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Born too soon: accelerating change to 2030 and beyond.
Get PDFPROGRESS NEEDED: Preterm birth rates have "flatlined" for a decade with major loss of human capital, hindering progress for many Sustainable Development Goals. Progress on the reduction of maternal, newborn and child mortality needs to accelerate by between 3 and 11-fold to reach national and global targets by 2030. PRIORITIES: Actions are required on two tracks: (1) prevention of preterm birth, including better management for women in preterm labour, and (2) provision of high-quality care to vulnerable newborns, including those born into fragile and conflict-affected settings. Together these tracks have potential for high impact in terms of millions of lives saved, and socioeconomic returns on investment. We can and must do more to provide quality and respectful reproductive, antenatal and birth care for all adolescent girls and women, everywhere, and close unacceptable survival gaps for small and sick newborns. New focus is essential on threats beyond the health sector, notably conflict and the climate crisis. PIVOTS: The cost of inaction is too high in every country. Four pivots are central to accelerating action: invest, implement, integrate, and innovate. More specifically these pivots include investments in systems including more skilled human resources; implementation of high-impact interventions with data used for quality improvement and accountability; innovations including new health technologies and also systems and social innovations; plus, integration with levels of the health sector and across sectors and the life-course, with families at the centre. Everyone has a role to play. Increasing speed now, and sustaining progress, requires multi-level leadership including from grassroots movements led by parents and affected people through to heads of state. Some countries provide examples of such change: The United States of America in data identified inequalities by state and ethnicity for preterm birth. Importantly noting drops in donor aid, India has made ambitious investment in the health sector and beyond, and United Republic of Tanzania in multi-level leadership. Changing gears requires the ambition and energy witnessed a generation ago for HIV/AIDS. We have the ability now to ensure that every baby born too soon - and their mothers - can survive and thrive. Our next generation depends on us acting now for more healthy starts and hopeful futures
Epidemiology of Group B Streptococcus: Maternal Colonization and Infant Disease in Kampala, Uganda.
Get PDFBACKGROUND: Child survival rates have improved globally, but neonatal mortality due to infections, such as group B Streptococcus (GBS), remains a significant concern. The global burden of GBS-related morbidity and mortality is substantial. However, data from low and middle-income countries are lacking. Vaccination during pregnancy could be a feasible strategy to address GBS-related disease burden. METHODS: We assessed maternal rectovaginal GBS colonization and neonatal disease rates in a prospective cohort of 6062 women-infant pairs. Surveillance for invasive infant disease occurred in parallel at 2 Kampala hospital sites. In a nested case-control study, we identified infants <90 days of age with invasive GBS disease (iGBS) (n = 24) and healthy infants born to mothers colonized with GBS (n = 72). We measured serotype-specific anticapsular immunoglobulin G (IgG) in cord blood/infant sera using a validated multiplex Luminex assay. RESULTS: We found a high incidence of iGBS (1.0 per 1000 live births) within the first 90 days of life across the surveillance sites, associated with a high case fatality rate (18.2%). Maternal GBS colonization prevalence was consistent with other studies in the region (14.7% [95% confidence interval, 13.7%-15.6%]). IgG geometric mean concentrations were lower in cases than controls for serotypes Ia (0.005 vs 0.12 µg/mL; P = .05) and III (0.011 vs 0.036 µg/mL; P = .07) and in an aggregate analysis of all serotypes (0.014 vs 0.05 µg/mL; P = .02). CONCLUSIONS: We found that GBS is an important cause of neonatal and young infant disease in Uganda and confirmed that maternally derived antibodies were lower in early-onset GBS cases than in healthy exposed controls
Incidence of Scrub Typhus in Rural South India.
