In Uganda, non-malarial febrile illnesses (NMFI) present serious health risks, especially for children living with HIV. Traditional diagnostic methods often fail to identify the wide range of pathogens involved. This study, led by EDCTP Career Development Fellow Dr Gerald Mboowa (Uganda), enrolled 144 HIV-infected children presenting with NMFI at the Baylor Children’s Clinic in Uganda. Stool samples were collected and analysed using shotgun metagenomic sequencing at the Chan Zuckerberg Biohub San Francisco to explore the stool microbial landscape and improve diagnostic accuracy for NMFI.

The study identified a diverse microbial composition, including potential pathogens such as Trichomonas vaginalis, Candida albicans, Giardia intestinalis, and Bacteroides spp. Variations in the distribution of these pathogens were observed based on gender and age, with specific microbes associated uniquely with males, females, or certain age groups. The pathogens were transmitted through various routes, including zoonotic, foodborne, and sexually transmitted infections. Although unique pathogen profiles were linked to different antiretroviral regimens, no statistically significant associations were found. Furthermore, the analysis of immune cell responses revealed correlations between pathogen dynamics and variations in white blood cell counts.

The findings of this research, published in BMC Infectious Diseases, demonstrate that shotgun metagenomics has proven to be a powerful tool for identifying pathogens in NMFI cases among HIV-infected children, offering a comprehensive view of microbial interactions. This approach could complement traditional diagnostics to improve early detection and targeted treatment, particularly in resource-limited settings.

Looking forward, integrating metagenomic sequencing into routine diagnostics holds promise for improving the management of infectious diseases in vulnerable populations. Future research should explore the long-term impact of antiretroviral regimens on microbial dynamics and immune responses, paving the way for more effective treatment strategies.