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Background: Hypoxaemic pneumonia mortality risk in low-income and middle-income countries is high in children who have been hospitalised, but unknown among outpatient children. We sought to establish the outpatient burden, mortality risk, and prognostic accuracy of death from hypoxaemia in children with suspected pneumonia in Bangladesh., Methods: We conducted a prospective community-based cohort study encompassing three upazila (subdistrict) health complex catchment areas in Sylhet, Bangladesh. Children aged 3-35 months participating in a community surveillance programme and presenting to one of three upazila health complex Integrated Management of Childhood Illness (IMCI) outpatient clinics with an acute illness and signs of difficult breathing (defined as suspected pneumonia) were enrolled in the study; because lower respiratory tract infection mortality mainly occurs in children younger than 1 year, the primary study population comprised children aged 3-11 months. Study physicians recorded WHO IMCI pneumonia guideline clinical signs and peripheral arterial oxyhaemoglobin saturations (SpO 2 ) in room air. They treated children with pneumonia with antibiotics (oral amoxicillin [40 mg/kg per dose twice per day for 5-7 days, as per local practice]), and recommended oxygen, parenteral antibiotics, and hospitalisation for those with an SpO 2 of less than 90%, WHO IMCI danger signs, or severe malnutrition. Community health workers documented the children's vital status and the date of any vital status changes during routine household surveillance (one visit to each household every 2 months). The primary outcome was death at 2 weeks after enrolment in children aged 3-11 months (primary study population) and 12-35 months (secondary study population). Primary analyses included estimating the outpatient prevalence, mortality risk, and prognostic accuracy of hypoxaemia for death in children aged 3-11 months with suspected pneumonia. Risk ratios were produced by fitting a multivariable model that regressed predefined SpO 2 ranges (<90%, 90-93%, and 94-100%) on the primary 2-week mortality outcome (binary outcome) using Poisson models with robust variance estimation. We established the prognostic accuracy of WHO IMCI guidelines for death with and without varying SpO 2 thresholds., Findings: Participants were recruited between Sept 1, 2015, to Aug 31, 2017. During the study period, a total of 7440 children aged 3-35 months with the first suspected pneumonia episode were enrolled, of whom 3848 (54·3%) with an attempted pulse oximeter measurement and 2-week outcome were included in our primary study population of children aged 3-11-months. Among children aged 3-11 months, an SpO 2 of less than 90% occurred in 102 (2·7%) of 3848 children, an SpO 2 of 90-93% occurred in 306 (8·0%) children, a failed SpO 2 measurement occurred in 67 (1·7%) children, and 24 (0·6%) children with suspected pneumonia died. Compared with an SpO 2 of 94-100% (3373 [87·7%] of 3848), the adjusted risk ratio for death was 10·3 (95% CI 3·2-32·3; p<0·001) for an SpO 2 of less than 90%, 4·3 (1·5-11·8; p=0·005) for an SpO 2 of 90-93%, and 11·4 (3·1-41·4; p<0·001) for a failed measurement. When not considering pulse oximetry, of the children who died, WHO IMCI guidelines identified only 25·0% (95% CI 9·7-46·7; six of 24 children) as eligible for referral to hospital. For identifying deaths, in children with an SpO 2 of less than 90% WHO IMCI guidelines had a 41·7% sensitivity (95% CI 22·1-63·4) and 89·7% specificity (88·7-90·7); for children with an SpO 2 of less than 90% or measurement failure the guidelines had a 54·2% sensitivity (32·8-74·4) and 88·3% specificity (87·2-89·3); and for children with an SpO 2 of less than 94% or measurement failure the guidelines had a 62·5% sensitivity (40·6-81·2) and 81·3% specificity (80·0-82·5)., Interpretation: These findings support pulse oximeter use during the outpatient care of young children with suspected pneumonia in Bangladesh as well as the re-evaluation of the WHO IMCI currently recommended threshold of an SpO 2 less than 90% for hospital referral., Funding: Fogarty International Center of the National Institutes of Health (K01TW009988), The Bill & Melinda Gates Foundation (OPP1084286 and OPP1117483), and GlaxoSmithKline (90063241)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Between 2013 and 2022, Nigeria did not meet globally defined targets for