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Malaria: The Past and the Present

Jasminka talapko.

1 Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Crkvena 21, HR-31000 Osijek, Croatia; rh.zmdf@okpalatj (J.T.); rh.zmdf@vecva (A.V.)

Ivana Škrlec

Tamara alebić.

2 Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, HR-31000 Osijek, Croatia; [email protected] (T.A.); moc.liamg@71ikujm (M.J.)

Melita Jukić

3 General Hospital Vukovar, Županijska 35, HR-32000 Vukovar, Croatia

Aleksandar Včev

Malaria is a severe disease caused by parasites of the genus Plasmodium , which is transmitted to humans by a bite of an infected female mosquito of the species Anopheles . Malaria remains the leading cause of mortality around the world, and early diagnosis and fast-acting treatment prevent unwanted outcomes. It is the most common disease in Africa and some countries of Asia, while in the developed world malaria occurs as imported from endemic areas. The sweet sagewort plant was used as early as the second century BC to treat malaria fever in China. Much later, quinine started being used as an antimalaria drug. A global battle against malaria started in 1955, and Croatia declared 1964 to be the year of eradication of malaria. The World Health Organization carries out a malaria control program on a global scale, focusing on local strengthening of primary health care, early diagnosis of the disease, timely treatment, and disease prevention. Globally, the burden of malaria is lower than ten years ago. However, in the last few years, there has been an increase in the number of malaria cases around the world. It is moving towards targets established by the WHO, but that progress has slowed down.

1. Introduction

Malaria affected an estimated 219 million people causing 435,000 deaths in 2017 globally. This burden of morbidity and mortality is a result of more than a century of global effort and research aimed at improving the prevention, diagnosis, and treatment of malaria [ 1 ]. Malaria is the most common disease in Africa and some countries in Asia with the highest number of indigenous cases. The malaria mortality rate globally ranges from 0.3–2.2%, and in cases of severe forms of malaria in regions with tropical climate from 11–30% [ 2 ]. Different studies showed that the prevalence of malaria parasite infection has increased since 2015 [ 3 , 4 ].

The causative agent of malaria is a small protozoon belonging to the group of Plasmodium species, and it consists of several subspecies. Some of the Plasmodium species cause disease in human [ 2 , 5 ]. The genus Plasmodium is an amoeboid intracellular parasite which accumulates malaria pigment (an insoluble metabolite of hemoglobin). Parasites on different vertebrates; some in red blood cells, and some in tissue. Of the 172 of Plasmodium species, five species can infect humans. These are P. malariae , P.falciparum , P.vivax , P.ovale , and P.knowlesi . In South-East Asia, the zoonotic malaria P.knowlesi is recorded. Other species rarely infect humans [ 5 , 6 , 7 , 8 ]. All the mentioned Plasmodium species cause the disease commonly known as malaria (Latin for Malus aer —bad air). Likewise, all species have similar morphology and biology [ 9 ].

The Plasmodium life cycle is very complex and takes place in two phases; sexual and asexual, the vector mosquitoes and the vertebrate hosts. In the vectors, mosquitoes, the sexual phase of the parasite’s life cycle occurs. The asexual phase of the life cycle occurs in humans, the intermediate host for malaria [ 9 , 10 ]. Human malaria is transmitted only by female mosquitoes of the genus Anopheles . The parasite, in the form of sporozoite, after a bite by an infected female mosquito, enters the human blood and after half an hour of blood circulation, enters the hepatocytes [ 11 ]. The first phase of Plasmodium asexual development occurs in the hepatocytes, and then in the erythrocytes. All Plasmodium species lead to the rupture of erythrocytes [ 7 , 9 , 12 , 13 ].

The most common species in the Americas and Europe are P.vivax and P.malariae , while in Africa it is P.falciparum [ 14 ].

2. Discovery of Malaria

It is believed that the history of malaria outbreaks goes back to the beginnings of civilization. It is the most widespread disease due to which many people have lost lives and is even thought to have been the cause of major military defeats, as well as the disappearance of some nations [ 15 ]. The first descriptions of malaria are found in ancient Chinese medical records of 2700 BC, and 1200 years later in the Ebers Papyrus [ 2 ]. The military leader Alexander the Great died from malaria [ 15 ]. The evidence that this disease was present within all layers of society is in the fact that Christopher Columbus, Albrecht Dürer, Cesare Borgia, and George Washington all suffered from it [ 16 , 17 ].

Although the ancient people frequently faced malaria and its symptoms, the fever that would occur in patients was attributed to various supernatural forces and angry divinities. It is, thus, stated that the Assyrian-Babylonian deity Nergal was portrayed as a stylized two-winged insect, as was the Canaan Zebub (‘Beelzebub, in translation: the master of the fly’) [ 17 ]. In the 4th century BC, Hippocrates described this disease in a way that completely rejected its demonic origins and linked it with evaporation from swamps which, when inhaled, caused the disease. That interpretation was maintained until 1880 and Laveran’s discovery of the cause of the disease [ 18 ]. Laveran, a French military surgeon, first observed parasites in the blood of malaria patients, and for that discovery he received the Nobel Prize in 1907 [ 19 ].

Cartwright and Biddis state that malaria is considered to be the most widespread African disease [ 14 ]. The causative agent of malaria is a small protozoon belonging to the group of Plasmodium species, and it consists of several subspecies [ 14 ].

3. The Development of Diagnostic Tests for Proving Malaria through History

Malaria can last for three and up to five years, if left untreated, and depending on the cause, may recrudesce. In P. vivax and ovale infections, the persistence of the merozoites in the blood or hypnozoites in hepatocytes can cause relapse months or years after the initial infection. Additionally, relapse of vivax malaria is common after P. falciparum infection in Southeast Asia. Relapse cases were observed in P. falciparum infections, which can lead to a rapid high parasitemia with subsequent destruction of erythrocytes [ 20 , 21 ]. Children, pregnant women, immunocompromised and splenectomized patients are especially vulnerable to malaria infection, as well as healthy people without prior contact with Plasmodium . A laboratory test for malaria should always confirm clinical findings. The proving of malaria is carried out by direct methods such as evidence of parasites or parts of parasites, and indirect methods that prove the antibodies to the causative agents ( Table 1 ) [ 2 , 5 , 22 ].

Diagnostic tests for proving malaria.

The gold standard method for malaria diagnosis is light microscopy of stained blood films by Giemsa. Due to a lack of proper staining material and trained technicians, this method is not available in many parts of sub-Saharan Africa. The sensitivity of the method depends on the professional expertise, and it is possible to detect an infection with 10–100 parasites/μL of blood. A negative finding in patients with symptoms does not exclude malaria, but smears should be repeated three times in intervals of 12–24 h if the disease is still suspected [ 23 , 24 ]. Diagnosis of malaria using serologic testing has traditionally been done by immunofluorescence antibody testing (IFA). IFA is time-consuming and subjective. It is valuable in epidemiological studies, for screening possible blood donors. It also demands fluorescence microscopy and qualified technicians [ 23 , 25 , 26 ].

