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Malaria
Classification and external resources

Plasmodium falciparum ring-forms and gametocytes in human blood.
ICD-10 B50.
ICD-9 084
OMIM 248310
DiseasesDB 7728
MedlinePlus 000621
eMedicine med/1385 emerg/305 ped/1357
MeSH C03.752.250.552

Malaria is a mosquito-borne infectious disease caused by a eukaryotic protist of the genus Plasmodium. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, there are approximately 350–500 million cases of malaria,[1] killing between one and three million people, the majority of whom are young children in sub-Saharan Africa.[2] Ninety percent of malaria-related deaths occur in sub-Saharan Africa. Malaria is commonly associated with poverty, but is also a cause of poverty[3] and a major hindrance to economic development.

Five species of the plasmodium parasite can infect humans; the most serious forms of the disease are caused by Plasmodium falciparum. Malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae causes milder disease in humans that is not generally fatal. A fifth species, Plasmodium knowlesi, is a zoonosis that causes malaria in macaques but can also infect humans[4][5].

Malaria is naturally transmitted by the bite of a female Anopheles mosquito. When a mosquito bites an infected person, a small amount of blood is taken, which contains malaria parasites. These develop within the mosquito, and about one week later, when the mosquito takes its next blood meal, the parasites are injected with the mosquito's saliva into the person being bitten. After a period of between 2 weeks and several months (occasionally years) spent in the liver, the malaria parasites start to multiply within red blood cells, causing symptoms that include fever and headache. In severe cases, the disease worsens, leading to coma and death.

A wide variety of antimalarial drugs are available to treat malaria. In the last 5 years, treatment of P. falciparum infections in endemic countries has been transformed by the use of combinations of drugs containing an artemisinin derivative. Severe malaria is treated with intravenous or intramuscular quinine or, increasingly, the artemisinin derivative artesunate[6]. Several drugs are also available to prevent malaria in travellers to malaria-endemic countries (prophylaxis). Resistance has developed to several antimalarial drugs, most notably chloroquine[7].

Malaria transmission can be reduced by preventing mosquito bites with mosquito nets and insect repellents, or by mosquito control measures such as spraying insecticides inside houses and draining standing water where mosquitoes lay their eggs.

Although many are under development, the challenge of producing a widely available vaccine that provides a high level of protection for a sustained period is still to be met[8].

Contents

Signs and symptoms

Main symptoms of malaria.[9]

Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), hemoglobinuria, retinal damage,[10] and convulsions. The classic symptom of malaria is cyclical occurrence of sudden coldness followed by rigor and then fever and sweating lasting four to six hours, occurring every two days in P. vivax and P. ovale infections, while every three for P. malariae.[11] P. falciparum can have recurrent fever every 36–48 hours or a less pronounced and almost continuous fever. For reasons that are poorly understood, but that may be related to high intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign indicating severe brain damage.[12] Malaria has been found to cause cognitive impairments, especially in children. It causes widespread anemia during a period of rapid brain development and also direct brain damage. This neurologic damage results from cerebral malaria to which children are more vulnerable.[13][14] Cerebral malaria is associated with retinal whitening,[15] which may be a useful clinical sign in distinguishing malaria from other causes of fever.[16]

Species Appearance Periodicity Persistent in liver?
Plasmodium vivax
Plasmodium vivax 01.png
tertian yes
Plasmodium ovale
Plasmodium ovale 01.png
tertian yes
Plasmodium falciparum
Plasmodium falciparum 01.png
tertian no
Plasmodium malariae
Mature Plasmodium malariae schizont PHIL 2715 lores.jpg
quartan no

Severe malaria is almost exclusively caused by P. falciparum infection, and usually arises 6–14 days after infection.[17] Consequences of severe malaria include coma and death if untreated—young children and pregnant women are especially vulnerable. Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly (enlarged liver), hypoglycemia, and hemoglobinuria with renal failure may occur. Renal failure may cause blackwater fever, where hemoglobin from lysed red blood cells leaks into the urine. Severe malaria can progress extremely rapidly and cause death within hours or days.[17] In the most severe cases of the disease, fatality rates can exceed 20%, even with intensive care and treatment.[18] In endemic areas, treatment is often less satisfactory and the overall fatality rate for all cases of malaria can be as high as one in ten.[19] Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.[20]

Chronic malaria is seen in both P. vivax and P. ovale, but not in P. falciparum. Here, the disease can relapse months or years after exposure, due to the presence of latent parasites in the liver. Describing a case of malaria as cured by observing the disappearance of parasites from the bloodstream can, therefore, be deceptive. The longest incubation period reported for a P. vivax infection is 30 years.[17] Approximately one in five of P. vivax malaria cases in temperate areas involve overwintering by hypnozoites (i.e., relapses begin the year after the mosquito bite).[21]

Causes

A Plasmodium sporozoite traverses the cytoplasm of a mosquito midgut epithelial cell in this false-color electron micrograph.

Malaria parasites

Malaria parasites are members of the genus Plasmodium (phylum Apicomplexa). In humans malaria is caused by P. falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi.[22][23] P. falciparum is the most common cause of infection and is responsible for about 80% of all malaria cases, and is also responsible for about 90% of the deaths from malaria.[24] Parasitic Plasmodium species also infect birds, reptiles, monkeys, chimpanzees and rodents.[25] There have been documented human infections with several simian species of malaria, namely P. knowlesi, P. inui, P. cynomolgi,[26] P. simiovale, P. brazilianum, P. schwetzi and P. simium; however, with the exception of P. knowlesi, these are mostly of limited public health importance.[27]

Mosquito vectors and the Plasmodium life cycle

The parasite's primary (definitive) hosts and transmission vectors are female mosquitoes of the Anopheles genus, while humans and other vertebrates are secondary hosts. Young mosquitoes first ingest the malaria parasite by feeding on an infected human carrier and the infected Anopheles mosquitoes carry Plasmodium sporozoites in their salivary glands. A mosquito becomes infected when it takes a blood meal from an infected human. Once ingested, the parasite gametocytes taken up in the blood will further differentiate into male or female gametes and then fuse in the mosquito gut. This produces an ookinete that penetrates the gut lining and produces an oocyst in the gut wall. When the oocyst ruptures, it releases sporozoites that migrate through the mosquito's body to the salivary glands, where they are then ready to infect a new human host. This type of transmission is occasionally referred to as anterior station transfer.[28] The sporozoites are injected into the skin, alongside saliva, when the mosquito takes a subsequent blood meal.

Only female mosquitoes feed on blood, thus males do not transmit the disease. The females of the Anopheles genus of mosquito prefer to feed at night. They usually start searching for a meal at dusk, and will continue throughout the night until taking a meal. Malaria parasites can also be transmitted by blood transfusions, although this is rare.[29]

Pathogenesis

The life cycle of malaria parasites in the human body. A mosquito infects a person by taking a blood meal. First, sporozoites enter the bloodstream, and migrate to the liver. They infect liver cells (hepatocytes), where they multiply into merozoites, rupture the liver cells, and escape back into the bloodstream. Then, the merozoites infect red blood cells, where they develop into ring forms, then trophozoites (a feeding stage), then schizonts (a reproduction stage), then back into merozoites. Sexual forms called gametocytes are also produced, which, if taken up by a mosquito, will infect the insect and continue the life cycle.

Malaria in humans develops via two phases: an exoerythrocytic and an erythrocytic phase. The exoerythrocytic phase involves infection of the hepatic system, or liver, whereas the erythrocytic phase involves infection of the erythrocytes, or red blood cells. When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver. Within 30 minutes of being introduced into the human host, the sporozoites infect hepatocytes, multiplying asexually and asymptomatically for a period of 6–15 days. Once in the liver, these organisms differentiate to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells, thus beginning the erythrocytic stage of the life cycle.[30] The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.[31]

Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their hosts to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.

Some P. vivax and P. ovale sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging from several months (6–12 months is typical) to as long as three years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in these two species of malaria.[32]

The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen.[33] This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. High endothelial venules (the smallest branches of the circulatory system) can be blocked by the attachment of masses of these infected red blood cells. The blockage of these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria the sequestrated red blood cells can breach the blood brain barrier possibly leading to coma.[34]

Although the red blood cell surface adhesive proteins (called PfEMP1, for Plasmodium falciparum erythrocyte membrane protein 1) are exposed to the immune system, they do not serve as good immune targets, because of their extreme diversity; there are at least 60 variations of the protein within a single parasite and effectively limitless versions within parasite populations.[33] The parasite switches between a broad repertoire of PfEMP1 surface proteins, thus staying one step ahead of the pursuing immune system.

