Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female mosquitoes.
The most common time for these mosquitoes to be active is between dusk and dawn.
In 2015, 95 countries and territories had ongoing malaria transmission.
An estimated 3.4 billion people in 106 countries and territories are at risk of malaria - nearly half of the world's population.
Malaria is preventable and curable, and increased efforts are dramatically reducing the malaria burden in many places.
Between 2000 and 2015, malaria incidence among populations at risk (the rate of new cases) fell by 37% globally. In that same period, malaria death rates among populations at risk fell by 60% globally among all age groups and by 65% among children under 5.
Sub-Saharan Africa carries a disproportionately high share of the global malaria burden. In 2015, the region was home to 88% of malaria cases and 90% of malaria deaths.
Malaria was first identified in 1880 as a disease caused by parasitic infection.
The name of the disease comes from the Italian word mal'aria, meaning "bad air".
Malaria was eliminated from the US in the early 1950s, but the mosquitoes that carry and transmit the malaria parasite still remain, creating a constant risk of reintroduction.
Reported malaria cases in the US reached a 40-year high of 1,925 in 2011.
Researchers are working hard on improving the prevention of malarial infection, early diagnosis and treatment, with just one malaria vaccine close to being licensed so far in Europe.
Annual funding for malaria control in 2013 was three times the amount spent in 2005, yet it represented only 53% of global funding needs.
The World Health Organization (WHO) has set out to reduce all malaria cases and deaths by 90% by 2030.
Malaria is caused by Plasmodium parasites. The parasites are spread to people through the bites of infected female Anopheles mosquitoes, called "malaria vectors". There are 5 parasite species that cause malaria in humans, and 2 of these species (P. falciparum and P. vivax) pose the greatest threat.
P. falciparum is the most prevalent malaria parasite on the African continent. It is responsible for most malaria-related deaths globally.
P. vivax is the dominant malaria parasite in most countries outside of sub-Saharan Africa.
Malaria is an acute febrile illness. In a non-immune individual, symptoms appear 7 days or more (usually 10–15 days) after the infectous mosquito bite.
The first symptoms – fever, headache, chills and vomiting – may be mild and difficult to recognize as malaria. If not treated within 24 hours, P. falciparum malaria can progress to severe illness, often leading to death.
Children with severe malaria frequently develop one or more of the following symptoms: severe anaemia, respiratory distress in relation to metabolic acidosis, or cerebral malaria. In adults, multi-organ involvement is also frequent. In malaria endemic areas, people may develop partial immunity, allowing asymptomatic infections to occur.
The signs and symptoms of malaria typically begin 8–25 days following infection; however, symptoms may occur later in those who have taken anti-malarial medications as prevention. Initial manifestations of the disease (common to all malaria species) are similar to flu-like symptoms, and can resemble other conditions such as sepsis, gastroenteritis, and viral diseases. The presentation may include headache, fever, shivering, joint-pain, vomiting, hemolytic anemia, jaundice, hemoglobin in the urine, retinal damage, and convulsions.
The classic symptom of malaria is paroxysm—a cyclical occurrence of sudden coldness followed by shivering and then fever and sweating, occurring every two days (tertian fever) in P. vivax and P. ovale infections, and every three days (quartan fever) for P. malariae.
P. falciparum infection can cause recurrent fever every 36–48 hours, or a less pronounced and almost continuous fever.
Severe malaria is usually caused by P. falciparum (often referred to as falciparum malaria). Symptoms of falciparum malaria arise 9–30 days after infection. Individuals with cerebral malaria frequently exhibit neurological symptoms, including abnormal posturing, nystagmus, conjugate gaze palsy (failure of the eyes to turn together in the same direction), opisthotonus, seizures, or coma.
TRANSMISSION (LIFE CYCLE)
In most cases, malaria is transmitted through the bites of female Anopheles mosquitoes. There are more than 400 different species of Anopheles mosquito; around 30 are malaria vectors of major importance. All of the important vector species bite between dusk and dawn. The intensity of transmission depends on factors related to the parasite, the vector, the human host, and the environment.
Anopheles mosquitoes lay their eggs in water, which hatch into larvae, eventually emerging as adult mosquitoes. The female mosquitoes seek a blood meal to nurture their eggs. Each species of Anopheles mosquito has its own preferred aquatic habitat; for example, some prefer small, shallow collections of fresh water, such as puddles and hoof prints, which are abundant during the rainy season in tropical countries.
In the life cycle of Plasmodium, a female Anopheles mosquito (the definitive host) transmits a motile infective form (called the sporozoite) to a vertebrate host such as a human (the secondary host), thus acting as a transmission vector. A sporozoite travels through the blood vessels to liver cells (hepatocytes), where it reproduces asexually (tissue schizogony), producing thousands of merozoites. These infect new red blood cells and initiate a series of asexual multiplication cycles (blood schizogony) that produce 8 to 24 new infective merozoites, at which point the cells burst and the infective cycle begins anew.
