Declining Onchocerca volvulus transmission despite limited ivermectin delivery in the Kakoi-Koda focus, Ituri, Democratic Republic of the Congo: An epidemiological, entomological and landscape evidence synthesis.

BACKGROUND: The Kakoi-Koda focus in Ituri Province was historically hyperendemic for onchocerciasis, yet screening for a recent trial suggested a marked decline, including in Logo Health Zone, which had never received routine ivermectin. We explored whether this decline extended across the focus and how infection indicators corresponded spatially with ivermectin delivery, entomological observations and deforestation. METHODOLOGY: We conducted a scoping evidence synthesis of epidemiological, programmatic, entomological and geospatial sources. Against a 2003 nodule-mapping baseline, change was assessed from repeated cross-sectional moxidectin trial screenings in 2010-11 and 2021-2023, which applied the same four-skin-snip protocol to community-recruited residents aged ≥12 years. Anti-Ov16 serology (2015-21), two-skin-snip surveys (2015/17), exploratory blackfly observations (2009-18) and remotely sensed tree-cover loss (2001-24) provided further contextual evidence. PRINCIPAL FINDINGS: Between the two trial screenings, microfilarial prevalence significantly declined from 79.0% to 9.0% (Draju) and 68.9% to 8.6% (Kanga) in Logo, similar to declines observed in villages of Nyarambe Health Zone (72.2% to 2.9%), which received routine ivermectin for lymphatic filariasis. Mean infection intensity mirrored this pattern, from 17-26 to 1 microfilariae per milligram of skin in Logo, and 11 to 0.4 in Nyarambe. Seroprevalence in children aged 3-10 years from 2016 onward was low (0-5%), geographically circumscribed and broadly concordant with the skin-snip spatial pattern. Opportunistic blackfly collections and breeding-site prospections detected Simulium dentulosum and S. vorax as the current anthropophagic species, with no evidence of S. neavei after 2009. Extensive dense forest loss (75-90% in historically hyperendemic Logo) and canopy opening are consistent with a shift from crab-associated S. neavei habitats towards more open-habitat vectors, providing a plausible ecological mechanism. SIGNIFICANCE: Parasitological, serological, entomological and geospatial evidence consistently indicates substantial declines in O. volvulus infection indicators across Kakoi-Koda, compatible with reduced transmission. Residual positive indicators were spatially circumscribed, including in Logo where no routine ivermectin was delivered. Whether the current simuliid species can sustain transmission above elimination thresholds remains uncertain. Standardised, representative surveys in the Muda/Kuda and Lebu River basins are warranted to guide decisions on starting and stopping ivermectin delivery.