Tropical Diseases: Dengue Fever, Yellow Fever, Elephantiasis

by Food and Drug Administration (FDA)

(Page 2 of 4)

In the United States, Barat says, oral quinine given together with either tetracycline or sulfadoxine-pyrimethamine (Fansidar) is the best regimen for treatment of mild to moderate falciparum malaria acquired in areas where resistance to chloroquine has been identified. For patients with complicated malaria who are too ill to take oral medicine, intravenous quinidine is used in the United States. Mefloquine (Lariam) and halofantrine (Halfan) are also used to treat chloroquine-resistant falciparum malaria. Halofantrine is not currently marketed here. Intravenous quinine is used in other countries.

The incidence of malaria continues to increase, Gwadz says, "in part due to the spread of resistance to chloroquine and several of its substitutes, but also to reduced effectiveness and acceptability of mosquito-killing insecticides."

In 1995, the World Health Organization established a system to monitor the drug resistance in Southeast Asia and the Western Pacific.

The parasite can be difficult to treat because it can change form to escape the human immune system, says Neil Goldman, Ph.D., associate director for research at FDA's Center for Biologics Evaluation and Research. Goldman says scientists at the center's Laboratory of Parasitic Biology and Biochemistry conduct research "to learn how this process takes place and figure out how to interrupt it. If we make a break in the circle, maybe we can stop infection."

Gwadz and colleagues are studying how to give mosquitoes a beneficial gene that prevents transmission of the parasite. To learn more about mosquito biology, they collaborate with scientists at West Africa's National School of Medicine and Pharmacy, in Mali.

NIAID scientists also are conducting the first human trial of a vaccine to block transmission of malaria parasites from infected people.

More from Mosquitoes: Dengue Fever, Yellow Fever

Aedes mosquitoes, mainly A. aegypti, an urban-dwelling insect, can transmit four types of dengue viruses, causing about 20 million cases of disease in more than 100 countries each year. A. aegypti mosquitoes tend to bite in the daytime, especially just after dawn and just before dark.

Dengue fever begins suddenly with high fever, severe frontal headache, joint and muscle pain, and sometimes vomiting and rash. Patients usually recover without complications. More serious, dengue hemorrhagic fever can lead to shock, bleeding and death. There is no specific treatment. Symptoms can be treated with bed rest, intravenous fluids, and drugs to reduce fever.

In 1995, the worst dengue epidemic in 15 years hit Latin America and the Caribbean. Worldwide, the more than 600,000 cases of hemorrhagic fever caused 24,000 deaths. CDC in 1995 diagnosed dengue fever in 86 U.S. travelers, up from 46 during 1993-1994 and 17 in 1992.

A. aegypti mosquitoes also spread the yellow fever virus. Peru in 1995 had the biggest yellow fever epidemic in the Americas since 1950. West Africa also experienced an epidemic that year.

Mild yellow fever causes flu-like symptoms. Severe cases may involve bleeding and liver problems, sometimes leading to delirium, convulsions, coma, and death. Treatment is symptomatic. Prevention consists of vaccination and personal protection against mosquitoes.

Yellow fever vaccine must be approved by WHO and given at approved vaccination centers. The Pan American Health Organization (PAHO) helped in the vaccination campaign that controlled the Peru epidemic. PAHO is the regional WHO office for the Americas.

Elephantiasis and River Blindness

Worms related to the heartworms that can hurt dogs, can give humans lymphatic filariasis, a disease affecting about 120 million people worldwide. Infected female Aedes, Anopheles, and various other mosquitoes deposit the worm larvae while biting.

The adult worm can damage the lymph system, resulting in elephantiasis — disfiguring swelling in the legs, arms, and other areas. FDA has approved diethylcarbamazine (Hetrazan) for treatment. Surgery may be needed if certain areas, such as the scrotum, are affected.

River blindness (onchocerciasis) is caused by pre-larval and adult stages of Onchocerca volvulus, a filarial parasite transmitted by female black flies. Living near rapidly flowing rivers and streams, black flies bite by day. Most of the 17.6 million people who have onchocerciasis are in Africa, though the disease is common in certain areas of Central America as well. Short-term travelers appear to be at low risk for infection, which is usually found in Americans only when they stay in these areas a long time in roles such as missionaries, field scientists, and Peace Corps volunteers.

Symptoms include an extremely itchy rash, lumps under the skin, and eye inflammation that can lead to blindness.

Ivermectin kills the parasite at the stage when it causes symptoms. Merck, Sharp & Dohme provides this drug free to countries where river blindness is common. It is available here from CDC under an agreement with FDA. According to John Becher, one of two pharmacists who oversee the drug service, "We provide certain drugs and biologics as a public health service. Most are for rare diseases." Ivermectin and other drugs for tropical diseases available through the service are not approved in the United States but are provided under investigational drug exemptions granted by FDA.

NIAID's Laboratory of Parasitic Diseases conducts research toward vaccines for elephantiasis and river blindness. While nearly everyone exposed becomes infected, a few individuals are resistant, says Thomas Nutman, M.D., who heads one immunology section. "These resistant individuals have antibodies in their blood that are specific to certain important parasite proteins. We identify the proteins, clone them, manufacture enough so we can study them, and then test them." Testing is in test tubes instead of in animals, which don't take the infection as humans do.

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