pneumonia control, despite some scale-up of vaccinations, oxygen and antibiotics. A deliberate focus on community-based programs is needed to improve coverage of protective, preventive and treatment interventions. We therefore aimed to describe caregiver knowledge and care seeking behaviour for childhood pneumonia, in a high child mortality setting in Nigeria, to inform the development of effective community-based interventions for pneumonia control., Methods: We conducted a cross-sectional household survey in Kiyawa Local Government Area, Jigawa State, Nigeria between December 2019 and March 2020. We asked caregivers about their knowledge of pneumonia symptoms, prevention, risks, and treatment. A score of 1 was assigned for each correct response. We showed them videos of pneumonia specific symptoms and asked (1) if their child had any respiratory symptoms in the 2-weeks prior; (2) their subsequent care-seeking behaviour. Multivariate regressions explored socio-demographic and clinical factors associated with care seeking., Results: We surveyed 1,661 eligible women, with 2,828 children under-five. Only 4.9% of women could name both cough and difficulty/fast breathing as pneumonia symptoms, and the composite knowledge scores for pneumonia prevention, risks and treatment were low. Overall, 19.0% (536/2828) of children had a report of pneumonia specific symptoms in the prior two-weeks, and of these 32.3% (176/536) were taken for care. The odds of care seeking was higher among children: with fever (AOR:2:45 [95% CI: 1.38-4.34]); from wealthiest homes (AOR: 2:13 [95% CI: 1.03-4.38]) and whose mother first married at 20-26 years compared to 15-19 years (AOR: 5.15 [95% CI: 1.38-19.26]). Notably, the caregiver's knowledge of pneumonia was not associated with care seeking., Conclusion: While some socio-demographic factors were associated with care seeking for children with symptoms of Acute Respiratory Infection (ARI), caregiver's knowledge of the disease was not. Therefore, when designing public health interventions to address child mortality, information-giving alone is likely to be insufficient., Competing Interests: TO was employed by GlaxoSmithKline (GSK), Lagos, Nigeria. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bakare, King, Salako, Bakare, Uchendu, Burgess, Shittu, Iuliano, Isah, Ahmed, Ahmar, Valentine, Olowookere, McCollum, Colbourn, Falade and Graham.)

Objectives: We determined the pulse oximetry benefit in pediatric pneumonia mortality risk stratification and chest-indrawing pneumonia in-hospital mortality risk factors., Methods: We report the characteristics and in-hospital pneumonia-related mortality of children aged 2-59 months who were included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest-indrawing pneumonia to identify mortality risk factors., Results: Among 285,839 children, 164,244 (57.5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5.8%, 95% confidence interval [CI] 5.6-5.9% vs 2.1%, 95% CI 1.9-2.4%). One in five children with chest-indrawing pneumonia was hypoxemic (19.7%, 95% CI 19.0-20.4%), and the hypoxemic CFR was 10.3% (95% CI 9.1-11.5%). Other mortality risk factors were younger age (either 2-5 months [adjusted odds ratio (aOR) 9.94, 95% CI 6.67-14.84] or 6-11 months [aOR 2.67, 95% CI 1.71-4.16]), moderate malnutrition (aOR 2.41, 95% CI 1.87-3.09), and female sex (aOR 1.82, 95% CI 1.43-2.32)., Conclusion: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest-indrawing pneumonia were hypoxemic and one in 10 died. Young age and moderate malnutrition were risk factors for in-hospital chest-indrawing pneumonia-related mortality. Pulse oximetry should be integrated in pneumonia hospital care for children under 5 years., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines., Methods: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set., Results: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285 839 children with pneumonia (244 323 in the hospital and 41 516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285 839 episodes, 280 998 occurred in children 0-59 months old, of which 129 584 (46%) were 2-11 months of age and 152 730 (54%) were males., Conclusions: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: YBN is staff member of the World Health Organization., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Objective: To estimate the point prevalence of pneumonia and malnutrition and explore associations with household socioeconomic factors., Design: