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HIV matters when diagnosing TB in young children: an ancillary analysis in children enrolled in the INPUT stepped wedge cluster randomized study
Open accessAbstract
BACKGROUND: Children under age five years, particularly those living with HIV (CLHIV), are at risk for rapid progression of tuberculosis (TB). We aimed to describe TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV compared to children without HIV in Cameroon and Kenya. METHODS: This sub-analysis of a cluster-randomized trial evaluating the integration of pediatric TB services from May 2019 to March 2021 enrolled children age < 5 years with TB. We estimated the HIV infection rate with 95% confidence interval (CI). We compared TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV and children without HIV. Finally, we investigated whether HIV infection was associated with a shorter time to TB diagnosis (≤ 3 months from symptoms onset) after adjusting for covariates. Univariable and multivariable logistic regression analysis were performed with adjusted odds ratios (AORs) presented as measures of the association of covariates with HIV status and with shorter time to TB diagnosis. RESULTS: We enrolled 157 children with TB (mean age was 1.5 years) and 22/157 (14.0% [9.0-20.4%]) were co-infected with HIV. CLHIV were more likely to initially present with acute malnutrition (AOR 3.16 [1.14-8.71], p = 0.027). Most TB diagnoses (140/157, 89%) were made clinically with pulmonary TB being the most common presentation; however, there was weak evidence of more frequent bacteriologic confirmation of TB in CLHIV, 18% vs. 9% (p = 0.067), due to the contribution of lateral-flow urine lipoarabinomannan to the diagnosis. HIV positivity (AOR: 6.10 [1.32-28.17], p = 0.021) was independently associated with a shorter time to TB diagnosis as well as fatigue (AOR: 6.58 [2.28-18.96], p = 0.0005), and existence of a household contact diagnosed with TB (AOR: 5.60 [1.58-19.83], p = 0.0075), whereas older age (AOR: 0.35 [0.15-0.85], p = 0.020 for age 2-5 years), night sweats (AOR: 0.24 [0.10-0.60], p = 0.0022) and acute malnutrition (AOR: 0.36 [0.14-0.92], p = 0.034) were associated with a delayed diagnosis. The case fatality rate was 9% (2/22) in CLHIV and 4% (6/135) in children without HIV, p = 0.31. CONCLUSIONS: These results altogether advocate for better integration of TB services into all pediatric entry points with a special focus on nutrition services, and illustrate the importance of non-sputum-based TB diagnostics especially in CLHIV. TRIAL REGISTRATION: NCT03862261, first registration 05/03/2019.
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“A multi-national, cluster-randomized, stepped-wedge trial.”
From Applications and implementation considerations for stepped-wedge designs in sub-Saharan Africa: a systematic review (2026) · cites this paper as [75]
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- World Health Organization: Roadmap towards ending TB in children and adolescents. In., Second edition edn. Geneva, Switzerland; 2018.
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Otchere, I. D., Aboagye, S. Y., Arthur, P. K., & Asante-Poku, A. (2024) · Frontiers in Tropical Diseases · doi:10.3389/fitd.2024.1443248 · Cited by 15
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Self-citationMusa, Z. A., Akinsolu, F. T., Salako, A. O., Abodunrin, O. R., Ola, O. M., & Ezechi, O. C. (2026) · Frontiers in Epidemiology · doi:10.3389/fepid.2026.1529289
Metadata
- Authors
- Powell, L., Denoeud-Ndam, L., Herrera, N., Masaba, R., Tchounga, B., Siamba, S., Ouma, M., Petnga, S., Machekano, R., Pamen, B., Okomo, G., Simo, L., Casenghi, M., Rakhmanina, N., & Tiam, A.
- Affiliations
- Medical University of South Carolina (US)
- Elizabeth Glaser Pediatric AIDS Foundation (US)
- Ministry of Health (KE)
- Venue
- BMC Infectious Diseases
- Published
- 2023-04-17
- Volume
- 23
- Issue
- 1
- Pages
- 234-234
- ISSN
- 1471-2334 (ISSN-L)
- PMC
- PMC10107571
- OpenAlex
- W4366189536
- Cited by
- 8
- References
- 32
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Infectious Diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- UNITAID
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
- Keywords
- pediatric tuberculosis, HIV-infected children, HIV/TB coinfection, acute malnutrition, tuberculosis treatment outcomes, antiretroviral therapy, tuberculosis treatment, Cameroon, Kenya, young children
- MeSH terms
- Child, Child, Preschool, Humans, Infant, Tuberculosis, Tuberculosis, Pulmonary, HIV Infections, Treatment Outcome, Malnutrition
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