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Malaria

Health    Malaria

Malaria is a serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito which feeds on humans. People who get malaria are typically very sick with high fevers, shaking chills, and flu-like illness. Although malaria can be a deadly disease, illness and death from malaria can usually be prevented.

Biology

Human Factors and Malaria

Genetic Factors

Biologic characteristics present from birth can protect against certain types of malaria. Two genetic factors, both associated with human red blood cells, have been shown to be epidemiologically important.

Other genetic factors related to red blood cells also influence malaria, but to a lesser extent. Various genetic determinants (such as the "HLA complex," which plays a role in control of immune responses) may equally influence an individual's risk of developing severe malaria.

Acquired Immunity

Acquired immunity greatly influences how malaria affects an individual and a community. After repeated attacks of malaria a person may develop a partially protective immunity. As these antibodies decrease with time, these young children become vulnerable to disease and death by malaria.

If they survive repeated infections to an older age (2-5 years) they will have reached a protective semi-immune status. Thus in high transmission areas, young children are a major risk group and are targeted preferentially by malaria control interventions.

Mother and her newborn in Jabalpur Hospital, State of Madhya Pradesh, India. The mother had malaria, with infection of the placenta.

Pregnancy and Malaria

Pregnancy decreases immunity against many infectious diseases. Women who have developed protective immunity against P. falciparum tend to lose this protection when they become pregnant (especially during the first and second pregnancies). Malaria during pregnancy is harmful not only to the mothers but also to the unborn children.

The latter are at greater risk of being delivered prematurely or with low birth weight, with consequently decreased chances of survival during the early months of life. For this reason pregnant women are also targeted (in addition to young children) for protection by malaria control programs in endemic countries.

Behavioral Factors

Human behavior, often dictated by social and economic reasons, can influence the risk of malaria for individuals and communities. For example:

  • Poor rural populations in malaria-endemic areas often cannot afford the housing and bed nets that would protect them from exposure to mosquitoes. These persons often lack the knowledge to recognize malaria and to treat it promptly and correctly. Often, cultural beliefs result in use of traditional, ineffective methods of treatment.
  • Travelers from non-endemic areas may choose not to use insect repellent or medicines to prevent malaria. Reasons may include cost, inconvenience, or a lack of knowledge.
  • Human activities can create breeding sites for larvae (standing water in irrigation ditches, burrow pits)
  • Agricultural work such as harvesting (also influenced by climate) may force increased nighttime exposure to mosquito bites
  • Raising domestic animals near the household may provide alternate sources of blood meals for Anopheles mosquitoes and thus decrease human exposure
  • War, migrations (voluntary or forced) and tourism may expose non-immune individuals to an environment with high malaria transmission.

Human behavior in endemic countries also determines in part how successful malaria control activities will be in their efforts to decrease transmission. The governments of malaria-endemic countries often lack financial resources. As a consequence, health workers in the public sector are often underpaid and overworked. They lack equipment, drugs, training, and supervision. The local populations are aware of such situations when they occur, and cease relying on the public sector health facilities.

Conversely, the private sector suffers from its own problems. Regulatory measures often do not exist or are not enforced. This encourages private consultations by unlicensed, costly health providers, and the anarchic prescription and sale of drugs (some of which are counterfeit products). Correcting this situation is a tremendous challenge that must be addressed if malaria control and ultimately elimination is to be successful.

Disease

Infection with malaria parasites may result in a wide variety of symptoms, ranging from absent or very mild symptoms to severe disease and even death. Malaria disease can be categorized as uncomplicated or severe (complicated). In general, malaria is a curable disease if diagnosed and treated promptly and correctly.

All the clinical symptoms associated with malaria are caused by the asexual erythrocytic or blood stage parasites. When the parasite develops in the erythrocyte, numerous known and unknown waste substances such as hemozoin pigment and other toxic factors accumulate in the infected red blood cell. These are dumped into the bloodstream when the infected cells lyse and release invasive merozoites.

The hemozoin and other toxic factors such as glucose phosphate isomerase (GPI) stimulate macrophages and other cells to produce cytokines and other soluble factors which act to produce fever and rigors and probably influence other severe pathophysiology associated with malaria.

Plasmodium falciparum- infected erythrocytes, particularly those with mature trophozoites, adhere to the vascular endothelium of venular blood vessel walls and do not freely circulate in the blood. When this sequestration of infected erythrocytes occurs in the vessels of the brain it is believed to be a factor in causing the severe disease syndrome known as cerebral malaria, which is associated with high mortality.

Incubation Period

Following the infective bite by the Anopheles mosquito, a period of time (the "incubation period") goes by before the first symptoms appear. The incubation period in most cases varies from 7 to 30 days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.

Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria symptoms by weeks or months, long after the traveler has left the malaria-endemic area. (This can happen particularly with P. vivax and P. ovale, both of which can produce dormant liver stage parasites; the liver stages may reactivate and cause disease months after the infective mosquito bite.)

Such long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care provider. Returned travelers should always remind their health-care providers of any travel in areas where malaria occurs during the past 12 months.

