Bacterial and Candida Colonization of Neonates in a Regional Hospital in South Africa.

BACKGROUND: Neonatal colonization with multidrug-resistant (MDR) Enterobacter spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterococcus faecium (ESKAPE) and Candida spp. often precedes invasive hospital-acquired infections. We investigated the prevalence and dynamics of neonatal ESKAPE and Candida spp. colonization from hospital admission until discharge (or death) and followed up for invasive disease. METHODS: Prospective longitudinal surveillance for neonatal ESKAPE and Candida spp. colonization was conducted over 6 months at a South African regional hospital. Neonates enrolled at birth had swabs (nasal, 2× skin and rectal) collected within 24 hours and every 48-96 hours thereafter, until discharge or death. ESKAPE and Candida spp. were cultured for and antimicrobial susceptibility was performed on bacterial isolates. Whole-genome sequencing was undertaken on paired samples with the same bacterial species from colonizing and invasive disease episodes in the same child. RESULTS: Of 102 enrolled neonates, 79% (n = 81) were colonized by ≥1 ESKAPE organism by time of discharge or death. Forty-four percent (36/81) were colonized within 24 hours of birth. Common colonizers were K. pneumoniae (70%; n = 57) and Enterobacter spp. (43%; n = 35). Almost all MDR organisms (93%) were Gram-negative. Forty-two (45%, 42/93) newborns acquired Candida spp. (skin only) colonization, commonly Candida parapsilosis (69%; n = 29). For 2 children with K. pneumoniae colonization and sepsis, the bloodstream and colonizing isolates were genetically different, whereas the single A. baumannii colonizing and blood isolate pair were genetically identical. CONCLUSIONS: We report a high prevalence of MDR ESKAPE and Candida spp. colonization in a regional neonatal unit. Interventions to reduce the high incidence of hospital-acquired neonatal infections should include reducing high colonization rates.

Child deaths caused by Klebsiella pneumoniae in sub-Saharan Africa and south Asia: a secondary analysis of Child Health and Mortality Prevention Surveillance (CHAMPS) data.

BACKGROUND: Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterise child mortality associated with this pathogen in seven high-mortality settings. METHODS: We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for deaths in catchment populations and following reporting of an eligible death or stillbirth seek consent for minimally invasive tissue sampling followed by extensive aetiological testing (microbiological, molecular, and pathological); cases are reviewed by expert panels to assign immediate, intermediate, and underlying causes of death. We reported on susceptibility to antibiotics for which at least 30 isolates had been tested, and excluded data on antibiotics for which susceptibility testing is not recommended for Klebsiella spp due to lack of clinical activity (eg, penicillin and ampicillin). FINDINGS: Among 2352 child deaths with cause of death assigned, 497 (21%, 95% CI 20-23) had K pneumoniae in the causal chain of death; 100 (20%, 17-24) had K pneumoniae as the underlying cause. The frequency of K pneumoniae in the causal chain was highest in children aged 1-11 months (30%, 95% CI 26-34; 144 of 485 deaths) and 12-23 months (28%, 22-34; 63 of 225 deaths); frequency by site ranged from 6% (95% CI 3-11; 11 of 184 deaths) in Bangladesh to 52% (44-61; 71 of 136 deaths) in Ethiopia. K pneumoniae was in the causal chain for 450 (22%, 95% CI 20-24) of 2023 deaths that occurred in health facilities and 47 (14%, 11-19) of 329 deaths in the community. The most common clinical syndromes among deaths with K pneumoniae in the causal chain were sepsis (44%, 95% CI 40-49; 221 of 2352 deaths), sepsis in conjunction with pneumonia (19%, 16-23; 94 of 2352 deaths), and pneumonia (16%, 13-20; 80 of 2352 deaths). Among K pneumoniae isolates tested, 121 (84%) of 144 were resistant to ceftriaxone and 80 (75%) of 106 to gentamicin. INTERPRETATION: K pneumoniae substantially contributed to deaths in the first 2 years of life across multiple high-mortality settings, and resistance to antibiotics used for sepsis treatment was common. Improved strategies are needed to rapidly identify and appropriately treat children who might be infected with this pathogen. These data suggest a potential impact of developing and using effective K pneumoniae vaccines in reducing neonatal, infant, and child deaths globally. FUNDING: Bill & Melinda Gates Foundation.

Incidence, pathogens and antimicrobial resistance of blood and cerebrospinal fluid isolates from a tertiary neonatal unit in South Africa: A 10 year retrospective review.