Community-based cross-sectional study conducted in January-June 2021 among a random sample of households across all villages in the study area., Setting: Kiyawa Local Government Area, Jigawa state, Nigeria., Participants: Children aged 0-59 months who were permanent residents in Kiyawa and present at home at the time of the survey., Main Outcome Measures: Pneumonia (non-severe and severe) defined using WHO criteria (2014 revision) in children aged 0-59 months. Malnutrition (moderate and severe) defined using mid-upper arm circumference in children aged 6-59 months., Results: 9171 children were assessed, with a mean age of 24.8 months (SD=15.8); 48.7% were girls. Overall pneumonia (severe or non-severe) point prevalence was 1.3% (n=121/9171); 0.6% (n=55/9171) had severe pneumonia. Using an alternate definition that did not rely on caregiver-reported cough/difficult breathing revealed higher pneumonia prevalence (n=258, 2.8%, 0.6% severe, 2.2% non-severe). Access to any toilet facility was associated with lower odds of pneumonia (aOR: 0.56; 95% CI: 0.31 to 1.01). The prevalence of malnutrition (moderate or severe) was 15.6% (n=1239/7954) with 4.1% (n=329/7954) were severely malnourished. Being older (aOR: 0.22; 95% CI: 0.17 to 0.27), male (aOR: 0.77; 95% CI: 0.66 to 0.91) and having head of compound a business owner or professional (vs subsistence farmer, aOR 0.71; 95% CI: 0.56 to 0.90) were associated with lower odds of malnutrition., Conclusions: In this large, representative community-based survey, there was a considerable pneumonia and malnutrition morbidity burden. We noted challenges in the diagnosis of Integrated Management of Childhood Illness-defined pneumonia in this context., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings., Methods: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool., Results: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84)., Conclusions: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Child mortality remains unacceptably high, with Northern Nigeria reporting some of the highest rates globally (e.g. 192/1000 live births in Jigawa State). Coverage of key protect and prevent interventions, such as vaccination and clean cooking fuel use, is low. Additionally, knowledge, care-seeking and health system factors are poor. Therefore, a whole systems approach is needed for sustainable reductions in child mortality., Methods: This is a cluster randomised controlled trial, with integrated process and economic evaluations, conducted from January 2021 to September 2022. The trial will be conducted in Kiyawa Local Government Area, Jigawa State, Nigeria, with an estimated population of 230,000. Clusters are defined as primary government health facility catchment areas (n = 33). The 33 clusters will be randomly allocated (1:1) in a public ceremony, and 32 clusters included in the impact evaluation. The trial will evaluate a locally adapted 'whole systems strengthening' package of three evidence-based methods: community men's and women's groups, Partnership Defined Quality Scorecard and healthcare worker training, mentorship and provision of basic essential equipment and commodities. The primary outcome is mortality of children aged 7 days to 59 months. Mortality will be recorded prospectively using a cohort design, and secondary outcomes measured through baseline and endline cross-sectional surveys. Assuming the following, we will have a minimum detectable effect size of 30%: (a) baseline mortality of 100 per 1000 livebirths, (b) 4480 compounds with 3 eligible children per compound, (c) 80% power, (d) 5% significance, (e) intra-cluster correlation of 0.007 and (f) coefficient of variance of cluster size of 0.74. Analysis will be by intention-to-treat, comparing intervention and control clusters, adjusting for compound and trial clustering., Discussion: This study will provide robust evidence of the effectiveness and cost-effectiveness of community-based participatory learning and action, with integrated health system strengthening and accountability mechanisms, to reduce child mortality. The ethnographic process evaluation will allow for a rich understanding of how the intervention works in this context. However, we encountered a key challenge in calculating the sample size, given the lack of timely and reliable mortality data and the uncertain impacts of the COVID-19 pandemic., Trial Registration: ISRCTN 39213655 . Registered on 11 December 2019., (© 2021. The Author(s).)

