Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

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.

Quantifying health facility service readiness for small and sick newborn care: comparing standards-based and WHO level-2 + scoring for 64 hospitals implementing with NEST360 in Kenya, Malawi, Nigeria, and Tanzania.

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.

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.

Using interprofessional education to build dynamic teams to help drive collaborative, coordinated and effective newborn care.

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.

Target product profiles for neonatal care devices: systematic development and outcomes with NEST360 and UNICEF.

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.

Blood culture versus antibiotic use for neonatal inpatients in 61 hospitals implementing with the NEST360 Alliance in Kenya, Malawi, Nigeria, and Tanzania: a cross-sectional study.

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.

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.

Challenges and recommendations to improve implementation of phototherapy among neonates in Malawian hospitals.

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.

Point-of-care haemoglobin testing in African hospitals: a neglected essential diagnostic test.

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.

Transfusion management of severe anaemia in African children: a consensus algorithm.

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.

Early doxorubicin cardiotoxicity in Malawian children admitted to Queen Elizabeth Central Hospital, Malawi.

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/m2 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.

Health workers' views on factors affecting caregiver engagement with bubble CPAP.

BACKGROUND: Severe respiratory distress is a leading cause of mortality among neonates in Malawi. Despite evidence on the safety, cost effectiveness and efficacy of bubble continuous positive airway pressure (CPAP) in managing the condition, its use in Malawian health facilities is limited and little is known about caregivers' engagement with perspectives of bubble CPAP. The purpose of this study was to explore caregiver perspectives for bubble CPAP at both central and district hospitals and key factors that enable effective caregiver engagement in Malawi. METHODS: This was a descriptive qualitative study employing secondary analysis of 46 health care worker in-depth interviews. We interviewed the health workers about their thoughts on caregiver perspectives regarding use of bubble CPAP. We implemented the study at a tertiary facility and three district hospitals in southern Malawi. This was a part of a larger study to understand barriers and facilitators to implementing neonatal innovations in resource-constrained hospitals. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia). Health workers were purposively selected to include nurses, clinicians and district health management involved in the use of bubble CPAP. RESULTS: Emerging issues included caregiver fears around bubble CPAP equipment as potentially harmful to their new-borns and how inadequate information provided to caregivers exacerbated knowledge gaps and was associated with refusal of care. However, good communication between health care providers and caregivers was associated with acceptance of care. Caregivers' decision-making was influenced by relatives and peer advocates were helpful in supporting caregivers and alleviating fears or misconceptions about bubble CPAP. CONCLUSIONS: Since caregivers turn to relatives and peers for support, there is need to ensure that both relatives and peers are counselled on bubble CPAP for improved understanding and uptake. Health workers need to provide simplified, accurate, up-to-date information on the intervention as per caregivers' level of understanding. Notably, contextualised comprehensible information will help alleviate caregivers' fear and anxieties about bubble CPAP.

Triple therapy of vincristine, bleomycin and etoposide for children with Kaposi sarcoma: Results of a study in Malawian children.

BACKGROUND: Kaposi sarcoma (KS) is the most common paediatric cancer in human immunodeficiency virus (HIV) endemic countries of sub-Saharan Africa, but there is little research on management and outcomes. METHODS: Children with KS at Queen Elizabeth Central Hospital, Blantyre, Malawi treated between August 2012 and March 2015 with six courses of vincristine, bleomycin and etoposide combination chemotherapy, including antiretroviral therapy (ART) if HIV infected, were studied and outcomes compared with previously reported results. FINDINGS: Fifty-six children were included; 38 (68%) were male; and 48 (86%) were HIV positive, of whom 36 (77%) were on ART at diagnosis. Median age at diagnosis was 8 years (interquartile range [IQR] 3-12) and median follow-up was 16.9 months (IQR 3.4-36.4). Quality of life improved in 45 (80%) children; the median Lansky Score increased from 80% pre-treatment to 100% post-treatment. Eighteen (32%) children had complete response to treatment. At 12 months, overall survival was 71% (95% confidence interval [CI] 56-82) and event-free survival (event = death, loss to follow-up or relapse) was 50% (95% CI 36-63). At 1 year, the risk of loss to follow-up was 13.4%. In a previous, same-site, randomized controlled study of vincristine monotherapy, vincristine and bleomycin, or oral etoposide, oral etoposide monotherapy had the best outcome with survival at 12 month of 66% (95% CI 46-80) and event-free survival of 52% (95% CI 33-68); however, loss to follow-up was not reported. CONCLUSION: Overall survival, event-free survival and quality of life appear to have improved with this three-agent combination chemotherapy; however larger, randomized studies are needed to determine optimal management.

