COVID-19 pandemic effects on neonatal inpatient admissions and mortality: interrupted time series analysis of facilities implementing NEST360 in Kenya, Malawi, Nigeria, and Tanzania.

BACKGROUND: The emergence of COVID-19 precipitated containment policies (e.g., lockdowns, school closures, etc.). These policies disrupted healthcare, potentially eroding gains for Sustainable Development Goals including for neonatal mortality. Our analysis aimed to evaluate indirect effects of COVID-19 containment policies on neonatal admissions and mortality in 67 neonatal units across Kenya, Malawi, Nigeria, and Tanzania between January 2019 and December 2021. METHODS: The Oxford Stringency Index was applied to quantify COVID-19 policy stringency over time for Kenya, Malawi, Nigeria, and Tanzania. Stringency increased markedly between March and April 2020 for these four countries (although less so in Tanzania), therefore defining the point of interruption. We used March as the primary interruption month, with April for sensitivity analysis. Additional sensitivity analysis excluded data for March and April 2020, modelled the index as a continuous exposure, and examined models for each country. To evaluate changes in neonatal admissions and mortality based on this interruption period, a mixed effects segmented regression was applied. The unit of analysis was the neonatal unit (n = 67), with a total of 266,741 neonatal admissions (January 2019 to December 2021). RESULTS: Admission to neonatal units decreased by 15% overall from February to March 2020, with half of the 67 neonatal units showing a decline in admissions. Of the 34 neonatal units with a decline in admissions, 19 (28%) had a significant decrease of ≥ 20%. The month-to-month decrease in admissions was approximately 2% on average from March 2020 to December 2021. Despite the decline in admissions, we found no significant changes in overall inpatient neonatal mortality. The three sensitivity analyses provided consistent findings. CONCLUSION: COVID-19 containment measures had an impact on neonatal admissions, but no significant change in overall inpatient neonatal mortality was detected. Additional qualitative research in these facilities has explored possible reasons. Strengthening healthcare systems to endure unexpected events, such as pandemics, is critical in continuing progress towards achieving Sustainable Development Goals, including reducing neonatal deaths to less than 12 per 1000 live births by 2030.

Health facility assessment of small and sick newborn care in low- and middle-income countries: systematic tool development and operationalisation with NEST360 and UNICEF.

BACKGROUND: Each year an estimated 2.3 million newborns die in the first 28 days of life. Most of these deaths are preventable, and high-quality neonatal care is fundamental for surviving and thriving. Service readiness is used to assess the capacity of hospitals to provide care, but current health facility assessment (HFA) tools do not fully evaluate inpatient small and sick newborn care (SSNC). METHODS: Health systems ingredients for SSNC were identified from international guidelines, notably World Health Organization (WHO), and other standards for SSNC. Existing global and national service readiness tools were identified and mapped against this ingredients list. A novel HFA tool was co-designed according to a priori considerations determined by policymakers from four African governments, including that the HFA be completed in one day and assess readiness across the health system. The tool was reviewed by > 150 global experts, and refined and operationalised in 64 hospitals in Kenya, Malawi, Nigeria, and Tanzania between September 2019 and March 2021. RESULTS: Eight hundred and sixty-six key health systems ingredients for service readiness for inpatient SSNC were identified and mapped against four global and eight national tools measuring SSNC service readiness. Tools revealed major content gaps particularly for devices and consumables, care guidelines, and facility infrastructure, with a mean of 13.2% (n = 866, range 2.2-34.4%) of ingredients included. Two tools covered 32.7% and 34.4% (n = 866) of ingredients and were used as inputs for the new HFA tool, which included ten modules organised by adapted WHO health system building blocks, including: infrastructure, pharmacy and laboratory, medical devices and supplies, biomedical technician workshop, human resources, information systems, leadership and governance, family-centred care, and infection prevention and control. This HFA tool can be conducted at a hospital by seven assessors in one day and has been used in 64 hospitals in Kenya, Malawi, Nigeria, and Tanzania. CONCLUSION: This HFA tool is available open-access to adapt for use to comprehensively measure service readiness for level-2 SSNC, including respiratory support. The resulting facility-level data enable comparable tracking for Every Newborn Action Plan coverage target four within and between countries, identifying facility and national-level health systems gaps for action.

