Malaria
Encyclopedia
Malaria is a mosquito-borne infectious disease
of humans and other animals caused by eukaryotic protists of the genus Plasmodium
. The disease results from the multiplication of Plasmodium parasites within red blood cell
s, causing symptoms that typically include fever
and headache
, in severe cases progressing to coma
or death
. It is widespread in tropical
and subtropical regions, including much of Sub-Saharan Africa
, Asia
, and the Americas
.
Five species of Plasmodium can infect and be transmitted by humans. Severe disease is largely caused by Plasmodium falciparum
while the disease caused by Plasmodium vivax
, Plasmodium ovale
, and Plasmodium malariae
is generally a milder disease that is rarely fatal. 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 mosquito net
s and insect repellent
s, or by mosquito-control measures such as spraying insecticide
s and draining standing water (where mosquitoes breed). The challenge of producing a widely available vaccine
that provides a high level of protection for a sustained period is still to be met, although several are under development. A number of medications are also available to prevent malaria in travelers to malaria-endemic
countries (prophylaxis
).
A variety of antimalarial medications are available. Severe malaria is treated with intravenous or intramuscular quinine or, since the mid-2000s, the artemisinin
derivative artesunate
, which is superior to quinine
in both children and adults. Resistance has developed to several antimalarial drugs, most notably chloroquine
.
There were an estimated 225 million cases of malaria worldwide in 2009.. An estimated 781,000 people died from malaria in 2009 according to the World Health Organization
's 2010 World Malaria Report, accounting for 2.23% of deaths worldwide. Ninety percent of malaria-related deaths occur in sub-Saharan Africa, with the majority of deaths being young children. Plasmodium falciparum
, the most severe form of malaria, is responsible for the vast majority of deaths associated with the disease. Malaria is commonly associated with poverty, and can indeed be a cause of poverty and a major hindrance to economic development
.
Symptoms of malaria include fever
, shivering
, arthralgia
(joint pain), vomiting
, anemia
(caused by hemolysis
), hemoglobinuria
, retinal damage
, and convulsion
s. 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, and 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 Plasmodium 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.
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
. While P. vivax is responsible for the largest number of malaria infections worldwide, infections by P. falciparum account 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; however, with the exception of P. knowlesi, these are mostly of limited public health importance.
Malaria parasites contain apicoplast
s, 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.
are humans and other vertebrates. Female mosquito
es of the Anopheles
genus are primary hosts and transmission vectors. 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 gland
s. 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's 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. The sporozoites are injected into the skin, alongside saliva, when the mosquito takes a subsequent blood meal.
Only female mosquitoes feed on blood while male mosquitoes feed on plant nectar, 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 transfusion
s, although this is rare.
areas involve overwintering by hypnozoites (i.e., relapses begin the year after the mosquito bite).
Malaria 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 minutes of being introduced into the human host, the sporozoites infect hepatocyte
s, multiplying asexually and asymptomatically for a period of 8–30 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 cell
s, thus beginning the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.
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.
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 protein
s 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. 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.
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 even more variants within whole parasite populations. 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 gametocyte
s. Since the gametocytes are formed in the blood of the vertebrate host, the vertebrate host is the definitive host of the disease. 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. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes, and malaria in pregnant women
is an important cause of stillbirth
s, infant mortality and low birth weight, particularly in P. falciparum infection, but also in other species infection, such as P. vivax.
on the human genome
in recent history. This is due to the high levels of mortality
and morbidity caused by malaria, especially the P. falciparum
species. A number of diseases may provide some resistance to it including sickle cell disease, thalassaemias, glucose-6-phosphate dehydrogenase
, Duffy antigen
s, and possibly others.
s. Although blood is the sample most frequently used to make a diagnosis, both saliva and urine have been investigated as alternative, less invasive specimens. More recently, modern techniques utilizing antigen tests or polymerase chain reaction
have been discovered, though these are not widely implemented in malaria endemic regions. Areas that cannot afford laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria.
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.
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 the 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. The economist 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.
may be used where the parasite is still sensitive. However due to resistance one of three medications: mefloquine
(Lariam), doxycycline
(available generically), and the combination of atovaquone
and proguanil
hydrochloride (Malarone) is frequently needed. Doxycycline and the atovaquone and proguanil combination are the best tolerated with mefloquine associated with higher rates of neurological and psychiatric symptoms.
The prophylactic effect does not begin immediately upon starting 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 effect
s 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.
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 most parts of the USA in the early 20th century by such methods, and the use of the pesticide
DDT
and other means eliminated it from the remaining pockets in the South by 1951 (see National Malaria Eradication Program
). 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.
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, with the first plasmodium-resistant species announced by a team at Case Western Reserve University
in Ohio
in 2002. 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.
Another way of reducing the malaria transmitted to humans from mosquitoes has been developed by the University of Arizona. They have engineered a mosquito to become resistant to malaria. This was reported on the 16 July 2010 in the journal PLoS Pathogens
. With the ultimate end being that the release of this GM mosquito into the environment, Gareth Lycett, a malaria researcher from Liverpool School of Tropical Medicine told the BBC that "It is another step on the journey towards potentially assisting malaria control through GM mosquito release."
The first pesticide used for IRS was DDT
. 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
.
The World Health Organization
(WHO) currently advises the use of 12 different insecticides in IRS operations, including DDT as well as alternative insecticides (such as the pyrethroids permethrin
and deltamethrin
). This public health use of small amounts of DDT is permitted under the Stockholm Convention
on Persistent Organic Pollutant
s (POPs), which prohibits the agricultural use of DDT. However, because of its legacy, many developed countries previously discouraged DDT use even in small quantities.
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.
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.
is not yet available for malaria, although several vaccines are under development. SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective. Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have also been insufficient on their own. Several potential vaccines targeting the pre-erythrocytic stage are being developed, with RTS,S
showing the most promising results so far.
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.
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. 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 administration
s and intermittent preventive therapy
.
Furthering attempts to reduce transmission rates, a proposed alternative to mosquito nets is the mosquito laser
, or photonic fence, which identifies female mosquitoes and shoots them using a medium-powered laser
. The device is currently undergoing commercial development, although instructions for a DIY
version of the photonic fence have also been published.
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 estimated that malaria causes 250 million cases of fever and approximately one million deaths annually. The vast majority of cases occur in children under 5 years old; 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. Indeed, if the prevalence of malaria stays on its present upwards course, the death rate could 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 or the means to afford health care. As a consequence, the majority of cases are undocumented.
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. 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.
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. The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other. Malaria is prevalent in tropical regions because of the significant amounts of rainfall and consistent high temperatures; warm, consistent temperatures and high humidity, along with stagnant waters in which their larvae mature, providing mosquitoes with the environment they need for continuous breeding. In drier areas, outbreaks of malaria can be predicted with reasonable accuracy by mapping rainfall. 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, several cities in Vietnam
, Laos
and Cambodia
are essentially malaria-free, but the disease is present in many rural regions. By contrast, in Africa malaria is present in both rural and urban areas, though the risk is lower in the larger cities. The global endemic
levels of malaria have not been mapped since the 1960s. However, the Wellcome Trust
, UK, has funded the Malaria Atlas Project
to rectify this, providing a more contemporary and robust means with which to assess current and future malaria disease burden
.
By 2010 countries with the highest death rate per 100,000 population are Cote d'Ivoire
with (86.15), Angola
(56.93) and Burkina Faso
(50.66) - all in Africa.
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
— "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."
. 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
.
in Algeria
named Charles Louis Alphonse Laveran
observed parasites for the first time, inside the red blood cell
s 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. 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
.
, a Cuban doctor treating patients with yellow fever
in Havana
, provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by Josiah C. Nott
, and work by Sir Patrick Manson, The Father of Tropical Medicine, on the transmission of filariasis
.