Other merozoites develop into immature gametocytes, which are the precursors of male and female gametes. When a fertilised mosquito bites an infected person, gametocytes are taken up with the blood and mature in the mosquito gut. The male and female gametocytes fuse and form an ookinete (a fertilized, motile zygote). Ookinetes develop into new sporozoites that migrate to the insect's salivary glands, ready to infect a new vertebrate host. The sporozoites are injected into the skin, in the saliva, when the mosquito takes a subsequent blood meal.
Only female mosquitoes feed on blood; male mosquitoes feed on plant nectar, and do not transmit the disease. The females of the Anopheles genus of mosquito prefer to feed at night. They usually start searching for a meal at dusk, and will continue throughout the night until taking a meal. Malaria parasites can also be transmitted by blood transfusions, although this is rare.
Transmission is more intense in places where the mosquito lifespan is longer (so that the parasite has time to complete its development inside the mosquito) and where it prefers to bite humans rather than other animals. The long lifespan and strong human-biting habit of the African vector species is the main reason why nearly 90% of the world's malaria cases are in Africa.
Transmission also depends on climatic conditions that may affect the number and survival of mosquitoes, such as rainfall patterns, temperature and humidity. In many places, transmission is seasonal, with the peak during and just after the rainy season. Malaria epidemics can occur when climate and other conditions suddenly favour transmission in areas where people have little or no immunity to malaria. They can also occur when people with low immunity move into areas with intense malaria transmission, for instance to find work, or as refugees.
Human immunity is another important factor, especially among adults in areas of moderate or intense transmission conditions. Partial immunity is developed over years of exposure, and while it never provides complete protection, it does reduce the risk that malaria infection will cause severe disease. For this reason, most malaria deaths in Africa occur in young children, whereas in areas with less transmission and low immunity, all age groups are at risk.
Vector control is the main way to prevent and reduce malaria transmission. If coverage of vector control interventions within a specific area is high enough, then a measure of protection will be conferred across the community.
WHO recommends protection for all people at risk of malaria with effective malaria vector control. Two forms of vector control – insecticide-treated mosquito nets and indoor residual spraying – are effective in a wide range of circumstances.
INSECTICIDE-TREATED MOSQUITO NETS
Long-lasting insecticidal nets (LLINs) are the preferred form of insecticide-treated mosquito nets (ITNs) for public health programmes. In most settings, WHO recommends LLIN coverage for all people at risk of malaria. The most cost-effective way to achieve this is by providing LLINs free of charge, to ensure equal access for all. In parallel, effective behaviour change communication strategies are required to ensure that all people at risk of malaria sleep under a LLIN every night, and that the net is properly maintained.
INDOOR SPRAYING WITH RESIDUAL INSECTICIDES
Indoor residual spraying (IRS) with insecticides is a powerful way to rapidly reduce malaria transmission. Its full potential is realized when at least 80% of houses in targeted areas are sprayed. Indoor spraying is effective for 3–6 months, depending on the insecticide formulation used and the type of surface on which it is sprayed. In some settings, multiple spray rounds are needed to protect the population for the entire malaria season.
Anti-malarial medicines can also be used to prevent malaria. For travellers, malaria can be prevented through chemoprophylaxis, which suppresses the blood stage of malaria infections, thereby preventing malaria disease. For pregnant women living in moderate-to-high transmission areas, WHO recommends intermittent preventive treatment with sulfadoxine-pyrimethamine, at each scheduled antenatal visit after the first trimester. Similarly, for infants living in high-transmission areas of Africa, 3 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine are recommended, delivered alongside routine vaccinations.
In 2012, WHO recommended Seasonal Malaria Chemoprevention as an additional malaria prevention strategy for areas of the Sahel sub-Region of Africa. The strategy involves the administration of monthly courses of amodiaquine plus sulfadoxine-pyrimethamine to all children under 5 years of age during the high transmission season.
Much of the success in controlling malaria is due to vector control. Vector control is highly dependent on the use of pyrethroids, which are the only class of insecticides currently recommended for ITNs or LLINs.
In recent years, mosquito resistance to pyrethroids has emerged in many countries. In some areas, resistance to all 4 classes of insecticides used for public health has been detected. Fortunately, this resistance has only rarely been associated with decreased efficacy of LLINs, which continue to provide a substantial level of protection in most settings. Rotational use of different classes of insecticides for IRS is recommended as one approach to manage insecticide resistance.