Uncomplicated Malaria

The classical (but rarely observed) malaria attack lasts 6–10 hours. It consists of

Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).

More commonly, the patient presents with a combination of the following symptoms:

In countries where cases of malaria are infrequent, these symptoms may be attributed to influenza, a cold, or other common infections, especially if malaria is not suspected. Conversely, in countries where malaria is frequent, residents often recognize the symptoms as malaria and treat themselves without seeking diagnostic confirmation ("presumptive treatment"). Physical findings may include the following:

  • Elevated temperatures
  • Perspiration
  • Weakness
  • Enlarged spleen
  • Mild jaundice
  • Enlargement of the liver
  • Increased respiratory rate

Diagnosis of malaria depends on the demonstration of parasites in the blood, usually by microscopy. Additional laboratory findings may include mild anemia, mild decrease in blood platelets (thrombocytopenia), elevation of bilirubin, and elevation of aminotransferases.

Severe Malaria

Severe malaria occurs when infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism. The manifestations of severe malaria include the following:

  • Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities
  • Severe anemia due to hemolysis (destruction of the red blood cells)
  • Hemoglobinuria (hemoglobin in the urine) due to hemolysis
  • Acute respiratory distress syndrome (ARDS), an inflammatory reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment
  • Abnormalities in blood coagulation
  • Low blood pressure caused by cardiovascular collapse
  • Acute kidney injury
  • Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites
  • Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia
  • Hypoglycemia (low blood glucose). Hypoglycemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.

Severe malaria is a medical emergency and should be treated urgently and aggressively.

Malaria Relapses

In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites ("hypnozoites") that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.

Other Manifestations of Malaria

  • Neurologic defects may occasionally persist following cerebral malaria, especially in children. Such defects include trouble with movements (ataxia), palsies, speech difficulties, deafness, and blindness.
  • Recurrent infections with P. falciparum may result in severe anemia. This occurs especially in young children with frequent infections that are inadequately treated.
  • Malaria during pregnancy (especially P. falciparum) may cause severe disease in the mother, and may lead to premature delivery or delivery of a low-birth-weight baby.
  • On rare occasions, P. vivax malaria can cause rupture of the spleen.
  • Nephrotic syndrome (a chronic, severe kidney disease) can result from chronic or repeated infections with P. malariae.
  • Hyperreactive malarial splenomegaly (also called "tropical splenomegaly syndrome") occurs infrequently and is attributed to an abnormal immune response to repeated malarial infections. The disease is marked by a very enlarged spleen and liver, abnormal immunologic findings, anemia, and a susceptibility to other infections (such as skin or respiratory infections).

Where Malaria Occurs

Where malaria is found depends mainly on climatic factors such as temperature, humidity, and rainfall. Malaria is transmitted in tropical and subtropical areas, where

  • Anopheles mosquitoes can survive and multiply, and
  • Malaria parasites can complete their growth cycle in the mosquitoes ("extrinsic incubation period").

Temperature is particularly critical. For example, at temperatures below 20°C (68°F), Plasmodium falciparum (which causes severe malaria) cannot complete its growth cycle in the _Anopheles_mosquito, and thus cannot be transmitted.

In many malaria-endemic countries, malaria transmission does not occur in all parts of the country. Even within tropical and subtropical areas, transmission will not occur

  • At very high altitudes;
  • During colder seasons in some areas;
  • In deserts (excluding the oases); and
  • In some countries where transmission has been interrupted through successful control/elimination programs.

Generally, in warmer regions closer to the equator

  • Transmission will be more intense, and
  • Malaria is transmitted year-round.

In cooler regions, transmission will be less intense and more seasonal. There, P. vivax might be more prevalent because it is more tolerant of lower ambient temperatures.

In many temperate areas, economic development and public health measures have succeeded in eliminating malaria. However, most of these areas have Anopheles mosquitoes that can transmit malaria, and reintroduction of the disease is a constant risk.

How Can Malaria Cases and Deaths Be Reduced?

The goal of most current National Malaria Control Programs and most malaria activities is to _reduce_the number of malaria-related cases and deaths. To reduce malaria transmission to a level where it is no longer a public health problem is the goal of what is called malaria "control."

"Control" of malaria differs from "elimination" or "eradication of malaria." "Elimination" is local or regional in scope. Eradication is "global elimination." Eradication is not achieved until malaria is gone from the natural world. These terms can be defined differently for different illnesses.

Recent increases in resources, political will, and commitment have led to discussion of the possibility of malaria elimination and, ultimately, eradication.

Many reasons account for this: an efficient mosquito that transmits the infection, a high prevalence of the most deadly species of the parasite, favorable climate, weak infrastructure to address the disease, and high intervention costs that are difficult to bear in poor countries.

However, the scale-up of effective, safe, and proven prevention and control interventions made possible by global support and national commitment has shown that the impact of malaria on residents of malaria-endemic countries can be dramatically reduced when these are used together.

Malaria Treatment and Prevention Interventions

Malaria control is carried out through the following recommended malaria treatment and prevention interventions. The choice of interventions depends on the malaria transmission level in the area (e.g., in areas of low transmission level, intermittent preventive treatment for pregnant women IPTp is usually not recommended).

