Onchocerca volvulus-specific antibody and cellular responses in onchocerciasis patients treated annually with ivermectin for 30 years and exposed to parasite transmission in central Togo
Authors: Johanns Saskia I. , Gantin Richard G. , Wangala Bawoubadi , Komlan Kossi , Halatoko Wemboo A. , Banla Meba , Karabou Potchoziou , Luty Adrian JF , Schulz-Key Hartwig , Köhler Carsten , Soboslay Peter T. 
Published: May 2022

BackgroundAnnual mass drug administrations (MDA) of ivermectin will strongly reduceOnchocerca volvulusmicrofilariae (mf) in the skin and in the onchocerciasis patients’ eyes. Ivermectin treatment will also affect the expression of immunity in patients, such that activated immune defenses may help control and contribute to clearance of mf ofO.volvulus. Longitudinal surveys are a prerequisite to determining the impact of ivermectin on the status of anti-parasite immunity, notably in risk zones where parasite transmission and activeO.volvulusinfections persist.Methodology/Principal findingsOnchocerciasis patients were treated annually with ivermectin and theirOnchocerca volvulusantigen (OvAg) specific IgG and cellular responses were investigated before and at 30 years post initial ivermectin treatment (30yPT).Repeated annual ivermectin treatments eliminated persistingO.volvulusmicrofilariae (mf) from the skin of patients and abrogated patent infections. The OvAg-specific IgG1 and IgG4 responses were diminished at 30yPT to the levels observed in endemic controls. Prior to starting ivermectin treatment, OvAg-induced cellular productions of IL-10, IFN-γ, CCL13, CCL17 and CCL18 were low in patients, and at 30yPT, cellular cytokine and chemokine responses increased to the levels observed in endemic controls. In contrast, mitogen(PHA)- induced IL-10, IFN-γ, CCL17 and CCL18 cellular production was diminished. This divergent response profile thus revealed increased parasite antigen-specific but reduced polyclonal cellular responsiveness in patients. The transmission ofO.volvuluscontinued at the patients’ location in the Mô river basin in central Togo 2018 and 2019 when 0.58% and 0.45%, respectively, ofSimulium damnosum s.l. vector blackflies carriedO.volvulusinfections.Conclusions/SignificanceRepeated annual ivermectin treatment of onchocerciasis patients durably inhibited their patentO.volvulusinfections despite ongoing low-level parasite transmission in the study area. Repeated MDA with ivermectin affects the expression of immunity in patients.O.volvulusparasite-specific antibody levels diminished to levels seen in infection-free endemic controls. With low antibody levels, antibody-dependent cellular cytotoxic responses against tissue-dwellingO.volvuluslarvae will weaken.O.volvulusantigen inducible cytokine and chemokine production increased in treated mf-negative patients, while their innate responsiveness to mitogen declined. Such lower innate responsiveness in elderly patients could contribute to reduced adaptive immune responses to parasite infections and vaccines. On the other hand, increased specific cellular chemokine responses in mf-negative onchocerciasis patients could reflect effector cell activation against tissue invasive larval stages ofO.volvulus. The annualSimulium damnosums.l. biting rate observed in the Mô river basin was similar to levels prior to initiation of MDA with ivermectin, and the positive rtPCR results reported here confirm ongoingO.volvulustransmission.