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What is malaria?

Malaria is an infectious disease caused by a parasite, Plasmodium, which infects red blood cells. Malaria is characterized by cycles of chills, fever, pain, and sweating. Historical records suggest malaria has infected humans since the beginning of mankind. The name "mal aria" (meaning "bad air" in Italian) was first used in English in 1740 by H. Walpole when describing the disease. The term was shortened to "malaria" in the 20th century. C. Laveran in 1880 was the first to identify the parasites in human blood. In 1889, R. Ross discovered that mosquitoes transmitted malaria. Of the four common species that cause malaria, the most serious type is Plasmodium falciparum malaria. It can be life-threatening. However, another relatively new species, Plasmodium knowlesi, is also a dangerous species that is typically found only in long-tailed and pigtail macaque monkeys. Like P. falciparum, P. knowlesi may be deadly to anyone infected. The other three common species of malaria (P. vivax, P. malariae, and P. ovale) are generally less serious and are usually not life-threatening. It is possible to be infected with more than one species of Plasmodium at the same time.

Currently, about 2 million deaths per year worldwide are due to Plasmodium infections. The majority occur in children under 5 years of age in sub-Saharan African countries. There are about 400 million new cases per year worldwide. Most people diagnosed in the U.S. obtained their infection outside of the country, usually while living or traveling through an area where malaria is endemic.

What are malaria symptoms and signs?

The symptoms characteristic of malaria include flulike illness with fever, chills, muscle aches, and headache. Some patients develop nausea, vomiting, cough, and diarrhea. Cycles of chills, fever, and sweating that repeat every one, two, or three days are typical. There can sometimes be vomiting, diarrhea, coughing, and yellowing (jaundice) of the skin and whites of the eyes due to destruction of red blood cells and liver cells.

People with severe P. falciparum malaria can develop bleeding problems, shock, liver or kidney failure, central nervous system problems, coma, and can die from the infection or its complications. Cerebral malaria (coma, or altered mental status or seizures) can occur with severe P. falciparum infection. It is lethal if not treated quickly; even with treatment, about 15%-20% die.

How is malaria transmitted?

The life cycle of the malaria parasite (Plasmodium) is complicated and involves two hosts, humans and Anopheles mosquitoes. The disease is transmitted to humans when an infected Anopheles mosquito bites a person and injects the malaria parasites (sporozoites) into the blood. This is shown in Figure 1, where the illustration shows a mosquito taking a blood meal (circle label 1 in Figure 1).
Figure 1: CDC illustration of the life cycles of malaria parasites, Plasmodium spp.
Figure 1: CDC illustration of the life cycles of malaria parasites, Plasmodium spp. SOURCE: CDC

Sporozoites travel through the bloodstream to the liver, mature, and eventually infect the human red blood cells. While in red blood cells, the parasites again develop until a mosquito takes a blood meal from an infected human and ingests human red blood cells containing the parasites. Then the parasites reach the Anopheles mosquito's stomach and eventually invade the mosquito salivary glands. When an Anopheles mosquito bites a human, these sporozoites complete and repeat the complex Plasmodium life cycle. P. ovale and P. vivax can further complicate the cycle by producing dormant stages (hypnozoites) that may not develop for weeks to years.
Malaria Treatment

Learn about the pill (drugs) used in the treatment of malaria.Three main factors determine treatments: the infecting species of Plasmodium parasite, the clinical situation of the patient (for example, adult, child, or pregnant female with either mild or severe malaria), and the drug susceptibility of the infecting parasites. Drug susceptibility is determined by the geographic area where the infection was acquired. Different areas of the world have malaria types that are resistant to certain medications. The correct drugs for each type of malaria must be prescribed by a doctor who is familiar with malaria treatment protocols. Since people infected with P. falciparum malaria can die (often because of delayed treatment), immediate treatment for P. falciparum malaria is necessary.

Learn more about malaria treatment »

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Where is malaria a particular problem?

Malaria is a particular problem and a major one in areas of Asia, Africa, and Central and South America. Unless precautions are taken, anyone living in or traveling to a country where malaria is present can get the disease. Malaria occurs in about 100 countries; approximately 40% of the world population is at risk for contracting malaria. To get information on countries that have current malaria infection problems, the CDC (Centers for Disease Control) has a constantly updated web site (http://www.cdc.gov/malaria/travelers/
country_table/a.html) that lists the problem areas in detail.

