"Getting pregnant during COVID-19 was a big risk because getting help from the clinic was not easy": COVID-19 experiences of women and healthcare providers in Harare, Zimbabwe.

The COVID-19 pandemic and associated measures may have disrupted delivery of maternal and neonatal health services and reversed the progress made towards dual elimination of mother-to-child transmission of HIV and syphilis in Zimbabwe. This qualitative study explores the impact of the pandemic on the provision and uptake of prevention of mother-to-child transmission (PMTCT) services from the perspectives of women and maternal healthcare providers. Longitudinal in-depth interviews were conducted with 20 pregnant and breastfeeding women aged 20-39 years living with HIV and 20 healthcare workers in two maternity polyclinics in low-income suburbs of Harare, Zimbabwe. Semi-structured interviews were held after the second and third waves of COVID-19 in March and November 2021, respectively. Data were analysed using a modified grounded theory approach. While eight antenatal care contacts are recommended by Zimbabwe's Ministry of Health and Child Care, women reported only being able to access two contacts. Although HIV testing, antiretroviral therapy (ART) refills and syphilis screening services were accessible at first contact, other services such as HIV-viral load monitoring and enhanced adherence counselling were not available for those on ART. Closure of clinics and shortened operating hours during the second COVID-19 wave resulted in more antenatal bookings occurring later during pregnancy and more home deliveries. Six of the 20 (33%) interviewed women reported giving birth at home, assisted by untrained traditional midwives as clinics were closed. Babies delivered at home missed ART prophylaxis and HIV testing at birth despite being HIV-exposed. Although women faced multiple challenges, they continued to attempt to access services after delivery. These findings underline the importance of investing in robust health systems that can respond to emergency situations to ensure continuity of essential HIV prevention, treatment, and care services.

Effects of the COVID-19 pandemic on the outcomes of HIV-exposed neonates: a Zimbabwean tertiary hospital experience.

INTRODUCTION: The COVID-19 pandemic has globally impacted health service access, delivery and resources. There are limited data regarding the impact on the prevention of mother to child transmission (PMTCT) service delivery in low-resource settings. Neotree ( www.neotree.org ) combines data collection, clinical decision support and education to improve care for neonates. Here we evaluate impacts of COVID-19 on care for HIV-exposed neonates. METHODS: Data on HIV-exposed neonates admitted to the neonatal unit (NNU) at Sally Mugabe Central Hospital, Zimbabwe, between 01/06/2019 and 31/12/2021 were analysed, with pandemic start defined as 21/03/2020 and periods of industrial action (doctors (September 2019-January 2020) and nurses (June 2020-September 2020)) included, resulting in modelling during six time periods: pre-doctors' strike (baseline); doctors' strike; post-doctors' strike and pre-COVID; COVID and pre-nurses' strike; nurses' strike; post nurses' strike. Interrupted time series models were used to explore changes in indicators over time. RESULTS: Of 8,333 neonates admitted to the NNU, 904 (11%) were HIV-exposed. Mothers of 706/765 (92%) HIV-exposed neonates reported receipt of antiretroviral therapy (ART) during pregnancy. Compared to the baseline period when average admissions were 78 per week (95% confidence interval (CI) 70-87), significantly fewer neonates were admitted during all subsequent periods until after the nurses' strike, with the lowest average number during the nurses' strike (28, 95% CI 23-34, p < 0.001). Across all time periods excluding the nurses strike, average mortality was 20% (95% CI 18-21), but rose to 34% (95% CI 25, 46) during the nurses' strike. There was no evidence for heterogeneity (p > 0.22) in numbers of admissions or mortality by HIV exposure status. Fewer HIV-exposed neonates received a PCR test during the pandemic (23%) compared to the pre-pandemic periods (40%) (RR 0.59, 95% CI 0.41-0.84, p < 0.001). The proportion of HIV-exposed neonates who received antiretroviral prophylaxis during admission was high throughout, averaging between 84% and 95% in each time-period. CONCLUSION: While antiretroviral prophylaxis for HIV-exposed neonates remained high throughout, concerning data on low admissions and increased mortality, similar in HIV-exposed and unexposed neonates, and reduced HIV testing, suggest some aspects of care may have been compromised due to indirect effects of the pandemic.