Some merozoites turn into male and female gametocytes. If a mosquito pierces the skin of an infected person, it potentially picks up gametocytes within the blood. Fertilization and sexual recombination of the parasite occurs in the mosquito's gut, thereby defining the mosquito as the definitive host of the disease. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes,[35] and malaria in pregnant women is an important cause of stillbirths, infant mortality and low birth weight,[36] particularly in P. falciparum infection, but also in other species infection, such as P. vivax.[37]

Diagnosis

Blood smear from a P. falciparum culture (K1 strain). Several red blood cells have ring stages inside them. Close to the center there is a schizont and on the left a trophozoite.

Since Charles Laveran first visualised the malaria parasite in blood in 1880,[38] the mainstay of malaria diagnosis has been the microscopic examination of blood.

Fever and septic shock are commonly misdiagnosed as severe malaria in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria, because parasitemia can be incidental to other concurrent disease. Recent investigations suggest that malarial retinopathy is better (collective sensitivity of 95% and specificity of 90%) than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma.[39]

Although blood is the sample most frequently used to make a diagnosis, both saliva and urine have been investigated as alternative, less invasive specimens.[38]

Symptomatic diagnosis

Areas that cannot afford even simple laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria. Using Giemsa-stained blood smears from children in Malawi, one study showed that when clinical predictors (rectal temperature, nailbed pallor, and splenomegaly) were used as treatment indications, rather than using only a history of subjective fevers, a correct diagnosis increased from 21% to 41% of cases, and unnecessary treatment for malaria was significantly decreased. [40]

Microscopic examination of blood films

The most economic, preferred, and reliable diagnosis of malaria is microscopic examination of blood films because each of the four major parasite species has distinguishing characteristics. Two sorts of blood film are traditionally used. Thin films are similar to usual blood films and allow species identification because the parasite's appearance is best preserved in this preparation. Thick films allow the microscopist to screen a larger volume of blood and are about eleven times more sensitive than the thin film, so picking up low levels of infection is easier on the thick film, but the appearance of the parasite is much more distorted and therefore distinguishing between the different species can be much more difficult. With the pros and cons of both thick and thin smears taken into consideration, it is imperative to utilize both smears while attempting to make a definitive diagnosis.[41]

From the thick film, an experienced microscopist can detect parasite levels (or parasitemia) down to as low as 0.0000001% of red blood cells. Diagnosis of species can be difficult because the early trophozoites ("ring form") of all four species look identical and it is never possible to diagnose species on the basis of a single ring form; species identification is always based on several trophozoites.

Field tests

In areas where microscopy is not available, or where laboratory staff are not experienced at malaria diagnosis, there are antigen detection tests that require only a drop of blood.[42] Immunochromatographic tests (also called: Malaria Rapid Diagnostic Tests, Antigen-Capture Assay or "Dipsticks") have been developed, distributed and fieldtested. These tests use finger-stick or venous blood, the completed test takes a total of 15–20 minutes, and a laboratory is not needed. The threshold of detection by these rapid diagnostic tests is in the range of 100 parasites/µl of blood compared to 5 by thick film microscopy. The first rapid diagnostic tests were using P. falciparum glutamate dehydrogenase as antigen.[43] PGluDH was soon replaced by P.falciparum lactate dehydrogenase, a 33 kDa oxidoreductase [EC 1.1.1.27]. It is the last enzyme of the glycolytic pathway, essential for ATP generation and one of the most abundant enzymes expressed by P.falciparum. PLDH does not persist in the blood but clears about the same time as the parasites following successful treatment. The lack of antigen persistence after treatment makes the pLDH test useful in predicting treatment failure. In this respect, pLDH is similar to pGluDH. The OptiMAL-IT assay can distinguish between P. falciparum and P. vivax because of antigenic differences between their pLDH isoenzymes. OptiMAL-IT will reliably detect P. falciparum down to 0.01% parasitemia and other species down to 0.1%. Paracheck-Pf will detect parasitemias down to 0.002% but will not distinguish between falciparum and non-falciparum malaria. Parasite nucleic acids are detected using polymerase chain reaction. This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory. Moreover, levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-tech diagnosis tools need to be developed in order to detect low levels of parasitemia in the field.

Molecular methods

Molecular methods are available in some clinical laboratories and rapid real-time assays (for example, QT-NASBA based on the polymerase chain reaction)[44] are being developed with the hope of being able to deploy them in endemic areas.

Rapid antigen tests

OptiMAL-IT will reliably detect falciparum down to 0.01% parasitemia and non-falciparum down to 0.1%. Paracheck-Pf will detect parasitemias down to 0.002% but will not distinguish between falciparum and non-falciparum malaria. Parasite nucleic acids are detected using polymerase chain reaction. This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory. Moreover, levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-tech diagnosis tools need to be developed in order to detect low levels of parasitaemia in the field. [45]

Prevention

Anopheles albimanus mosquito feeding on a human arm. This mosquito is a vector of malaria and mosquito control is a very effective way of reducing the incidence of malaria.

Methods used to prevent the spread of disease, or to protect individuals in areas where malaria is endemic, include prophylactic drugs, mosquito eradication, and the prevention of mosquito bites. The continued existence of malaria in an area requires a combination of high human population density, high mosquito population density, and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite will sooner or later disappear from that area, as happened in North America, Europe and much of Middle East. However, unless the parasite is eliminated from the whole world, it could become re-established if conditions revert to a combination that favors the parasite's reproduction. Many countries are seeing an increasing number of imported malaria cases due to extensive travel and migration.

Many researchers argue that prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the capital costs required are out of reach of many of the world's poorest people. Economic adviser Jeffrey Sachs estimates that malaria can be controlled for US$3 billion in aid per year.

The distribution of funding varies among countries. Countries with large populations do not receive the same amount of support. The 34 countries that received a per capita annual support of less than $1 included some of the poorest countries in Africa.

Brazil, Eritrea, India, and Vietnam have, unlike many other developing nations, successfully reduced the malaria burden. Common success factors included conducive country conditions, a targeted technical approach using a package of effective tools, data-driven decision-making, active leadership at all levels of government, involvement of communities, decentralized implementation and control of finances, skilled technical and managerial capacity at national and sub-national levels, hands-on technical and programmatic support from partner agencies, and sufficient and flexible financing.[46]

Vector control

Efforts to eradicate malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the United States and southern Europe, but vector control programs, in conjunction with the monitoring and treatment of infected humans, eliminated it from those regions. In some areas, the draining of wetland breeding grounds and better sanitation were adequate. Malaria was eliminated from the northern parts of the USA in the early 20th century by such methods, and the use of the pesticide DDT eliminated it from the South by 1951.[47] In 2002, there were 1,059 cases of malaria reported in the US, including eight deaths, but in only five of those cases was the disease contracted in the United States.

Before DDT, malaria was successfully eradicated or controlled also in several tropical areas by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larva stages, for example by filling or applying oil to places with standing water. These methods have seen little application in Africa for more than half a century.[48] In the 1950s and 1960s, there was a major public health effort to eradicate malaria worldwide by selectively targeting mosquitoes in areas where malaria was rampant.[49] However, these efforts have so far failed to eradicate malaria in many parts of the developing world—the problem is most prevalent in Africa.

Sterile insect technique is emerging as a potential mosquito control method. Progress towards transgenic, or genetically modified, insects suggest that wild mosquito populations could be made malaria-resistant. Researchers at Imperial College London created the world's first transgenic malaria mosquito,[50] with the first plasmodium-resistant species announced by a team at Case Western Reserve University in Ohio in 2002.[51] Successful replacement of current populations with a new genetically modified population, relies upon a drive mechanism, such as transposable elements to allow for non-Mendelian inheritance of the gene of interest. However, this approach contains many difficulties and success is a distant prospect.[52] An even more futuristic method of vector control is the idea that lasers could be used to kill flying mosquitoes.[53]

Prophylactic drugs

Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Generally, these drugs are taken daily or weekly, at a lower dose than would be used for treatment of a person who had actually contracted the disease. Use of prophylactic drugs is seldom practical for full-time residents of malaria-endemic areas, and their use is usually restricted to short-term visitors and travelers to malarial regions. This is due to the cost of purchasing the drugs, negative side effects from long-term use, and because some effective anti-malarial drugs are difficult to obtain outside of wealthy nations.

Quinine was used starting in the 17th century as a prophylactic against malaria. The development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the 20th century reduced the reliance on quinine. Today, quinine is still used to treat chloroquine resistant Plasmodium falciparum, as well as severe and cerebral stages of malaria, but is not generally used for prophylaxis.

Modern drugs used preventively include mefloquine (Lariam), doxycycline (available generically), and the combination of atovaquone and proguanil hydrochloride (Malarone). The choice of which drug to use depends on which drugs the parasites in the area are resistant to, as well as side-effects and other considerations. The prophylactic effect does not begin immediately upon starting taking the drugs, so people temporarily visiting malaria-endemic areas usually begin taking the drugs one to two weeks before arriving and must continue taking them for 4 weeks after leaving (with the exception of atovaquone proguanil that only needs be started 2 days prior and continued for 7 days afterwards).