Background: Existing scores to identify children at risk of hospitalized pneumonia-related mortality lack broad external validation. Our objective was to externally validate three such risk scores., Methods: We applied the Respiratory Index of Severity in Children (RISC) for HIV-negative children, the RISC-Malawi, and the Pneumonia Etiology Research for Child Health (PERCH) scores to hospitalized children in the Pneumonia REsearch Partnerships to Assess WHO REcommendations (PREPARE) data set. The PREPARE data set includes pooled data from 41 studies on pediatric pneumonia from across the world. We calculated test characteristics and the area under the curve (AUC) for each of these clinical prediction rules., Results: The RISC score for HIV-negative children was applied to 3574 children 0-24 months and demonstrated poor discriminatory ability (AUC = 0.66, 95% confidence interval (CI) = 0.58-0.73) in the identification of children at risk of hospitalized pneumonia-related mortality. The RISC-Malawi score had fair discriminatory value (AUC = 0.75, 95% CI = 0.74-0.77) among 17 864 children 2-59 months. The PERCH score was applied to 732 children 1-59 months and also demonstrated poor discriminatory value (AUC = 0.55, 95% CI = 0.37-0.73)., Conclusions: In a large external application of the RISC, RISC-Malawi, and PERCH scores, a substantial number of children were misclassified for their risk of hospitalized pneumonia-related mortality. Although pneumonia risk scores have performed well among the cohorts in which they were derived, their performance diminished when externally applied. A generalizable risk assessment tool with higher sensitivity and specificity to identify children at risk of hospitalized pneumonia-related mortality may be needed. Such a generalizable risk assessment tool would need context-specific validation prior to implementation in that setting., Competing Interests: Competing interests: The authors have completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author), and declare no conflicts of interest. YBN is staff member of the World Health Organization., (Copyright © 2021 by the Journal of Global Health. All rights reserved.)

Background: The mortality impact of pulse oximetry use during infant and childhood pneumonia management at the primary healthcare level in low-income countries is unknown. We sought to determine mortality outcomes of infants and children diagnosed and referred using clinical guidelines with or without pulse oximetry in Malawi., Methods and Findings: We conducted a data linkage study of prospective health facility and community case and mortality data. We matched prospectively collected community health worker (CHW) and health centre (HC) outpatient data to prospectively collected hospital and community-based mortality surveillance outcome data, including episodes followed up to and deaths within 30 days of pneumonia diagnosis amongst children 0-59 months old. All data were collected in Lilongwe and Mchinji districts, Malawi, from January 2012 to June 2014. We determined differences in mortality rates using <90% and <93% oxygen saturation (SpO2) thresholds and World Health Organization (WHO) and Malawi clinical guidelines for referral. We used unadjusted and adjusted (for age, sex, respiratory rate, and, in analyses of HC data only, Weight for Age Z-score [WAZ]) regression to account for interaction between SpO2 threshold (pulse oximetry) and clinical guidelines, clustering by child, and CHW or HC catchment area. We matched CHW and HC outpatient data to hospital inpatient records to explore roles of pulse oximetry and clinical guidelines on hospital attendance after referral. From 7,358 CHW and 6,546 HC pneumonia episodes, we linked 417 CHW and 695 HC pneumonia episodes to 30-day mortality outcomes: 16 (3.8%) CHW and 13 (1.9%) HC patients died. SpO2 thresholds of <90% and <93% identified 1 (6%) of the 16 CHW deaths that were unidentified by integrated community case management (iCCM) WHO referral protocol and 3 (23%) and 4 (31%) of the 13 HC deaths, respectively, that were unidentified by the integrated management of childhood illness (IMCI) WHO protocol. Malawi IMCI referral protocol, which differs from WHO protocol at the HC level and includes chest indrawing, identified all but one of these deaths. SpO2 < 90% predicted death independently of WHO danger signs compared with SpO2 ≥ 90%: HC Risk Ratio (RR), 9.37 (95% CI: 2.17-40.4, p = 0.003); CHW RR, 6.85 (1.15-40.9, p = 0.035). SpO2 < 93% was also predictive versus SpO2 ≥ 93% at HC level: RR, 6.68 (1.52-29.4, p = 0.012). Hospital referrals and outpatient episodes with referral decision indications were associated with mortality. A substantial proportion of those referred were not found admitted in the inpatients within 7 days of referral advice. All 12 deaths in 73 hospitalised children occurred within 24 hours of arrival in the hospital, which highlights delay in appropriate care seeking. The main limitation of our study was our ability to only match 6% of CHW episodes and 11% of HC episodes to mortality outcome data., Conclusions: Pulse oximetry identified fatal pneumonia episodes at HCs in Malawi that would otherwise have been missed by WHO referral guidelines alone. Our findings suggest that pulse oximetry could be beneficial in supplementing clinical signs to identify children with pneumonia at high risk of mortality in the outpatient setting in health centres for referral to a hospital for appropriate management., Competing Interests: The authors have declared that no competing interests exist.

