Diagnosis and Acute Management of COVID-19 and Multisystem Inflammatory Syndrome in Children.

ABSTRACT: Most children with coronavirus disease 2019 (COVID-19) infection are asymptomatic or have mild disease. About 5% of infected children will develop severe or critical disease. Rapid identification and treatment are essential for children who are critically ill with signs and symptoms of respiratory failure, septic shock, and multisystem inflammatory syndrome in children. This article is intended for pediatricians, pediatric emergency physicians, and individuals involved in the emergency care of children. It reviews the current epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, summarizes key aspects of clinical assessment including identification of high-risk patients and manifestations of severe disease, and provides an overview of COVID-19 management in the emergency department based on clinical severity.

'Not all fevers are malaria': a mixed methods study of non-malarial fever management in rural southern Malawi.

INTRODUCTION: With the ability to diagnose malaria with rapid diagnostic tests (mRDT), interest in improving diagnostics for non-malarial fevers has increased. Understanding how health providers diagnose and treat fevers is important for identifying additional tools to improve outcomes and reduce unnecessary antibiotic prescribing, particularly in areas where access to laboratory diagnostics is limited. This study aimed to understand rural health providers' practice patterns, both quantitatively and qualitatively, and influences on diagnostic and treatment decision-making. METHODS: A mixed-methods study was conducted in Mulanje and Phalombe districts in southern Malawi. Retrospective data on diagnoses and treatments of febrile illness from seven mobile clinic logbooks were collected for a 2-month period in both the dry and wet seasons. Mobile health clinics visited remote villages in southern Malawi once every 7 days. Records from all patients with a recorded axillary temperature of 37.5ºC or higher or reported history of fever within 48 hours, and a negative mRDT, were included in the analysis. Key informant interviews were conducted with 31 mobile clinic health workers who triage, diagnose, and treat patients as well as dispense medication. RESULTS: In total, 30 672 febrile patients were seen during the study period. Of those, 9924 (32%) tested negative for malaria by mRDT. Acute respiratory infection was the most common diagnosis for mRDT-negative patients (44.6%), and this number increased in the rainy season as compared to the dry season (odds ratio=2.18, 95% confidence interval=2.01-2.36). Over half (60%) of mRDT-negative patients received antibiotics as a treatment. Almost all the health providers in this study reported limited training in non-malarial fever management, despite the fact that roughly 30% of all patients with fever seen at the mobile clinics tested negative by mRDT. Without diagnostic tools beyond mRDTs, providers relied heavily on patient history to guide treatment decisions. CONCLUSION: Additional simple-to-use diagnostic tests as well as additional training in patient examination and clinical assessment are needed in rural settings where health providers risk over-prescribing antibiotics or missing a potentially dangerous infection in febrile patients who test negative for malaria.

Linguistic isolation correlates with length of stay and mortality for pediatric oncology patients in California.

OBJECTIVE: To evaluate social drivers of health and how they impact pediatric oncology patients' clinical outcomes during pediatric intensive care unit (PICU) admission via correlation with patient ZIP codes. METHODS: Demographic, clinical, and outcome variables from Virtual Pediatric Systems®, LLC for oncology patients (2009-2021) in California PICUs (excluding postoperative) using 3-digit ZIP Codes with social drivers of health variables linguistic isolation, poverty, race/ethnicity, and education abstracted from American Community Survey data for 3-digit ZIP Codes using the Environmental Protection Agency's EJScreen tool. Outcomes of length of stay (LOS), mortality, acuity scores, were compared with social variables. RESULTS: Positive correlation between mortality and minority racial groups (Hispanic/Latino) across ZIP Codes (correlation coefficients of 0.45 (95% CI: 0.22-0.64, p < 0.001) in 2017, 0.50 (95% CI: 0.27-0.68, p < 0.001) in 2018, 0.33 (95% CI: 0.07-0.54, p = 0.013) in 2020, and 0.32 (95% CI: 0.06-0.53, p = 0.018) in 2021). Median PICU length of stay significantly correlated with linguistic isolation (coefficient of 0.42 (95% CI: 0.18-0.61, p = 0.001) in 2021 versus -0.41 (95% CI: -0.61 to -0.16, p = 0.002) in 2019), which included PRISMIII (n = 7417). Mixed effects logistic regression model for other constant variables (PRISMIII, cancer type, race/ethnicity, year), random effect of patient, linguistic isolation (percentage as a continuous value) was significantly associated (95% CI: 1.01-1.06; p = 0.02) with mortality; (OR = 1.03). CONCLUSIONS: Linguistic isolation was correlated with LOS and mortality, however variable year to year.

