•The utility of clinical assessment every 3 hours in children with pneumonia was evaluated.•Despite frequent assessments, post-discharge treatment failure was not identified.•Reliable parameters for ...risk stratification in childhood pneumonia are needed.
Malaria remains a significant cause of morbidity and mortality in Malawi, with an estimated 18-19% prevalence of Plasmodium falciparum in children 2-10 years in 2015-2016. While children report the ...highest rates of clinical disease, adults are thought to be an important reservoir to sustained transmission due to persistent asymptomatic infection. The 2015-2016 Malawi Demographic and Health Survey was a nationally representative household survey which collected dried blood spots from 15,125 asymptomatic individuals ages 15-54 between October 2015 and February 2016. We performed quantitative polymerase chain reaction on 7,393 samples, detecting an overall P. falciparum prevalence of 31.1% (SE = 1.1). Most infections (55.6%) had parasitemias ≤ 10 parasites/µL. While 66.2% of individuals lived in a household that owned a bed net, only 36.6% reported sleeping under a long-lasting insecticide-treated net (LLIN) the previous night. Protective factors included urbanicity, greater wealth, higher education, and lower environmental temperatures. Living in a household with a bed net (prevalence difference 0.02, 95% CI - 0.02 to 0.05) and sleeping under an LLIN (0.01; - 0.02 to 0.04) were not protective against infection. Our findings demonstrate a higher parasite prevalence in adults than published estimates among children. Understanding the prevalence and distribution of asymptomatic infection is essential for targeted interventions.
High vaccination coverage with Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines is critical to addressing childhood pneumonia's high mortality. The Innovative Treatments in ...Pneumonia project in Lilongwe, Malawi collected Hib and pneumococcal vaccination information from children's health passports and found the majority demonstrated inadequate and inconsistent documentation. We were unable to confidently assess the impact of Hib and pneumococcal vaccination on pneumonia treatment failure in our study population. Whether it be that enrolled children did not receive age-eligible vaccines or there was poor vaccination record-keeping, we do not know. A shift to an electronic data collection system may help ensure capture of essential vaccination data and provide more accurate records of both individual and population vaccination coverage in Malawi.
Pneumonia is a leading cause of mortality in children <5 years globally. Early identification of hospitalized children with pneumonia who may fail antibiotics could improve outcomes. We conducted a ...secondary analysis from the Malawi CPAP IMPACT trial evaluating risk factors for antibiotic failure among children hospitalized with pneumonia.
Participants were 1-59 months old with World Health Organization-defined severe pneumonia and hypoxemia, severe malnutrition, and/or HIV exposure/infection. All participants received intravenous antibiotics per standard care. First-line antibiotics were benzylpenicillin and gentamicin for five days. Study staff assessed patients for first-line antibiotic failure daily between days 3-6. When identified, patients failing antibiotics were switched to second-line ceftriaxone. Analyses excluded children receiving ceftriaxone and/or deceased by hospital day two. We compared characteristics between patients with and without treatment failure and fit multivariable logistic regression models to evaluate associations between treatment failure and admission characteristics.
From June 2015-March 2018, 644 children were enrolled and 538 analyzed. Antibiotic failure was identified in 251 (46.7%) participants, and 19/251 (7.6%) died. Treatment failure occurred more frequently with severe malnutrition (50.2% (126/251) vs 28.2% (81/287), p<0.001) and amongst those dwelling ≥10km from a health facility (22.3% (56/251) vs 15.3% (44/287), p = 0.026). Severe malnutrition occurred more frequently among children living ≥10km from a health facility than those living <10km (49.0% (49/100) vs 35.7% (275/428), p = 0.014). Children with severe malnutrition (adjusted odds ratio (aOR) 2.2 (95% CI 1.52, 3.24), p<0.001) and pre-hospital antibiotics ((aOR 1.47, 95% CI 1.01, 2.14), p = 0.043) had an elevated aOR for antibiotic treatment failure.
Severe malnutrition and pre-hospital antibiotic use predicted antibiotic treatment failure in this high-risk severe pneumonia pediatric population in Malawi. Our findings suggest addressing complex sociomedical conditions like severe malnutrition and improving pneumonia etiology diagnostics will be key for better targeting interventions to improve childhood pneumonia outcomes.
•One hundred and fifty infections occurred in eighty-nine paediatric oncology patients.•Gram-positive bacteria were the main cause for bloodstream infection.•Most infections occurred in haematology ...cancers, neutropaenia and recent chemotherapy.•Fungal bloodstream infection was associated with a higher rate of complications.•A low percentage of Gram-negative isolates was resistant to carbapenem antibiotics.
This study was performed to investigate the epidemiology of bloodstream infection (BSI) in oncology patients at Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, with focus placed on the most common causes, complications, and antimicrobial susceptibilities in BSI.
