Safety and efficacy of co-administered diethylcarbamazine, albendazole and ivermectin during mass drug administration for lymphatic filariasis in Haiti: Results from a two-armed, open-label, cluster-randomized, community study

Abstract

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared

An open label, block randomized, community study of the safety and efficacy of co-administered ivermectin, diethylcarbamazine plus albendazole vs. diethylcarbamazine plus albendazole for lymphatic filariasis in India

“…CFA clearance after treatment was somewhat more frequent in those who had lower baseline FTS scores, particularly in children, and this is probably because of their worm loads at baseline. Although CFA clearance rates were higher in the Haiti IDA safety study (20.5-25.5%) than in this study, the Haiti study also found no difference in CFA clearance after IDA or DA [23]. In contrast to our results, clearance of CFA was higher among adults in Haiti.…”

“…Mf clearance rates 12-month post-treatment with either IDA (84%) or DA (62%) were lower in this study than those reported from the parallel study in Haiti (IDA vs DA: 94.4% vs 75.9) [23]. It is possible that this is due to the fact that DEC dosing was based on weight in Haiti and by age in our study.…”

“…Pre-treatment Mf counts in microfilaremic individuals in our study were much lower compared to those in prior clinical trials or in the community IDA safety study in Haiti [23]. IDA and DA were almost equally effective in this study for clearing Mf when baseline Mf counts were low, while IDA was much more effective for clearing Mf in persons with higher baseline Mf counts.…”

“…However, this does not explain the higher frequency of AE in females, because infections were more common in PLOS NEGLECTED TROPICAL DISEASES males in both treatment areas. It is likely that males tended to ignore or underreport mild AEs, and this has been as observed in other studies [23]. Adults had higher AE frequencies than children because of their higher infection prevalences.…”

Lymphatic filariasis epidemiology in Samoa in 2018: Geographic clustering and higher antigen prevalence in older age groups

“…Similar results were observed in PNG, where a 50% reduction in Og4C3 Ag level was observed at 12 months [ 32 ]. Studies in PNG [ 35 , 36 ] and Haiti [ 37 ] reported that after a single dose of IDA, 95%-97% and 79.5% of Ag-positive participants were still positive after 12 months, respectively. These findings suggest that after treatment with IDA, Ag-positivity is likely to persist for months in the majority of people.…”