in this part of the world is resistant to most antimalarial drugs, the few effective drugs are reserved for the treatment of confirmed cases of malaria. To complicate matters, there are no health services in the forest to treat patients, and the health clinics in Thailand are overburdened by the high demand for treating those with severe malaria, most of whom are returning gem miners. A similar scenario involving over 400,000 people exists among gold miners in Rondonia, Brazil.
Each year, over seven million U.S. citizens visit parts of the world where malaria is present. Many, at the recommendation of their travel agent or physician, take antimalarial medications as a preventive measure, but a significant number do not. Tourists and other travelers who have never been exposed to malaria, and therefore have never developed protective immunity, are at great risk for contracting severe disease. Ironically, it is not the infection itself that poses the biggest danger, but the chance that treatment will be delayed because of misdiagnosis upon the individual's return to the United States. Most U.S. doctors have never seen a patient with malaria, are often confused by the wide array of symptoms, and are largely unaware that malaria in a nonimmune person can be a medical emergency, sometimes rapidly fatal.
Prior to 1950, malaria was the major cause of death in the central highlands of the African island nation of Madagascar. In the late 1950s, an aggressive program of indoor insecticide spraying rid the area of malaria-carrying mosquitoes, and malaria virtually disappeared. By the 1970s, confident of a victory in the battle against malaria, Madagascar began to phase out its spraying program; in some areas spraying was halted altogether. In the early 1980s, the vector mosquitoes reinvaded the central highlands, and in 1986 a series of devastating epidemics began. The older members of the population had long since lost the partial immunity they once had, and the younger island residents had no immunity at all. During the worst of the epidemics, tens of thousands of people died in one three-month period. The tragedy of this story is that it could have been prevented. A cheap antimalarial drug, chloroquine, could have been a powerful weapon in Madagascar, where drug resistance was not a significant concern. Because of problems in international and domestic drug supply and delivery, however, many people did not receive treatment and many died. In the last 18 months, surveillance has improved, spraying against the mosquito has resumed, and more effective drug distribution networks have been established. Malaria-related mortality has declined sharply as a result.
Malaria, once endemic in the southern United States, occurs relatively infrequently. Indeed, there have been only 23 outbreaks of malaria since 1950, and the majority of these occurred in California. But for each of the past three years, the San Diego County Department of Health Services has had to conduct an epidemiologic investigation into local transmission of malaria. An outbreak in the late summer of 1988 involved 30 persons, the largest such outbreak in the United States since 1952. In the summer of 1989, three residents of San Diego County—a migrant worker and two permanent residents—were diagnosed with malaria; in 1990, a teenager living in a suburb of San Diego County fell ill with malaria. All of the cases were treated successfully, but these incidents raise questions about the possibility of new and larger outbreaks in the future. Malaria transmission in San Diego County (and in much of California) is attributed to the presence of individuals from malaria-endemic regions who lack access to medical care, the poor shelter and sanitation facilities of migrant workers, and the ubiquitous presence of Anopheles mosquitoes in California.
A 24-year-old pregnant Yao woman from the Mangochi District in Malawi visited the village health clinic monthly to receive prenatal care. While waiting to be seen by the health provider, she and other women present listened to health education talks which were often about the dangers of malaria during pregnancy, and the need to install screens around the house to keep the mosquitoes away, to sleep under a bednet, and to take a chloroquine tablet once a week. Toward the end of her second trimester of pregnancy, the woman returned home from her prenatal visit with her eight tablets of chloroquine wrapped in a small packet of brown paper. She promptly gave the medicine to her husband to save for the next time he or one of their children fell ill. The next week she developed a very high malarial fever and went into labor prematurely. The six-month-old fetus was born dead.
Over a two-week period in the summer of 1989, five Swiss citizens living within a mile of Geneva International Airport presented at several hospitals with acute fever and chills. All had malaria. Four of the five had no history of travel to a malarious region; none had a history of intravenous drug use or blood transfusion. Apart from their symptoms, the only thing linking the five was their proximity to the airport. A subsequent epidemiologic investigation suggested that the malaria miniepidemic was caused by the bite of stowaway mosquitoes en route from a malaria- endemic country. The warm weather, lack of systematic spraying of aircraft, and the close proximity of residential areas to the airport facilitated the transmission of the disease.
Malaria is a part of everyday life in Africa south of the Sahara. Its impact on children is particularly severe. Mothers who bring unconscious children to the hospital often report that the children were playing that morning, convulsed suddenly, and have been unconscious ever since. These children are suffering from the most frequently fatal complication of the disease, cerebral malaria. Other children succumb more slowly to malaria, becoming progressively more anemic with each subsequent infection. By the time they reach the hospital, they are too weak to sit and are literally gasping for breath. Many children are brought to hospitals as a last resort, after treatment given for “fever” at the local health center has proved ineffective. Overall, children with malaria account for a third of all hospital admissions. A third of all children hospitalized for malaria die. In most parts of Africa, there are no effective or affordable options to prevent the disease, so children are at high risk until they have been infected enough times to develop a partial immunity.
A 52-year-old American woman, the secretary to the U.S. ambassador in Tanzania, had been taking a weekly dose of chloroquine to prevent malaria since her arrival in the country the year before. She arrived at work one morning complaining of exhaustion, a throbbing headache, and fever. A blood sample was taken and microscopically examined for malaria parasites. She was found to be infected with P. falciparum , and was treated immediately with high doses of chloroquine. That night, she developed severe diarrhea, and by morning she was found to be disoriented and irrational. She was diagnosed as having cerebral malaria, and intravenous quinine treatment was started. Her condition gradually deteriorated—she became semicomatose and anemic, and approximately 20 percent of her red blood cells were found to be infected with malaria parasites. After continued treatment for several days, no parasites were detected in her blood. Despite receiving optimal care, other malaria-related complications developed and she died just nine days after the illness began. The cause of death: chloroquine-resistant P. falciparum .