The use of prophylactic drugs where malaria-bearing mosquitoes are present may encourage the development of partial immunity.[54]

Indoor residual spraying

Indoor residual spraying (IRS) is the practice of spraying insecticides on the interior walls of homes in malaria affected areas. After feeding, many mosquito species rest on a nearby surface while digesting the bloodmeal, so if the walls of dwellings have been coated with insecticides, the resting mosquitos will be killed before they can bite another victim, transferring the malaria parasite.

The first pesticide used for IRS was DDT.[47] Although it was initially used exclusively to combat malaria, its use quickly spread to agriculture. In time, pest-control, rather than disease-control, came to dominate DDT use, and this large-scale agricultural use led to the evolution of resistant mosquitoes in many regions. The DDT resistance shown by Anopheles mosquitoes can be compared to antibiotic resistance shown by bacteria. The overuse of anti-bacterial soaps and antibiotics led to antibiotic resistance in bacteria, similar to how overspraying of DDT on crops led to DDT resistance in Anopheles mosquitoes. During the 1960s, awareness of the negative consequences of its indiscriminate use increased, ultimately leading to bans on agricultural applications of DDT in many countries in the 1970s. Since the use of DDT has been limited or banned for agricultural use for some time, DDT may now be more effective as a method of disease-control.

Although DDT has never been banned for use in malaria control and there are several other insecticides suitable for IRS, some advocates have claimed that bans are responsible for tens of millions of deaths in tropical countries where DDT had once been effective in controlling malaria. Furthermore, most of the problems associated with DDT use stem specifically from its industrial-scale application in agriculture, rather than its use in public health.[55]

The World Health Organization (WHO) currently advises the use of 12 different insecticides in IRS operations. These include DDT and a series of alternative insecticides (such as the pyrethroids permethrin and deltamethrin), to combat malaria in areas where mosquitoes are DDT-resistant and to slow the evolution of resistance.[56] This public health use of small amounts of DDT is permitted under the Stockholm Convention on Persistent Organic Pollutants (POPs), which prohibits the agricultural use of DDT.[57] However, because of its legacy, many developed countries discourage DDT use even in small quantities.[58][59]

One problem with all forms of Indoor Residual Spraying is insecticide resistance via evolution of mosquitos. According to a study published on Mosquito Behavior and Vector Control, mosquito species that are affected by IRS are endophilic species (species that tend to rest and live indoors), and due to the irritation caused by spraying, their evolutionary descendants are trending towards becoming exophilic (species that tend to rest and live out of doors), meaning that they are not as affected—if affected at all—by the IRS, rendering it somewhat useless as a defense mechanism.[60]

Mosquito nets and bedclothes

Mosquito nets help keep mosquitoes away from people and greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier and they are often treated with an insecticide designed to kill the mosquito before it has time to search for a way past the net. Insecticide-treated nets (ITN) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net.[61]. Although ITN are proven to be very effective against malaria, less than 2% of children in urban areas in Sub-Saharan Africa are protected by ITNs. Since the Anopheles mosquitoes feed at night, the preferred method is to hang a large "bed net" above the center of a bed such that it drapes down and covers the bed completely.

The distribution of mosquito nets impregnated with insecticides such as permethrin or deltamethrin has been shown to be an extremely effective method of malaria prevention, and it is also one of the most cost-effective methods of prevention. These nets can often be obtained for around $2.50–$3.50 (2–3 euros) from the United Nations, the World Health Organization (WHO), and others. ITNs have been shown to be the most cost-effective prevention method against malaria and are part of WHO’s Millennium Development Goals (MDGs).

For maximum effectiveness, the nets should be re-impregnated with insecticide every six months. This process poses a significant logistical problem in rural areas. New technologies like Olyset or DawaPlus allow for production of long-lasting insecticidal mosquito nets (LLINs), which release insecticide for approximately 5 years,[62] and cost about US$5.50. ITNs protect people sleeping under the net and simultaneously kill mosquitoes that contact the net. Some protection is also provided to others by this method, including people sleeping in the same room but not under the net.

While distributing mosquito nets is a major component of malaria prevention, community education and awareness on the dangers of malaria are associated with distribution campaigns to make sure people who receive a net know how to use it. "Hang Up" campaigns such as the ones conducted by volunteers of the International Red Cross and Red Crescent Movement consist of visiting households that received a net at the end of the campaign or just before the rainy season, ensuring that the net is being used properly and that the people most vulnerable to malaria, such as young children and the elderly, sleep under it. A study conducted by the CDC in Sierra Leone showed a 22 percent increase in net utilization following a personal visit from a volunteer living in the same community promoting net usage. A study in Togo showed similar improvements.[63]

Mosquito nets are often unaffordable to people in developing countries, especially for those most at risk. Only 1 out of 20 people in Africa own a bed net. Nets are also often distributed though vaccine campaigns using voucher subsidies, such as the measles campaign for children. A study among Afghan refugees in Pakistan found that treating top-sheets and chaddars (head coverings) with permethrin has similar effectiveness to using a treated net, but is much cheaper.[64] Another alternative approach uses spores of the fungus Beauveria bassiana, sprayed on walls and bed nets, to kill mosquitoes. While some mosquitoes have developed resistance to chemicals, they have not been found to develop a resistance to fungal infections.[65]

Vaccination

Immunity (or, more accurately, tolerance) does occur naturally, but only in response to repeated infection with multiple strains of malaria.[66]

Vaccines for malaria are under development, with no completely effective vaccine yet available. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunizing mice with live, radiation-attenuated sporozoites, providing protection to about 60% of the mice upon subsequent injection with normal, viable sporozoites.[67] Since the 1970s, there has been a considerable effort to develop similar vaccination strategies within humans. It was determined that an individual can be protected from a P. falciparum infection if they receive over 1,000 bites from infected, irradiated mosquitoes.[68]

It has been generally accepted that it is impractical to provide at-risk individuals with this vaccination strategy, but that has been recently challenged with work being done by Dr. Stephen Hoffman, one of the key researchers who originally sequenced the genome of Plasmodium falciparum. His work most recently has revolved around solving the logistical problem of isolating and preparing the parasites equivalent to 1000 irradiated mosquitoes for mass storage and inoculation of human beings. The company has recently received several multi-million dollar grants from the Bill & Melinda Gates Foundation and the U.S. government to begin early clinical studies in 2007 and 2008.[69] The Seattle Biomedical Research Institute (SBRI), funded by the Malaria Vaccine Initiative, assures potential volunteers that "the [2009] clinical trials won't be a life-threatening experience. While many volunteers [in Seattle] will actually contract malaria, the cloned strain used in the experiments can be quickly cured, and does not cause a recurring form of the disease." "Some participants will get experimental drugs or vaccines, while others will get placebo."[70]

Instead, much work has been performed to try and understand the immunological processes that provide protection after immunization with irradiated sporozoites. After the mouse vaccination study in 1967,[67] it was hypothesized that the injected sporozoites themselves were being recognized by the immune system, which was in turn creating antibodies against the parasite. It was determined that the immune system was creating antibodies against the circumsporozoite protein (CSP) which coated the sporozoite.[71] Moreover, antibodies against CSP prevented the sporozoite from invading hepatocytes.[72] CSP was therefore chosen as the most promising protein on which to develop a vaccine against the malaria sporozoite. It is for these historical reasons that vaccines based on CSP are the most numerous of all malaria vaccines.

Presently, there is a huge variety of vaccine candidates on the table. Pre-erythrocytic vaccines (vaccines that target the parasite before it reaches the blood), in particular vaccines based on CSP, make up the largest group of research for the malaria vaccine. Other vaccine candidates include: those that seek to induce immunity to the blood stages of the infection; those that seek to avoid more severe pathologies of malaria by preventing adherence of the parasite to blood venules and placenta; and transmission-blocking vaccines that would stop the development of the parasite in the mosquito right after the mosquito has taken a bloodmeal from an infected person.[73] It is hoped that the knowledge of the P. falciparum genome, the sequencing of which was completed in 2002[74], will provide targets for new drugs or vaccines.[75]

The first vaccine developed that has undergone field trials, is the SPf66, developed by Manuel Elkin Patarroyo in 1987. It presents a combination of antigens from the sporozoite (using CS repeats) and merozoite parasites. During phase I trials a 75% efficacy rate was demonstrated and the vaccine appeared to be well tolerated by subjects and immunogenic. The phase IIb and III trials were less promising, with the efficacy falling to between 38.8% and 60.2%. A trial was carried out in Tanzania in 1993 demonstrating the efficacy to be 31% after a years follow up, however the most recent (though controversial) study in The Gambia did not show any effect. Despite the relatively long trial periods and the number of studies carried out, it is still not known how the SPf66 vaccine confers immunity; it therefore remains an unlikely solution to malaria. The CSP was the next vaccine developed that initially appeared promising enough to undergo trials. It is also based on the circumsporoziote protein, but additionally has the recombinant (Asn-Ala-Pro15Asn-Val-Asp-Pro)2-Leu-Arg(R32LR) protein covalently bound to a purified Pseudomonas aeruginosa toxin (A9). However at an early stage a complete lack of protective immunity was demonstrated in those inoculated. The study group used in Kenya had an 82% incidence of parasitaemia whilst the control group only had an 89% incidence. The vaccine intended to cause an increased T-lymphocyte response in those exposed, this was also not observed.