In April 1894, a Scottish physician Sir Ronald Ross
visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research which culminated in 1898 when Ross, who was working in the Presidency General Hospital in Calcutta
, proved the complete life-cycle of the malaria parasite in mosquitoes; thus proving that the mosquito was the vector for malaria in humans. He did this by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. 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
. The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed
in 1900. Its recommendations were 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 the disease.
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.
, which contains quinine
. This tree grows on the slopes of the Andes
, mainly in Peru
. The indigenous peoples
of Peru made a tincture
of cinchona to control malaria. The Jesuits noted the efficacy of the practice and introduced the treatment to Europe during the 1640s, where it was rapidly accepted. 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
. In the 20th century, chloroquine replaced quinine as treatment of both uncomplicated and severe falciparum malaria until resistance supervened. Artemisinins, discovered by Chinese scientists in the 1970s, are now recommended treatment for falciparum malaria, administered in combination with other antimalarials as well as in severe disease.
. 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. 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.
Poverty is both cause and effect, however, since the poor do not have the financial capacities to prevent or treat the disease. 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. 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.
The demographic transition
in Africa is slow and malaria may provide part of the answer. Total fertility
rates were best explained by child mortality
, as measured indirectly by infant mortality
, in a 2007 study.
A study on the effect of malaria on IQ in a sample of Mexicans found that exposure during the birth year to malaria eradication was associated with increases in IQ. It also increased the probability of employment in a skilled occupation. The author suggests that this may be one explanation for the Flynn effect
and that this may be an important explanation for the link between national malaria burden and economic development. A literature review of 44 papers states that cognitive abilities and school performance were shown to be impaired in sub-groups of patients (with either cerebral malaria or uncomplicated malaria) when compared with healthy controls. Studies comparing cognitive functions before and after treatment for acute malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery. Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups. April 25 is World Malaria Day
.
, China
, Indonesia
, Laos
, Thailand
, Vietnam
and are an important cause of avoidable death in those countries.
WHO
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. 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.
In 1910, Nobel Prize in Medicine-winner Ronald Ross
(himself a malaria survivor), published a book titled The Prevention of Malaria that included the chapter: "The Prevention of Malaria in War." The chapter's author, Colonel C. H. Melville, Professor of Hygiene at Royal Army Medical College in London, addressed the prominent role that malaria has historically played during wars and advised: "A specially selected medical officer should be placed in charge of these operations with executive and disciplinary powers [...]."
Significant financial investments have been made to procure existing and create new anti-malarial agents. During World War I
and World War II
, the supplies of the natural anti-malaria drugs, cinchona bark and quinine
, proved to be inadequate to supply military personnel and substantial funding was funnelled into research and development
of other drugs and vaccines. American military organizations conducting such research initiatives include the Navy Medical Research Center, Walter Reed Army Institute of Research
, and the U.S. Army Medical Research Institute of Infectious Diseases of the US Armed Forces.
Additionally, initiatives have been founded such as Malaria Control in War Areas (MCWA), established in 1942, and its successor, the Communicable Disease Center (now known as the Centers for Disease Control) established in 1946. According to the CDC, MCWA "was established to control malaria around military training bases in the southern United States and its territories, where malaria was still problematic" and, during these activities, to "train state and local health department officials in malaria control techniques and strategies." The CDC's Malaria Division continued that mission, successfully reducing malaria in the United States, after which the organization expanded its focus to include "prevention, surveillance, and technical support both domestically and internationally."
set a public goal of eliminating malaria from Africa by 2015, and the organization plans to dissolve if that goal is accomplished. Several malaria vaccine
s are in clinical trials, which are intended to provide protection for children in endemic areas and reduce the speed of transmission of the disease. The Global Fund to Fight AIDS, Tuberculosis and Malaria
has distributed more than 160 million insecticide-treated nets intended to stop mosquito-born transmission of malaria. According to director Inder Singh
, the U.S.-based Clinton Foundation
has reduced the cost of drugs to treat malaria by 60%, and is working to further reduce the spread of the disease. Other efforts, such as the Malaria Atlas Project
focus on analyzing climate and weather information required to accurately predict the spread of malaria based on the availability of habitat of malaria-carrying parasites.
parasites, new strategies are required to combat the widespread disease. One such approach lies in the introduction of synthetic pyridoxal
-amino acid adducts, which are channelled into the parasite. Thus, trapped upon phosphorylation
by plasmodial PdxK (pyridoxine/pyridoxal kinase
), the proliferation of Plasmodium parasites is effectively hindered by a novel compound, PT3, a cyclic pyridoxyl-tryptophan methyl ester, without harming human cells.
Malaria vaccines have been an elusive goal of research. 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. 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 yet irradiated mosquitoes.
In October 2011, preliminary findings from a Phase III trial of an experimental vaccine known as RTS,S
reported that it may protect approximately 50% of inoculated infants and children (decline in final mortality rate unverified). The RTS,S vaccine was engineered using genes from the outer protein of Plasmodium falciparum malaria parasite and a portion of a hepatitis B virus and a chemical adjuvant to boost the immune system response. The RTS,S-based vaccine formulation had previously been demonstrated to be safe, well tolerated, immunogenic, and to potentially confer partial efficacy in both malaria-naive and -experienced adults as well as children, although further research was considered necessary to improve the effectiveness of the vaccine. It is being developed by PATH
and GlaxoSmithKline
(GSK) and Bill and Melinda Gates Foundation
Mosquito-borne disease
Mosquitoes are a vector agent that carries mosquito-borne disease, transmitting viruses and parasites from person to person without catching the disease themselves.-Action in mosquitoes:...
of humans and other animals caused by eukaryotic protists of the genus Plasmodium
Plasmodium
Plasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known...
. The disease results from the multiplication of Plasmodium parasites within red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s, causing symptoms that typically include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
and headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, in severe cases progressing to coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
or death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
. It is widespread in tropical
Tropics
The tropics is a region of the Earth surrounding the Equator. It is limited in latitude by the Tropic of Cancer in the northern hemisphere at approximately N and the Tropic of Capricorn in the southern hemisphere at S; these latitudes correspond to the axial tilt of the Earth...
and subtropical regions, including much of Sub-Saharan Africa
Sub-Saharan Africa
Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...
, Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, and the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...
.
Five species of Plasmodium can infect and be transmitted by humans. Severe disease is largely caused by Plasmodium falciparum
Plasmodium falciparum
Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
while the disease caused by Plasmodium vivax
Plasmodium vivax
Plasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of the four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the...
, Plasmodium ovale
Plasmodium ovale
Plasmodium ovale is a species of parasitic protozoa that causes tertian malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax, which are responsible for most malaria. It is rare compared to these two parasites, and substantially less dangerous than P...
, and Plasmodium malariae
Plasmodium malariae
Plasmodium malariae is a parasitic protozoa that causes malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that...
is generally a milder disease that is rarely fatal. Plasmodium knowlesi
Plasmodium knowlesi
Plasmodium knowlesi is a primate malaria parasite commonly found in Southeast Asia. It causes malaria in long-tailed macaques , but it may also infect humans, either naturally or artificially....
is a zoonosis
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...
that causes malaria in macaques but can also infect humans.
Malaria transmission can be reduced by preventing mosquito bites by distribution of mosquito net
Mosquito net
A mosquito net offers protection against mosquitos, flies, and other insects, and thus against diseases such as malaria, dengue fever, yellow fever, and various forms of encephalitis, including the West Nile virus, if used properly and especially if treated with an insecticide, which can double...
s and insect repellent
Insect repellent
An insect repellent is a substance applied to skin, clothing, or other surfaces which discourages insects from landing or climbing on that surface. There are also insect repellent products available based on sound production, particularly ultrasound...
s, or by mosquito-control measures such as spraying insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...
s and draining standing water (where mosquitoes breed). The challenge of producing a widely available vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
that provides a high level of protection for a sustained period is still to be met, although several are under development. A number of medications are also available to prevent malaria in travelers to malaria-endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
countries (prophylaxis
Malaria prophylaxis
Malaria prophylaxis is a preventative treatment of malaria.Most adults from endemic areas have a degree of long-term infection, which tends to recur, and also possess partial immunity ; the resistance reduces with time, and such adults may become susceptible to severe malaria if they have spent a...