Get PDFBACKGROUND: Hospital studies suggest that scrub typhus is a leading cause of severe undifferentiated fever in regions across Asia where the disease is endemic, but the population-based incidence of infection and illness has been little studied. METHODS: We conducted a population-based cohort study to assess epidemiologic and clinical characteristics of scrub typhus in 37 villages in Tamil Nadu, India, where the disease is highly endemic. Study participants were visited every 6 to 8 weeks over a period of 2 years; a venous blood sample was obtained from those who had had fever since the last visit. A subcohort of participants underwent blood sampling to estimate the incidence of serologically confirmed Orientia tsutsugamushi infection. RESULTS: We systematically assessed 32,279 participants from 7619 households for acute febrile illness. During 54,588 person-years of follow-up, we observed 6175 episodes of fever. A blood sample was obtained in 4474 episodes (72.5%), of which 328 (7.3%) met the clinical case definition of scrub typhus (detection of IgM against O. tsutsugamushi on enzyme-linked immunosorbent assay [ELISA] or detection of O. tsutsugamushi on polymerase-chain-reaction assay). The incidence of clinical infection was 6.0 cases per 1000 person-years (95% confidence interval [CI], 4.8 to 7.5). A total of 71 clinical cases (21.6%) resulted in hospitalization (incidence, 1.3 events per 1000 person-years; 95% CI, 1.0 to 1.7). A total of 29 clinical cases (8.8%) were severe, as indicated by the presence of organ dysfunction or adverse pregnancy outcomes (incidence, 0.5 cases per 1000 person-years; 95% CI, 0.4 to 0.8). Among 2128 participants in the subcohort who provided samples at the beginning and end of a study year, the incidence of seroconversion independent of any symptoms was 81.2 events per 1000 person-years (95% CI, 70.8 to 91.6). The incidence of clinical infection was higher in older age groups than in younger age groups and higher among female participants than among male participants. By contrast, the age-adjusted rate of severe infection was similar among male and female participants. Among 5602 participants assessed at the start of the first year of the study, the seroprevalence of IgG as assessed with ELISA was 42.8% (95% CI, 35.8 to 50.2). IgG seropositivity at the beginning of years 1 or 2 did not protect against clinical illness during the subsequent year but was associated with less severe disease than IgG seronegativity. CONCLUSIONS: We describe the burden of scrub typhus, including the incidence of asymptomatic infection, in a region of Asia where the disease is endemic. (Funded by the U.K. Medical Research Council; ClinicalTrials.gov number, NCT04506944.)
Temporal complexity in missed doses of rifampicin-sensitive anti-tuberculosis treatment: a prospective cohort study in Tanzania.
Get PDFBACKGROUND: Non-adherence to anti-tuberculosis (TB) regimens is not simplistic; rather, doses are missed in complex patterns. In a cohort of individuals being treated for rifampicin-sensitive pulmonary TB in Tanzania, we sought to examine how doses were missed across the treatment course and within a day, as well as the reasons for missed dose periods. METHODS: 200 participants aged ≥18 years treated with the standard 6-month regimen were recruited from March 2022 to June 2023. Missed doses were measured using evriMED pillboxes and by pill count. The reasons for up to three missed dose periods per month were collected. Patterns of missed doses-across treatment and within a day-and their reasons were visualised and described. FINDINGS: Two participants died early in treatment, leaving 198 with missed dose data. The increase in the percentage of participants that missed any given dose as time progressed was driven by early discontinuation (median doses missed 0.0% in month 1 vs 6.7% in month 6) from treatment, as opposed to sporadic missed doses (median doses missed 3.1% in month 1 vs 4.1% in month 6). There was a median of one sporadic missed dose period (ranging between 0 and 42 doses in length) per participant. Out of all the reported reasons for missed dose periods, forgetting or forgetting and inconvenience were the most common (59.6%). INTERPRETATION: Missing doses of anti-TB treatment is a temporally complex phenomenon and the result of the intersection of multifaceted day-to-day events in an individual's life, with complicated implications for effective drug levels across the treatment course. This complexity limits our ability to predict an individual's missed doses at the start of treatment
Accounting for stillbirths in maternal health metrics: a cross-country analysis.