OBJECTIVE: To determine trends in incidence, etiology and antimicrobial susceptibility of blood and cerebrospinal fluid (CSF) culture confirmed infections in hospitalized infants in a large tertiary neonatal unit in South Africa. METHODS: Single-center, retrospective review of laboratory records of bacteria and fungi, and their susceptibility profiles, isolated from blood and CSF of infants hospitalized in the neonatal unit at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, from 1st January 2010 to 31st December 2019. Laboratory data on isolates and their antimicrobial susceptibilities were collected. Coagulase-negative Staphylococcus, Corynebacteria and Bacillus spp. were excluded. Patient-level clinical and laboratory data were not available. RESULTS: There were 8,319 significant isolates, giving an infection rate of 14.3/1000 patient-days. Infection rates increased from 12.0 to 15.7/1000 patient-days (estimated average yearly change 0.6[95%CI, 0.5-0.7];p = <0.001). Gram-negative infection rates increased from 4.3 to 10.8/1000 patient-days (estimated average yearly change 0.7[95%CI,0.6-0.8];p = <0.001). The 2 most commonly isolated Gram-negative organisms were Acinetobacter baumannii (44%) and Klebsiella pneumoniae (39%). Carbapenem resistance was seen in 31% of all Gram-negatives and increased over time (estimated average yearly change 4.8%[95%CI,4.2%-5.3%];p<0.001). Gram-positive infection rates decreased (estimated average yearly change -0.1[95%CI,-0.2- -0.05];p = <0.001). Staphylococcus aureus was the most common Gram-positive isolated. Rates of methicillin-resistant Staphylococcus aureus decreased from 91% to 55%(estimated average yearly change -2.8%[95%CI,-3.5%-2%],p< 0.001). Rates of fungal isolates decreased (estimated average yearly change -0.06[95%CI,-0.1 --0.02]);p = 0.007). Candida parapsilosis (52%) and Candida albicans (35%) were the most common fungi isolated. CONCLUSIONS: There has been a marked overall increase in rates of blood and/or CSF infections, with an absolute increase in Gram-negative infections observed, replacing Gram-positive and fungal pathogens. Extended spectrum beta-lactamase Gram-negative isolates are being replaced by carbapenem resistance, with around one third of all significant Gram-negative isolates now carbapenem resistant. Research into hospital based novel treatment and prevention interventions for neonatal sepsis should be urgently prioritized.

Long-term impact of serious neonatal bacterial infections on neurodevelopment.

BACKGROUND: Neonatal bacterial infections have long been recognized as an important cause of acute morbidity and mortality, but long-term neurodevelopmental consequences have not been comprehensively described and discussed. OBJECTIVES: We aimed to summarize evidence on the pathogenesis, diagnosis, and epidemiology of long-term sequelae after neonatal bacterial sepsis and meningitis. We also discuss approaches for future studies to quantify the public health impact of neonatal infection-associated neurodevelopmental impairment. SOURCES: We identified studies, both research articles and reviews, which provide mechanistic information on the long-term disease, as well as epidemiological studies that describe the frequency of neurodevelopmental impairment in children with and, for comparison, without a history of neonatal bacterial infection. Tools currently used in clinical practice and research settings to assess neurodevelopmental impairment were also reviewed. CONTENT: We first enumerate potential direct and indirect mechanisms that can lead to brain injury following neonatal infections. We then discuss summary data, either frequencies or measures of association, from epidemiological studies. Risk factors that predict long-term outcomes are also described. Finally, we describe clinical approaches for identifying children with neurodevelopmental impairment and provide an overview of common diagnostic tools. IMPLICATIONS: The limited number of studies that describe the long-term consequences of neonatal infections, often undertaken in high-income settings and using variable designs and diagnostic tools, are not sufficient to inform clinical practice and policy prioritization. Multi-country studies with follow-up into adolescence, standardized diagnostic approaches, and local comparator groups are needed, especially in low and middle-income countries where the incidence of neonatal sepsis is high.

A multicentre neonatal interventional randomised controlled trial of nebulized surfactant for preterm infants with respiratory distress: Neo-INSPIRe trial protocol.