Background: Appropriate and timely care seeking can reduce pneumonia deaths, but are influenced by caregivers and community norms of health and illness. We explore caregiver and community perceptions, and care-seeking experience, of childhood pneumonia, to understand contexts that drive pediatric service uptake in Nigeria., Methods: Community group discussions and qualitative interviews with caregivers in Lagos and Jigawa states were completed between 1 November 2018 and 31 May 2019. Participants were recruited from purposively sampled health facility catchment areas with assistance from facility staff. We used episodic interviews, asking caregivers (Jigawa = 20; Lagos = 15) to recount specific events linked to quests for therapy. Community group discussions (n = 3) used four vignettes from real pneumonia cases to frame a discussion around community priorities for healthcare and community-led activities to improve child survival. Data were analyzed using the framework method., Results: We found poor knowledge of pneumonia-specific symptoms and risk factors among caregivers and community members, with many attributing pneumonia to cold air exposure. Interviews highlighted that care-seeking decision making involved both husbands and wives, but men often made final decisions. In Lagos, older female relatives also shaped quests for therapy. Cost was a major consideration. In both states, there were accounts of dissatisfaction with health workers' attitudes and a general acceptance of vaccination services., Conclusion: There is a need for community-based approaches to improve caregiver knowledge and care seeking for under-five children with pneumonia. Messaging should attend to knowledge of symptoms, risk factors, family dynamics, and community responsibilities in healthcare service delivery and utilization., (© 2020 Wiley Periodicals, Inc.)

Background: Case fatality rates for childhood pneumonia in Nigeria remain high. There is a clear need for improved case management of pneumonia, through the sustainable implementation of the Integrated Management of Childhood Illnesses (IMCI) diagnostic and treatment algorithms. We explored barriers and opportunities for improved case management of childhood pneumonia in Lagos and Jigawa states, Nigeria., Methods: A mixed-method analysis was conducted to assess the current health system capacity to deliver quality care. This was done through audits of 16 facilities in Jigawa and 14 facilities in Lagos, questionnaires (n = 164) and 13 focus group discussions with providers. Field observations provided context for data analysis and triangulation., Results: There were more private providers in Lagos (4/8 secondary facilities) and more government providers in Jigawa (4/8 primary, 3/3 secondary, and 1/1 tertiary facilities). Oxygen and pulse oximeters were available in two of three in Jigawa and six of eight in Lagos of the sampled secondary care facilities. None of the eight primary facilities surveyed in Jigawa had oxygen or pulse oximetry available while in Lagos two of three primary facilities had oxygen and one of three had pulse oximeters. Other IMCI and emergency equipment were also lacking including respiratory rate timers, particularly in Jigawa state. Health care providers scored poorly on knowledge of IMCI, though previous IMCI training was associated with better knowledge. Key enabling factors in delivering pediatric care highlighted by health care providers included accountability procedures and feedback loops, the provision of free medication for children, and philanthropic acts. Common barriers to provide care included the burden of out-of-pocket payments, challenges in effective communication with caregivers, delayed presentation, and lack of clear diagnosis, and case management guidelines., Conclusion: There is an urgent need to improve how the prevention and treatment of pediatric pneumonia is directed in both Lagos and Jigawa. Priority areas for reducing pediatric pneumonia burden are training and mentoring of health care providers, community health education, and introduction of oximeters and oxygen supply., (© 2020 Wiley Periodicals, Inc.)