).
A variety of antimalarial medications are available. Severe malaria is treated with intravenous or intramuscular quinine or, since the mid-2000s, the artemisinin
Artemisinin
Artemisinin , also known as Qinghaosu , and its derivatives are a group of drugs that possess the most rapid action of all current drugs against falciparum malaria. Treatments containing an artemisinin derivative are now standard treatment worldwide for falciparum malaria...
derivative artesunate
Artesunate
Artesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
, which is superior to quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
in both children and adults. Resistance has developed to several antimalarial drugs, most notably chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
.
There were an estimated 225 million cases of malaria worldwide in 2009.. An estimated 781,000 people died from malaria in 2009 according to the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
's 2010 World Malaria Report, accounting for 2.23% of deaths worldwide. Ninety percent of malaria-related deaths occur in sub-Saharan Africa, with the majority of deaths being young children. Plasmodium falciparum
Plasmodium falciparum
Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
, the most severe form of malaria, is responsible for the vast majority of deaths associated with the disease. Malaria is commonly associated with poverty, and can indeed be a cause of poverty and a major hindrance to economic development
Economic development
Economic development generally refers to the sustained, concerted actions of policymakers and communities that promote the standard of living and economic health of a specific area...
.
Signs and symptoms
Symptoms of malaria include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, shivering
Shivering
Shivering is a bodily function in response to early hypothermia in warm-blooded animals. When the core body temperature drops, the shivering reflex is triggered to maintain homeostasis. Muscle groups around the vital organs begin to shake in small movements in an attempt to create warmth by...
, arthralgia
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
(joint pain), vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
(caused by hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
), hemoglobinuria
Hemoglobinuria
In medicine, hemoglobinuria or haemoglobinuria is a condition in which the oxygen transport protein hemoglobin is found in abnormally high concentrations in the urine. The condition is often associated with hemolytic anemia, in which red blood cells are destroyed, thereby increasing levels of free...
, retinal damage
Retinopathy
Retinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
, and convulsion
Convulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...
s. The classic symptom of malaria is cyclical occurrence of sudden coldness followed by rigor
Rigor (medicine)
Rigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....
and then fever and sweating lasting four to six hours, occurring every two days in P. vivax and P. ovale infections, and 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
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
, children with malaria frequently exhibit abnormal posturing
Abnormal posturing
Abnormal posturing is an involuntary flexion or extension of the arms and legs, indicating severe brain injury. It occurs when one set of muscles becomes incapacitated while the opposing set is not, and an external stimulus such as pain causes the working set of muscles to contract. The posturing...
, a sign indicating severe brain damage. Malaria has been found to cause cognitive impairments, especially in children. It causes widespread anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
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 Plasmodium falciparum infection, and usually arises 6–14 days after infection. Consequences of severe malaria include coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
and death if untreated—young children and pregnant women are especially vulnerable. Splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
(enlarged spleen), severe headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, cerebral ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, hepatomegaly
Hepatomegaly
Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...
(enlarged liver), hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, and hemoglobinuria with renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
may occur. Renal failure is a feature of blackwater fever
Blackwater fever
Blackwater fever is a complication of malaria in which red blood cells burst in the bloodstream , releasing hemoglobin directly into the blood vessels and into the urine, frequently leading to kidney failure...
, 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
Plasmodium
Plasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known...
(phylum Apicomplexa
Apicomplexa
The Apicomplexa are a large group of protists, most of which possess a unique organelle called apicoplast and an apical complex structure involved in penetrating a host's cell. They are unicellular, spore-forming, and exclusively parasites of animals. Motile structures such as flagella or...
). In humans malaria is caused by P. falciparum
Plasmodium falciparum
Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
, P. malariae
Plasmodium malariae
Plasmodium malariae is a parasitic protozoa that causes malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that...
, P. ovale
Plasmodium ovale
Plasmodium ovale is a species of parasitic protozoa that causes tertian malaria in humans. It is closely related to Plasmodium falciparum and Plasmodium vivax, which are responsible for most malaria. It is rare compared to these two parasites, and substantially less dangerous than P...
, P. vivax
Plasmodium vivax
Plasmodium vivax is a protozoal parasite and a human pathogen. The most frequent and widely distributed cause of recurring malaria, P. vivax is one of the four species of malarial parasite that commonly infect humans. It is less virulent than Plasmodium falciparum, which is the deadliest of the...
and P. knowlesi
Plasmodium knowlesi
Plasmodium knowlesi is a primate malaria parasite commonly found in Southeast Asia. It causes malaria in long-tailed macaques , but it may also infect humans, either naturally or artificially....
. While P. vivax is responsible for the largest number of malaria infections worldwide, infections by P. falciparum account 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; however, with the exception of P. knowlesi, these are mostly of limited public health importance.
Malaria parasites contain apicoplast
Apicoplast
An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including malaria parasites such as Plasmodium falciparum, but not in others such as Cryptosporidium. It originated from an algae through secondary endosymbiosis...
s, an organelle usually found in plants, complete with their own functioning genomes. These apicoplast are thought to have originated through the endosymbiosis
Endosymbiont
An endosymbiont is any organism that lives within the body or cells of another organism, i.e. forming an 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.
Life cycle
The parasite's secondary (intermediate) hostsHost (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...
are humans and other vertebrates. Female mosquito
Mosquito
Mosquitoes are members of a family of nematocerid flies: the Culicidae . The word Mosquito is from the Spanish and Portuguese for little fly...
es of the Anopheles
Anopheles
Anopheles is a genus of mosquito. There are approximately 460 recognized species: while over 100 can transmit human malaria, only 30–40 commonly transmit parasites of the genus Plasmodium, which cause malaria in humans in endemic areas...
genus are primary hosts and transmission vectors. 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 gland
Salivary gland
The salivary glands in mammals are exocrine glands, glands with ducts, that produce saliva. They also secrete amylase, an enzyme that breaks down starch into maltose...
s. 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's 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. The sporozoites are injected into the skin, alongside saliva, when the mosquito takes a subsequent blood meal.
Only female mosquitoes feed on blood while male mosquitoes feed on plant nectar, 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 transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s, although this is rare.
Recurrent malaria
Malaria recurs after treatment for three reasons. Recrudescence occurs when parasites are not cleared by treatment, whereas reinfection indicates complete clearance with new infection established from a separate infective mosquito bite; both can occur with any malaria parasite species. Relapse is specific to P. vivax and P. ovale and involves re-emergence of blood-stage parasites from latent parasites (hypnozoites) 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. Approximately one in five of P. vivax malaria cases in temperateTemperate
In geography, temperate or tepid latitudes of the globe lie between the tropics and the polar circles. The changes in these regions between summer and winter are generally relatively moderate, rather than extreme hot or cold...
areas involve overwintering by hypnozoites (i.e., relapses begin the year after the mosquito bite).
Pathogenesis
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Within minutes of being introduced into the human host, the sporozoites infect hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
s, multiplying asexually and asymptomatically for a period of 8–30 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 cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s, thus beginning the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.
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.
The parasite is relatively protected from attack by the body's immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
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
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
. To avoid this fate, the P. falciparum parasite displays adhesive protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s 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. This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. High endothelial venules
High endothelial venules
High endothelial venules are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thiner endothelial cells found in regular 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
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
possibly leading to coma.