INTRODUCTION: Respiratory distress syndrome in preterm infants is an important cause of morbidity and mortality. Less invasive methods of surfactant administration, along with the use of continuous positive airway pressure (CPAP), have improved outcomes of preterm infants. Aerosolized surfactant can be given without the need for airway instrumentation and may be employed in areas where these skills are scarce. Recent trials from high-resourced countries utilising aerosolized surfactant have had a low quality of evidence and varying outcomes. METHODS AND ANALYSIS: The Neo-INSPIRe trial is an unblinded, multicentre, randomised trial of a novel aerosolized surfactant drug/device combination. Inclusion criteria include preterm infants of 27-34+6 weeks' gestational age who weigh 900-1999g and who require CPAP with a fraction of inspired oxygen (FiO2) of 0.25-0.35 in the first 2-24 h of age. Infants are randomised 1:1 to control (CPAP alone) or intervention (CPAP with aerosolized surfactant). The primary outcome is the need for intratracheal bolus surfactant instillation within 72 h of age. Secondary outcomes include the incidence of reaching failure criteria (persistent FiO2 of > 0.40, severe apnoea or severe work of breathing), the need for and duration of ventilation and respiratory support, bronchopulmonary dysplasia and selected co-morbidities of prematurity. Assuming a 40% relative risk reduction to reduce the proportion of infants requiring intratracheal bolus surfactant from 45 to 27%, the study will aim to enrol 232 infants for the study to have a power of 80% to detect a significant difference with a type 1 error of 0.05. ETHICS AND DISSEMINATION: Ethical approval has been granted by the relevant human research ethics committees at University of Cape Town (HREC 681/2022), University of the Witwatersrand HREC (221112) and Stellenbosch University (M23/02/004). TRIAL REGISTRATION: PACTR202307490670785.

Stillbirths and Neonatal Deaths Caused by Group B Streptococcus in Africa and South Asia Identified Through Child Health and Mortality Prevention Surveillance (CHAMPS).

Background: Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). Methods: Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. Results: We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). Conclusions: Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs.

Provider adherence to clinical care recommendations for infants and children who died in seven low- and middle-income countries in the Child Health and Mortality Prevention Surveillance (CHAMPS) network.

Background: Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children. Methods: We conducted a retrospective, descriptive study examining clinical data for children aged 1-59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016-June 2021. Catchment areas included: Baliakandi and Faridpur, Bangladesh; Kersa, Haramaya, and Harar, Ethiopia; Kisumu and Siaya, Kenya; Bamako, Mali; Manhiça and Quelimane, Mozambique; Makeni, Sierra Leone; Soweto, South Africa. We reviewed medical records of those who died from lower respiratory tract infections, sepsis, malnutrition, malaria, and diarrheal diseases to determine the proportion who received recommended treatments and compared adherence by hospitalization duration. Findings: CHAMPS enrolled 460 hospitalized children who died from the leading causes (median age 12 months, 53.0% male). Median hospital admission was 31 h. There were 51.0% (n = 127/249) of children who died from lower respiratory tract infections received supplemental oxygen. Administration of intravenous fluids for sepsis (15.9%, n = 36/226) and supplemental feeds for malnutrition (14.0%, n = 18/129) were uncommon. There were 51.4% (n = 55/107) of those who died from malaria received antimalarials. Of the 80 children who died from diarrheal diseases, 76.2% received intravenous fluids. Those admitted for ≥24 h more commonly received antibiotics for lower respiratory tract infections and sepsis, supplemental feeds for malnutrition, and intravenous fluids for sepsis than those admitted <24 h. Interpretation: Provision of recommended clinical care for leading causes of death among young children was suboptimal. Further studies are needed to understand the reasons for deficits in clinical care recommendation adherence. Funding: Bill & Melinda Gates Foundation.

Candida auris Clinical Isolates Associated with Outbreak in Neonatal Unit of Tertiary Academic Hospital, South Africa.

Candida auris was first detected at a university-affiliated hospital in Johannesburg, South Africa, in 2009. We used whole-genome sequencing to describe the molecular epidemiology of C. auris in the same hospital during 2016-2020; the neonatal unit had a persistent outbreak beginning in June 2019. Of 287 cases with culture-confirmed C. auris infection identified through laboratory surveillance, 207 (72%) had viable isolates and 188 (66%) were processed for whole-genome sequencing. Clade III (118/188, 63%) and IV (70/188, 37%) isolates co-circulated in the hospital. All 181/188 isolates that had a fluconazole MIC >32 µg/mL had ERG11 mutations; clade III isolates had VF125AL substitutions, and clade IV isolates had K177R/N335S/E343D substitutions. Dominated by clade III, the neonatal unit outbreak accounted for 32% (91/287) of all cases during the study period. The outbreak may have originated through transmission from infected or colonized patients, colonized healthcare workers, or contaminated equipment/environment.