Get PDFBACKGROUND: Live birth is only one of four potential pregnancy outcomes, alongside stillbirth, miscarriage, and induced abortion. While morbidity and mortality associated with all pregnancy outcomes are included in the numerator of many maternal metrics, often only live births are included in the denominator. This inconsistency makes interpreting trends challenging and may exacerbate the deprioritisation of monitoring other pregnancy outcomes. We assess the effect of using (1) total births (live births and stillbirths) or (2) total pregnancies (total births plus miscarriages/induced abortions) as the denominator on estimates of maternal and pregnancy-related mortality ratios (MMR and PRMR). METHODS: Using data from Demographic and Health Surveys (DHS) conducted from 1996 to 2023, we estimated the proportion of pregnancies reported to end in live birth, stillbirth, or miscarriage/induced abortion in full pregnancy histories (DHS-VIII) or reproductive calendars (DHS-VII and earlier) for 46 countries in Africa, Asia, Latin American and the Caribbean, and Oceania. We calculated MMR and PRMR from the DHS sibling survival histories, adjusting the denominator by the reported distribution of pregnancy outcomes to account for either total births or total pregnancies. FINDINGS: There was substantial cross-country heterogeneity in the proportion of pregnancies reported as ending in a live birth, ranging from 70% (Cambodia 2021) to 96% (Papua New Guinea 2017). Pregnancies reported as ending in stillbirth ranged from 0.3% (Timor-Leste 2016) to 4.1% (Lesotho 2014). Variability across countries might reflect differences in the distribution of pregnancy outcomes, temporal trends, and reporting practices. These differences result in non-uniform biases from using live births as the denominator. Using total births reduced the MMR and PRMR by up to 2.8% (Cote-d'ivoire 2021). Using total pregnancies reduced the MMR and PRMR by up to 23% (Cambodia 2021). INTERPRETATION: Pregnancy-related morbidity and mortality can occur with any pregnancy outcome, not only live births. Progress in the availability of global stillbirth estimates means using total births as the denominator in maternal metrics is increasingly feasible in some countries and, in turn, could further strengthen momentum to institutionalise stillbirth reporting in civil registration systems. As the end of the SDG era approaches, the use of a more conceptually accurate maternal denominator based on total births should be explored in parallel with existing measures. However, better estimates of miscarriage and induced abortion are needed before total pregnancies can be used in global maternal metrics. FUNDING: UG and JW were supported by the UK Research and Innovation (EP/Y031172/1) and the Leverhulme Trust (RC-2018-003) for the Leverhulme Centre for Demographic Science. HES and LL were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD107015) and the Gates Foundation Child and Adolescent Causes of Death Estimation (CA-CODE, INV-038624)
Corticosteroids for treatment of leptospirosis.
