Treatment Failures and Excess Mortality Among HIV-Exposed, Uninfected Children With Pneumonia

Kelly, Matthew S.; Wirth, Kathleen E.; Steenhoff, Andrew P.; Cunningham, Coleen K.; Arscott-Mills, Tonya; Boiditswe, Sefelani; Patel, Mohamed Z.; Shah, Samir S.; Finalle, Rodney; Makone, Ishmael; Feemster, Kristen A.

doi:10.1093/jpids/piu092

Cited by 46 publications

(30 citation statements)

References 32 publications

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“…In our population, HIV status was missing in 73% of cases, something that is unfortunately common for children in many HIV-endemic clinical settings with weak pediatric HIV testing programs [22]. Despite this, performance was reasonable, although expectedly lower than that seen in the original study, with 95% confidence intervals of the c-statistics for all HIV status subgroups in the range of the original RISC study (0.92, 95% CI: 0.74–0.93) (S4 Table).…”

Section: Discussionmentioning

confidence: 99%

Predicting Hospitalised Paediatric Pneumonia Mortality Risk: An External Validation of RISC and mRISC, and Local Tool Development (RISC-Malawi) from Malawi

et al. 2016

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BackgroundPneumonia is the leading infectious cause of under-5 mortality in sub-Saharan Africa. Clinical prediction tools may aide case classification, triage, and allocation of hospital resources. We performed an external validation of two published prediction tools and compared this to a locally developed tool to identify children admitted with pneumonia at increased risk for in-hospital mortality in Malawi.MethodsWe retrospectively analyzed the performance of the Respiratory Index of Severity in Children (RISC) and modified RISC (mRISC) scores in a child pneumonia dataset prospectively collected during routine care at seven hospitals in Malawi between 2011–2014. RISC has both an HIV-infected and HIV-uninfected tool. A local score (RISC-Malawi) was developed using multivariable logistic regression with missing data multiply imputed using chained equations. Score performances were assessed using c-statistics, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood statistics.Results16,475 in-patient pneumonia episodes were recorded (case-fatality rate (CFR): 3.2%), 9,533 with complete data (CFR: 2.0%). The c-statistic for the RISC (HIV-uninfected) score, used to assess its ability to differentiate between children who survived to discharge and those that died, was 0.72. The RISC-Malawi score, using mid-upper arm circumference as an indicator of malnutrition severity, had a c-statistic of 0.79. We were unable to perform a comprehensive external validation of RISC (HIV-infected) and mRISC as both scores include parameters that were not routinely documented variables in our dataset.ConclusionIn our population of Malawian children with WHO-defined pneumonia, the RISC (HIV-uninfected) score identified those at high risk for in-hospital mortality. However the refinement of parameters and resultant creation of RISC-Malawi improved performance. Next steps include prospectively studying both scores to determine if incorporation into routine care delivery can have a meaningful impact on in-hospital CFRs of children with WHO-defined pneumonia.

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Section: Discussionmentioning

confidence: 99%

Predicting Hospitalised Paediatric Pneumonia Mortality Risk: An External Validation of RISC and mRISC, and Local Tool Development (RISC-Malawi) from Malawi

et al. 2016

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“…One hundred fifty-nine of these children received antibiotic therapy during the first 48 hours that was in accordance with WHO guidelines. 11,19 In sensitivity analyses among children receiving WHO guideline-driven antibiotic treatment, the effect of chest radiographic classification on the risk of treatment failure at 48 hours was substantively unchanged (primary end-point pneumonia vs. no significant pathology, RR: 2.55, 95% CI: 1.10, 5.89, P =0.03; other infiltrate/abnormality vs. no significant pathology, RR: 1.40, 95% CI: 0.59, 3.36, P =0.45).…”

Section: Resultsmentioning

confidence: 99%

“…As antibiotic treatment may be an important determinant of outcomes and was likely informed in part by radiographic findings, we repeated primary analyses while restricting the cohort to children who received antibiotic therapy consistent with current WHO recommendations, as previously described. 11, 19 Briefly, these guidelines classify children as having non-severe or severe pneumonia, and recommend specific treatment for children with known or suspected HIV infection. For HIV-uninfected children, ampicillin or benzylpenicillin with gentamicin is recommended for severe pneumonia, while high-dose oral amoxicillin can be given for non-severe disease.…”

