Malaria

Picture of red blood cells infected with malaria parasites. The parasites look like rings inside the cells. SOURCE: CDC/Steven Glenn, Laboratory & Consultation Division

Definition of Malaria

Malaria is caused by parasites from the genus Plasmodium, which are spread to people through the bite of infected mosquitoes of the Anopheles species.

Approximately 1,500 to 2,000 cases are diagnosed in the U.S. each year, largely as a result of international travel or immigration.

Signs and Symptoms of Malaria

The hallmark of malaria is fever. Initially, symptoms may mimic the flu. Fever may be accompanied by shaking chills and muscle aches. Anemia is common.

How Do I Know if I Have Malaria?

Malaria is diagnosed from a blood smear when the parasite is seen under the microscope. Other tests are available, but microscopy remains the cornerstone of diagnosis. Malaria is treated with specific medications. Oral medications are usually used, except in severe cases.

Severe cases may cause organ failure or death. Travelers are much more vulnerable to severe malaria than residents of areas where malaria is present; travelers lack the partial immunity that protects residents who are frequently exposed to malaria.

Malaria Treatment

Most patients recover completely after being treated. However, infection with P. vivax or P. ovale may be associated with organisms that hide in the liver for months or years, resisting treatment. Special medications are used to help eradicate these organisms, so it is important to closely follow medical directions when taking preventive medicines. Never stop the medication early if instructed to continue taking it for a few weeks after leaving the area where malaria is present.

Malaria Prevention

People who travel to areas with malaria should visit their physician several weeks prior to departure to ensure all preventive measures are completed before travel. The risk of malaria may be reduced by taking medications and using precautions to prevent mosquito bites, including insecticides containing DEET.

Malaria Prognosis

The history of malaria and other human diseases is interesting. The gene that causes sickle cell disease is more common in areas where malaria is common, because it offers some protection. People who have sickle cell disease (two sickle cell genes) have very abnormal hemoglobin that leads to many complications, including early death. However, people who have sickle cell trait (only one sickle cell gene) do not have the complications of sickle cell disease, but their hemoglobin is just abnormal enough to make red blood cells inhospitable to the malaria parasite. Thus, sickle cell trait provides some protection against malaria, especially during infancy and toddlerhood, until the child can produce immune defenses against malaria on its own.

Malaria is caused by protozoa of the genus Plasmodium and is transmitted to humans by mosquitoes. The history of malaria shows that it was difficult to determine the disease's mode of transmission. When some cultures reviewed the facts available to them, they concluded that malaria was caused by bad air without realizing that the same swamps that created foul-smelling air also were excellent breeding grounds for mosquitoes. In 1880, the parasite was identified in an infected patient's blood.

There are several stages in the life cycle of Plasmodium, including sporozoites, merozoites, and gametocytes. The bite of an infected mosquito transmits the sporozoite stage of the organism to humans. The parasite travels into the bloodstream and eventually makes its way to the liver, where it begins to multiply by producing merozoites. The merozoites leave the liver and enter red blood cells to reproduce. Soon, young parasites burst out in search of new red blood cells to infect.

Sometimes, the reproducing Plasmodia will create a form known as a gametocyte in the human bloodstream. If a mosquito takes a blood meal when gametocytes are present, the parasite begins to reproduce in the insect and create sporozoites that are infectious to people, completing the life cycle.

There are five species of Plasmodium that infect humans:

• P. vivax: This species is most commonly found in Asia, Latin America, and parts of Africa. Infections can sometimes lead to life-threatening rupture of the spleen. This type of malaria can hide in the liver (this is called the "hepatic phase" of the life cycle). It may then return later to cause a relapse years after the first infection. Special medications are used to eradicate P. vivax from the liver.
• P. ovale: This species is rarely found outside Africa or the western Pacific islands. Symptoms are similar to those of P. vivax. Like P. vivax, P. ovale can hide in the liver for years before bursting out again and causing symptoms.
• P. malariae: It is found worldwide but is less common than the other forms. This form of malaria is hard to diagnose because there are usually very few parasites in the blood. If untreated, the infection can last many years.
• P. falciparum: This is the most life-threatening species of malaria. Although present throughout much of the tropical and subtropical world, it is particularly common in sub-Saharan Africa. P. falciparum is resistant to many of the older drugs used to treat or prevent malaria. Unlike P. vivax and P. ovale, this species does not hide in the liver.
• P. knowlesi: Found predominantly in Malaysia, the Philippines, and Southeast Asia, this species can also cause high levels of parasites in the blood, leading to organ failure or death.

