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BACKGROUND: There are limited data on the epidemiology of sexually transmitted infections (STI) and their contribution to adverse birth outcomes (ABO) in sub-Saharan Africa (SSA). We performed a case-control study to assess the prevalence of STI and their association with ABO among women attending Queen Elizabeth Central Hospital, Blantyre, Malawi. METHODS: A composite case definition for ABO included stillborn, preterm and low birthweight infants and infants admitted to neonatal intensive care unit within 24 hours of birth. Following recruitment of an infant with an ABO, the next born healthy infant was recruited as a control. Multiplex PCR for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV) was performed on maternal vaginal swabs. HIV and syphilis status was determined on maternal and infant serum. For syphilis, we used combined treponemal/non-treponemal rapid point-of-care tests in parallel with rapid plasma reagin tests, PCR for Treponema pallidum and clinical parameters to diagnose and stage the infection. We compared STI positivity between cases and controls. RESULTS: We included 259 cases and 251 controls. Maternal prevalence of STI was 3.1%, 2.7% and 17.1% for NG, CT and TV, respectively. Maternal prevalence of untreated syphilis was 2.0% and 6.1% for early stage and late/unknown stage, respectively; prevalence of treated syphilis was 2.7%. The HIV prevalence was 16.5%. HIV infection significantly increased the odds for ABO (OR=3.31; 95% CI 1.10 to 9.91) as did NG positivity (OR=4.30; 95% CI 1.16 to 15.99). We observed higher rates of ABO among women with untreated maternal syphilis (early: OR=7.13; 95% CI 0.87 to 58.39, late/unknown stage: OR=1.43; 95% CI 0.65 to 3.15). Maternal TV and CT infections were not associated with ABO. CONCLUSION: STI prevalence among pregnant women in Malawi is comparable to other SSA countries. HIV, NG and untreated syphilis prevalence was higher among women with ABO compared with women with healthy infants.
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BACKGROUND: The emergence of COVID-19 precipitated containment policies (e.g., lockdowns, school closures, etc.). These policies disrupted healthcare, potentially eroding gains for Sustainable Development Goals including for neonatal mortality. Our analysis aimed to evaluate indirect effects of COVID-19 containment policies on neonatal admissions and mortality in 67 neonatal units across Kenya, Malawi, Nigeria, and Tanzania between January 2019 and December 2021. METHODS: The Oxford Stringency Index was applied to quantify COVID-19 policy stringency over time for Kenya, Malawi, Nigeria, and Tanzania. Stringency increased markedly between March and April 2020 for these four countries (although less so in Tanzania), therefore defining the point of interruption. We used March as the primary interruption month, with April for sensitivity analysis. Additional sensitivity analysis excluded data for March and April 2020, modelled the index as a continuous exposure, and examined models for each country. To evaluate changes in neonatal admissions and mortality based on this interruption period, a mixed effects segmented regression was applied. The unit of analysis was the neonatal unit (n = 67), with a total of 266,741 neonatal admissions (January 2019 to December 2021). RESULTS: Admission to neonatal units decreased by 15% overall from February to March 2020, with half of the 67 neonatal units showing a decline in admissions. Of the 34 neonatal units with a decline in admissions, 19 (28%) had a significant decrease of ≥ 20%. The month-to-month decrease in admissions was approximately 2% on average from March 2020 to December 2021. Despite the decline in admissions, we found no significant changes in overall inpatient neonatal mortality. The three sensitivity analyses provided consistent findings. CONCLUSION: COVID-19 containment measures had an impact on neonatal admissions, but no significant change in overall inpatient neonatal mortality was detected. Additional qualitative research in these facilities has explored possible reasons. Strengthening healthcare systems to endure unexpected events, such as pandemics, is critical in continuing progress towards achieving Sustainable Development Goals, including reducing neonatal deaths to less than 12 per 1000 live births by 2030.
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COVID-19 , Mortalidade Infantil , Análise de Séries Temporais Interrompida , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/mortalidade , Recém-Nascido , Tanzânia/epidemiologia , Quênia/epidemiologia , Mortalidade Infantil/tendências , Malaui/epidemiologia , Nigéria/epidemiologia , Admissão do Paciente/estatística & dados numéricos , Unidades de Terapia Intensiva Neonatal , Hospitalização/estatística & dados numéricos , Pandemias , LactenteRESUMO
We conducted a propensity score-matched multivariable regression analysis of 1050 culture-negative neonatal sepsis cases in Malawi, where 160 (15.2%) died. Mortality among neonates with culture-negative sepsis was associated with very low birth weight (adjusted OR (AOR) 12.82, 95% CI 1.23 to 137.49), respiratory distress syndrome (AOR 13.20, 95% CI 2.58 to 83.66), a low Apgar score at 1 min (AOR 3.50, 95% CI 1.21 to 10.72) and at 5 min (AOR 4.77, 95% CI 1.94 to 12.50). Addressing maternal and perinatal factors around health and delivery of care is key to improving outcomes in the context of culture-negative sepsis in neonates from low-income country settings like Malawi.
