Assessing <i>Onchocerca volvulus</i> Intensity of Infection and Genetic Diversity Using Mitochondrial Genome Sequencing of Single Microfilariae Obtained before and after Ivermectin Treatment
Shannon M. Hedtke,
Young-Jun Choi,
Anusha Kode,
Gowtam C. Chalasani,
Neha Sirwani,
Stephen R. Jada,
An Hotterbeekx,
Michel Mandro,
Joseph N. Siewe Fodjo,
Glory Ngongeh Amambo,
Raphael A. Abong,
Samuel Wanji,
Annette C. Kuesel,
Robert Colebunders,
Makedonka Mitreva,
Warwick N. Grant
Affiliations
Shannon M. Hedtke
Department of Environment and Genetics, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia
Young-Jun Choi
Department of Medicine, Washington University in St. Louis and McDonnell Genome Institute, St. Louis, MO 63108, USA
Anusha Kode
Department of Environment and Genetics, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia
Gowtam C. Chalasani
Department of Environment and Genetics, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia
Neha Sirwani
Department of Environment and Genetics, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia
Stephen R. Jada
Amref South Sudan, Juba P.O. Box 30125, South Sudan
An Hotterbeekx
Global Health Institute, University of Antwerp, Doornstraat 331, 2610 Antwerp, Belgium
Michel Mandro
Provincial Health Division Ituri, Ministry of Health, Bunia P.O. Box 57, Democratic Republic of the Congo
Joseph N. Siewe Fodjo
Global Health Institute, University of Antwerp, Doornstraat 331, 2610 Antwerp, Belgium
Glory Ngongeh Amambo
Parasites and Vectors Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon
Raphael A. Abong
Parasites and Vectors Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon
Samuel Wanji
Parasites and Vectors Research Unit, Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea P.O. Box 63, Cameroon
Annette C. Kuesel
UNICEF/UNDP/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases (TDR), World Health Organization, 1202 Geneva, Switzerland
Robert Colebunders
Global Health Institute, University of Antwerp, Doornstraat 331, 2610 Antwerp, Belgium
Makedonka Mitreva
Department of Medicine, Washington University in St. Louis and McDonnell Genome Institute, St. Louis, MO 63108, USA
Warwick N. Grant
Department of Environment and Genetics, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC 3086, Australia
Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4–5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample (n = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission.
