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OBJECTIVE: To assess the impact of HIV infection and exposure on survival in critically ill children requiring resuscitation. METHODS: A 6-month descriptive prospective cohort study of all live admissions to the resuscitation room of an urban paediatric emergency department in Blantyre, Malawi. RESULTS: 583 children were resuscitated, of whom 401 (69%) survived to hospital discharge. 26% of all children tested positive for HIV infection (152/576), and this was highest in patients presenting with shock (66%; 162/247), clinically diagnosed septicaemia (57%; 125/218) and malnutrition (40%; 24/60). Of 152 HIV-seropositive children, 30 (20%) died within 24h, while among 424 seronegative children 36 (8.4%) died within 24h (p<0.001). Later deaths (>24h) were also more common in HIV-seropositive children compared with HIV-uninfected patients (24.3% vs 12.3%; p<0.001). Survival to 24h was 80% (122/152) and to discharge 56% (85/152) in HIV-seropositive children. In HIV-uninfected children survival to 24h was 92% (388/424) and to discharge 79% (336/424). CONCLUSION: Early and late case death rates are greater in HIV-seropositive than in HIV-uninfected children. 80% of HIV-infected children survived the period most influenced by the process of resuscitation, that is, the first 24h. HIV status alone should not influence the limitation of intervention decisions in the resuscitation room when faced with a critically ill child. [ABSTRACT FROM AUTHOR]

Aim: To assess guidelines for the emergency triage, assessment, and treatment (ETAT) of sick children presenting to hospitals in the developing world. This study pretested the guidelines in Malawi, assessing their performance when used by nurses compared to doctors trained in advanced paediatric life support (APLS).Methods: Triage was performed simultaneously by a nurse and assessing doctor on 2281 children presenting to the under 5s clinic. Each patient was allocated one of three priorities, according to the ETAT guidelines. Any variation between nurse and assessor was recorded on the assessment forms.Results: Nurses identified 92 children requiring emergency treatment and 661 with signs indicating a need for urgent medical assessment. One hundred and forty two (6.2%) had different priorities allocated by the APLS trained doctor, but these children did not tend to need subsequent admission. Eighty five per cent of admissions were prioritised to an emergency or urgent category.Conclusion: Although there are no gold standards for comparison the ETAT guidelines appear to reliably select out the majority of patients requiring admission. [ABSTRACT FROM AUTHOR]

Great progress has been made in the care of children with cancer in recent decades. Worldwide, more than 80% of children with cancer live in resource-limited countries where access to care is poor. Sub-Saharan Africa is the world's poorest region. Child mortality is high, caused by largely preventable and treatable conditions. Paediatric cancer accounts for only a small fraction of deaths and understandably receives little attention from local policy makers or global health agencies. The survival of children with cancer is very poor. Challenges to improving survival include advanced-stage disease at presentation, failure to start or complete treatment (abandonment), inadequate hospital infrastructure and medications, lack of trained health care providers, lack of cancer registration and follow-up and lack of treatment guidelines adapted to local medical facilities. We propose a stepwise approach that integrates paediatric cancer treatment with existing general paediatric care. Priority is given to interventions (improvement of supportive care, diagnostic facilities) that also improve general paediatric care. Minimal requirements for diagnostic procedures include complete blood counts, HIV and malaria tests, blood cultures, histopathology and simple imaging (X-ray and ultrasonography). Feasible interventions include adequate palliative care, curative treatment for Burkitt lymphoma and Wilms tumour and symptomatic treatment for Kaposi sarcoma. [ABSTRACT FROM AUTHOR]

