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

Study Overview
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Brief Summary
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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%.

Detailed Description
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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.

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

Conditions
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HIV Infection

Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: Critically ill patients will not be recruited.

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of microbial pathogens in NMFIs HIV-infected children and adolescents | Microbial pathogens in NMFIs HIV-infected children and adolescents in Uganda | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalent comorbidities in NMFIs HIV-infected children and adolescents | Comorbidities in NMFIs HIV-infected children and adolescents in Uganda | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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shotgun metagenomics, microbial pathogens, non-malarial febrile illnesses