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Malaria mə-ˈler-ē-ə

By Richard D. Pearson, MD, Emeritus Professor of Medicine, University of Virginia School of Medicine

Malaria is infection of red blood cells with one of five species of Plasmodium, a protozoan. Malaria causes fever, chills, sweating, an enlarged spleen, and anemia (due to the breakdown of infected red blood cells).

  • Usually, malaria is spread through the bite of an infected female mosquito.

  • People have a shaking chill, followed by a fever, and may have a headache, body aches, and nausea and feel tired.

  • One type of malaria causes serious symptoms, such as delirium, confusion, seizures, coma, severe breathing problems, kidney failure, and sometimes death.

  • Doctors diagnose the infection by identifying the protozoa in a sample of blood.

  • Eliminating mosquito breeding areas, killing larvae in standing water, preventing mosquito bites, and taking preventive drugs before traveling to affected areas can help.

  • Various antimalarial drugs are used to treat and to prevent infection (which drug is used depends on the malaria species causing the infection, the likelihood of drug resistance in the area where the infection was acquired, and the drug's side effects and cost).

Malaria is a protozoan infection that is spread by the bite of an infected female mosquito. Very rarely, the disease is transmitted from an infected mother to her fetus, through transfusion of contaminated blood, through transplantation of a contaminated organ, or through injection with a needle previously used by a person with malaria.

Although drugs and insecticides have made malaria rare in the United States and in most developed countries, the disease remains common and deadly in other areas. Worldwide, about 300 to 500 million people are infected with malaria, and about 655,000 deaths occur each year. Most of these deaths occur in children who are younger than 5 years and live in Africa. In the United States and other developed countries, malaria may occur in immigrants, visitors from the tropics, or North American travelers returning from tropical areas.

The cycle of malarial infection begins when a female mosquito bites a person with malaria. The mosquito ingests blood that contains reproductive cells of the parasite. Once inside the mosquito, the parasite reproduces, develops, and migrates to the mosquito’s salivary gland. When the mosquito bites another person, parasites are injected along with the mosquito’s saliva. Inside the newly infected person, the parasites move to the liver and multiply again. They typically mature over an average of 1 to 3 weeks, then leave the liver and invade the person’s red blood cells. The parasites multiply yet again inside the red blood cells, eventually causing the infected cells to rupture, releasing parasites to invade other red blood cells.

Did You Know...

  • About 300 to 500 million people throughout the world are infected with malaria, and each year, 655,000 people die.

  • Symptoms of malaria sometimes do not appear until years after the initial infection.

Types of malaria

Five species of malaria parasites infect people:

  • Plasmodium falciparum

  • Plasmodium vivax

  • Plasmodium ovale

  • Plasmodium malariae

  • Plasmodium knowlesi

Plasmodium vivax and Plasmodium ovale can remain in the liver in a dormant form that periodically releases mature parasites into the bloodstream, causing recurring attacks of symptoms. The dormant form is not killed by many antimalarial drugs.

Plasmodium falciparum and Plasmodium malariae do not persist in the liver. However, mature forms of Plasmodium malariae can persist in the bloodstream for months or even years before they cause symptoms.

Symptoms and Complications of Malaria

After infection occurs, malaria symptoms usually appear within a few weeks to several months, but they may not occur until years later.

The initial symptoms of all forms of malaria are similar. As the infected red blood cells rupture and release parasites, a person typically develops a shaking chill followed by a fever that can exceed 104° F (40° C). Fatigue and vague discomfort (malaise), headache, body aches, and nausea are common. The fever typically falls after several hours, and heavy sweating and extreme fatigue follow. Fevers occur unpredictably at first, but with time, they may become periodic. Fevers occur at 48-hour intervals with Plasmodium vivax and Plasmodium ovale and at 72-hour intervals with Plasmodium malariae. The fevers caused by Plasmodium falciparum are often not periodic, but sometimes occur at 48-hour intervals.

