Malaria

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

Malaria 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, or through injection with a needle previously used by a person with malaria. The four species of malaria parasites that infect people are—Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae.

Although drugs and insecticides have made malaria rare in the United States and in most industrialized countries, the disease remains common and deadly in other areas. Worldwide, about 300 to 500 million people are infected with malaria, and 1 to 2 million 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 industrialized 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.

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

After infection occurs, 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 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.The level of sugar (glucose) in the blood can fall in people infected with Plasmodium falciparum. The level may be life-threateningly low in people who have a large number of parasites in their blood—particularly if they are treated with the drug quinine.

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. Cerebral malaria is a particularly dangerous complication that can produce 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. In falciparum malaria, fluid can accumulate in the lungs and cause severe breathing problems. Damage to several organs can cause a fall in blood pressure. Other symptoms include diarrhea, kidney failure, and jaundice.

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

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 less than half of American travelers with malaria but, when present, suggests the diagnosis. Identification of parasites by microscopic examination of a blood sample confirms the diagnosis. More than one sample may be needed. 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

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 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: 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 species. 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 specific sites is available from the Centers for Disease Control and Prevention.
Vaccines for preventing malaria are still in the experimental stage.

Treatment

For treatment, the choice of drug is based on the infecting species of Plasmodium. Chloroquine is the drug of choice in areas where Plasmodium species have not developed resistance to it. Primaquine is added to kill persistent parasites in the liver of people infected with Plasmodium vivax or Plasmodium ovale. Before primaquine is given, a blood test is done to look for a relatively common enzyme deficiency (G6PD deficiency). In people with G6PD deficiency, primaquine may cause breakdown of their red blood cells.

Malaria in areas with known chloroquine resistance can be treated with quinine plus doxycycline or, if uncomplicated, atovaquone-proguanil. Atovaquone-proguanil has fewer side effects than quinine. Mefloquine can be used in higher doses than those recommended for prevention, but side effects are common. If the person cannot take drugs by mouth, quinidine may be given intravenously, but the person must be monitored in the hospital because intravenous quinidine can cause low blood pressure and abnormal heart rhythms. A number of artemisinin drugs, which are typically given with a second antimalarial drug to prevent recurrence, are now widely used to treat acute Plasmodium falciparum malaria in Southeast Asia and China and are being increasingly used in Africa and elsewhere. A combination of artemether and lumefantrine is widely used. Artemisinin drugs act rapidly and are generally well tolerated. None are available in the United States.

Travelers who develop a fever while in areas where malaria is prevalent should be examined by a doctor immediately. If medical care is not available, self-treatment for presumed malaria with atovaquone-proguanil is sometimes recommended until medical evaluation is possible. This approach should be discussed with a doctor before traveling.
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 severe sunburn in a small percentage of people. It should be taken with a full glass of liquid, and the recipient 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 produce severe 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. Occasionally, 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, especially if they are traveling, should ask for written information about the side effects.
Atovaquone-proguanil is the best tolerated of the drugs used to prevent and treat malaria, but it occasionally causes a rash or intestinal symptoms.

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.
Artemisinin drugs are derived from a Chinese medicinal herbal called quinghaosu. It comes from the wormwood plant and is used to treat malaria. Some artemisinin drugs are given by mouth, and others are given by injection or suppository. Side effects are uncommon and include abdominal pain, diarrhea and fever. They are not available in the United States.

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

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




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