No full textBACKGROUND: Leptospirosis is a bacterial disease caused by Leptospira spp, a zoonotic pathogen spread via contaminated soil and water. Corticosteroids have been used for the treatment or prevention of severe manifestations of disease, but the indications for their use and treatment efficacy remain uncertain. This review evaluates the existing evidence for the use of corticosteroids in leptospirosis from randomised trials. OBJECTIVES: To assess the benefits and harms of corticosteroids versus no intervention, no intervention beyond standard of care, or placebo for the treatment of people with leptospirosis. SEARCH METHODS: Electronic searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, and other resources were conducted. We searched online clinical trial registries to identify unpublished or ongoing trials, and reviewed reference lists from the identified publications for potential trials. We contacted authors of identified trials, relevant individuals, and organisations for additional information. The last search date was 10 April 2025. SELECTION CRITERIA: We considered the inclusion of randomised clinical trials of any trial design which assessed corticosteroids for the treatment of leptospirosis. We imposed no restrictions on age, sex, occupation, comorbidity of trial participants, or outcomes reported. We looked for trials assessing corticosteroids irrespective of type, route of administration, dosage, and schedule versus no intervention, placebo, or no intervention beyond standard care. We included trials meeting any of these criteria, irrespective of the manuscript's primary language. DATA COLLECTION AND ANALYSIS: We adhered to Cochrane methodology. Data entry and analysis were facilitated by the use of the Review Manager. The primary outcomes were all-cause mortality and the proportion of individuals experiencing serious adverse events. The secondary outcomes were quality of life, the proportion of individuals experiencing non-serious adverse events, days of hospitalisation, and the proportion of individuals experiencing Jarisch-Herxheimer reactions. We employed the risk of bias 2 tool (RoB 2) to assess the bias risk of included trials. We used the GRADEPro software to evaluate the certainty of evidence. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We applied a random-effects meta-analysis for the primary analysis and a fixed-effect model for the sensitivity analyses. Our primary outcome analyses included trial data at the longest follow-up. We analysed the outcome data regardless of the risk of bias. MAIN RESULTS: Four randomised trials were included in this review, with a pooled total of 253 participants. Each of the trials compared a corticosteroid (prednisolone, hydrocortisone, a combined treatment regimen of dexamethasone and prednisolone, or methylprednisolone) versus no intervention, no intervention beyond standard of care, or placebo. Participants in three trials received similarly administered co-interventions as standard of care, and had no further intervention in the fourth trial. All participants were recruited from populations presenting to general hospitals in leptospirosis endemic settings. The ages of the participants ranged from six years to 65 years. Depending on the trial, the treatment duration ranged from over four hours to seven days. All included trials were judged to have either some concerns or to be at high risk of bias. The certainty of evidence for all evaluated outcomes was judged to be very low. Quality of evidence was downgraded for risk of bias arising from the randomisation process, measurement of outcome, and selection of reporting of results; indirectness of evidence due to choice of intervention; inconsistency due to different point estimates and unexplained heterogeneity; and imprecision attributable to confidence intervals (CI) crossing clinically important thresholds, failure to meet optimal information size, or an upper/lower CI boundary more than three risk ratios. Corticosteroids compared with no intervention beyond standard of care or placebo may have little to no effect on all-cause mortality (RR 1.04, 95% CI 0.38 to 2.80, I2 = 0%, 3 trials, 123 participants, very low-certainty evidence) and on the proportion of individuals experiencing serious adverse events (RR 1.15, 95% CI 0.32 to 4.11, I2 = 62%, 3 trials, 123 participants, very low-certainty evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention beyond standard of care or placebo may increase the proportion of individuals experiencing non-serious adverse events (RR 2.00, 95% CI 0.21 to 18.98, 1 trial, 22 participants, very low-certainty evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention beyond standard of care or placebo may decrease the number of days of hospitalisation (MD 0.46, 95% CI -1.81 to 2.73, I2 = 83%, 3 trials, 123 participants, very low-certainty of evidence), but the evidence is very uncertain. Corticosteroids compared to no intervention may reduce the risk of Jarisch-Herxheimer reaction events (RR 0.13, 95% CI 0.04 to 0.41, 1 trial, 130 participants, very low-certainty evidence), but the evidence is very uncertain. None of the four trials assessed health-related quality of life. We have listed one trial registered as 'randomised' in studies awaiting classification because we could not identify further information. We have listed one trial in the ongoing section because trial recruitment has not yet started. AUTHORS' CONCLUSIONS: Based on the very low certainty of evidence attributable to our analyses, we do not know whether corticosteroids compared with no intervention, no intervention beyond standard of care, or placebo, reduce all-cause mortality, increase the risk of serious or non-serious adverse events, decrease days of hospitalisation, or decrease the proportion of people experiencing Jarisch-Herxheimer reaction events. None of the four trials assessed health-related quality of life. There is a lack of harmonised treatment strategies, clinically relevant outcome definitions, and definitive and rigorously designed randomised trials to support the use of corticosteroids for leptospirosis. Future research should focus on these evidence gaps
Adverse drug reactions, particularly liver disorders, drive interruptions in anti-tuberculosis treatment: A retrospective cohort study.