Rapid Diagnostic Tests (RDT) for the detection of antigens in the blood are immunochromatographic tests to prove the presence of parasite antigens. No electrical equipment, and no special experience or skills are required to perform these tests. The RDTs are now recommended by WHO as the first choice of test all across the world in all malaria-endemic areas. The sensitivity of the antigen test varies depending on the selected antigens represented in the test. For some RDTs is 50–100 parasites/μL (PfHRP2) to <100 parasites/μL [ 27 , 28 ]. The FDA approved the first RDT test in 2007. It is recommended that the results of all RDT tests should be confirmed by microscopic blood analysis [ 29 ]. It is known that antigens detected with RDT test remain in the blood after antimalarial treatment, but the existence of these antigens varies after treatment. The false-positive rates should be less than 10% [ 30 ]. Several RDT tests in the eight rounds of testing revealed malaria at a low-density parasite (200 parasites/μL), had low false-positive rates and could detect P. falciparum or P. vivax infections or both [ 30 ]. False-positive rates of P. vivax were typically small, between 5% and 15%. On the other hand, the false-positive rates of P. falciparum range from 3–32% [ 30 , 31 ]. Good RDTs might occasionally give false-negative results if the parasite density is low, or if variations in the production of parasite antigen reduce the ability of the RDT to detect the parasite. False negative results of the RDT test for P. falciparum ranged between 1% and 11% [ 31 , 32 , 33 , 34 ]. The overall sensitivity of RDTs is 82% (range 81–99%), and specificity is 89% (range 88–99%) [ 35 ].

Polymerase chain reaction (PCR) is another method in the detection of malaria. This method is more sensitive and more specific than all conventional methods in the detection of malaria. It can detect below one parasite/μL. PCR test confirms the presence of parasitic nucleic acid [ 23 , 36 ]. PCR results are often not available fast enough to be useful in malaria diagnosis in endemic areas. However, this method is most helpful in identifying Plasmodium species after diagnosis by microscopy or RDT test in laboratories that might not have microscopic experts. Additionally, PCR is useful for the monitoring of patients receiving antimalaria treatment [ 36 , 37 ].

Indirect methods are used to demonstrate antibodies to malaria-causing agents. Such methods are used in testing people who have been or might be at risk of malaria, such as blood donors and pregnant women. The method is based on an indirect immunofluorescence assay (IFA) or an ELISA test. The IFA is specific and sensitive but not suitable for a large number of samples, and the results are subjective evaluations. For serological testing, ELISA tests are more commonly used [ 26 ].

Rapid and accurate diagnosis of malaria is an integral part of appropriate treatment for affected person and the prevention of the further spread of the infection in the community.

4. Malaria Treatment through History

Already in the 2nd century BC, a sweet sagewort plant named Qinghai (Latin Artemisia annua ) was used for the treatment of malaria in China [ 38 ]. Much later, in the 16th century, the Spanish invaders in Peru took over the cinchona medication against malaria obtained from the bark of the Cinchona tree (Latin Cinchona succirubra ). From this plant in 1820 the French chemists, Pierre Joseph Pelletie, and Joseph Bienaimé Caventou isolated the active ingredient quinine, which had been used for many years in the chemoprophylaxis and treatment of malaria. In 1970, a group of Chinese scientists led by Dr. Youyou Tu isolated the active substance artemisinin from the plant Artemisia annua , an antimalarial that has proved to be very useful in treating malaria. For that discovery, Youyou Tu received the Nobel Prize for Physiology and Medicine in 2015 [ 39 , 40 , 41 ]. Most of the artemisinin-related drugs used today are prodrugs, which are activated by hydrolysis to the metabolite dihydroartemisinin. Artemisinin drugs exhibit its antimalarial activity by forming the radical via a peroxide linkage [ 42 ]. WHO recommends the use of artemisinin-based combination therapies (ACT) to ensure a high cure rate of P. falciparum malaria and reduce the spread of drug resistance. ACT therapies are used due to high resistance to chloroquine, sulfadoxine-pyrimethamine, and amodiaquine [ 1 ]. Due to the unique structure of artemisinins, there is much space for further research. Extensive efforts are devoted to clarification of drug targets and mechanisms of action, the improvement of pharmacokinetic properties, and identifying a new generation of artemisinins against resistant Plasmodium strains [ 42 ].

The German chemist Othmer Zeidler synthesized dichlorodiphenyltrichloroethane (DDT) in 1874 during his Ph.D. At that time, no uses of DDT was found, and it just became a useless chemical [ 43 ]. The insecticide property of DDT was discovered in 1939 by Paul Müller in Switzerland. DDT began to be used to control malaria at the end of the Second World War [ 40 ]. During the Second World War, the success of DDT quickly led to the introduction of other chlorinated hydrocarbons which were used in large amounts for the control of diseases transmitted by mosquito [ 43 ]. From the late Middle Ages until 1940, when DDT began to be applied, two-thirds of the world’s population had been exposed to malaria, a fact that represented a severe health, demographic, and economic problem [ 29 , 40 , 41 , 44 , 45 ]. DDT is an organochlorine pesticide which was applied in liquid and powder form against the insects. During the Second World War people were sprayed with DDT. After the war, DDT became a powerful way of fighting malaria by attacking the vector [ 43 ].

Five Nobel Prizes associated with malaria were awarded: Youyou Tu in 2015. Ronald Ross received the Nobel Prize in 1902 for the discovery and significance of mosquitoes in the biology of the causative agents in malaria. In 1907, the Nobel was awarded to the already-mentioned Charles Louis Alphonse Laveran for the discovery of the causative agent. Julius Wagner-Jauregg received it in 1927 for the induction of malaria as a pyrotherapy procedure in the treatment of paralytic dementia. In 1947 Paul Müller received it for the synthetic pesticide formula dichlorodiphenyltrichloroethane.

Attempts to produce an effective antimalarial vaccine and its clinical trials are underway. Over the past several decades’ numerous efforts have been made to develop effective and affordable preventive antimalaria vaccines. Numerous clinical trials are completed in the past few years. Nowadays are ongoing clinical trials for the development of next-generation malaria vaccines. The main issue is P. vivax vaccine, whose research requires further investigations to identify novel vaccine candidates [ 46 , 47 , 48 ]. Despite decades of research in vaccine development, an effective antimalaria vaccine has not yet been developed (i.e., with efficacy higher than 50%) [ 49 , 50 , 51 ]. The European Union Clinical Trials Register currently displays 48 clinical trials with a EudraCT protocol for malaria, of which 13 are still ongoing clinical trials [ 52 ]. The malaria parasite is a complex organism with a complex life cycle which can avoid the immune system, making it very difficult to create a vaccine. During the different stages of the Plasmodium life cycle, it undergoes morphological changes and exhibits antigenic variations. Plasmodium proteins are highly polymorphic, and its functions are redundant. Also, the development of malaria disease depends on the Plasmodium species. That way, a combination of different adjuvants type into antigen-specific formulations would achieve a higher efficacy [ 53 , 54 ]. Drugs that underwent clinical trials proved to be mostly ineffective [ 5 , 7 , 55 ]. However, many scientists around the world are working on the development of an effective vaccine [ 56 , 57 , 58 ]. Since other methods of suppressing malaria, including medication, insecticides, and bed nets treated with pesticides, have failed to eradicate the disease, and the search for a vaccine is considered to be one of the most important research projects in public health by World Health Organization (WHO).

The best way to fight malaria is to prevent insect bites. Malaria therapy is administered using antimalarial drugs that have evolved from quinine. According to its primary effect, malarial vaccines are divided into pre-erythrocytic (sporozoite and liver-stage), blood-stage, and transmission-blocking vaccines [ 9 , 54 ]. Most medications used in the treatment are active against parasitic forms in the blood (the type that causes disease) ( Table 2 ) [ 59 ]. The two crucial antimalarial medications currently used are derived from plants whose medical importance has been known for centuries: artemisinin from the plant Qinghao ( Artemisia annua L, China, 4th century) and quinine from Cinchona (South America, 17th century). Side-by-side with artemisinin, quinine is one of the most effective antimalarial drugs available today [ 13 , 39 , 40 ]. Doxycycline is indicated for malaria chemoprophylaxis for travel in endemic areas. It is also used in combination with the quinine or artesunate for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. The disadvantage of doxycycline is that children and pregnant women cannot use it [ 29 ]. Due to the global resistance of P. falciparum to chloroquine, ACTs are recommended for the treatment of malaria, except in the first trimester of pregnancy. ACTs consist of a combination of an artemisinin derivative that fast decreases parasitemia and a partner drug that eliminates remaining parasites over a more extended period. The most common ACTs in use are artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, artesunate-mefloquine, and artesunate with sulfadoxine-pyrimethamine. The ACTs were very efficient against all P. falciparum until recently when numbers of treatment failures raised in parts of Southeast Asia. Atovaquone-proguanil is an option non-artemisinin-based treatment that is helpful for individual cases which have failed therapy with usual ACTs. Although, it is not approved for comprehensive implementation in endemic countries because of the ability for the rapid development of atovaquone resistance. Quinine remains efficient, although it needs a long course of treatment, is poorly tolerated, especially by children, and must be combined with another drug, such as doxycycline or clindamycin. Uncomplicated vivax, malariae, and ovale malaria are handled with chloroquine except in case of chloroquine-resistant P. vivax when an ACT is used [ 7 , 29 , 60 , 61 , 62 ].