INTRODUCTION: In developing countries, patients with a Wilms' tumour often present late with a high degree of malnutrition and large tumours. We investigated whether this affects vincristine pharmacokinetics. METHODS: Patients newly diagnosed with Wilms' tumour in Malawi and the UK were included. We documented anthropometric parameters, nutritional status and tumour size. Vincristine (1.50 mg/m(2)) was administered as part of the standard chemotherapy regimen. Vincristine plasma concentrations were measured at several time points by liquid chromatography-mass spectrometry. Vincristine pharmacokinetic parameters (clearance and area under the curve) were calculated by non-compartmental analysis. RESULTS: Eleven Malawian and 8 UK patients were included. Mean Z-score of (corrected) weight for height was significantly lower in the Malawian patients than in the UK patients (-2.3 versus 0.42, p<0.0001). Mean tumour weight at diagnosis was significantly larger in Malawian patients (2.8 kg versus 0.7 kg, p=0.007). Mean vincristine logClearance was lower in Malawian as compared to UK patients (2.2 versus 2.6 ml/min, p=0.001). Mean logAUC values were higher in Malawian than in UK patients (3.8 versus 3.5 microg/mlmin, p=0.003). This difference is reflected in the, on average, 1.98-fold larger vincristine AUC values for Malawian patients. The difference in AUC values was statistically significantly explained by nutritional status (p=0.043). CONCLUSION: Malnourished patients in Malawi exhibited lower vincristine clearance rates and thus higher AUC values than a comparable patient population with a better nutritional status in the UK. In malnourished patients, dose reductions may need to be considered to prevent an increased incidence and severity of toxicity. [ABSTRACT FROM AUTHOR]

Collaborative research generating local evidence is key to closing the research and survival gap between sub-Saharan Africa and high-income countries. Lessons learned by CANCaRe Africa, the Collaborative African Network for Childhood Cancer Care and Research while pioneering such research are being discussed together with recommendations for the future., (© 2024 Wiley Periodicals LLC.)

Objectives . Preterm infants are at risk of hypothermia. This study described the available infant warming devices (IWDs) and explored the barriers and facilitators to their implementation in neonates in Malawi. Methods . A qualitative descriptive study was conducted among 19 health care workers in Malawi from January to March 2020. All interviews were digitally recorded, transcribed, and managed using NVivo and analyzed using a thematic approach. Results . The warming devices included radiant warmers, Blantyre hot-cots, wall-mounted heaters, portable warmers, and incubators. Inadequate equipment and infrastructure and gaps in staff knowledge and capacity were reported as the main challenges to optimal IWD implementation. Caregiver acceptance was described as the main facilitator. Strategies to optimize implementation of IWD included continuous practical training and adequate availability of equipment and spare parts. Conclusion . Implementation of warming devices for the management of neonatal hypothermia is effective when there are adequate human and material resources., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Service readiness tools are important for assessing hospital capacity to provide quality small and sick newborn care (SSNC). Lack of summary scoring approaches for SSNC service readiness means we are unable to track national targets such as the Every Newborn Action Plan targets., Methods: A health facility assessment (HFA) tool was co-designed by Newborn Essential Solutions and Technologies (NEST360) and UNICEF with four African governments. Data were collected in 68 NEST360-implementing neonatal units in Kenya, Malawi, Nigeria, and Tanzania (September 2019-March 2021). Two summary scoring approaches were developed: a) standards-based, including items for SSNC service readiness by health system building block (HSBB), and scored on availability and functionality, and b) level-2 + , scoring items on readiness to provide WHO level-2 + clinical interventions. For each scoring approach, scores were aggregated and summarised as a percentage and equally weighted to obtain an overall score by hospital, HSBB, and clinical intervention., Results: Of 1508 HFA items, 1043 (69%) were included in standards-based and 309 (20%) in level-2 + scoring. Sixty-eight neonatal units across four countries had median standards-based scores of 51% [IQR 48-57%] at baseline, with variation by country: 62% [IQR 59-66%] in Kenya, 49% [IQR 46-51%] in Malawi, 50% [IQR 42-58%] in Nigeria, and 55% [IQR 53-62%] in Tanzania. The lowest scoring was family-centred care [27%, IQR 18-40%] with governance highest scoring [76%, IQR 71-82%]. For level-2 + scores, the overall median score was 41% [IQR 35-51%] with variation by country: 50% [IQR 44-53%] in Kenya, 41% [IQR 35-50%] in Malawi, 33% [IQR 27-37%] in Nigeria, and 41% [IQR 32-52%] in Tanzania. Readiness to provide antibiotics by culture report was the highest-scoring intervention [58%, IQR 50-75%] and neonatal encephalopathy management was the lowest-scoring [21%, IQR 8-42%]. In both methods, overall scores were low (< 50%) for 27 neonatal units in standards-based scoring and 48 neonatal units in level-2 + scoring. No neonatal unit achieved high scores of > 75%., Discussion: Two scoring approaches reveal gaps in SSNC readiness with no neonatal units achieving high scores (> 75%). Government-led quality improvement teams can use these summary scores to identify areas for health systems change. Future analyses could determine which items are most directly linked with quality SSNC and newborn outcomes., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