Amoxicillin for 3 or 5 Days for Chest-Indrawing Pneumonia in Malawian Children.

BACKGROUND: Evidence regarding the appropriate duration of treatment with antibiotic agents in children with pneumonia in low-resource settings in Africa is lacking. METHODS: We conducted a double-blind, randomized, controlled, noninferiority trial in Lilongwe, Malawi, to determine whether treatment with amoxicillin for 3 days is less effective than treatment for 5 days in children with chest-indrawing pneumonia (cough lasting <14 days or difficulty breathing, along with visible indrawing of the chest wall with or without fast breathing for age). Children not infected with human immunodeficiency virus (HIV) who were 2 to 59 months of age and had chest-indrawing pneumonia were randomly assigned to receive amoxicillin twice daily for either 3 days or 5 days. Children were followed for 14 days. The primary outcome was treatment failure by day 6; noninferiority of the 3-day regimen to the 5-day regimen would be shown if the percentage of children with treatment failure in the 3-day group was no more than 1.5 times that in the 5-day group. Prespecified secondary analyses included assessment of treatment failure or relapse by day 14. RESULTS: From March 29, 2016, to April 1, 2019, a total of 3000 children underwent randomization: 1497 children were assigned to the 3-day group, and 1503 to the 5-day group. Among children with day 6 data available, treatment failure had occurred in 5.9% in the 3-day group (85 of 1442 children) and in 5.2% (75 of 1456) in the 5-day group (adjusted difference, 0.7 percentage points; 95% confidence interval [CI], -0.9 to 2.4) - a result that satisfied the criterion for noninferiority of the 3-day regimen to the 5-day regimen. Among children with day 14 data available, 176 of 1411 children (12.5%) in the 3-day group and 154 of 1429 (10.8%) in the 5-day group had had treatment failure by day 6 or relapse by day 14 (between-group difference, 1.7 percentage points; 95% CI, -0.7 to 4.1). The percentage of children with serious adverse events was similar in the two groups (9.8% in the 3-day group and 8.8% in the 5-day group). CONCLUSIONS: In HIV-uninfected Malawian children, treatment with amoxicillin for chest-indrawing pneumonia for 3 days was noninferior to treatment for 5 days. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT02678195.).

Neonatal inpatient dataset for small and sick newborn care in low- and middle-income countries: systematic development and multi-country operationalisation with NEST360.