Overview of the most commonly used antimalarials.

CNS—central nervous system.

4.1. Malaria in Europe

In Europe, malaria outbreaks occurred in the Roman Empire [ 63 , 64 ] and the 17th century. Up until the 17th century it was treated as any fever that people of the time encountered. The methods applied were not sufficient and included the release of blood, starvation, and body cleansing. As the first effective antimalarial drug, the medicinal bark of the Cinchona tree containing quinine was mentioned and was initially used by the Peruvian population [ 14 ]. It is believed that in the fourth decade of the 17th century it was transferred to Europe through the Spanish Jesuit missionaries who spread the treatment to Europe [ 65 ].

Contemporary knowledge of malaria treatment is the result of the work of a few researchers. Some of researchers are Alphonse Laveran, Ronald Ross, and Giovanni Battista Grassi. In November 1880, Laveran, who worked as a military doctor in Algeria, discovered the causative agents of malaria in the blood of mosquitoes and found that it was a kind of protozoa [ 66 ]. Laveran noticed that protozoa could, just like bacteria, live a parasitic way of life within humans and thus cause disease [ 66 ]. Nearly two decades later, more precisely in 1898, Ronald Ross, a military doctor in India, discovered the transmission of bird malaria in the saliva of infected mosquitos, while the Italian physician Giovanni Battista Grassi proved that malaria was transmitted from mosquitoes to humans, in the same year. He also proved that not all mosquitoes transmit malaria, but only a specific species ( Anopheles ) [ 17 ]. This discovery paved the way for further research.

The global battle against malaria started in 1955, and the program was based on the elimination of mosquitoes using DDT and included malarial areas of the United States, Southern Europe, the Caribbean, South Asia, but only three African countries (South Africa, Zimbabwe, and Swaziland). In 1975, the WHO announced that malaria had been eradicated in Europe and all recorded cases were introduced through migration [ 67 , 68 ].

4.2. Malaria in Croatia

In Croatia, the first written document that testifies to the prevention of malaria is the Statute of the town of Korčula from 1265. In 1874, the Law on Health Care of Croatia and Slavonia established the public health service that was directed towards treating malaria. There was no awareness nor proper medical knowledge about malaria, but the drainage was carried out to bring the ‘healthy air’ in the cities [ 69 , 70 ]. In 1798 physician Giuseppe Arduino notified the Austrian government about malaria in Istria. A government representative Vincenzo Benini accepted a proposed sanitary measure of the drainage of wetlands [ 71 ]. In 1864, the drainage of wetlands around Pula and on the coastal islands began, and since 1902 a program for the suppression of malaria by treatment of patients using quinine has been applied [ 72 ]. In 1922, the Institute for Malaria was founded in Trogir. In 1923, on the island of Krk, a project was started to eradicate malaria by the sanitation of water surfaces and the treatment of the patients with quinine, led by Dr. Otmar Trausmiller [ 66 ]. Since 1924, besides chemical treatment, biological control of mosquitoes has been established by introducing the fish Gambusia holbrooki to Istria and the coast [ 73 ]. In 1930 legislation was passed to enforce village sanitation, which included the construction of water infrastructure and safe wells, contributing to the prevention of malaria. Regular mosquito fogging with arsenic green (copper acetoarsenite) was introduced, and larvicidal disinfection of stagnant water was carried out.

Since malaria occurs near swamps, streams, ravines, and places where mosquitoes live near water, this disease has been present throughout history in Croatia, and it has often become an epidemic [ 74 ]. It was widespread in the area of Dalmatia, the Croatian Littoral region, Istria, and river flows. In the area of the Croatian Littoral, it was widespread on some islands, such as Krk, Rab, and Pag, while the mainland was left mainly clear of it [ 75 ]. The ethnographer Alberto Fortis (1741–1803) who traveled to Dalmatia, noted impressions recording details of malaria that was a problem in the Neretva River valley. Fortis wanted to visit that area, but the sailors on ship were afraid, probably because the were afraid to go to a place where there had been a disease outbreak known as the Neretva plague [ 76 ]. This Neretva plague was, in fact, malaria, and it is believed that due to it, the Neretva was nicknamed “Neretva—damned by God” [ 77 , 78 ]. Speaking of the Neretva region, Fortis states that the number of mosquitoes in that wetland area was so high that people had to sleep in stuffy canopy tents to defend themselves. Fortis also states that there were so many mosquitoes that he was affected by it. During the stay, Fortis met a priest who had a bump on the head claiming it had occurred after a mosquito bite and believed that the fever that infected the people of the Neretva Valley was also a consequence of the insect bites there [ 76 ]. In a manuscript, Dugački described some of the epidemics in Croatia. Thus, noted the small population of Nin in 1348, which was the result of the unhealthy air and high mortality of the population. Three centuries later, in 1646, the fever was mentioned in Novigrad, while the year 1717 was crucial for to the Istrian town of Dvigrad, which was utterly deserted due to malaria. At the beginning of the 20th century, more precisely in 1902, the daily press reported that the Provincial Hospital in Zadar was full of people affected by malaria. The extent to which this illness was widespread is proved by the fact that at the beginning of the 20th century about 180,000 people suffered from it in Dalmatia [ 18 ]. The volume and frequency of epidemics in Dalmatia resulted in the arrival of the Italian malariologist Grassi and the German parasitologist Schaudin. The procedures of quininization began to be applied, and in 1908 25 physicians and 423 pill distributors were to visit the villages and divide pills that had to be taken regularly to the people to eradicate malaria [ 75 ].

Likewise, in Slavonia, malaria had also a noticeable effect, and it was widespread in the 18th century due to a large number of swamps that covered the region. Such areas were extremely devastating for settlers who were more vulnerable to the disease than its domestic population [ 79 ]. Friedrich Wilhelm von Taube (1728–1778) recorded the disease and stated that the immigrant Germans were primarily affected by malaria and that the cities of Osijek and Petrovaradin can be nicknamed "German Cemeteries" [ 80 ]. According to Skenderović, the high mortality of German settlers from malaria was not limited only to the Slavonia region but also to the Danubian regions in which the Germans had settled in the 18th century, with Banat and Bačka [ 79 ] having the most significant number of malaria cases. The perception of Slavonia in the 18th century was not a positive one. Even Taube stated that Slavonia was not in good standing in the Habsburg Monarchy and that the nobility avoided living there. As some of the reasons for this avoidance, Taube mentioned the unhealthy air and the many swamps in the area around in which there was a multitude of insects. Taube noted that mosquitoes appear to be larger than in Germany and that its bite was much more painful. A change in the situation could only be brought about by drying the swamp, in his opinion [ 80 ]. Since malaria had led to the death of a large number of people, the solution had to be found to stop its further spread. Swamp drying was finally accepted by the Habsburg Monarchy and some European countries as a practical solution and, thus, its drainage began during the 18th century, resulting in cultivated fields [ 79 ].

