Volume 99, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Onchocerciasis is a neglected parasitic disease targeted for elimination. Current World Health Organization guidelines for elimination include monitoring antibody responses to the recombinant antigen OV-16 in children to demonstrate the absence of transmission. We report the performance characteristics of a modified OV-16 enzyme-linked immunosorbent assay (ELISA) and describe anti–OV-16 responses in serum samples from laboratory-inoculated nonhuman primates (NHPs) in relation to microfilariae (mf) in skin snip biopsies. This OV-16 IgG4 ELISA had sensitivity and specificity of 88.2% and 99.7%, respectively, as determined by receiver operator characteristic analysis using a serum panel of 110 positive and 287 negative samples from people infected with other filariae or other parasitic infections. Anti–OV-16 responses in inoculated NHP ( = 9) were evaluated at quarterly intervals for IgM and the four IgG subclasses. Enzyme-linked immunosorbent assay results showed a well-defined IgG4 reactivity pattern and moderate IgG1 antibody responses. Meanwhile, the reactivity by IgG2, IgG3, or IgM did not show a clear pattern. Temporal evolution of IgG4 reactivity was evaluated through monthly testing, showing that NHPs developed anti–OV-16 IgG4 on average at 15 months postinoculation (range: 10–18 months). The average time to detectable mf was also 15 months (range: 11–25). The OV-16 ELISA used in this study was robust and allowed the detection of IgG4 responses, which were observed only among animals with detectable mf ( = 5), four of which showed declines in antibody responses once mf cleared. These findings also confirmed that the most informative antibody subclass responses to OV-16 are IgG4.


