Most of us think of the mosquito-borne disease malaria as ancient history, but the truth is it remains a threat in tropical areas that are home to three billion people, killing between one and three million each year. Mosquito control has eliminated malaria in the U.S. and Canada, but it survives and has even made a comeback in many parts of the world. Despite promising new research efforts, malaria continues to be a major world health problem.
Almost all deaths from malaria are caused by the first one on the list, falciparum malaria. Human infection occurs when a female anopheles mosquito bites a person and transmits cells called sporozoites from its salivary gland to a person's bloodstream.
After reentering the bloodstream the infected merozoites rapidly invade red blood cells. By the end of 48 hours, (72 hours for P. malariae), the parasite has grown to occupy most of the affected red blood cells. Multiple nuclear divisions then occur and the red blood cell then ruptures to release 6 to 30 daughter merozoites, each potentially capable of invading a new red blood cell.
The disease we call malaria is a result of the direct and indirect effects of red blood cell invasion and destruction by the parasite
The disease we call malaria is a result of the direct and indirect effects of red blood cell invasion and destruction by the parasite. After a series of asexual reproduction cycles (P. falciparum) or immediately after release from the liver (P. vivax, P. ovale, P. malariae), some of the parasites develop into distinct, longer-lived sexual forms (gametocytes) that continue the cycle of malaria transmissionafater ingestion of gametocytes by the mosquito.
The lifecycle of the the parasite within the mosquito continues in the following manner. After being ingested along with human blood by a biting female anopheles mosquito, male and female gametocytes form a cell called a zygote in the insect's stomach. This develops into something called an oocyst, which expands asexually, by division, until it bursts to liberate many sporozoites, which then migrate to the salivary gland of the mosquito to await transmission to another human at the next feeding.
Malaria is an epidemic disease in northern India, Sri Lanka, Afghanistan, the Sahel areas of Africa, Ethiopia, the East African highlands, Burundi, Rwanda, Madagascar and Brazil. Outside of these areas, an epidemic can develop when there are heavy rains following drought or after people migrate from a non-malaria infected region to an area of high transmission. Breakdowns in malaria control and the local health care system can intensify an epidemic. Urban malaria is increasingly common, as cities grow rapidly in many malaria-infected areas.
The transmission of malaria is directly proportional to the population density of the mosquitoes that carry the disease, the number of human bites per day per mosquito and the probability of the mosquito's surviving for 1 day.
[A]n epidemic can develop when there are heavy rains following drought or after people migrate from a non-malaria infected region to an area of high transmission.
Mosquito longevity is particularly important because in order to transmit malaria, the mosquito must survive for at least seven days to accommodate the portion of the parasite's life cycle that takes place within the mosquito.
The most effective mosquito carrier of malaria is anopheles gambiae, an African mosquito that is long-lived, occurs in high densities in tropical climates, breeds readily and prefers human blood to animal blood.
The classic malaria attack that most people are familiar with — in which fever spikes and chills come and go in waves — is relatively unusual. The temperature of infected adults and children can exceed above 40°C or 104°F and is accompanied by increased heart rate and delirium. Although any of the types of malaria may cause childhood convulsions, seizures are specifically associated with the most common form — falciparum malaria and may indicate the development of cerebral malaria (see below).
Most victims have few physical symptoms other than fever, malaise, mild anemia and, sometimes, a swollen spleen. Splenic enlargement is found in many otherwise healthy individuals in malaria-infested areas and is a sign of repeated infections. Enlargement of the liver among young children and mild jaundice among adults are also common.
Retinal hemorrhages occur in 30 to 40% of those with cerebral malaria. Other eye symptoms include retinal opacification, papilledema (swelling of the eye), "cotton wool" spots and loss of color in a retinal vessel or part of a vessel.
= very frequent
In other areas, pregnant women are prone to severe infections and are particularly vulnerable to fetal distress, premature labor and stillbirth or low birth weight. P. vivax malaria in pregnancy is also associated with low birth weight.
Those with severe malaria or those unable to take medicine orally should be given antimalarial drugs by injection or IV.
The treatment of falciparum malaria has changed radically in recent years. In endemic areas the World Health Organization now recommends artemisinin-based combinations (ACTs) as the first line of treatment for falciparum malaria. These reliable and rapidly effective drugs are often unavailable in temperate countries such as the United States. In August 2007, the Food and Drug Administration (FDA) gave the Centers for Disease Control and Prevention (CDC) permission to provide intravenous artesunate for severe malaria. The availability of antimalarial drugs varies considerably from one country to another. Fake or adulterated drugs, including antimalarial agents, are being sold in many developing countries.
Fake or adulterated drugs, including antimalarial agents, are being sold in many developing countries.