  • Case management (diagnosis and treatment) of patients with malaria
  • Prevention
    • Insecticide-treated nets (ITNs)
    • Intermittent preventive treatment of malaria in pregnant women (IPTp)
    • Intermittent preventive treatment of malaria in infancy (IPTi)
    • Indoor residual spraying (IRS)

In most malaria-endemic countries, four interventions—case management (diagnosis and treatment), ITNs, IPTp, and IRS—make up the essential package of malaria interventions.

Occasionally, other interventions are used:

  • Larval control and other vector control interventions
  • Mass drug administration and Mass fever treatment

In addition, several companies and groups are at work on developing a malaria vaccine, but there is currently no effective malaria vaccine on the market.

Diagnosis and Treatment of Malaria in the Malaria-Endemic World

Malaria must be diagnosed and treated promptly with a recommended antimalarial drug to keep the illness from progressing and to help prevent further spread of infection in the community.

In the malaria-endemic world, diagnosis of malaria can be difficult for several reasons:

  • Malaria's clinical symptoms are shared with other diseases and conditions, and many malaria-endemic countries lack resources, such as microscopes and rapid diagnostic tests (RDTs), to make a definitive diagnosis.
  • Health personnel in these areas are often undertrained, underequipped and underpaid.
  • Health personnel in the malaria-endemic world often face excessive patient loads, and must divide their attention between malaria and other equally severe infectious diseases such as pneumonia, diarrhea, tuberculosis, and HIV/AIDS.

Malaria may be "uncomplicated" or "severe."

  • Uncomplicated malaria: Symptoms may include fever, chills, sweats, headaches, muscle pains, nausea and vomiting.
  • Severe malaria: Symptoms may include confusion, coma, focal neurologic signs, severe anemia, and respiratory difficulties. A patient with symptoms of severe malaria should be assessed quickly and treated immediately. Severe malaria is most often caused by the most dangerous parasite, Plasmodium falciparum.

Diagnosis of Malaria

When a patient with fever is brought to a health facility in the malaria-endemic world, a health worker may suspect that the patient has malaria based on the patient's symptoms, although these symptoms are not specific to malaria.

For many years, NMCP recommended treating children under 5 years with fever for malaria, based on symptoms alone, because most health facilities did not have working microscopes, a trained microscopist, and necessary equipment (slides, stains) to perform a laboratory test. Malaria was extremely common and potentially fatal, and providing treatment based on clinical diagnosis alone could save the child's life. However, if the child had an illness other than malaria, it would go untreated.

As malaria interventions have been scaled up in sub-Saharan Africa in the last decade, rapid diagnostic tests for malaria have become available in health facilities, microscopes have been provided, and microscopists have been trained.

In 2010, the World Health Organization recommended that all suspected cases of malaria be confirmed with a diagnostic test prior to treatment. The Roll Back Malaria Partnership has set new targets of universal access to malaria diagnostic testing in public and private sectors as well as at the community level. In many countries, community health workers (CHWs) have been trained on integrated community case management of common childhood illnesses, including malaria, pneumonia, and diarrhea.

Many CHWs are being trained to use rapid diagnostic tests for febrile children and to treat them with recommended antimalarials if they are positive.

Diagnosis Based on Laboratory Methods

Microscopy and rapid diagnostic tests can be used to make a definitive diagnosis of malaria.

Microscopy

Malaria parasites can be identified by examining a drop of the patient's blood under the microscope. This drop is spread out as a "blood smear" on a microscope slide. Before the slide is examined, the blood specimen is stained (most often with the Giemsa stain) to give the parasites a distinctive appearance.

This technique is the gold standard for laboratory confirmation of malaria. However, it depends on the quality of the reagents, the quality of the microscope, and the experience of the laboratory technician.

Rapid Diagnostic Tests

Over the last fifteen years, test kits have become available that can detect antigens derived from malaria parasites in a person's blood. These immunologic ("immunochromatographic") tests are referred to as RDTs and provide results quickly—depending on the test, in about 20 minutes.

RDTs offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in many clinical settings and programs in countries where malaria is transmitted.

Treatment

The World Health Organization recommends that patients in malaria-endemic areas be treated within 24 hours after their first symptoms appear.

Treatment of a patient with malaria depends on the country's national guidelines, which typically take the following into consideration:

  • Type (species) of the infecting parasite
  • Clinical status of the patient
  • Any accompanying illness(es) or condition(s)
  • Pregnancy
  • Drug allergies, or other medications taken by the patient
  • Where the infection was acquired and the presence of antimalarial drug resistance there.

Uncomplicated Malaria

Patients who have uncomplicated malaria can be treated on an outpatient basis; however, patients with severe malaria should be hospitalized.

Most drugs recommended for treatment of uncomplicated malaria cases in the malaria-endemic world are active against the parasite forms in the blood (the form that causes disease). Listed below are some of the drugs approved by the World Health Organization and those most commonly recommended by national malaria control programs in the malaria-endemic world:

  • Artemesinin-based combination treatments, (e.g, artemether-lumefantrine, artesunate-amodiaquine)
  • Chloroquine*
  • Doxycycline
  • Mefloquine*
  • Quinine

*Two of these drugs, chloroquine and mefloquine, are no longer effective in some or many parts of the world.

