Pathogen detection in HIV-infected children and adolescents with non-malarial febrile illnesses using metagenomic next-generation sequencing approach in Uganda
EDCTP Project Call
Career Development Fellowship (CDF)
1. To identify and characterize microbial pathogens in HIV-infected Ugandan children and adolescents admitted to Mulago National Referral Hospital, Baylor-Uganda clinic with non-malarial febrile illness (NMFI)
2. To identify and describe the frequency of comorbidities in children with perinatally acquired HIV-infection with NMFI in Uganda
In Uganda, 98,000 children (0-14 years of age) were living with HIV in 2020 and ranked among the top 20 high-burden countries contributing 5% of AIDS-related deaths among adolescents. In 2018, nearly 450 infants acquired HIV every day globally; most of them during childbirth. These children are at extremely high risk of dying in the first two years of life from treatable infections which normally present with fever. While fevers are commonly attributed to malaria, most fevers in African children are not due to malaria and clinicians are challenged by the similar clinical features of a wide spectrum of potential etiologies. Rapid diagnostic tests (RDTs) for malaria have highlighted the decreasing proportion of malaria-attributable fevers in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the effective management of febrile illness in low-resource settings. RDTs for non-malarial tropical infections currently rely on the detection of host antibodies against a single infectious agent yet their sensitivities and specificities are inherently limited. It should be noted that the causes of NMFI in HIV-infected children in Uganda remain scarce. Furthermore, there's minimal guidance on how to manage HIV-infected children with NMFI. Thus, other causes of fever in African children must be better characterized to facilitate the optimization of diagnostic and therapeutic algorithms as well as inform clinical guidelines for management of HIV-infected children in Uganda. There is a pressing need for deployment of modern ultra-sensitive pathogen-detection approaches such as shotgun metagenomics sequencing (sMGS) to ensure rapid, accurate, and timely response to infectious diseases. The important common transmission route for pathogens in children is fecal-oral but conventional laboratory assays fail to detect causative agents in approximately 40% of gastroenteritis. Ultimately, we are ushering a genomics-informed, real-time, pathogen detection and characterization. Deployment of sequencing technologies such as Illumina, PacBio, and Oxford Nanopore sequencing to tropical fevers is urgently needed to enable effective management of severe and treatable infections, especially among HIV-infected children and other vulnerable populations. This project aims to utilize shotgun metagenomic sequencing to comprehensively characterize microbial pathogens in NMFI HIV-infected Ugandan children admitted to Baylor College of Medicine Children's Foundation–HIV treatment clinic and describe associated clinical presentations/comorbidities.
African Center of Excellence in Bioinformatics and Data-Intensive Sciences
The Infectious Diseases Institute
BMC Infectious Diseases
INFECTIOUS DISEASES INSTITUTE
Current Job Title
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