Differential susceptibility of Onchocerca volvulus microfilaria to ivermectin in two areas of contrasting history of mass drug administration in Cameroon: relevance of microscopy and molecular techniques for the monitoring of skin microfilarial repopulation within six months of direct observed treatment

Abstract

Background Ivermectin is an excellent microfilaricide against Onchocerca volvulus. However, in some regions, long term use of ivermectin has resulted in sub-optimal responses to the treatment. More data to properly document the phenomenon in various contexts of ivermectin mass drug administration (IVM-MDA) is needed. Also, there is a need to accurately monitor a possible repopulation of skin by microfilariae following treatment. Skin snip microscopy is known to have a low sensitivity in individuals with light infections, which can be the case following treatment. This study was designed with two complementary objectives: (i) to assess the susceptibility of O. volvulus microfilariae to ivermectin in two areas undergoing IVM-MDA for different lengths of time, and (ii) to document the repopulation of skin by the O. volvulus microfilariae following treatment, using 3 independent diagnostic techniques. Method Identified microfilaridermic individuals were treated with ivermectin and re-examined after 1, 3, and 6 months using microscopy, actin real-time PCR (actin-qPCR) and O-150 LAMP assays. Susceptibility to ivermectin and trends in detecting reappearance of skin microfilariae were determined using three techniques. Microscopy was used as an imperfect gold standard to determine the performance of actin-qPCR and LAMP. Results In Bafia with over 20 years of IVM-MDA, 11/51 (21.6%) direct observe treated microfilaridemic participants were still positive for skin microfilariae after 1 month. In Melong, with 10 years of IVM-MDA, 2/29 (6.9%) treated participants were still positive. The microfilarial density reduction per skin biopsy within one month following treatment was significantly lower in participants from Bafia. In both study sites, the molecular techniques detected higher proportions of infected individuals than microscopy at all monitoring time points. LAMP demonstrated the highest levels of sensitivity and real-time PCR was found to have the highest specificity. Conclusion Patterns in skin mirofilariae clearance and repopulation were established. O. volvulus worms from Bafia with higher number of annual MDA displayed a lower clearance and higher repopulation rate after treatment with ivermectin. Molecular assays displayed higher sensitivity in monitoring O. volvulus microfilaridemia within six months following treatment.

Onchocerciasis in the Ntui Health District of Cameroon: epidemiological, entomological and parasitological findings in relation to elimination prospects

“…Following treatment with ivermectin, skin repopulation by O. volvulus mf has been shown to slowly resume within 3 to 6 months, but not reaching the initial infection intensity [ 35 , 36 ]. Additionally, previous research in endemic communities in Cameroon has suggested that in villages with > 20 years of CDTI as is the case with our study sites, there is a lower mf clearance and higher repopulation rate after treatment with ivermectin [ 37 ]. One can reasonably argue that, despite the sub-optimal coverage, the ivermectin treatment had lowered the community microfilarial load in the study villages such that the probability of a black fly taking up mf during a blood meal would also be low.…”

Urine metabolites for the identification of Onchocerca volvulus infections in patients from Cameroon

“…This will allow for faster decision making without the need for a second-stage mapping with larger samples sizes and the associated financial and logistical costs. We will test this hypothesis and establish an initial cutoff, with the aid of modeling, using urine from an upcoming study funded by COR-NTD that will compare O-150 serology to the O-150 LAMP assay [ 30 ].…”

Development of emodepside as a possible adulticidal treatment for human onchocerciasis—The fruit of a successful industrial–academic collaboration

“…Additionally, program fatigue in MDA has been reported after years of implementation, and an individual in an endemic area may find repeated MDA inconvenient or lose confidence in the MDA campaign. Furthermore, alarming reports of reduced drug efficacy in Ghana and Cameroon may also signal the development of resistance [18,19]. This situation, coupled with the risk of ivermectin resistance, presents an urgent need for a novel anthelmintic drug that preferably possesses macrofilaricidal or permanent sterilizing activity.…”