High Prevalence of Candida auris Colonization during Protracted Neonatal Unit Outbreak, South Africa.

One third of patients were colonized by Candida auris during a point-prevalence survey in a neonatal unit during an outbreak in South Africa. The sensitivity of a direct PCR for rapid colonization detection was 44% compared with culture. The infection incidence rate decreased by 85% after the survey and implementation of isolation/cohorting.

Single surgeon case series of myelomeningocele repairs in a developing world setting: Challenges and lessons.

Purpose: Neural Tube Defects are the second most common group of birth malformations following congenital heart anomalies, with myelomeningoceles being the most severe manifestation (MMC). They require expedited surgical repair, preferably within 72 â€‹h of birth. In low- and middle-income countries (LMIC) where resources are limited, timing to MMC repair is not optimal and leads to undesirable outcomes. The purpose of this study was to determine whether a proactive approach in a setting from a LMIC could achieve repair within 72 â€‹h. Methods: A concerted effort to expedite repair of all neonates referred with a MMC was undertaken from 01 January 2014 to 1 August 2015. A consensus was reached between neonatologists and neurosurgeons that neonates born or admitted with a MMC are referred immediately to surgeons and that repair will be performed within 72 â€‹h of birth. Hospital records of neonates who had MMC repaired during this period were reviewed for infant characteristics and hospital outcomes. Results: 24 patients with a MMC were operated upon by the senior author (CP) during the study period. Only 13 of these patients were born at the treating institution and 11 were referred from outside hospitals. Most MMCs were in the lumbosacral region and mean MMC surface area was 19.4 â€‹cm2. Mean time to repair for the entire series was 13.6 days. Patients born at the treating institution has a mean time to repair of 10.5 days and patients referred from outside had a mean time to repair of 17.3 days. Series wide, only 21% of neonates were operated upon in less than 72 â€‹h. Conclusion: Despite a pro-active commitment to repairing MMCs within 72 â€‹h for the duration of this series, satisfactory time to repair was not achieved. Late referral, referral from outside hospitals and operating theatre availability were the predominant factors leading to delay in MMC repair. Nevertheless, time to repair in our series was significantly shorter than that reported in MMC repair series based in similar environments. This suggests that even if the gold-standard of a 72-h window cannot be achieved, neonates benefit from much quicker repair when a concerted effort to minimise repair time is employed. This study also highlights the urgent need to address health care constraints in LMIC to improve outcomes for this vulnerable group.

Characteristics and outcomes of neonates with intrapartum asphyxia managed with therapeutic hypothermia in a public tertiary hospital in South Africa.

BACKGROUND: In randomized clinical trials, therapeutic hypothermia (TH) has been shown to reduce death and/or moderate-to-severe disability in neonates with hypoxic ischemic encephalopathy (HIE) in high-income countries, while this has not consistently been the case in low-and middle-income countries (LMICs). Many studies reporting on outcomes of neonates with HIE managed with TH are those conducted under controlled study conditions, and few reporting in settings where this intervention is offered as part of standard of care, especially from LMICs. In this study we report on short-term outcomes of neonates with moderate-to-severe HIE where TH was offered as part of standard of care. OBJECTIVE: To determine characteristics and mortality rate at hospital discharge in neonates with moderate-to-severe HIE. METHODS: Hospital records of neonates with intrapartum asphyxia were reviewed for clinical findings, management with TH (cooled or non-cooled) and mortality at hospital discharge. Inclusion criteria were birthweight ≥ 1800 g, gestational age ≥ 36 weeks and moderate-to-severe HIE. Comparisons were made between survivors and non-survivors in cooled and/or non-cooled neonates. RESULTS: Intrapartum asphyxia was diagnosed in 856 neonates, with three having no recorded HIE status; 30% (258/853) had mild HIE, and 595/853 (69%) with moderate-to-severe HIE. The overall incidence of intrapartum asphyxia was 8.8/1000 live births. Of the 595 with moderate-to-severe HIE, three had no records on cooling and 67% (399/592) were cooled. Amongst 193 non-cooled neonates, 126 (67%) had documented reasons for not being cooled with common reasons being a moribund neonate (54.0%), equipment unavailability (11.1%), pulmonary hypertension (9.5%), postnatal age > 6 h on admission (8.7%), and improvement in severity of encephalopathy (8.7%). Overall mortality was 29.0%, being 17.0% and 53.4% in cooled and non-cooled infants respectively. On multivariate analysis, the only factor associated with mortality was severe encephalopathy. CONCLUSION: Overall mortality in neonates with moderate-to-severe HIE was 29.0% and 17.0% in those who were cooled. Cooling was not offered to all neonates mainly because of severe clinical illness, equipment unavailability and delayed presentation, making it difficult to assess overall impact of this intervention. Prospective clinical studies need to be conducted in LMIC to further assess effect of TH in short and long-term outcomes.

