Malaria is a mosquito-borne infectious disease of humans caused by eukaryotic protists of the genus Plasmodium. It is widespread in tropical and subtropical regions, including much of Sub-Saharan Africa, Asia and the Americas. Malaria is very prevalent in these regions because they have significant amounts of rain fall and consistent hot temperatures. These warm, consistent temperatures and moisture provide mosquitos with the environment they need to breed continuously. The disease results from the multiplication of malaria parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases progressing to coma, and death.
Four species of Plasmodium can infect and be transmitted by humans. Severe disease is largely caused by Plasmodium falciparum. Malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae is generally a milder disease that is rarely fatal. A fifth species, Plasmodium knowlesi, is a zoonosis that causes malaria in macaques but can also infect humans.
Malaria transmission can be reduced by preventing mosquito bites by distribution of inexpensive 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. Two drugs are also available to prevent malaria in travellers to malaria-endemic countries (prophylaxis).
A variety of antimalarial medications are available. 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 which is superior to quinine in both children and adults. Resistance has developed to several antimalarial drugs, most notably chloroquine.
Each year, there are more than 225 million cases of malaria, killing around 781,000 people each year according to the World Health Organisation's 2010 World Malaria Report, 2.23% of deaths worldwide. The majority of deaths are of young children in sub-Saharan Africa. Ninety percent of malaria-related deaths occur in sub-Saharan Africa. Malaria is commonly associated with poverty, and can indeed be a cause of poverty and a major hindrance to economic development.
Signs and symptoms
Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), hemoglobinuria, retinal damage, 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 days for P. malariae. 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. 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. Cerebral malaria is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever.
Severe malaria is almost exclusively caused by P. falciparum infection, and usually arises 6–14 days after infection. 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 is a feature of 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. In the most severe cases of the disease, fatality rates can exceed 20%, even with intensive care and treatment. 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. Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.
Cause
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. P. falciparum is the most common cause of infection, and is also responsible for about 90% of the deaths from malaria. Parasitic Plasmodium species also infect birds, reptiles, monkeys, chimpanzees and rodents. There have been documented human infections with several simian species of malaria, namely P. knowlesi, P. inui, P. cynomolgi, P. simiovale, P. brazilianum, P. schwetzi and P. simium; however, with the exception of P. knowlesi, these are mostly of limited public health importance.
Malaria parasites contain apicoplasts, an organelle usually found in plants, complete with their own functioning genomes. These apicoplast are thought to have originated through the endosymbiosis of algae and play a crucial role in various aspects of parasite metabolism e.g. fatty acid bio-synthesis. To date, 466 proteins have been found to be produced by apicoplasts and these are now being looked at as possible targets for novel anti-malarial drugs.
Prevention
Methods used in order 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 favours the parasite's reproduction. Many countries are seeing an increasing number of imported malaria cases owing 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.
A 2008 study that examined international financing of malaria control found large regional variations in the levels of average annual per capita funding ranging from US$0.01 in Myanmar to US$147 in Suriname. The study found 34 countries where the funding was less than US$1 per capita, including 16 countries where annual malaria support was less than US$0.5. The 16 countries included 710 million people or 50% of the global population exposed to the risks of malaria transmission, including seven of the poorest countries in Africa (Côte d'Ivoire, Republic of the Congo, Chad, Mali, Democratic Republic of the Congo, Somalia, and Guinea) and two of the most densely populated stable endemic countries in the world (Indonesia and India).
Brazil, Eritrea, India, and Vietnam, unlike many other developing nations, have successfully reduced the malaria burden. Common success factors have 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.
Medications
Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Modern drugs used include mefloquine (Lariam), doxycycline (available generically), and the combination of atovaquone and proguanil hydrochloride (Malarone). Doxycycline and the atovaquone and proguanil combination are the best tolerated with mefloquine associated with higher rates of neurological and psychiatric symptoms. 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). 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 historically, however the development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the 20th century reduced its use. Today, quinine is not generally used for prophylaxis. The use of prophylactic drugs where malaria-bearing mosquitoes are present may encourage the development of partial immunity.
Treatment
When properly treated, a patient with malaria can expect a complete recovery. The treatment of malaria depends on the severity of the disease; whether patients who can take oral drugs have to be admitted depends on the assessment and the experience of the clinician. Uncomplicated malaria is treated with oral drugs. The most effective strategy for P. falciparum infection recommended by WHO is the use of artemisinins in combination with other antimalarials artemisinin-combination therapy, ACT, in order to avoid the development of drug resistance against artemisinin-based therapies.
Severe malaria requires the parenteral administration of antimalarial drugs. Until recently the most used treatment for severe malaria was quinine but artesunate has been shown to be superior to quinine in both children and adults. Treatment of severe malaria also involves supportive measures.
Infection with P. vivax, P. ovale or P. malariae is usually treated on an outpatient basis. Treatment of P. vivax requires both treatment of blood stages (with chloroquine or ACT) as well as clearance of liver forms with primaquine.
It is advised to be cautious diagnosing and treating without the presence of a headache, as it is possible that the patient has dengue; not malaria.
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. Close relatives of the human malaria parasites remain common in chimpanzees. Some new evidence suggests that the most virulent strain of human malaria may have originated in gorillas.
References to the unique periodic fevers of malaria are found throughout recorded history, beginning in 2700 BC in China. Malaria may have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was known as the "Roman fever". The term malaria originates from Medieval Italian: mala aria — "bad air"; the disease was formerly called ague or marsh fever due to its association with swamps and marshland. Malaria was once common in most of Europe and North America, where it is no longer endemic, though imported cases do occur.
Malaria was the most important health hazard encountered by U.S. troops in the South Pacific during World War II, where about 500,000 men were infected. According to Joseph Patrick Byrne, "Sixty thousand American soldiers died of malaria during the African and South Pacific campaigns.
Prevention
An early effort at malaria prevention occurred in 1896, just before the mosquito malaria link was confirmed in India by a British physician, Ronald Ross. An 1896 Uxbridge malaria outbreak prompted health officer, Dr. Leonard White, to write a report to the Massachusetts State Board of Health, which led to study of mosquito-malaria links, and the first efforts for malaria prevention. Massachusetts State pathologist Theobald Smith, asked that White's son collect mosquito specimens for further analysis, and that citizens 1) add screens to windows, and 2) drain collections of water. Carlos Finlay was also engaged in mosquito related research, and mosquito borne disease theory, in the 1880s in Cuba, basing his work on the study of Yellow Fever.
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