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

Kathrin Arndts,Sabine Specht,Sabine Mand,Mark Taylor,Alexander Kwarteng,Achim Hoerauf,Francesca Tamarozzi,Ute Klarmann Schulz,Ohene Adjei,Linda Batsa,Coralie Martin,Laura E Layland,Alexander Y Debrah,Peter U Fischer

doi:10.1371/journal.pntd.0002679

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.

Highlights

Infections with Onchocerca volvulus commence with the transmission of larvae by biting vector hosts [1,2]
Using multivariable regression analysis our data suggests that MF or IVM therapy can differently influence certain immune parameters
The data provides initial evidence that in response to diverse stimuli the secretion of a single cytokine (IL-10) from the same individual can be influenced by different factors

Summary

Introduction

Infections with Onchocerca volvulus commence with the transmission of larvae by biting vector hosts (black flies) [1,2]. Through mass drug administration (MDA) programmes, cases of river blindness are Author Summary. Infected individuals usually present a generalized form which is characterized by low inflammation, tightly-controlled immune responses and high parasite burden. Current disease control is based on mass drug administration (MDA) with ivermectin (IVM) which mainly eliminates microfilariae (MF), the transmission life-stage. In areas that have been part of MDA programmes, individuals have been identified that present nodules but are amicrofilaridermic (a-MF). Multivariable regression analysis revealed that immune responses were correlated to covariates MF, IVM or even the residing area (implying differing rounds of IVM MDA). The data imply that this ‘‘man-made’’ group has a distinct immune profile and suggests that immune responses are affected by the amount of IVM intake on both the individual and community level (region)

Methods

Results

Conclusion