With malaria, the patient develops a high fever, which comes and goes. The pattern of fevers may vary according to the species of malaria. However, there does not have to be a pattern to the fever. Initially, malaria feels like the flu with high fever, fatigue, and body aches, with hot and cold stages. Signs and symptoms in children may be nonspecific, leading to delays in diagnosis. People also may have headache, nausea, shaking chills (rigors), sweating, and weakness. Anemia is common in patients with malaria, in part due to the effects of the Plasmodium parasite on the red cells. It is extremely uncommon for malaria to cause skin lesions or rash.

P. falciparum causes a particularly severe form of malaria. In addition to fever, patients may experience complications such as severe hemolytic anemia caused by the destruction of the red cells, yellow skin discoloration, kidney failure, pulmonary edema (fluid in the lungs), cerebral malaria, convulsions, coma, or death.

People who have lived for years in areas with malaria may develop a partial immunity to new infections, although this will wane if they leave the area.

Is Malaria Contagious?

Fortunately, malaria is not contagious except in rare situations; it is not spread directly from person to person with the following exceptions.

• A few cases have occurred in other countries through blood transfusion, intravenous drug abuse with shared needles, or organ transplantation. An infected mother can spread malaria through the placenta to her unborn child. Except for these rare situations, transmission only occurs when a person is bitten by an infected mosquito. The infected person is not contagious to other individuals, and there is no need to isolate or quarantine the person to protect others from direct transmission. However, depending on the local public-health situation, an infected traveler returning home may be asked to stay indoors until well.
• Some areas may have mosquitoes that are able to transmit malaria, and transmission of malaria from a returning traveler by local mosquitoes has been reported. Public-health authorities may increase mosquito-control measures in the area, as well, to reduce this risk.

The incubation period between infection with malaria by a mosquito bite and initial symptoms may range from one week to one year. Generally, the incubation period ranges from nine to 14 days for P. falciparum, 12-18 days for P. vivax, and 18-40 days for P. ovale.

Risk factors include recent history of travel to an area in which malaria exists. If one has traveled to such an area and develops a high fever, he/she should seek urgent medical evaluation at a facility where malaria blood smears can be promptly performed, such as a hospital's emergency department. Additional risk factors in travelers to malarious areas include not taking preventive medications or not using precautions to prevent mosquito bites. However, neither medications nor mosquito precautions are perfect, and travelers should not overlook any fever that occurs while in or after being in malarious areas. Complications most often occur when symptoms or signs of possible malaria are ignored or diagnosed late in the course of illness. Pregnant mothers who have been exposed to malaria are at high risk for severe disease. Malaria can be cured with early diagnosis and treatment.

Many diseases cause fever in the tropical and subtropical world, including malaria, tuberculosis, yellow fever, dengue fever, typhoid, pneumonia, and many more. Each of these is managed differently. Thus it is very important to make a specific diagnosis.

Malaria is diagnosed by seeing the parasite under the microscope. Blood taken from the patient is smeared on a slide for examination. Special stains are used to help highlight the parasite. Sometimes, it is possible to identify the species of Plasmodium by the shape of the parasite, especially if gametocytes are seen. Whenever possible, smears should be reviewed by someone with expertise in the diagnosis of malaria. The Centers for Disease Control and Prevention can provide this expertise (http://www.cdc.gov). If the smears are negative, they can be repeated every 12 hours. Smears that are repeatedly negative suggest another diagnosis should be considered.

Two types of other tests are available for diagnosis of malaria.

• Rapid tests can detect proteins called antigens that are present in Plasmodium. These tests take less than 30 minutes to perform. However, the reliability of rapid tests varies significantly from product to product. Thus, it is recommended that rapid tests be used in conjunction with microscopy.
• The second type of test is the polymerase chain reaction (PCR), which detects malaria DNA. Because this test is not widely available, it is important not to delay treatment while waiting for results.

• Malaria requires prescription medications and can be fatal if left untreated.
• Any traveler to areas where malaria is endemic who develops a fever up to one year after leaving the area should seek urgent evaluation for malaria, regardless of preventive treatment.
• There are no effective home remedies for malaria, and individuals must seek urgent medical care and follow all medical instructions carefully.
• Milder cases of malaria may be treated at home with oral medications and fluids. Severe infections require IV drug therapy.
• People who have malaria should drink lots of fluids. Hydration will not treat or cure malaria, but it will reduce side effects associated with dehydration.