Development and Implementation of Digital Diagnostic Algorithms for Neonatal Units in Zimbabwe and Malawi: Development and Usability Study.

BACKGROUND: Despite an increase in hospital-based deliveries, neonatal mortality remains high in low-resource settings. Due to limited laboratory diagnostics, there is significant reliance on clinical findings to inform diagnoses. Accurate, evidence-based identification and management of neonatal conditions could improve outcomes by standardizing care. This could be achieved through digital clinical decision support (CDS) tools. Neotree is a digital, quality improvement platform that incorporates CDS, aiming to improve neonatal care in low-resource health care facilities. Before this study, first-phase CDS development included developing and implementing neonatal resuscitation algorithms, creating initial versions of CDS to address a range of neonatal conditions, and a Delphi study to review key algorithms. OBJECTIVE: This second-phase study aims to codevelop and implement neonatal digital CDS algorithms in Malawi and Zimbabwe. METHODS: Overall, 11 diagnosis-specific web-based workshops with Zimbabwean, Malawian, and UK neonatal experts were conducted (August 2021 to April 2022) encompassing the following: (1) review of available evidence, (2) review of country-specific guidelines (Essential Medicines List and Standard Treatment Guidelinesfor Zimbabwe and Care of the Infant and Newborn, Malawi), and (3) identification of uncertainties within the literature for future studies. After agreement of clinical content, the algorithms were programmed into a test script, tested with the respective hospital's health care professionals (HCPs), and refined according to their feedback. Once finalized, the algorithms were programmed into the Neotree software and implemented at the tertiary-level implementation sites: Sally Mugabe Central Hospital in Zimbabwe and Kamuzu Central Hospital in Malawi, in December 2021 and May 2022, respectively. In Zimbabwe, usability was evaluated through 2 usability workshops and usability questionnaires: Post-Study System Usability Questionnaire (PSSUQ) and System Usability Scale (SUS). RESULTS: Overall, 11 evidence-based diagnostic and management algorithms were tailored to local resource availability. These refined algorithms were then integrated into Neotree. Where national management guidelines differed, country-specific guidelines were created. In total, 9 HCPs attended the usability workshops and completed the SUS, among whom 8 (89%) completed the PSSUQ. Both usability scores (SUS mean score 75.8 out of 100 [higher score is better]; PSSUQ overall score 2.28 out of 7 [lower score is better]) demonstrated high usability of the CDS function but highlighted issues around technical complexity, which continue to be addressed iteratively. CONCLUSIONS: This study describes the successful development and implementation of the only known neonatal CDS system, incorporated within a bedside data capture system with the ability to deliver up-to-date management guidelines, tailored to local resource availability. This study highlighted the importance of collaborative participatory design. Further implementation evaluation is planned to guide and inform the development of health system and program strategies to support newborn HCPs, with the ultimate goal of reducing preventable neonatal morbidity and mortality in low-resource settings.

Development and Pilot Implementation of Neotree, a Digital Quality Improvement Tool Designed to Improve Newborn Care and Survival in 3 Hospitals in Malawi and Zimbabwe: Cost Analysis Study.

