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

BMC Infectious Diseases

Kebede Deribe¹  Ritter Manuel²  Kenneth Pfarr³  Achim Hoerauf³  Clotilde K. S. Carlow⁴  Catherine B. Poole⁴  Abdel Jelil Njouendou⁵  Glory N. Amambo⁶  Patrick W. Chounna Ndongmo⁶  Jerome Fru-Cho⁶  Raphael Awah Abong⁶  Peter Ivo Enyong⁶  Amuam Andrew Beng⁶  Samuel Wanji⁶  Fanny F. Fombad⁶  Mathias Eyong Esum⁶  Theobald Mue Nji⁷ 

[1]Global Health and Infection Department, Brighton and Sussex Medical School, BN1 9PX, Brighton, UK

[2]School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia

[3]Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany

[4]Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany

[5]German Center for Infection Research (DZIF), partner site Bonn-Cologne, Bonn, Germany

[6]New England Biolabs, Ipswich, MA, USA

[7]Parasites and Vector Research Unit (PAVRU), Department of Microbiology and Parasitology, University of Buea, P.O. Box 63, Buea, Cameroon

[8]Department of Biomedical science, Faculty of Health Sciences, University of Buea, P.O. Box 63, Buea, Cameroon

[9]Parasites and Vector Research Unit (PAVRU), Department of Microbiology and Parasitology, University of Buea, P.O. Box 63, Buea, Cameroon

[10]Research Foundation in Tropical Diseases and Environment (REFOTDE), P.O. Box 474, Buea, Cameroon

[11]Research Foundation in Tropical Diseases and Environment (REFOTDE), P.O. Box 474, Buea, Cameroon

[12]Department of Sociology and Anthropology, University of Buea, Buea, Cameroon

关键词: Susceptibility;    Monitoring;    O. volvulus;    Microfilaridemia;    Microscopy;    Real-time PCR;    LAMP;    Microfilaricides;   

DOI  :  10.1186/s12879-020-05444-2

来源: Springer

【 摘 要 】

BackgroundIvermectin 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.MethodIdentified 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.ResultsIn 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.ConclusionPatterns 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.

【 授权许可】

CC BY