There are several medications available to treat malaria, including

• chloroquine (Aralen);
• Artemether-lumefantrine (Coartem);
• Artesunate-amodiaquine (Amonate);
• Artesunate-mefloquine;
• Dihydroartemisinin-piperaquine;
• Artesunate-sulfadoxine-pyrimethamine (SP), in areas with known SP sensitivity;
• atovaquone-proguanil (Malarone) (Note: Mepron is the trade name for atovaquone alone; it is not used by itself to treat malaria but only in combination with proguanil as Malarone.);
• mefloquine (Lariam);
• quinine (Qualaquin);
• quinidine (Quinaglute Dura-Tabs, Quinidex Extentabs, Quin-Release);
• doxycycline (Adoxa, Avidoxy, Acticlate, Doryx, Monodox, Oraxyl, Vibramycin, Vibramycin Calcium, Vibramycin Monohydrate, Vibra-Tabs, used in combination with quinine);
• clindamycin (Cleocin HCl, Cleocin Pediatric, used in combination with quinine);
• artesunate (available only through the CDC).

The choice of drug depends on the species of Plasmodium and if the parasite is drug-resistant. The risk of drug resistance depends on the area where the malaria was acquired. In sub-Saharan Africa, for example, older drugs like chloroquine are largely ineffective.

Most medications are available only as tablets or pills. Intravenous treatment with quinidine may be needed in severe malaria or when the patient cannot take oral medications.

Malaria during pregnancy is very serious even in the best of hands and requires treatment by someone who is an expert in this area. Complications of malaria in pregnancy can include premature birth, miscarriage, and stillbirth, as well as severe complications in the mother. Patients with P. vivax or P. ovale may not be completely cured by the above medications, even though the symptoms resolve. This is because the parasites can hide in the liver. A medication called primaquine is used to eradicate the liver form, but this drug cannot be given to people who are deficient in an enzyme called G6PD.

Importantly, the CDC maintains a malaria hotline. Clinicians can telephone the CDC for advice on diagnosis and treatment of the disease (http://www.cdc.gov).

• Patients should report any recurrent fever or symptoms to their doctor because treatment failures may occur.
• People who have had malaria should not donate blood for at least three years after treatment and should notify the donation center that they have had malaria.
• People who traveled to areas where malaria occurs also should not donate blood or other blood products for a period of time, which varies according to the circumstance. Contact the donation center for specific advice.

• If promptly diagnosed and treated, malaria is usually not fatal.
• Long-term effects are uncommon with prompt treatment.
• Delays in diagnosis come because the disease is rarely seen by clinicians in the United States and often patients may ignore early symptoms.
• Delays increase the risk of serious complications or death.
• Because of the large burden of disease, scientists have been trying to make a malaria vaccine.

There is no malaria vaccine commercially available to prevent malaria at the time of this writing. However, the Centers for Disease Control is conducting a vaccine trial with the Kenya Medical Research Institute, and so far the vaccine has had promising results. If the vaccine continues to perform well, the vaccine could become available for use within the decade.

Malaria is a potentially fatal illness. People planning to travel to an area with malaria should see their physician before travel, preferably at least six weeks before departure. Travelers should use mosquito repellent and barrier techniques (long sleeves and long pants) to reduce the chance of mosquito bites and take medications to reduce the risk of disease. Malaria in pregnancy is very serious and often life-threatening to both the mother and fetus. Because prevention is not perfect, and malaria is so serious, travel to areas where malaria is endemic should be discussed with a health-care professional and avoided if at all possible by women who are or may become pregnant.

Breastfeeding mothers may safely take some preventive medications, however, these will not protect an infant from malaria. There are safe medications for infants who are dosed by weight. Travel with children of all ages should be discussed with a health-care professional.

Mosquito-bite precautions include wearing light-colored protective clothing and using window screens and bed nets when available. The mosquito that spreads malaria is active between dusk and dawn. Insect repellants should be used and should contain DEET. Room sprays and insecticides may be used to reduce the mosquito population in sleeping areas.

Several medications are available to prevent malaria. The choice of medication used for prophylaxis depends on the area of the world that is being visited and the drug-resistance pattern in that area. In general, the medications are started before travel, taken while in the malarious area, and continued for a period of time after leaving the area.

Any traveler to areas where malaria is endemic who develops a fever up to one year after leaving the area should seek urgent evaluation for malaria, regardless of preventive treatment.

The Centers for Disease Control maintains a web page (http://www.cdc.gov/travel) that gives specific recommendations for every country.