However, malaria-endemic areas of sub-Saharan Africa and India are causing significant concern due to high levels of malaria transmission and widespread reports of insecticide resistance. The use of 2 different insecticides in a mosquito net offers an opportunity to mitigate the risk of the development and spread of insecticide resistance; developing these new nets is a priority. Several promising products for both IRS and nets are in the pipeline.
Detection of insecticide resistance should be an essential component of all national malaria control efforts to ensure that the most effective vector control methods are being used. The choice of insecticide for IRS should always be informed by recent, local data on the susceptibility of target vectors.
To ensure a timely and coordinated global response to the threat of insecticide resistance, WHO worked with a wide range of stakeholders to develop the "Global Plan for Insecticide Resistance Management in Malaria Vectors (GPIRM)", which was released in May 2012.
DIAGNOSIS AND TREATMENT
Early diagnosis and treatment of malaria reduces disease and prevents deaths. It also contributes to reducing malaria transmission. The best available treatment, particularly for P. falciparum malaria, is artemisinin-based combination therapy (ACT).
WHO recommends that all cases of suspected malaria be confirmed using parasite-based diagnostic testing (either microscopy or rapid diagnostic test) before administering treatment. Results of parasitological confirmation can be available in 30 minutes or less. Treatment, solely on the basis of symptoms should only be considered when a parasitological diagnosis is not possible.
ANTI-MALARIAL DRUG RESISTANCE
Resistance to antimalarial medicines is a recurring problem. Resistance of P. falciparum to previous generations of medicines, such as chloroquine and sulfadoxine-pyrimethamine (SP), became widespread in the 1970s and 1980s, undermining malaria control efforts and reversing gains in child survival.
WHO recommends the routine monitoring of antimalarial drug resistance, and supports countries to strengthen their efforts in this important area of work.
An ACT contains both the drug artemisinin and a partner drug. In recent years, parasite resistance to artemisinins has been detected in 5 countries of the Greater Mekong sub-region: Cambodia, Lao People’s Democratic Republic, Myanmar, Thailand and Viet Nam. Studies have confirmed that artemisinin resistance has emerged independently in many areas of this sub-region. Most patients are cured when treated with an ACT if there is no resistance to the partner drug.
However, in parts of Cambodia and Thailand, P. falciparum resistance to both artemisinin and partner drugs (multi-drug resistance) has developed.
There are concerns that P. falciparum malaria in Cambodia and Thailand is becoming increasingly difficult to treat, and that multi-drug resistance could spread to other regions with dire public health consequences. Consequently, WHO’s Malaria Policy Advisory Committee in September 2014 recommended adopting the goal of eliminating P. falciparum malaria in this sub-region by 2030. WHO launched the Strategy for Malaria Elimination in the Greater Mekong Sub-region (2015–2030) at the World Health Assembly in May 2015, which was endorsed by all the countries in the sub-region.
Malaria elimination is defined as the interruption of local transmission of a specified malaria parasite in a defined geographical area as a result of deliberate efforts. Continued measures are required to prevent re-establishment of transmission.
Malaria eradication is defined as the permanent reduction to 0 of the worldwide incidence of malaria infection caused by human malaria parasites as a result of deliberate efforts. Once eradication has been achieved, intervention measures are no longer needed.
The rate of progress in a particular country will depend on the strength of its national health system, the level of investment in malaria control, and a number of other factors, including: biological determinants, the environment, and the social, demographic, political, and economic realities of a particular country.
In countries with high or moderate rates of malaria transmission, national malaria control programmes aim to maximize the reduction of malaria cases and deaths.
As countries approach elimination, enhanced surveillance systems can help ensure that every infection is detected, treated and reported to a national malaria registry. Patients diagnosed with malaria should be treated promptly with effective antimalarial medicines for their own health and to prevent onward transmission of the disease in the community.
Countries that have achieved at least 3 consecutive years of 0 local cases of malaria are eligible to apply for the WHO certification of malaria elimination. In recent years, 5 countries have been certified by the WHO Director-General as having eliminated malaria: United Arab Emirates (2007), Morocco (2010), Turkmenistan (2010), Armenia (2011) and Maldives (2015). Recently 3 other countries started the certification process: Argentina, Kyrgyzstan and Sri Lanka.
VACCINES AGAINST MALARIA
There are currently no licensed vaccines against malaria or any other human parasite. One research vaccine against P. falciparum, known as RTS, S/AS01, is most advanced. This vaccine has been evaluated in a large clinical trial in 7 countries in Africa and received a positive opinion by the European Medicines Agency in July 2015.
In October 2015, 2 WHO advisory groups recommended pilot implementations of RTS, S/AS01 in a limited number of African countries. WHO has adopted these recommendations and is strongly supportive of the need to proceed with these pilots as the next step for the world’s first malaria vaccine. These pilot projects could pave the way for wider deployment of the vaccine in 3 to 5 years, if safety and effectiveness are considered acceptable.
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