BACKGROUND: Every Newborn Action Plan (ENAP) coverage target 4 necessitates national scale-up of Level-2 Small and Sick Newborn Care (SSNC) (with Continuous Positive Airway Pressure (CPAP)) in 80% of districts by 2025. Routine neonatal inpatient data is important for improving quality of care, targeting equity gaps, and enabling data-driven decision-making at individual, district, and national-levels. Existing neonatal inpatient datasets vary in purpose, size, definitions, and collection processes. We describe the co-design and operationalisation of a core inpatient dataset for use to track outcomes and improve quality of care for small and sick newborns in high-mortality settings. METHODS: A three-step systematic framework was used to review, co-design, and operationalise this novel neonatal inpatient dataset in four countries (Malawi, Kenya, Tanzania, and Nigeria) implementing with the Newborn Essential Solutions and Technologies (NEST360) Alliance. Existing global and national datasets were identified, and variables were mapped according to categories. A priori considerations for variable inclusion were determined by clinicians and policymakers from the four African governments by facilitated group discussions. These included prioritising clinical care and newborn outcomes data, a parsimonious variable list, and electronic data entry. The tool was designed and refined by > 40 implementers and policymakers during a multi-stakeholder workshop and online interactions. RESULTS: Identified national and international datasets (n = 6) contained a median of 89 (IQR:61-154) variables, with many relating to research-specific initiatives. Maternal antenatal/intrapartum history was the largest variable category (21, 23.3%). The Neonatal Inpatient Dataset (NID) includes 60 core variables organised in six categories: (1) birth details/maternal history; (2) admission details/identifiers; (3) clinical complications/observations; (4) interventions/investigations; (5) discharge outcomes; and (6) diagnosis/cause-of-death. Categories were informed through the mapping process. The NID has been implemented at 69 neonatal units in four African countries and links to a facility-level quality improvement (QI) dashboard used in real-time by facility staff. CONCLUSION: The NEST360 NID is a novel, parsimonious tool for use in routine information systems to inform inpatient SSNC quality. Available on the NEST360/United Nations Children's Fund (UNICEF) Implementation Toolkit for SSNC, this adaptable tool enables facility and country-level comparisons to accelerate progress toward ENAP targets. Additional linked modules could include neonatal at-risk follow-up, retinopathy of prematurity, and Level-3 intensive care.

Clinical diagnosis in paediatric patients at urban primary health care facilities in southern Malawi: a longitudinal observational study.

BACKGROUND: Despite health centres being the first point of contact of care, there are challenges faced in providing care to patients at this level. In Malawi, service provision barriers reported at this level included long waiting times, high numbers of patients and erratic consultation systems which lead to mis-diagnosis and delayed referrals. Proper case management at this level of care is critical to prevent severe disease and deaths in children. We aimed to adopt Emergency, Triage, Assessment and Treatment algorithm (ETAT) to improve ability to identify severe illness in children at primary health centre (PHC) through comparison with secondary level diagnoses. METHODS: We implemented ETAT mobile Health (mHealth) at eight urban PHCs in Blantyre, Malawi between April 2017 and September 2018. Health workers and support staff were trained in mHealth ETAT. Stabilisation rooms were established and equipped with emergency equipment. All PHCs used an electronic tracking system to triage and track sick children on referral to secondary care, facilitated by a unique barcode. Support staff at PHC triaged sick children using ETAT Emergency (E), Priority (P) and Queue (Q) symptoms and clinician gave clinical diagnosis. The secondary level diagnosis was considered as a gold standard. We used statistical computing software R (v3.5.1) and used exact 95% binomial confidence intervals when estimating diagnosis agreement proportions. RESULTS: Eight-five percentage of all cases where assigned to E (9.0%) and P (75.5%) groups. Pneumonia was the most common PHC level diagnosis across all three triage groups (E, P, Q). The PHC level diagnosis of trauma was the most commonly confirmed diagnosis at secondary level facility (85.0%), while a PHC diagnosis of pneumonia was least likely to be confirmed at secondary level (39.6%). The secondary level diagnosis least likely to have been identified at PHC level was bronchiolitis 3 (5.2%). The majority of bronchiolitis cases (n = 50; (86.2%) were classified as pneumonia at the PHC level facility. CONCLUSIONS: Implementing a sustainable and consistent ETAT approach with stabilisation and treatment capacity at PHC level reinforce staff capacity to diagnose and has the potential to reduce other health system costs through fewer, timely and appropriate referrals.

Simulation and Active Learning Decreases Training Time of an Emergency Triage Assessment and Treatment Course in Pilot Study in Malawi: Implications for Increasing Efficiency and Workforce Capacity in Low-Resource Settings.