Improving the outcome of bacterial meningitis in newborn infants in Africa: reflections on recent progress.

PURPOSE OF REVIEW: There has been a reduction in overall under fives mortality (UFM) but neonatal mortality has not fallen at the same rate as for older children. Bacterial meningitis remains a common, often unrecognized and devastating illness in many African newborns with high mortality and morbidity. Further progress in reducing UFM has to focus on quality of care for neonates. Recent efforts to improve diagnosis, treatment and outcome are reviewed. RECENT FINDINGS: Diagnosis is often unsupported by laboratory tests and efforts have been made to improve the clinical diagnosis of bacterial meningitis. Simpler, robust bedside tests are being devised. The cause of bacterial meningitis is changing and first-line antimicrobial therapy and adjuvant therapies are evaluated. Programmes to reduce risk factors and prevent neonatal infections are identified. SUMMARY: Neonatal care needs to improve in first referral hospitals with simple, low-cost, validated measures provided as bundles of care for both mother and child. First-line antibiotic therapy must be reconsidered in the light of increased infections by multiresistant and Gram-negative bacteria. Studies are needed for effective and safe lengths of antimicrobial therapy, the role of adjuvant therapy and the best anticonvulsants to use.

Outcomes of Patients with Respiratory Distress Treated with Bubble CPAP on a Pediatric Ward in Malawi.

OBJECTIVE: To describe the outcomes of infants and young children with respiratory distress when treated with a novel, low-cost, stand-alone bubble Continuous Positive Airway Pressure (bCPAP) system in a resource-limited setting. METHODS: A non-randomized, convenience sample study in a pediatric unit in Blantyre, Malawi, 2013. Patients weighing ≤10 kg with respiratory distress were eligible. We compared outcomes for patients with bronchiolitis, pneumonia and Pneumocystis jiroveci pneumonia (PJP) after treatment with bCPAP. RESULTS: Seventy percent of patients treated with bCPAP survived. Outcomes were best for patients with bronchiolitis and worst for those with PJP. Most survivors (80%) showed improvement within 24 h. All treating physicians found bCPAP useful, leading to a change in practice. CONCLUSIONS: Bubble CPAP was most beneficial to patients with bronchiolitis. Children, who were going to get well, tended to get well quickly. Physicians believed the bCPAP system provided a higher level of care than nasal oxygen.

Bacterial meningitis in Malawian adults, adolescents, and children during the era of antiretroviral scale-up and Haemophilus influenzae type b vaccination, 2000-2012.

BACKGROUND: We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART). METHODS: We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 2000 and 2012. RESULTS: There was a significant decline in the total number of CSF isolates over 12 years (incident rate ratio [IRR], 0.93; 95% CI, .92-.94; P < .001). This decline was entirely in children aged <5 years (IRR, 0.87; 95% CI, .85-.88; P < .001) and coincided with the introduction of Hib vaccination. The number of adult isolates has remained unchanged (IRR, 0.99; 95% CI, .97-1.0; P = .135) despite rapid scale-up of ART provision. In children aged <5 years, Streptococcus pneumoniae, nontyphoidal salmonellae (NTS), and Hib were the most frequently isolated pathogens, and have declined over this time period. Streptococcus pneumoniae was the most frequently isolated pathogen in older children and adults. Estimated incidence of bacterial meningitis in 2012 was 20 per 100,000 cases in children aged <14 years, 6 per 100,000 adolescents, and 10 per 100,000 adults. CONCLUSIONS: Rates of bacterial meningitis have declined in children, but not adults, coinciding with the introduction of Hib vaccination. The highly successful rollout of ART has not yet resulted in a reduction in the incidence in adults where the burden remains high. Long-term surveillance of bacterial meningitis outside of the epidemic "meningitis belt" in Africa is essential.

Factors Influencing the Implementation of Infant Warming Devices Among Healthcare Workers in Malawian Hospitals.

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.

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

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