As the infection progresses, the spleen enlarges, and anemia may become severe. Jaundice may develop.

Falciparum malaria

This infection, caused by Plasmodium falciparum, is the most dangerous form of malaria and can be fatal. In falciparum malaria, infected red blood cells stick to the walls of small blood vessels and clog them, damaging many organs—particularly the brain (cerebral malaria), lungs, kidneys, and gastrointestinal tract.

In falciparum malaria, fluid can accumulate in the lungs and cause severe breathing problems. Damage to internal organs can cause blood pressure to fall. Other symptoms of falciparum malaria include diarrhea, jaundice, and kidney failure. The level of sugar (glucose) in the blood can fall. The level may become life-threateningly low in people who have a large number of parasites in their blood, particularly if they are treated with quinine.

Cerebral malaria is a particularly dangerous complication that can cause a high fever, headache, drowsiness, delirium, confusion, seizures, and coma. It most commonly occurs in infants, young children, pregnant women, and people who have never been exposed to malaria and who travel to high-risk areas.

Blackwater fever is an uncommon complication of falciparum malaria. It is caused by the rupture of large numbers of red blood cells, which releases blood pigment (hemoglobin) into the bloodstream. The released hemoglobin is excreted in the urine, which turns the urine dark. Kidney damage may be severe enough to require dialysis. Blackwater fever is more likely to develop in people who have taken quinine for treatment.

Diagnosis of Malaria

  • A blood test and/or examination of a blood sample under a microscope

A doctor suspects malaria when a person develops fever and other characteristic symptoms during or after travel to an area where malaria is present. Periodic fever develops in fewer than half of American travelers with malaria but, when present, suggests the diagnosis of malaria.

Identification of parasites by a blood test that provides results rapidly and/or by microscopic examination of a blood sample confirms the diagnosis of malaria. When diagnosis is based on microscopic examination, more than one sample may be needed to find the parasites. Laboratories try to identify the species of Plasmodium found in the sample because the treatment, complications, and prognosis vary depending on the species involved.

Plasmodium falciparum infection is an emergency and requires immediate evaluation and treatment.

Prevention of Malaria

Mosquito control measures, which include eliminating breeding areas and killing larvae in the standing water where they live, are very important.

Also, people who live in or travel to areas where malaria is prevalent can take precautions to limit mosquito exposure:

  • Using insecticide (permethrin or pyrethrum) sprays in homes and outbuildings

  • Placing screens on doors and windows

  • Using permethrin-impregnated mosquito netting over beds

  • Applying mosquito repellents containing DEET (diethyltoluamide) on exposed areas of the skin

  • Wearing long pants and long-sleeved shirts, particularly between dusk and dawn, to protect against mosquito bites

  • If mosquito exposure is likely to be long or involve many mosquitoes, spraying permethrin on clothing before it is worn

Drugs to prevent malaria

Drugs should be taken to prevent malaria during travel in areas where it is prevalent. The preventive drug is started before travel begins, continued throughout the stay, and extended for a time (which varies for each drug) after the person leaves the high-risk area. Preventive drugs reduce but do not eliminate the risk of malaria. Several drugs can be used to prevent (and treat) malaria.

Drug resistance is a serious problem, particularly with the dangerous Plasmodium falciparum. The prevalence of drug-resistant strains varies in different parts of the world. Thus for prevention, the choice of drug varies by geographic location. Information about travel to specific sites is available from the Centers for Disease Control and Prevention (CDC: Malaria and Travelers).

The drugs used most frequently for preventing malaria are

  • Doxycycline (an antibiotic)

  • The combination of atovaquone and proguanil

Both treatments are effective for preventing malaria.

Doxycycline is taken daily starting 2 to 3 days before a trip. People continue to take the drug while they remain in an area where malaria is known to occur and for 4 weeks after they leave the area. It is usually tolerated well but has side effects. It is not given to women who are pregnant or breastfeeding or to children under 8 years old. It does not prevent recurring attacks of symptoms caused by Plasmodium vivax or Plasmodium ovale.

