Triple-drug therapy improves clearance of microfilaremia in elephantiasis

When treating lymphatic filariasis, also known as elephantiasis, adding ivermectin to diethylcarbamazine and albendazole works better than two-drug therapy alone, researchers report in Thursday's New England Journal of Medicine.

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The triple-drug combination, given just once, was superior to the two-drug combination given once and noninferior to the two-drug regimen given once a year for 3 years.

Clearance of the microfilaremia with the three-drug combination had a 96% success rate at the 12-month, 24-month, and 36-month marks.

In contrast, one-time administration of diethylcarbamazine and albendazole, which is the standard regimen in campaigns to eliminate lymphatic filariasis outside sub-Saharan Africa, produced clearance rates of 32% at 12 months, 56% at 24 months, and 83% at 36 months.

Once-a-year treatment with the double-drug combination produced rates of 34%, 75%, and 98% respectively.

The test was done in Papua New Guinea.

Preliminary results of the test prompted the World Health Organization to change its treatment guidelines last year, chief author Dr. Christopher King of the Case Western Reserve University School of Medicine in Cleveland, OH told Reuters Health by email. The new findings may prompt countries that have not been following those guidelines to do so.

The WHO has called for eliminating the mosquito-borne parasitic infection by 2020. Dr. King said that goal is "totally unrealistic. There is discussion of 2025 which might be achieved with this new drug therapy, but treating affected people in the most remote areas is an extreme challenge and final elimination may take quite some time."

The three-drug treatment alone is not practical for many parts of Africa, according to an editorial by David Molyneux of the Liverpool School of Tropical Medicine. That's because use of one of the drugs can cause complications in people with common diseases such as river blindness and Loa.

Dr. King said he and his colleagues are starting a test in sub-Saharan Africa to see if people can first be given ivermectin to clear the river blindness, "then follow up with triple-drug therapy" to deal with lymphatic filariasis.

The rate of grade 2 or 3 adverse events was significantly higher with the three-drug regimen, seen in 27% of patients vs a rate of 5% when the therapy was the two drugs (P < 0.001).

The rates for worse-than-mild fatigue, headache, myalgia, scrotal pain, or swelling or a combination of nausea, vomiting, or both were at least four times higher in the triple-drug group.

Only one patient, a 52-year-old woman in the triple-drug group, had severe side effects that began as headache, nausea, and chills. A physical examination uncovered a fever, orthostatic hypotension, and tachycardia. She recovered after a day of treatment with oral fluids and acetaminophen.

"Because adverse events are probably triggered by microfilarial death, it is not surprising that these were more common in people who received treatment with two potent microfilaricidal drugs (diethylcarbamazine and ivermectin)," the researchers wrote.

"When we tell people that some side effects mean that drugs are killing the worms and will resolve in a day or two, they are happy with this explanation," said Dr. King, a professor of international health, pathology, and medicine at Case Western.

In fact, "When treated again and they have no symptoms (the microfilariae are gone), they wonder whether the drugs are working," he said.

—Gene Emery

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