A retrospective cross-sectional study was conducted in the Haematology–Oncology Unit of RCWMCH. All positive blood cultures from RCWMCH oncology patients obtained in 2012 to 2014 were retrieved to identify cases of BSI.
Three hundred and forty-three positive cultures were identified, for 150 BSI episodes among 89 patients; 49.1% of the culture isolates were Gram-positive bacteria, 41.6% were Gram-negative bacteria, and 9.3% were fungal. Coagulase-negative Staphylococcus and viridans group Streptococcus were the most common Gram-positive isolates. Escherichia coli and Klebsiella species were the most common Gram-negative isolates. The majority of BSI episodes occurred in patients with haematological malignancies (74%), in the presence of severe neutropenia (76.4%), and were associated with chemotherapy (88%). Complications occurred in 14% of BSI. Fungal infections had the highest prevalence of complications (21.4%). Three children died during BSI, giving a case-fatality rate of 2%.
BSI in these patients was caused mainly by Gram-positive bacteria and was associated with a low case-fatality rate. These results are consistent with worldwide experience of BSI in paediatric oncology.
RTS,S/AS01 is the first vaccine against malaria to undergo pilot implementation, beginning in 2019 and vaccinating 360,000 children per year in Malawi, Ghana, and Kenya. The four-dose vaccine is ...given as a primary three-dose series with a fourth dose given approximately 18 months later. The efficacy of RTS,S/AS01 was variable among the 11 sites participating in the 2009-2014 phase III trial (MALARIA-055, NCT00866619), possibly due to differences in transmission intensity. However, a within-site examination of environmental factors related to transmission intensity and their impact on vaccine efficacy has yet to be conducted.
We implemented the phase III RTS,S/AS01 trial at the Malawi site, which enrolled 1578 infants (6-12 weeks) and children (5-17 months) living in the Lilongwe District in Central Malawi and followed them for 3 years between 2009 and 2014. A global positioning system survey and an ecological questionnaire were conducted to collect participant household locations and characteristics, while additional data on background malaria prevalence were obtained from a concurrent Malaria Transmission Intensity (MTI) survey. Negative binomial regression models were used to assess whether the efficacy of the vaccine varied by estimated background malaria prevalence, household roof type, or amount of nearby vegetation.
Vaccine efficacy did not significantly vary by estimated malaria prevalence or by roof type. However, increased vegetation cover was associated with an increase in the efficacy of the three-dose primary RTS,S/AS01 series in the 18 months before the fourth dose and a decrease in the efficacy of the primary vaccine series in the second 18 months following, if the fourth dose was not given. Vegetation cover did not alter the efficacy of the fourth dose in a statistically or practically significant manner.
Vegetation coverage in this study site might be a proxy for nearness to rivers or branching, shallow wetlands called "dambos" which could serve as breeding sites for mosquitoes. We observed statistically significant modification of the efficacy of RTS,S/AS01 by forest cover, suggesting that initial vaccine efficacy and the importance of the fourth dose varies based on ecological context.
Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. falciparum Infection in Infants and Children in Africa. NCT00866619 prospectively registered 20 March 2009.
RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission ...settings, possibly due to the more rapid development of naturally acquired immunity in the control group.
To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009-2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01.
We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series.
We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.
Due to increasing antimicrobial resistance in low-resource settings, strategies to rationalize antibiotic treatment of children unlikely to have a bacterial infection are needed. This study's ...objective was to utilize a database of placebo treated Malawian children with World Health Organization (WHO) fast breathing pneumonia to develop a prognostic risk score that could aid antibiotic decision making.
We conducted a secondary analysis of children randomized to the placebo group of the Innovative Treatments in Pneumonia (ITIP) fast breathing randomized, controlled, noninferiority trial. Participants were low-risk HIV-uninfected children 2-59 months old with WHO fast breathing pneumonia in Lilongwe, Malawi. Study endpoints were treatment failure, defined as either disease progression at any time on or before Day 4 of treatment or disease persistence on Day 4, or relapse, considered as the recurrence of pneumonia or severe disease among previously cured children between Days 5 and 14. We utilized multivariable linear regression and stepwise model selection to develop a model to predict the probability of treatment failure or relapse.
Treatment failure or relapse occurred in 11.5% (61/526) of children included in this analysis. The final model incorporated the following predictors: heart rate terms, mid-upper arm circumference, malaria status, water source, family income, and whether or not a sibling or other child in the household received childcare outside the home. The model's area under the receiver operating characteristic score was 0.712 (95% confidence interval 0.66, 0.78) and it explained 6.1% of the variability in predicting treatment failure or relapse (R2, 0.061). For the model to categorize all children with treatment failure or relapse correctly, 77% of children without treatment failure or relapse would require antibiotics.
The model had inadequate discrimination to be appropriate for clinical application. Different strategies will likely be required for models to perform accurately among similar pediatric populations.
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