Another drug, primaquine, is used as an adjunct for certain species of malaria (e.g., P. falciparum, P. vivax, and P. ovale). It is active against the dormant parasite liver forms (hypnozoites) and can prevent relapses of P. vivax and P. ovale. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD (glucose-6-phosphate dehydrogenase).

Patients should not take primaquine until a screening test has excluded G6PD deficiency or unless the risk of deficiency in the surrounding population is known to be low, because primaquine given to people with G6PD deficiency can cause hemolytic anemia. In some countries, primaquine is also used in a single dose to prevent secondary transmission of P. falciparum.

Counterfeit and substandard drugs are sold in some areas and should be avoided.

Severe Malaria

Severe malaria occurs when an infection is complicated by serious organ failure or abnormalities in the patient's blood or metabolism.

Patients who have severe P. falciparum malaria or who cannot take oral medications should be given treatment by continuous parenteral infusion in a hospital. The World Health Organization External recommends parenteral artesunate for treatment of severe P. falciparum malaria in both adults and children.

However, if artesunate is not available, parenteral artemether and quinine are acceptable alternatives for treatment of severe malaria. Some malaria-endemic countries recommend pre-referral drugs be given by suppository or injection before a severely ill patient is referred to a hospital for definitive care.

Intravenous treatment must be followed up with a complete course of oral antimalarial drugs, usually an artemisinin-based combination therapy or, when the preceding is not available, quinine plus doxycycline or quinine plus clindamycin.

Insecticide-Treated Bed Nets

Insecticide-treated bed nets (ITNs) are a form of personal protection that has been shown to reduce malaria illness, severe disease, and death due to malaria in endemic regions. In community-wide trials in several African settings, ITNs were shown to reduce the death of children under 5 years from all causes by about 20%.

How Do ITNs Work?

Bed nets form a protective barrier around people sleeping under them. However, bed nets treated with an insecticide are much more protective than untreated nets.

The insecticides that are used for treating bed nets kill mosquitoes, as well as other insects. The insecticides also repel mosquitoes, reducing the number that enter the house and attempt to feed on people inside. In addition, if high community coverage is achieved, the numbers of mosquitoes, as well as their length of life will be reduced.

When this happens, all members of the community are protected, regardless of whether or not they are using a bed net. To achieve such effects, more than half of the people in a community must use an ITN.

Net Materials and Insecticides

Nets may vary by size, shape, color, material, and/or insecticide treatment status. Most nets are made of polyester, polyethylene, or polypropylene.

Only two insecticides classes are approved for use on ITNs (pyrroles and pyrethroids). These insecticides have been shown to pose very low health risks to humans and other mammals, but are toxic to insects and kill them. Previously, nets had to be retreated every 6 to 12 months, or even more frequently if the nets were washed.

Nets were retreated by simply dipping them in a mixture of water and insecticide and allowing them to dry in a shady place. The need for frequent retreatment was a major barrier to widespread use of ITNs in endemic countries. In addition, the additional cost of the insecticide and the lack of understanding its importance resulted in very low retreatment rates in most countries.

Recent studies have suggested that the rise of pyrethroid resistance may undermine the effectiveness of nets. To help manage resistance, some net products incorporate piperonyl butoxide (PBO) along with a pyrethroid insecticide, but there is not yet evidence that this significantly improves ITN effectiveness in areas with high levels of pyrethroid resistance, and WHO currently does not consider nets that incorporate PBO to be tools for managing pyrethroid resistance.

Intermittent Preventive Treatment of Malaria for Pregnant Women (IPTp)

Why Pregnant Women Are Especially at Risk

Adults who have survived repeated malaria infections throughout their lifetimes may become partially immune to severe or fatal malaria. However, because of the changes in women's immune systems during pregnancy and the presence of a new organ (the placenta) with new places for parasites to bind, pregnant women lose some of their immunity to malaria infection.

Malaria infection during pregnancy can have adverse effects on both mother and fetus, including maternal anemia, fetal loss, premature delivery, intrauterine growth retardation, and delivery of low birth-weight infants (<2500 g or <5.5 pounds), a risk factor for death.

It is a particular problem for women in their first and second pregnancies and for women who are HIV-positive.

Adverse Effects Vary by Transmission Level

The problems that malaria infection causes differ somewhat by the type of malaria transmission area: stable (high) or unstable (low) transmission.

  • In high transmission areas, women have developed immunity that generally prevents severe disease, however, parasite specifically target the placenta, leading in an increased risk during pregnancy gained a level of immunity to malaria that wanes somewhat during pregnancy. Malaria infection is more likely to contribute to maternal anemia and delivery of low birth-weight infants (<2500 g or <5.5 pounds). It is a particular problem for women in their first and second pregnancies, for younger women, and for women who are HIV-positive.
  • In low transmission areas, women generally have developed no immunity to malaria. Malaria infection is more likely to result in severe malaria disease, maternal anemia, premature delivery, or fetal loss.