It is against this backdrop of a worsening worldwide malaria situation that the Institute of Medicine was asked to convene a multidisciplinary committee to assess the current status of malaria research and control and to make recommendations to the U.S. government on promising and feasible strategies to address the problem. During the 18-month study, the committee reviewed the state of the science in the major areas of malariology, identified gaps in knowledge within each of the major disciplines, and developed recommendations for future action in malaria research and control.

Organization

Sponsorship

CONCLUSIONS AND RECOMMENDATIONS

Commitment and Sustainability

Surveillance

Inter-Sectoral Cooperation

New Tools for Malaria Control

The committee believes that, as a policy directive, it is important to support research activities to develop new tools for malaria control. The greatest momentum for the development of new tools exists in vaccine and drug development, and the committee believes it essential that this momentum be maintained. The committee recognizes that commendable progress has been made in defining the characteristics of antigens and delivery systems needed for effective vaccines, but that the candidates so far tested fall short of the goal. Much has been learned which supports the hope that useful vaccines can be developed. To diminish activity in vaccine development at this stage would deal a severe blow to one of our best chances for a technological breakthrough in malaria control.

The committee recommends that vaccine development continue to be a priority of U.S.-funded malaria research.

The committee strongly recommends that drug discovery and development activities at WRAIR receive increased and sustained support.

The next recommendation on policy directions reflects the committee's concern about the lack of involvement in malaria research by the private sector. The committee believes that the production of candidate malaria vaccines and antimalarial drugs for clinical trials has been hampered by a lack of industry involvement. Greater cooperation and a clarification of the contractual relationships between the public and private sectors would greatly enhance the development of drugs and vaccines.

Coordination and Integration

The committee is concerned that there is inadequate joint planning and coordination among U.S.-based agencies that support malaria research and control activities. Four government agencies and many nongovernmental organizations in the United States are actively involved in malaria-related activities. There are also numerous overseas organizations, governmental and nongovernmental, that actively support such activities worldwide.

The committee strongly recommends the establishment of a national advisory body on malaria.

Malaria Research Priorities

Research in Support of Available Control Measures

The committee recommends that epidemiologic studies on the risk factors for severe and complicated malaria be supported.

Social Science Research The impact of drugs to control disease or programs to reduce human-mosquito contact is mediated by local practices and beliefs about malaria and its treatment. Most people in malaria- endemic countries seek initial treatment for malaria outside of the formal health sector. Programs that attempt to influence this behavior must understand that current practices satisfy, at some level, local concerns regarding such matters as access to and effectiveness of therapy, and cost. These concerns may lead to practices at odds with current medical practice. Further, many malaria control programs have not considered the social, cultural, and behavioral dimensions of malaria, thereby limiting the effectiveness of measures undertaken. The committee recognizes that control programs often fail to incorporate household or community concerns and resources into program design. In most countries, little is known about how the demand for and utilization of health services is influenced by such things as user fees, location of health clinics, and the existence and quality of referral services. The committee concludes that modern social science techniques have not been effectively applied to the design, implementation, and evaluation of malaria control programs.