Background: Pneumonia is a leading killer of children under-5 years, with a high burden in Nigeria. We aimed to quantify the regional burden and risks of pediatric pneumonia in Nigeria, and specifically the states of Lagos and Jigawa., Methods: We conducted a scoping literature search for studies of pneumonia morbidity and mortality in under-5 children in Nigeria from 10th December 2018 to 26th April 2019, searching: Cochrane, PubMed, and Web of Science. We included grey literature from stakeholders' websites and information shared by organizations working in Nigeria. We conducted multivariable logistic regression using the 2016 to 2017 Multiple Cluster Indicators Survey data set to explore factors associated with pneumonia. Descriptive analyses of datasets from 2010 to 2019 was done to estimate trends in mortality, morbidity, and vaccination coverage., Results: We identified 25 relevant papers (10 from Jigawa, 8 from Lagos, and 14 national data). None included data on pneumonia or acute respiratory tract infection burden in the health system, inpatient case-fatality rates, severity, or age-specific pneumonia mortality rates at state level. Secondary data analysis found that no household or caregiver socioeconomic indicators were consistently associated with self-reported symptoms of cough and/or difficulty breathing, and seasonality was inconsistently associated, dependant on region., Conclusion: There is a clear evidence gap around the burden of pediatric pneumonia in Nigeria, and challenges with the interpretation of existing household survey data. Improved survey approaches are needed to understand the risks of pediatric pneumonia in Nigeria, alongside the need for investment in reliable routine data systems to provide data on the clinical pneumonia burden in Nigeria., (© 2020 Wiley Periodicals, Inc.)

Background: Interventions to reduce pneumonia mortality exist; however, stakeholder engagement is needed to prioritize these. We explored diverse stakeholder opinions on current policy challenges and priorities for pediatric pneumonia in Nigeria., Methods: We conducted a mixed-methods study, with a web-survey and semi-structured interviews, to explore stakeholder roles, policy barriers, opportunities, and priorities. Web-survey participants were identified through stakeholder mapping, including researchers' networks, academic and grey literature, and "Every Breath Counts" coalition membership. Stakeholders included actors involved in pediatric pneumonia in Nigeria from non-governmental, government, academic, civil society, private, and professional organizations. Stakeholder interviews were conducted with local government, healthcare managers, professional associations, and local leaders in Lagos and Jigawa states. Quantitative data were analyzed descriptively; qualitative data were analyzed using a thematic framework., Results: Of 111 stakeholders, 38 (34%) participated in the web-survey and 18 stakeholder interviews were conducted. Four thematic areas emerged: current policy, systems barriers, intervention priorities, and champions. Interviewees reported a lack of pneumonia-specific policies, despite acknowledging guidelines had been adopted in their settings. Barriers to effective pneumonia management were seen at all levels of the system, from the community to healthcare to policy, with key issues of resourcing and infrastructure. Intervention priorities were the strengthening of community knowledge and improving case management, focused on primary care. While stakeholders identified several key actors for pediatric pneumonia, they also highlighted a lack of champions., Conclusion: Consistent messages emerged to prioritize community and primary care initiatives, alongside improved access to oxygen, and pulse oximetry. There is a need for clear pneumonia policies, and support for adoption at a state level., (© 2019 Wiley Periodicals, Inc.)