Recommended Interventions

The currently recommended interventions for pregnant women are

  • Use of insecticide-treated bed nets
  • Intermittent preventive treatment (IPTp) (for HIV negative women in high transmission areas).
  • Effective case management (diagnosis and treatment of illness)

Women should also receive iron/folate supplementation to protect them against anemia, a common occurrence among all pregnant women.

IPTp

IPTp entails administration of a curative dose of an effective antimalarial drug (currently sulfadoxine-pyrimethamine) to all pregnant women without testing whether or not they are infected with the malaria parasite. IPTp should be given at each routine antenatal care visit, starting as early as possible in the second trimester.

Pregnant women are routinely given folic acid supplementation to prevent neural tube defects in their infants. However, high doses of folic acid counteract the effect of sulfadoxine-pyrimethamine.

Therefore, it is preferred that women take only the recommended 0.4 mg daily dose of folic acid. In some countries, 5 mg of folic acid are used, and in those countries, it is recommended to withhold folic acid supplementation for two weeks after taking IPTp with sulfadoxine-pyrimethamine to ensure optimal efficacy.

Indoor Residual Spraying

Many malaria vectors are considered "endophilic"; that is, the mosquito vectors rest inside houses after taking a blood meal. These mosquitoes are particularly susceptible to control through indoor residual spraying (IRS).

What Is Indoor Residual Spraying?

As its name implies, IRS involves coating the walls and other surfaces of a house with a residual insecticide. For several months, the insecticide will kill mosquitoes and other insects that come in contact with these surfaces. IRS does not directly prevent people from being bitten by mosquitoes.

Rather, it usually kills mosquitoes after they have fed if they come to rest on the sprayed surface. IRS thus prevents transmission of infection to other persons. To be effective, IRS must be applied to a very high proportion of households in an area (usually >80%).

History of IRS

IRS with DDT was the primary malaria control method used during the Global Malaria Eradication Campaign (1955-1969). The campaign did not achieve its stated objective but it did eliminate malaria from several areas and sharply reduced the burden of malaria disease in others.

Concern over the environmental impact of DDT led to the introduction of other, more expensive insecticides. As the eradication campaign wore on, the responsibility for maintaining it was shifted to endemic countries that were not able to shoulder the financial burden. The campaign collapsed and in many areas, malaria soon returned to pre-campaign levels.

As a result of the cost of IRS, the negative publicity due to the failure of the Malaria Eradication Campaign, and environmental concerns about residual insecticides, IRS programs were largely disbanded other than in a few countries with resources to continue them. However, the recent success of IRS in reducing malaria cases in South Africa by more than 80% has revived interest in this malaria prevention tool.

Larval Control and Other Vector Control Interventions

Larval Control

Interventions targeting the larval stages of the mosquito have been used effectively for decades, but their effectiveness varies widely from species to species. In general, if habitats are large and amenable to environmental modification, the intervention is effective, but if habitats are small, widely dispersed, and transient the intervention is less effective.

Anopheles gambiae, one of the primary vectors of malaria in Africa, breeds in numerous small pools of water that form due to rainfall. The larvae develop within a few days, escaping their aquatic environment before it dries out. It is difficult, if not impossible, to predict when and where the breeding sites will form, and to find and treat them before the adults emerge.

Therefore, larval mosquito control for the prevention of malaria in Africa has not been attempted on a large scale. It may, however, be appropriate for specific settings such as urban environments or desert fringe areas where habitats are more stable and predictable. In contrast, in Southeast Asia, Europe and the Americas, larval control has proven extremely effective.

Larval control may be implemented through environmental modification – draining and filling – or through use of larvacides. Though biological control using fish is often used, evidence for its effectiveness is limited.

Source Reduction

Source reduction is removal or permanent destruction of mosquito breeding sites. The larval habitats may be destroyed by filling depressions that collect water, by draining swamps or by ditching marshy areas to remove standing water. Mosquitoes that breed in irrigation water can be controlled through careful water management.

Chemical Larviciding

For some mosquito species, habitat elimination is not possible. For these species, chemical insecticides can be applied directly to the larval habitats. Other methods, which are less disruptive to the environment, are usually preferred:

  • Oils may be applied to the water surface, suffocating the larvae and pupae. Most oils in use today are rapidly biodegraded.
  • Toxins from the bacterium Bacillus thuringiensis var. israelensis (Bti) can be applied in the same way as chemical insecticides. They are very specific, affecting only mosquitoes, black flies, and midges.
  • Insect growth regulators such as methroprene are specific to mosquitoes and can be applied in the same way as chemical insecticides.

Biological Control

Potential biological control agents, such as fungi (e.g., Laegenidium giganteum) or mermithid nematodes (e.g., Romanomermis culicivorax), parasitize and kill larval mosquitoes but they are not efficient for mosquito control and are not widely used. Likewise, mosquito fish (including Gambusia affinis) have largely been ineffective.