The true global burden of paediatric critical illness remains unknown. Studies on children with life-threatening conditions are hindered by the absence of a common definition for acute paediatric critical illness (DEFCRIT) that outlines components and attributes of critical illness and does not depend on local capacity to provide critical care. We present an evidence-informed consensus definition and framework for acute paediatric critical illness. DEFCRIT was developed following a scoping review of 29 studies and key concepts identified by an interdisciplinary, international core expert panel (n=24). A modified Delphi process was then done with a panel of multidisciplinary health-care global experts (n=109) until consensus was reached on eight essential attributes and 28 statements as the basis of DEFCRIT. Consensus was reached in two Delphi rounds with an expert retention rate of 89%. The final consensus definition for acute paediatric critical illness is: an infant, child, or adolescent with an illness, injury, or post-operative state that increases the risk for or results in acute physiological instability (abnormal physiological parameters or vital organ dysfunction or failure) or a clinical support requirement (such as frequent or continuous monitoring or time-sensitive interventions) to prevent further deterioration or death. The proposed definition and framework provide the conceptual clarity needed for a unified approach for global research across resource-variable settings. Future work will centre on validating DEFCRIT and determining high priority measures and guidelines for data collection and analysis that will promote its use in research., Competing Interests: Declaration of interests AA reports funding from the National Institutes of Health National Cancer Institute (R37CA276215–01) outside of this Health Policy. BMM reports funding from Eurogol and the National Research Foundation; reports royalties from the Society of Critical Care Medicine as Senior Associate Editor of Pediatric Critical Care Medicine; receives support for travel and meetings from the European Cystic Fibrosis Society, Critical Care Society of Southern Africa, and the South Africa Thoracic Society, all outside of this Health Policy; and is the unpaid President for the World Federation of Pediatric Intensive and Critical Care Society and the Critical Care Society of Southern Africa. JHL reports funding from the National Research Medical Council of Singapore and the Thrasher Foundation in the USA, outside of this Health Policy. VMN is the President of the Society of Critical Care Medicine. The views expressed in this Health Policy do not necessarily reflect those of the institutions to which the authors are affiliated. All other authors declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10 -6 ), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10 -8 ), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10 -6 ). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk., (© 2023 Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10 -11 and 3.74×10 -2 , respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Thirty million small and sick newborns worldwide require inpatient care each year. Many receive antibiotics for clinically diagnosed infections without blood cultures, the current 'gold standard' for neonatal infection detection. Low neonatal blood culture use hampers appropriate antibiotic use, fuelling antimicrobial resistance (AMR) which threatens newborn survival. This study analysed the gap between blood culture use and antibiotic prescribing in hospitals implementing with Newborn Essential Solutions and Technologies (NEST360) in Kenya, Malawi, Nigeria, and Tanzania., Methods: Inpatient data from every newborn admission record (July 2019-August 2022) were included to describe hospital-level blood culture use and antibiotic prescription. Health Facility Assessment data informed performance categorisation of hospitals into four tiers: (Tier 1) no laboratory, (Tier 2) laboratory but no microbiology, (Tier 3) neonatal blood culture use < 50% of newborns receiving antibiotics, and (Tier 4) neonatal blood culture use > 50%., Results: A total of 144,146 newborn records from 61 hospitals were analysed. Mean hospital antibiotic prescription was 70% (range = 25-100%), with 6% mean blood culture use (range = 0-56%). Of the 10,575 blood cultures performed, only 24% (95%CI 23-25) had results, with 10% (10-11) positivity. Overall, 40% (24/61) of hospitals performed no blood cultures for newborns. No hospitals were categorised as Tier 1 because all had laboratories. Of Tier 2 hospitals, 87% (20/23) were District hospitals. Most hospitals could do blood cultures (38/61), yet the majority were categorised as Tier 3 (36/61). Only two hospitals performed > 50% blood cultures for newborns on antibiotics (Tier 4)., Conclusions: The two Tier 4 hospitals, with higher use of blood cultures for newborns, underline potential for higher blood culture coverage in other similar hospitals. Understanding why these hospitals are positive outliers requires more research into local barriers and enablers to performing blood cultures. Tier 3 facilities are missing opportunities for infection detection, and quality improvement strategies in neonatal units could increase coverage rapidly. Tier 2 facilities could close coverage gaps, but further laboratory strengthening is required. Closing this culture gap is doable and a priority for advancing locally-driven antibiotic stewardship programmes, preventing AMR, and reducing infection-related newborn deaths., (© 2023. The Author(s).)