OBJECTIVES: The aim of the Emergency Triage Assessment and Treatment (ETAT) plus trauma course is to improve the quality of care provided to infants and children younger than 5 years. The curriculum was revised and shortened from 5 to 2.5 days by enhancing simulation and active learning opportunities. The aim of this study was to examine the feasibility and value of the new short-form ETAT course by assessing postcourse knowledge and satisfaction. METHODS: We delivered the short-form ETAT course to a group of interdisciplinary health workers in Malawi. Precourse and postcourse knowledge was assessed using a standardized 20 questions short answer test used previously in the 5-day courses. A 13-statement survey with 2 open-ended questions was used to examine participant satisfaction. RESULTS: Participants' postcourse knowledge improved significantly (P < 0.001) after the shorter ETAT course. Participants reported high levels of satisfaction with the short-form ETAT. CONCLUSIONS: Simulation and other active learning strategies reduced training time by 50% in the short-form ETAT course. Participants with and without previous ETAT training improved their knowledge after participating in the short-form ETAT course. Reduced training time is beneficial in settings already burdened by scarce human resources, may facilitate better access to in-service training, and build capacity while conserving resources in low-resource settings.

Predictive value of pulse oximetry for mortality in infants and children presenting to primary care with clinical pneumonia in rural Malawi: A data linkage study.

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.

Accessibility of basic paediatric emergency care in Malawi: analysis of a national facility census.

BACKGROUND: Emergency care is among the weakest parts of health systems in low-income countries with both quality and accessibility constraints. Previous studies estimated accessibility to surgical or emergency care based on population travel times to nearest hospital with no assessment of hospital readiness to provide such care. We analysed a Malawi national facility census with comprehensive inventory audits and geocoded facility locations to identify hospitals equipped to provide basic paediatric emergency care with estimated travel times to these hospitals from non-equipped facilities and in relation to Malawi's population distribution. METHODS: We analysed a Malawi national facility census in 2013-2014 to identify hospitals equipped to manage critically ill children according to an extended version of WHO Emergency Triage, Assessment and Treatment (ETAT) guidelines. These guidelines include 25 components including staff, transport, equipment, diagnostics, medications, fluids, feeds and consumables that defined an emergency-equipped hospital in our study. We estimated travel times to emergency-equipped hospitals from non-equipped facilities and relative to population distributions using geocoded facility locations and an established accessibility mapping approach using global road network datasets from OpenStreetMap and Google. RESULTS: Four (3.5, 95% CI: 1.3-8.9) of 116 Malawi hospitals were emergency-equipped. Least available items were nasogastric tubes in 34.5% of hospitals (95% CI: 26.4-43.6), blood typing services (40.4, 95% CI: 31.9-49.6), micro nebulizers (50.9, 95% CI: 41.9-60.0), and radiology (54.2, 95% CI: 45.1-63.0). Nationally, the median travel time from non-equipped facilities to the nearest emergency-equipped hospital was 73 min (95% CI: 67-77) ranging 1-507 min. Approximately one-quarter (27%) of Malawians lived over 120 min from an emergency-equipped hospital with significantly better accessibility in Central than North and South regions (16% vs. 38 and 35%, p < 0.001). CONCLUSIONS: There are unacceptable deficiencies in accessibility of basic paediatric emergency care in Malawi. Reliable supply chains for essential drugs and commodities are needed, particularly nasogastric tubes, asthma drugs and blood, along with improved capacity for time-sensitive referral. Further child mortality reductions will require substantial investments to expand basic paediatric emergency care into all Malawi hospitals for better managing critically ill children at highest mortality risk.

Using a peer mentorship approach improved the use of neonatal continuous positive airway pressure and related outcomes in Malawi.