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Sepse Neonatal , Pontuação de Propensão , Humanos , Malaui/epidemiologia , Recém-Nascido , Sepse Neonatal/mortalidade , Feminino , Fatores de Risco , Masculino , Índice de Apgar , Recém-Nascido de muito Baixo Peso , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidadeRESUMO
BACKGROUND: While a systematic review exists detailing neonatal sepsis outcomes from clinical trials, there remains an absence of a qualitative systematic review capturing the perspectives of key stakeholders. OBJECTIVES: Our aim is to identify outcomes from qualitative research on any intervention to prevent or improve the outcomes of neonatal sepsis that are important to parents, other family members, healthcare providers, policymakers, and researchers as a part of the development of a core outcome set (COS) for neonatal sepsis. SEARCH STRATEGY: A literature search was carried out using MEDLINE, EMBASE, CINAHL, and PsycInfo databases. SELECTION CRITERIA: Publications describing qualitative data relating to neonatal sepsis outcomes were included. DATA COLLECTION AND ANALYSIS: Drawing on the concepts of thematic synthesis, texts related to outcomes were coded and grouped. These outcomes were then mapped to the domain headings of an existing model. MAIN RESULTS: Out of 6777 records screened, six studies were included. Overall, 19 outcomes were extracted from the included studies. The most frequently reported outcomes were those in the domains related to parents, healthcare workers and individual organ systemas such as gastrointestinal system. The remaining outcomes were classified under the headings of general outcomes, miscellaneous outcomes, survival, and infection. CONCLUSIONS: The outcomes identified in this review are different from those reported in neonatal sepsis clinical trials, thus highlighting the importance of incorporating qualitative studies into COS development to encapsulate all relevant stakeholders' perspectives.
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BACKGROUND: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. METHODS: We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. RESULTS: We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. CONCLUSIONS: Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.
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Infecções por Klebsiella , Klebsiella pneumoniae , Klebsiella pneumoniae/genética , Humanos , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Estudos Longitudinais , Vacinas Bacterianas/imunologia , Adulto , Feminino , Hospitais , Criança , Masculino , Pré-Escolar , Lactente , Pessoa de Meia-Idade , África Subsaariana/epidemiologia , Infecção Hospitalar/microbiologia , Adolescente , Genoma Bacteriano , Farmacorresistência Bacteriana Múltipla/genética , Recém-Nascido , Malaui/epidemiologia , Adulto JovemRESUMO
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.
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BACKGROUND: Data on SARS-CoV-2 infection in pregnancy and infancy has accumulated throughout the course of the pandemic, though evidence regarding asymptomatic SARS-CoV-2 infection and adverse birth outcomes are scarce. Limited information is available from countries in sub-Saharan Africa (SSA). The pregnant woman and infant COVID in Africa study (PeriCOVID Africa) is a South-South-North partnership involving hospitals and health centres in five countries: Malawi, Uganda, Mozambique, The Gambia, and Kenya. The study leveraged data from three ongoing prospective cohort studies: Preparing for Group B Streptococcal Vaccines (GBS PREPARE), SARS-CoV-2 infection and COVID-19 in women and their infants in Kampala and Mukono (COMAC) and Pregnancy Care Integrating Translational Science Everywhere (PRECISE). In this paper we describe the seroepidemiology of SARS-CoV-2 infection in pregnant women enrolled in sites in Uganda and Malawi, and the impact of SARS-CoV-2 infection on pregnancy and infant outcomes. OUTCOME: Seroprevalence of SARS-CoV-2 antibodies in maternal blood, reported as the proportion of seropositive women by study site and wave of COVID-19 within each country. METHODS: The PeriCOVID study was a prospective mother-infant cohort study that recruited pregnant women at any gestation antenatally or on the day of delivery. Maternal and cord blood samples were tested for SARS-CoV-2 antibodies using Wantai and Euroimmune ELISA. In periCOVID Uganda and Malawi nose and throat swabs for SARS-Cov-2 RT-PCR were obtained. RESULTS: In total, 1379 women were enrolled, giving birth to 1387 infants. Overall, 63% of pregnant women had a SARS-CoV-2 positive serology. Over subsequent waves (delta and omicron), in the absence of vaccination, seropositivity rose from 20% to over 80%. The placental transfer GMR was 1.7, indicating active placental transfer of anti-spike IgG. There was no association between SARS-CoV-2 antibody positivity and adverse pregnancy or infancy outcomes.