Background: Two-thirds of the 2.4 million newborn deaths that occurred in 2020 within the first 28 days of life might have been avoided by implementing existing low-cost evidence-based interventions for all sick and small newborns. An open-source digital quality improvement tool (Neotree) combining data capture with education and clinical decision support is a promising solution for this implementation gap. Objective: We present results from a cost analysis of a pilot implementation of Neotree in 3 hospitals in Malawi and Zimbabwe. Methods: We combined activity-based costing and expenditure approaches to estimate the development and implementation cost of a Neotree pilot in 1 hospital in Malawi, Kamuzu Central Hospital (KCH), and 2 hospitals in Zimbabwe, Sally Mugabe Central Hospital (SMCH) and Chinhoyi Provincial Hospital (CPH). We estimated the costs from a provider perspective over 12 months. Data were collected through expenditure reports, monthly staff time-use surveys, and project staff interviews. Sensitivity and scenario analyses were conducted to assess the impact of uncertainties on the results or estimate potential costs at scale. A pilot time-motion survey was conducted at KCH and a comparable hospital where Neotree was not implemented. Results: Total cost of pilot implementation of Neotree at KCH, SMCH, and CPH was US $37,748, US $52,331, and US $41,764, respectively. Average monthly cost per admitted child was US $15, US $15, and US $58, respectively. Staff costs were the main cost component (average 73% of total costs, ranging from 63% to 79%). The results from the sensitivity analysis showed that uncertainty around the number of admissions had a significant impact on the costs in all hospitals. In Malawi, replacing monthly web hosting with a server also had a significant impact on the costs. Under routine (nonresearch) conditions and at scale, total costs are estimated to fall substantially, up to 76%, reducing cost per admitted child to as low as US $5 in KCH, US $4 in SMCH, and US $14 in CPH. Median time to admit a baby was 27 (IQR 20-40) minutes using Neotree (n=250) compared to 26 (IQR 21-30) minutes using paper-based systems (n=34), and the median time to discharge a baby was 9 (IQR 7-13) minutes for Neotree (n=246) compared to 3 (IQR 2-4) minutes for paper-based systems (n=50). Conclusions: Neotree is a time- and cost-efficient tool, comparable with the results from limited similar mHealth decision-support tools in low- and middle-income countries. Implementation costs of Neotree varied substantially between the hospitals, mainly due to hospital size. The implementation costs could be substantially reduced at scale due to economies of scale because of integration to the health systems and reductions in cost items such as staff and overhead. More studies assessing the impact and cost-effectiveness of large-scale mHealth decision-support tools are needed.

Impact of the COVID-19 pandemic on the provision and uptake of services for the prevention of mother-to-child transmission of HIV in Zimbabwe.

Zimbabwe is targeting elimination of mother-to-child transmission of HIV by December 2025, however the COVID-19 pandemic challenged health service delivery globally. Monthly aggregated data were extracted from DHIS-2 for all facilities delivering antenatal care (ANC). ZIMSTAT and Spectrum demographic estimates were used for population-level denominators. Programme indicators are among those in HIV care and population indicators reflect the total population. The mean estimated proportion of pregnant women booking for ANC per month did not change (91% pre-pandemic vs 91% during pandemic, p = 0.95), despite dropping to 47% in April 2020. At a programme-level, the estimated proportion of women who received at least one HIV test fell in April 2020 (3.6% relative reduction vs March (95% CI 2.2-5.1), p<0.001) with gradual recovery towards pre-pandemic levels. The estimated proportion of women who were retested among those initially negative in pregnancy fell markedly in April 2020 (39% reduction (32-45%), p<0.001) and the subsequent increase was much slower, only reaching 39% by September 2021 compared to average 53% pre-pandemic. The mean estimated proportion of pregnant women with HIV on ART was unchanged at programme-level (98% vs 98%, p = 0.26), but decreased at population-level (86% vs 80%, p = 0.049). Antiretroviral prophylaxis coverage decreased among HIV-exposed infants, at programme- (94% vs 87%, p = 0.001) and population-levels (76% vs 68%, p<0.001). There was no significant change in HIV-exposed infants receiving EID (programme: 107% vs 103%, p = 0.52; population: 87% vs 79%, p = 0.081). The estimated proportion of infants with HIV diagnosed fell from 27% to 18%, (p<0.001), while the estimated proportion on ART was stable at a programme (88% vs 90%, p = 0.82) but not population (22% vs 16%, p = 0.004) level. Despite a drop at the start of the pandemic most programme indicators rapidly recovered. At a population-level indicators were slower to return, suggesting less women with HIV identified in care.

Diagnosing early-onset neonatal sepsis in low-resource settings: development of a multivariable prediction model.

