HIV InfectionPHICAMSNCT05085158
Pathogen Detection in HIV-infected Children With Non-malarial Febrile Illnesses Using Metagenomic Sequencing
An observational study of HIV Infection, run by Makerere University at 1 site in Uganda.
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. Read more about this study
- Who is it for?
- Ages 3 months to 14 years
- Conditions the study is for
- HIV Infection
- How many people
- 138 participants
- Where
- 1 siteUganda
- Study dates
- 1 Jan 2023to 1 Oct 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 14 years
- All sexes
- No healthy volunteers
- Child
Study population: HIV-infected Ugandan children and adolescents admitted with non-malarial febrile illnesses (NMFIs) to Baylor College of Medicine Children's Foundation - Uganda
Who may be able to join
- 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.
Who cannot join
- Critically ill patients will not be recruited.
Trial locations and contacts
1 site in 1 country.
Uganda1 site
Baylor College of Medicine Children's Foundation-Uganda
Mulago, 256
About this study
Official title: Pathogen Detection in HIV-infected Children and Adolescents With Non-malarial Febrile Illnesses Using Metagenomic Next-generation Sequencing Approach in Uganda
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%.
Read the 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.
- Conditions
- HIV Infection
- Keywords
- shotgun metagenomics, microbial pathogens, non-malarial febrile illnesses
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of microbial pathogens in NMFIs HIV-infected children and adolescents
Microbial pathogens in NMFIs HIV-infected children and adolescents in Uganda
Measured: 36 months
Secondary outcomes (1)
Prevalent comorbidities in NMFIs HIV-infected children and adolescents
Comorbidities in NMFIs HIV-infected children and adolescents in Uganda
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2021
- Study start1 Jan 2023
- Primary completion30 Jun 2024 (estimated)
- Study completion1 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Makerere University
- Sponsor type
- University, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Responsible party
- Sponsor
- Investigators
- Gerald Mboowa, PhD, Principal investigator, Infectious Diseases Institute, Makerere University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05085158
- Sponsor's protocol ID
- EDCTP - TMA2020CDF-3159
- Acronym
- PHICAMS
- Status last verified
- Oct 2023
- First submitted
- 7 Oct 2021
- Last updated
- 19 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Upon reasonable request to the PI
Publications
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.
PubMed 31313805Ramesh 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.
PubMed 31220115Maze 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.
PubMed 29454844Decuypere 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.
PubMed 26943791Pondei, Kemebradikumo, Onyaye E. Kunle-Olowu, and Oliemen Peterside.
https://www.unaids.org/en/resources/presscentre/featurestories/2019/december/uganda-treating-hiv-positive-children-speed-and-skill
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.
PubMed 30992304Schlaberg 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.
PubMed 28169558Moreira-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.
PubMed 24324741Gu 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.
PubMed 30355154Naccache 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.
PubMed 24899342Kalantar 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.
PubMed 33057676Gyarmati 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.
PubMed 26996149Kwak 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.
PubMed 30390617
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pathogen Detection in HIV-infected Children and Adolescents With Non-malarial Febrile Illnesses Using Metagenomic Next-generation Sequencing Approach in Uganda
- ClinicalTrials.gov ID
- NCT05085158
- Acronym / sponsor ID
- PHICAMS / EDCTP - TMA2020CDF-3159
- Conditions
- HIV Infection
- Keywords
- shotgun metagenomics, microbial pathogens, non-malarial febrile illnesses
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- Makerere UniversityUniversity, hospital or other
- Collaborators
- European and Developing Countries Clinical Trials Partnership (EDCTP)
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 30 Jun 2024 (estimated)
- Study completion
- 1 Oct 2024 (estimated)
- First posted
- 20 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 3 months to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- HIV-infected Ugandan children and adolescents admitted with non-malarial febrile illnesses (NMFIs) to Baylor College of Medicine Children's Foundation - Uganda
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- Critically ill patients will not be recruited.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of microbial pathogens in NMFIs HIV-infected children and adolescents
Time frame: 36 months
Microbial pathogens in NMFIs HIV-infected children and adolescents in Uganda
1 secondary outcome
Prevalent comorbidities in NMFIs HIV-infected children and adolescents
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2024.
- Background: PubMed 31313805Pokharel 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.
- Results publication: PubMed 31220115Ramesh 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.
- Results publication: PubMed 29454844Maze 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.
- Results publication: PubMed 26943791Decuypere 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.
- Results publicationPondei, Kemebradikumo, Onyaye E. Kunle-Olowu, and Oliemen Peterside.
- Results publicationhttps://www.unaids.org/en/resources/presscentre/featurestories/2019/december/uganda-treating-hiv-positive-children-speed-and-skill
- Results publication: PubMed 30992304Miller 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.
- Results publication: PubMed 28169558Schlaberg 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.
- Results publication: PubMed 24324741Moreira-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.
- Results publication: PubMed 30355154Gu 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.
- Results publication: PubMed 24899342Naccache 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.
- Results publication: PubMed 33057676Kalantar 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.
- Individual participant dataSharing planned: Undecided. Upon reasonable request to the PI
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gerald Mboowa, PhD principal investigator
Infectious Diseases Institute, Makerere University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infection, run by Makerere University at 1 site in Uganda.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of microbial pathogens in NMFIs HIV-infected children and adolescents (time frame: 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05085158, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2024.