AIM: This study evaluated whether peer mentorship was an effective and sustainable way of improving and maintaining knowledge and skills on neonatal continuous positive airway pressure (CPAP) in a low-resource setting with a high turnover of healthcare providers. METHODS: The Malawi Ministry of Health recruited five nurses with considerable CPAP experience and provided them with mentorship training from July to August 2014. The mentors then provided 1-week on-site mentorship for 113 colleagues at 10 secondary and one tertiary hospital where gaps in neonatal CPAP use had been identified. CPAP competencies and outcomes were compared 3 months before and after each mentorship. RESULTS: In the 3 months before and after mentorship, the average CPAP competency score increased from 32 ± 4% to 97 ± 2%, while CPAP usage increased from 7% to 23% among eligible neonates. Survival following CPAP mentorship increased from 23% to 35%, but this was not significant due to the small sample size. Both mentees and mentors reported useful transfers of knowledge and skills when using CPAP. CONCLUSION: Mentorship effectively bridged the knowledge and skills gaps among health workers and increased CPAP use, competency scores and survival rates.

Bubble CPAP and oxygen for child pneumonia care in Malawi: a CPAP IMPACT time motion study.

BACKGROUND: In some low-resource settings bubble continuous positive airway pressure (bCPAP) is increasingly used to treat children with pneumonia. However, the time required for healthcare workers (HCWs) to administer bCPAP is unknown and may have implementation implications. This study aims to compare HCW time spent administering bCPAP and low-flow nasal oxygen care at a district hospital in Malawi during CPAP IMPACT (Improving Mortality for Pneumonia in African Children Trial). METHODS: Eligible participants were 1-59 months old with WHO-defined severe pneumonia and HIV-infection, HIV-exposure, severe malnutrition, or hypoxemia and were randomized to either bCPAP or oxygen. We used time motion techniques to observe hospital care in four hour blocks during treatment initiation or follow up (maintenance). HCW mean time per patient at the bedside over the observation period was calculated by study arm. RESULTS: Overall, bCPAP required an average of 34.71 min per patient more than low-flow nasal oxygen to initiate (bCPAP, 118.18 min (standard deviation (SD) 42.73 min); oxygen, 83.47 min (SD, 20.18 min), p < 0.01). During initiation, HCWs spent, on average, 12.45 min longer per patient setting up bCPAP equipment (p < 0.01) and 11.13 min longer per patient setting up the bCPAP nasal interface (p < 0.01), compared to oxygen equipment and nasal cannula set-up. During maintenance care, HCWs spent longer on average per patient adjusting bCPAP, compared to oxygen equipment (bCPAP 4.57 min (SD, 4.78 min); oxygen, 1.52 min (SD, 2.50 min), p = 0.03). CONCLUSION: Effective bCPAP implementation in low-resource settings will likely create additional HCW burden relative to usual pneumonia care with oxygen. TRIAL REGISTRATION: Clinicaltrials.gov NCT02484183 , June 29, 2015.

Methods for conducting a double-blind randomized controlled clinical trial of three days versus five days of amoxicillin dispersible tablets for chest indrawing childhood pneumonia among children two to 59 months of age in Lilongwe, Malawi: a study protocol.

BACKGROUND: Pneumonia is the leading infectious cause of death in children under 5 years of age around the globe. In addition to preventing pneumonia, there is a critical need to provide greater access to appropriate and effective treatment. Studies in Asia have evaluated the effectiveness of 3 days of oral amoxicillin for the treatment of fast-breathing pneumonia; however, further evidence is needed to determine if 3 days of oral amoxicillin is also effective for the treatment of chest indrawing pneumonia. METHODS: This is a double-blind, randomized, non-inferiority trial with the objective to assess the effectiveness of shorter duration amoxicillin dispersible tablet (DT) treatment of chest indrawing childhood pneumonia in a malaria-endemic region of Malawi. The primary objective of this study is to determine whether 3 days of treatment with oral amoxicillin DT in HIV-uninfected Malawian children two to 59 months of age with chest indrawing pneumonia is as effective as 5 days of treatment. The study will enroll 2000 children presenting to Kamuzu Central or Bwaila District Hospitals in Lilongwe, Malawi. Each child will be randomized to either 3 days of amoxicillin DT followed by 2 days of placebo DT or 5 days of amoxicillin DT. Children in the study will be hospitalized for 48 h after enrollment and will have scheduled study visits at Days 2, 4, 6 and 14. Treatment failure by Day 6 is the primary outcome. We hypothesize that the rates of treatment failure will be similar in both arms and that 3 days of treatment will be non-inferior to 5 days of amoxicillin DT for chest indrawing pneumonia using a relative non-inferiority margin of 1.5. This trial was approved by the Western Institutional Review Board and Malawi College of Medicine Research and Ethics Committee. DISCUSSION: Given the paucity of data from Africa, African-based research is necessary to establish appropriate duration of treatment with amoxicillin DT for chest indrawing childhood pneumonia in malaria-endemic settings in the region. An expanded evidence base will contribute to future iterations of World Health Organization Integrated Management of Childhood Illness guidelines. TRIAL REGISTRATION: NCT02678195 : Pre-results. Date registered February 9, 2016.