OBJECTIVE: To develop a clinical prediction model to diagnose neonatal sepsis in low-resource settings. DESIGN: Secondary analysis of data collected by the Neotree digital health system from 1 February 2019 to 31 March 2020. We used multivariable logistic regression with candidate predictors identified from expert opinion and literature review. Missing data were imputed using multivariate imputation and model performance was evaluated in the derivation cohort. SETTING: A tertiary neonatal unit at Sally Mugabe Central Hospital, Zimbabwe. PATIENTS: We included 2628 neonates aged <72 hours, gestation ≥32+0 weeks and birth weight ≥1500 g. INTERVENTIONS: Participants received standard care as no specific interventions were dictated by the study protocol. MAIN OUTCOME MEASURES: Clinical early-onset neonatal sepsis (within the first 72 hours of life), defined by the treating consultant neonatologist. RESULTS: Clinical early-onset sepsis was diagnosed in 297 neonates (11%). The optimal model included eight predictors: maternal fever, offensive liquor, prolonged rupture of membranes, neonatal temperature, respiratory rate, activity, chest retractions and grunting. Receiver operating characteristic analysis gave an area under the curve of 0.74 (95% CI 0.70-0.77). For a sensitivity of 95% (92%-97%), corresponding specificity was 11% (10%-13%), positive predictive value 12% (11%-13%), negative predictive value 95% (92%-97%), positive likelihood ratio 1.1 (95% CI 1.0-1.1) and negative likelihood ratio 0.4 (95% CI 0.3-0.6). CONCLUSIONS: Our clinical prediction model achieved high sensitivity with low specificity, suggesting it may be suited to excluding early-onset sepsis. Future work will validate and update this model before considering implementation within the Neotree.

Development and implementation experience of a learning healthcare system for facility based newborn care in low resource settings: The Neotree.

Introduction: Improving peri- and postnatal facility-based care in low-resource settings (LRS) could save over 6000 babies' lives per day. Most of the annual 2.4 million neonatal deaths and 2 million stillbirths occur in healthcare facilities in LRS and are preventable through the implementation of cost-effective, simple, evidence-based interventions. However, their implementation is challenging in healthcare systems where one in four babies admitted to neonatal units die. In high-resource settings healthcare systems strengthening is increasingly delivered via learning healthcare systems to optimise care quality, but this approach is rare in LRS. Methods: Since 2014 we have worked in Bangladesh, Malawi, Zimbabwe, and the UK to co-develop and pilot the Neotree system: an android application with accompanying data visualisation, linkage, and export. Its low-cost hardware and state-of-the-art software are used to support healthcare professionals to improve postnatal care at the bedside and to provide insights into population health trends. Here we summarise the formative conceptualisation, development, and preliminary implementation experience of the Neotree. Results: Data thus far from ~18 000 babies, 400 healthcare professionals in four hospitals (two in Zimbabwe, two in Malawi) show high acceptability, feasibility, usability, and improvements in healthcare professionals' ability to deliver newborn care. The data also highlight gaps in knowledge in newborn care and quality improvement. Implementation has been resilient and informative during external crises, for example, coronavirus disease 2019 (COVID-19) pandemic. We have demonstrated evidence of improvements in clinical care and use of data for Quality Improvement (QI) projects. Conclusion: Human-centred digital development of a QI system for newborn care has demonstrated the potential of a sustainable learning healthcare system to improve newborn care and outcomes in LRS. Pilot implementation evaluation is ongoing in three of the four aforementioned hospitals (two in Zimbabwe and one in Malawi) and a larger scale clinical cost effectiveness trial is planned.

Diagnostic accuracy of multiplex respiratory pathogen panels for influenza or respiratory syncytial virus infections: systematic review and meta-analysis.

Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG respiratory pathogen panels (RPPs)™ (index) against other RPPs (comparator) for detection of RSV and influenza viruses. Studies comparing human clinical respiratory samples tested with the index and at least one comparator test were included. A random-effect latent class meta-analysis was performed to assess the specificity and sensitivity of the index test for RSV and influenza. Risk of bias was assessed using the QUADAS-2 tool and certainty of evidence using GRADE. Ten studies were included. For RSV, predicted sensitivity was 99% (95% credible interval [CrI] 96-100%) and specificity 100% (95% CrI 98-100%). For influenza A and B, predicted sensitivity was 97% (95% CrI 89-100) and 98% (95% CrI 88-100) respectively; specificity 100% (95% CrI 99-100) and 100% (95% CrI 99-100), respectively. Evidence was low certainty. Although index sensitivity and specificity were excellent, comparators' performance varied. Further research with clear patient recruitment strategies could ascertain performance across different populations.Protocol Registration: Prospero CRD42021272062.

Protocol for an intervention development and pilot implementation evaluation study of an e-health solution to improve newborn care quality and survival in two low-resource settings, Malawi and Zimbabwe: Neotree.

