Merck Manual

Please confirm that you are not located inside the Russian Federation

Loading

Malaria

By

Richard D. Pearson

, MD, University of Virginia School of Medicine

Last full review/revision Oct 2019| Content last modified Oct 2019
Click here for the Professional Version
GET THE QUICK FACTS
NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
Click here for the Professional Version
Topic Resources

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 may feel tired.

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

  • Doctors diagnose the infection by identifying the protozoa in a sample of blood or by doing other blood tests, or both.

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

  • 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.

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. In 2015, about 214 million cases of malaria and about 438,000 deaths occurred worldwide. Most deaths occur in children who are younger than 5 years and live in Africa.

In the United States, about 1500 cases of malaria are reported each year. Most occur in immigrants, visitors from the tropics, or travelers returning from tropical areas. However, a few result from blood transfusions or from the bite of a local mosquito that had bitten an infected immigrant or returning traveler.

Did You Know...

  • In 2015, about 214 million cases of malaria and about 438,000 deaths occurred worldwide.

  • In some people symptoms of malaria may not appear until months or years after the bite of an infected mosquito.

Transmission of malaria

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.

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.

Types of malaria

Five species of malaria parasites can infect people:

  • Plasmodium falciparum

  • Plasmodium vivax

  • Plasmodium ovale

  • Plasmodium malariae

  • Plasmodium knowlesi (rarely)

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 an infected mosquito bites a person, malaria symptoms usually begin after 7 to 30 days, but they may not occur until months or even years later.

The initial symptoms of all forms of malaria are similar. They include

  • Fever and shaking chills (rigors)

  • An enlarged spleen

As the infected red blood cells rupture and release parasites, a person typically develops a shaking chill followed by a fever that can reach 105.8° F (41° 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. Periodic fevers come and go at regular intervals. Fevers tend to 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 without treatment. 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, sometimes resulting in shock. Other symptoms of falciparum malaria include diarrhea, jaundice, and kidney failure. The level of sugar (glucose) in the blood can fall (called hypoglycemia). The blood sugar 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 of falciparum malaria 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 and 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.

If pregnant women get malaria, their baby may have a low birth weight or be infected. Also, these women are more likely to have a miscarriage or stillbirth.

Diagnosis

  • A rapid diagnostic blood test

  • 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.

Malaria is diagnosed when Plasmodium parasites are detected by

  • A rapid diagnostic blood test that detects proteins released by malaria parasites (for this test, a blood sample and certain chemicals are placed on the test card, and after about 20 minutes, specific bands appear on the card if the person has malaria)

  • Microscopic examination of a blood sample

Both tests should be done when possible. If doctors do not see malaria parasites during microscopic examination but they still suspect malaria, they take additional blood samples every 4 to 6 hours to check for the parasites.

Laboratories try to identify the species of Plasmodium because the treatment, complications, and prognosis vary depending on the species involved. The rapid diagnostic blood test can detect Plasmodium falciparum malaria as effectively as microscopic examination, but it is not as reliable for detecting other Plasmodium species. That is why both the rapid diagnostic test and microscopic examination of blood should be done if available.

If Plasmodium falciparum infection is suspected, immediate evaluation and treatment are needed.

Prevention

Prevention involves

  • Controlling mosquitoes

  • Avoiding mosquito bites

  • Taking preventive drugs (malaria prophylaxis)

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- or pyrethrum-saturated 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, applying permethrin to clothing before it is worn

Treating clothing and gear with products containing permethrin helps. Permethrin remains protective through several washings. Pretreated clothing is available and can protect much longer.

People who plan to use repellents that contain DEET should be instructed to

  • Apply repellents only to exposed skin as directed on the label, and use them sparingly around ears (they should not be applied to or sprayed in the eyes or mouth).

  • Wash their hands after application.

  • Not allow children to handle repellents (adults should apply the repellent to their hands first, then spread it on the child's skin).

  • Apply just enough repellent to cover the exposed area.

  • Wash the repellant off after returning indoors.

  • Wash clothing before wearing again unless indicated otherwise by the product label.

Drugs to prevent malaria

Drugs should be taken to prevent malaria during travel in areas where it is present. 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 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 that are used frequently for preventing malaria are

  • Doxycycline

  • The combination of atovaquone and proguanil (in one tablet)

The effectiveness of these two treatments is similar, but they vary in side effects. Atovaquone plus proguanil is generally tolerated better than doxycycline.

Doxycycline is taken daily starting 1 to 2 days before a trip. People continue to take the drug daily 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 1 to 2 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 or children who weigh less than about 11 pounds. It does not prevent recurring attacks of symptoms caused by Plasmodium vivax or Plasmodium ovale.

Chloroquine is taken once a week starting 1 or 2 weeks before a trip. People continue to take the drug weekly during their stay and for 4 weeks after they leave the area. Chloroquine is used to prevent malaria in the few parts of the world where Plasmodium species have not developed resistance to it. These include Haiti, the Dominican Republic, Central America west and north of the Panama Canal, and most of the Middle East. 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 chloroquine.

Hydroxychloroquine, which is also used to treat autoimmune disorders, is effective against the same Plasmodium species as chloroquine.

Mefloquine is taken once a week starting 2 or more weeks before the trip. People continue to take the drug during their stay and for 4 weeks after they leave the area. Mefloquine is effective for prevention in many areas, but it is rarely used because it can have severe psychiatric and other 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 (see Table: More About Some Causes of Anemia). People with this deficiency should not take primaquine because the drug may cause their red blood cells to break down. Primaquine is administered once a day starting 1 to 2 days before the trip. People continue to take it daily during their stay and for 7 days after they leave the area. Primaquine taken daily for 14 days is also used to prevent recurring attacks of malaria 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.