The efficacy of Patarroyo's vaccine has been disputed with some US scientists concluding in The Lancet (1997) that "the vaccine was not effective and should be dropped" while the Colombian accused them of "arrogance" putting down their assertions to the fact that he came from a developing country.

The RTS,S/AS02A vaccine is the candidate furthest along in vaccine trials. It is being developed by a partnership between the PATH Malaria Vaccine Initiative (a grantee of the Gates Foundation), the pharmaceutical company, GlaxoSmithKline, and the Walter Reed Army Institute of Research[76] In the vaccine, a portion of CSP has been fused to the immunogenic "S antigen" of the hepatitis B virus; this recombinant protein is injected alongside the potent AS02A adjuvant.[73] In October 2004, the RTS,S/AS02A researchers announced results of a Phase IIb trial, indicating the vaccine reduced infection risk by approximately 30% and severity of infection by over 50%. The study looked at over 2,000 Mozambican children.[77] More recent testing of the RTS,S/AS02A vaccine has focused on the safety and efficacy of administering it earlier in infancy: In October 2007, the researchers announced results of a phase I/IIb trial conducted on 214 Mozambican infants between the ages of 10 and 18 months in which the full three-dose course of the vaccine led to a 62% reduction of infection with no serious side-effects save some pain at the point of injection.[78] Further research will delay this vaccine from commercial release until around 2011.[79]

Other methods

Education in recognizing the symptoms of malaria has reduced the number of cases in some areas of the developing world by as much as 20%. Recognizing the disease in the early stages can also stop the disease from becoming a killer. Education can also inform people to cover over areas of stagnant, still water e.g. Water Tanks which are ideal breeding grounds for the parasite and mosquito, thus cutting down the risk of the transmission between people. This is most put in practice in urban areas where there are large centers of population in a confined space and transmission would be most likely in these areas.

The Malaria Control Project is currently using downtime computing power donated by individual volunteers around the world (see Volunteer computing and BOINC) to simulate models of the health effects and transmission dynamics in order to find the best method or combination of methods for malaria control. This modeling is extremely computer intensive due to the simulations of large human populations with a vast range of parameters related to biological and social factors that influence the spread of the disease. It is expected to take a few months using volunteered computing power compared to the 40 years it would have taken with the current resources available to the scientists who developed the program.[80]

An example of the importance of computer modeling in planning malaria eradication programs is shown in the paper by Águas and others. They showed that eradication of malaria is crucially dependent on finding and treating the large number of people in endemic areas with asymptomatic malaria, who act as a reservoir for infection.[81] The malaria parasites do not affect animal species and therefore eradication of the disease from the human population would be expected to be effective.

Other interventions for the control of malaria include mass drug administrations and intermittent preventive therapy.

Treatment

Active malaria infection with P. falciparum is a medical emergency requiring hospitalization. Infection with P. vivax, P. ovale or P. malariae can often be treated on an outpatient basis. Treatment of malaria involves supportive measures as well as specific antimalarial drugs. Most antimalarial drugs are produced industrially and are sold at pharmacies. However, as the cost of such medicins are often too high for most people in the developing world, some herbal remedies (such as Artemisia annua tea[82] have also been developed, and have gained support from international organisations as Médicins Sans Frontières. When properly treated, someone with malaria can expect a complete recovery.[83]

Counterfeit drugs

Sophisticated counterfeits have been found in several Asian countries such as Cambodia,[84] China,[85] Indonesia, Laos, Thailand, Vietnam and are an important cause of avoidable death in those countries.[86] WHO have said that studies indicate that up to 40% of artesunate based malaria medications are counterfeit, especially in the Greater Mekong region and have established a rapid alert system to enable information about counterfeit drugs to be rapidly reported to the relevant authorities in participating countries.[87] There is no reliable way for doctors or lay people to detect counterfeit drugs without help from a laboratory. Companies are attempting to combat the persistence of counterfeit drugs by using new technology to provide security from source to distribution.

Epidemiology

Countries which have regions where malaria is endemic as of 2003 (coloured yellow).[88 ] Countries in green are free of indigenous cases of malaria in all areas.
Disability-adjusted life year for malaria per 100,000 inhabitants in 2002.
     no data      ≤10      10-50      50-100      100-250      250-500      500-1000      1000-1500      1500-2000      2000-2500      2500-3000      3000-3500      ≥3500

Malaria causes about 250 million cases of fever and approximately one million deaths annually.[89] The vast majority of cases occur in children under 5 years old;[90] pregnant women are also especially vulnerable. Despite efforts to reduce transmission and increase treatment, there has been little change in which areas are at risk of this disease since 1992.[91] Indeed, if the prevalence of malaria stays on its present upwards course, the death rate could double in the next twenty years.[92] Precise statistics are unknown because many cases occur in rural areas where people do not have access to hospitals or the means to afford health care. As a consequence, the majority of cases are undocumented.[92]

Although co-infection with HIV and malaria does cause increased mortality, this is less of a problem than with HIV/tuberculosis co-infection, due to the two diseases usually attacking different age-ranges, with malaria being most common in the young and active tuberculosis most common in the old.[93] Although HIV/malaria co-infection produces less severe symptoms than the interaction between HIV and TB, HIV and malaria do contribute to each other's spread. This effect comes from malaria increasing viral load and HIV infection increasing a person's susceptibility to malaria infection.[94]

Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur.[95] The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other.[96] In drier areas, outbreaks of malaria can be predicted with reasonable accuracy by mapping rainfall.[97] Malaria is more common in rural areas than in cities; this is in contrast to dengue fever where urban areas present the greater risk.[98] For example, the cities of Vietnam, Laos and Cambodia are essentially malaria-free, but the disease is present in many rural regions.[99] By contrast, in Africa malaria is present in both rural and urban areas, though the risk is lower in the larger cities.[100] The global endemic levels of malaria have not been mapped since the 1960s. However, the Wellcome Trust, UK, has funded the Malaria Atlas Project[101] to rectify this, providing a more contemporary and robust means with which to assess current and future malaria disease burden.

History

Malaria has infected humans for over 50,000 years, and Plasmodium may have been a human pathogen for the entire history of the species.[102] Close relatives of the human malaria parasites remain common in chimpanzees.[103] References to the unique periodic fevers of malaria are found throughout recorded history, beginning in 2700 BC in China.[104] The term malaria originates from Medieval Italian: mala aria—"bad air"; and the disease was formerly called ague or marsh fever due to its association with swamps and marshland.[105] Malaria was once common in most of Europe and North America, where it is no longer endemic[106], though imported cases do occur.

Scientific studies on malaria made their first significant advance in 1880, when a French army doctor working in the military hospital of Constantine in Algeria named Charles Louis Alphonse Laveran observed parasites for the first time, inside the red blood cells of people suffering from malaria. He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease.[107] For this and later discoveries, he was awarded the 1907 Nobel Prize for Physiology or Medicine. The malarial parasite was called Plasmodium by the Italian scientists Ettore Marchiafava and Angelo Celli.[108] A year later, Carlos Finlay, a Cuban doctor treating patients with yellow fever in Havana, provided strong evidence that mosquitoes were transmitting disease to and from humans.[109] This work followed earlier suggestions by Josiah C. Nott,[110] and work by Patrick Manson on the transmission of filariasis.[111]

However, it was Britain's Sir Ronald Ross working in the Presidency General Hospital in Calcutta who finally proved in 1898 that malaria is transmitted by mosquitoes. He did this by showing that certain mosquito species transmit malaria to birds and isolating malaria parasites from the salivary glands of mosquitoes that had fed on infected birds.[112] For this work Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly-established Liverpool School of Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius.[113] The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900, and its recommendations implemented by William C. Gorgas in the health measures undertaken during construction of the Panama Canal. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against this disease.