INTRODUCTION: Every year 2.4 million deaths occur worldwide in babies younger than 28 days. Approximately 70% of these deaths occur in low-resource settings because of failure to implement evidence-based interventions. Digital health technologies may offer an implementation solution. Since 2014, we have worked in Bangladesh, Malawi, Zimbabwe and the UK to develop and pilot Neotree: an android app with accompanying data visualisation, linkage and export. Its low-cost hardware and state-of-the-art software are used to improve bedside postnatal care and to provide insights into population health trends, to impact wider policy and practice. METHODS AND ANALYSIS: This is a mixed methods (1) intervention codevelopment and optimisation and (2) pilot implementation evaluation (including economic evaluation) study. Neotree will be implemented in two hospitals in Zimbabwe, and one in Malawi. Over the 2-year study period clinical and demographic newborn data will be collected via Neotree, in addition to behavioural science informed qualitative and quantitative implementation evaluation and measures of cost, newborn care quality and usability. Neotree clinical decision support algorithms will be optimised according to best available evidence and clinical validation studies. ETHICS AND DISSEMINATION: This is a Wellcome Trust funded project (215742_Z_19_Z). Research ethics approvals have been obtained: Malawi College of Medicine Research and Ethics Committee (P.01/20/2909; P.02/19/2613); UCL (17123/001, 6681/001, 5019/004); Medical Research Council Zimbabwe (MRCZ/A/2570), BRTI and JREC institutional review boards (AP155/2020; JREC/327/19), Sally Mugabe Hospital Ethics Committee (071119/64; 250418/48). Results will be disseminated via academic publications and public and policy engagement activities. In this study, the care for an estimated 15 000 babies across three sites will be impacted. TRIAL REGISTRATION NUMBER: NCT0512707; Pre-results.

Healthcare-Associated Infection Prevention Interventions for Neonates in Resource-Limited Settings.

Healthcare-associated infections (HAIs) and antimicrobial-resistant (AMR) infections are leading causes of neonatal morbidity and mortality, contributing to an extended hospital stay and increased healthcare costs. Although the burden and impact of HAI/AMR in resource-limited neonatal units are substantial, there are few HAI/AMR prevention studies in these settings. We reviewed the mechanism of action and evidence supporting HAI/AMR prevention interventions, including care bundles, for hospitalized neonates in low- and middle-income countries (LMIC).

Indirect impacts of the COVID-19 pandemic at two tertiary neonatal units in Zimbabwe and Malawi: an interrupted time series analysis.

OBJECTIVES: To examine indirect impacts of the COVID-19 pandemic on neonatal care in low-income and middle-income countries. DESIGN: Interrupted time series analysis. SETTING: Two tertiary neonatal units in Harare, Zimbabwe and Lilongwe, Malawi. PARTICIPANTS: We included a total of 6800 neonates who were admitted to either neonatal unit from 1 June 2019 to 25 September 2020 (Zimbabwe: 3450; Malawi: 3350). We applied no specific exclusion criteria. INTERVENTIONS: The first cases of COVID-19 in each country (Zimbabwe: 20 March 2020; Malawi: 3 April 2020). PRIMARY OUTCOME MEASURES: Changes in the number of admissions, gestational age and birth weight, source of admission referrals, prevalence of neonatal encephalopathy, and overall mortality before and after the first cases of COVID-19. RESULTS: Admission numbers in Zimbabwe did not initially change after the first case of COVID-19 but fell by 48% during a nurses' strike (relative risk (RR) 0.52, 95% CI 0.41 to 0.66, p<0.001). In Malawi, admissions dropped by 42% soon after the first case of COVID-19 (RR 0.58, 95% CI 0.48 to 0.70, p<0.001). In Malawi, gestational age and birth weight decreased slightly by around 1 week (beta -1.4, 95% CI -1.62 to -0.65, p<0.001) and 300 g (beta -299.9, 95% CI -412.3 to -187.5, p<0.001) and outside referrals dropped by 28% (RR 0.72, 95% CI 0.61 to 0.85, p<0.001). No changes in these outcomes were found in Zimbabwe and no significant changes in the prevalence of neonatal encephalopathy or mortality were found at either site (p>0.05). CONCLUSIONS: The indirect impacts of COVID-19 are context-specific. While our study provides vital evidence to inform health providers and policy-makers, national data are required to ascertain the true impacts of the pandemic on newborn health.

