Exposure to Invasive Anopheles stephensi in the Peri-Domestic Environment Is Associated with Increased Individual Malaria Infection Risk in Metehara, Central Ethiopia: A Case Control Study

Background: Anopheles stephensi, an urban-adapted Asian malaria vector, is spreading across Africa amid rapid urbanization, yet its contribution to malaria transmission remains unclear, especially in typical situations where other vector species co-occur. Here, we quantified the association between peri-domestic An. stephensi exposure and individual malaria risk in Metehara town, central Ethiopia, alongside the role of native vectors.

Methods: An age-matched case-control study (1:2 ratio) was conducted from October 2023 to November 2025. Cases were febrile outpatients with microscopy-confirmed Plasmodium falciparum or Plasmodium vivax infection. Controls were afebrile, microscopy-negative outpatients recruited from the same health facility within 72 hours of case enrolment. Field teams conducted household and entomological assessment within 48 hours of enrolment. The primary exposure variable was the presence of An. stephensi in or around participants’ households.

Findings: Of the 1806 enrolled participants, 486 cases and 915 controls were analyzed. Most cases were P. falciparum (83·1%), followed by mixed (9·7%) and P. vivax (7·2%) infections. Adult anophelines were detected more often in case households (58·0%) than in controls (40·3%), the majority being An. arabiensis (79·6%). Anopheles stephensi was more common in case households at both adult (6·6% versus 4·2%) and immature stages (12·7% versus 6·3%) than controls. In adjusted models, the presence of adult (adjusted odds ratio [AOR]=2·80, 95% CI 1·64–4·79) and immature An. stephensi (AOR=2·46, 95% CI 1·61–3·74) was independently associated with case status, with effect sizes comparable to those observed for native adult malaria vectors (AOR=2·71, 95% CI 2·02–3·62). Combined exposure to adult and/or immature stages of An. stephensi showed similar associations (AOR = 2·80, 95% CI: 1·98–3·96), with a magnitude of risk comparable to that of native vectors (AOR = 2·61, 95% CI 1·99-3·41).

Interpretation: In this urban setting, co-endemic for native malaria vectors, peri-domestic exposure to An. stephensi was an independent predictor of malaria case status, with an effect comparable to that of native vectors. These findings reinforce the importance of integrated, urban-focused vector surveillance and control strategies across Africa.