HIV (AIDS) and malaria co-infection is a significant problem across Asia and sub-Saharan Africa. Research suggests that malaria and HIV co-infection can lead to worse clinical outcomes in patients. It seems that co-infections enhance the disease process of both pathogens.

What is the incubation period for malaria?

The period between the mosquito bite and the onset of the malarial illness is usually one to three weeks (seven to 21 days). This initial time period is highly variable as reports suggest that the range of incubation periods may range from four days to one year. The usual incubation period may be increased when a person has taken an inadequate course of malaria prevention medications. Certain types of malaria (P. vivax and P. ovale) parasites can also take much longer, as long as eight to 10 months, to cause symptoms. These parasites remain dormant (inactive or hibernating) in the liver cells during this time. Unfortunately, some of these dormant parasites can remain even after a patient recovers from malaria, so the patient can get sick again. This situation is termed relapsing malaria.

How is malaria diagnosed?

Clinical symptoms associated with travel to countries that have identified malarial risk (listed above) suggest malaria as a diagnosis. Malaria tests are not routinely ordered by most physicians so recognition of travel history is essential. Unfortunately, many diseases can mimic symptoms of malaria (for example, yellow fever, dengue fever, typhoid fever, cholera, filariasis, and even measles and tuberculosis). Consequently, physicians need to order the correct special tests to diagnose malaria, especially in industrialized countries where malaria is seldom seen. Without the travel history, it is likely that other tests will be ordered initially. In addition, the long incubation periods may tend to allow people to forget the initial exposure to infected mosquitoes.

The classic and most used diagnostic test for malaria is the blood smear on a microscope slide that is stained (Giemsa stain) to show the parasites inside red blood cells (see Figure 2).
Figure 2: CDC slide of a Giemsa stained smear of red blood cells showing Plasmodium malariae and Plasmodium falciparum parasites.
Figure 2: CDC slide of a Giemsa stained smear of red blood cells showing Plasmodium malariae and Plasmodium falciparum parasites. SOURCE: CDC/Steven Glenn, Laboratory & Consultation Division

Although this test is easily done, correct results are dependent on the technical skill of the lab technician who prepares and examines the slides with a microscope. Other tests based on immunologic principles exist; including RDTs (rapid diagnostic tests) approved for use in the U.S. in 2007 and polymerase chain reaction (PCR) tests. These are not yet widely available and are more expensive than the traditional Giemsa blood smear. Some investigators suggest such immunologic based tests be confirmed with a Giemsa blood smear.
What is the treatment for malaria?

Three main factors determine treatments: the infecting species of Plasmodium parasite, the clinical situation of the patient (for example, adult, child, or pregnant female with either mild or severe malaria), and the drug susceptibility of the infecting parasites. Drug susceptibility is determined by the geographic area where the infection was acquired. Different areas of the world have malaria types that are resistant to certain medications. The correct drugs for each type of malaria must be prescribed by a doctor who is familiar with malaria treatment protocols. Since people infected with P. falciparum malaria can die (often because of delayed treatment), immediate treatment for P. falciparum malaria is necessary.

Mild malaria can be treated with oral medication; severe malaria (one or more symptoms of either impaired consciousness/coma, severe anemia, renal failure, pulmonary edema, acute respiratory distress syndrome, shock, disseminated intravascular coagulation, spontaneous bleeding, acidosis, hemoglobinuria [hemoglobin in the urine], jaundice, repeated generalized convulsions, and/or parasitemia [parasites in the blood] of > 5%) requires intravenous (IV) drug treatment and fluids in the hospital.