Antibiotics needed to treat multidrug-resistant infections in neonates.

Infections remain a leading cause of death in neonates. The sparse antibiotic development pipeline and challenges in conducting neonatal research have resulted in few effective antibiotics being adequately studied to treat multidrug-resistant (MDR) infections in neonates, despite the increasing global mortality burden caused by antimicrobial resistance. Of 40 antibiotics approved for use in adults since 2000, only four have included dosing information for neonates in their labelling. Currently, 43 adult antibiotic clinical trials are recruiting patients, compared with only six trials recruiting neonates. We review the World Health Organization (WHO) priority pathogens list relevant to neonatal sepsis and propose a WHO multiexpert stakeholder meeting to promote the development of a neonatal priority antibiotic development list. The goal is to develop international, interdisciplinary consensus for an accelerated neonatal antibiotic development programme. This programme would enable focused research on identified priority antibiotics for neonates to reduce the excess morbidity and mortality caused by MDR infections in this vulnerable population.

Les infections demeurent l'une des principales causes de décès chez les nouveau-nés. Les rares projets de développement d'antibiotiques et les défis posés par la recherche néonatale ont entraîné une pénurie d'antibiotiques efficaces spécialement étudiés pour traiter les infections multirésistantes (MR) chez les nouveau-nés, en dépit d'une mortalité galopante due à une résistance accrue aux antimicrobiens. Sur 40 antibiotiques autorisés pour les adultes depuis 2000, quatre à peine sont munis d'un étiquetage indiquant la posologie adaptée aux nouveau-nés. Actuellement, 43 essais cliniques portant sur des antibiotiques recrutent des patients du côté des adultes, contre six seulement du côté des nouveau-nés. Dans le présent document, nous passons en revue la liste prioritaire d'agents pathogènes établie par l'Organisation mondiale de la Santé (OMS) pour soigner la septicémie néonatale et proposons de réunir, sous l'égide de l'OMS, des parties prenantes issues de plusieurs domaines d'expertise afin de promouvoir la création d'une liste prioritaire de développement d'antibiotiques destinés aux nouveau-nés. Objectif: parvenir à un consensus international et interdisciplinaire visant à accélérer le programme de mise au point d'antibiotiques à usage néonatal. Ce programme permettrait d'orienter les recherches vers des antibiotiques identifiés comme prioritaires pour les nouveau-nés, en vue de faire baisser les taux de morbidité et de mortalité excessifs qu'engendrent les infections MR au sein de cette population vulnérable.

Las infecciones siguen siendo una de las principales causas de muerte en los recién nacidos. Debido al escaso desarrollo de los antibióticos y a las dificultades para llevar a cabo la investigación neonatal, son pocos los antibióticos eficaces que se estudian de manera adecuada para tratar las infecciones multirresistentes (MR) en los recién nacidos, a pesar de la creciente carga de mortalidad mundial causada por la resistencia a los antimicrobianos. De los 40 antibióticos aprobados para su uso en adultos desde el 2000, solo cuatro han incluido información sobre la dosis para recién nacidos en su etiquetado. En la actualidad, 43 ensayos clínicos con antibióticos para adultos están reclutando pacientes, en comparación con solo seis ensayos que reclutan recién nacidos. Se revisa la lista de patógenos prioritarios de la Organización Mundial de la Salud (OMS) relevantes para la sepsis neonatal y se propone una reunión de la OMS con múltiples expertos para promover el desarrollo de una lista de antibióticos prioritarios para los recién nacidos. El objetivo es desarrollar un consenso internacional e interdisciplinario para establecer un programa acelerado de desarrollo de antibióticos neonatales. Este programa permitiría centrar la investigación en los antibióticos prioritarios identificados para los recién nacidos con el fin de reducir el exceso de morbilidad y mortalidad causado por las infecciones MR en esta población vulnerable.

Prioritizing Health Care Strategies to Reduce Childhood Mortality.

