The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji

Abstract

Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in Samoa in relation to the annual single-dose MDAs revealed that low density mf carriers, who have a very low mf count of 1-20/ml of venous blood, could not play a significant role in filariasis transmission.From around 1990, studies on spaced low-dose DEC treatments and various types of combination chemotherapy with DEC and ivermectin increased. Albendazole, a well-known anti-intestinal helminths agent, was later added to the combination. The main findings of these studies with W. bancrofti are: (i) a single dose of DEC at 6 mg/kg reduced mean mf density by ca. 90% 1 year after treatment; (ii) the same dose could damage/kill adult worms; (iii) a single dose of ivermectin at ca. 400 µg/kg was more effective than DEC in reducing mf density during the first year and was similarly or less effective in the second year; (iv) ivermectin probably could not kill adult worms; (v) a single combined dose of albendazole (400 mg) and DEC (6 mg/kg) was effective to reduce mf density by 85 to nearly 100% 12-24 months after treatment; and (vi) ivermectin or albendazole incl...

Study of the distribution and abundance of the eggs of Aedes aegypti and Aedes albopictus according to the habitat and meteorological variables, municipality of São Sebastião, São Paulo State, Brazil

“…Reiter [20] reported that the oviposition behavior in the field might vary significantly both between species and within a species, albeit in different regions. Such differences are apparently related to environmental heterogeneity and the impact that human activities have on these mosquitoes [5,7,37,38]. …”

Mosquito-Parasite Interactions Can Shape Filariasis Transmission Dynamics and Impact Elimination Programs

“…However, in order to reach the goal of elimination by the year 2020, numerous challenges must be overcome. Elimination of LF requires annual MDA with high coverage and compliance for at least 5 years in order to interrupt transmission through the lifespan of adult worms [3], [4], [5], a difficult undertaking in light of logistical and financial constraints. Perhaps most importantly, thresholds for transmission cessation are currently unknown and are site-specific.…”

A mass treatment model for endemic reduction of filaria disease with pre-testing

“…At this level the worms become infective and can transmit the disease. It takes about 10-14 days to develop from L1 to L3 [8]. When the infective mosquitoes bite the human, the worms move to human body.…”

“…WHO has determined that one of the drugs used is Diethylcarbamazine (DEC). Drug mass administration was conducted once every year for 4-6 years [8]. This treatment can kill microfilaria and partially kill adult worms.…”

“…In 1974, WHO Expert Committee endorse that the standard dose for mass administration are 72 mg/kg of body weight given in 12 divided doses, monthly or weekly, at 6 mg/kg. sometime later, in French Polynesia, single dose treatment at 6 mg/kg, which is one twelfth of the WHO-recommended dose in a year was effective [8].…”