Background: Medical devices are critical to providing high-quality, hospital-based newborn care, yet many of these devices are unavailable in low- and middle-income countries (LMIC) and are not designed to be suitable for these settings. Target Product Profiles (TPPs) are often utilised at an early stage in the medical device development process to enable user-defined performance characteristics for a given setting. TPPs can also be applied to assess the profile and match of existing devices for a given context., Methods: We developed initial TPPs for 15 newborn product categories for LMIC settings. A Delphi-like process was used to develop the TPPs. Respondents completed an online survey where they scored their level of agreement with each of the proposed performance characteristics for each of the 15 devices. Characteristics with < 75% agreement between respondents were discussed and voted on using Mentimeter™ at an in-person consensus meeting., Findings: The TPP online survey was sent to 180 people, of which 103 responded (57%). The majority of respondents were implementers/clinicians (51%, 53/103), with 50% (52/103) from LMIC. Across the 15 TPPs, 403 (60%) of the 668 performance characteristics did not achieve > 75% agreement. Areas of disagreement were voted on by 69 participants at an in-person consensus meeting, with consensus achieved for 648 (97%) performance characteristics. Only 20 (3%) performance characteristics did not achieve consensus, most (15/20) relating to quality management systems. UNICEF published the 15 TPPs in April 2020, accompanied by a report detailing the online survey results and consensus meeting discussion, which has been viewed 7,039 times (as of January 2023)., Conclusions: These 15 TPPs can inform developers and enable implementers to select neonatal care products for LMIC. Over 2,400 medical devices and diagnostics meeting these TPPs have been installed in 65 hospitals in Nigeria, Tanzania, Kenya, and Malawi through the NEST360 Alliance. Twenty-three medical devices identified and qualified by NEST360 meet nearly all performance characteristics across 11 of the 15 TPPs. Eight of the 23 qualified medical devices are available in the UNICEF Supply Catalogue. Some developers have adjusted their technologies to meet these TPPs. There is potential to adapt the TPP process beyond newborn care., (© 2023. The Author(s).)