Atovaquone-proguanil, given in one tablet, is taken daily starting 2 to 3 days before a trip. People continue to take the drug while they remain in an area where malaria is known to occur and for 7 days after they leave. It is the best-tolerated drug, but it can have side effects. It is not given to women who are pregnant or breastfeeding. It does not prevent recurring attacks of symptoms caused by Plasmodium vivax or Plasmodium ovale.

Chloroquine, taken once a week, is used to prevent malaria in the few parts of the world where Plasmodium species have not developed resistance to it. Chloroquine is the only preventive drug that can safely be taken by pregnant women. Thus, doctors advise pregnant women not to travel to areas where Plasmodium species are resistant to this drug.

Mefloquine, taken once a week, is effective for prevention in many areas, but it is rarely used because it may have severe psychiatric side effects. It is ineffective or less effective for prevention of Plasmodium falciparum in some areas of Southeast Asia and occasionally elsewhere.

Primaquine is another alternative for prevention, primarily for people traveling to areas where malaria is mainly due to Plasmodium vivax. However, before people start the drug, they need to have their blood tested for a relatively common enzyme deficiency called glucose-6-phosphate dehydrogenase (G6PD) deficiency. People with this deficiency should not take primaquine because the drug may cause their red blood cells to break down. Primaquine is also used to prevent recurring attacks of symptoms in travelers who are taking other antimalarial drugs (such as doxycycline or atovaquone-proguanil) and who have had heavy exposure to Plasmodium vivax or Plasmodium ovale. Primaquine is not effective in some people because they have certain genetic variations.

Vaccines for preventing malaria are still in the experimental stage.

Treatment of Malaria

  • Drugs to treat malaria

After beginning treatment of malaria, most people improve within 24 to 48 hours, but with malaria due to Plasmodium falciparum, fever can persist for 5 days.

For treatment of acute malaria, the choice of drug is based on

  • The infecting species of Plasmodium

  • The likelihood that the parasite is resistant

Whether the parasite is likely to be resistant varies with

  • The Plasmodium species

  • The geographic location where people were infected

Chloroquine was once widely used to treat malaria, but resistance is now widespread among Plasmodium falciparum and, in some areas, among Plasmodium vivax. When the species of Plasmodium or the likelihood of chloroquine resistance is uncertain, people are treated as if they have chloroquine-resistant malaria.

Malaria due to Plasmodium falciparum

Commonly used treatments that are taken by mouth include

  • Artemether-lumefantrine

  • Atovaquone-proguanil for malaria without complications

Drugs that were developed from artemisinin (such as artemether and artesunate)are now used throughout the world to treat Plasmodium falciparum malaria. Artemisinin is derived from a Chinese medicinal herbal called qinghaosu, which comes from the sweet wormwood plant. Some artemisinin drugs are given by mouth, and others are given by injection or suppository. None stays in the body long enough to be used for prevention of malaria. However, these drugs are useful for treatment because they act more rapidly than other antimalarial drugs and are generally well-tolerated. They are given with a second drug to prevent development of drug resistance. One such drug combination is artemether and lumefantrine (given in one tablet). This combination is used all over the world and is available in the United States.

When there are no complications, malaria due to Plasmodium falciparum may be treated with the combination of atovaquone and proguanil.

Quinine plus either the antibiotic doxycycline or sometimes clindamycin was once widely used, but artemether-lumefantrine or atovaquone-proguanil has fewer side effects. These drug combinations have largely replaced treatments that involve quinine.

Mefloquine given in higher doses than those recommended for prevention is an alternative, but it is not used unless other options are unavailable because it may have severe psychiatric side effects. Also, resistance is well-documented in Southeast Asia and some other areas.