Since epidemics of malaria continued to occur, there is one more significant record of the disease in the Medical Journal of 1877. In it, the physician A. Holzer cites his experiences from Lipik and Daruvar where he had been a spa physician for a long time. Holzer warns of the painful illness noticed at spa visitors suffering from the most in July and August. As a physician, Holzer could not remain indifferent to the fact that he did not see anyone looking healthy. It also pointed out that other parts of Croatia were not an exception. As an example, Holzer noted Virovitica County, where malaria was also widespread. He wanted to prevent the development and spread of the illness. Believing that preventing the toxic substances from rising into the air would stop the disease, the solution was to use charcoal that has the properties of absorbing various gases and, thus, prevents vapor rising from the ground [ 81 ].

Dr. Andrija Štampar (1888–1958) holds a prominent place in preventing the spread of malaria. Štampar founded the Department of Malaria, and numerous antimalaria stations, hygiene institutes, and homes of national health. Dr. Štampar devoted his life to educating the broader population about healthy habits and, thus, prevents the spread of infectious diseases. Many films were shown, including a film entitled ‘Malaria of Trogir’ in Osijek in 1927, with numerous health lectures on malaria [ 82 ]. After the end of the Second World War, a proposal for malaria eradication measures was drafted by Dr. Branko Richter. These measures, thanks to Dr. Andrija Štampar, are being used in many malaria-burdened countries. For the eradication of malaria in Croatia and throughout Yugoslavia, DDT has been used since 1947 [ 83 ].

Malaria is still one of the most infectious diseases that cause far more deaths than all parasitic diseases together. Malaria was eradicated in Europe in 1975. After that year, malaria cases in Europe are linked to travel and immigrants coming from endemic areas. Although the potential for malaria spreading in Europe is very low, especially in its western and northern parts, it is still necessary to raise awareness of this disease and keep public health at a high level in order to prevent the possibility of transmitting the disease to the most vulnerable parts of Europe [ 84 ].

Unofficial data show that malaria disappeared from Croatia in 1958, while the World Health Organization cites 1964 as the year when malaria was officially eradicated in Croatia [ 45 , 75 ]. Nonetheless, some cases of imported malaria have been reported in Croatia since 1964. The imported malaria is evident concerning Croatia’s orientation to maritime affairs, tourism, and business trips. Namely, malaria is introduced to Croatia by foreign and domestic sailors, and in rare cases by tourists, mainly from the countries of Africa and Asia [ 75 , 85 ]. According to the reports of the Croatian Institute of Public Health, since the eradication of this disease 423 malaria cases have been reported, all imported [ 86 ]. Figure 1 shows the number of imported malaria cases in Croatia from 1987–2017, and Figure 2 the causative Plasmodium species of those cases ( Figure 1 and Figure 2 ) [ 86 , 87 ].

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Imported malaria cases in Croatia from 1987–2017.

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The causative agents of imported malaria in Croatia.

There is also massive and uncontrollable migration from Africa and Asia (mostly due to climate change) of both humans and birds, from countries with confirmed epidemics. This issue is an insurmountable problem if measured by the traditional approach. Insecticides (DDT, malathion, etc.) synthetic pyrethroids, in addition to inefficiency, impact the environment (harm bees, fruits, vines, etc.). Consequently, scientists have patiently established a mosquito control strategy (University of Grenoble, Montpellier) which includes a meticulous solution to the mosquito vector effect (malaria, arbovirus infection, West Nile virus) by changes in agriculture, urbanism, public services hygiene [ 88 ].

Northeastern Slavonia is committed to applying methods that are consistent with such achievements, with varying success, as certain limitations apply to protected natural habitats (Kopački rit) [ 89 ].

There is a historical link between population movement and global public health. Due to its unique geostrategic position, in the past, Croatia has been the first to experience epidemics that came to Europe through land and sea routes from the east. Adriatic ports and international airports are still a potential entry for the import of individual cases of communicable diseases. Over the past few years, sailors, as well as soldiers who worked in countries with endemic malaria, played a significant role in importing malaria into Croatia. Successful malaria eradication has been carried out in Croatia. Despite that in Croatia are still many types of Anopheles , which means that the conditions of transmission of the imported malaria from the endemic areas still exist. The risk of malaria recrudesce is determined by the presence of the vector, but also by the number of infected people in the area. Due to climate change, it is necessary to monitor the vectors and people at risk of malaria. Naturally- and artificially-created catastrophes, such as wars and mass people migration from endemic areas, could favor recrudescing of malaria. Once achieved, eradication would be maintained if the vector capacities are low and prevention measures are implemented. The increased number of malaria cases worldwide, the recrudesce of indigenous malaria cases in the countries where the disease has been eradicated, the existence of mosquitoes that transmit malaria and the number of imported malaria cases in Croatia are alarming facts. Health surveillance, including obligatory and appropriate prophylaxis for travelers to endemic areas, remains a necessary public health care measure pointed at managing malaria in Croatia.

5. Malaria Trends in the World

The WHO report on malaria in 2017 shows that it is difficult to achieve two crucial goals of a Global Technical Strategy for Malaria. These are a reduction in mortality and morbidity by at least 40% by 2020. Since 2010, there has been a significant reduction in the burden of malaria, but analysis suggests a slowdown, and even an increase in the number of cases between 2015 and 2017. Thus, the number of malaria cases in 2017 has risen to 219 million, compared to 214 million cases in 2015 and 239 million cases in 2010. Figure 3 presents the reported number of malaria cases per WHO region from 1990–2017 [ 1 , 90 ]. The most critical step in the global eradication of malaria is to reduce the number of cases in countries with the highest burden (many in Africa). The number of deaths from disease is declining, thus, in 2017 there were 435,000 deaths from malaria globally, compared with 451,000 in 2016, and 607,000 deaths in 2010. Figure 4 presents the number of malaria deaths from 1990-2017 [ 1 , 90 ]. Despite the delay in global progress, there are countries with decreasing malaria cases during 2017. Thus, India in 2017, compared with 2016, recorded a 24% decline of malaria cases. The number of countries reporting less than 10,000 malaria cases is growing, from 37 countries in 2010, to 44 in 2016, and to 46 in 2017. Furthermore, the number of countries with fewer than 100 indigenous malaria cases growing from 15 in 2010, to 26 countries in 2017 [ 1 ].

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Reported malaria cases per WHO region from 1990–2017.

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Reported malaria deaths per WHO region from 1990–2017.

Funding in malaria has not changed much. During 2017, US$3.1 billion was invested in malaria control and elimination globally. That was 47% of the expected amount by 2020. The USA was the largest single international donor for malaria in 2017 [ 1 , 91 ].

The most common global method of preventing malaria is insecticide-treated bed nets (ITNs). The WHO report on insecticide resistance showed that mosquitoes became resistant to the four most frequently used classes of insecticides (pyrethroids, organochlorines, carbamates, and organophosphates), which are widespread in all malaria-endemic countries [ 1 , 7 , 92 ].

Drug resistance is a severe global problem, but the immediate threat is low, and ACT remains an effective therapy in most malaria-endemic countries [ 1 , 93 ].

According to the WHO, Africa still has the highest burden of malaria cases, with 200 million cases (92%) in 2017, then Southeast Asia (5%), and the Eastern Mediterranean region (2%). The WHO Global Technical Strategy for Malaria by 2020 is the eradication of malaria from at least ten countries that were malaria-endemic in 2015 [ 1 ].

The march towards malaria eradication is uneven. Indigenous cases in Europe, Central Asia, and some countries in Latin America are now sporadic. However, in many sub-Saharan African countries, elimination of malaria is more complicated, and there are indications that progress in this direction has delayed. Elimination of vivax and human knowlesi malaria infections are another challenge [ 7 ].