The Impact of Interventions to Prevent Neonatal Healthcare-associated Infections in Low- and Middle-income Countries: A Systematic Review.

BACKGROUND: Clinically suspected and laboratory-confirmed bloodstream infections are frequent causes of morbidity and mortality during neonatal care. The most effective infection prevention and control interventions for neonates in low- and middle-income countries (LMIC) are unknown. AIM: To identify effective interventions in the prevention of hospital-acquired bloodstream infections in LMIC neonatal units. METHODS: Medline, PUBMED, the Cochrane Database of Systematic Reviews, EMBASE and PsychInfo (January 2003 to October 2020) were searched to identify studies reporting single or bundled interventions for prevention of bloodstream infections in LMIC neonatal units. RESULTS: Our initial search identified 5206 articles; following application of filters, 27 publications met the inclusion and Integrated Quality Criteria for the Review of Multiple Study Designs assessment criteria and were summarized in the final analysis. No studies were carried out in low-income countries, only 1 in Sub-Saharan Africa and just 2 in multiple countries. Of the 18 single-intervention studies, most targeted skin (n = 4) and gastrointestinal mucosal integrity (n = 5). Whereas emollient therapy and lactoferrin achieved significant reductions in proven neonatal infection, glutamine and mixed probiotics showed no benefit. Chlorhexidine gluconate for cord care and kangaroo mother care reduced infection in individual single-center studies. Of the 9 studies evaluating bundles, most focused on prevention of device-associated infections and achieved significant reductions in catheter- and ventilator-associated infections. CONCLUSIONS: There is a limited evidence base for the effectiveness of infection prevention and control interventions in LMIC neonatal units; bundled interventions targeting device-associated infections were most effective. More multisite studies with robust study designs are needed to inform infection prevention and control intervention strategies in low-resource neonatal units.

Software development process of Neotree - a data capture and decision support system to improve newborn healthcare in low-resource settings.

The global priority of improving neonatal survival could be tackled through the universal implementation of cost-effective maternal and newborn health interventions. Despite 90% of neonatal deaths occurring in low-resource settings, very few evidence-based digital health interventions exist to assist healthcare professionals in clinical decision-making in these settings. To bridge this gap, Neotree was co-developed through an iterative, user-centered design approach in collaboration with healthcare professionals in the UK, Bangladesh, Malawi, and Zimbabwe. It addresses a broad range of neonatal clinical diagnoses and healthcare indicators as opposed to being limited to specific conditions and follows national and international guidelines for newborn care. This digital health intervention includes a mobile application (app) which is designed to be used by healthcare professionals at the bedside. The app enables real-time data capture and provides education in newborn care and clinical decision support via integrated clinical management algorithms. Comprehensive routine patient data are prospectively collected regarding each newborn, as well as maternal data and blood test results, which are used to inform clinical decision making at the bedside. Data dashboards provide healthcare professionals and hospital management a near real-time overview of patient statistics that can be used for healthcare quality improvement purposes. To enable this workflow, the Neotree web editor allows fine-grained customization of the mobile app. The data pipeline manages data flow from the app to secure databases and then to the dashboard. Implemented in three hospitals in two countries so far, Neotree has captured routine data and supported the care of over 21,000 babies and has been used by over 450 healthcare professionals. All code and documentation are open source, allowing adoption and adaptation by clinicians, researchers, and developers.

Risk factors of mortality in neonates with neonatal encephalopathy in a tertiary newborn care unit in Zimbabwe over a 12-month period.