Pulse oximetry for children with pneumonia treated as outpatients in rural Malawi.

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.

Measurement and valuation of health providers' time for the management of childhood pneumonia in rural Malawi: an empirical study.

BACKGROUND: Human resources are a major cost driver in childhood pneumonia case management. Introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in Malawi can lead to savings on staff time and salaries due to reductions in pneumonia cases requiring admission. Reliable estimates of human resource costs are vital for use in economic evaluations of PCV-13 introduction. METHODS: Twenty-eight severe and twenty-four very severe pneumonia inpatients under the age of five were tracked from admission to discharge by paediatric ward staff using self-administered timesheets at Mchinji District Hospital between June and August 2012. All activities performed and the time spent on each activity were recorded. A monetary value was assigned to the time by allocating a corresponding percentage of the health workers' salary. All costs are reported in 2012 US$. RESULTS: A total of 1,017 entries, grouped according to 22 different activity labels, were recorded during the observation period. On average, 99 min (standard deviation, SD = 46) were spent on each admission: 93 (SD = 38) for severe and 106 (SD = 55) for very severe cases. Approximately 40 % of activities involved monitoring and stabilization, including administering non-drug therapies such as oxygen. A further 35 % of the time was spent on injecting antibiotics. Nurses provided 60 % of the total time spent on pneumonia admissions, clinicians 25 % and support staff 15 %. Human resource costs were approximately US$ 2 per bed-day and, on average, US$ 29.5 per severe pneumonia admission and US$ 37.7 per very severe admission. CONCLUSIONS: Self-reporting was successfully used in this context to generate reliable estimates of human resource time and costs of childhood pneumonia treatment. Assuming vaccine efficacy of 41 % and 90 % coverage, PCV-13 introduction in Malawi can save over US$ 2 million per year in staff costs alone.

Child acute illness presentation and referrals at primary health clinics in Malawi: a secondary analysis of ASPIRE.

OBJECTIVES: We aimed to assess the prevalence, presentation and referral patterns of children with acute illness attending primary health centres (PHCs) in a low-resource setting. DESIGN, SETTING AND PARTICIPANTS: We conducted a secondary analysis of ASPIRE. Children presenting at eight PHCs in urban Blantyre district in southern Malawi with both recorded clinician and mHealth (non-clinician) triage data were included, and patient records from different data collection points along the patient healthcare seeking pathway were consolidated and analysed. RESULTS: Between April 2017 and September 2018, a total of 204 924 children were triaged, of whom 155 931 had both recorded clinician and mHealth triage data. The most common presenting symptoms at PHCs were fever (0.3%), cough (0.2%) and difficulty breathing (0.2%). The most common signs associated with referral for under-5 children were trauma (26.7%) and temperature (7.4%). The proportion of emergency and priority clinician triage were highest among young infants <2 months (0.2% and 81.4%, respectively). Of the 3004 referrals (1.9%), 1644 successfully reached the referral facility (54.7%). Additionally, 372 children were sent home from PHC who subsequently self-referred to the referral facility (18.7%). CONCLUSIONS: Fever and respiratory symptoms were the most common presenting symptoms, and trauma was the most common reason for referral. Rates of referral were low, and of successful referral were moderate. Self-referrals constituted a substantial proportion of attendance at the referral facility. Reducing gaps in care and addressing dropouts as well as self-referrals along the referral pathway could improve child health outcomes.