6. Conclusions

The campaign to eradicate malaria began in the 1950s but failed globally due to problems involving the resistance of mosquitoes to the insecticides used, the resistance of malaria parasites to medication used in the treatment, and administrative issues. Additionally, the first eradication campaigns never included most of Africa, where malaria is the most common. Although the majority of forms of malaria are successfully treated with the existing antimalarials, morbidity and mortality caused by malaria are continually increasing. This issue is the consequence of the ever-increasing development of parasite resistance to drugs, but also the increased mosquito resistance to insecticides, and has become one of the most critical problems in controlling malaria over recent years. Resistance has been reported to all antimalarial drugs. Therefore, research into finding and testing new antimalarials, as well as a potential vaccine, is still ongoing, mainly due to the sudden mass migration of humans (birds, parasite disease vector insects) from areas with a large and diverse infestation.

The process towards eradication in some countries confirms that current tools could be sufficient to eradicate malaria. The spread of insecticide resistance among the vectors and the rising ACT failures indicate that eradication of malaria by existing means might not be enough.

Thus, given the already complicated problem of overseeing and preventing the spread of the disease, it will be necessary to supplement and change the principles, strategic control, and treatment of malaria.

Abbreviations

Author contributions.

Writing the manuscript: J.T., I.Š., and T.A.; updating the text: J.T., I.Š., T.A., and A.V.; literature searches: J.T., I.Š., T.A., and M.J.; tables and figures drawing: I.Š. and M.J.; critical reviewing of the manuscript: A.V.; organization and editing of the manuscript: I.Š. and A.V.

This research received no external funding. The article processing charges (APC) was funded by Faculty of Dental Medicine and Health, Osijek, Croatia.

Conflicts of Interest

The authors declare no conflict of interest.

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What to Know About Malaria in the U.S.

The U.S. has recorded its first homegrown malaria cases in decades—but there’s no need to panic.

Annalies Winny

For the first time in 20 years, the U.S. has recorded homegrown malaria cases.

The country sees about 2,000–2,500 malaria cases each year linked to travel to malaria-endemic areas such as sub-Saharan Africa and parts of South America and Southeast Asia—but the nine locally transmitted cases seen so far this year were contracted by people who hadn’t recently traveled to these areas. Seven cases were recorded in Florida, and one each in Texas and Maryland.

Malaria experts say this handful of cases is no cause for panic—catching malaria in the U.S. is still highly unlikely. But they also underscore that if malaria and other diseases are re-emerging, or emerging in places where they haven’t previously been, it is a cause for concern.

Malaria's History in North America

In the early 20th century, “malaria was common even as far north as Cleveland,” says  Prakash Srinivasan, PhD, MS, an assistant professor in  Molecular Microbiology and Immunology and at the  Johns Hopkins Malaria Research Institute .

The disease was endemic in the U.S. until the 1950s. In 1951, malaria was  considered eliminated from the country.  

Many factors contributed to achieving that status. Industrialization, the clearing of wetlands where mosquitoes breed, the use of insecticides and window screens—on top of public health measures like malaria-preventing drugs and improved diagnostics—were “game changers” in the U.S. and most other Western countries in terms of stamping out the disease, says Srinivasan.

Anopheles mosquitoes—the genus that carries malaria—is still present in the U.S. “But because malaria transmission in the United States has not been a big issue, there is no surveillance of Anopheles populations,” explains  Photini Sinnis, MD , a professor in MMI and at the Johns Hopkins Malaria Research Institute.

The Vectors and the Parasites

Malaria transmission “is a relationship between a mosquito, a parasite, and a person,” says Sinnis. A female Anopheles mosquito must be infected with the malaria parasite in order to pass on an infection. But there are many variables.

The lifespan of an Anopheles mosquito is typically a few weeks to a month, and in that time female mosquitoes feed on blood, which they need as a source of energy to mature eggs. A mosquito will typically take a couple of blood meals during its lifespan. The malaria parasite can persist in the mosquito for weeks, so it does have the potential to transmit to multiple people—but “the chances are pretty low,” explains Srinivasan.

And that’s why we’re seeing isolated cases, and not clusters or larger outbreaks. 

Another factor: Not all Anopheles species transmit malaria the same way.

“It's about how anthropophilic the mosquito is—how much it prefers to bite humans. Malaria parasites are very species-specific,” Sinnis explains. The various species of Anopheles in the U.S. will bite humans “maybe 30% to 50% of the time.” If a human is not available, they may bite a dog or another mammal instead, breaking the cycle of human infection.

The Anopheles mosquitoes found in sub-Saharan Africa, on the other hand, bite humans 98% of the time—making it far easier for the cycle of human infections to continue.

Another reason that not all malaria infections are the same: There are multiple malaria-causing parasites. The most deadly is Plasmodium falciparum , says Sinnis, which is most common in sub-Saharan Africa, where malaria kills over 600,000 people every year—95% of them children under age 5.

“It is estimated that one child dies of malaria every minute,” says Srinivasan.

Another malaria parasite, Plasmodium vivax , is more prevalent in South America and Southeast Asia and generally causes less severe disease—and is therefore less deadly.

How Malaria Likely (re)Appeared in the U.S.

Anopheles mosquitoes capable of carrying malaria are still very much present in the U.S.—they’ve just had very few opportunities to transmit the parasite because there are so few infected people to feed on.

Experts believe that this new spate of locally transmitted cases likely occurred because a specific set of circumstances aligned: A person infected with malaria traveled to the U.S. from a malaria-endemic area and was bitten by a local Anopheles mosquito, which picked up the parasite and then bit someone else, passing on the parasite.

While the case in Maryland is confirmed as linked to P. falciparum , those in Florida and Texas are believed to be linked to P. vivax , more likely originating in travelers from South America.

Symptoms and Treatments

Malaria causes flu-like symptoms like fever, body aches, vomiting, and chills. The disease can be treated with effective antimalarials and IV fluids, but it’s essential to catch it early.

A telltale sign of infection is cycles of fever every couple of days, which coincide with the life cycle of the parasite in the blood.

People in the U.S. needn’t panic, or even avoid spending time outdoors in hot and humid areas where mosquitoes thrive. But it’s worth knowing the symptoms and risks, Srinivasan advises: “If you have a fever, and they can't figure out why you have a fever, [and] if you spend a lot of time outside where there’s a lot of heat and humidity, [malaria] should be considered, particularly because when you catch it early, you can treat it.” 

Without treatment, the disease can progress to very severe or cerebral malaria. “Once you reach the cerebral malaria stage, even after anti-malarial treatment, [the] mortality rate can be as high as 20% to 25%,” Srinivasan says.

Malaria's Expanding Territory and What We Can Expect in the Future

The U.S. does not currently have the conditions for a major outbreak, Sinnis explains. The country doesn’t have the species of mosquito that makes malaria so prevalent in sub-Saharan Africa— Anopheles gambiae . Plus, the cold of winter wipes out mosquito populations each year.

But conditions are becoming more favorable for malaria transmission. Warmer winters are giving the Anopheles mosquitoes an opportunity to start reproducing earlier—meaning that their populations grow to the point where they have a higher probability of biting an infected person who has been to a malaria-endemic area. 

“These changes in the environment could be more conducive for these mosquitoes to establish a niche,” says Srinivasan. Plus, the uptick of travel since the downturn of COVID—and globalization in general—makes it easier for malaria to move around.   

The post-COVID surge in travel has increased the reservoir for infection. Mosquitoes can reach new locations by “hitching a ride on cargo planes or ships, or passenger planes,” he says.

It remains to be seen whether more homegrown cases can be expected in the U.S. Sinnis says the next five years will be critical to understanding how much of a threat malaria really poses to the U.S. Either way, she hopes that this year’s cases will encourage more surveillance of Anopheles mosquitoes in the U.S.  

