Malawian children with chest-indrawing pneumonia with and without comorbidities or danger signs (original) (raw)
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Malawian children with fast-breathing pneumonia with and without comorbidities
Pneumonia, 2021
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 t...
BMC infectious diseases, 2018
Pneumonia is the leading infectious cause of death in children under 5 years of age around the globe. In addition to preventing pneumonia, there is a critical need to provide greater access to appropriate and effective treatment. Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin for the treatment of fast-breathing pneumonia; however, further evidence is needed to determine if 3 days of oral amoxicillin is also effective for the treatment of chest indrawing pneumonia. This is a double-blind, randomized, non-inferiority trial with the objective to assess the effectiveness of shorter duration amoxicillin dispersible tablet (DT) treatment of chest indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary objective of this study is to determine whether 3 days of treatment with oral amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with chest indrawing pneumonia is as effective as 5 days of treatment. The study w...
Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children
New England Journal of Medicine
BACKGROUND Evidence regarding the appropriate duration of treatment with antibiotic agents in children with pneumonia in low-resource settings in Africa is lacking. METHODS We conducted a double-blind, randomized, controlled, noninferiority trial in Lilongwe, Malawi, to determine whether treatment with amoxicillin for 3 days is less effective than treatment for 5 days in children with chest-indrawing pneumonia (cough lasting <14 days or difficulty breathing, along with visible indrawing of the chest wall with or without fast breathing for age). Children not infected with human immunodeficiency virus (HIV) who were 2 to 59 months of age and had chestindrawing pneumonia were randomly assigned to receive amoxicillin twice daily for either 3 days or 5 days. Children were followed for 14 days. The primary outcome was treatment failure by day 6; noninferiority of the 3-day regimen to the 5-day regimen would be shown if the percentage of children with treatment failure in the 3-day group was no more than 1.5 times that in the 5-day group. Prespecified secondary analyses included assessment of treatment failure or relapse by day 14. RESULTS From March 29, 2016, to April 1, 2019, a total of 3000 children underwent randomization: 1497 children were assigned to the 3-day group, and 1503 to the 5-day group. Among children with day 6 data available, treatment failure had occurred in 5.9% in the 3-day group (85 of 1442 children) and in 5.2% (75 of 1456) in the 5-day group (adjusted difference, 0.7 percentage points; 95% confidence interval [CI], −0.9 to 2.4)-a result that satisfied the criterion for noninferiority of the 3-day regimen to the 5-day regimen. Among children with day 14 data available, 176 of 1411 children (12.5%) in the 3-day group and 154 of 1429 (10.8%) in the 5-day group had had treatment failure by day 6 or relapse by day 14 (betweengroup difference, 1.7 percentage points; 95% CI, −0.7 to 4.1). The percentage of children with serious adverse events was similar in the two groups (9.8% in the 3-day group and 8.8% in the 5-day group). CONCLUSIONS In HIV-uninfected Malawian children, treatment with amoxicillin for chest-indrawing pneumonia for 3 days was noninferior to treatment for 5 days. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02678195.
JMIR Research Protocols
Background Pneumonia is the leading infectious cause of death worldwide among children below 5 years of age. Clinical trials are conducted to determine optimal treatment; however, these trials often exclude children with comorbidities and severe illness. Conclusions Given the paucity of data from Africa, African-based research is necessary to establish optimal management of childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base that includes children with pneumonia and other comorbidities, who are at high risk for mortality or have other complications and are therefore typically excluded from childhood pneumonia clinical trials, can contribute to future iterations of the World Health Organization Integrated Management of Childhood Illness guidelines. Methods The study enrolled 1000 children with pneumonia presenting to the outpatient departments of Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi, who were excluded from concurrent ran...