Other Vector Control Interventions

Fogging or Area Spraying

Fogging or ultra-low volume spraying or area spraying is primarily reserved for emergency situations such as epidemics. Fogging has not been shown to be effective in any malaria-endemic areas. Fogging and area sprays must be properly timed to coincide with the time of peak adult mosquito activity, because resting mosquitoes are often found in areas that are difficult for the insecticide to reach (e.g., under leaves, in small crevices).

In addition, fogging and area spraying will have to be repeatedly applied to have an impact, and it can easily become too costly to maintain.

Personal Protection Measures

Personal protection measures include the use of window screens, ITNs, and repellents (such as DEET) and wearing of light-colored clothes, long pants, and long-sleeved shirts. Well-constructed houses with window screens are effective for preventing biting by mosquitoes that bite indoors and may have contributed to the elimination of malaria.

Recent evidence suggests that repellents may be effective in reducing malaria transmission and may be appropriate for areas where mosquitoes bite outdoors or early in the evening when people are not using ITNs.

However, while repellents are recommended for travelers to malaria-endemic areas, further work to develop repellent formulations that are easily deployed in endemic countries is needed.

Sterile Male Release

Introducing sterile male mosuitoes into an area has been successfully applied in several small-scale areas. However, the need for large numbers of mosquitoes for release makes this approach impractical for most areas.

Genetic Modification of Malaria Vectors

Genetic modification aims to develop mosquitoes that are not susceptible to the parasite. This approach is still years from application in field settings, though there have been remarkable advances in recent years in technology to allow direct modification of the mosquito genome.

Use of Antimalarials to Reduce Malaria Transmission

A number of strategies use antimalarial drugs to reduce transmission by clearing the affected population of malaria parasites. The best known of these is mass drug administration (MDA).

MDA has been implemented in the past as part of attempts to eliminate malaria from an area and to respond to malaria epidemics caused by P. falciparum, the most lethal of the malaria parasites, and P. vivax. MDA and related strategies that deploy antimalarials to reduce malaria transmission are described below.

Mass Drug Administration

(MDA) is the administration of antimalarial treatment to every member of a defined population or every person living in a defined geographical area (except those for whom the medicine in contraindicated) at approximately the same time and often at repeated intervals.

The World Health Organization currently recommends MDA for malaria in the following settings:

  • Use of MDA to interrupt transmission of falciparum malaria can be considered in endemic island communities and in low-endemic non-island settings approaching elimination, where there is minimal risk of re-introduction of infection, good access to treatment, and implementation of vector control and surveillance.
  • In view of the growing threat of multidrug resistance and the need to use extreme measures, MDA can be considered as a component of malaria elimination efforts in the Greater Mekong subregion, in areas with good access to treatment, vector control and good surveillance.
  • Use of MDA to rapidly reduce malaria morbidity and mortality can be considered for epidemic control as part of the immediate response, while other interventions are put in place.
  • Use of MDA to reduce malaria morbidity and mortality can be considered during exceptional circumstances, where the health system is overwhelmed and unable to serve the affected communities.

WHO concluded in 2016 that there is insufficient evidence to provide guidance on use of MDA in settings with moderate or high transmission.

Variations of MDA:

  • Targeted mass drug administration (TMDA) is MDA implemented over a smaller high-risk area, such as a house, village, or hot spot.
  • Intermittent preventive treatment (IPT), which is endorsed by WHO, is administration of a curative dose of an antimalarial drug to the entire population of asymptomatic individuals at discrete periods of time (frequently more than once). Various forms of IPT exist to address specific populations:
    • Pregnant women (IPTp)
    • Infants (IPTi)
    • Children (IPTc – also referred to as seasonal malaria chemoprevention SMC)
    • Schoolchildren (IPTsc)

Mass Screening and Treatment

MSAT refers to screening all people in a population with an appropriate malaria diagnostic test and providing treatment to those with a positive test result. This intervention is based on the assumption that most of the people who can serve to infect mosquitoes will have high enough levels of parasites or antigen in their blood to be detected at the time of screening.

Focal screen and treat (FSaT) is a variation of an MSaT performed in a smaller geographic area, such as a household, village, or hot spot. WHO does not currently recommend MSAT and FSAT as suitable interventions to reduce malaria transmission using current diagnostic tests.

Mass Fever Treatment

MFT like MDA, refers to the treatment of malaria with a curative dose of an antimalarial drug within a well-defined population without testing, but unlike MDA, only persons with a fever are treated.

MFT is a rapid measure that can be considered as part of an outbreak response. The criteria for choosing an antimalarial drug for MFT are the same as for the national policy for treating uncomplicated malaria (most likely an artemisinin-based combination therapy ACT). WHO states that mass treatment of fever cases with an ACT is appropriate as a strategy to reduce mortality once malaria has been established as the cause of the epidemic.

This strategy aims to get treatment to people with probable malaria cases as quickly as possible to cure illness, avert death, and help contain the epidemic. After the outbreak response is more fully implemented in the community, laboratory confirmation of malaria parasites will precede treatment.

Vaccines

Although progress has been made in the last 10 years toward developing malaria vaccines, there is currently no licensed malaria vaccine on the market.