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COVID-19 , Complicações Infecciosas na Gravidez , Lactente , Humanos , Feminino , Gravidez , SARS-CoV-2 , Gestantes , COVID-19/epidemiologia , Estudos Prospectivos , Estudos Soroepidemiológicos , Malaui/epidemiologia , Estudos de Coortes , Uganda/epidemiologia , Placenta , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controleRESUMO
Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients' parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.
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Sepse Neonatal , Recém-Nascido , Humanos , Sepse Neonatal/terapia , Projetos de Pesquisa , Técnica Delphi , Consenso , Avaliação de Resultados em Cuidados de Saúde/métodos , Resultado do Tratamento , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Health system shocks are increasing. The COVID-19 pandemic resulted in global disruptions to health systems, including maternal and newborn healthcare seeking and provision. Yet evidence on mitigation strategies to protect newborn service delivery is limited. We sought to understand what mitigation strategies were employed to protect small and sick newborn care (SSNC) across 65 facilities Kenya, Malawi, Nigeria and Tanzania, implementing with the NEST360 Alliance, and if any could be maintained post-pandemic. METHODS: We used qualitative methods (in-depth interviews n=132, focus group discussions n=15) with purposively sampled neonatal health systems actors in Kenya, Malawi, Nigeria and Tanzania. Data were collected from September 2021 - August 2022. Topic guides were co-developed with key stakeholders and used to gain a detailed understanding of approaches to protect SSNC during the COVID-19 pandemic. Questions explored policy development, collaboration and investments, organisation of care, human resources, and technology and device innovations. Interviews were conducted by experienced qualitative researchers and data were collected until saturation was reached. Interviews were digitally recorded and transcribed verbatim. A common coding framework was developed, and data were coded via NVivo and analysed using a thematic framework approach. FINDINGS: We identified two pathways via which SSNC was strengthened. The first pathway, COVID-19 specific responses with secondary benefit to SSNC included: rapid policy development and adaptation, new and collaborative funding partnerships, improved oxygen systems, strengthened infection prevention and control practices. The second pathway, health system mitigation strategies during the pandemic, included: enhanced information systems, human resource adaptations, service delivery innovations, e.g., telemedicine, community engagement and more emphasis on planned preventive maintenance of devices. Chronic system weaknesses were also identified that limited the sustainability and institutionalisation of actions to protect SSNC. CONCLUSION: Innovations to protect SSNC in response to the COVID-19 pandemic should be maintained to support resilience and high-quality routine SSNC delivery. In particular, allocation of resources to sustain high quality and resilient care practices and address remaining gaps for SSNC is critical.
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COVID-19 , Telemedicina , Recém-Nascido , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Nigéria , MalauiRESUMO
BACKGROUND: Millions of newborns die annually from preventable causes, with the highest rates occurring in Africa. Reducing neonatal mortality requires investment to scale hospital care, which includes providing hospitals with appropriate technology to care for small and sick newborns. Expensive medical devices designed for high-resource settings often fail to withstand conditions in low-resource hospitals, including humidity, dust, frequent user turnover, complex maintenance, lack of stable power, or difficulty sourcing expensive consumables. Rigorous evaluation protocols are needed to identify effective, affordable, rugged, and easy-to-use medical devices appropriate for quality hospital-based newborn care in low-resource hospitals. METHODS: We developed an evidence-based technology review process to identify medical devices suitable for small and sick newborn care in low-resource hospitals. The eight-step process consists of: identifying devices needed for effective newborn care; defining Target Product Profiles (TPPs); identifying commercially-available products that may meet TPPs; conducting desk research to evaluate technologies against TPPs; performing technical performance verification testing under laboratory conditions; verifying technical performance after exposure to heat, humidity, dust, and power loss; performing usability evaluations with nurses, and qualifying devices that pass all steps. Devices were purchased, installed, and monitored in newborn wards across Kenya, Malawi, Nigeria, and Tanzania. RESULTS: Of 271 devices considered, only 45 (16.6%) met corresponding TPPs based on desk research. Thirty-nine were purchased and evaluated in the laboratory; five (12.8%) failed to meet TPPs. Thirty-four products passing laboratory evaluation underwent short-term environmental testing; only one (2.9%) device failed. Thirty-seven products underwent usability testing with 127 clinicians; surprisingly, 14 (37.8%) failed to meet TPPs. Twenty-three products passed all evaluations, and 2457 devices were installed across 65 newborn wards in Kenya, Malawi, Nigeria, and Tanzania. Continuous device monitoring reported minimal device failures, with failed devices typically returned to service within two days, resulting in an average uptime (service days divided by days installed) of 99%. CONCLUSION: An evidence-based device selection process can improve procurement of effective, affordable, rugged, usable newborn care devices for low-resource hospitals, and feedback to manufacturers can improve device quality. Similar processes could be adapted beyond newborn care to identify medical devices suitable for implementation in any low-resource setting.
