Project Title

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)

Project Objectives

• To identify microbial pathogens in HIV-infected Ugandan children and adolescents admitted to Mulago National Referral Hospital, Baylor-Uganda clinic with NMFIs • To characterize the clinical presentations and determine associations between specific clinical syndromes with both known and novel pathogens in clinical specimens of HIV-infected Ugandan children and adolescents with NMFIs • To identify and describe the frequency of comorbidities in children and adolescents with perinatally acquired HIV-infection with NMFIs in Uganda in the era of antiretroviral therapy

Study Design

Cross-sectional diagnostic study

Project Summary

Rapid diagnostic tests (RDTs) for malaria have highlighted the decreasing proportion of malaria-attributable illnesses in endemic areas. Unfortunately, once malaria is excluded, there are few accessible diagnostic tools to guide the management of severe febrile illnesses in low-resource settings. RDTs for non-malarial tropical infections currently rely on detecting host antibodies against a single infectious agent, yet their sensitivities and specificities are inherently limited. It should be noted that causes of non-malarial febrile illnesses (NMFIs) in HIV-infected children in Uganda remain scarce. There's minimal guidance on how to manage HIV-infected children who present with NMFIs. Thus, it is important that other causes of fever in African children be better characterized to facilitate the optimization of diagnostic and therapeutic algorithms. Considering these limitations, there is a pressing need for more sensitive genomic-based approaches such as shotgun metagenomics sequencing (sMNGS). Ultimately, the integration of whole-genome-based approaches such as long-read sequencing technologies to tropical fevers is urgently needed to improve the management of severe and treatable infections, especially among vulnerable groups such as HIV-infected children and adolescents presenting with NMFIs. This project titled Pathogen Detection in HIV-infected Children with Non-malarial Febrile Illnesses Using Metagenomic Sequencing (PHICAMS) aims to utilize sMNGS to characterize microbial pathogens in HIV-infected Ugandan children and adolescents admitted to Baylor College of Medicine Children's Foundation - Uganda with NMFIs and associated clinical presentations or comorbidities. The following tasks are included in the PHICAMS work packages: 1) Conduct a cross-sectional study aims to characterize microbial pathogens in stool specimens of non-malarial febrile illnesses in HIV-infected Ugandan children and adolescents; 2) Identify comorbidities in NMFIs HIV-infected children and adolescents; 3) recruit and supervise at least two MSc in Bioinformatics students at Makerere University; and 4) Deliver selected training including GCP, GCLP, Protection of Human Research Subjects, Metagenomics data analysis and interpretation, Grant & Manuscript writing to project fellows. The following describes the work done during the first reporting period. Project and data management, coordination (WP1), ethical and administrative approval secured. The clinical study was initiated, including recruitment of study participants (WP2), sample collection and storage (WP3). Sample processing, Nucleic acid extraction, sequencing, analysis, interpretation, and dissemination (WP4) are the four work packages for PHICAMS. This project is currently focused on the execution of work packages 1, 2, and 3. These WPs have been executed to our satisfaction. Work Package 4 is anticipated to be initiated in the 3rd-year project period. Year 2 of PHICAMS has involved a lot of capacity-building activities. The two PHICAMS project fellows have taken several professional courses and completed their two-year Master’s degree program at Makerere University. We have also collected our proposed samples and are ready to perform DNA extraction and sequencing in the 3rd year of the project.

Host Organisation

Current Organisation

INFECTIOUS DISEASES INSTITUTE

Current Job Title

Scientist

Biography

Publications