The first effective treatment for malaria came from the bark of cinchona tree, which contains quinine. This tree grows on the slopes of the Andes, mainly in Peru. A tincture made of this natural product was used by the inhabitants of Peru to control malaria, and the Jesuits introduced this practice to Europe during the 1640s, where it was rapidly accepted.[114] However, it was not until 1820 that the active ingredient, quinine, was extracted from the bark, isolated and named by the French chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou.[115]

In the early 20th century, before antibiotics became available, Julius Wagner-Jauregg discovered that patients with syphilis could be treated by intentionally infecting them with malaria; the resulting fever would kill the syphilis spirochetes, and quinine would then be administered to control the malaria. Although some patients died from malaria, this was considered preferable to the almost-certain death from syphilis.[116]

A continuous P. falciparum culture was established in 1976.

The first successful continuous malaria culture was established in 1976 by William Trager and James B. Jensen, which facilitated research into the molecular biology of the parasite and the development of new drugs substantially.[117][118]

Although the blood stage and mosquito stages of the malaria life cycle were identified in the 19th and early 20th centuries, it was not until the 1980s that the latent liver form of the parasite was observed.[119][120] The discovery of this latent form of the parasite finally explained why people could appear to be cured of malaria but still relapse years after the parasite had disappeared from their bloodstreams.

Evolutionary pressure of malaria on human genes

Malaria is thought to have been the greatest selective pressure on the human genome in recent history.[121] This is due to the high levels of mortality and morbidity caused by malaria, especially the P. falciparum species.

Sickle-cell disease

Frequency and origin of malaria cases in 1996.[122]

The most-studied influence of the malaria parasite upon the human genome is a hereditary blood disease, sickle-cell disease. The sickle-cell trait causes disease, but even those only partially affected by sickle-cell have substantial protection against malaria.

In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta-globin subunit of haemoglobin. The normal allele encodes a glutamate at position six of the beta-globin protein, whereas the sickle-cell allele encodes a valine. This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a "sickle" shape. Such deformed cells are cleared rapidly from the blood, mainly in the spleen, for destruction and recycling.

In the merozoite stage of its life cycle, the malaria parasite lives inside red blood cells, and its metabolism changes the internal chemistry of the red blood cell. Infected cells normally survive until the parasite reproduces, but, if the red cell contains a mixture of sickle and normal haemoglobin, it is likely to become deformed and be destroyed before the daughter parasites emerge. Thus, individuals heterozygous for the mutated allele, known as sickle-cell trait, may have a low and usually-unimportant level of anaemia, but also have a greatly reduced chance of serious malaria infection. This is a classic example of heterozygote advantage.

Individuals homozygous for the mutation have full sickle-cell disease and in traditional societies rarely live beyond adolescence. However, in populations where malaria is endemic, the frequency of sickle-cell genes is around 10%. The existence of four haplotypes of sickle-type hemoglobin suggests that this mutation has emerged independently at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions. There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC, which are common in Southeast Asia and Western Africa, respectively.

Thalassaemias

Another well-documented set of mutations found in the human genome associated with malaria are those involved in causing blood disorders known as thalassaemias. Studies in Sardinia and Papua New Guinea have found that the gene frequency of β-thalassaemias is related to the level of malarial endemicity in a given population. A study on more than 500 children in Liberia found that those with β-thalassaemia had a 50% decreased chance of getting clinical malaria. Similar studies have found links between gene frequency and malaria endemicity in the α+ form of α-thalassaemia. Presumably these genes have also been selected in the course of human evolution.

Duffy antigens

The Duffy antigens are antigens expressed on red blood cells and other cells in the body acting as a chemokine receptor. The expression of Duffy antigens on blood cells is encoded by Fy genes (Fya, Fyb, Fyc etc.). Plasmodium vivax malaria uses the Duffy antigen to enter blood cells. However, it is possible to express no Duffy antigen on red blood cells (Fy-/Fy-). This genotype confers complete resistance to P. vivax infection. The genotype is very rare in European, Asian and American populations, but is found in almost all of the indigenous population of West and Central Africa.[123] This is thought to be due to very high exposure to P. vivax in Africa in the last few thousand years.

G6PD

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme that normally protects from the effects of oxidative stress in red blood cells. However, a genetic deficiency in this enzyme results in increased protection against severe malaria.

HLA and interleukin-4

HLA-B53 is associated with low risk of severe malaria. This MHC class I molecule presents liver stage and sporozoite antigens to T-Cells. Interleukin-4, encoded by IL4, is produced by activated T cells and promotes proliferation and differentiation of antibody-producing B cells. A study of the Fulani of Burkina Faso, who have both fewer malaria attacks and higher levels of antimalarial antibodies than do neighboring ethnic groups, found that the IL4-524 T allele was associated with elevated antibody levels against malaria antigens, which raises the possibility that this might be a factor in increased resistance to malaria.[124]

Resistance in South Asia

The lowest Himalayan Foothills and Inner Terai or Doon Valleys of Nepal and India are highly malarial due to a warm climate and marshes sustained during the dry season by groundwater percolating down from the higher hills. Malarial forests were intentionally maintained by the rulers of Nepal as a defensive measure. Humans attempting to live in this zone suffered much higher mortality than at higher elevations or below on the drier Gangetic Plain, however the Tharu people had lived in this zone long enough to evolve resistance via multiple genes. Endogamy along caste and ethnic lines appear to have confined these to the Tharu community. Otherwise these genes probably would have become nearly universal in South Asia and beyond because of their considerable survival value and the apparent lack of negative effects comparable to Sickle Cell Anemia.

Society and culture

Malaria is not just a disease commonly associated with poverty but also a cause of poverty and a major hindrance to economic development. Tropical regions are affected most, however malaria’s furthest extent reaches into some temperate zones with extreme seasonal changes. The disease has been associated with major negative economic effects on regions where it is widespread. During the late 19th and early 20th centuries, it was a major factor in the slow economic development of the American southern states.[125]. A comparison of average per capita GDP in 1995, adjusted for parity of purchasing power, between countries with malaria and countries without malaria gives a fivefold difference ($1,526 USD versus $8,268 USD). In countries where malaria is common, average per capita GDP has risen (between 1965 and 1990) only 0.4% per year, compared to 2.4% per year in other countries.[126] Poverty is both cause and effect, however, since the poor do not have the financial capacities to prevent or treat the disease. The lowest income group in Malawi carries (1994) the burden of having 32% of their annual income used on this disease compared with the 4% of household incomes from low-to-high groups.[127] In its entirety, the economic impact of malaria has been estimated to cost Africa $12 billion USD every year. The economic impact includes costs of health care, working days lost due to sickness, days lost in education, decreased productivity due to brain damage from cerebral malaria, and loss of investment and tourism.[90] In some countries with a heavy malaria burden, the disease may account for as much as 40% of public health expenditure, 30-50% of inpatient admissions, and up to 50% of outpatient visits.[128]

See also

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External links

General information


Travel guide

Up to date as of January 14, 2010

From Wikitravel

Areas affected by malaria (dark blue)
Areas affected by malaria (dark blue)

This article is a travel topic.

Malaria is a serious and sometimes fatal tropical disease. Four kinds of malaria parasites can infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae; infection with P. falciparum, if not promptly and correctly treated, can be fatal in as little as one or two days.

Competent advice from an up-to-date source of information, such as the tropical diseases department of a major hospital, is essential.

Transmission

According to the CDC, Malaria is transmitted in large areas of Central and South America, the island of Hispaniola (includes Haiti and the Dominican Republic), Africa, Asia (including the Indian subcontinent, Southeast Asia and the Middle East), and a few areas of Eastern Europe and the South Pacific.

In general, the risk of contracting malaria is higher in rural areas and lower in urban areas. Often there is also a correlation to the mosquito population, with the rainy season creating stagnant pools of water where mosquitoes can breed.

Symptoms

Symptoms of malaria mimic common flu, with an infected person suffering fever, headache, and vomiting usually within 10 to 15 days after the mosquito bite. This means that you may become sick when you're already back at home, so be aware of that.

Malaria is life-threatening, and requires immediate treatment. No vaccine is currently available, but methods of prevention include avoiding mosquito bites and preventative drugs (prophylaxis). Note that some drugs are not effective for all areas. If a person who has visited a malaria risk zone contracts a fever within one year, their physician should be informed of the possibility of malaria. Less serious forms (such as P. vivax) can mimic symptoms of the flu. Physicians who rarely, if ever, examine malaria patients may need to be reminded of this fact. The standard laboratory test for malaria is a thick and thin blood smear on a glass slide viewed under the microscope. Self-test kits are highly unreliable.