Importance: Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking. Objective: To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network. Design, Setting, and Participants: This cross-sectional study used longitudinal, population-based, and mortality surveillance data collected by CHAMPS to understand preventable causes of death. Overall, 3390 eligible deaths across all 7 CHAMPS sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) between December 9, 2016, and December 31, 2021 (1190 stillbirths, 1340 neonatal deaths, 860 infant and child deaths), were included. Deaths were investigated using minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and fluids. Main Outcomes and Measures: For each death, an expert multidisciplinary panel reviewed case data to determine the plausible pathway and causes of death. If the death was deemed preventable, the panel identified which of 10 predetermined health system gaps could have prevented the death. The health system improvements that could have prevented the most deaths were evaluated for each age group: stillbirths, neonatal deaths (aged <28 days), and infant and child deaths (aged 1 month to <5 years). Results: Of 3390 deaths, 1505 (44.4%) were female and 1880 (55.5%) were male; sex was not recorded for 5 deaths. Of all deaths, 3045 (89.8%) occurred in a healthcare facility and 344 (11.9%) in the community. Overall, 2607 (76.9%) were deemed potentially preventable: 883 of 1190 stillbirths (74.2%), 1010 of 1340 neonatal deaths (75.4%), and 714 of 860 infant and child deaths (83.0%). Recommended measures to prevent deaths were improvements in antenatal and obstetric care (recommended for 588 of 1190 stillbirths [49.4%], 496 of 1340 neonatal deaths [37.0%]), clinical management and quality of care (stillbirths, 280 [23.5%]; neonates, 498 [37.2%]; infants and children, 393 of 860 [45.7%]), health-seeking behavior (infants and children, 237 [27.6%]), and health education (infants and children, 262 [30.5%]). Conclusions and Relevance: In this cross-sectional study, interventions prioritizing antenatal, intrapartum, and postnatal care could have prevented the most deaths among children younger than 5 years because 75% of deaths among children younger than 5 were stillbirths and neonatal deaths. Measures to reduce mortality in this population should prioritize improving existing systems, such as better access to antenatal care, implementation of standardized clinical protocols, and public education campaigns.

An outbreak of infection due to severe acute respiratory corona virus-2 in a neonatal unit from a low and middle income setting.

Introduction: The provision of kangaroo mother care (KMC) involving continuous skin-to-skin care (SSC) is an important intervention in neonatal care, which is recommended even when women are infected with severe acute respiratory syndrome coronavirus (SARS-CoV-2). We report on a nosocomial outbreak of SARS-CoV-2 infections in a KMC ward. Methods: Contact tracing was conducted following the diagnosis of SARS-CoV-2 in a mother lodging in the KMC ward. All mother-newborn dyads in the KMC and healthcare workers (HCW) were tested for SARS-CoV-2 within 24-72 h of diagnosing the index case. Nasopharyngeal swab samples were obtained and tested from contacts, with a nucleic acid amplification test (NAAT) assay. Next-generation sequencing was done on positive samples. The secondary attack rate (SAR) was calculated assuming that the mother who presented with symptoms was the source of infection. Results: Twelve (70.6%) of 17 mothers and 8 (42.1%) of 19 neonates who were in the KMC ward with the index case were found to be positive with SARS-CoV-2. Seven (87.5%) of the 8 neonates who tested positive had mothers who also tested positive. Seventy-five percent (9/12) of the mothers and 62.5% (5/8) of the neonates who tested positive were asymptomatic. Eight (27.6%) of 29 HCW were found to be positive and were all asymptomatic. One neonate died from Acinetobacter baumannii sepsis, and his post-mortem lung histopathology showed features compatible with SARS-CoV-2 pneumonia. The sequencing of 13 specimens, which included 1 mother-newborn dyad, indicated clustering to the same phylogenetic lineage with identical mutations. In assessing for factors contributing to this outbreak, it was found that spaces between beds were less than 1 m and mothers had their meals around the same table at the same time. Conclusion: We report on a nosocomial outbreak of SARS-CoV-2 in a KMC ward, affecting a high number of mothers and neonates, and to a lesser extent HCWs. Although it is difficult to point to the index case as the source of this outbreak, as asymptomatic individuals can spread infection, the inadequate adherence to non-pharmaceutical interventions was assessed to have contributed to the spread of infection. This highlights the need for awareness and adherence to mitigation strategies to avoid SARS-CoV-2 outbreaks.