“Is this just a random event? Or is this a harbinger of things to come? It may be that there are going to be sporadic cases here to stay. We don't know yet. Time will tell,” says Sinnis.

Annalies Winny is a producer and writer at the Johns Hopkins Bloomberg School of Public Health

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A perspective on Oxford’s R21/Matrix-M™ malaria vaccine and the future of global eradication efforts

Malaria affects millions of lives annually, particularly in tropical and subtropical regions. Despite being largely preventable, 2021 witnessed 247 million infections and over 600,000 deaths across 85 countrie...

Understanding psychosocial determinants of malaria behaviours in low-transmission settings: a scoping review

Recent estimates show progress toward malaria elimination is slowing in many settings, underscoring the need for tailored approaches to fight the disease. In addition to essential structural changes, human beh...

Anopheles arabiensis continues to be the primary vector of Plasmodium falciparum after decades of malaria control in southwestern Ethiopia

Investigating the species distribution and their role in malaria transmission is important as it varies from place to place and is highly needed to design interventions appropriate to the site. The current stu...

Characterization of a nuclear transport factor 2-like domain-containing protein in Plasmodium berghei

Plasmodium lacks an mRNA export receptor ortholog, such as yeast Mex67. Yeast Mex67 contains a nuclear transport factor 2 (NTF2)-like domain, suggesting that NTF2-like domain-containing proteins might be associa...

Baseline susceptibility of Anopheles gambiae to clothianidin in northern Ghana

Clothianidin, an insecticide with a novel mode of action, has been deployed in the annual indoor residual spraying programme in northern Ghana since March 2021. To inform pragmatic management strategies and gu...

Early warning systems for malaria outbreaks in Thailand: an anomaly detection approach

Malaria continues to pose a significant health threat. Rapid identification of malaria infections and the deployment of active surveillance tools are crucial for achieving malaria elimination in regions where ...

Immunofluorescence study of cytoskeleton in endothelial cells induced with malaria sera

Endothelial cells (ECs) play a major role in malaria pathogenesis, as a point of direct contact of parasitized red blood cells to the blood vessel wall. The study of cytoskeleton structures of ECs, whose main ...

In vitro delayed response to dihydroartemisinin of malaria parasites infecting sickle cell erythocytes

Decreased efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to i...

Mosquito control by abatement programmes in the United States: perspectives and lessons for countries in sub-Saharan Africa

Africa and the United States are both large, heterogeneous geographies with a diverse range of ecologies, climates and mosquito species diversity which contribute to disease transmission and nuisance biting. I...

Perspectives of primary care physicians in Spain on malaria: a cross-sectional survey and retrospective review of cases

In Spain, the risk of imported malaria has increased in recent years due to the rise in international travel and migration. Little is known about the knowledge, information sources, clinical practice, and spec...

Uptake of intermittent preventive treatment of malaria in pregnancy and risk factors for maternal anaemia and low birthweight among HIV-negative mothers in Dschang, West region of Cameroon: a cross sectional study

Approximately 32 million pregnant women are at risk of malaria with up to 10,000 maternal deaths and 200,000 neonates at risk annually. Intermittent Preventive Treatment (IPT) with sulfadoxine-pyrimethamine (S...

Malaria elimination in Ghana: recommendations for reactive case detection strategy implementation in a low endemic area of Asutsuare, Ghana

Progress toward malaria elimination is increasing as many countries near zero indigenous malaria cases. In settings nearing elimination, interventions will be most effective at interrupting transmission when t...

Urban–rural differences in seasonal malaria chemoprevention coverage and characteristics of target populations in nine states of Nigeria: a comparative cross-sectional study

Differences between urban and rural contexts in terms of sociodemographic characteristics, geographical features and risk perceptions may lead to disparities in coverage and related outcomes of community-based...

Limited threat of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletion to the utility of HRP2-based malaria RDTs in Northern Uganda

Rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein-2 (PfHRP2) are exclusively deployed in Uganda, but deletion of the pfhrp2/3 target gene threatens their usefulness as malaria...

Expanding the roles of community health workers to sustain programmes during malaria elimination: a meeting report on operational research in Southeast Asia

In Southeast Asia malaria elimination is targeted by 2030. Cambodia aims to achieve this by 2025, driven in large part by the urgent need to control the spread of artemisinin-resistant falciparum malaria infec...

Factors influencing patients’ adherence to malaria artemisinin-based combination therapy in Kamuli District, Uganda

Patients’ adherence to artemisinin-based combination therapy (ACT) is a malaria control strategy. Studies report varied experiences regarding patients’ adherence to ACT. The study aimed at determining factors ...

Vectorial competence, insecticide resistance in Anopheles funestus and operational implications for malaria vector control strategies in Benin Republic

The primary reason for the failure of malaria vector control across endemic regions is the widespread insecticide resistance observed in Anopheles vectors. The most dominant African vectors of malaria parasites a...

Perspectives of African stakeholders on gene drives for malaria control and elimination: a multi-country survey

Gene drive modified mosquitoes (GDMMs) have the potential to address Africa’s persistent malaria problem, but are still in early stages of development and testing. Continuous engagement of African stakeholders...

Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials?

Early phase malaria vaccine field trials typically measure malaria infection by PCR or thick blood smear microscopy performed on serially sampled blood. Vaccine efficacy (VE) is the proportion reduction in an ...

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Malaria Journal

ISSN: 1475-2875

CDC’s Research Resources

Cdc’s insectary.

CDC’s insectary maintains colonies of Anopheles mosquitoes collected from areas of the world where malaria is or can be transmitted. The mosquitoes are raised in a climate-controlled insectary with additional rooms for secure biological containment of malaria-infected vectors. These vector species are used for both transmission experiments and vector genetics and behavioral studies.

Mosquitoes being fed experimentally using a parafilm membrane; the blood meal is pumped on top of the membrane.

Mosquitoes being fed experimentally using a parafilm membrane; the blood meal is pumped on top of the membrane.

The facilities also serve as a repository for the active collection and study of over a dozen species and numerous isolates of malaria parasites of human and nonhuman primates. The investigations are carried out in vivo in animals or mosquito vectors and in vitro where possible through tissue culture of the parasite.

Mosquito Colonies

The vector colonies are from the United States ( Anopheles quadrimaculatus and An. freeborni ); India ( An. stephensi ); Africa ( An. gambiae and An. arabiensis ); Southeast Asia/Thailand ( An. dirus , An. sawadwongporni , and An. minimus ); Papua New Guinea ( An. farauti ); Spain ( An. atroparvus ); and El Salvador ( An. albimanus ).

CDC’s Animal Facility

CDC maintains a large modern animal facility in Chamblee, Georgia, approved by the American Association for the Accreditation of Laboratory Animal Care, International. This resource provides a platform for transmission, infection, and disease models to help provide the knowledge that will facilitate the improvement and development of new malaria interventions through vaccines, chemotherapy, or transmission reduction and elimination.

Primate Malaria Species and Their Use

Sixteen species of primate malaria parasites are maintained in laboratory cultures or experimental animals, or stored frozen in liquid nitrogen. These include isolates of all four species of human malaria parasites ( Plasmodium falciparum , P. vivax , P. ovale , and P. malariae ) collected from different areas of the world at different times. They also include monkey malaria parasites ( P. cynomolgi , P. knowlesi , P. inui , P. gonderi , P. fieldi , P. simiovale , P. coatneyi , P. fragile , P. simium , and P. brasilianum ) that have strong similarities to human malaria parasites. The recent finding that P. knowlesi , a species of malaria that naturally infects macaques in Southeast Asia, also infects humans (“zoonotic” malaria) highlights the value of maintaining these parasites for studies.