Prophylaxis

Any malaria prophylaxis must be taken before, during, and (especially) after traveling to a malaria-risk zone. Anti-malarial drugs are highly effective in preventing malaria. As with all drugs, anti-malarials may cause side-effects, and their effectiveness may be compromised by various factors (e.g. resistance); a specialist doctor should be consulted beforehand. Seldom will malaria be the sole health concern, and the physician will need to assess all the health risks the traveler will face. Most often a general practitioner cannot prescribe medications or give vaccinations for third-world travel. Prophylaxis is cheaper and more up to date in countries with Malaria. However, one must obtain it from a reliable chemist, usually in a high-end or tourist area. Sometimes, the pills might be placebos, there have been many cases of this of pills coming from China. gu

Pregnant women should be especially careful, as some anti-malarials must not be taken during pregnancy, and malaria during pregnancy is usually more severe and is always considered to be a serious emergency. As with most prophylaxis, anti-malarials are not 100% effective; however studies have shown that when taken as directed, the most common drugs (e.g. doxycycline, Malarone) are ~98%~99% effective. The choice of a malaria prophylaxis should be made carefully with one's physician, taking into account drug resistance in the traveler's destination; possible side effects, interactions, and contraindications; and finally the preferred frequency per dose (daily, weekly, etc.)

Even before considering prophylactic medications, there are important anti-insect measures that should be used. Avoiding mosquito bites (i.e. using DEET, screens, and proper bed netting) when mosquitoes are obviously present is important as well. For those sensitive to DEET, or dislike its smell, repellents containing Picaridin (e.g. Cutter Advanced) are available in limited areas. This has been shown to be as effective as DEET, and has almost no odor.

The most common anti-malarials include:

  • Doxycycline is highly effective and can be very inexpensive. Possible disadvantages include increased sun sensitivity (sunburning easier), and nausea and stomach pain; some sources caution that it may reduce the effectiveness of birth control pills.
  • Lariam (mefloquine), or it's generic Mefliam, is highly effective, has a simple weekly dose and can be taken for extended periods. It does have a number of contra-indications and must be prescribed by a doctor, and has also been known to have very rare but severe neurological side effects. More common side effects include nausea,stomach cramps and lucid dreams. Not to be used if you plan on scuba diving or high altitude climbing. Your doctor may advise that you start using it several weeks before leaving, in order to check for possible side effects. There are resistant mosquitoes in Southeast Asia, and West and East Africa. Find out the latest information on this drug from a professional before purchase.
  • Malarone (atovaquone + proguanil) is highly effective, has a very low incidence of side effects, and only needs to be taken for one week after leaving the risk area; however it is expensive.
  • Chloroquine (Daramal / Nivaquine / Promal) in combination with proguanil (Paludrine) may sometimes be recommended, and is generally well tolerated. Problems include people having difficulty adhering to the prescribed regime due to its complexity, and widespread resistance.

There has been some debate recently over whether pre-travel malaria prophylaxis is being started early enough. For example, mefloquine is normally taken one week prior to travel. Some feel this is inadequate if the person is unfortunate enough to be exposed to malaria shortly upon arrival. Those who have concerns may wish to discuss with their physician the option of doubling the time period (not the dosage) that their malaria prophylaxis will be taken prior to travel. In addition to providing better protection, there will be more time to switch to another anti-malaria medication, if necessary.

Aspirin must never be taken as an antipyretic (fever reducer) when malaria or dengue fever is a possibility. (Continuing daily low-dose 81 mg aspirin therapy during and after third-world travel should be discussed with your physician.) Acetaminophen (paracetamol) and ibuprofen are considered safe alternatives provided all of their precautions are observed. Malaria, dengue fever, and typhoid fever all tend to have somewhat similar symptoms at first and should not be self-diagnosed.

Travel

Travel to rural areas always involves more potential exposure to malaria than in the larger cities. (This is in contrast to dengue fever where cities present the greater risk.) For example, the capital cities of the Philippines, Thailand and Sri Lanka are essentially malaria-free. However, malaria is present in many other places (especially rural areas) of these countries. By contrast, in West Africa, Ghana and Nigeria have malaria throughout the entire country. However, the risk will always be lower in the larger cities. Travelers should never assume that their choice of malaria prophylaxis is available in the country that they will be visiting. Many third-world countries stock only chloroquine and possibly doxycycline. Quinine might also be available, but is not recommended as a prophylactic anti-malarial.

  • WHO - Malaria. [1] World wide information on malaria.
  • MAP (Malaria Atlas Project), [2]
  • MARA (Mapping Malaria Risk in Africa), [3], a malaria atlas for Africa
  • South African Department of Health, [4]
  • Scottish National Health Service, [5] Interactive World map showing malarial hotspotsi kno dion

Study guide

Up to date as of January 14, 2010

From Wikiversity

Malaria is a vector-borne infectious disease that is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. Each year, it causes disease in approximately 650 million people and kills between one and three million, most of them young children in Sub-Saharan Africa. Malaria is commonly-associated with poverty, but is also a cause of poverty and a major hindrance to economic development.

Malaria is one of the most common infectious diseases and an enormous public-health problem. The disease is caused by protozoan parasites of the genus Plasmodium. The most serious forms of the disease are caused by Plasmodium falciparum and Plasmodium vivax, but other related species (Plasmodium ovale, Plasmodium malariae, and sometimes Plasmodium knowlesi) can also infect humans. This group of human-pathogenic Plasmodium species is usually referred to as malaria parasites.

Malaria parasites are transmitted by female Anopheles mosquitoes. The parasites multiply within red blood cells, causing symptoms that include symptoms of anemia (light headedness, shortness of breath, tachycardia etc.), as well as other general symptoms such as fever, chills, nausea, flu-like illness, and in severe cases, coma and death. Malaria transmission can be reduced by preventing mosquito bites with mosquito nets and insect repellents, or by mosquito control by spraying insecticides inside houses and draining standing water where mosquitoes lay their eggs.

No vaccine is currently available for malaria; preventative drugs must be taken continuously to reduce the risk of infection. These prophylactic drug treatments are often too expensive for most people living in endemic areas. Most adults from endemic areas have a degree of long-term recurrent infection and also of partial resistance; the resistance reduces with time and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Malaria infections are treated through the use of antimalarial drugs, such as quinine or artemisinin derivatives, although drug resistance is increasingly common.

Contents

Causes

A Plasmodium sporozoite traverses the cytoplasm of a mosquito midgut epithelial cell in this false-color electron micrograph.

Malaria parasites

Malaria is caused by protozoan parasites of the genus Plasmodium (phylum Apicomplexa). In humans malaria is caused by P. falciparum, P. malariae, P. ovale, and P. vivax. However, P. falciparum is the most important cause of disease and responsible for about 80% of infections and 90% of deaths.[1] Parasitic Plasmodium species also infect birds, reptiles, monkeys, chimpanzees and rodents.[2] There have been documented human infections with several simian species of malaria, namely P. knowlesi, P. inui, P. cynomolgi[3], P. simiovale, P. brazilianum, P. schwetzi and P. simium; however these are mostly of limited public health importance. Although avian malaria can kill chickens and turkeys, this disease does not cause serious economic losses to poultry farmers.[4] However, since being accidentally introduced by humans it has decimated the endemic birds of Hawaii, which evolved in its absence and lack any resistance to it.[5]

Pathogenesis

Malaria in humans develops via two phases: an exoerythrocytic (hepatic) and an erythrocytic phase. When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver. Within 30 minutes of being introduced into the human host, they infect hepatocytes, multiplying asexually and asymptomatically for a period of 6–15 days. During this so-called dormant time in the liver, the sporozoites are often referred to as hypnozoites. Once in the liver these organisms differentiate to yield thousands of merozoites which, following rupture of their host cells, escape into the blood and infect red blood cells, thus beginning the erythrocytic stage of the life cycle.[6] The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.[7]

Within the red blood cells the parasites multiply further, again asexually, periodically breaking out of their hosts to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.

Some P. vivax and P. ovale sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging from several months (6–12 months is typical) to as long as three years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in these two species of malaria.[8]

The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen.[9] This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. High endothelial venules (the smallest branches of the circulatory system) can be blocked by the attachment of masses of these infected red blood cells. The blockage of these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria the sequestrated red blood cells can breach the blood brain barrier possibly leading to coma.[10]

Although the red blood cell surface adhesive proteins (called PfEMP1, for Plasmodium falciparum erythrocyte membrane protein 1) are exposed to the immune system they do not serve as good immune targets because of their extreme diversity; there are at least 60 variations of the protein within a single parasite and perhaps limitless versions within parasite populations.[9] Like a thief changing disguises or a spy with multiple passports, the parasite switches between a broad repertoire of PfEMP1 surface proteins, thus staying one step ahead of the pursuing immune system.

