We conducted a cost analysis of Haiti's Ministry of Public Health and Population neglected tropical disease program, Projet des Maladies Tropicales Negligées and collected data for 9 of 55 communes participating in the May 2008-April 2009 mass drug administration (MDA). The Projet des Maladies Tropicales Negligées Program partnered with IMA World Health and Hôpital Ste. Croix to implement MDA for treatment of lymphatic filariasis and soil-transmitted helminthiasis by using once a year treatment with albendazole and diethylcarbamazine in a population of approximately 8 million persons. Methods included analyzing partner financial records and conducting retrospective surveys of personnel. In the nine communes, 633,261 persons were treated at a cost of U.S.$0.64 per person, which included the cost of donated drugs, and at a cost of U.S.$0.42 per person treated, when excluding donated drug costs. The MDA for lymphatic filariasis in Haiti began in 2000, with the treatment of 105,750 persons at a cost per person of U.S.$2.23. The decrease in cost per person treated is the result of cumulative implementation experience and economies of scale.

Citing earlier advances in the treatment of lymphatic filariasis [particularly the effectiveness of single-dose diethylcarbamazine (DEC) in reducing microfilaraemia and its enhanced effectiveness when co-administered with single-dose ivermectin], Eric Ottesen, Mahroof Ismail and John Horton consider recent studies on the antifilarial activity of albendazole that have led to the current recommendations for its use in single-dose regimens in conjunction with either DEC or ivermectin for large-scale control/elimination programmes. Furthermore, the potential of albendazole as a macrofilaricide for treating individual patients with lymphatic filarial infections is emphasized as one of a number of important research questions that remain to be explored.

Diethylcarbamazine (DEC) is an effective microfilaricidal drug against Wuchereria bancrofti, Brugia malayi, and Brugia timori--the three lymphatic-dwelling filariae infecting humans. However, effectiveness in killing the adult stage of these parasites has been more difficult to establish. The present review of available evidence from the literature suggests that:(1) in addition to being a microfilaricidal agent, DEC in conventional dosages effectively kills adult worms of these three parasites in many patients;(2) relatively high total dosages of DEC (including dosages considerably in excess of those currently recommended) generally give better long-term therapeutic results than lower dosages;(3) spaced doses of DEC (weekly or monthly) are more effective than the same total dosage given in consecutive daily doses;(4) chronic administration of low-dose DEC, as in medicated salt, can effectively control filariasis caused by W. bancrofti or B. malayi; and (5) rational determination of the DEC regimen ideal for the killing of adult filarial parasites awaits the development of assays capable of sensitively detecting the presence of living adult parasites.

BACKGROUND The global initiative to eradicate bancroftian filariasis currently relies on mass treatment with four to six annual doses of antifilarial drugs. The goal is to reduce the reservoir of microfilariae in the blood to a level that is insufficient to maintain transmission by the mosquito vector. METHODS In nearly 2500 residents of Papua New Guinea, we prospectively assessed the effects of four annual treatments with a single dose of diethylcarbamazine plus ivermectin or diethylcarbamazine alone on the incidence of microfilariae-positive infections, the severity of lymphatic disease, and the rate of transmission of Wuchereria bancrofti by mosquitoes. Random assignment to treatment regimens was carried out according to the village of residence, and villages were categorized as having moderate or high rates of transmission. RESULTS The four annual treatments with either drug regimen were taken by 77 to 86 percent of the members of the population who were at least five years old; treatments were well tolerated. The proportion with microfilariae-positive infections decreased by 86 to 98 percent, with a greater reduction in areas with a moderate rate of transmission than in those with a high rate. The respective aggregate frequencies of hydrocele and leg lymphedema were 15 percent and 5 percent before the trial began, and 5 percent (P<0.001) and 4 percent (P=0.04) after five years. Hydrocele and leg lymphedema were eliminated in 87 percent and 69 percent, respectively, of those who had these conditions at the outset. The rate of transmission by mosquitoes decreased substantially, and new microfilariae-positive infections in children were almost completely prevented over the five-year study period. CONCLUSIONS Annual mass treatment with drugs such as diethylcarbamazine can virtually eliminate the reservoir of microfilariae and greatly reduce the frequency of clinical lymphatic abnormalities due to bancroftian filariasis. Eradication may be possible in areas with moderate rates of transmission, but longer periods of treatment or additional control measures may be necessary in areas with high rates of transmission.

