Malawian children with fast-breathing pneumonia with and without comorbidities
Amy Sarah Ginsburg, Tisungane Mvalo, Jun Hwang, Melda Phiri, Eric D McCollum, Madalitso Maliwichi, Robert Schmicker, Ajib Phiri, Norman Lufesi, Susanne May, Amy Sarah Ginsburg, Tisungane Mvalo, Jun Hwang, Melda Phiri, Eric D McCollum, Madalitso Maliwichi, Robert Schmicker, Ajib Phiri, Norman Lufesi, Susanne May
Abstract
Background: Due to high risk of mortality, children with comorbidities are typically excluded from trials evaluating pneumonia treatment. Understanding heterogeneity of outcomes among children with pneumonia and comorbidities is critical to ensuring appropriate treatment.
Methods: We explored whether the percentage of children with fast-breathing pneumonia cured at Day 14 was lower among those with selected comorbidities enrolled in a prospective observational study than among those enrolled in a concurrent randomized controlled trial evaluating treatment with amoxicillin in Lilongwe, Malawi.
Results: Among 79 children with fast-breathing pneumonia in the prospective observational cohort, 57 (72.2%) had HIV infection/exposure, 20 (25.3%) had malaria, 2 (2.5%) had severe acute malnutrition, and 17 (21.5%) had anemia. Treatment failure rate was slightly (not significantly) lower in children with comorbidities (4.1%, 3/73) compared to those without comorbidities (4.5%, 25/552) similarly treated. There was no significant difference in clinical cure rates by Day 14 (95.8% with vs 96.7% without comorbidity).
Conclusions: Children with fast-breathing pneumonia excluded from a concurrent clinical trial due to comorbidities did not fare worse. Children at higher risk whose caregivers seek care early and who receive appropriate risk assessment (e.g., pulse oximetry, hemoglobin, HIV/malaria testing) and treatment, can achieve clinical cure by Day 14.
Trial registration: ClinicalTrials.gov NCT02960919 ; registered November 8, 2016.
Keywords: Africa; Community-acquired pneumonia; Comorbidity; Fast-breathing.
Conflict of interest statement
The authors declare that they have no competing interests.
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References
- Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430–440. doi: 10.1016/S0140-6736(14)61698-6.
- Ginsburg AS, Mvalo T, Nkwopara E, McCollum ED, Ndamala CB, Schmicker R, et al. Placebo vs Amoxicillin for Nonsevere Fast-Breathing Pneumonia in Malawian Children Aged 2 to 59 Months: A Double-blind, Randomized Clinical Noninferiority Trial. JAMA Pediatr. 2019;173(1):21–28. doi: 10.1001/jamapediatrics.2018.3407.
- Lazzerini M, Seward N, Lufesi N, Banda R, Sinyeka S, Masache G, et al. Mortality and its risk factors in Malawian children admitted to hospital with clinical pneumonia, 2001-12: a retrospective observational study. Lancet Glob Health. 2016;4(1):e57–e68. doi: 10.1016/S2214-109X(15)00215-6.
- Lazzerini M, Sonego M, Pellegrin MC. Hypoxaemia as a mortality risk factor in acute lower respiratory infections in children in low and middle-income countries: systematic review and meta-analysis. PLoS One. 2015;10(9):e0136166. doi: 10.1371/journal.pone.0136166.
- McCollum ED, Nambiar B, Deula R, Zadutsa B, Bondo A, King C, et al. Impact of the 13-Valent pneumococcal conjugate vaccine on clinical and hypoxemic childhood pneumonia over three years in Central Malawi: an observational study. PLoS One. 2017;12(1):e0168209. doi: 10.1371/journal.pone.0168209.
- Fancourt N, Deloria Knoll M, Baggett HC, Brooks WA, Feikin DR, Hammitt LL, et al. Chest Radiograph Findings in Childhood Pneumonia Cases From the Multisite PERCH Study. Clin Infect Dis. 2017;64(suppl_3):S262–SS70. doi: 10.1093/cid/cix089.
- Pneumonia Etiology Research for Child Health (PERCH) Study Group. Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet. 2019;394(10200):757–79. 10.1016/S0140-6736(19)30721-4.
- Sonego M, Pellegrin MC, Becker G, Lazzerini M. Risk factors for mortality from acute lower respiratory infections (ALRI) in children under five years of age in low and middle-income countries: a systematic review and meta-analysis of observational studies. PLoS One. 2015;10(1):e0116380. doi: 10.1371/journal.pone.0116380.
- Ginsburg AS, May S, Nkwopara E, Ambler G, McCollum ED, Mvalo T, et al. Clinical outcomes of pneumonia and other comorbidities in children aged 2-59 months in Lilongwe, Malawi: protocol for the prospective observational study "innovative treatments in pneumonia". JMIR Res Protoc. 2019;8(7):e13377. doi: 10.2196/13377.
- World Health Organization . (WHO) recommendations on child health: guidelines approved by the WHO Guidelines Review Committee. Geneva: WHO; 2017.
- World Health Organization (WHO) Global update on HIV treatment 2013: results, impact and opportunities: WHO report in partnership with UNICEF and UNAIDS. 2013.
- Nosek CA, Buck WC, Caviness AC, Foust A, Nyondo Y, Bottomani M, et al. Hospital admissions from a pediatric HIV care and treatment program in Malawi. BMC Pediatr. 2016;16:22. doi: 10.1186/s12887-016-0556-3.
- Tickell KD, Mangale DI, Tornberg-Belanger SN, Bourdon C, Thitiri J, Timbwa M, et al. A mixed method multi-country assessment of barriers to implementing pediatric inpatient care guidelines. PLoS One. 2019;14(3):e0212395. doi: 10.1371/journal.pone.0212395.
- King C, McCollum ED, Mankhambo L, Colbourn T, Beard J, Hay Burgess DC, et al. Can we predict Oral antibiotic treatment failure in children with fast-breathing pneumonia managed at the community level? A prospective cohort study in Malawi. PLoS One. 2015;10(8):e0136839. doi: 10.1371/journal.pone.0136839.
- King C, Colbourn T, Mankhambo L, Beard J, Hay Burgess DC, Costello A, et al. Non-treatment of children with community health worker-diagnosed fast-breathing pneumonia in rural Malawi: exploratory subanalysis of a prospective cohort study. BMJ Open. 2016;6(11):e011636. doi: 10.1136/bmjopen-2016-011636.
Source: PubMed