Etiology of hospital mortality in children living in low- and middle-income countries: a systematic review and meta-analysis.

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%-4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9-14)]; respiratory [9 (95% CI 5-13)]; and gastrointestinal [9 (95% CI 6-11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231-280)]; infectious [214 (95% CI 193-234)]; and gastrointestinal [166 (95% CI 143-190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation.

A research definition and framework for acute paediatric critical illness across resource-variable settings: a modified Delphi consensus.

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research.

Stages of change: Strategies to promote use of a Pediatric Early Warning System in resource-limited pediatric oncology centers.

BACKGROUND: Pediatric Early Warning Systems (PEWS) assist early detection of clinical deterioration in hospitalized children with cancer. Relevant to successful PEWS implementation, the "stages of change" model characterizes stakeholder support for PEWS based on willingness and effort to adopt the new practice. METHODS: At five resource-limited pediatric oncology centers in Latin America, semi-structured interviews were conducted with 71 hospital staff involved in PEWS implementation. Purposive sampling was used to select centers requiring variable time to complete PEWS implementation, with low-barrier centers (3-4 months) and high-barrier centers (10-11 months). Interviews were conducted in Spanish, professionally transcribed, and translated into English. Thematic content analysis explored "stage of change" with constant comparative analysis across stakeholder types and study sites. RESULTS: Participants identified six interventions (training, incentives, participation, evidence, persuasion, and modeling) and two policies (environmental planning and mandates) as effective strategies used by implementation leaders to promote stakeholder progression through stages of change. Key approaches involved presentation of evidence demonstrating PEWS effectiveness, persuasion and incentives addressing specific stakeholder interests, enthusiastic individuals serving as models for others, and policies enforced by hospital directors facilitating habitual PEWS use. Effective engagement targeted hospital directors during early implementation phases to provide programmatic legitimacy for clinical staff. CONCLUSION: This study identifies strategies to promote adoption and maintained use of PEWS, highlighting the importance of tailoring implementation strategies to the motivations of each stakeholder type. These findings can guide efforts to implement PEWS and other evidence-based practices that improve childhood cancer outcomes in resource-limited hospitals.

Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda.

BACKGROUND: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies. METHODS: Secondary analysis of verbal autopsy data from children admitted to 6 hospitals across Uganda from July 2017 to March 2020. Structured verbal autopsy interviews were conducted for all deaths within 6 months after discharge. Two physicians independently classified a primary cause of death, up to 4 alternative causes, and up to 5 contributing conditions using the Start-Up Mortality List, with discordance resolved by consensus. RESULTS: Verbal autopsies were completed for 361 (98.6%) of the 366 (5.9%) children who died among 6191 discharges (median admission age: 5.4 months [interquartile range, 1.8-16.7]; median time to mortality: 28 days [interquartile range, 9-74]). Most deaths (62.3%) occurred in the community. Leading primary causes of death, assigned in 356 (98.6%) of cases, were pneumonia (26.2%), sepsis (22.1%), malaria (8.5%), and diarrhea (7.9%). Common contributors to death were malnutrition (50.5%) and anemia (25.7%). Reviewers were less confident in their causes of death for neonates than older children (P < .05). CONCLUSIONS: Postdischarge mortality frequently occurred in the community in children admitted for suspected sepsis in Uganda. Analyses of the probable causes for these deaths using verbal autopsies suggest potential areas for interventions, focused on early detection of infections, as well as prevention and treatment of underlying contributors such as malnutrition and anemia.

The Burden of Critical Illness in Hospitalized Children in Low- and Middle-Income Countries: Protocol for a Systematic Review and Meta-Analysis.

Background: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality. Objective: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature. Data Sources and Search Strategy: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded. Study Selection: We will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located. Data Extraction: Data extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes. Data Synthesis: We will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow. Conclusions: By understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs.

Common data elements for predictors of pediatric sepsis: A framework to standardize data collection.

