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

HIV Infection Clinical Trial

— PHICAMS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05085158
• Other study ID #: EDCTP - TMA2020CDF-3159
• Status: Active, not recruiting
• Start date: January 1, 2023
• Est. completion date: October 1, 2024

Study information

• Verified date: October 2023
• Source: Makerere University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 138
• Est. completion date: October 1, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 14 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fever
• HIV Infection
• HIV Infections
• Hyperthermia

Locations

Country	Name	City	State
Uganda	Baylor College of Medicine Children's Foundation-Uganda	Mulago

Sponsors (2)

Lead Sponsor	Collaborator
Makerere University	European and Developing Countries Clinical Trials Partnership (EDCTP)

Country where clinical trial is conducted

Uganda, 

References & Publications (14)

Decuypere S, Maltha J, Deborggraeve S, Rattray NJ, Issa G, Berenger K, Lompo P, Tahita MC, Ruspasinghe T, McConville M, Goodacre R, Tinto H, Jacobs J, Carapetis JR. Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics A — View Citation

Gu W, Miller S, Chiu CY. Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection. Annu Rev Pathol. 2019 Jan 24;14:319-338. doi: 10.1146/annurev-pathmechdis-012418-012751. Epub 2018 Oct 24. — View Citation

Gyarmati P, Kjellander C, Aust C, Song Y, Ohrmalm L, Giske CG. Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia. Sci Rep. 2016 Mar 21;6:23532. doi: 10.1038/srep23532. — View Citation

https://www.unaids.org/en/resources/presscentre/featurestories/2019/december/uganda-treating-hiv-positive-children-speed-and-skill

Kalantar KL, Carvalho T, de Bourcy CFA, Dimitrov B, Dingle G, Egger R, Han J, Holmes OB, Juan YF, King R, Kislyuk A, Lin MF, Mariano M, Morse T, Reynoso LV, Cruz DR, Sheu J, Tang J, Wang J, Zhang MA, Zhong E, Ahyong V, Lay S, Chea S, Bohl JA, Manning JE, — View Citation

Kwak J, Park J. What we can see from very small size sample of metagenomic sequences. BMC Bioinformatics. 2018 Nov 3;19(1):399. doi: 10.1186/s12859-018-2431-8. — View Citation

Maze MJ, Bassat Q, Feasey NA, Mandomando I, Musicha P, Crump JA. The epidemiology of febrile illness in sub-Saharan Africa: implications for diagnosis and management. Clin Microbiol Infect. 2018 Aug;24(8):808-814. doi: 10.1016/j.cmi.2018.02.011. Epub 2018 — View Citation

Miller S, Naccache SN, Samayoa E, Messacar K, Arevalo S, Federman S, Stryke D, Pham E, Fung B, Bolosky WJ, Ingebrigtsen D, Lorizio W, Paff SM, Leake JA, Pesano R, DeBiasi R, Dominguez S, Chiu CY. Laboratory validation of a clinical metagenomic sequencing — View Citation

Moreira-Silva SF, Zandonade E, Frauches DO, Machado EA, Lopes LI, Duque LL, Querido PP, Miranda AE. Comorbidities in children and adolescents with AIDS acquired by HIV vertical transmission in Vitoria, Brazil. PLoS One. 2013 Dec 4;8(12):e82027. doi: 10.13 — View Citation

Naccache SN, Federman S, Veeraraghavan N, Zaharia M, Lee D, Samayoa E, Bouquet J, Greninger AL, Luk KC, Enge B, Wadford DA, Messenger SL, Genrich GL, Pellegrino K, Grard G, Leroy E, Schneider BS, Fair JN, Martinez MA, Isa P, Crump JA, DeRisi JL, Sittler T — View Citation

Pokharel S, White LJ, Aguas R, Celhay O, Pelle KG, Dittrich S. Algorithm in the Diagnosis of Febrile Illness Using Pathogen-specific Rapid Diagnostic Tests. Clin Infect Dis. 2020 May 23;70(11):2262-2269. doi: 10.1093/cid/ciz665. — View Citation

Pondei, Kemebradikumo, Onyaye E. Kunle-Olowu, and Oliemen Peterside.

Ramesh A, Nakielny S, Hsu J, Kyohere M, Byaruhanga O, de Bourcy C, Egger R, Dimitrov B, Juan YF, Sheu J, Wang J, Kalantar K, Langelier C, Ruel T, Mpimbaza A, Wilson MR, Rosenthal PJ, DeRisi JL. Metagenomic next-generation sequencing of samples from pediat — View Citation

Schlaberg R, Chiu CY, Miller S, Procop GW, Weinstock G; Professional Practice Committee and Committee on Laboratory Practices of the American Society for Microbiology; Microbiology Resource Committee of the College of American Pathologists. Validation of — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Prevalent comorbidities in NMFIs HIV-infected children and adolescents	Comorbidities in NMFIs HIV-infected children and adolescents in Uganda	36 months