Background: As countries strive to achieve sustainable development goal 3.2, high-quality medical education is crucial for high-quality neonatal care. Women are encouraged to deliver in health units attended by a skilled team. Traditionally, the team is doctors and nurses, but they are members of a large group of interdependent experts from other disciplines. Each discipline trains separately, yet the goal of good neonatal care is common to all. The use of interprofessional education breaks down these professional silos improving collaborative practice and promoting excellent clinical care. Introduction of new educational materials and training requires a rigorous approach to ensure sustainability., Methods: An extensive needs assessment identified gaps in neonatal training. Specifically, there was a lack of inclusion of medical devices used in clinical care. In each country, national key stakeholders came together to develop and revise their own neonatal curricula, trainings or guidelines. A core writing education team were tasked to develop evidence-based materials on pertinent medical devices to include in these national materials. These then underwent internal and external review. A provider course for biomedical engineers and technicians was introduced. Skills labs were established to improve practical skills teaching. To improve the quality of teaching, a NEST360 generic instructors course (GIC) was developed., Results: Twenty modules, 14 scenarios, 17 job aids and 34 videos have been published to date. Materials have been embedded into neonatal curricula and national trainings. Forty-one skills labs were installed in pre-service learning institutions and, up to June 2022, have been used by 7281 students. Pre- and in-service interprofessional training was implemented at all NEST360 institutions (clinical and biomedical). GIC courses were conducted at least twice a year in all countries. Three hundred seventeen nurses, biomedical and clinical staff have undertaken the GIC in all four countries. GIC participants report that the course has very positively influenced their teaching practice., Conclusions: Inclusion of key stakeholders throughout has ensured training is embedded within the four countries. Use of interprofessional education and inclusion of biomedical engineers and technicians has been very successful. Introduction of the GIC has developed a pool of high-quality educators for neonatal care. This approach has ensured that high-quality interprofessional neonatal training is included within national agendas for neonatal care and beyond., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele ( IFNL4 -dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia. The negative selection of IFNL4 -dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case-control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6-9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4 -dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.

Improving breastfeeding practices is key to reducing child mortality globally. Sub-optimal exclusive breastfeeding rates may be associated with inadequate hospital-based postpartum breastfeeding support, particularly in resource-limited health settings such as Malawi. While almost all children in Malawi are breastfed, it is a concern that exclusive breastfeeding rates in Malawi are declining. The objective of this study is to understand postpartum breastfeeding support after delivery at Malawian hospitals from the perspectives of health workers and caregivers. We conducted a secondary analysis of a descriptive qualitative study on health worker and caregiver experiences of breastfeeding support at health facilities in southern Malawi as part of the Innovating for Maternal and Child Health in Africa Initiative. In-depth interviews following a semi-structured topic guide were conducted at three secondary-level district hospitals and one tertiary-level central hospital. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). We interviewed a total of 61 participants, including 30 caregivers and 31 health care workers. Participants shared the following themes: 1) a focus on early initiation of breastfeeding, 2) inadequate follow-up on breastfeeding practice, and 3) feasibility challenges and local solutions. There was an emphasis on early initiation of breastfeeding, which was challenged by maternal exhaustion after delivery. Study participants reported poor follow-up on breastfeeding practice after initial counselling and reacting to adverse outcomes in lieu of adequate monitoring, with a reliance on caregivers to follow-up on challenges. There was poor support for facility-based breastfeeding after initial counselling post-delivery, which revealed an overall neglect in hospital postpartum care for those considered to be in good health after initial assessment. We recommend the development of indicators to track continued facility-based breastfeeding, identify vulnerable infants at-risk of feeding problems, and strengthening care in postnatal wards, which is currently as neglected component of maternity care., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ALNM is an editorial board member of the journal. All other authors have declared that no competing interests exist., (Copyright: © 2022 Kinshella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Severe neonatal jaundice can result in long term morbidities and mortality when left untreated. Phototherapy is the main-stay intervention for treating moderate jaundice and for prevention of the development of severe jaundice. However, in resource-limited health care settings, phototherapy has been inconsistently used. The objective of this study is to evaluate barriers and facilitators for phototherapy to treat neonatal jaundice at Malawian hospitals., Methods: We conducted a convergent mixed-method study comprised of a facility assessment and qualitative interviews with healthcare workers and caregivers in southern Malawi. The facility assessment was conducted at three secondary-level hospitals in rural districts. In-depth interviews following a semi-structured topic guide were conducted at a district hospital and a tertiary-level hospital. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia)., Results: The facility assessment found critical gaps in initiating and monitoring phototherapy in all facilities. Based on a total of 31 interviews, participants identified key challenges in diagnosing neonatal jaundice, counselling caregivers, and availability of infrastructure. Participants emphasized the need for transcutaneous bilirubinometers to guide treatment decisions. Caregivers were sometimes fearful of potential harmful effects of phototherapy, which required adequate explanation to mothers and family members in non-medical language. Task shifting and engaging peer support for caregivers with concerns about phototherapy was recommended., Conclusion: Implementation of a therapeutic intervention is limited if accurate diagnostic tests are unavailable. The scale up of therapeutic interventions, such as phototherapy for neonatal jaundice, requires careful holistic attention to infrastructural needs, supportive services such as laboratory integration as well as trained human resources., (© 2022. The Author(s).)