Neonatal encephalopathy (NE) accounts for ~23% of the 2.4 million annual global neonatal deaths. Approximately 99% of global neonatal deaths occur in low-resource settings, however, accurate data from these low-resource settings are scarce. We reviewed risk factors of neonatal mortality in neonates admitted with neonatal encephalopathy from a tertiary neonatal unit in Zimbabwe. A retrospective review of risk factors of short-term neonatal encephalopathy mortality was conducted at Sally Mugabe Central Hospital (SMCH) (November 2018 -October 2019). Data were gathered using a tablet-based data capture and quality improvement newborn care application (Neotree). Analyses were performed on data from all admitted neonates with a diagnosis of neonatal encephalopathy, incorporating maternal, intrapartum, and neonatal risk predictors of the primary outcome: mortality. 494/2894 neonates had neonatal encephalopathy on admission and were included. Of these, 94 died giving a neonatal encephalopathy-case fatality rate (CFR) of 190 per 1000 admitted neonates. Caesarean section (odds ratio (OR) 2.95(95% confidence interval (CI) 1.39-6.25), convulsions (OR 7.13 (1.41-36.1)), lethargy (OR 3.13 (1.24-7.91)), Thompson score "11-14" (OR 2.98 (1.08-8.22)) or "15-22" (OR 17.61 (1.74-178.0)) were significantly associated with neonatal death. No maternal risk factors were associated with mortality. Nearly 1 in 5 neonates diagnosed with neonatal encephalopathy died before discharge, similar to other low-resource settings but more than in typical high-resource centres. The Thompson score, a validated, sensitive and specific tool for diagnosing neonates with neonatal encephalopathy was an appropriate predictive clinical scoring system to identify at risk neonates in this setting. On univariable analysis time-period, specifically a period of staff shortages due to industrial action, had a significant impact on neonatal encephalopathy mortality. Emergency caesarean section was associated with increased mortality, suggesting perinatal care is likely to be a key moment for future interventions.

Evaluation of a Novel Culture System for Rapid Pathogen Identification and Detection of Cephalosporin Resistance in Neonatal Gram-negative Sepsis at a Tertiary Referral Unit in Harare, Zimbabwe.

BACKGROUND: Neonatal sepsis accounts for a large proportion of neonatal deaths in sub-Saharan Africa. The lack of access to diagnostic testing and excessively long turnaround times to result contributes to delays in sepsis identification and initiation of appropriate treatment. This study aims to evaluate the novel InTrays COLOREX Screen and extended-spectrum beta-lactamase for rapid identification of bacterial pathogens causing sepsis and detection of resistance. METHODS: Neonates with suspected sepsis admitted to the Harare Central Hospital were prospectively enrolled. One blood culture was collected and incubated using the BacT/ALERT automated system. Positive blood cultures with potential pathogens identified by Gram stain were inoculated on the InTray COLOREX Screen and extended-spectrum beta-lactamase culture plates. RESULTS: A total of 216 neonates with suspected sepsis were recruited. Pathogens were isolated from blood cultures in 56 (25.9%) neonates of which 54 were Klebsiella pneumoniae. All K. pneumoniae were resistant to ceftriaxone and 53 (98%) were resistant to gentamicin. Sensitivity and specificity for ceftriaxone-resistant K. pneumoniae detection using InTrays were 100%. InTrays results were interpretable as early as 5-10 hours (median 7 hours, interquartile range 7-7) post blood culture positivity enabling rapid identification and notification of result and leading to a 60% reduction in time to result from blood culture collection. CONCLUSIONS: This study shows that the implementation of a novel culture method was feasible and reduced turnaround times for results by 60% compared with standard microbiologic techniques. An impact on patient outcomes and cost-effectiveness of this method needs to be demonstrated.

Refining clinical algorithms for a neonatal digital platform for low-income countries: a modified Delphi technique.

OBJECTIVES: To determine whether a panel of neonatal experts could address evidence gaps in local and international neonatal guidelines by reaching a consensus on four clinical decision algorithms for a neonatal digital platform (NeoTree). DESIGN: Two-round, modified Delphi technique. SETTING AND PARTICIPANTS: Participants were neonatal experts from high-income and low-income countries (LICs). METHODS: This was a consensus-generating study. In round 1, experts rated items for four clinical algorithms (neonatal sepsis, hypoxic ischaemic encephalopathy, respiratory distress of the newborn, hypothermia) and justified their responses. Items meeting consensus for inclusion (≥80% agreement) were incorporated into the algorithms. Items not meeting consensus were either excluded, included following revisions or included if they contained core elements of evidence-based guidelines. In round 2, experts rated items from round 1 that did not reach consensus. RESULTS: Fourteen experts participated in round 1, 10 in round 2. Nine were from high-income countries, five from LICs. Experts included physicians and nurse practitioners with an average neonatal experience of 20 years, 12 in LICs. After two rounds, a consensus was reached on 43 of 84 items (52%). Per experts' recommendations, items in line with local and WHO guidelines yet not meeting consensus were still included to encourage consistency for front-line healthcare workers. As a result, the final algorithms included 53 items (62%). CONCLUSION: Four algorithms in a neonatal digital platform were reviewed and refined by consensus expert opinion. Revisions to NeoTree will be made in response to these findings. Next steps include clinical validation of the algorithms.