BACKGROUND: Standardized collection of predictors of pediatric sepsis has enormous potential to increase data compatibility across research studies. The Pediatric Sepsis Predictor Standardization Working Group collaborated to define common data elements for pediatric sepsis predictors at the point of triage to serve as a standardized framework for data collection in resource-limited settings. METHODS: A preliminary list of pediatric sepsis predictor variables was compiled through a systematic literature review and examination of global guideline documents. A 5-round modified Delphi that involved independent voting and active group discussions was conducted to select, standardize, and prioritize predictors. Considerations included the perceived predictive value of the candidate predictor at the point of triage, intra- and inter-rater measurement reliability, and the amount of time and material resources required to reliably collect the predictor in resource-limited settings. RESULTS: We generated 116 common data elements for implementation in future studies. Each common data element includes a standardized prompt, suggested response values, and prioritization as tier 1 (essential), tier 2 (important), or tier 3 (exploratory). Branching logic was added to the predictors list to facilitate the design of efficient data collection methods, such as low-cost electronic case report forms on a mobile application. The set of common data elements are freely available on the Pediatric Sepsis CoLab Dataverse and a web-based feedback survey is available through the Pediatric Sepsis CoLab. Updated iterations will continuously be released based on feedback from the pediatric sepsis research community and emergence of new information. CONCLUSION: Routine use of the common data elements in future studies can allow data sharing between studies and contribute to development of powerful risk prediction algorithms. These algorithms may then be used to support clinical decision making at triage in resource-limited settings. Continued collaboration, engagement, and feedback from the pediatric sepsis research community will be important to ensure the common data elements remain applicable across a broad range of geographical and sociocultural settings.

Delayed Presentation and Mortality in Children With Sepsis in a Public Tertiary Care Hospital in Tanzania.

Background: Over 40% of the global burden of sepsis occurs in children under 5 years of age, making pediatric sepsis the top cause of death for this age group. Prior studies have shown that outcomes in children with sepsis improve by minimizing the time between symptom onset and treatment. This is a challenge in resource-limited settings where access to definitive care is limited. Methods: A secondary analysis was performed on data from 1,803 patients (28 days-14 years old) who presented to the emergency department (ED) at Muhimbili National Hospital (MNH) from July 1, 2016 to June 30, 2017 with a suspected infection and ≥2 clinical systemic inflammatory response syndrome criteria. The objective of this study was to determine the relationship between delayed presentation to definitive care (>48 h between fever onset and presentation to the ED) and mortality, as well as the association between socioeconomic status (SES) and delayed presentation. Multivariable logistic regression models tested the two relationships of interest. We report both unadjusted and adjusted odds ratios and 95% confidence intervals. Results: During the study period, 11.3% (n = 203) of children who presented to MNH with sepsis died inhospital. Delayed presentation was more common in non-survivors (n = 90/151, 60%) compared to survivors (n = 614/1,353, 45%) (p ≤ 0.01). Children who had delayed presentation to definitive care, compared to those who did not, had an adjusted odds ratio for mortality of 1.85 (95% CI: 1.17-3.00). Conclusions: Delayed presentation was an independent risk factor for mortality in this cohort, emphasizing the importance of timely presentation to care for pediatric sepsis patients. Potential interventions include more efficient referral networks and emergency transportation systems to MNH. Additional clinics or hospitals with pediatric critical care may reduce pediatric sepsis mortality in Tanzania, as well as parental education programs for recognizing pediatric sepsis.

Functional Outcomes and Morbidity in Pediatric Sepsis Survivors: A Tanzanian Experience.

Pediatric sepsis remains a significant cause of childhood morbidity and mortality, disproportionately affecting resource-limited settings. As more patients survive, it is paramount that we improve our understanding of post-sepsis morbidity and its impact on functional outcomes. The functional status scale (FSS) is a pediatric validated outcome measure quantifying functional impairment, previously demonstrating decreased function following critical illnesses, including sepsis, in resource-rich settings. However, functional outcomes utilizing the FSS in pediatric sepsis survivors have never been studied in resource-limited settings or in non-critically ill septic children. In a Tanzanian cohort of pediatric sepsis patients, we aimed to evaluate morbidity associated with an acute septic episode using the FSS modified for resource-limited settings. This was a prospective cohort study at an urban referral hospital in Tanzania, including children with sepsis aged 28 days to 14 years old over a 12-month period. The FSS was adapted to the site's available resources. Functional status scale scores were obtained by interviewing guardians both at the time of presentation to determine the child's baseline and at 28-day follow-up. The primary outcome was "decline in functional status," as defined by a change in FSS score of at least 3. In this cohort, 4.3% of the 1,359 surviving children completing 28-day follow-up had a "decline in functional status." Conversely, 13.8% of guardians reported that their child was not yet back to their pre-illness state. Three-quarters of children reported as not fully recovered were not identified via the FSS as having a decline in functional status. In our cohort of pediatric sepsis patients, we identified a low rate of decline in functional status when using the FSS adapted for resource-limited settings. A higher proportion of children were subjectively identified as not being recovered to baseline. This suggests that the FSS has limitations in this population, despite being adapted for resource-limited settings. Next steps include developing and validating a further revised FSS to better capture patients identified as not recovered but missed by the current FSS.

