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

NCT05085158 | Unknown DMC

• 1 other identifier: EDCTP - TMA2020CDF-3159
• Study Type: observational
• Target: 138
• Locations: 1 country
• Sites: 1

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%.

Conditions

HIV Infection

Keywords

shotgun metagenomics; microbial pathogens; non-malarial febrile illnesses

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Prevalent comorbidities in NMFIs HIV-infected children and adolescents

  36 months

Study Arms (2)

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

Eligibility Criteria

• Age: 3 Months - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected Ugandan children and adolescents admitted with non-malarial febrile illnesses (NMFIs) to Baylor College of Medicine Children's Foundation - Uganda

You may qualify if:

• 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.

You may not qualify if:

• Critically ill patients will not be recruited.

Sponsors & Collaborators

• Makerere University: lead
• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator

Study Sites (1)

Baylor College of Medicine Children's Foundation-Uganda

Mulago, 256, Uganda

Location

Related Publications (14)

• 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.

  PMID: 31313805 BACKGROUND

• 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 pediatric febrile illness in Tororo, Uganda. PLoS One. 2019 Jun 20;14(6):e0218318. doi: 10.1371/journal.pone.0218318. eCollection 2019.

  PMID: 31220115 RESULT

• 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 Feb 15.

  PMID: 29454844 RESULT

• 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 Approach. PLoS Negl Trop Dis. 2016 Mar 4;10(3):e0004480. doi: 10.1371/journal.pntd.0004480. eCollection 2016 Mar.

  PMID: 26943791 RESULT

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

  RESULT

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

  RESULT

• 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 assay for pathogen detection in cerebrospinal fluid. Genome Res. 2019 May;29(5):831-842. doi: 10.1101/gr.238170.118. Epub 2019 Apr 16.

  PMID: 30992304 RESULT

• 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 Metagenomic Next-Generation Sequencing Tests for Universal Pathogen Detection. Arch Pathol Lab Med. 2017 Jun;141(6):776-786. doi: 10.5858/arpa.2016-0539-RA. Epub 2017 Feb 7.

  PMID: 28169558 RESULT

• 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: 10.1371/journal.pone.0082027. eCollection 2013.

  PMID: 24324741 RESULT

• 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.

  PMID: 30355154 RESULT

• 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, Hackett J Jr, Miller S, Chiu CY. A cloud-compatible bioinformatics pipeline for ultrarapid pathogen identification from next-generation sequencing of clinical samples. Genome Res. 2014 Jul;24(7):1180-92. doi: 10.1101/gr.171934.113. Epub 2014 Jun 4.

  PMID: 24899342 RESULT

• 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, Tato CM, DeRisi JL. IDseq-An open source cloud-based pipeline and analysis service for metagenomic pathogen detection and monitoring. Gigascience. 2020 Oct 15;9(10):giaa111. doi: 10.1093/gigascience/giaa111.

  PMID: 33057676 RESULT

• 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.

  PMID: 26996149 RESULT

• 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.

  PMID: 30390617 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

A cross-sectional study aims to characterize microbial pathogens in stool specimens of non-malarial febrile illnesses (NMFIs) HIV-infected Ugandan children and adolescents

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Gerald Mboowa, PhD

  Infectious Diseases Institute, Makerere University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: October 20, 2021
• Study Start: January 1, 2023
• Primary Completion: June 30, 2024
• Study Completion: October 1, 2024
• Last Updated: March 19, 2024

Record last verified: 2023-10

Locations

UG (1)