BACKGROUND: WHO has targeted lymphatic filariasis for elimination. Studies of vector-parasite relations of Wuchereria bancrofti suggest that a reduction in the microfilarial reservoir by mass chemotherapy may interrupt transmission and thereby eliminate infection. However, no field data exist on the impact of chemotherapy alone on vector efficiency and transmission intensity of W bancrofti. We compared the impact of an annual community-wide single-dose treatment with diethylcarbamazine alone or with ivermectin on rate and intensity of microfilaraemia, and transmission intensity in an area of Papua New Guinea endemic for intense W bancrofti transmission. METHODS: We carried out clinical and parasitological surveys in 14 communities in matched pairs. People aged 5 years or older in seven communities received randomly assigned diethylcarbamazine 6 mg/kg and people in the other seven communities received diethylcarbamazine 6 mg/kg plus ivermectin 400 micrograms/kg. We made physical examinations for hydroceles and leg oedema and investigated microfilarial densities by membrane filtration before and after treatment. We selected five communities for monthly entomological surveys between September, 1993, and September, 1995. Mosquitoes were collected in these communities by the all-night landing catch method and were individually dissected to identify rates of infection and infectiveness. FINDINGS: 2219 (87.6%) of 2534 eligible people received treatment. Microfilarial rate and density had decreased 1 year after treatment in all 14 communities; this decrease was significantly higher in communities given combined therapy than in those given diethylcarbamazine alone (mean decreases 57.5% and 30.6%, respectively; p = 0.0013). Greater decreases were also seen in community-specific microfilarial intensity with combined therapy (mean reductions 91.1% and 69.8%, respectively; p = 0.0047). The rate of leg oedema was not altered, but the frequency of advanced hydroceles decreased by 47% with combined therapy and 56% with diethylcarbamazine alone. 26,641 Anopheles punctulatus mosquitoes were caught during 499 person-nights of landing catches. Exposure to infective third-stage larvae decreased in all monitored five communities. Annual transmission potential decreased by between 75.7% and 98.8% in combined-therapy communities and between 75.6% and 79.4% in communities given diethylcarbamazine alone. Transmission was almost interrupted in two communities treated with combined therapy. INTERPRETATION: Annual single-dose community-wide treatment with diethylcarbamazine alone or with ivermectin is effective for the control of lymphatic filariasis in highly endemic areas, but combination therapy brings about greater decreases in rates and intensity of microfilaraemia.

To compare the efficacy and tolerability of various combinations of low- and high-dose ivermectin and diethylcarbamazine (DEC), 59 persons with Wuchereria bancrofti microfilaremia were enrolled in a double-blinded six-arm clinical trial in Leogane, Haiti. On day 1, study participants were treated with low clearing doses of ivermectin, DEC, or placebo; on day 5 they received 200-400 micrograms/kg of ivermectin or 6 mg/kg of DEC. Adverse reactions, which were generally mild, occurred more frequently with ivermectin than with DEC. One year after treatment, the geometric mean microfilarial density returned to 0.9% of pretreatment levels for persons who received a total of 420 micrograms/kg of ivermectin. This rate was significantly lower than 5.6% for persons who were treated with 220 micrograms/kg of ivermectin (P = 0.02) and 9.3% for those receiving 6 or 7 mg/kg of DEC (P = 0.006). Persons treated with a clearing dose of ivermectin followed by 6 mg/kg of DEC also had low microfilarial densities (1.7% of pretreatment levels), suggesting an additive or synergistic effect of the two drugs. The addition of a clearing dose neither reduced the severity of adverse reactions nor improved the efficacy of high-dose ivermectin. Community-based intervention trials are now warranted to determine the feasibility and effectiveness of mass chemotherapy with single high-dose ivermectin for the prevention and control of lymphatic filariasis.