Culture-confirmed neonatal bloodstream infections and meningitis in South Africa, 2014-19: a cross-sectional study.

BACKGROUND: Few population-level estimates of invasive neonatal infections have been reported from sub-Saharan Africa. We estimated the national incidence risk, aetiology, and pathogen antimicrobial susceptibility for culture-confirmed neonatal bloodstream infections and meningitis in South Africa. METHODS: We conducted a cross-sectional study of neonates (<28 days of life) admitted to neonatal or paediatric wards of 256 public sector health facilities in South Africa during 2014-19. Diagnostic pathology records from Jan 1, 2014, to Dec 31, 2019, were extracted from a national pathology data warehouse. A case was defined as a neonate with at least one positive blood or cerebrospinal fluid culture during a 14-day period. Incidence risk was calculated using annual numbers of registered livebirths. Among the causative pathogens identified, we calculated the proportion of cases attributed to each of them, as well as the rates of antibiotic susceptibility of Gram-positive and Gram-negative bacteria. FINDINGS: Among 43 438 records of positive cultures, there were 37 631 incident cases of neonatal infection with at least one pathogen isolated. The overall incidence risk of culture-confirmed infections was 6·0 per 1000 livebirths (95% CI 6·0-6·1). The incidence risk of late-onset sepsis (days 3-27 of life) was 4·9 per 1000 livebirths (4·9-5·0) and that of early-onset sepsis (days 0-2 of life) was 1·1 per 1000 livebirths (1·1-1·1); risk ratio 4·4 (95% CI 4·3-4·5). The cause of infection differed by syndrome, timing of infection onset, facility, and province, although Klebsiella pneumoniae (26%), Acinetobacter baumannii (13%), and Staphylococcus aureus (12%) were the dominant pathogens overall. Gram-negative bacteria had declining susceptibility to most antibiotics over the study period. INTERPRETATION: We found a high incidence risk of late-onset sepsis with provincial variations, predominance of K pneumoniae, and declining antibiotic susceptibility among Gram-negative bacteria. This national surveillance in an upper-middle-income country provides a baseline burden of neonatal infections against which the impact of future clinical and public health interventions can be measured. FUNDING: Bill & Melinda Gates Foundation.

Effect of Training Healthcare Providers in Helping Babies Breathe Program on Neonatal Mortality Rates.

Background: Training in the Helping Babies Breathe (HBB) Program has been associated with a reduction in early neonatal mortality rate (ENMR), the neonatal mortality rate (NMR), and fresh stillbirth rate (FSBR) in low- and middle-income countries (LMICs). This program was implemented in five different healthcare facilities in the Oliver Reginald Tambo (ORT) District, South Africa from September 2015 to December 2020. Objective: To determine and compare the FSBR, ENMR, and NMR between 2015 before initiation of the program (baseline) and subsequent years up to 2020 following the implementation of facility-based training of HBB in five hospitals in ORT District. Methods: Records of perinatal statistics from January 2015 to December 2020 were reviewed to calculate FSBR, ENMR, and NMR. Data were collected from the five healthcare facilities which included two district hospitals (Hospital A&B), two regional hospitals (Hospital C&D), and one tertiary hospital (Hospital E). Comparisons were made between pre- (2015) and post- (2016-2020) HBB implementation periods. Differences in changes over time were also assessed using linear regression analysis. Results: There were 19,275 births in 2015, increasing to 22,192 in 2020 with the majority (55.3%) of births occurring in regional hospitals. There were significant reductions in ENMR (OR-0.78, 95% CI 0.70-0.87) and NMR (OR-0.81, 95% CI 0.73-0.90), but not in FSBR, in the five hospitals combined when comparing the two time periods. Significant reduction was also noted in trends over time in ENMR (r 2 = 0.45, p = 0.001) and NMR (r 2 = 0.23, p = 0.026), but not in FSBR (r 2 = 0.0, p = 0.984) with all hospitals combined. In looking at individual hospitals, Hospital A (r 2 = 0.61, p < 0.001) and Hospital E (r 2 = 0.19, p = 0.048) showed a significant reduction in ENMR over time, but there were no significant changes in all mortality rates for Hospitals B, C, and D, and for the district or regional hospitals combined. Conclusion: There was an overall reduction of 22% and 19% in ENMR and NMR, respectively, from pre- to post-HBB implementation periods, although there were variations from year to year over the 5-year period and, across hospitals. These differences suggest that there were other factors that affected the perinatal/neonatal outcomes in the hospital sites in addition to the implementation of training in HBB.