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Cemitérios , Hospitais , Recém-Nascido , Humanos , Mortalidade Infantil , Quênia , PoeiraRESUMO
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.
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Países em Desenvolvimento , Pacientes Internados , Criança , Recém-Nascido , Gravidez , Humanos , Feminino , Qualidade da Assistência à Saúde , Parto , TanzâniaRESUMO
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.
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Antibacterianos , Hemocultura , Recém-Nascido , Humanos , Antibacterianos/uso terapêutico , Estudos Transversais , Quênia , Pacientes Internados , Malaui , Tanzânia , Nigéria , HospitaisRESUMO
Neonatal jaundice is an important cause of morbidity and mortality worldwide, and neonates born in low and middle-income countries bear a disproportionate burden. We previously developed a low-cost, point-of-care system to measure total serum bilirubin (TSB) in neonates. This device was effective at detecting and monitoring jaundice; however, the disposable strips were difficult to produce at scale. Here, we report a new lateral flow cassette design, called BiliDx, that was produced at scale using traditional manufacturing techniques. We evaluated the performance of BiliDx at sites in Nigeria and Malawi. The lateral flow strip consists of plasma separation membranes, nitrocellulose, and a plastic cassette. We evaluated the performance of the strips and reader at two hospitals located in Nigeria and Malawi compared to reference standard TSB. We also assessed performance for samples with high direct bilirubin (DB) and high hematocrit (HCT). We collected 1,144 samples from 758 neonates (TSB ranged from 0.2 to 45.9 mg/dL). The mean bias of BiliDx measurements in the validation set was +0.75 mg/dL, and 95% limits of agreement were -2.57 to 4.07 mg/dL. The mean bias and limits of agreement were comparable for samples with HCT < 60% and HCT ≥ 60%, and for samples with low and intermediate DB levels; the samples with high DB levels had wider 95% limits of agreement (-4.50 to +3.03 mg/dL). Error grid analysis shows that 96.9% of samples measured with BiliDx would have resulted in the same clinical decision as the reference standard. This performance is comparable to previous results that used a handmade two-dimensional strip. Additionally, error grid analysis shows that all 20 samples with high DB levels would have resulted in the same clinical decision as the reference standard. This evaluation supports the use of BiliDx lateral flow cassettes to provide accurate point-of-care measurements in low-resource settings.