Barriers to Developing a Malaria Vaccine

The development of a malaria vaccine has faced several obstacles: the lack of a traditional market, few developers, and the technical complexity of developing any vaccine against a parasite.

Malaria parasites have a complex life cycle, and there is poor understanding of the complex immune response to malaria infection. Malaria parasites are also genetically complex, producing thousands of potential antigens. Unlike the diseases for which we currently have effective vaccines, exposure to malaria parasites does not confer lifelong protection. Acquired immunity only partially protects against future disease, and malaria infection can persist for months without symptoms of disease.

Diagnosis (Microscopy)

Microscopic examination remains the gold standard for laboratory confirmation of malaria in the malaria-endemic world.

Technique

A blood specimen collected from the patient is spread as a thick or thin blood smear, stained with a Romanovsky stain (most often Giemsa), and examined with a 100X oil immersion objective. Visual criteria are used to detect malaria parasites and to differentiate (when possible) the various species and life cycle stages.

Advantages and Disadvantages

Advantages

Microscopy is an established, relatively simple technique that is familiar to most laboratorians in endemic countries. In such areas, microscopy is a standard technique used for diagnosing other diseases (such as tuberculosis), often by the same laboratorians using the same facilities and equipment. Blood slide microscopy makes it possible to count the number of parasites and is more useful than rapid diagnostic tests for monitoring the effectiveness of malaria treatment.

Disadvantages

Microscopy requires a level of skill often not available in many health facilities in several malaria-endemic countries, especially in remote rural areas, where most malaria transmission occurs. In addition, lack of functional microscopes or electricity to run them, lack of or sub-standard reagents such as stains, and high workloads may affect the quality of results.

Rapid Diagnostic Tests: How They Work

Rapid diagnostic tests (RDTs) most often use a dipstick or cassette format, and provide results in about 20 minutes. A blood specimen collected from the patient is applied to the sample pad on the test card along with certain reagents. Currently approved RDTs for use in the malaria-endemic world can detect 2 types of malaria antigens; one is specific for P. falciparum and the other is found in all 4 human species of malaria.

After 15 to 20 minutes (depending on the test), the presence of specific bands in the test card window indicates whether the patient is infected with P. falciparum or one of the other 3 species of human malaria.

RDTs' Importance in Diagnosis and Treatment in the Malaria-Endemic World

Rapid diagnostic tests (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available—or is not available right away. This is the case in most of the malaria-endemic world.

Malaria RDTs are being widely used in malaria-endemic countries, but the use of an RDT does not completely eliminate the need for malaria microscopy.

Because RDTs may not be able to detect some infections with lower numbers of malaria parasites in the patient's blood and the less common species of malaria, P. ovale and P. malariae, in the malaria-endemic world,

  • Patients with negative RDT results can be followed up by microscopy where available to confirm the result.
  • Patients with positive RDT results who are not responding to initial antimalarial treatment should be evaluated for other causes of their symptoms to determine whether the treatment was appropriate and to examine parasites in the blood by microscopy to determine the possibility of drug resistance.

Other Considerations

Test Performance and Cost

For RDTs to be optimally useful, the tests must perform well. At this time, product testing has shown that some tests on the market perform much better than others. In addition, care must be taken during transport and storage of RDTs. High temperatures and high humidity in particular can contribute to poor performance.

The tests must also be affordable to national malaria programs. The costs of the tests have fallen in the last few years; even so, many malaria control programs find that procuring the large numbers of test kits needed to ensure universal diagnosis is a considerable expense.

Health-Worker Training

New methodologies require training. Health-care workers need training both in the new test methodology, as well as in using the results to treat patients. Available resources can limit the amount and quality of training available under real-world conditions.

Drug Resistance in the Malaria-Endemic World

The development of resistance to drugs poses one of the greatest threats to malaria control and results in increased malaria morbidity and mortality. Resistance to currently available antimalarial drugs has been confirmed in only two of the four human malaria parasite species, Plasmodium falciparum and P. vivax. It is unknown if P. malariae or P. ovale has developed resistance to any antimalarial drugs.

Counterfeit and Substandard Antimalarial Drugs

What are counterfeit and substandard antimalarial drugs, and why are they important to public health?

Counterfeit (fake) and substandard antimalarial drugs may contain no active ingredients, less than the required amount of active ingredients, or ingredients not described on the package label. Manufacturers of counterfeit drugs tend to copy more expensive brands of drugs and make them look like brand-name drugs.

They may also repackage expired products and substitute a later expiration date, or they may package another drug or alternative substance as if it were an active product. Substandard drugs are made by manufacturers trying to avoid costly quality control and good manufacturing practices; these can result from deliberate or unintended lapses in the manufacturing process.

These medicines may have too little or too much of the active ingredients and may not be absorbed properly by the body. If they are taken to treat an illness like malaria, they may be incompletely effective or altogether useless. A counterfeit or substandard treatment can prolong illness and increase the risk of severe disease or death. If substandard medicines are widely used, they can also select for drug-resistant parasites.

Where can they be found?