Quinidine gluconate is as effective as quinine and is more readily available. Therefore it has replaced quinine for the treatment of malaria in the United States.
To prevent resistance, falciparum malaria should be treated with drug combinations, particularly in endemic areas. This means simultaneous use of two or more drugs: one, usually an artemisinin derivative (artesunate, artemether or dihydroartemisinin); and the other, a slower-acting antimalarial to which P. falciparum is sensitive. Artemisinin combination treatments are now recommended as the first-line treatment for falciparum malaria.
Artesunate or quinine plus tetracycline, doxycycline or clindamycin are all effective as second-line treatments. Tetracycline and doxycycline cannot be given to pregnant women or to children younger than eight. Oral quinine is extremely bitter and has unpleasant side effects such as ringing in the ears, partial deafness, nausea, vomiting and irritability.
If there is any doubt as to the identity of the infecting malarial species, treatment for falciparum malaria should be given.
- The first line of defense against malaria is to reduce your risk of mosquito bites in malarious areas.
- Stay inside at peak feeding times (dusk and dawn) and throughout the night
- Use insect repellents containing DEET or picardin
- Wear clothing that covers as much skin as possible
- Use insecticide-impregnated bed nets and other materials
Preventive drugs are never foolproof and malaria should always be considered as a possible cause of fever in people who have traveled to areas where it is common, even if they have been taking antimalarial drugs.
Pregnant women traveling to malarious areas should strongly consider the potential risks. All pregnant women in endemic areas should have regular check-ups with an OB-GYN. Apart from mefloquine, the safety of preventive antimalarial drugs for pregnant women is uncertain.
Travelers should start taking antimalarial drugs at least a week before departure in case they have a bad reaction. They should then continue for four weeks after the traveler has left the endemic area...
Preventive antimalarial drugs have been shown to reduce mortality in children between the ages of 3 months and 4 years in malaria endemic areas but they are too expensive for many developing countries. An alternative, giving intermittent treatment doses (IPT), has shown promise in infants, young children and pregnant women. Children born to non-immune mothers in endemic areas (usually expatriates moving to malaria endemic areas) should receive preventive drugs from birth.
Atovaquone-proguanil is a fixed-combination once-daily preventive treatment for both adults and children; it has fewer gastrointestinal side effects than chloroquine-proguanil and fewer central nervous system side effects than mefloquine. Atovaquone-proguanil is best taken with food or a milky drink. There are insufficient data on the safety of this treatment in pregnancy.
Mefloquine has been widely used because of its effectiveness against multidrug-resistant falciparum malaria and its relatively few side effects. Mild nausea, dizziness, fuzzy thinking, disturbed sleep patterns, vivid dreams and malaise are the most common. Approximately 1 in every 10,000 recipients develops an acute, but reversible, neuropsychiatric reaction causing confusion, psychosis and convulsions.
Doxycycline is an effective alternative to atovaquone-proguanil or mefloquine. Doxycycline is generally well tolerated but may cause thrush, diarrhea and photosensitivity and cannot be used by children under eight or by pregnant women.
Chloroquine remains the drug of choice for the prevention of infection with drug-sensitive P. falciparum and with the other human malarial species. Chloroquine has few side effects, although some are unable to take the drug because of malaise, headache, vision problems, gastrointestinal intolerance or (in dark-skinned people) itchy skin. Chloroquine is safe for pregnant women.
Primaquine has proven safe and effective in the prevention of drug-resistant falciparum and vivax malaria in adults. This drug can be considered for travelers who are intolerant to other drugs. Abdominal pain and a blood condition called oxidant hemolysis, the principal side effects, are not common as long as the drug is taken with food. Primaquine should not be given to pregnant women or newborns.
Still, the total eradication of malaria remains an elusive goal because of the widespread distribution of anopheles breeding sites; the great number of infected people; the continued use of ineffective antimalarial drugs; and the widespread lack of trained treatment and research personel, material resources, infrastructure and control programs.
Malaria may someday be contained by judicious use of insecticides to kill the mosquito; rapid diagnosis and more effective treatment; and the administration of preventive drugs to high-risk groups. Toward this end, malaria researchers are intensifying their efforts to better understand the parasite-human-mosquito cycle.
Despite the enormous current investment in efforts to develop a malaria vaccine, no safe, effective, long-lasting vaccine is likely to be available for general use in the near future. While one or more malaria vaccines may be on the distant horizon, our primary weapons against this dreadful disease remain prevention, mosquito control measures and rapid drug treatment.
Regional and disease-specific documents may be requested from the CDC Fax Information Service (888-232-3299). Consultation for the evaluation of prophylaxis failures or treatment of malaria can be obtained from state and local health departments and the CDC Malaria Hotline (770-488-7788) or the CDC Emergency Operations Center (770-488-7100).