The Lancet Global Health, 2016
Background Few studies have reported long-term data on mortality rates for children admitted to hospital with pneumonia in Africa. We examined trends in case fatality rates for all-cause clinical pneumonia and its risk factors in Malawian children between 2001 and 2012. Methods Individual patient data for children (<5 years) with clinical pneumonia who were admitted to hospitals participating in Malawi's Child Lung Health Programme between 2001 and 2012 were recorded prospectively on a standardised medical form. We analysed trends in pneumonia mortality and children's clinical characteristics, and we estimated the association of risk factors with case fatality for children younger than 2 months, 2-11 months of age, and 12-59 months of age using separate multivariable mixed eff ects logistic regression models. Findings Between November, 2012, and May, 2013, we retrospectively collected all available hard copies of yellow forms from 40 of 41 participating hospitals. We examined 113 154 pneumonia cases, 104 932 (92∧7%) of whom had mortality data and 6903 of whom died, and calculated an overall case fatality rate of 6•6% (95% CI 6•4-6•7). The case fatality rate signifi cantly decreased between 2001 (15•2% [13•4-17•1]) and 2012 (4•5% [4•1-4•9]; p trend <0•0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors signifi cantly associated with increased odds of mortality were female sex, young age, very severe pneumonia, clinically suspected Pneumocystis jirovecii infection, moderate or severe underweight, severe acute malnutrition, disease duration of more than 21 days, and referral from a health centre. Increasing year between 2001 and 2012 and increasing age (in months) were associated with reduced odds of mortality. Fast breathing was associated with reduced odds of mortality in children 2-11 months of age. However, case fatality rate in 2012 remained high for children with very severe pneumonia (11•8%), severe undernutrition (15•4%), severe acute malnutrition (34•8%), and symptom duration of more than 21 days (9•0%). Interpretation Pneumonia mortality and its risk factors have steadily improved in the past decade in Malawi; however, mortality remains high in specifi c subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of suffi cient data on quality of care indicators and the potential of socioeconomic and other improvements outside the hospital precludes adequate assessment of why case-fatality rates fell. Results from this study emphasise the importance of eff ective national systems for data collection. Further work combining this with data on trends in the incidence of pneumonia in the community are needed to estimate trends in the overall risk of mortality from pneumonia in children in Malawi. Funding Bill & Melinda Gates Foundation.
Analysis of serious adverse events in a paediatric fast breathing pneumonia clinical trial in Malawi
BMJ Open Respiratory Research
IntroductionPneumonia is the leading infectious killer of children. We conducted a double-blind, randomised controlled non-inferiority trial comparing placebo to amoxicillin treatment for fast breathing pneumonia in HIV-negative children aged 2–59 months in Malawi. Occurrence of serious adverse events (SAEs) during the trial were examined to assess disease progression, co-morbidities, recurrence of pneumonia and side effects of amoxicillin.MethodsEnrolled children with fast breathing for age and a history of cough <14 days or difficult breathing were randomised to either placebo or amoxicillin for 3 days, and followed for 14 days to track clinical characteristics and outcomes. Medical history, physical exam, laboratory results and any chest radiographs collected at screening, enrolment and during hospitalisation were evaluated. All SAE reports were reviewed for additional information regarding hospitalisation, course of treatment and outcome.ResultsIn total, 102/1126 (9.0%) enrol...
Aetiology and severity of childhood pneumonia in primary care in Malawi: a cohort study
BMJ Open, 2021
ObjectiveTo determine the aetiology of community acquired pneumonia in children presenting to primary care in Northern Malawi, and to ascertain predictors for identification of children requiring hospitalisation.DesignThe BIOmarkers TO diagnose PnEumonia study was a prospective cohort study conducted from March to June 2016.SettingPrimary care in Northern Malawi.Patients494 children aged 2 –59 months with WHO defined pneumonia.Main outcome(s) and measure(s)Number of children with bacterial infection identified and the sensitivity/specificity of WHO markers of severity for need for hospitalisation.Results13 (2.6%) children had a bacterium consistent with pneumonia identified. A virus consistent with pneumonia was identified in in 448 (90.7%) of children. 56 children were admitted to hospital and two children died within 30 days. 442 (89.5%) received antibiotic therapy. Eleven children (2.6%) had HIV. WHO severity markers at baseline demonstrated poor sensitivity for the need for hosp...