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BACKGROUND: Bacteria of the order Enterobacterales are common pathogens causing bloodstream infections in sub-Saharan Africa and are frequently resistant to third-generation cephalosporin antibiotics. Although third-generation cephalosporin resistance is believed to lead to adverse outcomes, this relationship is difficult to quantify and has rarely been studied in this region. We aimed to measure the effects associated with resistance to third-generation cephalosporins in hospitalised patients with Enterobacterales bloodstream infection in Africa. METHODS: We conducted a prospective, matched, parallel cohort study at eight hospitals across sub-Saharan Africa. We recruited consecutive patients of all age groups with laboratory-confirmed Enterobacterales bloodstream infection and matched them to at least one patient without bloodstream infection on the basis of age group, hospital ward, and admission date. Date of infection onset (and enrolment) was defined as the day of blood sample collection for culturing. Patients infected with bacteria with a cefotaxime minimum inhibitory concentration of 1 mg/L or lower were included in the third-generation cephalosporin-susceptible (3GC-S) cohort, and the remainder were included in the third-generation cephalosporin-resistant (3GC-R) cohort. The primary outcomes were in-hospital death and death within 30 days of enrolment. We used adjusted multivariable regression models to first compare patients with bloodstream infection against matched patients within the 3GC-S and 3GC-R cohorts, then compared estimates between cohorts. FINDINGS: Between Nov 1, 2020, and Jan 31, 2022, we recruited 878 patients with Enterobacterales bloodstream infection (221 [25·2%] to the 3GC-S cohort and 657 [74·8%] to the 3GC-R cohort) and 1634 matched patients (420 [25·7%] and 1214 [74·3%], respectively). 502 (57·2%) bloodstream infections occurred in neonates and infants (age 0-364 days). Klebsiella pneumoniae (393 [44·8%] infections) and Escherichia coli (224 [25·5%] infections) were the most common Enterobacterales species identified. The proportion of patients who died in hospital was higher in patients with bloodstream infection than in matched controls in the 3GC-S cohort (62 [28·1%] of 221 vs 22 [5·2%] of 420; cause-specific hazard ratio 6·79 [95% CI 4·06-11·37] from Cox model) and the 3GC-R cohort (244 [37·1%] of 657 vs 115 [9·5%] of 1214; 5·01 [3·96-6·32]). The ratio of these cause-specific hazard ratios showed no significant difference in risk of in-hospital death in the 3GC-R cohort versus the 3GC-S cohort (0·74 [0·42-1·30]). The ratio of relative risk of death within 30 days (0·82 [95% CI 0·53-1·27]) also indicated no difference between the cohorts. INTERPRETATION: Patients with bloodstream infections with Enterobacterales bacteria either resistant or susceptible to third-generation cephalosporins had increased mortality compared with uninfected matched patients, with no differential effect related to third-generation cephalosporin-resistance status. However, this finding does not account for time to appropriate antibiotic treatment, which remains clinically important to optimise. Measures to prevent transmission of Enterobacterales could reduce bloodstream infection-associated mortality from both drug-resistant and drug-susceptible bacterial strains in Africa. FUNDING: Bill & Melinda Gates Foundation.
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Cefalosporinas , Sepse , Recém-Nascido , Humanos , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Estudos Prospectivos , Resistência às Cefalosporinas , Estudos de Coortes , Mortalidade Hospitalar , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Sepse/tratamento farmacológico , HospitaisRESUMO
Background: The location of Plasmodium falciparum within the body is determined by the life cycle of the parasite; young rings are in the peripheral blood, whereas mature parasites are sequestered in deep tissues. We can calculate a "ring ratio," the proportion of parasites in the periphery to the total number of parasites in the body. Artesunate acts on all parasite life stages, whereas quinine is effective only on sequestered parasites. Children with cerebral malaria (CM) treated with artesunate clear parasites faster than those treated with quinine. In this study, we established the relationship between ring ratio and parasite clearance rate and used the ring ratio to determine if the benefit derived from artesunate treatment could be attributed to its broader effect on life cycle stages. Methods: Ring ratios were calculated for 400 hospitalized children with CM in Blantyre, Malawi between 2010 and 2019 (quinine: 2010-2013, artesunate: 2014-2019). Results: In both treatment groups, parasite clearance rates were positively associated with the ring ratios, with a stronger association in the artesunate era than the quinine era. In the quinine era, an increase of 1-unit log10 difference between parasitemia and plasma P falciparum histidine-rich protein 2 (a proxy for ring ratio) resulted in a 0.27-unit increase in the parasite clearance rate, whereas in the artesunate era an equal increase resulted in a 0.41-unit increase (P = .04 for the difference). Conclusions: This analysis provides in vivo evidence supporting the hypothesis that more rapid parasite clearance rates in artesunate recipients are due to its superiority over quinine in killing ring-stage parasites.
