Infectious Pathogens Associated With Stillbirth and Under-five Mortality in Western Kenya and the Effect of Sickle Cell Condition

Background: Infectious Pathogens (IP) remain a significant contributor to stillbirths and under-five deaths in resource-limited settings. Children with sickle cell disease (SCD) are susceptible due to weakened immunity, influencing infection outcomes. This sub-study, nested within the Kenya Child Health and Mortality Prevention Surveillance (CHAMPS) network, investigated infectious pathogens associated with stillbirths and under-five deaths in Western Kenya, as well as the role of the sickle cell condition. Methods: We analysed stillbirths (n=387) and ≤ 5 child deaths (n=945) enrolled in CHAMPS in Karemo (Siaya) and Manyatta (Kisumu), both in western Kenya, between May 2017 and Dec 2024. Minimally invasive tissue sampling (MITS) specimens were processed on a TaqMan Array Card using the QuantStudio 7 real-time PCR (TAC qPCR) and cultured. All participants were screened for sickle cell status using the point-of-care Gazelle™ Hb Variant device, and confirmed by High Performance Liquid Chromatography (HPLC) and pathological diagnosis. Statistical analyses were performed using R programming software (version 4.5.1). Findings : A total of 1,332 cases were investigated, 499, 37.5% (95% CI:34.9-40.1) had an infectious pathogen (IP), with lower prevalence among stillbirths (4.1%, 95%CI:2.6-6.6) and higher prevalence among under-five deaths (51.1%, 95%CI:47.9-54.3). SCD was identified in 46 cases (3.5%) and sickle cell trait in 256 cases (19.2%), for a total of 302 cases (22.7%) with SCD/trait. IP prevalence was higher in SCD (60.9%, 95%CI: 46.3-73.9) than in sickle cell trait (25.8%, 95%CI: 20.6-31.6). Among SCD and sickle cell trait cases, the most frequently identified pathogens were Plasmodium falciparum (39.3% and 18.2%), Klebsiella pneumoniae (7.1% and 37.9%), and Streptococcus pneumoniae (21.4% and 9.1%), respectively. Overall, the leading pathogens associated with death in both SCD/trait and non-SCD/trait groups were K. pneumoniae (28.7% vs 25.5%), P. falciparum (24.5% vs 35.9%), S. pneumoniae (12.8% vs 12.1%), HIV (8.5% vs 8.7%), cytomegalovirus (7.4% vs 7.4%), and respiratory syncytial virus (3.2% vs 1.5%). Conclusions: Infectious pathogens contribute substantially to stillbirth and under-five mortality in Western Kenya, highlighting the need to strengthen infection prevention, diagnosis, and management during pregnancy and early childhood in line with WHO recommendations and targeted preventive care for vulnerable populations like those with SCD.