Improving care pathways for children with severe illness through implementation of the ASPIRE mHealth primary ETAT package in Malawi.

Providing emergency care in low resource settings relies on delivery by lower cadres of health workers (LCHW). We describe the development, implementation and mixed methods evaluation of a mobile health (mHealth) triage algorithm based on the WHO Emergency, Triage, Assessment, and Treatment (ETAT) for primary-level care. We conducted an observational study design of implementation research. Key stakeholders were engaged throughout implementation. Clinicians and LCHW at eight primary health centres in Blantyre district were trained to use an mHealth algorithm for triage. An mHealth patient surveillance system monitored patients from presentation through referral to tertiary and final outcome. A total of 209,174 children were recorded by ETAT between April 2017 and September 2018, and 155,931 had both recorded mHealth and clinician triage outcome data. Concordance between mHealth triage by lower cadres of HCW and clinician assessment was 81·6% (95% CI [81·4, 81·8]) over all outcomes (kappa: 0·535 (95% CI [0·530, 0·539]). Concordance for mHealth emergency triage was 0.31 with kappa 0.42. The most common mHealth recorded emergency sign was breathing difficulty (74·1% 95% CI [70·1, 77·9]) and priority sign was raised temperature (76·2% (95% CI [75·9, 76·6]). A total of 1,644 referrals out of 3,004 (54·7%) successfully reached the tertiary site. Both providers and carers expressed high levels of satisfaction with the mHealth ETAT pathway. An mHealth triage algorithm can be used by LCHWs with moderate concordance with clinician triage. Implementation of ETAT through an mHealth algorithm documented successful referrals from primary to tertiary, but half of referred patients did not reach the tertiary site. Potential harms of such systems, such as cases requiring referral being missed during triage, require further evaluation. The ASPIRE mHealth primary ETAT approach can be used to prioritise acute illness and support future resource planning within both district and national health system.

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes.

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here provide the mechanistic evidence in support of the relevance for these observations. Angiopoetin-1 (Ang-1), which promotes vascular integrity, was decreased in blood plasma of human and murine septic newborns. In preclinical models, administration of Ang-1 provided prophylactic protection from septic death. Arachidonic acid metabolism appears to be functionally connected to Ang-1 via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Strengthening this intersection via oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death while also increasing plasma Ang-1 levels among septic newborns. Our data highlight that targeting angiogenesis-associated pathways with interventions that increase Ang-1 activity directly or indirectly through ROS/eNOS provide promising avenues to prevent and/or treat severe neonatal sepsis.

Task shifting an inpatient triage, assessment and treatment programme improves the quality of care for hospitalised Malawian children.

OBJECTIVE: We aimed to improve paediatric inpatient surveillance at a busy referral hospital in Malawi with two new programmes: (i) the provision of vital sign equipment and implementation of an inpatient triage programme (ITAT) that includes a simplified paediatric severity-of-illness score, and (ii) task shifting ITAT to a new cadre of healthcare workers called 'vital sign assistants' (VSAs). METHODS: This study, conducted on the paediatric inpatient ward of a large referral hospital in Malawi, was divided into three phases, each lasting 4 weeks. In Phase A, we collected baseline data. In Phase B, we provided three new automated vital sign poles and implemented ITAT with current hospital staff. In Phase C, VSAs were introduced and performed ITAT. Our primary outcome measures were the number of vital sign assessments performed and clinician notifications to reassess patients with high ITAT scores. RESULTS: We enrolled 3994 patients who received 5155 vital sign assessments. Assessment frequency was equal between Phases A (0.67 assessments/patient) and B (0.61 assessments/patient), but increased 3.6-fold in Phase C (2.44 assessments/patient, P < 0.001). Clinician notifications increased from Phases A (84) and B (113) to Phase C (161, P = 0.002). Inpatient mortality fell from Phase A (9.3%) to Phases B (5.7) and C (6.9%). CONCLUSION: ITAT with VSAs improved vital sign assessments and nearly doubled clinician notifications of patients needing further assessment due to high ITAT scores, while equipment alone made no difference. Task shifting ITAT to VSAs may improve outcomes in paediatric hospitals in the developing world.