This double-blind study compared the clinical safety and parasitologic efficacy of single-dose regimens of diethylcarbamazine (DEC) and ivermectin for treatment of bancroftian filariasis in Papua New Guinea. Five groups of 10 men each with mean levels of parasitemia ranging from 2,985 to 5,185 microfilariae (mf)/ml were given DEC (6 mg/kg of body weight one time or 1 mg/kg, then 6 mg/kg four days later) or ivermectin (220 micrograms/kg; 20 micrograms/kg, then 200 micrograms/kg four days later or 20 micrograms/kg, then 400 micrograms/kg four days later). No significant side effects (e.g., acute adenolymphangitis, fever lasting more than eight hours, hypotension) were observed in any of the five treatment groups. The magnitude of reduction in microfilaremia was greater (P < 0.01) for the three ivermectin groups versus the two DEC groups in the first 30 days after drug administration (mf levels < 1% of pretreatment values versus 22.6-41.5%, respectively). At 90 and 180 days, mf levels continued to decrease in the DEC groups whereas they increased in the ivermectin groups given a total dose of 220 micrograms/kg. Eighteen months after drug administration, individuals given DEC or 420 micrograms/kg of ivermectin had the greatest degree of reduction in microfilaremia (86-90% compared with the pretreatment values). Decreases in parasite antigenemia measured by enzyme-linked immunosorbent assay for a secreted 200-kD adult worm antigen were greatest for the single-dose DEC group (39.7% decrease relative to the pretreatment level versus 7.8-15.7% for the ivermectin groups). These results indicate that single-dose DEC and ivermectin are well-tolerated by Wuchereria bancrofti-infected individuals with high levels of microfilaremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Ivermectin is a new antifilarial drug that can be given in a single oral dose. To compare the efficacy and side effects of ivermectin with those of diethylcarbamazine, the standard antifilarial treatment, we conducted a randomized, double-blind trial in 40 South Indian men with lymphatic filariasis caused by Wuchereria bancrofti. Patients were randomly assigned to one of three treatments: a single low dose of ivermectin (mean [+/- SE], 21.3 +/- 0.7 micrograms per kilogram of body weight; n = 13) followed by placebo for 12 days; a single high dose of ivermectin (mean, 126.2 +/- 3.7 micrograms per kilogram; n = 13) followed by placebo for 12 days; or diethylcarbamazine for 13 days (6 mg per kilogram per day for 12 days preceded by 3 mg per kilogram for 1 day; n = 14). Eleven patients were initially assigned to receive placebo and after five days were reassigned to one of the three treatment groups. At day 12 there was complete clearance of microfilariae from the blood in all 26 men who took ivermectin and in 11 of the 14 men who took diethylcarbamazine. At six months the numbers of detectable microfilariae (as a percentage of the pretreatment values) were 18.3 percent after low-dose ivermectin and 19.5 percent after high-dose ivermectin, as compared with 6.0 percent after diethylcarbamazine (P less than 0.05). The side effects were confined to the first five days and were similar in the three treatment groups. We conclude that in lymphatic filariasis, the clinical response to a single dose of ivermectin compares favorably with that after the standard 12-day course of diethylcarbamazine. Given the practical advantages of single-dose administration, ivermectin should become a useful medication for the control of bancroftian filariasis.

OBJECTIVE To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems.

Circulating filarial antigen (CFA), determined with Og4C3 ELISA, is a marker of Wuchereria bancrofti adult worm infection. The reduction of CFA over 2 years was determined in 185 microfilaremic and 111 amicrofilaremic but CFA+ adults given an annual dose of either diethylcarbamazine (DEC) or ivermectin or the two combined. Reduction of CFA level was good with DEC but weak with ivermectin and followed the same pattern in amicrofilaremic and microfilaremic groups. Combinations and DEC alone had a similar impact on CFA level. CFA clearance was observed in amicrofilaremic but not in microfilaremic persons in all DEC-containing treatments. However, the highest clearance rate was observed in persons treated with DEC at 6 mg/kg combined with ivermectin. Continuous reduction of CFA level after repeated treatments shows that elimination of W. bancrofti infection, monitored by CFA clearance, might be achieved within a few years with annual treatments of DEC combined with ivermectin.

In a 'blinded' trial (in Sri Lanka, 1996-98) of 47 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of 3 single-dose combination regimens were compared: albendazole 400 mg with ivermectin 200 micrograms/kg, albendazole 400 mg with diethylcarbamazine citrate (DEC) 6 mg/kg or albendazole 600 mg with ivermectin 400 micrograms/kg. Treated subjects were followed-up for 24 months. This represents the first long-term study using combinations of albendazole with DEC or ivermectin in the above doses against bancroftian filariasis. All subjects had pre-treatment microfilaria (mf) counts over 100/mL. All 3 treatments significantly reduced mf counts, with the albendazole-DEC-treated group showing the lowest mf levels at 18 and 24 months post-treatment. Filarial antigen tests suggested that all 3 treatments had significant activity against adult W. bancrofti; albendazole-DEC combination had the greatest activity according to this test, with antigen levels decreasing to 30.5% of pre-treatment antigen levels, 24 months after therapy. All 3 treatments were clinically safe and well tolerated. These results suggest that a single dose of albendazole 400 mg together with DEC 6 mg/kg is a safe and effective combination for suppression of microfilaraemia of bancroftian filariasis that could be considered for use in filariasis control programmes based on mass treatment of endemic populations.