Immunoepidemiological profiling of onchocerciasis patients reveals associations with microfilaria loads and ivermectin intake on both individual and community levels

PLoS Negl Trop Dis. 2014 Feb 20;8(2):e2679. doi: 10.1371/journal.pntd.0002679. eCollection 2014 Feb.

Abstract

Mass drug administration (MDA) programmes against Onchocerca volvulus use ivermectin (IVM) which targets microfilariae (MF), the worm's offspring. Most infected individuals are hyporesponsive and present regulated immune responses despite high parasite burden. Recently, with MDA programmes, the existence of amicrofilaridermic (a-MF) individuals has become apparent but little is known about their immune responses. Within this immunoepidemiological study, we compared parasitology, pathology and immune profiles in infection-free volunteers and infected individuals that were MF(+) or a-MF. The latter stemmed from villages in either Central or Ashanti regions of Ghana which, at the time of the study, had received up to eight or only one round of MDA respectively. Interestingly, a-MF patients had fewer nodules and decreased IL-10 responses to all tested stimuli. On the other hand, this patient group displayed contrary IL-5 profiles following in vitro stimulation or in plasma and the dampened response in the latter correlated to reduced eosinophils and associated factors but elevated neutrophils. Furthermore, multivariable regression analysis with covariates MF, IVM or the region (Central vs. Ashanti) revealed that immune responses were associated with different covariates: whereas O. volvulus-specific IL-5 responses were primarily associated with MF, IL-10 secretion had a negative correlation with times of individual IVM therapy (IIT). All plasma parameters (eosinophil cationic protein, IL-5, eosinophils and neutrophils) were highly associated with MF. With regards to IL-17 secretion, although no differences were observed between the groups to filarial-specific or bystander stimuli, these responses were highly associated with the region. These data indicate that immune responses are affected by both, IIT and the rounds of IVM MDA within the community. Consequently, it appears that a lowered infection pressure due to IVM MDA may affect the immune profile of community members even if they have not regularly participated in the programmes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antibodies, Helminth / blood
  • Antiparasitic Agents / administration & dosage*
  • Antiparasitic Agents / therapeutic use
  • Cohort Studies
  • Cytokines / blood
  • Female
  • Humans
  • Ivermectin / administration & dosage*
  • Ivermectin / therapeutic use
  • Male
  • Middle Aged
  • Onchocerca / immunology*
  • Onchocerciasis / epidemiology*
  • Onchocerciasis / immunology*
  • Parasite Load
  • Young Adult

Substances

  • Antibodies, Helminth
  • Antiparasitic Agents
  • Cytokines
  • Ivermectin

Grants and funding

This work was funded by through a grant from the Liverpool School of Tropical Medicine as part of the A-WOL Consortium funded by the Bill and Melinda Gates Foundation. In addition, the study was supported by the European Commission (grant No. 242121, EPIAF), the German Research Foundation (DGF, grants Ho2009/8-1), the BONFOR intramural funding program of the Medical Faculty of Bonn University, and a European Foundation Initiative into African Research in Neglected Tropical diseases (EFINTD) awarded to AYD (grant 1/81995 and 86 52). AH is a member of the Excellence Cluster Immunosensation (DFG, EXC 1023). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.