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 even more variants within whole parasite populations. 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 gametocyte
Gametocyte
A gametocyte is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into gametids during gametogenesis. Male gametocytes are called spermatocytes, and female gametocytes are called oocytes....
s. Since the gametocytes are formed in the blood of the vertebrate host, the vertebrate host is the definitive host of the disease. 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. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes, and malaria in pregnant women
Pregnancy-associated malaria
Pregnancy-associated malaria is a presentation of the common illness that is particularly life threatening to both mother and developing fetus. PAM is caused primarily by infection with Plasmodium falciparum, the most dangerous of the four species of malaria-causing parasites that infect humans...
is an important cause of stillbirth
Stillbirth
A stillbirth occurs when a fetus has died in the uterus. The Australian definition specifies that fetal death is termed a stillbirth after 20 weeks gestation or the fetus weighs more than . Once the fetus has died the mother still has contractions and remains undelivered. The term is often used in...
s, infant mortality and low birth weight, particularly in P. falciparum infection, but also in other species infection, such as P. vivax.
Genetic resistance
Malaria is thought to have been the greatest selective pressureSelection
In the context of evolution, certain traits or alleles of genes segregating within a population may be subject to selection. Under selection, individuals with advantageous or "adaptive" traits tend to be more successful than their peers reproductively—meaning they contribute more offspring to the...
on the human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
in recent history. This is due to the high levels of mortality
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
and morbidity caused by malaria, especially the P. falciparum
Plasmodium falciparum
Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by the female Anopheles mosquito. Malaria caused by this species is the most dangerous form of malaria, with the highest rates of complications and mortality...
species. A number of diseases may provide some resistance to it including sickle cell disease, thalassaemias, glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
, Duffy antigen
Duffy antigen
Duffy antigen/chemokine receptor also known as Fy glycoprotein or CD234 is a protein that in humans is encoded by the DARC gene....
s, and possibly others.
Diagnosis
The mainstay of malaria diagnosis has been the microscopic examination of blood, utilizing blood filmBlood film
A blood film or peripheral blood smear is a thin layer of blood smeared on a microscope slide and then stained in such a way to allow the various blood cells to be examined microscopically...
s. Although blood is the sample most frequently used to make a diagnosis, both saliva and urine have been investigated as alternative, less invasive specimens. More recently, modern techniques utilizing antigen tests or polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
have been discovered, though these are not widely implemented in malaria endemic regions. Areas that cannot afford laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria.
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.
Prevention
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
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
, Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
and much of the Middle East
Middle East
The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far 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. The economist Jeffrey Sachs
Jeffrey Sachs
Jeffrey David Sachs is an American economist and Director of The Earth Institute at Columbia University. One of the youngest economics professors in the history of Harvard University, Sachs became known for his role as an adviser to Eastern European and developing country governments in the...
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
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
, Eritrea
Eritrea
Eritrea , officially the State of Eritrea, is a country in the Horn of Africa. Eritrea derives it's name from the Greek word Erethria, meaning 'red land'. The capital is Asmara. It is bordered by Sudan in the west, Ethiopia in the south, and Djibouti in the southeast...
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, and Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...
, 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. ChloroquineChloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
may be used where the parasite is still sensitive. However due to resistance one of three medications: mefloquine
Mefloquine
Mefloquine hydrochloride is an orally administered medication used in the prevention and treatment of malaria. Mefloquine was developed in the 1970s at the United States Department of Defense's Walter Reed Army Institute of Research as a synthetic analogue of quinine...
(Lariam), doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
(available generically), and the combination of atovaquone
Atovaquone
Atovaquone is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about US$2.13 per standard 250 mg. tablet...
and proguanil
Proguanil
Proguanil is a prophylactic antimalarial drug.Proguanil is effective against sporozoites.Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.-Mechanism:...
hydrochloride (Malarone) is frequently needed. Doxycycline and the atovaquone and proguanil combination are the best tolerated with mefloquine associated with higher rates of neurological and psychiatric symptoms.
The prophylactic effect does not begin immediately upon starting 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 effect
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s from long-term use, and because some effective anti-malarial drugs are difficult to obtain outside of wealthy nations.
Quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
was used historically, however the development of more effective alternatives such as quinacrine
Quinacrine
Quinacrine is a drug with a number of different medical applications. It is related to mefloquine.-Uses:Its main effects are as an antiprotozoal, antirheumatic and an intrapleural sclerosing agent....
, chloroquine
Chloroquine
Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of malaria.-History:Chloroquine , N'--N,N-diethyl-pentane-1,4-diamine, was discovered in 1934 by Hans Andersag and co-workers at the Bayer laboratories who named it "Resochin". It was ignored for a decade because it was...
, and primaquine
Primaquine
Primaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
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.
Vector control
Efforts to eradicateEradication of infectious diseases
Eradication is the reduction of an infectious disease's prevalence in the global host population to zero. It is sometimes confused with elimination, which describes either the reduction of an infectious disease's prevalence in a regional population to zero, or the reduction of the global prevalence...
malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
and southern Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, 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 most parts of the USA in the early 20th century by such methods, and the use of the pesticide
Pesticide
Pesticides are substances or mixture of substances intended for preventing, destroying, repelling or mitigating any pest.A pesticide may be a chemical unicycle, biological agent , antimicrobial, disinfectant or device used against any pest...
DDT
DDT
DDT is one of the most well-known synthetic insecticides. It is a chemical with a long, unique, and controversial history....
and other means eliminated it from the remaining pockets in the South by 1951 (see National Malaria Eradication Program
National Malaria Eradication Program
In the United States, the National Malaria Eradication Program was launched on 1 July 1947. This federal program — with state and local participation — had succeeded in eradicating malaria in the United States by 1951.-History:...
). 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.
Sterile insect technique
Sterile insect technique
The sterile insect technique is a method of biological control, whereby overwhelming numbers of sterile insects are released. The released insects are normally male as it is the female that causes the damage, usually by laying eggs in the crop, or, in the case of mosquitoes, taking a bloodmeal from...
is emerging as a potential mosquito control method. Progress towards transgenic, or genetically modified
Genetically modified organism
A genetically modified organism or genetically engineered organism is an organism whose genetic material has been altered using genetic engineering techniques. These techniques, generally known as recombinant DNA technology, use DNA molecules from different sources, which are combined into one...
, insects suggest that wild mosquito populations could be made malaria-resistant. Researchers at Imperial College London
Imperial College London
Imperial College London is a public research university located in London, United Kingdom, specialising in science, engineering, business and medicine...
created the world's first transgenic malaria mosquito, with the first plasmodium-resistant species announced by a team at Case Western Reserve University
Case Western Reserve University
Case Western Reserve University is a private research university located in Cleveland, Ohio, USA...
in Ohio
Ohio
Ohio is a Midwestern state in the United States. The 34th largest state by area in the U.S.,it is the 7th‑most populous with over 11.5 million residents, containing several major American cities and seven metropolitan areas with populations of 500,000 or more.The state's capital is Columbus...
in 2002. 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.
Another way of reducing the malaria transmitted to humans from mosquitoes has been developed by the University of Arizona. They have engineered a mosquito to become resistant to malaria. This was reported on the 16 July 2010 in the journal PLoS Pathogens
PLoS Pathogens
PLoS Pathogens is an open-access scientific journal published by the Public Library of Science. It publishes research and reviews on the biology of pathogens and host-pathogen interactions. The 2010 impact factor is 9.079....
. With the ultimate end being that the release of this GM mosquito into the environment, Gareth Lycett, a malaria researcher from Liverpool School of Tropical Medicine told the BBC that "It is another step on the journey towards potentially assisting malaria control through GM mosquito release."
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
DDT
DDT is one of the most well-known synthetic insecticides. It is a chemical with a long, unique, and controversial history....
. Although it was initially used exclusively to combat malaria, its use quickly spread to agriculture
Agriculture
Agriculture is the cultivation of animals, plants, fungi and other life forms for food, fiber, and other products used to sustain life. Agriculture was the key implement in the rise of sedentary human civilization, whereby farming of domesticated species created food surpluses that nurtured the...