Background: Health care-associated infections (HCAI) in neonatal units in low- and middle-income countries (LMIC) are a major cause of mortality. This scoping review aimed to synthesise published literature on infection prevention and care bundles addressing neonatal HCAI in LMICs and to construct a Classification Framework for their components (elements)., Methods: Five electronic databases were searched between January 2001 and July 2020. A mixed-methods approach was applied: qualitative content analysis was used to build a classification framework to categorise bundle elements and the contents of the classification groups were then described quantitatively., Findings: 3619 records were screened, with 44 eligible studies identified. The bundle element Classification Framework created involved: (1) Primary prevention, (2) Detection , (3) Case management , and Implementation (3 + I ) . The 44 studies included 56 care bundles with 295 elements that were then classified. Primary prevention elements (128, 43%) predominated of which 71 (55%) focused on central line catheters and mechanical ventilators. Only 12 elements (4%) were related to detection . A further 75 (25%) elements addressed case management and 66 (88%) of these aimed at outbreak control., Interpretation: The 3 + I Classification Framework was a feasible approach to reporting and synthesising research for infection-relevant bundled interventions in neonatal units. A shift towards the use in infection prevention and care bundles of primary prevention elements focused on the neonate and on commonly used hospital devices in LMIC (e.g., self-inflating bags, suctioning equipment) would be valuable to reduce HCAI transmission. Detection elements were a major gap., Funding: This work was made possible in part by the John D. and Catherine T. MacArthur Foundation, the Bill & Melinda Gates Foundation, ELMA Philanthropies, The Children's Investment Fund Foundation UK, The Lemelson Foundation, and the Ting Tsung and Wei Fong Chao Foundation under agreements to William Marsh Rice University. The project leading to these results has also received the support of a fellowship from the "la Caixa" Foundation (ID 100010434). The fellowship code is LCF/BQ/EU19/11710040. EJAF is an Academic Clinical Fellow whose salary is funded by the UK National Institute for Health Research (NIHR). NES receives a Research Training Program Scholarship (Australian Commonwealth Government)., Competing Interests: We declare no competing interests., (© 2021 The Authors.)

Background: Doxorubicin is known to cause chemotherapy-induced cardiotoxicity. In resource-poor settings, monitoring for cardiotoxicity is not routinely done, and its incidence is unknown. The aim of this study was to determine the proportion of children who developed doxorubicin-induced cardiotoxicity within 1 year of having received treatment at paediatric oncology ward., Methods: Children aged 3 months to 18 years with cancer were prospectively enrolled and followed up between January 2016 to June 2019. Transthoracic echocardiogram was done at baseline, 1 month, 6 months and a year after completion of therapy. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) of ≥10% to a final value of <50%. An overall incidence risk of developing cardiotoxicity was estimated. A one-way analysis of variance (ANOVA) was conducted to compare baseline LVEF with follow-up measurements., Findings: Ninety-one children were enrolled, 74% (68/91) were male, and 67% (62/91) were aged 5 months to 14 years. Most patients received a doxorubicin cumulative dose between 100 and 200 mg/m 2 and no cardiotoxicity was observed during the study period. However, of 77 children with at least one follow up, five children 6.54% (95% CI: 2.1-14.5) experienced LVEF reduction of >10%, though not to a final value of <50%. No deterioration of systolic function was found among 20 children who completed follow-up (F = 2.43, p-value = .07)., Interpretation: In this cohort of patients, most received a low cumulative doxorubicin dose and only 22% were available for evaluation at study end; no cardiotoxic events associated with doxorubicin administration were observed after 12 months., (© 2021 Wiley Periodicals LLC.)