Get PDFAIMS: Adverse drug reactions (ADRs) are a key driver of missed doses of anti-tuberculosis (TB) therapy. We aimed to determine the relative burden of ADR-driven missed doses, the missed dose patterns associated with ADRs, and the association between specific ADRs and missed doses. METHODS: In this retrospective cohort study, adults (≥18 years) who began the standard 6-month drug-sensitive anti-TB regimen in an outpatient facility in Riga, Latvia (May 2015-September 2022) and missed at least one dose of treatment were included. Data were collected from medical records and observed therapy records. Missed doses were subdivided into early discontinuation or sporadically missed. Descriptive analyses and lasagne plots were used. RESULTS: Across 174 patients, 54 (31.0%, CI: 24.2-37.9%) missed doses due to ADRs. Of 31 320 doses, 4217 (13.5%, CI: 13.1-13.9%) were missed, 20.9% (880/4217, CI: 19.6-22.1%) were due to ADRs. Eighteen (10.3%) of the 174 patients discontinued treatment early, two of which (11.1%) were due to ADRs. Doses missed due to ADRs caused longer yet less frequent periods of sporadic missed doses: 56.4% (479/849) of sporadic missed doses were 1 day in length vs. only 9.1% (7/77) for ADR-related ones. Hepatobiliary disorders were the leading ADR group causing missed doses. Hepatobiliary ADRs caused long median durations of missed doses (median 15.0, CI: 13.0-22.0). CONCLUSION: Our study underscores the importance of ADRs as a cause of missed doses of treatment, particularly hepatobiliary disorders. Regimens that are less prone to ADRs and strong healthcare system support structures for patients with ADRs are required to minimize missed doses, reducing unfavourable outcomes
Geographic equity in essential newborn care practices in Ethiopia: a cross-sectional study.
Get PDFBACKGROUND: Essential newborn care is a set of measures every newborn baby needs, regardless of its birthplace. Geographic equity in essential newborn care refers to the fairness of access to newborn care across different regions. These practices vary across different social groups, but evidence on the geographic equity of newborn care in Ethiopia is scarce. We aimed to assess the geographic distribution and equity of selected essential newborn care practices (initial skin-to-skin care, delayed bathing, proper cord care, timely breastfeeding initiation, and immunizations of BCG and first-dose polio vaccines) recommended by the World Health Organization among neonates born at health facilities and homes in Ethiopia. METHODS: We analyzed cross-sectional survey data from 2,493 neonates in the Performance Monitoring for Action (PMA) Ethiopia 2019-2020 survey in five regions and the Addis Ababa City Administration. The survey employed a cross-sectional study design, and the data were collected from 2019 to 2020. We studied the geographic variation of selected essential newborn care practices using Global Moran's I statistics and hot and cold spot analysis (Local Getis-Ord Gi* statistic), and the coverage of these practices were predicted for the whole country using Kriging interpolation. RESULTS: This study showed that selected essential newborn care practices were higher among neonates in health facilities, those born in Central, Northern, Southern, and a few areas in Southwest and Northwest Ethiopia. Geographic inequities were demonstrated in delayed bathing in facility and home births, proper cord care in facility births, and first immunizations in both facility and home births. Geographic inequities were not observed for initial skin-to-skin care and timely breastfeeding initiation. CONCLUSION: Selected essential newborn care practices were higher among neonates born in health facilities, and the recommended essential newborn care practices were higher in Central and Northern Ethiopia. There were geographic inequities in delayed bathing and immunizations of BCG and first-dose polio vaccines among neonates born in health facilities and homes. Enhancing facility delivery, availing first vaccinations in facilities, and improving discharge counseling for mothers during antenatal, delivery, and postnatal care are crucial to ensuring geographic equity in essential newborn care in Ethiopia
Genomic insights into Klebsiella pneumoniae: Virulence, resistance, and transmission in South and Southeast Asia.