. In time, pest-control, rather than disease-control, came to dominate DDT use, and this large-scale agricultural use led to the evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
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
Public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...
.
The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) currently advises the use of 12 different insecticides in IRS operations, including DDT as well as alternative insecticides (such as the pyrethroids permethrin
Permethrin
Permethrin is a common synthetic chemical, widely used as an insecticide, acaricide, and insect repellent. It belongs to the family of synthetic chemicals called pyrethroids and functions as a neurotoxin, affecting neuron membranes by prolonging sodium channel activation. It is not known to...
and deltamethrin
Deltamethrin
Deltamethrin is a pyrethroid ester insecticide.-Usage:Deltamethrin products are among the most popular and widely used insecticides in the world and have become very popular with pest control operators and individuals in the United States in the past five years. This material is a member of one of...
). This public health use of small amounts of DDT is permitted under the Stockholm Convention
Stockholm Convention
Stockholm Convention on Persistent Organic Pollutants is an international environmental treaty, signed in 2001 and effective from May 2004, that aims to eliminate or restrict the production and use of persistent organic pollutants .- History :...
on Persistent Organic Pollutant
Persistent organic pollutant
thumb|right|275px|State parties to the Stockholm Convention on Persistent Organic PollutantsPersistent organic pollutants are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes...
s (POPs), which prohibits the agricultural use of DDT. However, because of its legacy, many developed countries previously discouraged DDT use even in small quantities.
One problem with all forms of Indoor Residual Spraying is insecticide resistance
Pesticide resistance
Pesticide resistance is the adaptation of pest population targeted by a pesticide resulting in decreased susceptibility to that chemical. In other words, pests develop a resistance to a chemical through natural selection: the most resistant organisms are the ones to survive and pass on their...
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.
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 (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net. Although ITNs 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 AnophelesAnopheles
Anopheles is a genus of mosquito. There are approximately 460 recognized species: while over 100 can transmit human malaria, only 30–40 commonly transmit parasites of the genus Plasmodium, which cause malaria in humans in endemic areas...
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.
Immunization
Immunity (or, more accurately, tolerance) does occur naturally, but only in response to repeated infection with multiple strains of malaria. A completely effective vaccineVaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
is not yet available for malaria, although several vaccines are under development. SPf66 was tested extensively in endemic areas in the 1990s, but clinical trials showed it to be insufficiently effective. Other vaccine candidates, targeting the blood-stage of the parasite's life cycle, have also been insufficient on their own. Several potential vaccines targeting the pre-erythrocytic stage are being developed, with RTS,S
RTS,S
RTS,S or Mosquirix is vaccine for malaria developed by GlaxoSmithKline.In October 2011 it was reported to protect approximately 50% of inoculated infants and children....
showing the most promising results so far.
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
Volunteer computing
Volunteer computing is a type of distributed computing in which computer owners donate their computing resources to one or more "projects".-History:...
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.
An example of the importance of computer modeling in planning malaria eradication
Eradication of infectious diseases
Eradication is the reduction of an infectious disease's prevalence in the global host population to zero. It is sometimes confused with elimination, which describes either the reduction of an infectious disease's prevalence in a regional population to zero, or the reduction of the global prevalence...
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. 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 administration
Mass drug administration
The administration of drugs to whole populations irrespective of disease status is referred to as mass drug administration . This article describes the administration of antimalarial drugs to whole populations an intervention which has been used as a malaria-control measure for more than 70 years...
s and intermittent preventive therapy
Intermittent preventive therapy
Intermittent preventive therapy is a public health intervention aimed at treating and preventing malaria episodes in infants , children , schoolchildren and pregnant women...
.
Furthering attempts to reduce transmission rates, a proposed alternative to mosquito nets is the mosquito laser
Mosquito laser
The mosquito laser is a device invented by astrophysicist Lowell Wood to kill large numbers of mosquitoes to reduce the chance of people being infected with malaria. Mosquitoes can carry the blood parasite of the genus plasmodium, which causes malaria...
, or photonic fence, which identifies female mosquitoes and shoots them using a medium-powered laser
Laser
A laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...
. The device is currently undergoing commercial development, although instructions for a DIY
Do it yourself
Do it yourself is a term used to describe building, modifying, or repairing of something without the aid of experts or professionals...
version of the photonic fence have also been published.
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 WHOWho
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
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
Artemisinin
Artemisinin , also known as Qinghaosu , and its derivatives are a group of drugs that possess the most rapid action of all current drugs against falciparum malaria. Treatments containing an artemisinin derivative are now standard treatment worldwide for falciparum malaria...
-based therapies.
Severe malaria requires the parenteral administration of antimalarial drugs. Until recently the most used treatment for severe malaria was quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
but artesunate
Artesunate
Artesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
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
Primaquine
Primaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
.
Epidemiology
Although co-infection with HIV and malaria does cause increased mortality, this is less of a problem than with HIV/tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
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. 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
Viral load
Viral load is a measure of the severity of a viral infection, and can be calculated by estimating the amount of virus in an involved body fluid. For example, it can be given in RNA copies per milliliter of blood plasma...
and HIV infection increasing a person's susceptibility to malaria infection.
Malaria is presently endemic in a broad band around the equator, in areas of the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...
, many parts of Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, and much of Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur. The geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other. Malaria is prevalent in tropical regions because of the significant amounts of rainfall and consistent high temperatures; warm, consistent temperatures and high humidity, along with stagnant waters in which their larvae mature, providing mosquitoes with the environment they need for continuous breeding. In drier areas, outbreaks of malaria can be predicted with reasonable accuracy by mapping rainfall. Malaria is more common in rural areas than in cities; this is in contrast to dengue fever
Dengue fever
Dengue fever , also known as breakbone fever, is an infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles...
where urban areas present the greater risk. For example, several cities in Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...
, Laos
Laos
Laos Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ Sathalanalat Paxathipatai Paxaxon Lao, officially the Lao People's Democratic Republic, is a landlocked country in Southeast Asia, bordered by Burma and China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...
and Cambodia
Cambodia
Cambodia , officially known as the Kingdom of Cambodia, is a country located in the southern portion of the Indochina Peninsula in Southeast Asia...
are essentially malaria-free, but the disease is present in many rural regions. By contrast, in Africa malaria is present in both rural and urban areas, though the risk is lower in the larger cities. The global endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
levels of malaria have not been mapped since the 1960s. However, the Wellcome Trust
Wellcome Trust
The Wellcome Trust was established in 1936 as an independent charity funding research to improve human and animal health. With an endowment of around £13.9 billion, it is the United Kingdom's largest non-governmental source of funds for biomedical research...
, UK, has funded the Malaria Atlas Project
Malaria Atlas Project
The Malaria Atlas Project, abbreviated as MAP, is a non-profit project primarily funded by the Wellcome Trust, UK. MAP is a joint project between the Malaria Public Health & Epidemiology Group, Centre for Geographic Medicine, Kenya and the Spatial Ecology & Epidemiology Group, University of...
to rectify this, providing a more contemporary and robust means with which to assess current and future malaria disease burden
Disease burden
Disease burden is the impact of a health problem in an area measured by financial cost, mortality, morbidity, or other indicators. It is often quantified in terms of quality-adjusted life years or disability-adjusted life years , which combine the burden due to both death and morbidity into one...
.
By 2010 countries with the highest death rate per 100,000 population are Cote d'Ivoire
Côte d'Ivoire
The Republic of Côte d'Ivoire or Ivory Coast is a country in West Africa. It has an area of , and borders the countries Liberia, Guinea, Mali, Burkina Faso and Ghana; its southern boundary is along the Gulf of Guinea. The country's population was 15,366,672 in 1998 and was estimated to be...
with (86.15), Angola
Angola
Angola, officially the Republic of Angola , is a country in south-central Africa bordered by Namibia on the south, the Democratic Republic of the Congo on the north, and Zambia on the east; its west coast is on the Atlantic Ocean with Luanda as its capital city...