Assessing Implementation of Helping Babies Breathe Program Through Observing Immediate Care of Neonates at Time of Delivery.

Background: Training in neonatal resuscitation has been shown to reduce deaths related to intrapartum asphyxia. Helping Babies Breathe (HBB) is a simulation-based program focusing on training healthcare providers (HCPs) in immediate neonatal care including stimulation, initiating bag mask ventilation (BMV) in the absence of breathing by 1 min of life, and delayed (30-60 s after birth) umbilical cord clamping (DCC). Data on implementation of HBB posttraining are limited. Objective: To determine time from birth to spontaneous breathing, cord clamping, and initiation of BMV in a setting where the majority of HCPs are HBB trained. Methods: Two research nurses observed deliveries conducted in two referral hospitals. Timing included the onset of breathing, cord clamping, and initiation of BMV. Deliveries were grouped according to the mode of delivery. Results: In total, 496 neonates were observed; 410 (82.7%) neonates cried or had spontaneous breathing (median time 17 s) soon after birth, 25/86 (29%) of neonates not breathing responded to stimulation, 61 (12.3%) neonates required BMV, and 2 (0.4%) neonates required chest compression and/or adrenalin. Neonates delivered by cesarean section (CS) took longer to initiate first breath than those delivered vaginally (median time 19 vs. 14 s; p = 0.009). Complete data were available in 58/61 (95%) neonates receiving BMV, which was initiated in 54/58 (93%) cases within 60 s of life (the "Golden Minute"). Median time to cord clamping was 74 s, with 414 (83.5%) and 313 (63.0%) having cord clamped at ≥ 30 and ≥ 60 s, respectively. Factors associated with BMV were CS delivery [odds ratio (OR) 29.9; 95% CI 3.37-229], low birth weight (LBW) (birthweight < 2,500 g) (OR 2.47; 95% CI 1.93-5.91), and 1 min Apgar score < 7 (OR 149; 95% CI 49.3-5,021). DCC (≥ 60 s) was less likely following CS delivery (OR 0.14; 95% CI 0.02-0.99) and being LBW (OR 0.43; 95% CI 0.24-0.77). Conclusion: Approximately 83% of neonates initiated spontaneous breathing soon after birth and 29% of neonates not breathing responded to physical stimulation. BMV was initiated within the Golden Minute in most neonates, but under two-thirds had DCC (≥60 s). HBB implementation followed guidelines, suggesting that knowledge and skills taught from HBB are retained and applied by HCP.

The association between early-onset sepsis and neonatal encephalopathy.

OBJECTIVE: We evaluated the association between early-onset sepsis and neonatal encephalopathy in a low-middle-income setting. METHODS: We undertook a retrospective study in newborns with gestational age ≥35 weeks and/or birth weight ≥2500 grams, diagnosed with neonatal encephalopathy. Early-onset sepsis was defined as culture-confirmed sepsis or probable sepsis. RESULTS: Of 10,182 hospitalised newborns, 1027 (10.1%) were diagnosed with neonatal encephalopathy, of whom 52 (5.1%) had culture-confirmed and 129 (12.5%) probable sepsis. The case fatality rate for culture-confirmed sepsis associated neonatal encephalopathy was threefold higher compared to neonatal encephalopathy without sepsis (30.8% vs. 10.5%, p < 0.001). Predictors of mortality for culture-confirmed sepsis associated neonatal encephalopathy included severe neonatal encephalopathy (aOR 6.51, 95%CI: 1.03-41.44) and seizures (aOR 10.64, 95%CI: 1.05-107.39). CONCLUSION: In this setting, 5% of neonatal encephalopathy cases was associated with culture-confirmed sepsis and a high case fatality rate.

Management of mothers and neonates in low resources setting during covid-19 pandemia.

The coronavirus disease (COVID-19) epidemic started in the Hubei province of China, but is rapidly spreading all over the world. Much of the information and literature have been centered on the adult population while a few reports pertaining to COVID-19 and neonates have been published so far. Actual guidelines are based on expert opinion and show significant differences among the official neonatal societies around the world. Recommendations for the care of neonates born to suspected or confirmed COVD-19 positive mothers in low-resource settings are very limited. This perspective aims to provide practical support for the planning of delivery, resuscitating, stabilizing, and providing postnatal care to an infant born to a mother with suspected or confirmed COVID-19 in low-resource settings where resources for managing emergency situations are limited.