Development of New Tools

The committee recommends sustained support for research to identify mechanisms and targets of protective immunity and to exploit the use of novel scientific technologies to construct vaccines that induce immunity against all relevant stages of the parasite life cycle.

The committee recommends increased support for research on vector control that focuses on the development and field testing of methods for interrupting parasite transmission by vectors.

Malaria Control

Unfortunately, there is no “magic bullet” solution to the deteriorating worldwide malaria situation, and no single malaria control strategy will be applicable in all regions or epidemiologic situations. Given the limited available financial and human resources and a dwindling pool of effective antimalarial tools, the committee suggests that donor agencies support four priority areas for malaria control in endemic countries.

Organization of Malaria Control

The committee strongly encourages renewed commitment by donor agencies to support national control programs in malaria- endemic countries.

The committee believes that the development, implementation, and evaluation of such programs must follow a rigorous set of guidelines. These guidelines should include the following steps:

Identification of the problem

Determine the extent and variety of malaria. The paradigm approach described in Chapter 10 should facilitate this step.

Analyze current efforts to solve malaria problems.

Identify and characterize available in-country resources and capabilities.

Development of a plan

Design and prioritize interventions based on the epidemiologic situation and the available resources.

Design a training program for decision makers, managers, and technical staff to support and sustain the interventions.

Define specific indicators of the success or failure of the interventions at specific time points.

Develop a specific plan for reporting on the outcomes of interventions.

Develop a process for adjusting the program in response to successes and/or failures of interventions.

Review of the comprehensive plan by a donor agency review board

Modification of the plan based on comments of the review board

Implementation of the program

Yearly report and analysis of outcome variables

Paradigm Approach

The committee recommends that U.S. funding of each malaria control program include support for a senior manager who has responsibility for planning and coordinating malaria control activities. Where such an individual does not exist, a priority of the control effort should be to identify and support a qualified candidate. The manager should be supported actively by a multidisciplinary core group with expertise in epidemiology , entomology, the social sciences, clinical medicine, environmental issues, and vector control operations.

Monitoring and Evaluation

Problem Solving (Operational Research) and Evaluation

The committee recommends support for research training in malaria.

The committee recommends support for training in management, epidemiology , entomology, social sciences, and vector control. Such training for malaria control may be accomplished through U.S.-funded grant programs for long-term cooperative relationships between institutions in developed and developing countries; through the encouragement of both formal and informal linkages among malaria- endemic countries; through the use of existing training courses; and through the development of specific training courses.

Cite this Page Institute of Medicine (US) Committee for the Study on Malaria Prevention and Control; Oaks SC Jr., Mitchell VS, Pearson GW, et al., editors. Malaria: Obstacles and Opportunities. Washington (DC): National Academies Press (US); 1991. 1, Conclusions and Recommendations.
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Malaria: Obstacles and Opportunities (1991)

Organization

Sponsorship

CONCLUSIONS AND RECOMMENDATIONS

Commitment and Sustainability

Surveillance

Inter-Sectoral Cooperation

New Tools for Malaria Control

Coordination and Integration

Malaria Research Priorities

Research in Support of Available Control Measures

Development of New Tools

Malaria Control

Organization of Malaria Control

Paradigm Approach

Monitoring and Evaluation

Problem Solving (Operational Research) and Evaluation

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Plasmodium —a brief introduction to the parasites causing human malaria and their basic biology

Background: battle of humans against malaria—past and present

Malaria and Plasmodium biology

Recurrence of malaria and the hypnozoite

Gametocytes

Asymptomatic carriers

Apicoplast and plant-like metabolism

Antimalarial drugs and resistance

Conclusions

Availability of data and materials

Change history

Abbreviations

Acknowledgements

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Journal of Physiological Anthropology

Factors associated with malaria vaccine uptake in Nsanje district, Malawi

Study design

Study population

Sample size calculation

Sampling individual participants

Data collection

Data analysis

Socio-demographics characteristics of mothers/caregiver and their children

Uptake of malaria vaccine

Reasons for incomplete vaccination

Mother/caregiver and child characteristics associated with vaccine uptake

Multivariate analysis of associations between full uptake of malaria vaccine and mother/caregiver and child factors

Limitations of the study

Availability of data and materials

Abbreviations

Acknowledgements

Author information

Authors and Affiliations

Contributions

Corresponding author

Ethics declarations