(56.93) and Burkina Faso
Burkina Faso
Burkina Faso – also known by its short-form name Burkina – is a landlocked country in west Africa. It is surrounded by six countries: Mali to the north, Niger to the east, Benin to the southeast, Togo and Ghana to the south, and Côte d'Ivoire to the southwest.Its size is with an estimated...
(50.66) - all in Africa.
History
Malaria has infected humans for over 50,000 years, and Plasmodium may have been a human pathogenPathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
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
Roman Empire
The Roman Empire was the post-Republican period of the ancient Roman civilization, characterised by an autocratic form of government and large territorial holdings in Europe and around the Mediterranean....
, and was so pervasive in Rome that it was known as the "Roman fever
Roman Fever (disease)
Roman fever refers to a particularly deadly strain of malaria that affected Rome, Italy, throughout various epochs in history; an epidemic of Roman fever during the fifth century AD may have contributed to the fall of the Roman empire...
". The term malaria originates from Medieval
Middle Ages
The Middle Ages is a periodization of European history from the 5th century to the 15th century. The Middle Ages follows the fall of the Western Roman Empire in 476 and precedes the Early Modern Era. It is the middle period of a three-period division of Western history: Classic, Medieval and Modern...
— "bad air
Miasma theory of disease
The miasma theory held that diseases such as cholera, chlamydia or the Black Death were caused by a miasma , a noxious form of "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
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
, 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
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, 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 RossRonald Ross
Sir Ronald Ross KCB FRS was a British doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on malaria. He was the first Indian-born person to win a Nobel Prize...
. An 1896 Uxbridge
Uxbridge, Massachusetts
Uxbridge is a town in Worcester County, Massachusetts, in the United States. It was first settled in 1662, incorporated in 1727 at Suffolk County, and named for the Earl of Uxbridge. Uxbridge is south-southeast of Worcester, north-northwest of Providence, and southwest of Boston. It is part of...
malaria outbreak prompted health officer, Dr. Leonard White
Leonard White (physician)
Leonard D. White, MD was a late 19th century physician and one of the Health Officers in Massachusetts who was involved with the earliest study of mosquitoes and malaria and efforts for community prevention of malaria.-Early life:...
, to write a report to the Massachusetts
Massachusetts
The Commonwealth of Massachusetts is a state in the New England region of the northeastern United States of America. It is bordered by Rhode Island and Connecticut to the south, New York to the west, and Vermont and New Hampshire to the north; at its east lies the Atlantic Ocean. As of the 2010...
State Board of Health, which led to study of mosquito-malaria links, and the first efforts for malaria prevention
Preventive medicine
Preventive medicine or preventive care refers to measures taken to prevent diseases, rather than curing them or treating their symptoms...
. Massachusetts
Massachusetts
The Commonwealth of Massachusetts is a state in the New England region of the northeastern United States of America. It is bordered by Rhode Island and Connecticut to the south, New York to the west, and Vermont and New Hampshire to the north; at its east lies the Atlantic Ocean. As of the 2010...
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
Carlos Finlay
Carlos Juan Finlay was a Cuban physician and scientist recognized as a pioneer in yellow fever research.- Early life and education :...
was also engaged in mosquito related research, and mosquito borne disease theory, in the 1880s in Cuba
Cuba
The Republic of Cuba is an island nation in the Caribbean. The nation of Cuba consists of the main island of Cuba, the Isla de la Juventud, and several archipelagos. Havana is the largest city in Cuba and the country's capital. Santiago de Cuba is the second largest city...
, basing his work on the study of Yellow Fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
.
Discovery of the parasite
Scientific studies on malaria made their first significant advance in 1880, when a French army doctor working in the military hospital of ConstantineConstantine, Algeria
Constantine is the capital of Constantine Province in north-eastern Algeria. It was the capital of the same-named French département until 1962. Slightly inland, it is about 80 kilometres from the Mediterranean coast, on the banks of Rhumel river...
in Algeria
Algeria
Algeria , officially the People's Democratic Republic of Algeria , also formally referred to as the Democratic and Popular Republic of Algeria, is a country in the Maghreb region of Northwest Africa with Algiers as its capital.In terms of land area, it is the largest country in Africa and the Arab...
named Charles Louis Alphonse Laveran
Charles Louis Alphonse Laveran
Charles Louis Alphonse Laveran was a French physician.In 1880, while working in the military hospital in Constantine, Algeria, he discovered that the cause of malaria is a protozoan, after observing the parasites in a blood smear taken from a patient who had just died of malaria.He also helped...
observed parasites for the first time, inside the red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s 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. 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
Ettore Marchiafava
Ettore Marchiafava was an Italian physician and zoologist who worked on malariaEttore Marchiafava , was the personal doctor of three popes and the Royal House of Savoy, a senator and professor of Pathological Anatomy at the Sapienza University of Rome...
and Angelo Celli
Angelo Celli
Angelo Celli was an Italian physician and zoologist who studied malaria.Celli graduated in medicine in 1878 at the Sapienza University of Rome, where he became hygiene professor. In 1880 with Ettore Marchiafava he studied a new protozoan discovered by Alphonse Laveran and which they called...
.
Discovery of mosquito transmission
A year later, Carlos FinlayCarlos Finlay
Carlos Juan Finlay was a Cuban physician and scientist recognized as a pioneer in yellow fever research.- Early life and education :...
, a Cuban doctor treating patients with yellow fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
in Havana
Havana
Havana is the capital city, province, major port, and leading commercial centre of Cuba. The city proper has a population of 2.1 million inhabitants, and it spans a total of — making it the largest city in the Caribbean region, and the most populous...
, provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by Josiah C. Nott
Josiah C. Nott
Josiah Clark Nott was an American physician and surgeon. He was also an author of surgical, yellow fever, and race theories.-Biography:...
, and work by Sir Patrick Manson, The Father of Tropical Medicine, on the transmission of filariasis
Filariasis
Filariasis is a parasitic disease and is considered an infectious tropical disease, that is caused by thread-like nematodes belonging to the superfamily Filarioidea, also known as "filariae"....
.
In April 1894, a Scottish physician Sir Ronald Ross
Ronald Ross
Sir Ronald Ross KCB FRS was a British doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on malaria. He was the first Indian-born person to win a Nobel Prize...
visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research which culminated in 1898 when Ross, who was working in the Presidency General Hospital in Calcutta
Kolkata
Kolkata , formerly known as Calcutta, is the capital of the Indian state of West Bengal. Located on the east bank of the Hooghly River, it was the commercial capital of East India...
, proved the complete life-cycle of the malaria parasite in mosquitoes; thus proving that the mosquito was the vector for malaria in humans. He did this by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. 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
Liverpool School of Tropical Medicine
The Liverpool School of Tropical Medicine is a research and teaching institution focused on neglected tropical diseases and the control of diseases caused by poverty. It is a registered charity affiliated to the University of Liverpool...
and directed malaria-control efforts in Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
, Panama
Panama
Panama , officially the Republic of Panama , is the southernmost country of Central America. Situated on the isthmus connecting North and South America, it is bordered by Costa Rica to the northwest, Colombia to the southeast, the Caribbean Sea to the north and the Pacific Ocean to the south. The...
, Greece
Greece
Greece , officially the Hellenic Republic , and historically Hellas or the Republic of Greece in English, is a country in southeastern Europe....
and Mauritius
Mauritius
Mauritius , officially the Republic of Mauritius is an island nation off the southeast coast of the African continent in the southwest Indian Ocean, about east of Madagascar...