If people have severe malaria due to Plasmodium falciparum or cannot take drugs by mouth, quinidine plus either doxycycline or clindamycin may be given intravenously. People treated with quinidine must be monitored in an intensive care unit because when given intravenously, quinidine can cause low blood pressure and abnormal heart rhythms. An intravenous form of artesunate (available from the CDC) acts more rapidly and is better-tolerated than quinidine. When people given artesunate intravenously, they are also given atovaquone-proguanil or doxycycline, unless they are pregnant. If they are pregnant, they are given clindamycin instead. After people improve, they are switched to drugs taken by mouth.

Malaria due to Plasmodium vivax

Chloroquine remains the treatment of choice, except in a few areas where the parasites are known to be resistant to chloroquine. In these areas, people are usually given artemether-lumefantrine or atovaquone-proguanil.

Primaquine is given at the end of treatment to prevent recurring attacks of symptoms. Primaquine kills persistent parasites in the liver. Before primaquine is started, a blood test is done to check for G6PD deficiency. In people with this deficiency, primaquine may cause red blood cells to break down.

Malaria due to other species

Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi are susceptible to chloroquine. The drugs and drug combinations used to treat malaria due to Plasmodium falciparum that is resistant to chloroquine are also effective in treating malaria due to these species.

After treatment of malaria due to Plasmodium ovale, primaquine is given to prevent recurring attacks of symptoms, as for malaria due to Plasmodium vivax.

Treatment when medical care is unavailable

Travelers who develop a fever while in areas where malaria is prevalent should be examined by a doctor immediately. Some doctors advise travelers to remote, high-risk areas to take along a full course of the appropriate drugs for treatment. These drugs are to be used if a doctor confirms that a traveler has malaria and the appropriate drugs are not available in the area. This strategy also avoids depleting limited drug resources in the destination country.

If medical care is not available, self-treatment for presumed malaria with artemether-lumefantrine or atovaquone-proguanil is sometimes recommended until medical evaluation is possible. This approach should be discussed with a doctor before traveling.

Side effects of drugs used to treat malaria

Artemisinin drugs (such as artemether and artesunate) sometimes have side effects, which include headache, loss of appetite, dizziness, and weakness. When the combination of artemether-lumefantrine is used, lumefantrine can interact with other drugs, sometimes causing an abnormal heart rhythm. So people should make sure their doctor knows all the drugs they are taking so that drug-drug interactions can be avoided.

Atovaquone-proguanil is the best tolerated of the drugs used to prevent and treat malaria, but it occasionally causes a rash or intestinal symptoms. It is not given to women who are pregnant or breastfeeding.

Chloroquine is relatively safe for adults, children, and pregnant women. It has a bitter taste and can cause intestinal symptoms, such as abdominal pain, loss of appetite, nausea, and diarrhea. The drug must be kept away from children because overdoses can be fatal.

Doxycycline can cause intestinal symptoms, vaginal yeast infections in women, and sensitivity to sunlight, resulting in a sunburn-like reaction in a small percentage of people. People should take it with a full glass of liquid and should not lie down for several hours to ensure that the drug reaches the stomach. If the drug does not reach the stomach, it can cause irritation of the esophagus and cause severe chest pain. Because doxycycline can permanently stain the teeth of young children and fetuses, it should not be given to children younger than 8 years old or taken by pregnant women.

Mefloquine causes vivid dreams and insomnia. It can also have severe psychologic side effects. It can cause seizures in people with a seizure disorder and affect the heart in people taking certain drugs for heart disorders. Thus, mefloquine is avoided in people who are known to have a seizure disorder or psychiatric problems or who take certain drugs for heart disorders. People who are taking the drug are given written information about the side effects.

Quinine often causes headache, nausea, vomiting, visual disturbances, and ringing in the ears. This combination of symptoms is called cinchonism. Quinine may also cause a low blood sugar level in people infected with Plasmodium falciparum.

Antimalarial drugs may harm a fetus. Thus, an expert should be consulted if a pregnant woman is treated.

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