Malaria (from Medieval Italian: mala aria — "bad air"; formerly called ague or marsh fever) is an infectious disease that is widespread in many tropical and subtropical regions. It causes between one and three million deaths annually, mostly among young children in Sub-Saharan Africa. The disease is caused by a protistan parasite of the genus Plasmodium that is transmitted primarily by female Anopheles mosquitoes. Plasmodium invades and consumes the red blood cells of its host, which leads to symptoms including fever, anemia, and in severe cases, a coma potentially leading to death. Some techniques used to control the disease include mosquito eradication with insecticides, prevention of mosquito bites, and the use of drugs to prevent and treat infection.
Impact
Malaria causes about 350–500 million infections in humans and approximately 1.3–3 million deaths annually — this represents at least one death every 30 seconds. The vast majority of cases occur in children under the age of 5 years, and pregnant women are also vulnerable. The death rate is expected to double in the next twenty years. Precise statistics are unknown because many cases occur in rural areas where people do not have access to hospitals and/or the means to afford health care. Consequently, many cases are undocumented.
Sub-Saharan Africa accounts for 85–90% of malaria fatalities, but it is also prevalent in northern South America and South and Southeast Asia.
The geographic distribution of malaria within large regions generally considered malarial is complex, and malarial and malaria-free areas are often found close to each other. Malaria is more common in rural areas than in cities; this is in contrast to dengue fever where urban areas present the greater risk. For example, the cities of the Philippines, Thailand and Sri Lanka are essentially malaria-free, but the disease is present in many rural regions. By contrast, in West Africa, Ghana and Nigeria have malaria throughout the entire country, though the risk is lower in the larger cities.
Social and economic effects
The disease has been associated with major negative economic effects on regions where it is widespread. There has been demonstration of developmental impairments in children who have suffered episodes of severe malaria. A comparison of average per capita GDP in 1995, adjusted to give parity of purchasing power, between malarious and non-malarious countries demonstrate a five-fold difference (US$1,526 versus US$8,268). Moreover, 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. In its entirely, the economic impact of malaria has been estimated to cost Africa US$12 billion every year.
Transmission and symptoms
Malaria is caused by protozoan parasites of the genus Plasmodium (phylum Apicomplexa): P. falciparum, P. malariae, P. ovale, and P. vivax. P. falciparum is responsible for about eighty percent of infections and ninety percent of deaths. Infections with P. knowlesi and P. simiovale are also known to cause malaria but are of limited public health importance.
The parasite's primary hosts and transmission vectors are female mosquitos of genus Anopheles; humans act as intermediate hosts.
Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia caused by hemolysis, hemoglobinuria, and convulsions. There may be the feeling of tingling in the skin, particularly with malaria caused by P. falciparum. Consequences of infection with malaria include coma and death if untreated—young children and pregnant women are especially vulnerable. Splenomegaly (enlarged spleen), severe headache, cerebral ischemia and hemoglobinuria with renal failure may occur.
Mosquitoes
Only female mosquitoes feed on blood, thus males do not transmit the disease. The females of the Anopheles species 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. Young mosquitoes first ingest the malaria parasite by feeding on a human carrier. Infected female Anopheles mosquitoes carry Plasmodium sporozoites in their salivary glands.
Anopheles is a genus of mosquito (Culicidae). There are approximately 400 Anopheles species, of which 30-40 transmit four different species of parasites of the genus Plasmodium that cause malaria which affects humans in endemic areas. Anopheles gambiae is one of the best known, because of its predominant role in the transmission of the most dangerous Plasmodium falciparum.
Some species of Anopheles also can serve as the vectors for canine heartworm Dirofilaria immitis, the Filariidae Wuchereria bancrofti and Brugia malayi, and viruses like the one that is the cause of O'nyong'nyong fever. Mosquitoes in other genera (Aedes, Culex) can also serve as vectors of disease agents.
Treatment
There are several families of drugs used to treat malaria. Chloroquine was the antimalarial drug of choice for many years in most parts of the world. However, resistance of Plasmodium falciparum to chloroquine has spread recently from Asia to Africa, making the drug ineffective against the most dangerous Plasmodium strain in many affected regions of the world.
There are several other substances which are used for treatment and, partially, for prevention (prophylaxis). Many drugs can be used for both purposes; larger doses are used to treat cases of malaria. Their deployment depends mainly on the frequency of resistant parasites in the area where the drug is used.
Currently available anti-malarial drugs include:
Since 2001 the World Health Organization has recommended using artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria in areas experiencing resistance to older medications. The most recent WHO treatment guidelines for malaria recommend four different ACTs. While numerous contries, including most African nations, have adopted the change in their official malaria treatment policies, cost remains a major barrier to ACT implementation. Because ACTs cost up to twenty times as much as older medications, they remain unaffordable in many malaria-endemic countries.