Background: Pneumonia remains the leading cause of paediatric infectious mortality globally. Treatment failure, which can result from non-adherence to oral antibiotics, can lead to poor outcomes and therefore improving adherence could be a strategy to reduce pneumonia related morbidity and mortality. However, there is little published evidence from low-resource settings for the drivers of non-adherence to oral antibiotics in children., Objective: We aimed to investigate reasons for adherence and non-adherence in children diagnosed and treated in the community with fast-breathing pneumonia in rural Malawi., Methods: We conducted focus group discussions (FGDs) with caregivers of children known to have been diagnosed and treated with oral antibiotics for fast-breathing pneumonia in the community and key informant interviews with community healthcare workers (CHW). FGDs and interviews were conducted within communities in Chichewa, the local language. We used a framework approach to analyze the transcripts., Results: We conducted 4 FGDs with caregivers and 10 interviews with CHWs. We identified four themes, which were common across caregivers and CHWs: knowledge and understanding, effort, medication perceptions and community influences. Caregivers and CHWs demonstrated good knowledge of pneumonia and types of treatment, but caregivers showed confusion around dosing and treatment durations. Effort was needed to seek care, prepare medication and understand regimens, acting as a barrier to adherence. Perceptions of how well the treatment was working influenced adherence, with both quick recovery and slow recovery leading to non-adherence. Community influences were both supportive, with transport assistance for referrals and home visits to improve adherence, and detrimental, with pressure to share treatments., Conclusion: Adherence to oral antibiotic treatment for fast-breathing pneumonia was understood to be important, however considerable barriers we described within this rural low-resource setting, such as the effort preparing and administering medication, community pressures to share drugs and potential complexity of regimens., Competing Interests: The authors have declared that no competing interests exist.

Hypoxemia measured by pulse oximetry predicts child pneumonia mortality in low-resource settings (LRS). Existing pediatric oximeter probes are prohibitively expensive and/or difficult to use, limiting LRS implementation. Using a human-centered design, we developed a low-cost, reusable pediatric oximeter probe for LRS health-care workers (HCWs). Here, we report probe usability testing. Fifty-one HCWs from Malawi, Bangladesh, and the United Kingdom participated, and seven experts provided reference measurements. Health-care workers and experts measured the peripheral arterial oxyhemoglobin saturation (SpO 2 ) independently in < 5 year olds. Health-care worker measurements were classed as successful if recorded in 5 minutes (or shorter) and physiologically appropriate for the child, using expert measurements as the reference. All expert measurements were considered successful if obtained in < 5 minutes. We analyzed the proportion of successful SpO 2 measurements obtained in < 1, < 2, and < 5 minutes and used multivariable logistic regression to predict < 1 minute successful measurements. We conducted four testing rounds with probe modifications between rounds, and obtained 1,307 SpO 2 readings. Overall, 67% (876) of measurements were successful and achieved in < 1 minute, 81% (1,059) < 2 minutes, and 90% (1,181) < 5 minutes. Compared with neonates, increasing age (infant adjusted odds ratio [aOR]; 1.87, 95% confidence interval [CI]: 1.16, 3.02; toddler aOR: 4.33, 95% CI: 2.36, 7.97; child aOR; 3.90, 95% CI: 1.73, 8.81) and being asleep versus being calm (aOR; 3.53, 95% CI: 1.89, 6.58), were associated with < 1 minute successful measurements. In conclusion, we designed a novel, reusable pediatric oximetry probe that was effectively used by LRS HCWs on children. This probe may be suitable for LRS implementation.

