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. Microscopy is known to have low sensitivity to detect skin microfilariae, when their density is low following treatment. This study was designed with two complementary objectives: (i) to assess the susceptibility of O. volvulus microfilariae to ivermectin in situations of contrasting history of treatments, and (ii) to document the repopulation of skin by the O. volvulus microfilariae following treatment, comparing the performances of 3 independent diagnostic techniques.
Method
Identified microfilaridermic individuals were treated with ivermectin and re-examined after 1, 3, and 6 months using microscopy, real-time PCR and LAMP assays. Susceptibility to ivermectin and trends in detecting reappearance of skin microfilariae were reported for the three techniques. Microscopy was used as an imperfect gold standard to determine the performance characteristics of real-time PCR and LAMP assay.
Results
In Bafia with over 20 years of IVM-MDA, 11/51 (21.6%) treated microfilaridemic participants where 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, but the pattern in the two sites was similar.
In both study sites, the molecular techniques detected higher proportions of infected individuals than microscopy at all monitoring time points. LAMP assay showed lower specificity compared to real-time PCR and microscopy, but had comparable sensitivity to real-time PCR and significantly higher sensitivity than microscopy.
Conclusion
Patterns in skin mirofilarial clearance and repopulation were established. O . volvulus worms from Bafia with higher number of annual MDA were less susceptible to ivermectin. Molecular assays displayed higher sensitivity in monitoring O. volvulus microfilaridemia within six months following treatment.