Drug treatment of malaria is not always easy. Chloroquine phosphate (Aralen) is the drug of choice for all malarial parasites except for chloroquine-resistant Plasmodium strains. Although almost all strains of P. malariae are susceptible to chloroquine, P. falciparum, P. vivax, and even some P. ovale strains have been reported as resistant to chloroquine. Unfortunately, resistance is usually noted by drug-treatment failure in the individual patient. There are, however, multiple drug-treatment protocols for treatment of drug-resistant Plasmodium strains (for example, quinine sulfate plus doxycycline [Vibramycin, Oracea, Adoxa, Atridox] or tetracycline [Achromycin], or clindamycin [Cleocin], or atovaquone-proguanil [Malarone]). There are specialized labs that can test the patient's parasites for resistance, but this is not done frequently. Consequently, treatment is usually based on the majority of Plasmodium species diagnosed and its general drug-resistance pattern for the country or world region where the patient became infested. For example, P. falciparum acquired in the Middle East countries is usually susceptible to chloroquine, but if it's acquired in sub-Sahara African countries, it's usually resistant to chloroquine. The WHO's treatment policy, recently established in 2006, is to treat all cases of uncomplicated P. falciparum malaria with artemisinin-derived combination therapy (ACTs). ACTs are drug combinations (for example, artesunate-amodiaquine, artesunate-mefloquine, artesunate-pyronaridine, dihydroartemisinin-piperaquine, and chlorproguanil-dapsoneartesunate) used to treat drug-resistant P. falciparum. Unfortunately, as of 2009, a number of P. falciparum-infected individuals have parasites resistant to ACT drugs.

New drug treatments of malaria are currently under study because Plasmodium species continue to produce resistant strains that frequently spread to other areas. One promising drug class under investigation is the spiroindolones, which have been effective in stopping P. falciparum experimental infections.
Is malaria a particular problem during pregnancy?

Yes. Malaria may pose a serious threat to a pregnant woman and her fetus. Malaria infection in pregnant women may be more severe than in women who are not pregnant. Malaria may also increase the risk of problems with the pregnancy, including prematurity, abortion, and stillbirth. Statistics indicate that in sub-Saharan Africa, between 75,000-200,000 infants die from malaria per year; worldwide estimates indicate about 2 million children die from malaria each year. Therefore, all pregnant women who are living in or traveling to a malaria risk area should consult a doctor and take prescription drugs (for example, sulfadoxine-pyrimethamine) to avoid contracting malaria. Treatment of malaria in the pregnant female is similar to the usual treatment described above; however, drugs such as primaquine (Primaquine), tetracycline (Achromycin, Sumycin), doxycycline, and halofantrine (Halfan) are not recommended as they may harm the fetus. In addition to monitoring the patient for anemia, an OB/GYN specialist often is consulted for further management.

Is malaria a particular problem for children?

Yes. All children, including young infants, living in or traveling to malaria risk areas should take antimalarial drugs (for example, chloroquine and mefloquine [Lariam]). Although the recommendations for most antimalarial drugs are the same as for adults, it is crucial to use the correct dosage for the child. The dosage of drug depends on the age and weight of the child. A specialist in pediatric infectious diseases is recommended for consultation in prophylaxis (prevention) and treatment of children. Since an overdose of an antimalarial drug can be fatal, all antimalarial (and all other) drugs should be stored in childproof containers well out of the child's reach.

How do people avoid getting malaria?

If people must travel to an area known to have malaria, they need to find out which medications to take, and take them as prescribed. Current CDC recommendations suggest individuals begin taking antimalarial drugs about one to two weeks before traveling to a malaria infested area and for four weeks after leaving the area (prophylactic or preventative therapy). Doctors, travel clinics, or the health department can advise individuals as to what medicines to take to keep from getting malaria. Currently, there is no vaccine available for malaria, but researchers are trying to develop one.

Avoid travel to or through countries where malaria occurs if possible. If people must go to areas where malaria occurs, they should take all of the prescribed preventive medicine. In addition, the 2010 CDC international travel recommendations suggest the following precautions be taken in malaria and other disease-infested areas of the world; the following CDC recommendations are not unique for malaria but are posted by the CDC in their malarial prevention publication.

Avoid outbreaks: To the extent possible, travelers should avoid traveling in areas of known malaria outbreaks. The CDC Travelers' Health web page provides alerts and information on regional disease transmission patterns and outbreak alerts (http://www.cdc.gov/travel).


Be aware of peak exposure times and places: Exposure to arthropod bites may be reduced if travelers modify their patterns of activity or behavior. Although mosquitoes may bite at any time of day, peak biting activity for vectors of some diseases (for example, dengue, chikungunya) is during daylight hours. Vectors of other diseases (for example, malaria) are most active in twilight periods (for example, dawn and dusk) or in the evening after dark. Avoiding the outdoors or focusing preventive actions during peak hours may reduce risk.


Wear appropriate clothing: Travelers can minimize areas of exposed skin by wearing long-sleeved shirts, long pants, boots, and hats. Tucking in shirts and wearing socks and closed shoes instead of sandals may reduce risk. Repellents or insecticides such as permethrin can be applied to clothing and gear for added protection; this measure is discussed in detail below.