Some merozoites turn into male and female gametocytes. If a mosquito pierces the skin of an infected person, it potentially picks up gametocytes within the blood. Fertilization and sexual recombination of the parasite occurs in the mosquito's gut, thereby defining the mosquito as the definitive host of the disease. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes,[11] and malaria in pregnant women is an important cause of stillbirths, infant mortality and low birth weight.[12]

External links

References

  1. Mendis K, Sina B, Marchesini P, Carter R (2001). "The neglected burden of Plasmodium vivax malaria.". Am J Trop Med Hyg 64 (1-2 Suppl): 97-106. PMID 11425182.  
  2. Escalante A, Ayala F (1994). "Phylogeny of the malarial genus Plasmodium, derived from rRNA gene sequences.". Proc Natl Acad Sci U S A 91 (24): 11373-7. PMID 7972067.  
  3. Garnham, PCC (1966). Malaria parasites and other haemosporidia. Blackwell Scientific Publications.
  4. Investing in Animal Health Research to Alleviate Poverty. International Livestock Research Institute. Permin A. and Madsen M. (2001) Appendix 2: review on disease occurrence and impact (smallholder poultry). Accessed 29 Oct 2006
  5. Atkinson CT, Woods KL, Dusek RJ, Sileo LS, Iko WM (1995). "Wildlife disease and conservation in Hawaii: pathogenicity of avian malaria (Plasmodium relictum) in experimentally infected iiwi (Vestiaria coccinea)". Parasitology 111 Suppl: S59-69. PMID 8632925.  
  6. Bledsoe, G. H. (December 2005) "Malaria primer for clinicians in the United States" Southern Medical Journal 98(12): pp. 1197-204, (PMID: 16440920);
  7. Sturm A, Amino R, van de Sand C, Regen T, Retzlaff S, Rennenberg A, Krueger A, Pollok JM, Menard R, Heussler VT (2006). "Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids". Science 313: 1287-1490. PMID 16888102.  
  8. Cogswell F (1992). "The hypnozoite and relapse in primate malaria.". Clin Microbiol Rev 5 (1): 26-35. PMID 1735093.  
  9. 9.0 9.1 Chen Q, Schlichtherle M, Wahlgren M (2000). "Molecular aspects of severe malaria.". Clin Microbiol Rev 13 (3): 439-50. PMID 10885986.  
  10. Adams S, Brown H, Turner G (2002). "Breaking down the blood-brain barrier: signaling a path to cerebral malaria?". Trends Parasitol 18 (8): 360-6. PMID 12377286.  
  11. Lindsay S, Ansell J, Selman C, Cox V, Hamilton K, Walraven G (2000). "Effect of pregnancy on exposure to malaria mosquitoes.". Lancet 355 (9219): 1972. PMID 10859048.  
  12. van Geertruyden J, Thomas F, Erhart A, D'Alessandro U (2004). "The contribution of malaria in pregnancy to perinatal mortality.". Am J Trop Med Hyg 71 (2 Suppl): 35-40. PMID 15331817.  

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  • George-Cristian Potrivitu

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Wiktionary

Up to date as of January 15, 2010

Definition from Wiktionary, a free dictionary

See also malaria, and malária

German

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Malaria

Wikipedia de

Noun

Malaria f. (genitive Malaria, no plural)

  1. malaria

Synonyms

  • Sumpffieber, Wechselfieber

Simple English

[[File:|thumb|230px|Electron micrograph of a malaria sporozoite]]

Malaria is an infectious disease. It is caused by parasites. People catch malaria when the parasite enters the blood. A parasite is an organism that lives off of another organism called a host. A parasite takes from the host organism, but does not help it. Instead, it usually harms the host.

The parasite that causes malaria is a protozoan called Plasmodium. Protozoa are organisms with only one cell, but they are not bacteria. Bacteria are smaller and simpler than protozoa.

There are several species (kinds) of Plasmodium that cause malaria in people:

  • Plasmodium falciparum
  • Plasmodium knowesli
  • Plasmodium malariae
  • Plasmodium ovale
  • Plasmodium semiovale
  • Plasmodium vivax

P. vivax and P. falciparum cause the most malaria in people. Falciparum malaria is the worst kind, and kills the most people.

People usually get malaria from the Anopheles mosquitoes. The Plasmodium goes into people by mosquitoes bites. The Plasmodium is in the mosquito's saliva. (Saliva is moisture, or spit, made in the mouth.) The mosquito's saliva carries the Plasmodium into the person. The person is then infected with Plasmodium. This makes the person have the disease malaria.

The kind of mosquito that carries malaria is the anopheles mosquito. Only the female mosquito gives people malaria, because only the female mosquito bites.

Some people do not get malaria from mosquitoes. A baby can get it while inside its mother. This is called maternal-fetal transmission. People can also get malaria from a blood transfusion. This is when someone gives blood to another person. Another way people can catch malaria is by using a needle that someone with the disease used before them.

Contents

How Plasmodium lives in people

When Plasmodium enters the blood, they are then called sporozoites. Sporozoites go to the liver, where they make many more sporozoites. Then they change into a different form of Plasmodium. This form is the merozoite. The merozoites go into the red blood cells, then they make many more merozoites.

The merozoites break out of the red blood cells again and again. When they do this, the person gets very sick, and shows symptoms of malaria. This happens every few days, and is called a paroxysm.

P. vivax and P. ovale can live in the liver for a long time. A person can look well, but still have the Plasmodium in the liver. This is called a dormant phase. Weeks or months later, the Plasmodium can leave the liver to the blood, and the person will get sick again.

P. falciparum is the most dangerous type of malaria. It makes people sicker than those with other types of malaria, because there are more of them in the blood. Also, with falciparum malaria, the red blood cells are sticky. This makes the red blood cells block blood vessels. If blood vessels are blocked, this can hurt what the blood vessel brings blood to, and can hurt people's organs.

Who is affected by malaria

Pregnant women and children are hurt most by malaria. When they get malaria, they get sicker.

40% of people live in a place where there is malaria. Malaria is in these places:


Every year, 300 to 700 million people get malaria. It kills 1 million to 2 million people every year. The biggest problem is in Africa. 90% of the people who die from malaria are there. Most of the people who die from malaria are children. In Africa, 20% of children under five die from malaria. Even if children do not die, many have brain damage.

Most of these deaths could be stopped with medicine or with ways to stop mosquitoes. UNICEF says: the medicine that costs the most for malaria is only $2.40 to help one adult. But many of the places malaria may be found are in poor countries. These countries do not have enough money to stop the mosquitoes, or to give people medicine.

Symptoms of malaria

Symptoms are changes in someone's body that are signs for a disease. Most people who get malaria get symptoms 10–30 days after they get infected (the Plasmodium gets in their blood.) But some people can get symptoms after only a week, and some may be infected with malaria and not have symptoms for a year.

The most common symptom of malaria is fever, when the body temperature is high. The fever from malaria usually comes very suddenly. The people who have Malaria often feel like they had influenza.

Symptoms of malaria are:

  • Arthralgia (pain in joints)
  • Headache (pain in head)
  • Vomiting
  • Feeling very tired or sleepy
  • Anemia (low red blood cell levels in the blood)
  • Jaundice (yellow skin and eyes)
  • Cough
  • Enlargement of liver or spleen (enlargement means it gets bigger)
  • Sweating
  • Chills (feeling very cold)
  • Delirium (when people are very confused because of a disease. They may look drunk. They may not be able to talk.)
  • Coma (when people are not conscious. They look like they are asleep, but they cannot be woken. )
  • Fast heart rate
  • Low blood pressure

Complications from malaria

Complications are problems that happen because of a disease.

Pregnant women and young children have more complications. People who get malaria for the first time have more complications. Falciparum malaria has the most complications.

Complications of malaria are:

  • Cerebral malaria (brain malaria)
    • To have cerebral malaria, the following must be present:
      • P. falciparum in the blood.
      • Coma, many seizures, or long Delirium
    • If no medicine is given, people always die.
    • Even if medicine is given 15%-20% of people with it die.
  • Seizures (if only one seizure happens it is not cerebral malaria)
  • Damage to the brain
  • Blackwater fever
    • Many red blood cells break open and the hemoglobin in the cells gets into the blood.
    • This hemoglobin is put in the urine and makes it look very dark.
    • Without the right care this can make the kidneys stop working.
  • Pulmonary edema
    • This is fluid in the lungs that makes it hard to breathe.
    • Pregnant women get this much more.
    • 80% of people who get this complication die.
  • Very low blood sugar
    • Children and pregnant women get this more.
    • This can cause people to look like they are drunk or to be in a coma.
  • Hemolysis
    • This means breakdown of red blood cells.
    • It can cause blackwater fever, jaundice, and symptoms of anemia.
  • Coagulopathy (not being able to stop bleeding)

How doctors tell if someone has malaria

In places where malaria is, there may not be good medical care. People may diagnose malaria just by people having symptoms. Diagnose means to learn if a person has a disease. Doctors diagnose people sometimes just by symptoms. This is called a clinical diagnosis. Doctors also use tests to see if people have a disease.