Electronic application to improve management of infections in low-income neonatal units: pilot implementation of the NeoTree beta app in a public sector hospital in Zimbabwe.

There are 2. 4 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions are a lack of newborn-trained healthcare workers and a lack of data collection systems. NeoTree is a digital platform aiming to improve newborn care in low-resource settings through real-time data capture and feedback alongside education and data linkage. This project demonstrates proof of concept of the NeoTree as a real-time data capture tool replacing handwritten clinical paper notes over a 9-month period in a tertiary neonatal unit at Harare Central Hospital, Zimbabwe. We aimed to deliver robust data for monthly mortality and morbidity meetings and to improve turnaround time for blood culture results among other quality improvement indicators. There were 3222 admissions and discharges entered using the NeoTree software with 41 junior doctors and 9 laboratory staff trained over the 9-month period. The NeoTree app was fully integrated into the department for all admission and discharge documentation and the monthly presentations became routine, informing local practice. An essential factor for this success was local buy-in and ownership at each stage of the project development, as was monthly data analysis and presentations allowing us to rapidly troubleshoot emerging issues. However, the laboratory arm of the project was negatively affected by nationwide economic upheaval. Our successes and challenges piloting this digital tool have provided key insights for effective future roll-out in Zimbabwe and other low-income healthcare settings.

Clinical prediction models to diagnose neonatal sepsis: a scoping review protocol.

INTRODUCTION: Neonatal sepsis is responsible for significant morbidity and mortality worldwide. Diagnosis is often difficult due to non-specific clinical features and the unavailability of laboratory tests in many low-income and middle-income countries (LMICs). Clinical prediction models have the potential to improve diagnostic accuracy and rationalise antibiotic usage in neonatal units, which may result in reduced antimicrobial resistance and improved neonatal outcomes. In this paper, we outline our scoping review protocol to map the literature concerning clinical prediction models to diagnose neonatal sepsis. We aim to provide an overview of existing models and evidence underlying their use and compare prediction models between high-income countries and LMICs. METHODS AND ANALYSIS: The protocol was developed with reference to recommendations by the Joanna Briggs Institute. Searches will include six electronic databases (Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Global Index Medicus and the Cochrane Library) supplemented by hand searching of reference lists and citation analysis on included studies. No time period restrictions will be applied but only studies published in English or Spanish will be included. Screening and data extraction will be performed independently by two reviewers, with a third reviewer used to resolve conflicts. The results will be reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. ETHICS AND DISSEMINATION: The nature of the scoping review methodology means that this study does not require ethical approval. Results will be disseminated through peer-reviewed publications and conference presentations, as well as through engagement with peers and relevant stakeholders.

Assessment of antimicrobial use and prescribing practices among pediatric inpatients in Zimbabwe.

This study aims to assess antimicrobial consumption in the pediatric department of a tertiary care public hospital in Zimbabwe. Clinical records of pediatric inpatients admitted to Harare Central Hospital over a 3-week period were reviewed prospectively. Antimicrobial consumption was described as days of therapy per 100 inpatient days (DOT/100 PD). Adherence of antimicrobial drug prescriptions to the National Guidelines was also evaluated. A total of 121 (93.1%) children were prescribed at least one antimicrobial out of 130 children admitted. The median age was 14 months (IQR: 3 - 48 months). Overall antimicrobial consumption was 155.4 DOT/100 PD (95% CI 146-165.2). The most frequently prescribed antimicrobials were benzylpenicillin, gentamicin and ceftriaxone. Prescriptions were adherent to national guidelines in 57.7% of children. This study shows that there is high antimicrobial drug usage in hospitalized children in Zimbabwe and a considerable proportion of prescriptions are non-adherent with national guidelines.