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.

BACKGROUND: Annual mass drug administrations (MDA) of ivermectin will strongly reduce Onchocerca volvulus microfilariae (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 of O. 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 active O. volvulus infections persist. METHODOLOGY/PRINCIPAL FINDINGS: Onchocerciasis patients were treated annually with ivermectin and their Onchocerca volvulus antigen (OvAg) specific IgG and cellular responses were investigated before and at 30 years post initial ivermectin treatment (30yPT). Repeated annual ivermectin treatments eliminated persisting O. volvulus microfilariae (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 of O. volvulus continued at the patients' location in the Mô river basin in central Togo 2018 and 2019 when 0.58% and 0.45%, respectively, of Simulium damnosum s.l. vector blackflies carried O. volvulus infections. CONCLUSIONS/SIGNIFICANCE: Repeated annual ivermectin treatment of onchocerciasis patients durably inhibited their patent O. volvulus infections despite ongoing low-level parasite transmission in the study area. Repeated MDA with ivermectin affects the expression of immunity in patients. O. volvulus parasite-specific antibody levels diminished to levels seen in infection-free endemic controls. With low antibody levels, antibody-dependent cellular cytotoxic responses against tissue-dwelling O. volvulus larvae will weaken. O. volvulus antigen 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 of O. volvulus. The annual Simulium damnosum s.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 ongoing O. volvulus transmission.

Assessment of the usefulness of anti-Wb123 antibody for post-elimination surveillance of lymphatic filariasis.

BACKGROUND: The World Health Organization has targeted lymphatic filariasis (LF) for elimination as a public health problem and recommends, among other measures, post-elimination surveillance of LF. The identification of sensitive and specific surveillance tools is therefore a research priority. The Wuchereria bancrofti-specific antigen Wb123-based enzyme-linked immunosorbent assay (Wb123 ELISA) detects antibodies to the recombinant Wb123 antigen of W. bancrofti and may be useful as a surveillance tool for LF. Six years after stopping mass drug administration to eliminate LF and recording successful results on two post-treatment transmission assessment surveys, a study was conducted in Togo aimed at helping to identify the role of the Wb123 ELISA in post-validation surveillance of LF. METHODS: This was a cross-sectional study in eight previously LF-endemic districts and one non-endemic district in Togo. In each sub-district of these nine districts, two schools were selected and 15 children aged 6 to 9 years old at each school provided finger-stick blood for testing for antibodies to Wb123 using the Filaria Detect™ IgG4 ELISA kit® (InBios, International, Inc., Seattle, WA, USA). RESULTS: A total of 2654 children aged 6 to 9 years old were tested in 134 schools in the nine districts. Overall, 4.7% (126/2654) children tested positive for antibodies to the Wb123 antigen of W. bancrofti. The prevalence of Wb123 antibodies varied across the eight previously endemic LF districts, from 1.56 to 6.62%. The highest prevalence, 6.99%, was found in the non-endemic district, but this was not significantly different from the average of all the LF districts (4.49%, P = 0.062). CONCLUSIONS: The Wb123 ELISA was positive in 4.7% of Togolese school-age children who were almost certainly unexposed to LF. This apparent lack of specificity in the Togo context makes it difficult to establish a seroprevalence threshold that could serve to signal LF resurgence in the country, precluding the use of this test for post-validation surveillance in Togo. There remains a need to develop a useful and reliable test for post-elimination surveillance for LF in humans.