JAMA pediatrics, 2018
Pneumonia is the leading infectious killer of children. Rigorous evidence supporting antibiotic treatment of children with nonsevere fast-breathing pneumonia in low-resource African settings is lacking. To assess whether treatment with placebo for nonsevere fast-breathing pneumonia is substantively less effective than 3 days of treatment with amoxicillin. This double-blind, 2-arm, randomized clinical noninferiority trial with follow-up of 14 days screened 1343 HIV-uninfected children aged 2 to 59 months with nonsevere fast-breathing pneumonia at outpatient departments of hospitals in Lilongwe, Malawi, Africa, between June 2016 and June 2017. Placebo or amoxicillin dispersible tablets administered twice daily for 3 days. The primary end point was the proportion of children failing treatment by day 4 with a relative noninferiority margin of 1.5 times the failure rate in the amoxicillin group. Primary analyses were performed based on the intention-to-treat principle. Planned secondary ...
PLoS ONE, 2014
Objective: To evaluate the pneumonia specific case fatality rate over time following the implementation of a Child Lung Health Programme (CLHP) within the existing government health services in Malawi to improve delivery of pneumonia case management. Methods: A prospective, nationwide public health intervention was studied to evaluate the impact on pneumonia specific case fatality rate (CFR) in infants and young children (0 to 59 months of age) following the implementation of the CLHP. The implementation was step-wise from October 1 st 2000 until 31 st December 2005 within paediatric inpatient wards in 24 of 25 district hospitals in Malawi. Data analysis compared recorded outcomes in the first three months of the intervention (the control period) to the period after that, looking at trend over time and variation by calendar month, age group, severity of disease and region of the country. The analysis was repeated standardizing the follow-up period by using only the first 15 months after implementation at each district hospital. Findings: Following implementation, 47,228 children were admitted to hospital for severe/very severe pneumonia with an overall CFR of 9N8%. In both analyses, the highest CFR was in the children 2 to 11 months, and those with very severe pneumonia. The majority (64%) of cases, 2-59 months, had severe pneumonia. In this group there was a significant effect of the intervention Odds Ratio (OR) 0N70 (95%CI: 0N50-0N98); p = 0N036), while in the same age group children treated for very severe pneumonia there was no interventional benefit (OR 0N97 (95%CI: 0N72-1N30); p = 0N8). No benefit was observed for neonates (OR 0N83 (95%CI: 0N56-1N22); p = 0N335). Conclusions: The nationwide implementation of the CLHP significantly reduced CFR in Malawian infants and children (2-59 months) treated for severe pneumonia. Reasons for the lack of benefit for neonates, infants and children with very severe pneumonia requires further research.
Background: High mortality and disability due to pneumonia occur worldwide. The introduction of the Integrated Management of Childhood Illness strategy in Malawi brought with it hope of an improvement in the outcome of pneumonia. However, the risk of death and treatment outcomes remain unknown in many districts. Method: The medical records of 466 consecutive patients admitted to the Mchinji District Hospital from January 2004 to January 2006 whose disease met the World Health Organization criteria for pneumonia were reviewed. Data were collected from forms that had been fi lled out and different treatment outcomes and determinants of death were analyzed using logistic regression. Results: Of the 466 patients, 62.7% completed treatment, 15.9% had unknown outcomes, 12.9% died, 8.4% were lost to follow-up, 0.8% failed to improve with treatment, and 0.4% were transferred to other facilities. Independent predictors of death were: age less than 2 years, female sex, history of pneumonia, chest retractions, type of pneumonia, and central cyanosis. Conclusion: A high proportion of deaths and unknown outcomes occurred among participants. Young age, female sex, history of pneumonia, chest retractions and central cyanosis were associated with death. Mortality from pneumonia may be reduced by close monitoring of these risk factors and by improving health education programs and communicating these findings to parents and health workers. Further investigations of local reasons for high rates of unknown/unreported outcomes are welcome