Development of a severity of illness scoring system (inpatient triage, assessment and treatment) for resource-constrained hospitals in developing countries.

OBJECTIVE: To develop a new paediatric illness severity score, called inpatient triage, assessment and treatment (ITAT), for resource-limited settings to identify hospitalised patients at highest risk of death and facilitate urgent clinical re-evaluation. METHODS: We performed a nested case-control study at a Malawian referral hospital. The ITAT score was derived from four equally weighted variables, yielding a cumulative score between 0 and 8. Variables included oxygen saturation, temperature, and age-adjusted heart and respiratory rates. We compared the ITAT score between cases (deaths) and controls (discharges) in predicting death within 2 days. Our analysis includes predictive statistics, bivariable and multivariable logistic regression, and calculation of data-driven scores. RESULTS: A total of 54 cases and 161 controls were included in the analysis. The area under the receiver operating characteristic curve was 0.76. At an ITAT cut-off of 4, the sensitivity, specificity and likelihood ratio were 0.44, 0.86 and 1.70, respectively. A cumulative ITAT score of 4 or higher was associated with increased odds of death (OR 4.80; 95% CI 2.39-9.64). A score of 2 for all individual vital signs was a statistically significant independent predictor of death. CONCLUSIONS: We developed an inpatient triage tool (ITAT) appropriate for resource-constrained hospitals that identifies high-risk children after hospital admission. Further research is needed to study how best to operationalise ITAT in developing countries.

Implication of the 2014 World Health Organization Integrated Management of Childhood Illness Pneumonia Guidelines with and without pulse oximetry use in Malawi: A retrospective cohort study.

Background: Under-5 pneumonia mortality remains high in low-income countries. In 2014 the World Health Organization (WHO) advised that children with chest indrawing pneumonia, but without danger signs or peripheral oxygen saturation (SpO 2) < 90% be treated in the community, rather than hospitalized. In Malawi there is limited pulse oximetry availability. Methods: Secondary analysis of 13,413 under-5 pneumonia cases in Malawi. Pneumonia associated case fatality ratios (CFR) were calculated by disease severity under the assumptions of the 2005 and 2014 WHO Integrated Management of Childhood Illness (IMCI) guidelines, with and without pulse oximetry. We investigated if pulse oximetry readings were missing not at random (MNAR). Results: The CFR of patients classified as having non-severe pneumonia per the 2014 IMCI guidelines doubled under the assumption that pulse oximetry was not available (1.5% without pulse oximetry vs 0.7% with pulse oximetry, P<0.001). When 2014 IMCI guidelines were applied with pulse oximetry and a SpO 2 < 90% as the threshold for referral and/or admission, the number of cases meeting hospitalization criteria decreased by 70.3%. Unrecorded pulse oximetry readings were MNAR with an adjusted odds for mortality of 4.9 (3.8, 6.3), similar to that of a SpO 2 < 90%. Although fewer girls were hospitalized, female sex was an independent mortality risk factor. Conclusions: In Malawi, implementation of the 2014 WHO IMCI pneumonia guidelines, without pulse oximetry, will miss high risk cases. Alternatively, implementation of pulse oximetry may result in a large reduction in hospitalization rates without significantly increasing non-severe pneumonia associated CFR if the inability to obtain a pulse oximetry reading is considered a WHO danger sign.