Tafenoquine is an alternative for people (18 years of age and older) traveling to any area where malaria is common. However, as with primaquine, 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 tafenoquine because the drug may cause their red blood cells to break down. Tafenoquine is taken once a day for 3 days before the trip. People continue to take it every 7 days during their stay and once after their return, 7 days after the last dose taken during the trip. A single dose of tafenoquine is used to prevent recurring attacks of malaria in travelers who are taking other antimalarial drugs (such as doxycycline or atovaquone-proguanil) who have had heavy exposure to Plasmodium vivax or Plasmodium ovale.

Vaccines for preventing malaria are being developed, but when an effective vaccine will be available is unclear.

Treatment

  • 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 person's symptoms

  • 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

The treatment regimen is based on the results of the diagnostic tests and site of exposure. However, if doctors strongly suspect malaria, they may treat people for malaria even when the test results do not confirm the diagnosis because tests do not detects all cases, and if untreated, malaria can be life threatening. Doctors measure the person's the blood sugar (glucose) level, particularly in falciparum malaria, and give glucose if the level falls below normal.

Because malaria is potentially life-threatening, people are treated immediately. Most cases of malaria can be treated with oral drugs. In people who are unable to take drugs by mouth, artesunate can be given intravenously (available from the Centers for Disease Control and Prevention [CDC]). Severe malaria (see CDC: Severe Malaria for criteria) requires urgent treatment, preferably with artesunate given intravenously. When artesunate is not immediately available, interim oral treatment with artemether-lumefantrine, atovaquone-proguanil, quinine sulfate (plus doxycycline or clindamycin intravenously), or if nothing else is available, mefloquine is begun by mouth or with crushed pills delivered through a feeding tube in those who cannot take drugs orally.

In some areas where malaria is common, antimalarial drugs sold by local pharmacies may be counterfeit. Thus, doctors may advise travelers to remote, high-risk areas to take along a full course of the appropriate antimalarial drugs. These drugs are to be used if a local doctor confirms that the traveler has malaria. This strategy ensures that effective drugs are used and avoids depleting limited drug supplies in the country being visited.

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 malaria due to Plasmodium falciparum or other Plasmodium species. 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 the preferred treatment in the United States. When intravenous therapy is needed for severe malaria or for persons who are unable to take drugs by mouth, artesunate (available from the CDC) is the preferred treatment until oral therapy can be started.

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

Chloroquine is an option for falciparum malaria in Haiti, Dominican Republic, Central America west and north of the Panama Canal, and most of the Middle East, but resistance to chloroquine is now widespread among Plasmodium falciparum elsewhere in the world.

Quinine plus either the antibiotic doxycycline or sometimes clindamycin was once widely used, but artemether-lumefantrine and atovaquone-proguanil have 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 and other side effects. Also, resistance is well-documented in Southeast Asia and some other areas.

In some areas where malaria is common, antimalarial drugs sold by local pharmacies may be counterfeit. Thus, doctors may advise travelers to remote, high-risk areas to take along a full course of the appropriate antimalarial drugs. These drugs are to be used if a local doctor confirms that the traveler has malaria. This strategy ensures that effective drugs are used and avoids depleting limited drug supplies in the country being visited.

Malaria due to Plasmodium vivax and Plasmodium ovale

Chloroquine remains the treatment of choice, except in a areas like Papua New Guinea and Indonesia where Plasmodium vivax parasites are known to be resistant to chloroquine. In these areas, people are treated with artemether-lumefantrine or atovaquone-proguanil.

Primaquine taken daily for 14 days, or tafenoquine taken as a single dose in adults (16 years of age and older), is given at the end of treatment to prevent recurring attacks of malaria. Both drugs kill persistent parasites in the liver. Before they are started, a blood test is done to check for G6PD deficiency. In people with this deficiency, both primaquine and tafenoquine cause red blood cells to break down and cannot be used.

Malaria due to other species

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. They do not have persistent parasites in the liver.

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. Breakdown of red blood cells and anemia can occur in the weeks following administration of artesunate and, on occasion, other artemisinins. Artemisinin drugs are given to women who are pregnant only if there are no other alternatives and the potential benefit outweighs the potential risks to the fetus.

Atovaquone-proguanil is usually well-tolerated, but it occasionally causes an allergic rash or intestinal symptoms. It is given to women who are pregnant or breastfeeding only if there are no other alternatives and the potential benefit outweighs the potential risks to the fetus.

Chloroquine is relatively safe for adults, children, and pregnant women. It has a bitter taste and can cause itching and 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 irritate 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 when a pregnant woman is treated.

More Information

Drugs Mentioned In This Article

Generic Name Select Brand Names
PLAQUENIL
PERIOSTAT, VIBRAMYCIN
ARALEN
CLEOCIN
Artesunate
No US brand name
MEPRON
ELIMITE, NIX
QUALAQUIN
NOTE: This is the Consumer Version. DOCTORS: Click here for the Professional Version
Click here for the Professional Version
Others also read

Also of Interest

Videos

View All
Overview of Tuberculosis (TB)
Video
Overview of Tuberculosis (TB)
3D Models
View All
COVID-19 Virus
3D Model
COVID-19 Virus

SOCIAL MEDIA

TOP