Studying these parasites during passage through mosquitoes, monkeys, and culture allows the modeling of parasite-host relationships on immunity, pathology, and the effectiveness of antimalarial drugs. New isolates and strains of malaria parasites are collected, adapted to laboratory culture or nonhuman primates, and tested using the latest available treatments.

Primates and Their Contribution

The CDC Chamblee animal facility houses several New World primate species, such as Aotus nancymai , A. vociferans (owl monkeys), and Saimiri boliviensis (squirrel monkeys); and Old World monkeys, such as Macaca mulatta and M. fascicularis (both macaques) from regulated feral colonies, commercial breeders, or in-house laboratory-born under the direction of the resident clinical veterinarian. All protocols are reviewed and approved by the institutional Animal Care and Use Committee in accordance with procedures described in the U. S. Public Health Service Policy, 1986.

The New World primates are used for experimental infections with either human malaria species (except P. ovale ) or simian (monkey) malaria species (normally parasites of the Old World monkeys). New World primates are the only available animal models to study vaccine efficacy or drug susceptibility of human malaria parasites. The macaques, Old World primates, when infected with simian malaria parasites make excellent models for the biology of the human malarias. These nonhuman primate hosts of human and simian malaria parasites also offer faithful models to investigate mechanisms and treatments for severe pathology associated with malaria infections such as anemia, cerebral malaria, and malaria in pregnancy.

Malaria Research and Reference Reagent Resource Center (MR4)

CDC plays a vital role in the Malaria Research and Reference Reagent Resource Center (MR4) external icon , to provide vector-related materials to qualified MR4 users. These materials include approximately 40 strains and species of Anopheles mosquitoes, along with preserved material, genomic DNAs, information, and primers for vector species identification. CDC has also donated numerous Plasmodium parasites to MR4. Together, these constitute an unmatched biological resource, facilitating continued research on standardized strains and providing reference material to private, government, and academic researchers.

CDC maintains DPDx, a web site to strengthen the diagnosis of parasitic diseases, including malaria, both in the United States and abroad.

The site contains concise reviews of parasites and parasitic diseases, including an image library and a review of recommended procedures for collecting, shipping, processing, and examining biologic specimens and provides diagnostic assistance . Laboratorians and other health professionals can ask questions and/or send digital images of specimens for expedited review and consultation with CDC staff free of charge.

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New malaria vaccines will save lives. how can we ensure a sustainable rollout, chijioke okoro, noel chisaka, carolina kern, this page in:.

Jestina Wright a nurse (hands in far left) prepares to vaccinate children at Redemption Hospital in Monrovia, Liberia

Last month, Cameroon became the first country to start rolling out malaria vaccination as part of its routine immunization program, with Burkina Faso joining just yesterday . This follows successful malaria vaccine trials in Ghana, Kenya, and Malawi where over 2 million children participated in evaluating RTS, S – one of two WHO-recommended vaccines to fight malaria.

According to the Malaria Vaccine Implementation Programme —a body created to assess the public health use of the RTS, S— the vaccine prevents around 75% of malaria episodes when given seasonally in conjunction with other effective malaria interventions.   Implementation data also points to a substantial fall in severe malaria hospitalizations and a remarkable (13%) drop in all-cause mortality (i.e., not just from malaria) from use of the vaccine.

New tool in the fight against malaria

This is big news: malaria is one of the world’s deadliest diseases, killing over half a million people a year , mainly children under five years of age in sub-Saharan Africa. Lower immunity during pregnancy makes it a particularly dangerous disease for women as well, with up 25 million pregnant women affected annually .

Malaria has a major impact on families due to the heavy burden it places on households. Treatment is expensive – and must often be sought multiple times a year. It also puts a strain on health systems, especially primary health care services since clinics and dispensaries are the main providers of treatment and prevention interventions.

The economic costs of malaria are estimated to be huge – though difficult to quantify precisely due to gaps in data. Malaria causes missed days at work or school, as well as drops in productivity. One estimate suggests that, among countries with intense transmission, malaria reduces GDP growth by up to 1.3%.

Against this backdrop, there are several opportunities to support the sustainable rollout of new malaria vaccines, as part of a package of essential interventions.

  • Relentless focus on health systems

Malaria control has been an important part of the World Bank’s health portfolio for over three decades. Its experience in supporting health systems – through analytics, technical support, and financing – remains critical to providing support for this new vaccine, as part of routine immunization programs.

It is not a simple question of procuring enough doses, though even this isn’t always straightforward. Running a successful immunization program requires health ministries to train healthcare workers and ensure adequate vaccine storage. Robust information systems are also necessary to record vaccine doses delivered and rationalize how they fit with other vaccines that form part of a country’s immunization schedule.

Demand generation at community level is a major consideration since RTS, S – also known as Mosquirix – is currently set to be delivered in four doses. While most doses can be given along with other vaccines that fall within current immunization programs, an additional visit will likely be needed to adhere to the recommended regimen. Families will need to be convinced that this extra trip to the clinic is worth it. Combating vaccine hesitancy for other reasons – be it safety or perceived ineffectiveness – is another consideration.

There are also questions of how to sequence and coordinate the roll out and how to deliver the vaccine alongside other health and environmental interventions. Complementary control measures such as providing insecticide-treated nets, clearing vegetation, and draining stagnant water must continue to be incorporated as part of malaria control efforts, which means strong collaboration between numerous departments and ministries. This level of multisectoral collaboration may prove challenging given the vertical way in which most vaccine programs are delivered and how difficult it can be to change long established ways of workings.

  • Support for long term planning and budgeting

The World Bank’s support for strengthening planning and resource prioritization is critical in helping countries implement cost-effective and equitable interventions, while considering financial and health systems constraints.

This support will be critical given that there is a now a second vaccine – R21/Matrix-M – on the market that is about half the price of RTS, S and is easier to produce, meaning that there are likely to be fewer supply constraints.

But even with a cheaper vaccine, there are still likely to be significant financing gaps. In the short term, there may be scope for the World Bank to leverage existing immunization-focused operations to support countries with malaria vaccine delivery ( as is the plan in the case in Nigeria ) or to look at how broader health systems strengthen programs could play a role.

For countries that aren’t receiving vaccine delivery support in the short term, but who would like to introduce malaria vaccines, new World Bank financing could be considered as part of broader system financing. In the longer term, fiscal space analyses will be important as countries navigate the process of moving towards full self-financing of vaccines.

  • Strong partnerships

The important gains that have already been made on malaria prevention, control, and treatment would not have been possible without strong and sustained partnerships, and this must continue. 

The World Bank is proud to be a founding partner of Gavi, The Vaccine Alliance, who aims to introduce RTS, S in 20 African countries in 2024 reaching over 6 million children. The World Bank works closely with Gavi as a board member and technical partner at country level. In addition, it is part of various global technical teams including the Malaria Vaccine Coordination Team, which is helping countries with their grant applications to Gavi and is also part of broader prioritization discussions.

It has also recently committed to stronger collaboration with the Global Fund to Fight AIDS, Tuberculosis and Malaria, whose efforts to strengthen country malaria control/elimination interventions have been critical over the last two decades. Efforts to operationalize this pledge, especially at country level, are currently under way with work set to focus on climate and health, health financing and regional manufacturing – all highly relevant to malaria control.

These existing partnerships may provide an entry point to support Gavi and the Global Fund’s recent commitment to optimize the deployment of malaria vaccines ensuring that they are not delivered as a standalone intervention, but in conjunction with other proven, cost-effective measures.    