Extracts of the plant Artemisia annua, containing the compound artemisinin or semi-synthetic derivatives (a substance unrelated to quinine), offer over 90% efficacy rates, but their supply is not meeting demand.[citation needed] A 2005 study published in Nature Structural And Molecular Biology (NSMB) described possible drug resistance, although the finding could help the development of other drugs. These findings contradict other findings published at Plos Genetics which suggest the mitochondria as the major target of action of artemisinin and its analogs. The paper published at NSMB has gained support from the observation that mutations in the proposed target for artemisinins (PfATP6) are associated with decreased sensitivity to artemether in parasites studied in French Guiana by a team based at the Institute Pasteur.
In February 2002, the journal Science and other press outlets announced progress on a new treatment for infected individuals. A team of French and South African researchers had identified a new drug they were calling "G25." It cured malaria in test primates by blocking the ability of the parasite to copy itself within the red blood cells of its victims. In 2005 the same team of researchers published their research on achieving an oral form, which they refer to as "TE3" or "te3." As of early 2006, there is no information in the mainstream press as to when this family of drugs will become commercially available.
Although effective anti-malarial drugs are on the market, the disease remains a threat to people living in endemic areas who have no proper and prompt access to effective drugs. Access to pharmacies and health facilities, as well as drug costs, are major obstacles. Médecins Sans Frontières estimates that the cost to treat a malaria-infected person in an endemic country is between US$0.25 and $2.40.
There is a problem of availability of effective malaria treatments in the United States. Most hospitals in the United States do not stock intravenous quinine, and with the reduced use of quinidine by cardiologists, many hospitals have no access to intravenous anti-malarial drugs at all.
Prevention and disease control
The countries where malaria is known to occur are shown in red. Source: CDC (USA).
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. There is currently no vaccine that will prevent malaria, but this is an active field of research.
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. It has been argued that, in order to meet the Millennium Development Goals, money should be redirected from HIV/AIDS treatment to malaria prevention, which for the same amount of money would provide greater benefit to African economies.
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 potentially high cost of purchasing the drugs, because long-term use of some drugs may have negative side effects, and because some effective anti-malarial drugs are difficult to obtain outside of wealthy nations.
Quinine was used starting in the seventeenth century as a prophylactic against malaria. The development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the twentieth 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 for malaria prophylaxis.
Modern drugs used preventively include mefloquine (Lariam®), doxycycline (available generically), and atovaquone proguanil hydrochloride (Malarone®). The choice of which drug to use is usually driven by what 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 (atovaquone proguanil only needs be started 2 days prior and continued for 7 days afterwards).
Mosquito eradication
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 the draining of wetland breeding grounds and better sanitation, in conjunction with the monitoring and treatment of infected humans, eliminated it from affluent regions. In 2002, there were 1,059 cases of malaria reported in the US, including eight deaths. In five of those cases, the disease was contracted in the United States. Malaria was eliminated from the northern parts of the USA in the early twentieth century, and the use of the pesticide DDT eliminated it from the South by 1951. 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. However, these efforts have so far failed to eradicate malaria in many parts of the developing world - the problem is most prevalent in Africa.
DDT was developed as the first of the modern insecticides early in World War II. While it was initially used to combat malaria, its use spread to agriculture where it was used to eliminate insect pests. In time, pest-control, rather than disease-control, came to dominate DDT use, particularly in the developed world. During the 1960s, awareness of the negative consequences of its indiscriminate use increased, and ultimately led to bans in many countries in the 1970s. By this time, its large-scale use had already led to the evolution of resistant mosquitos in many regions.
However, given the continuing toll to malaria, particularly in developing countries, there is considerable controversy regarding the restrictions placed on the use of DDT. Some advocates claim that bans are responsible for tens of millions of deaths in tropical countries where previously DDT was 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.
The World Health Organisation (WHO) currently advises the use of DDT to combat malaria in endemic areas. For instance, DDT-spraying the interior walls of living spaces, where mosquitoes land, is an effective control. The WHO also recommends a series of alternative insecticides to both combat malaria in areas where mosquitos are DDT-resistant, and to slow the evolution of resistance. 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 for large-scale field spraying. However, because of its legacy, many developed countries discourage DDT use even in small quantities.
Mosquito nets and prevention of mosquito bites
Mosquito nets help keep mosquitoes away from people, and thus greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier, so 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.[3] 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 insecticide (often permethrin) 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 US$2.50 - $3.50 (2-3 euros) from the United Nations, the World Health Organization, and others.
For maximum effectiveness, the nets should be re-impregnated with insecticide every six months. This process poses a significant logistical problem in rural areas. A new type of impregnated net, called Olyset, releases insecticide for approximately 5 years[20], and costs about US$5.50. ITN's have the advantage of protecting people sleeping under the net and simultaneously killing mosquitoes that contact the net. This has the effect of killing the most dangerous mosquitoes. Some protection is also provided to others, including people sleeping in the same room but not under the net.
Unfortunately, the cost of treating malaria is high relative to income, and the illness results in lost wages. Consequently, the financial burden means that the cost of a mosquito net is 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.[3]
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.[21]
A new approach, announced in Science on June 10, 2005, uses inert 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.[