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  1. World Health Organization, 2016. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification of elimination of transmission in Guatemala. Wkly Epidemiol Rec 91: 501504. [Google Scholar]
  2. Allen JE, 2008. Of mice, cattle, and humans: the immunology and treatment of river blindness. PLoS Negl Trop Dis 2: e217. [Google Scholar]
  3. Abraham D, Lucius R, Trees AJ, , 2002. Immunity to Onchocerca spp. in animal hosts. Trends Parasitol 18: 164171. [Google Scholar]
  4. Lovato R, Guevara A, Guderian R, Proano R, Unnasch T, Criollo H, Hassan HK, Mackenzie CD, , 2014. Interruption of infection transmission in the onchocerciasis focus of Ecuador leading to the cessation of ivermectin distribution. PLoS Negl Trop Dis 8: e2821. [Google Scholar]
  5. Rodriguez-Perez MA, Dominguez-Vazquez A, Unnasch TR, Hassan HK, Arredondo-Jimenez JI, Orozco-Algarra ME, Rodriguez-Morales KB, Rodriguez-Luna IC, Prado-Velasco FG, , 2013. Interruption of transmission of Onchocerca volvulus in the southern Chiapas Focus, Mexico. PLoS Negl Trop Dis 7: e2133. [Google Scholar]
  6. Gonzalez RJ, 2009. Successful interruption of transmission of Onchocerca volvulus in the Escuintla-Guatemala Focus, Guatemala. PLoS Negl Trop Dis 3: e404. [Google Scholar]
  7. Lindblade KA, 2007. Elimination of Onchocercia volvulus transmission in the Santa Rosa focus of Guatemala. Am J Trop Med Hyg 77: 334341. [Google Scholar]
  8. World Health Organization, 2013. Progress towards eliminating onchocerciasis in the WHO Region of the Americas: verification by WHO of elimination of transmission in Colombia. Wkly Epidemiol Rec 88: 381385. [Google Scholar]
  9. Higazi TB, 2013. Interruption of Onchocerca volvulus transmission in the Abu Hamed Focus, Sudan. Am J Trop Med Hyg 89: 5157. [Google Scholar]
  10. Katabarwa M, 2014. Transmission of Onchocerca volvulus by Simulium neavei in Mount Elgon focus of eastern Uganda has been interrupted. Am J Trop Med Hyg 90: 11591166. [Google Scholar]
  11. Oguttu D, 2014. Serosurveillance to monitor onchocerciasis elimination: the Ugandan experience. Am J Trop Med Hyg 90: 339345. [Google Scholar]
  12. World Health Organization, 2014. Elimination of onchocerciasis in the WHO region of the Americas: Ecuador’s progress towards verification of elimination. Wkly Epidemiol Rec 89: 401405. [Google Scholar]
  13. World Health Organization, 2015. Progress toward eliminating onchocerciasis in the WHO region of the Americas: verification of elimination of transmission in Mexico. Wkly Epidemiol Rec 90: 577581. [Google Scholar]
  14. World Health Organization, 2010. African programme for onchocerciasis control—report of the sixth meeting of National Task Forces, October 2009. Wkly Epidemiol Rec 85: 2328. [Google Scholar]
  15. World Health Organization, 1995. Onchocerciasis and its control. Report of a WHO expert committee on onchocerciasis control. World Health Organ Tech Rep Ser 852: 1104. [Google Scholar]
  16. Bottomley C, Isham V, Vivas-Martinez S, Kuesel AC, Attah SK, Opoku NO, Lustigman S, Walker M, Basanez MG, , 2016. Modelling neglected tropical diseases diagnostics: the sensitivity of skin snips for Onchocerca volvulus in near elimination and surveillance settings. Parasit Vectors 9: 343. [Google Scholar]
  17. Thiele EA, Cama VA, Lakwo T, Mekasha S, Abanyie F, Sleshi M, Kebede A, Cantey PT, , 2016. Detection of Onchocerca volvulus in skin snips by microscopy and real-time polymerase chain reaction: implications for monitoring and evaluation activities. Am J Trop Med Hyg 94: 906911. [Google Scholar]
  18. Toe L, Boatin BA, Adjami A, Back C, Merriweather A, Unnasch TR, , 1998. Detection of Onchocerca volvulus infection by O-150 polymerase chain reaction analysis of skin scratches. J Infect Dis 178: 282285. [Google Scholar]
  19. Lobos E, Altmann M, Mengod G, Weiss N, Rudin W, Karam M, , 1990. Identification of an Onchocerca volvulus cDNA encoding a low-molecular-weight antigen uniquely recognized by onchocerciasis patient sera. Mol Biochem Parasitol 39: 135145. [Google Scholar]
  20. Lobos E, Weiss N, Karam M, Taylor HR, Ottesen EA, Nutman TB, , 1991. An immunogenic Onchocerca volvulus antigen: a specific and early marker of infection. Science 251: 16031605. [Google Scholar]
  21. Lazzeri M, Nutman T, Weiss N, , 1995. Nucleotide Molecule Enconding a Specific Onchocerca volvulus Antigen for the Immunodiagnosis of onchocerciasis. USPTO, ed. Washington, DC: United Stated Patent and Trademark Office. United States Patent Number: 5,416,009.
  22. Ogunrinade AF, Awolola SO, Rotimi O, Chandrashekar R, , 2000. Longitudinal studies of skin microfilaria and antibody conversion rates in children living in an endemic focus of onchocerciasis in Nigeria. J Trop Pediatr 46: 348351. [Google Scholar]
  23. Rodriguez-Perez MA, Unnasch TR, Dominguez-Vazquez A, Morales-Castro AL, Pena-Flores GP, Orozco-Algarra ME, Arredondo-Jimenez JI, Richards F, Jr. Vasquez-Rodriguez MA, Rendon VG, , 2010. Interruption of transmission of Onchocerca volvulus in the Oaxaca focus, Mexico. Am J Trop Med Hyg 83: 2127. [Google Scholar]
  24. Zarroug IM, 2016. The first confirmed elimination of an onchocerciasis focus in Africa: Abu Hamed, Sudan. Am J Trop Med Hyg 95: 10371040. [Google Scholar]
  25. Eberhard ML, Dickerson JW, Boyer AE, Tsang VC, Zea-Flores R, Walker EM, Richards FO, Zea-Flores G, Strobert E, , 1991. Experimental Onchocerca volvulus infections in mangabey monkeys (Cercocebus atys) compared to infections in humans and chimpanzees (Pan troglodytes). Am J Trop Med Hyg 44: 151160. [Google Scholar]
  26. Eberhard ML, 1995. Onchocerca volvulus: parasitologic and serologic responses in experimentally infected chimpanzees and mangabey monkeys. Exp Parasitol 80: 454462. [Google Scholar]
  27. Abraham D, Lange AM, Yutanawiboonchai W, Trpis M, Dickerson JW, Swenson B, Eberhard ML, , 1993. Survival and development of larval Onchocerca volvulus in diffusion chambers implanted in primate and rodent hosts. J Parasitol 79: 571582. [Google Scholar]
  28. Cruz-Ortiz N, Gonzalez RJ, Lindblade KA, Richards FO, Jr. Sauerbrey M, Zea-Flores G, Dominguez A, Oliva O, Catu E, Rizzo N, , 2012. Elimination of Onchocerca volvulus transmission in the Huehuetenango focus of Guatemala. J Parasitol Res 2012: 638429. [Google Scholar]
  29. Press WH, Flannery BP, Teukolski SA, Vetterling WT, , 1988. Numerical Recipes in C: The Art of Scientific Computing. New York, NY: Cambridge University Press.
  30. Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, Muller M, , 2011. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12: 77. [Google Scholar]
  31. Burbelo PD, Leahy HP, Iadarola MJ, Nutman TB, , 2009. A four-antigen mixture for rapid assessment of Onchocerca volvulus infection. PLoS Negl Trop Dis 3: e438. [Google Scholar]
  32. Golden A, 2013. Extended result reading window in lateral flow tests detecting exposure to Onchocerca volvulus: a new technology to improve epidemiological surveillance tools. PLoS One 8: e69231. [Google Scholar]
  33. Gass K, , 2018. Rethinking the serological threshold for onchocerciasis elimination. PLoS Negl Trop Dis 12: e0006249. [Google Scholar]
  34. Boyer AE, Tsang VC, Eberhard ML, Zea-Flores G, Hightower A, Pilcher JB, Zea-Flores R, Zhou W, Reimer CB, , 1991. Guatemalan human onchocerciasis. II. Evidence for IgG3 involvement in acquired immunity to Onchocerca volvulus and identification of possible immune-associated antigens. J Immunol 146: 40014010. [Google Scholar]
  35. Tsang VC, Boyer AE, Pilcher JB, Eberhard ML, Reimer CB, Zea-Flores G, Zea-Flores R, Zhou W, Richards FO, , 1991. Guatemalan human onchocerciasis. I. Systematic analysis of patient populations, nodular antigens, and specific isotypic reactions. J Immunol 146: 39934000. [Google Scholar]
  36. Weiss N, , 1986. Immunological approaches to the detection of prepatent onchocerciasis. J Commun Dis 18: 254260. [Google Scholar]
  37. Henry NL, Law M, Nutman TB, Klion AD, , 2001. Onchocerciasis in a nonendemic population: clinical and immunologic assessment before treatment and at the time of presumed cure. J Infect Dis 183: 512516. [Google Scholar]
  38. Evans DS, 2014. Status of Onchocerciasis transmission after more than a decade of mass drug administration for onchocerciasis and lymphatic filariasis elimination in central Nigeria: challenges in coordinating the stop MDA decision. PLoS Negl Trop Dis 8: e3113. [Google Scholar]

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  • Received : 13 Feb 2018
  • Accepted : 18 Jun 2018
  • Published online : 30 Jul 2018

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