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Senior Health Specialist, World Bank

Noel Chisaka profile picture

Health Specialist, World Bank

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Second malaria vaccine highly protective, trial results show

A doctor tests a child for malaria at the Ithani-Asheri Hospital in Arusha, Tanzania

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Jen reports on health issues affecting people around the world, from malaria to malnutrition. Part of the Health & Pharma team, recent notable pieces include an investigation into healthcare for young transgender people in the UK as well as stories on the rise in measles after COVID hit routine vaccination, as well as efforts to prevent the next pandemic. She previously worked at the Telegraph newspaper and Channel 4 News in the UK, as well as freelance in Myanmar and the Czech Republic.

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IMAGES

  1. Malaria Diagnostics Market Size And Share Report, 2026

    malaria research report

  2. Report of Malaria

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  3. (PDF) Malaria research in Malawi from 1984 to 2016: A literature review

    malaria research report

  4. World Malaria Report 2019 was released by the World Health Organization

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  5. Malaria Consortium

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  6. (PDF) Methods in Malaria Research

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COMMENTS

  1. Malaria: The Past and the Present

    1. Introduction Malaria affected an estimated 219 million people causing 435,000 deaths in 2017 globally. This burden of morbidity and mortality is a result of more than a century of global effort and research aimed at improving the prevention, diagnosis, and treatment of malaria [ 1 ].

  2. World malaria report 2022

    World malaria report 2022 The report highlights progress towards global targets and describes opportunities and challenges for curbing and eliminating malaria Download Read More Annexes in Excel format Despite continued impact of COVID-19, malaria cases and deaths remained stable in 2021

  3. The 2023 WHO World malaria report

    The estimated number of global malaria cases in 2022 exceeded pre-COVID-19 pandemic levels in 2019, according to WHO's 2023 World malaria report. Several threats to the malaria global response are highlighted in the report, including climate change. The report, an annual assessment of global trends in malaria control and elimination, noted ...

  4. Malaria

    Malaria is a mosquito-borne disease that is caused by Plasmodium parasites. Patients with malaria experience flu-like symptoms and, in severe cases, the disease can progress to neurological...

  5. PDF World malaria report 2023 -- spread view

    10.2 Climate and malaria - temperature, rainfall and humidity 94 10.3 Climate change predictions 96 10.4 Conceptual pathways of effect of climate change on malaria 98 10.5 The state of evidence - climate change effects on malaria transmission 100 10.6 Climate change preparedness of the global malaria response 104 11. Key findings and ...

  6. Malaria

    Overview Malaria is a life-threatening disease spread to humans by some types of mosquitoes. It is mostly found in tropical countries. It is preventable and curable. The infection is caused by a parasite and does not spread from person to person. Symptoms can be mild or life-threatening. Mild symptoms are fever, chills and headache.

  7. World malaria report 2023

    World malaria report 2023 Home / Publications / Overview / World malaria report 2023 World malaria report 2023 30 November 2023 | Global report Download (9.8 MB) Overview Each year, WHO's World malaria report provides a comprehensive and up-to-date assessment of trends in malaria control and elimination across the globe.

  8. PDF WORLD MALARIA REPORT 2020

    5.6eported malaria cases in R HBHI countries since 2018 and comparisons with estimated cases 48 6.vestments in malaria programmes and research In 52 6.1unding trends for malaria control and elimination 52F 6.2vestments in malaria-related R&D 56In 7.istribution and coverage of malaria prevention, diagnosis and treatment D 58

  9. Malaria in 2022: Increasing challenges, cautious optimism

    In 2020, malaria was estimated to have resulted in 627,000 deaths and 241 million cases, with 77% of deaths in children <5 years of age 1. Overall, 90% of malaria cases and deaths are reported in ...

  10. Malaria

    02 February 2024 | Open Access Malaria seroepidemiology in very low transmission settings in the Peruvian Amazon Bryan Fernandez-Camacho , Brian Peña-Calero & Gabriel Carrasco-Escobar Article 29...

  11. Malaria

    Malaria — Epidemiology, Treatment, and Prevention This documentary video discusses the epidemiology of malaria; strategies for prevention, including vector control and vaccines; and the pipeline ...

  12. Johns Hopkins Malaria Research Institute

    130+ Pilot grants awarded 250+ Mentions in major news outlets since 2020 500+ Publications and articles in scientific journals Malaria Research in Action | A Video Scientists at the Johns Hopkins Malaria Research Institute are working to better understand and fight malaria from the labs in Baltimore to the field in Southern and Central Africa.

  13. What to Know About Malaria in the U.S.

    In the early 20th century, "malaria was common even as far north as Cleveland," says Prakash Srinivasan, PhD, MS, an assistant professor in Molecular Microbiology and Immunology and at the Johns Hopkins Malaria Research Institute. The disease was endemic in the U.S. until the 1950s. In 1951, malaria was considered eliminated from the country.

  14. Home page

    Review 12 February 2024 Evaluation of the malaria elimination programme in Muara Enim Regency: a qualitative study from Indonesia Hamzah Hasyim, Heni Marini, Misnaniarti Misnaniarti, Rostika Flora, Iche Andriyani Liberty, Ahmed Elagali, Hartoni Hartoni and Fadhilah Eka Maharani Research 12 February 2024

  15. Malaria research

    Malaria research Malaria research Each year there are more than 200 million new cases of malaria, a preventable and treatable disease.

  16. Malaria vaccines: a test for global health

    Throughout recorded history, malaria has blighted populations across the globe. Today, by far, WHO's African region has the highest burden. In 2022, the region was home to 233 million (94%) malaria cases and 580 000 (95%) malaria deaths, about 80% of which were in children younger than 5 years. Despite ambitions to reduce this burden, efforts to control malaria have stagnated: global cases ...

  17. World malaria report 2021

    According to WHO's latest World malaria report, there were an estimated 241 million malaria cases and 627 000 malaria deaths worldwide in 2020. This represents about 14 million more cases in 2020 compared to 2019, and 69 000 more deaths.

  18. Articles

    Research Published on: 12 February 2024 Full Text PDF Artificial nighttime lighting impacts Plasmodium falciparum mature stage V gametocytes infectivity in Anopheles stephensi Malaria is one of the most important vector-borne diseases of humans with an estimated 241 million cases worldwide in 2020.

  19. CDC

    In 2020 an estimated 241 million cases of malaria occurred worldwide and 627,000 people died, mostly children in sub-Saharan Africa. About 2,000 cases of malaria are diagnosed in the United States each year.

  20. CDC

    CDC plays a vital role in the Malaria Research and Reference Reagent Resource Center (MR4), to provide vector-related materials to qualified MR4 users. These materials include approximately 40 strains and species of Anopheles mosquitoes, along with preserved material, genomic DNAs, information, and primers for vector species identification. CDC ...

  21. New malaria vaccines will save lives. How can we ensure a sustainable

    Malaria causes missed days at work or school, as well as drops in productivity. One estimate suggests that, among countries with intense transmission, malaria reduces GDP growth by up to 1.3%. Against this backdrop, there are several opportunities to support the sustainable rollout of new malaria vaccines, as part of a package of essential ...

  22. National Institute of Malaria Research-Malaria Dashboard (NIMR-MDB): A

    Undoubtedly, National Institute of Malaria Research-Malaria Dashboard (NIMR-MDB) by Yadav and colleagues (2022) is a useful resource for researchers. 1 However, real time reporting of data will be of better utility to policymakers for malaria containment in India. Yadav et al. created the MDB using the data available with the National Centre ...

  23. Second malaria vaccine highly protective, trial results show

    Jen reports on health issues affecting people around the world, from malaria to malnutrition. Part of the Health & Pharma team, recent notable pieces include an investigation into healthcare for ...

  24. World malaria report 2023

    Latest malaria report spotlights the growing threat of climate change The 2023 World malaria report delves into the nexus between climate change and malaria. Changes in temperature, humidity and rainfall can influence the behaviour and survival of the malaria-carrying Anopheles mosquito.