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Background: To implement the immediate Kangaroo mother care (iKMC) intervention in the previous multicentre, open-label, randomised controlled trial, the mother or a surrogate caregiver and neonate needed to be together continuously, which led to the concept of the Mother-Newborn Care Unit (MNCU). Health-care providers and administrators were concerned of the potential increase in infections caused by the continuous presence of mothers or surrogates in the MNCU. We aimed to assess the incidence of neonatal sepsis in sub-groups and the bacterial profile among intervention and control neonates in the study population. Methods: This is a post-hoc analysis of the previous iKMC trial, which was conducted in five level 2 Newborn Intensive Care Units (NICUs) one each in Ghana, India, Malawi, Nigeria, and Tanzania, in neonates with birth weight 1 to <1.8 kg. The intervention was KMC initiated immediately after birth and continued until discharge and compared to conventional care with KMC initiated after meeting stability criteria. The primary outcomes of this report were the incidence of neonatal sepsis in sub-groups, sepsis-related mortality and bacterial profile of isolates during hospital stay. The original trial is registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12618001880235) and the Clinical Trials Registry-India (CTRI/2018/08/01536). Findings: Between November 30, 2017, and January 20, 2020, 1609 newborns in the intervention group and in the control group 1602 newborns were enrolled in iKMC study. 1575 newborns in the intervention group and 1561 in the control group were clinically evaluated for sepsis. Suspected sepsis was 14% lower in intervention group in sub-group of neonates with birth weight 1.0-<1.5 kg; RR 0.86 (CI 0.75, 0.99). Among neonates with birth weight 1.5-<1.8 kg, suspected sepsis was reduced by 24%; RR 0.76 (CI 0.62, 0.93). Suspected sepsis rates were lower in intervention group than in the control group across all sites. Sepsis related mortality was 37% less in intervention group than the control group; RR 0.63 (CI 0.47-0.85) which was statistically significant. The intervention group had fewer cases of Gram-negative isolates (n = 9) than Gram positive isolates (n = 16). The control group had more cases of Gram-negative isolates (n = 18) than Gram positive (n = 12). Interpretation: Immediate Kangaroo Mother care is an effective intervention to prevent neonatal sepsis and sepsis related mortality. Funding: The original trial was funded by the Bill and Melinda Gates Foundation through a grant to the World Health Organization (grant No. OPP1151718).
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Aim: To investigate the safety of skin-to-skin contact initiated immediately after birth on cardiorespiratory parameters in unstable low birth weight infants. Methods: A randomized clinical trial was conducted in tertiary newborn units in Ghana, India, Malawi, Nigeria and Tanzania in 2017-2020, in infants with birth weight 1.0-1.799 kg. The intervention was Kangaroo mother care initiated immediately after birth and continued until discharge compared to conventional care with Kangaroo mother care initiated after meeting stability criteria. The results of the primary study showed that immediate Kangaroo mother care reduced neonatal mortality by 25% and the results have been published previously. The post-hoc outcomes of this study were mean heart rate, respiratory rate, oxygen saturation during the first four days and the need of respiratory support. Results: 1,602 infants were allocated to control and 1,609 to intervention. Mean birth weight was 1.5 kg (SD 0.2) and mean gestational age was 32.6 weeks (SD 2.9). Infants in the control group had a mean heart rate 1.4 beats per minute higher (95% CI -0.3-3.1, p = 0.097), a mean respiratory rate 0.4 breaths per minute higher (-0.7-1.5, p = 0.48) and a mean oxygen saturation 0.3% higher (95% CI -0.1-0.7, p = 0.14) than infants in the intervention group. Conclusion: There were no significant differences in cardiorespiratory parameters during the first four postnatal days. Skin-to-skin contact starting immediately after birth is safe in low birth weight infants in limited-resource settings.
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Background: While breast milk is widely accepted as the best source of nutrients for almost all newborns, breastfeeding can be especially challenging for preterm and low birth weight (LBW) infants. With increased risk of admission to neonatal intensive care units (NICUs) and separation from parents, this population experiences significant barriers to successful breastfeeding. Thus, it is crucial to identify interventions that can optimize breastfeeding for preterm and LBW infants that is continued from birth and admission, through to hospital discharge and beyond. Objectives: To identify and analyze evidence-based interventions that promote any and exclusive breastfeeding among preterm and LBW neonates at discharge and/or postdischarge from hospital. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. Searches were performed in the following databases: MEDLINE Ovid, EMBASE, Web of Science, and Cumulative Index to Nursing and Allied Health (CINAHL). Results: From the 42 studies included, 6 groups of intervention types were identified: educational and breastfeeding support programs, early discharge, oral stimulation, artificial teats and cups, kangaroo mother care (KMC), and supportive policies within NICUs. All groupings of interventions were associated with significantly increased rates of any breastfeeding at discharge. All types of interventions except artificial teats/cups and oral stimulation showed statistically significant increases in exclusive breastfeeding at discharge. KMC demonstrated the highest increased odds of breastfeeding at discharge among preterm and LBW infants. Conclusions: A variety of effective interventions exist to promote breastfeeding among hospitalized preterm and LBW infants. Hospital settings hold unique opportunities for successful breastfeeding promotion. PROSPERO registration: CRD42021252610.