Owing to the rapid turnaround time in the assessment of haemoglobin level by point-of-care tests (POC Hb), these have grown in popularity and scope in large parts of the world. However, whilst POC testing for malaria and HIV remains has been integrated into patient management in Africa, the use of POC haemoglobin testing remains neglected by health services. The main users of transfusions (paediatric, maternity and trauma services) present largely as emergencies. Ward-based POC Hb could result in more rapid and accurate diagnosis of anaemia, contributing to saving of lives and at the same time reduce unnecessary transfusions which deplete the limited supplies of donated blood in Africa. Severe anaemia requiring transfusion is a major cause of paediatric admission in Africa. At a dissemination meeting to discuss the results of a large phase III paediatric transfusion trial and steps to implementation of the findings participants strongly recommended that one of the most pressing actions required was to prioritise the use of POC haemoglobin testing. This would facilitate implementation of the new transfusion algorithm, developed at the meeting, which refines patient management including blood transfusions. We present the rationale for the strongly recommended prioritisation of POC Hb, using paediatric transfusion as an exemplar., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40-60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mortality, depending on fever status (>37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to Plasmodium falciparum ( Pf ) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of Pf genetic diversity is unclear. A potential role of Pf genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of Pf infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher Pf genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in Pf- serine repeat antigen-5 ( Pfsera5 ), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all Pf polymerase chain reaction (PCR)-positive, in Malawi., Methods: We performed Pfsera5 PCR and sequencing (~3.3 kb over exons II-IV) to determine single or mixed Pf SERA5 infection status. The patterns of Pfsera5 PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed Pfsera5 infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured Pf genetic diversity., Results: Pfsera5 PCR was positive in 108 eBL cases and 70 controls. Mixed Pf SERA5 infection was detected in 41.7% of eBL cases versus 24.3% of controls; the odds ratio (OR) was 2.18, and the 95% confidence interval (CI) was 1.12-4.26, which remained significant in adjusted results (adjusted odds ratio [aOR] of 2.40, 95% CI of 1.11-5.17). A total of 29 nucleotide variations and 96 haplotypes were identified, but these were unrelated to eBL., Conclusions: Our results increase the evidence supporting the hypothesis that infection with mixed Pf infection is increased with eBL and suggest that measuring Pf genetic diversity may provide new insights into the role of Pf infection in eBL.

Background: COVID-19 is disrupting health services for mothers and newborns, particularly in low- and middle-income countries (LMIC). Preterm newborns are particularly vulnerable. We undertook analyses of the benefits of kangaroo mother care (KMC) on survival among neonates weighing ≤2000 g compared with the risk of SARS-CoV-2 acquired from infected mothers/caregivers., Methods: We modelled two scenarios over 12 months. Scenario 1 compared the survival benefits of KMC with universal coverage (99%) and mortality risk due to COVID-19. Scenario 2 estimated incremental deaths from reduced coverage and complete disruption of KMC. Projections were based on the most recent data for 127 LMICs (~90% of global births), with results aggregated into five regions., Findings: Our worst-case scenario (100% transmission) could result in 1,950 neonatal deaths from COVID-19. Conversely, 125,680 neonatal lives could be saved with universal KMC coverage. Hence, the benefit of KMC is 65-fold higher than the mortality risk of COVID-19. If recent evidence of 10% transmission was applied, the ratio would be 630-fold. We estimated a 50% reduction in KMC coverage could result in 12,570 incremental deaths and full disruption could result in 25,140 incremental deaths, representing a 2·3-4·6% increase in neonatal mortality across the 127 countries., Interpretation: The survival benefit of KMC far outweighs the small risk of death due to COVID-19. Preterm newborns are at risk, especially in LMICs where the consequences of disruptions are substantial. Policymakers and healthcare professionals need to protect services and ensure clearer messaging to keep mothers and newborns together, even if the mother is SARS-CoV-2-positive., Funding: Eunice Kennedy Shriver National Institute of Child Health & Human Development; Bill & Melinda Gates Foundation; Elma Philanthropies; Wellcome Trust; and Joint Global Health Trials scheme of Department of Health and Social Care, Department for International Development, Medical Research Council, and Wellcome Trust., Competing Interests: We declare no competing interests., (© 2021 The Authors.)

