Artesunate for Falciparum Malaria

Malaria is an infectious disease that can be devastating. More than a million persons die each year out of hundreds of millions of cases of the disease. Malaria is caused by infection with one of four microscopic parasites: Plasmodium falciparum, P. vivax, P. malariae, or P. ovale. These are transmitted in the wild by the bite of an infected Anopheles mosquito. Most cases of malaria acquired by U.S. citizens are contracted in sub-Saharan Africa; most of the remainder are linked to travel in Southeast Asia, Central and South America, the Indian subcontinent, the Middle East, and Oceania.

When a female mosquito bites a human infected with malaria, it ingests an immature form of the parasite. In approximately two weeks, the parasite matures within the mosquito. When the infected mosquito bites a non-infected human, it releases malaria sporozoites (an immature form of the parasite), which mature in the human liver to become merozoites, and which then invade red blood cells. From these locations, the organisms can penetrate the vital organs, such as the brain, lungs, liver, and kidneys. Within a few days, the infected red blood cells burst and the parasites infect more red blood cells. The incubation period between acquisition of the parasites and the onset of symptoms is 8 to 40 days, depending on the species. Up to a third of victims may not show the disease until after 60 days from the time of the initial mosquito bite. Typical symptoms include a flu-like illness, with headache, chills, sweats, fatigue, loss of appetite, muscle aches, nausea, and vomiting. These are soon followed by episodes of headache, intense chills, high fever, and sweating. Jaundice and anemia may occur. The episodes last 1 to 8 hours and are separated by 2 to 3 days.

The most serious illnesses and deaths are attributed to Plasmodium falciparum.Persons infected with falciparum malaria may become dreadfully ill, with episodes of fever and chills at closer intervals than suffered with the other forms of malaria, and lasting sometimes for more than 30 hours. Severe malaria can be fatal or lead to anemia, heart and kidney failure, and/or coma; untreated infections can cause recurrent illness for years. Identification of the specific plasmodium is accomplished by observing the parasites under the microscope in blood smears.

In an article entitled "Artesunate for the treatment of severe falciparum malaria" (New England Journal of Medicine 358:1829-36), Dr. Philip J. Rosenthal notes that the most important new class of antimalarial drugs is the artemisinins, which are natural products that were first developed in China in the 1960s. Artemether (an artemisinin, or quinghaosu, derivative) has been shown to be as effective as quinine in the treatment of severe P. falciparum malaria. Other artemesinin derivatives include artesunate, artemotil, and dihydroartemisinin. One key advantage of these agents is that they are active against all of the red blood cell stages of the parasite. Also, so far there is limited if any resistance to these agents. Because all artemisinins are very effective in killing the parasites, they are rapidly cleared from the blood stream, so must be used in combination with longer acting drugs. Artemisinin-based drugs are used in combination with other drugs, such as mefloquine, lumefantrine, amodiaquine, or piperaquine as first-line therapies for uncomplicated malaria in countries other than the U.S. In the United States, intravenous artemesinin is still considered an investigational drug, so must be obtained from the Centers for Disease Control (CDC). It is used for 3 days, then followed by a longer-acting oral drug such as doxycycline, clindamycin, atovaquone-proguanil, or mefloquine.

Unfortunately, there is not yet a useful vaccine against malaria. Avoidance of mosquito bites is key to prevention. Because the Anopheles mosquito tends to feed during the evening and nighttime, it is particularly important to sleep under nets or screens; spray living quarters (with, for instance, a pyrethrin-containing product) and clothing (with, for example, permethrin 0.5%, Duranon, or Permanone; or concentrated Perma-Kill 4 Week Tick Killer, diluted and applied to clothing); and wear adequate clothing and insect repellent (N,N-diethyl-3-methylbenzamide, called DEET) at these times.

In an article entitled "Fake Artesunate In Southeast Asia" by Paul Newton, Stephane Proux, Michael Green, Frank Smithuis, Jan Rozendaal, Sompol Prakongpan, Kesinee Chotivanich, Mayfong Mayxay, Sornchai Looareesuwan, Jeremy Farrar, Francois Nosten, and Nicholas J White, the Global Pharma Health Fund instructs that artesunate is a key antimalarial drug in the treatment of multidrug-resistant Plasmodium falciparum malaria in southeast Asia. The authors investigated the distribution of counterfeit artesunate tablets using a special dye technique. Of 104 shop-bought "artesunate" samples from Cambodia, Laos, Myanmar (Burma), Thailand, and Vietnam, 38% did not contain artesunate. This illicit and murderous trade in counterfeit antimalarials is a great threat to the lives of patients with malaria.

To determine the malaria risk within a specific country and to learn of the most recent recommendations for prophylaxis and drug therapy, you can seek information from one of many sources on the Internet, such as http://www.cdc.gov/malaria/

Preview the 25th Anniversary & Annual Meeting of the Wilderness Medical Society, which will be held in Snowmass, Colorado July 25-30, 2008.

Tags: malaria, artesunate, wilderness medicine, outdoor medicine, healthline

Labels: artesunate, malaria

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