Check for ticks: Travelers should be advised to inspect themselves and their clothing for ticks during outdoor activity and at the end of the day. Prompt removal of attached ticks can prevent some infections.


Bed nets: When accommodations are not adequately screened or air conditioned, bed nets are essential to provide protection and to reduce discomfort caused by biting insects. If bed nets do not reach the floor, they should be tucked under mattresses. Bed nets are most effective when they are treated with an insecticide or repellent such as permethrin. Pretreated, long-lasting bed nets can be purchased prior to traveling, or nets can be treated after purchase. The permethrin will be effective for several months if the bed net is not washed. (Long-lasting pretreated nets may be effective for much longer.)


Insecticides: Aerosol insecticides, vaporizing mats, and mosquito coils can help to clear rooms or areas of mosquitoes; however, some products available internationally may contain pesticides that are not registered in the United States. Insecticides should always be used with caution, avoiding direct inhalation of spray or smoke.


Optimum protection can be provided by applying repellents. The CDC recommended insect repellent should contain up to 50% DEET (N,N-diethyl-m-toluamide), which is the most effective mosquito repellent for adults and children over 2 months of age.
What is the prognosis (outcome) for people with malaria?

The majority of people who become infected with P. malariae, vivax, or ovale do well and the fevers abate after about 96 hours. However, in endemic areas, reinfection is common. Malaria caused by P. falciparum or P. knowlesi, even when treated, have outcomes ranging from fair to poor, depending on how the parasites react to treatment. Untreated people often die from these infections. In general, patients who are infants, children under the age of 5 (especially in sub-Saharan countries), and those with depressed immune systems (for example, AIDS or cancer patients) have a more guarded prognosis.

Where can people get more information about malaria?

"The History of Malaria, an Ancient Disease," Centers for Disease Control and Prevention

"About Malaria," Centers for Disease Control and Prevention

Traveler's Health - Yellow Book, Centers for Disease Control and Prevention

"Malaria," eMedicine.com
Malaria At A Glance

Malaria is a disease caused by Plasmodium spp. parasites that infects about 400 million people per year with about 2 million deaths.
Symptoms include recurrent cycles (every one to three days) of fever, chills, muscle aches, headaches; nausea, vomiting, and jaundice also may occur.
Anopheles mosquitoes transmit the parasites to humans when they bite. The parasites undergo a complicated life cycle in both mosquitoes and humans; the cycle begins again when the mosquitoes take a blood meal from a human that is contaminated with mature parasites.
Africa, Asia, and Central and South America are the areas with high numbers of malarial infections.
The incubation period for malaria symptoms is about one to three weeks but may be extended to eight to 10 months after the initial infected mosquito bites occur. Some people may have dormant parasites that may get reactivated years after the initial infection.
Malaria is diagnosed by the patient's history of recurrent symptoms and the identification of the parasites in the patient's blood, usually by a Giemsa blood smear.
Malaria is usually treated by using combinations of two or more anti-parasite drugs incorporated into pills that are taken before exposure (prophylactic or preventative therapy) or during infection. More serious infections are treated by IV anti-parasitic drugs in the hospital.
Infants, children, and pregnant females, along with immunodepressed patients are at higher risk for worse outcomes when infected with malaria parasites.
To reduce the chance of getting malaria, people should avoid malaria-endemic areas of the world, use mosquito repellents, cover exposed skin, and use mosquito netting covered areas when sleeping.
The prognosis for the majority of malaria patients is good; most recover with no problems, unless infected with P. falciparum or P. knowlesi, which may have fair to poor outcomes unless treated immediately. Infants, children under 5 years of age, pregnant females, and those with depressed immune systems frequently have a fair to poor prognosis unless effectively treated early in the infection.

REFERENCES:

D'Acremont, V., C. Lengeler, and B. Genton. "Reduction in the Proportion of Fevers Associated With Plasmodium falciparum Parasitaemia in Africa: A Systematic Review." Malaria Journal 9.240 Aug. 22, 2010 doi:10.1186/1475-2875-9-240.

Rottmann, M., C. McNamara, B. Yeung, et al. "Spiroindolones, a Potent Compound Class for the Treatment of Malaria." Science 329 (2010): 1175-1180.