PHICAMS: Pathogen Detection in HIV-infected Children With Non-malarial Febrile Illnesses Using Metagenomic Sequencing

Sponsor

Makerere University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05085158

Collaborator

European and Developing Countries Clinical Trials Partnership (EDCTP) (Other)

200

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

In Uganda, 130,000 children (0-14 years of age) were living with HIV in 2018. Last year, nearly 450 infants acquired HIV every day; most of them during childbirth and these are at extremely high risk of dying in the first two years of life from treatable infections which 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 wide spectrum of potential aetiologies. The prevalence of treatable causes of non-malarial febrile illnesses in children in Africa has been reported to be 45%.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection

Detailed Description

Rapid diagnostic tests (RDTs) for malaria have highlighted the decreasing proportion of malaria-attributable illness 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 detection of 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 remains scarce. There's minimal guidance on how to manage HIV-infected children with NMFIs. Thus, it is important that other causes of fever in African children be better characterized to facilitate optimization of diagnostic and therapeutic algorithms.

Considering these limitations, there is a pressing need for sensitive pathogen-detection-based approaches such as shotgun metagenomics sequencing (sMGS). Ultimately, in the near future, integration of whole-genome based approaches such as long-read sequencing technologies to tropical fevers is urgently needed to improve management of severe and treatable infections especially among the vulnerable groups such as HIV-infected children and adolescents presenting with NMFIs.

This project aims to utilise sMGS 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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Pathogen Detection in HIV-infected Children and Adolescents With Non-malarial Febrile Illnesses Using Metagenomic Next-generation Sequencing Approach in Uganda

Anticipated Study Start Date :

Jun 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Group 1 HIV-infected children with non-malarial febrile illnesses (NMFIs) less than 5 years old
Group 2 HIV-infected children and adolescents with non-malarial febrile illnesses (NMFIs) but less than 15 years old

Outcome Measures

Primary Outcome Measures

Prevalence of microbial pathogens in NMFIs HIV-infected children and adolescents [36 months]
Microbial pathogens in NMFIs HIV-infected children and adolescents in Uganda

Secondary Outcome Measures

Prevalent comorbidities in NMFIs HIV-infected children and adolescents [36 months]
Comorbidities in NMFIs HIV-infected children and adolescents in Uganda

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Months to 14 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Study population will include a total of 200 (100 who are <5 years and 100 who are 6-to-14 years, including equal number of female and male study participants) HIV-infected Ugandan children and adolescents admitted with non-malarial febrile illnesses (NMFIs) to Baylor College of Medicine Children's Foundation - Uganda.