Impact of ivermectin and vector control on onchocerciasis transmission in Togo: Assessing the empirical evidence on trends in infection and entomological indicators.

BACKGROUND: The World Health Organization's 2021-2030 Road Map for Neglected Tropical Diseases boosted global commitment towards the elimination of onchocerciasis, but the timeline to elimination will vary strongly between countries in Africa. To assess progress towards elimination in the Republic of Togo, we reviewed the history of control and time trends in infection. METHODOLOGY/PRINCIPAL FINDINGS: We collated all available programmatic, entomological, and epidemiological data since the initiation of the Onchocerciasis Control Programme (OCP) in Togo through different data sources. We then visualised data trends over time, to assess the impact of interventions on infection and transmission levels. Vector control was initiated by OCP from 1977 (northern and central parts of Togo) or 1988 (southern regions) up to 2002 (most areas) or 2007 ("special intervention zones" [SIZ], parts of Northern and Central Togo). Between 1988 and 1991, Togo initiated ivermectin mass drug administration (MDA) in eligible communities. The impact of vector control was high in most river basins, resulting in low annual biting rates and annual transmission potential declining to very low levels; the impact was lower in river basins designated as SIZ. Repeated, longitudinal ivermectin mass treatments have overall strongly reduced onchocerciasis transmission in Togo. Epidemiological surveys performed between 2014 and 2017 showed that the prevalence of skin microfilariae (mf) and anti-OV16 IgG4 antibodies had declined to low levels in several districts of the Centrale, Plateaux, and Maritime region. Yet, relatively high mf prevalences (between 5.0% and 32.7%) were still found in other districts during the same period, particularly along the Kéran, Mô and Ôti river basins (SIZ areas). CONCLUSIONS/SIGNIFICANCE: Trends in infection prevalence and intensity show that onchocerciasis levels have dropped greatly over time in most areas. This demonstrates the large impact of long-term and wide-scale interventions, and suggest that several districts of Togo are approaching elimination.

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.

Mansonella perstans, Onchocerca volvulus and Strongyloides stercoralis infections in rural populations in central and southern Togo.

BACKGROUND: Mansonella perstans, Onchocerca volvulus and Strongyloides stercoralis are widespread helminth parasites in the tropics. Their distribution remains difficult to determine as it may change during national disease control programs and with regional mass drug administration (MDA). Epidemiological surveys are of importance to evaluate the geographical distribution of these helminth parasites and the diseases they may cause, however, up to date epidemiological evaluations on M. perstans and S. stercoralis in Togo are rare, and surveys on O. volvulus are important especially under the aspect of MDA of ivermectin which is performed since decades. METHODS: Dry blood samples (n = 924) were collected from rural populations in the Régions Central and Plateaux in Togo, and analyzed by parasite-specific real-time PCR and ELISA techniques. RESULTS: Dry blood samples from 733 persons where investigated by real-time PCR tested for DNA of blood-circulating M. perstans microfilaria, and a prevalence of 14.9% was detected. Distinct differences were observed between genders, positivity was higher in men increasing with age, and prevalence was highest in the Région Plateaux in Togo. IgG4 responses to O. volvulus antigen (OvAg) were studied in 924 persons and 59% were found positive. The distribution of parasite infestation between age and gender groups was higher in men increasing with age, and regional differences were detected being highest in the Région Plateaux. The diagnostic approach disclosed 64,5% positive IgG4 responses to S. stercoralis infective third-stage larvae-specific antigen (SsL3Ag) in the surveyed regions. Antigen cross reactivity of SsL3Ag with parasite co-infections may limit the calculated prevalence. Singly IgG4 positive for SsL3Ag were 13.9%, doubly positive for OvAg and SsL3Ag were 35.5% and triply positive for M. perstans, O. volvulus and S. stercoralis were 9.9%. CONCLUSIONS: Mansonelliasis, onchocerciasis and strongyloidiasis remain prevalent in the surveyed regions, yet with local differences. Our observations suggest that transmission of M. perstans, O. volvulus and S. stercoralis may be ongoing. The degree of positive test results in the examined rural communities advocate for the continuation of MDA with ivermectin and albendazole, and further investigations should address the intensity of transmission of these parasites.

Onchocerca volvulus infection and serological prevalence, ocular onchocerciasis and parasite transmission in northern and central Togo after decades of Simulium damnosum s.l. vector control and mass drug administration of ivermectin.

BACKGROUND: Mass drug administration (MDA) of ivermectin has become the main intervention to control onchocerciasis or "river blindness". In Togo, after many years of MDA, Onchocerca volvulus infection has declined dramatically, and elimination appears achievable, but in certain river basins the current situation remains unknown. We have conducted parasitological, serological, ophthalmological, and entomological assessments in northern and central Togo within the river basins of Ôti, Kéran and Mô. METHODOLOGY/PRINCIPAL FINDINGS: Examinations were completed in 1,455 participants from 11 onchocerciasis sentinel villages, and O. volvulus transmission by Simulium damnosum sensu lato (s.l.) was evaluated. In children (aged 1-10 years), the prevalence of microfilariae (Mf) was 2.3% and in adults it ranged from 5.1 to 13.3%. Positive IgG4 responses to O. volvulus adult (crude) worm antigen (OvAg) and the recombinant Ov16 antigen were in all-ages 48.7% and 34.4%, and 29.1% and 14.9% in children, respectively. In the river basin villages of Kéran, Mô and Ôti, the IgG4 seroprevalences to OvAg in children were 51.7%, 23.5% and 12.7%, respectively, and to the Ov16 antigen 33.3% (Kéran) and 5.2% (Ôti). Onchocerciasis ocular lesions (punctate keratitis, evolving iridocyclitis and chorioretinitis) were observed in children and young adults. O. volvulus-specific DNA (Ov150) was detected by poolscreen in vector samples collected from Tchitchira/Kéran(22.8%), Bouzalo/Mô(11.3%), Baghan/Mô(2.9%) and Pancerys/Ôti(4.9%); prevalences of O. volvulus infection in S. damnosum s.l. were, respectively, 1%, 0.5%, 0.1% and 0.2%. CONCLUSIONS/SIGNIFICANCE: In the northern and central river basins in Togo, interruption of O. volvulus transmission has not yet been attained. Patent O. volvulus infections, positive antibody responses, progressive ocular onchocerciasis were diagnosed, and parasite transmission by S. damnosum s.l. occurred close to the survey locations. Future interventions may require approaches selectively targeted to non-complying endemic populations, to the seasonality of parasite transmission and national onchocerciasis control programs should harmonize cross-border MDA as a coordinated intervention.