. The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed
Walter Reed
Major Walter Reed, M.D., was a U.S. Army physician who in 1900 led the team that postulated and confirmed the theory that yellow fever is transmitted by a particular mosquito species, rather than by direct contact...
in 1900. Its recommendations were implemented by William C. Gorgas
William C. Gorgas
William Crawford Gorgas KCMG was a United States Army physician and 22nd Surgeon General of the U.S. Army...
in the health measures undertaken
Health measures during the construction of the Panama Canal
One of the greatest challenges facing the builders of the Panama Canal was dealing with the tropical diseases rife in the area. The health measures taken during the construction contributed greatly to the success of the canal's construction...
during construction of the Panama Canal
Panama Canal
The Panama Canal is a ship canal in Panama that joins the Atlantic Ocean and the Pacific Ocean and is a key conduit for international maritime trade. Built from 1904 to 1914, the canal has seen annual traffic rise from about 1,000 ships early on to 14,702 vessels measuring a total of 309.6...
. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease.
The liver stage
Shortt and Garnham discovered the pre-erythrocytic liver stage, first in the primate parasite P. cynomolgi and subsequently the human malarias P. vivax and P. falciparum. Further work confirmed the transformation of sporozoites from mosquitoes into liver forms, essentially completing documentation of the lifecycle.In vitro culture
The first successful continuous in vitro malaria cultureMalaria culture
Malaria culture is the method to grow malaria parasites outside the body i.e. in an ex vivo environment.Plasmodium falciparum is currently the only human malaria parasite that has been successfully cultured continuously ex vivo...
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.
History of treatment
The first effective treatment for malaria came from the bark of cinchona treeCinchona
Cinchona or Quina is a genus of about 38 species in the family Rubiaceae, native to tropical South America. They are large shrubs or small trees growing 5–15 metres in height with evergreen foliage. The leaves are opposite, rounded to lanceolate and 10–40 cm long. The flowers are white, pink...
, which contains quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
. This tree grows on the slopes of the Andes
Andes
The Andes is the world's longest continental mountain range. It is a continual range of highlands along the western coast of South America. This range is about long, about to wide , and of an average height of about .Along its length, the Andes is split into several ranges, which are separated...
, mainly in Peru
Peru
Peru , officially the Republic of Peru , is a country in western South America. It is bordered on the north by Ecuador and Colombia, on the east by Brazil, on the southeast by Bolivia, on the south by Chile, and on the west by the Pacific Ocean....
. The indigenous peoples
Indigenous peoples
Indigenous peoples are ethnic groups that are defined as indigenous according to one of the various definitions of the term, there is no universally accepted definition but most of which carry connotations of being the "original inhabitants" of a territory....
of Peru made a tincture
Tincture
A tincture is an alcoholic extract or solution of a non-volatile substance . To qualify as a tincture, the alcoholic extract is to have an ethanol percentage of at least 40-60%...
of cinchona to control malaria. The Jesuits noted the efficacy of the practice and introduced the treatment to Europe during the 1640s, where it was rapidly accepted. 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
Pierre Joseph Pelletier
Pierre-Joseph Pelletier was a French chemist who did notable research on vegetable alkaloids, and was the co-discoverer of quinine and strychnine.- Further reading :...
and Joseph Bienaimé Caventou
Joseph Bienaimé Caventou
Joseph Bienaimé Caventou was a French chemist.He was a professor at the École de Pharmacie in Paris. He collaborated with Pierre-Joseph Pelletier in a Parisian laboratory located behind an apothecary. He was a pioneer in the use of mild solvents to isolate a number of active ingredients from...
. In the 20th century, chloroquine replaced quinine as treatment of both uncomplicated and severe falciparum malaria until resistance supervened. Artemisinins, discovered by Chinese scientists in the 1970s, are now recommended treatment for falciparum malaria, administered in combination with other antimalarials as well as in severe disease.
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 developmentEconomic development
Economic development generally refers to the sustained, concerted actions of policymakers and communities that promote the standard of living and economic health of a specific area...
. 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. A comparison of average per capita GDP in 1995, adjusted for parity of purchasing power
Purchasing power parity
In economics, purchasing power parity is a condition between countries where an amount of money has the same purchasing power in different countries. The prices of the goods between the countries would only reflect the exchange rates...
, 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.
Poverty is both cause and effect, however, since the poor do not have the financial capacities to prevent or treat the disease. 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. 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.
The demographic transition
Demographic transition
The demographic transition model is the transition from high birth and death rates to low birth and death rates as a country develops from a pre-industrial to an industrialized economic system. The theory is based on an interpretation of demographic history developed in 1929 by the American...
in Africa is slow and malaria may provide part of the answer. Total fertility
Fertility
Fertility is the natural capability of producing offsprings. As a measure, "fertility rate" is the number of children born per couple, person or population. Fertility differs from fecundity, which is defined as the potential for reproduction...
rates were best explained by child mortality
Child mortality
Child mortality, also known as under-5 mortality, refers to the death of infants and children under the age of five. In 2010, 7.6 million children under five died , down from 8.1 million in 2009, 8.8 million in 2008, and 12.4 million in 1990. About half of child deaths occur in Africa....
, as measured indirectly by infant mortality
Infant mortality
Infant mortality is defined as the number of infant deaths per 1000 live births. Traditionally, the most common cause worldwide was dehydration from diarrhea. However, the spreading information about Oral Re-hydration Solution to mothers around the world has decreased the rate of children dying...
, in a 2007 study.
A study on the effect of malaria on IQ in a sample of Mexicans found that exposure during the birth year to malaria eradication was associated with increases in IQ. It also increased the probability of employment in a skilled occupation. The author suggests that this may be one explanation for the Flynn effect
Flynn effect
The Flynn effect is the name given to a substantial and long-sustained increase in intelligence test scores measured in many parts of the world. When intelligence quotient tests are initially standardized using a sample of test-takers, by convention the average of the test results is set to 100...
and that this may be an important explanation for the link between national malaria burden and economic development. A literature review of 44 papers states that cognitive abilities and school performance were shown to be impaired in sub-groups of patients (with either cerebral malaria or uncomplicated malaria) when compared with healthy controls. Studies comparing cognitive functions before and after treatment for acute malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery. Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups. April 25 is World Malaria Day
World Malaria Day
World Malaria Day is commemorated every year on 25 April and recognizes global efforts to control malaria. Globally, 3.3 billion people in 106 countries are at risk of malaria...
.
Counterfeit drugs
Sophisticated counterfeits have been found in several Asian countries such as CambodiaCambodia
Cambodia , officially known as the Kingdom of Cambodia, is a country located in the southern portion of the Indochina Peninsula in Southeast Asia...
, China
People's Republic of China
China , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...
, Indonesia
Indonesia
Indonesia , officially the Republic of Indonesia , is a country in Southeast Asia and Oceania. Indonesia is an archipelago comprising approximately 13,000 islands. It has 33 provinces with over 238 million people, and is the world's fourth most populous country. Indonesia is a republic, with an...
, Laos
Laos
Laos Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ Sathalanalat Paxathipatai Paxaxon Lao, officially the Lao People's Democratic Republic, is a landlocked country in Southeast Asia, bordered by Burma and China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...
, Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...
, Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...
and are an important cause of avoidable death in those countries.
WHO
Who
Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...
said that studies indicate that up to 40% of artesunate
Artesunate
Artesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
based malaria medications are counterfeit, especially in the Greater Mekong
Mekong
The Mekong is a river that runs through China, Burma, Laos, Thailand, Cambodia and Vietnam. It is the world's 10th-longest river and the 7th-longest in Asia. Its estimated length is , and it drains an area of , discharging of water annually....
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. 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.
War
Throughout history, the contraction of malaria (via natural outbreaks as well as via infliction of the disease as a biological warfare agent) has played a prominent role in the fortunes of government rulers, nation-states, military personnel, and military actions. "Malaria Site: History of Malaria During Wars" addresses the devastating impact of malaria in numerous well-known conflicts, beginning in June 323 B.C. That site's authors note: "Many great warriors succumbed to malaria after returning from the warfront and advance of armies into continents was prevented by malaria. In many conflicts, more troops were killed by malaria than in combat." The Centers for Disease Control ("CDC") traces the history of malaria and its impacts farther back, to 2700 BCE.In 1910, Nobel Prize in Medicine-winner Ronald Ross
Ronald Ross
Sir Ronald Ross KCB FRS was a British doctor who received the Nobel Prize for Physiology or Medicine in 1902 for his work on malaria. He was the first Indian-born person to win a Nobel Prize...