They can be found anywhere, but they are especially prevalent in developing countries lacking effective drug regulatory agencies as well as resources required to effectively evaluate drug quality or enforce drug quality regulations.

What types of antimalarial drug quality issues can be found?

  • Drugs with too little, too much, or absolutely no active ingredient, due to intentional fraud or poor manufacturing and quality control practice.
  • A tablet's inability to release drug, due to poor formulation techniques.
  • Chemical breakdown of drugs caused by storage conditions, especially in warm, humid climates.
  • Contamination with other substances due to poor manufacturing procedures.
  • Incomplete, inaccurate or misleading packaging and labeling.

How can I avoid buying counterfeit or substandard antimalarial drugs to prevent malaria when I travel to an area with malaria transmission?

  • Buy the antimalarial drugs you need in your home country and keep the original packaging.
  • Write down the drug's generic and brand names as well as the name of the manufacturer so in case you run out, you can look for the correct product.
  • If you need to purchase medicine in the country you are visiting, inspect and compare the packaging of the medicine available for sale in that country with the original. Many times poor quality printing or paper indicates a counterfeited product.
  • Be suspicious of tablets that have a peculiar odor, taste, or color, or ones that are extremely brittle. Ill-defined imprints on the tablet may indicate a counterfeit.

The quality of commercially available drugs varies greatly in malaria-endemic countries:

  • The amount of the active ingredient can vary due to lack of regulations and poor quality control practices.
  • Some pills may release very little if any drug due to poor formulation techniques.
  • Chemical break-down of some drugs can occur due to poor storage conditions, especially in warm and humid tropical climates.
  • Some drugs may be contaminated with other substances.
  • Counterfeiters may also obtain expired drugs and repackage them with false or missing expiration dates.

Determine if malaria transmission occurs at the destinations

Obtain a detailed itinerary including all possible destinations that may be encountered during the trip and check to see if malaria transmission occurs in these locations. The Malaria Information by Country Table provides detailed information about the specific parts of countries where malaria transmission does or does not occur. It also provides additional information including the species of malaria that occur there and the presence of drug resistance.

Conduct an individualized risk assessment

Prevention of malaria involves a balance between ensuring that all people who will be at risk of infection use the appropriate prevention measures, while preventing adverse effects of those interventions among people using them unnecessarily.

An individual risk assessment should be conducted for every traveler, taking into account not only the destination country, but also the detailed itinerary, including specific cities, types of accommodation, season, and style of travel. In addition, conditions such as pregnancy or the presence of antimalarial drug resistance at the destination may modify the risk assessment.

Choose the most appropriate malaria prevention measures

Based on the risk assessment, specific malaria prevention interventions should be used by the traveler. Often this includes avoiding mosquito bites through the use of repellents or insecticide treated bed nets, and specific medicines to prevent malaria.

The Drugs for Malaria Prevention table provides prescription dosing information for both adults and children.

In some countries (including those with malaria risk), drugs may be sold that are counterfeit ("fake") or substandard. Such drugs may not be effective. Antimalarial drugs should always be purchased before traveling overseas!

Know the symptoms of malaria

The interventions used to prevent malaria can be very effective when used properly, but none of them are 100% effective.

If symptoms of malaria occur, the traveler should seek immediate medical attention.

Malaria is always a serious disease and may be a deadly illness. Travelers who become ill with a fever or flu-like illness either while traveling in a malaria-risk area or after returning home (for up to 1 year) should seek immediate medical attention and should tell the physician their travel history.

Travelers who are assessed at being at high risk of developing malaria while traveling should consider carrying a full treatment course of malaria medicines with them. Providing this reliable supply of medicine (formerly referred to as standby or emergency self-treatment) will ensure that travelers have immediate access to an appropriate and high quality medicine if they are diagnosed with malaria while abroad.

Depending on the medicine they are using for prevention, this could either be atovaquone/proguanil or artemether/lumefantrine.

Be aware of blood donation eligibility

Travelers are often surprised to learn that even if they adhered to all of the prevention advice and did not become sick with malaria, recent travel to a place where malaria transmission occurs is an exclusion criterion for blood donation.

Malaria Diagnosis

Clinical Diagnosis

Clinical diagnosis is based on the patient's symptoms and on physical findings at examination.

The first symptoms of malaria (most often fever, chills, sweats, headaches, muscle pains, nausea and vomiting) are often not specific and are also found in other diseases (such as the "flu" and common viral infections). Likewise, the physical findings are often not specific (elevated temperature, perspiration, tiredness).

In severe malaria (primarily caused by Plasmodium falciparum), clinical findings (confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties) are more striking and may increase the index of suspicion for malaria.

Clinical findings should always be confirmed by a laboratory test for malaria.

In addition to ordering the malaria specific diagnostic tests described below, the health-care provider should conduct an initial workup and request a complete blood count and a routine chemistry panel.

In the event that the person does have a positive malaria test, these additional tests will be useful in determining whether the patient has uncomplicated or severe manifestations of the malaria infection. Specifically, these tests can detect severe anemia, hypoglycemia, renal failure, hyperbilirubinemia, and acid-base disturbances.

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