Get PDFBACKGROUND: Klebsiella pneumoniae has long posed a significant challenge in clinical settings worldwide, particularly due to its carbapenemase production and multidrug-resistant (MDR) characteristics. While extensive genomic studies of K. pneumoniae have been conducted globally, research in Asia, particularly South Asia, remains limited. OBJECTIVES: This study aims to address and compare the genomic characteristics of K. pneumoniae isolates from South Asia and Southeast Asia, including virulence, antimicrobial resistance (AMR), plasmids, and mobile genetic elements (MGE) profiles, as well as potential transmission dynamics. METHODS: A total of 463 K. pneumoniae genomes were included from collected samples and public databases. All genomes underwent comprehensive analysis, including pan-genome profiling, multi-locus sequence typing (MLST), annotation of virulence factors, AMR genes, plasmids, and MGEs, as well as SNP distance-based analysis to infer transmission dynamics, using established bioinformatic tools. RESULTS: K. pneumoniae isolates exhibited diverse virulence determinants. Hypervirulent isolates were primarily associated with ST23 and ST86, and commonly harbour aerobactin, salmochelin, and rmpA. The majority of isolates were predicted to be MDR, with those from Southeast Asia showing a higher relative abundance of AMR genes associated with the antibiotic classes examined in this study. Among all isolates, the predominant carbapenemase-associated gene was blaNDM-1. Col440I_1 was the most prevalent plasmid replicon, although it did not co-occur with any AMR genes. Association between the IncFII_1_pKP9 plasmid replicon and resistance genes sul-5, blaCTX-M, and blaTEM was found. ISSen9 was the dominant MGE, frequently co-occurring with the plasmid replicons IncFIB(K)_1_Kpn3 and IncFII_1_pKP91. Transmission analysis indicated that the highest isolate similarity occurred within MLST and country. However, clustering based on plasmid replicon profiles revealed that some clusters comprised isolates from multiple countries. CONCLUSION: This study provides a comprehensive analysis of the genomic characteristics and transmission patterns of K. pneumoniae in South and Southeast Asia, contributing to our understanding of its virulence and resistance mechanisms. These findings further suggest that plasmid replicons may play a critical role in shaping transmission dynamics and provide valuable insights to inform future AMR surveillance and control strategies
Profiling insecticide resistance phenotypes and genotypes in Aedes aegypti populations across four regions in Puerto Rico.
Get PDFVector-borne diseases exert a considerable toll on global health. The efficacy of vector control strategies is being threatened by the emergence and spread of insecticide resistance worldwide. In this study, we collected Aedes aegypti mosquitoes from five regions of Puerto Rico to investigate their insecticide resistance phenotypes and genotypes. Insecticide resistance intensity CDC bioassays were employed to determine the response to deltamethrin and malathion. In parallel, next generation targeted amplicon sequencing was used to investigate the presence of insecticide resistance-conferring mutations in nine targets across four genes: the voltage gated sodium channel (vgsc); GABA receptor (resistance to dieldrin, rdl); acetylcholinesterase (ace-1); and glutathione-S-transferase epsilon 2 (GSTe2). We observed high resistance intensity to deltamethrin and malathion in Ae. aegypti mosquitoes Resistance was supported by molecular evidence revealing five mutations (V410L (vgsc), V1016I/G (vgsc), F1534C (vgsc), A296S (rdl)), previously linked to insecticide resistance. A previously undocumented mutation, L944I (L921I in Ae. aegypti, vgsc), was identified. While not yet reported in Aedes spp. vectors, this mutation has been associated with pyrethroid resistance in other medically important vectors and agricultural pests. Our research highlights the presence of insecticide resistance and associated mutations in Puerto Rico, which is valuable for vector control programs, providing information to guide decisions regarding the implementation of effective control interventions