(himself a malaria survivor), published a book titled The Prevention of Malaria that included the chapter: "The Prevention of Malaria in War." The chapter's author, Colonel C. H. Melville, Professor of Hygiene at Royal Army Medical College in London, addressed the prominent role that malaria has historically played during wars and advised: "A specially selected medical officer should be placed in charge of these operations with executive and disciplinary powers [...]."
Significant financial investments have been made to procure existing and create new anti-malarial agents. During World War I
World War I
World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...
and World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, the supplies of the natural anti-malaria drugs, cinchona bark and quinine
Quinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
, proved to be inadequate to supply military personnel and substantial funding was funnelled into research and development
Research and development
The phrase research and development , according to the Organization for Economic Co-operation and Development, refers to "creative work undertaken on a systematic basis in order to increase the stock of knowledge, including knowledge of man, culture and society, and the use of this stock of...
of other drugs and vaccines. American military organizations conducting such research initiatives include the Navy Medical Research Center, Walter Reed Army Institute of Research
Walter Reed Army Institute of Research
This article is about the U.S. Army medical research institute . Otherwise, see Walter Reed .The Walter Reed Army Institute of Research is the largest biomedical research facility administered by the U.S. Department of Defense...
, and the U.S. Army Medical Research Institute of Infectious Diseases of the US Armed Forces.
Additionally, initiatives have been founded such as Malaria Control in War Areas (MCWA), established in 1942, and its successor, the Communicable Disease Center (now known as the Centers for Disease Control) established in 1946. According to the CDC, MCWA "was established to control malaria around military training bases in the southern United States and its territories, where malaria was still problematic" and, during these activities, to "train state and local health department officials in malaria control techniques and strategies." The CDC's Malaria Division continued that mission, successfully reducing malaria in the United States, after which the organization expanded its focus to include "prevention, surveillance, and technical support both domestically and internationally."
Eradication efforts
Several notable attempts are being made to eliminate the parasite from sections of the world, or to eradicate it worldwide. In 2006, the organization Malaria No MoreMalaria No More
Malaria No More is a nonprofit organization that aims to end death caused by malaria in Africa by 2015. Malaria No More is known for its participation in the Idol Gives Back charity specials.- History :...
set a public goal of eliminating malaria from Africa by 2015, and the organization plans to dissolve if that goal is accomplished. Several malaria vaccine
Malaria vaccine
Malaria vaccines are an area of intensive research. However, there is no effective vaccine that has been introduced into clinical practice.The global burden of P. falciparum malaria increased through the 1990s due to drug-resistant parasites and insecticide-resistant mosquitoes; this is illustrated...
s are in clinical trials, which are intended to provide protection for children in endemic areas and reduce the speed of transmission of the disease. The Global Fund to Fight AIDS, Tuberculosis and Malaria
The Global Fund to Fight AIDS, Tuberculosis and Malaria
The Global Fund to Fight AIDS, Tuberculosis and Malaria is an international financing organization that aims to "[a]ttract and disburse additional resources to prevent and treat HIV and AIDS, tuberculosis and malaria." A public–private partnership, the organization has its secretariat in Geneva,...
has distributed more than 160 million insecticide-treated nets intended to stop mosquito-born transmission of malaria. According to director Inder Singh
Inder Singh (philanthropist)
Inder Singh is Executive Vice President of the multi-national Clinton Health Access Initiative, a global not-for-profit organization fighting malaria and other diseases. Mr. Singh has become known for his worldwide presence actions for global health, particularly regarding malaria eradication. He...
, the U.S.-based Clinton Foundation
Clinton Foundation
The William J. Clinton Foundation is a foundation established by former President of the United States Bill Clinton with the stated mission to "strengthen the capacity of people throughout the world to meet the challenges of global interdependence." The Foundation focuses on four critical areas:...
has reduced the cost of drugs to treat malaria by 60%, and is working to further reduce the spread of the disease. Other efforts, such as the Malaria Atlas Project
Malaria Atlas Project
The Malaria Atlas Project, abbreviated as MAP, is a non-profit project primarily funded by the Wellcome Trust, UK. MAP is a joint project between the Malaria Public Health & Epidemiology Group, Centre for Geographic Medicine, Kenya and the Spatial Ecology & Epidemiology Group, University of...
focus on analyzing climate and weather information required to accurately predict the spread of malaria based on the availability of habitat of malaria-carrying parasites.
Research
With the onset of drug resistant PlasmodiumPlasmodium
Plasmodium is a genus of parasitic protists. Infection by these organisms is known as malaria. The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. Currently over 200 species of this genus are recognized and new species continue to be described.Of the over 200 known...
parasites, new strategies are required to combat the widespread disease. One such approach lies in the introduction of synthetic pyridoxal
Pyridoxal
Pyridoxal is one of the three natural forms of vitamin B6, along with pyridoxamine and pyridoxine . All of these forms are converted in the human body into a single biologically active form, pyridoxal 5-phosphate. All three forms of vitamin B6 are heterocyclic organic compounds...
-amino acid adducts, which are channelled into the parasite. Thus, trapped upon phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
by plasmodial PdxK (pyridoxine/pyridoxal kinase
Pyridoxal kinase
In enzymology, a pyridoxal kinase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are ATP and pyridoxal, whereas its two products are ADP and pyridoxal 5'-phosphate....
), the proliferation of Plasmodium parasites is effectively hindered by a novel compound, PT3, a cyclic pyridoxyl-tryptophan methyl ester, without harming human cells.
Malaria vaccines have been an elusive goal of research. The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunizing mice with live, radiation-attenuated
Attenuator (genetics)
Attenuation is a regulatory feature found throughout Archaea and Bacteria causing premature termination of transcription. Attenuators are 5'-cis acting regulatory regions which fold into one of two alternative RNA structures which determine the success of transcription...
sporozoites, providing protection to about 60% of the mice upon subsequent injection with normal, viable sporozoites. 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 yet irradiated mosquitoes.
In October 2011, preliminary findings from a Phase III trial of an experimental vaccine known as RTS,S
RTS,S
RTS,S or Mosquirix is vaccine for malaria developed by GlaxoSmithKline.In October 2011 it was reported to protect approximately 50% of inoculated infants and children....
reported that it may protect approximately 50% of inoculated infants and children (decline in final mortality rate unverified). The RTS,S vaccine was engineered using genes from the outer protein of Plasmodium falciparum malaria parasite and a portion of a hepatitis B virus and a chemical adjuvant to boost the immune system response. The RTS,S-based vaccine formulation had previously been demonstrated to be safe, well tolerated, immunogenic, and to potentially confer partial efficacy in both malaria-naive and -experienced adults as well as children, although further research was considered necessary to improve the effectiveness of the vaccine. It is being developed by PATH
Program for Appropriate Technology in Health
The Program for Appropriate Technology in Health is an international, nonprofit global health organization based in Seattle, Washington , with 900+ employees in more than 30 offices around the world. Its president and CEO is Dr...
and GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
(GSK) and Bill and Melinda Gates Foundation
Further reading
excerpt and text search excerpt and text searchExternal links
- WHO site on malaria
- Global Malaria action Plan
- Malaria Atlas Project
- Medicines for Malaria Venture (MMV)
- World Malaria Report 2005
- Doctors Without Borders/Médecins Sans Frontières – Malaria information pages
- Medline Plus – Malaria
- Who/TDR Malaria Database
- Anti malaria and sustainable development
- Worldwide Antimalarial Resistance Network (WWARN)