Section: Methodsmentioning

confidence: 99%

Chest Radiographic Findings and Outcomes of Pneumonia Among Children in Botswana

Kelly¹,

Crotty

Rattan

et al. 2016

Pediatric Infectious Disease Journal

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Background Chest radiography is increasingly used to diagnose pneumonia in low- and middle-income countries. Few studies examined whether chest radiographic findings predict outcomes of children with clinically suspected pneumonia in these settings. Methods Hospital-based, prospective cohort study of children 1-23 months of age meeting clinical criteria for pneumonia in Botswana. Chest radiographs were reviewed by two pediatric radiologists to generate a consensus interpretation using standardized World Health Organization criteria. We assessed whether final chest radiograph classification was associated with our primary outcome, treatment failure at 48 hours, and secondary outcomes. Results From April 2012 to November 2014, we enrolled 249 children with evaluable chest radiographs. Median age was 6.1 months and 58% were male. Chest radiograph classifications were primary end-point pneumonia (35%), other infiltrate/abnormality (42%), or no significant pathology (22%). The prevalence of end-point consolidation was higher in children with HIV infection (P=0.0005), while end-point pleural effusions were more frequent among children with moderate or severe malnutrition (P=0.0003). Ninety-one (37%) children failed treatment and 12 (4.8%) children died. Primary end-point pneumonia was associated with an increased risk of treatment failure at 48 hours (P=0.002), a requirement for more days of respiratory support (P=0.002), and a longer length of stay (P=0.0003) compared with no significant pathology. Primary end-point pneumonia also predicted a higher risk of treatment failure than other infiltrate/abnormality (P=0.004). Conclusions Chest radiograph provides useful prognostic information for children meeting clinical criteria for pneumonia in Botswana. These findings highlight the potential benefit of expanded global access to diagnostic radiology services.

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“…41–43 In Southern Africa, HEU infants have the same rate of all pneumonia as HU infants but have a greater risk for severe pneumonia and empiric pneumonia treatment failure. 8,13,16,18 Early studies observed a larger relative difference in infant mortality than in morbidity or hospitalization when comparing HEU and HU infants, possibly indicating more severe disease in HEU infants. 10–12 Our observation that HEU infants have a higher probability of very severe infections even when breastfed supports previous observations.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Cohort Study of Common Childhood Infections in South African HIV-exposed Uninfected and HIV-unexposed Infants

Slogrove

Esser

Cotton

et al. 2017

Pediatric Infectious Disease Journal

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Background:Much evidence of HIV-exposed uninfected (HEU) infant infectious morbidity predates availability of maternal combination antiretroviral therapy and does not control for universal risk factors (preterm birth, low birth weight, suboptimal breastfeeding and poverty).Methods:This prospective cohort study identified HIV-infected and HIV-uninfected mothers and their newborns from South African community midwife unit. The primary outcome, infectious cause hospitalization or death before 6 months of age, was compared between HEU and HIV-unexposed (HU) infants and classified for type and severity using validated study-specific case definitions. Adjusted odds ratios (aORs) were calculated by logistic regression including stratified analyses conditioned on breastfeeding.Results:One hundred and seventy-six (94 HEU and 82 HU) mother–infant pairs were analyzed. HIV-infected mothers were older (median, 27.8 vs. 24.7 years; P < 0.01) and HU infants more often breastfed (81/82 vs. 35/94; P < 0.001). Groups were similar for maternal education, antenatal course, household characteristics, birth weight, gestational age and immunizations. The primary outcome occurred in 17 (18%) HEU and 10 (12%) HU infants [aOR, 1.45; 95% confidence interval (CI): 0.44–4.55]. In stratified analysis restricted to breastfed infants, the aOR for hospitalization due to very severe infection or death was 4.2 (95% CI: 1.00–19.2; P = 0.05) for HEU infants. Hospitalization for diarrhea was more common in HEU than HU infants [8/94 (8.5%) vs. 1/82 (1.2%); P = 0.04].Conclusion:The difference between HEU and HU infants in the probability of infectious cause hospitalization or death in the first 6 months of life was not significant. However, among breastfed infants, severe infectious morbidity occurred more often in HEU than HU infants.

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Treatment Failures and Excess Mortality Among HIV-Exposed, Uninfected Children With Pneumonia

Abstract: HIV-EU children with pneumonia have higher rates of treatment failure and in-hospital mortality than HIV-unexposed children during the first 6 months of life. Treatment with a third-generation cephalosporins did not improve outcomes among HIV-EU children.

Cited by 46 publications

References 32 publications

Predicting Hospitalised Paediatric Pneumonia Mortality Risk: An External Validation of RISC and mRISC, and Local Tool Development (RISC-Malawi) from Malawi

Predicting Hospitalised Paediatric Pneumonia Mortality Risk: An External Validation of RISC and mRISC, and Local Tool Development (RISC-Malawi) from Malawi

Chest Radiographic Findings and Outcomes of Pneumonia Among Children in Botswana

A Prospective Cohort Study of Common Childhood Infections in South African HIV-exposed Uninfected and HIV-unexposed Infants

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