Background: Pneumonia 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., Methods: We 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., Results: 16,475 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., Conclusion: In 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., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate implementation of outpatient pulse oximetry among children with pneumonia, in Malawi., Methods: In 2011, 72 health-care providers at 18 rural health centres and 38 community health workers received training in the use of pulse oximetry to measure haemoglobin oxygen saturations. Data collected, between 1 January 2012 and 30 June 2014 by the trained individuals, on children aged 2-59 months with clinically diagnosed pneumonia were analysed., Findings: Of the 14 092 children included in the analysis, 13 266 (94.1%) were successfully checked by oximetry. Among the children with chest indrawing and/or danger signs, those with a measured oxygen saturation below  90% were more than twice as likely to have been referred as those with higher saturations (84.3% [385/457] vs 41.5% [871/2099]; P  < 0.001). The availability of oximetry appeared to have increased the referral rate for severely hypoxaemic children without chest indrawing or danger signs from 0% to 27.2% ( P  < 0.001). In the absence of oximetry, if the relevant World Health Organization (WHO) guidelines published in 2014 had been applied, 390/568 (68.7%) severely hypoxaemic children at study health centres and 52/84 (61.9%) severely hypoxaemic children seen by community health workers would have been considered ineligible for referral., Conclusion: Implementation of pulse oximetry by our trainees substantially increased the referrals of Malawian children with severe hypoxaemic pneumonia. When data from oximetry were excluded, retrospective application of the guidelines published by WHO in 2014 failed to identify a considerable proportion of severely hypoxaemic children eligible only via oximetry.

Background: Despite recent progress, pneumonia remains the largest infectious killer of children globally. This paper describes outcomes of not treating community-diagnosed fast-breathing pneumonia on patient recovery., Methods: We conducted an exploratory subanalysis of an observational prospective cohort study in Malawi. We recruited children (2-59 months) diagnosed by community health workers with fast-breathing pneumonia using WHO integrated community case management (iCCM) guidelines. Children were followed at days 5 and 14 with a clinical assessment of recovery. We conducted bivariate and multivariable logistic regression for the association between treatment of fast-breathing pneumonia and recovery, adjusting for potential confounders., Results: We followed up 847 children, of whom 78 (9%) had not been given antibiotics (non-treatment). Non-treatment cases had higher baseline rates of diarrhoea, non-severe hypoxaemia and fever. Non-recovery (persistence or worsening of symptoms) was 13% and 23% at day 5 in those who did receive and those who did not receive co-trimoxazole. Non-recovery, when defined as worsening of symptoms only, at day 5 was 7% in treatment and 10% in non-treatment cases. For both definitions, combined co-trimoxazole and lumefantrine-artemether (LA) treatment trended towards protection (adjusted OR (aOR) 0.28; 95% CI 0.12 to 0.68/aOR 0.29; 95% CI 0.08 to 1.01)., Conclusion: We found that children who did not receive co-trimoxazole treatment had worse clinical outcomes; malaria co-diagnosis and treatment also play a significant role in non-recovery. Further research into non-treatment of fast-breathing pneumonia, using a pragmatic approach with consideration for malaria co-diagnosis and HIV status is needed to guide refinement of community treatment algorithms in this region., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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 effects 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 significantly decreased between 2001 (15·2% [13·4-17·1]) and 2012 (4·5% [4·1-4·9]; ptrend<0·0001). Univariable analyses indicated that the decrease in case fatality rate was consistent across most subgroups. In multivariable analyses, the risk factors significantly 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 specific subgroups. Improvements in hospital care may have reduced case fatality rates though a lack of sufficient 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 effective 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., (Copyright © 2016 Lazzerini et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa., Method: We prospectively followed a cohort of children (2-59 months), diagnosed by community health workers with fast-breathing pneumonia using World Health Organisation (WHO) integrated community case management guidelines. Cases were followed at days 5 and 14 by study data collectors, who assessed a range of pre-determined clinical features for treatment outcome. We built the prognostic model using eight pre-defined parameters, using multivariable logistic regression, validated through bootstrapping., Results: We assessed 1,542 cases of which 769 were included (32% ineligible; 19% defaulted). The treatment failure rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis (OR: 1.62; 95% CI: 1.06, 2.47) and moderate malnutrition (OR: 1.88; 95% CI: 1.09, 3.26) were associated with treatment failure. The model demonstrated poor calibration and discrimination (c-statistic: 0.56)., Conclusion: This study suggests that it may be difficult to create a pragmatic community-level prognostic child pneumonia tool based solely on clinical markers and pulse oximetry in an HIV and malaria endemic setting. Further work is needed to identify more accurate and reliable referral algorithms that remain feasible for use by community health workers.