Global PARITY: Study Design for a Multi-Centered, International Point Prevalence Study to Estimate the Burden of Pediatric Acute Critical Illness in Resource-Limited Settings.

BACKGROUND: The burden of pediatric critical illness and resource utilization by children with critical illness in resource limited settings (RLS) are largely unknown. Without specific data that captures key aspects of critical illness, disease presentation, and resource utilization for pediatric populations in RLS, development of a contextual framework for appropriate, evidence-based interventions to guide allocation of limited but available resources is challenging. We present this methods paper which describes our efforts to determine the prevalence, etiology, hospital outcomes, and resource utilization associated with pediatric acute, critical illness in RLS globally. METHODS: We will conduct a prospective, observational, multicenter, multinational point prevalence study in sixty-one participating RLS hospitals from North, Central and South America, Africa, Middle East and South Asia with four sampling time points over a 12-month period. Children aged 29 days to 14 years evaluated for acute illness or injury in an emergency department) or directly admitted to an inpatient unit will be enrolled and followed for hospital outcomes and resource utilization for the first seven days of hospitalization. The primary outcome will be prevalence of acute critical illness, which Global PARITY has defined as death within 48 hours of presentation to the hospital, including ED mortality; or admission/transfer to an HDU or ICU; or transfer to another institution for a higher level-of-care; or receiving critical care-level interventions (vasopressor infusion, invasive mechanical ventilation, non-invasive mechanical ventilation) regardless of location in the hospital, among children presenting to the hospital. Secondary outcomes include etiology of critical illness, in-hospital mortality, cause of death, resource utilization, length of hospital stay, and change in neurocognitive status. Data will be managed via REDCap, aggregated, and analyzed across sites. DISCUSSION: This study is expected to address the current gap in understanding of the burden, etiology, resource utilization and outcomes associated with pediatric acute and critical illness in RLS. These data are crucial to inform future research and clinical management decisions and to improve global pediatric hospital outcomes.

A 14-day follow-up of adult non-malarial fever patients seen by mobile clinics in rural Malawi.

Background: While health providers consistently use malaria rapid diagnostic tests to rule out malaria, they often lack tools to guide treatment for those febrile patients who test negative. Without the tools to provide an alternative diagnosis, providers may prescribe unnecessary antibiotics or miss a more serious condition, potentially contributing to antibiotic resistance and/or poor patient outcomes. Methods: This study ascertained which diagnoses and treatments might be associated with poor outcomes in adults who test negative for malaria. Adult patients for rapid diagnostic test of malaria seen in mobile health clinics in Mulanje and Phalombe districts were followed for 14 days. Participants were interviewed on sociodemographic characteristics, health-seeking behaviour, diagnosis, treatment and access to care. Mobile clinic medical charts were reviewed. Two weeks (±2 days) following clinic visit, follow-up interviews were conducted to assess whether symptoms had resolved. Results: Initially, 115 adult patients were enrolled and 1 (0.88%) was lost to follow-up. Of the 114 adult patients remaining in the study, 55 (48%) were seen during the dry season and 59 (52%) during the wet season. Symptoms resolved in 90 (80%) patients at the 14-day follow-up visit (n=90) with the rest (n=24) reporting no change in symptoms. None of the patients in the study died or were referred for further care. Almost all patients received some type of medication during their clinic visit (98.2%). Antibiotics were given to 38.6% of patients, and virtually all patients received pain or fever relief (96.5%). However, no anti-malarials were prescribed. Conclusions: Mobile clinics provide important health care where access to care is limited. Although rapid tests have guided appropriate treatment, challenges remain when a patient's presenting complaint is less well defined. In rural areas of southern Malawi, simple diagnostics are needed to guide treatment decisions.

Quality and capacity indicators for hospitalized pediatric oncology patients with critical illness: A modified delphi consensus.

BACKGROUND: Hospitalized pediatric hematology-oncology (PHO) patients are at high risk for critical illness, especially in resource-limited settings. Unfortunately, there are no established quality indicators to guide institutional improvement for these patients. The objective of this study was to identify quality indicators to include in PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), an assessment tool to evaluate the capacity and quality of pediatric critical care services offered to PHO patients. METHODS: A comprehensive literature review identified relevant indicators in the areas of structure, performance, and outcomes. An international focus group sorted potential indicators using the framework of domains and subdomains. A modified, three-round Delphi was conducted among 36 international experts with diverse experience in PHO and critical care in high-resource and resource-limited settings. Quality indicators were ranked on relevance and actionability via electronically distributed surveys. RESULTS: PROACTIVE contains 119 indicators among eight domains and 22 subdomains, with high-median importance (≥7) in both relevance and actionability, and ≥80% evaluator agreement. The top five indicators were: (a) A designated PICU area; (b) Availability of a pediatric intensivist; (c) A PHO physician as part of the primary team caring for critically ill PHO patients; (d) Trained nursing staff in pediatric critical care; and (e) Timely PICU transfer of hospitalized PHO patients requiring escalation of care. CONCLUSIONS: PROACTIVE is a consensus-derived tool to assess the capacity and quality of pediatric onco-critical care in resource-limited settings. Future endeavors include validation of PROACTIVE by correlating the proposed indicators to clinical outcomes and its implementation to identify service delivery gaps amenable to improvement.