File:P vivax
Giemsa stain shows malaria trophozoite in red blood cell

If a person has symptoms and is in a place where there is malaria, they might have malaria. To see if they have malaria, doctors may do a blood test. This test is called a Giemsa blood smear. Blood is put on a slide which is a thin piece of glass. The Giemsa stain is put on the slide. This stain helps doctors see the malaria. Then they look at the slide under a microscope. The Plasmodium is seen in the red blood cells.

Sometimes the blood smear will not show Plasmodium even if the person has malaria. This can be because the stain was not good. It can also be because the microscope was not good. Or it can be because the person looking in the microscope did not know what Plasmodium look like. But often it is because the number of malaria parasites present in the blood is so low that they are not present in the section of the blood that was looked at.

There are other tests to diagnose malaria. These are more expensive. People do not use them as much. Sometimes people test to see if the Plasmodium is resistant to medicines to treat malaria. Resistance means the medicine cannot hurt the Plasmodium. This means that taking the medicine will not cure someone with malaria, because it will not kill the Plasmodium.

How to treat malaria

People with different kinds of malaria need different medicines. The medicine that works for one kind of malaria may not for another kind. So it is very important to know which species of Plasmodium the person has.

If the species is not known, the person should be given medicine and care like they have falciparum malaria - the worst kind.

It is also important to know where the person got malaria. Plasmodium in some places are resistant to some medicines. So the medicines to treat malaria in Africa are different from the medicines to treat malaria from South America.

It is important for doctors to learn about malaria treatment. Resistance to medicines changes. Places where there was no resistance can get resistant malaria. So doctors need to know when this changes. If a doctor treats a person with malaria, he should know what places in the world have resistant malaria. If he has not treated a person in a long time, he should check before treating people.

Treatment of malaria other than falciparum

Everywhere except New Guinea, the treatment is the same. In New Guinea most P. vivax is resistant to chloroquine. It can be treated with quinine, but this medicine can make people sick. Everywhere else, non-falciparum malaria is treated with chloroquine.

Chloroquine kills the Plasmodium in the blood. But the Plasmodium in the liver is not killed by chloroquine. P. vivax and P. ovale both stay in the liver a long time. This is the dormant phase. Another medicine must be given with chloroquine for P. vivax and P. ovale. This is to kill the Plasmodium in the liver. If this other medicine is not given, malaria can come back after months. It can even come back five years later.

The medicine used to kill malaria in the liver is primaquine. In southeast Asia, some P. vivax is resistant to primaquine. Most other places, primaquine works very well.

Some people get very sick from primaquine. Some people do not make enough of an enzyme in the blood. This enzyme is called Glucose-6-Phosphate-Dehydrogenase (Acronym G6PD). People who do not have enough have a disease called G6PD deficiency (or favism). People with G6PD-deficiency get very very sick if they take primaquine. It makes their red blood cells all die. This can even kill them. So people have to be tested to see if they have G6PD-deficiency before they take primaquine.

Medicines to kill P. vivax and P. ovale in the liver are not safe for pregnant women. So a pregnant woman must usually take chloroquine until she has her baby.

Treatment of falciparum malaria

Falciparum is the worst kind of malaria. Most people who die from malaria have falciparum.

Many people with falciparum malaria must be treated in a hospital. People with falciparum malaria should be treated in a hospital if they are:

  • Very sick
  • Children
  • Pregnant
  • Having malaria for the first time
  • Not able to take medicines by mouth

Even people who are treated with medicines at home should stay with the doctor for 8 hours. This is to make sure they do not get sicker. It also makes sure they can take the medicines by mouth.

Falciparum malaria also has more resistance to medicines. This makes it much harder to treat. Falciparum malaria is always treated with two or more medicines. Doctors choose the medicines by where in the world the person got malaria. Different places have P. falciparum that is resistant to different medicines.

The most important resistance is chloroquine-resistance. In some places in the world, P. falciparum is killed by chloroquine. In some places it is chloroquine-resistant. This means chloroquine does not kill it. In these places quinine can be used.

If people are very sick and cannot swallow medicines, they get intravenous (acronym IV) medicine. Intravenous means given into a vein. The IV medicine used for very bad chloroquine-resistant falciparum malaria is quinine. If people got malaria in a place with no chloroquine-resistance other medicines can be used. But sometimes doctors still use IV quinine. This is to be very certain they will kill the P. falciparum.

If the P. falciparum is not chloroquine-resistant people do not usually take quinine. This is because quinine can make people sick. If people get sick from quinine, it is called Cinchonism. Symptoms of cinchonism are:

Quinine is also taken by mouth.

How to prevent malaria

The best way to treat malaria is to not get it!

There are three ways to prevent malaria:

  • Control mosquitoes
  • Keep mosquitoes from biting
  • Take medicine to keep from getting sick after a bite, especially in those parts of the world where people get malaria.

Control mosquitoes

Vector control is one way to stop malaria. Vector means an organism that carries an infectious disease to another organism. For malaria, the vector is the anopheles mosquito. It carries Plasmodium to people.

There are many ways to conduct a good vector control. The best ways are different in different places. This depends on the environment. It also depends on how much malaria is in the place. So the best way to do vector control in the United States is different than the best way to do vector control in South Africa.

The most used method of vector control is pesticides. These are chemicals that kill the mosquito. The first pesticide used for vector control was DDT (dichlorodiphenyltrichloroethane.) DDT was first used in World War II.

DDT worked very well for vector control. It killed mosquitoes. It did not make people very sick at the time it was used. It did not cost very much money. Other chemicals for vector control had not been invented yet.

In many places mosquitos became resistant to DDT. This meant that DDT did not work anymore in these areas. The places where mosquitoes are DDT-resistant are:

The EPA (Environmental Protection Agency) classifies DDT as a Persistent Bioaccumulative Toxin (PBT)meaning that it builds up over time in the bodies of plants,animals and humans.DDT can be passed on from water to fish or some plants, and consequently passed from plant/fish on to humans who may eat them.

Possible Harmful Effects include:

  • Possible human carcinogen(cancer causing agent)
  • Damage to the liver
  • Can cause liver cancer
  • Temporarily damages the nervous system
  • Damage to reproductive system

Scientists also worried that DDT was making people and animals sick. Scientists think it might cause hormones to not work right. It might also make people and animals have trouble reproducing (getting pregnant and making babies.) It killed a lot of wildlife too.

They learned that DDT stays in the environment for a long time. They learned also that DDT used in one place may go all over the world. DDT used in Africa may go to Europe. So people are worried that DDT used today will stay in the world for a long time. This is why DDT is not allowed to be used in farming anymore.

For these reasons, people mostly use other chemicals for vector control. Organophosphate or carbamate pesticides are used, like malathion or bendiocarb. These cost more money than DDT. And there are ways to control malaria that do not use chemicals at all.

Vector control is not the only way to stop malaria. And DDT is not the only chemical that can be used for vector control. The best way to stop malaria is to use a combination of methods. In some places, DDT may be a useful part of a program to stop malaria. This is why DDT is still allowed to be used for controlling malaria.

Keeping mosquitoes from biting

The mosquito that carries malaria comes more at dawn (when the sun comes up) and dusk (when the sun goes down.) Be most careful at these times.

Wear long pants and shirts with long sleeves.

Wear mosquitoes repellent (this is a chemical that mosquitoes do not like, so they do not bite.) Mosquitoes will bite through thin cloth. So repellent should be used on skin and clothes.

Pesticides can be used in rooms to kill mosquitoes.

When sleeping outside, people use a mosquito net. This is made from cloth that air can go through but keeps mosquitoes out. It is put over a bed where people sleep to keep mosquitoes out. Sometimes people also use it when they are not sleeping. It is best to use mosquito nets that have been treated with Permethrin, which repels and kills mosquitoes.

Taking medicine to not get sick

People can take medicine when they are in a place where there is malaria. This reduces the chances that they contract malaria. This is called prophylaxis.

Some people take prophylactic medicines for years. Many people in areas where there is malaria do not have the money to buy this medicine.

People who live where there is no malaria usually have not had malaria. The first case malaria is usually much worse. So people from places where there is no malaria may take prophylactic medicines when they go to places where there is malaria.

The kind of prophylactic medicines people take depends on where they are. This is because not all medicines work on the malaria in every place. Some Plasmodium are resistant. Even if the right medicine is used, it does not always work. Sometimes people get malaria even if they take prophylaxis. Sometimes this is because people do not take the medicine the right way. But even if it is taken right, it does not always work.

To make them work best, prophylactic medicines have to be taken the right way. The medicine should start before going to an area with malaria. Most medicines should be taken for 4 weeks after coming home. One medicine (Malarone) only needs to be used for one week after coming home.

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