Introduction: Kangaroo mother care (KMC) involves continuous skin-to-skin contact of baby on mother's chest to provide warmth, frequent breastfeeding, recognizing danger signs of illness, and early discharge. Though KMC is safe, effective and recommended by the World Health Organization, implementation remains limited in practice. The objective of this study is to understand barriers and facilitators to KMC practice at tertiary and secondary health facilities in southern Malawi from the perspective of health workers., Methods: This study is part of the "Integrating a neonatal healthcare package for Malawi" project in the Innovating for Maternal and Child Health in Africa initiative. In-depth interviews were conducted between May-Aug 2019 with a purposively drawn sample of service providers and supervisors working in newborn health at a large tertiary hospital and three district-level hospitals in southern Malawi. Data were analyzed using a thematic approach using NVivo 12 software (QSR International, Melbourne, Australia)., Findings: A total of 27 nurses, clinical officers, paediatricians and district health management officials were interviewed. Staff attitudes, inadequate resources and reliance on families emerged as key themes. Health workers from Malawi described KMC practice positively as a low-cost, low-technology solution appropriate for resource-constrained health settings. However, staff perceptions that KMC babies were clinically stable was associated with lower prioritization in care and poor monitoring practices. Neglect of the KMC ward by medical staff, inadequate staffing and reliance on caregivers for supplies were associated with women self-discharging early., Conclusion: Though routine uptake of KMC was policy for stable low birthweight and preterm infants in the four hospitals, there were gaps in monitoring and maintenance of practice. While conceptualized as a low-cost intervention, sustainable implementation requires investments in technologies, staffing and hospital provisioning of basic supplies such as food, bedding, and KMC wraps. Strengthening hospital capacities to support KMC is needed as part of a continuum of care for premature infants., Competing Interests: The authors have declared that no competing interests exist.

Background: While Malawi has achieved success in reducing overall under-five mortality, reduction of neonatal mortality remains a persistent challenge. There has, therefore, been a push to strengthen the capacity for quality newborn care at district hospitals through the implementation of innovative neonatal technologies such as bubble continuous positive airway pressure (CPAP). This study investigates tertiary- versus secondary-level hospital differences in capacities for bubble CPAP use and implications for implementation policies., Methods: A secondary analysis of interviews was conducted with 46 health workers at one tertiary hospital and three secondary hospitals in rural Southern Malawi. Grounded theory was utilized to explore the emerging themes according to health worker cadres (nurse, clinician, district health management) and facility level (tertiary- and secondary-level facilities), which were managed using NVivo 12 (QSR International, Melbourne, Australia)., Results: We identified frequent CPAP use and the availability of neonatal nurses, physicians, and reliable electricity as facilitators for CPAP use at the tertiary hospital. Barriers at the tertiary hospital included initiation eligibility disagreements between clinicians and nurses and insufficient availability of the CPAP machines. At secondary-level hospitals, the use was supported by decision-making and initiation by nurses, involving caretakers to assist in monitoring and reliable availability of CPAP machines. Bubble CPAP was hindered by unreliable electricity, staffing shortages and rotation policies, and poor systems of accountability., Conclusion: While this study looked at the implementation of bubble CPAP in Malawi, the findings may be applicable for scaling up other novel neonatal technologies in low-resource settings. Implementation policies must consider staffing and management structures at different health services levels for effective scale-up.