Distinct Biomarker Profiles Distinguish Malawian Children with Malarial and Non-malarial Sepsis.

Presently, it is difficult to accurately diagnose sepsis, a common cause of childhood death in sub-Saharan Africa, in malaria-endemic areas, given the clinical and pathophysiological overlap between malarial and non-malarial sepsis. Host biomarkers can distinguish sepsis from uncomplicated fever, but are often abnormal in malaria in the absence of sepsis. To identify biomarkers that predict sepsis in a malaria-endemic setting, we retrospectively analyzed data and sera from a case-control study of febrile Malawian children (aged 6-60 months) with and without malaria who presented to a community health center in Blantyre (January-August 2016). We characterized biomarkers for 29 children with uncomplicated malaria without sepsis, 25 without malaria or sepsis, 17 with malaria and sepsis, and 16 without malaria but with sepsis. Sepsis was defined using systemic inflammatory response criteria; biomarkers (interleukin-6 [IL-6], tumor necrosis factor receptor-1, interleukin-1 ß [IL-1ß], interleukin-10 [IL-10], von Willebrand factor antigen-2, intercellular adhesion molecule-1, and angiopoietin-2 [Ang-2]) were measured with multiplex magnetic bead assays. IL-6, IL-1ß, and IL-10 were elevated, and Ang-2 was decreased in children with malaria compared with non-malarial fever. Children with non-malarial sepsis had greatly increased IL-1ß compared with the other subgroups. IL-1ß best predicted sepsis, with an area under the receiver operating characteristic (AUROC) of 0.71 (95% CI: 0.57-0.85); a combined biomarker-clinical characteristics model improved prediction (AUROC of 0.77, 95% CI: 0.67-0.85). We identified a distinct biomarker profile for non-malarial sepsis and developed a sepsis prediction model. Additional clinical and biological data are necessary to further explore sepsis pathophysiology in malaria-endemic regions.

Characterizing Pediatric Non-Malarial Fever and Identifying the At-Risk Child in Rural Malawi.

Objective. To characterize children with non-malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods. This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non-malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results. A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion. Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa.

Bubble continuous positive airway pressure in the treatment of severe paediatric pneumonia in Malawi: a cost-effectiveness analysis.

OBJECTIVES: Pneumonia is the largest infectious cause of death in children under 5 years globally, and limited resource settings bear an overwhelming proportion of this disease burden. Bubble continuous positive airway pressure (bCPAP), an accepted supportive therapy, is often thought of as cost-prohibitive in these settings. We hypothesise that bCPAP is a cost-effective intervention in a limited resource setting and this study aims to determine the cost-effectiveness of bCPAP, using Malawi as an example. DESIGN: Cost-effectiveness analysis. SETTING: District and central hospitals in Malawi. PARTICIPANTS: Children aged 1 month-5 years with severe pneumonia, as defined by WHO criteria. INTERVENTIONS: Using a decision tree analysis, we compared standard of care (including low-flow oxygen and antibiotics) to standard of care plus bCPAP. PRIMARY AND SECONDARY OUTCOME MEASURES: For each treatment arm, we determined the costs, clinical outcomes and averted disability-adjusted life years (DALYs). We assigned input values from a review of the literature, including applicable clinical trials, and calculated an incremental cost-effectiveness ratio (ICER). RESULTS: In the base case analysis, the cost of bCPAP per patient was $15 per day and $41 per hospitalisation, with an incremental net cost of $64 per pneumonia episode. bCPAP averts 5.0 DALYs per child treated, with an ICER of $12.88 per DALY averted compared with standard of care. In one-way sensitivity analyses, the most influential uncertainties were case fatality rates (ICER range $9-32 per DALY averted). In a multi-way sensitivity analysis, the median ICER was $12.97 per DALY averted (90% CI, $12.77 to $12.99). CONCLUSION: bCPAP is a cost-effective intervention for severe paediatric pneumonia in Malawi. These results may be used to inform policy decisions, including support for widespread use of bCPAP in similar settings.