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Measles deaths highlight immunization program gaps. In the Child Health and Mortality Prevention Surveillance study in Mali, we observed a rise in under-5 measles-related deaths in 2022 that corresponded with increased measles cases at the same time and a decline in measles vaccine coverage in Mali in 2020. [ABSTRACT FROM AUTHOR]

Background The Enterics for Global Health (EFGH) Peru site will enroll subjects in a periurban area of the low Amazon rainforest. The political department of Loreto lags behind most of Peru in access to improved sources of water and sanitation, per capita income, children born <2.5 kg, and infant and child mortality. Chronic undernutrition as manifested by linear growth shortfalls is common, but wasting and acute malnutrition are not. Methods The recruitment of children seeking care for acute diarrheal disease takes place at a geographic cluster of government-based primary care centers in an area where most residents are beneficiaries of free primary healthcare. Results Rates of diarrheal disease, dysentery, and Shigella are known to be high in the region, with some of the highest rates of disease documented in the literature and little evidence in improvement over the last 2 decades. This study will update estimates of shigellosis by measuring the prevalence of Shigella by polymerase chain reaction and culture in children seeking care and deriving population-based estimates by measuring healthcare seeking at the community level. Conclusions Immunization has been offered universally against rotavirus in the region since 2009, and in a context where adequate water and sanitation are unlikely to obtain high standards in the near future, control of principal enteropathogens through immunization may be the most feasible way to decrease the high burden of disease in the area in the near future. [ABSTRACT FROM AUTHOR]

Background Respiratory viral infections are common among pediatric transplant patients, with human rhinovirus (HRV) being the most frequent. In pediatric patients undergoing hemopoietic cell transplant (HCT), infection with HRV has been associated with progression to lower respiratory tract infection (LRTI) and adverse outcomes. We describe the clinical presentation and outcomes of HRV infection in children undergoing HCT. Methods Single-center retrospective study. HCT recipients who were positive for HRV/EV (HRV+) or negative for any respiratory virus (VN) by BioFire® FilmArray® panel between October 2014 and December 2017, were included. Primary outcomes were progression to LRTI, ICU admission, all-cause mortality at 3 and 6 months, and respiratory event-related mortality at 6 months. Results 227 patients (160 allogeneic HCT) were included. Of all patients, 108/227 (47.6%) were HRV+. From all HRV+, 95/108 (88%) were symptomatic and 68/107 (63.6%) of the diagnosis were made pretransplant. The median age of HRV+ was significantly lower than VN patients (5 vs 10 years). Cough and rhinorrhea were more frequently observed in HRV+ (53.7 and 60% vs 19.8 and 22.8%, respectively). No differences were found between both groups pretransplant and overall in rates progression to LRTI, ICU admission, mechanical ventilation, all-cause within 3 and 6 months, and mortality related with respiratory failure. No significant association was found between the severity of respiratory disease and the type of conditioning, type of transplant, or absolute lymphocyte count. Conclusions HRV infection is frequently detected in HCT recipients but is not associated with severity of respiratory disease, need for intensive care unit or mortality, including those diagnosed before transplant, suggesting that delaying HCT in this scenario may not be needed. Multicenter larger studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background COVID-19 pandemic measures resulted in the de-escalation of non-COVID-19 healthcare provision. Methods A retrospective cross-sectional study of routinely collected data was done to investigate the effect of COVID-19 policies on the healthcare utilization and mortality of children younger than 5 years in Eastern Cape Town, South Africa. We compared visits to primary and urgent care facilities, hospitalization, in-hospital deaths, and vaccine uptake from 1 January to 31 December 2020 to similar periods in 2018 and 2019. Results During April and May 2020, the most restricted period, visits to primary care facilities declined from 126 049 in 2019 to 77 000 (1.8-fold; p  < 0.05). This corresponded with a 1.2-fold reduction in the provision of the first dose of measles vaccine at 6 months compared to 2019. Throughout 2020 there was a 4-fold decline in the number of fully immunized children at 1 year of age (p  = 0.84). Emergency room visits fell by 35.7% in 2020 (16 368) compared to 2019 (25 446). Hospital admissions decreased significantly (p  < 0.01) in 2020 (9810) compared to 2018 (11 698) and 2019 (10 247). The in-hospital mortality rate increased from 2.3% (96/4163) in 2019 to 3.8% (95/2498) (p  < 0.01) in Tygerberg Hospital, where 80% (95/119) of deaths were recorded. Twelve of the 119 (10%) deaths occurred in HIV-positive children (p  = <0.01). Conclusion Measures instituted during the COVID-19 pandemic disrupted access to healthcare services for children. This resulted in an immediate, and potential future, indirect effect on child morbidity and mortality in Cape Town. [ABSTRACT FROM AUTHOR]

Background According to the United Nations, the third Sustainable Development Goal, 'Ensure Healthy Lives and Promote Well-Being at All Ages', set numerous targets on child and maternal health. Universal health insurance is broadly seen as a solution to fulfil these targets. West Africa is known to have the most severe maternal mortality and under-five mortality rates in the world. This review seeks to understand whether health insurance provides increased access to services for mothers and children in this region. Methods The protocol for this review is registered in the International Prospective Register of Systematic Reviews database (CRD42020203859). A search was conducted in the MEDLINE Complete, Embase, CINAHL Complete and Global Health databases. Eligible studies were from West African countries. The population of interest was mothers and children and the outcome of interest was the impact of health insurance on access to services. Data were extracted using a standardized form. The primary outcome was the impact of health insurance on the rate of utilization and access to services. The Joanna Briggs Institute Critical Appraisal Tool was used for methodological assessment. Results Following screening, we retained 49 studies representing 51 study settings. In most study settings, health insurance increased access to child and maternal health services. Other determinants of access were socio-economic factors such as wealth and education. Conclusions Our findings suggest that health insurance may be a viable long-term strategy to alleviate West Africa's burden of high maternal and child mortality rates. An equity lens must guide future policy developments and significant research is needed to determine how to provide access reliably and sustainably to services for mothers and children in the near and long term. [ABSTRACT FROM AUTHOR]

Background The grandmother is an important kin member whose contribution to childcare and survival has been recognized in the literature, hence the Grandmother Hypothesis. This article examines the effect of the presence of a grandmother on child mortality. Methods Data were obtained from the Navrongo Health and Demographic Surveillance System, located in the Upper East Region of Ghana. Children born between January 1999 and December 2018 were included in the analysis. Person-months lived for each child were generated. The multilevel Poisson regression technique was employed to investigate the effect of a grandmother on child survival. Results In all, 57 116 children were included in the analysis, of which 7% died before age 5 y. Person-months were generated for the children, which produced 2.7 million records, with about 487 800 person-years. After controlling for confounders, results showed that children in households with paternal grandmothers are 11% less likely to die compared with those without paternal grandmothers. However, when other confounders were taken into accounts, the beneficial effect of maternal grandmothers disappeared. Conclusions We conclude that the presence of grandmothers improves child survival, thus sustaining the Grandmother Hypothesis. The experiences of these grandmothers should be tapped to improve child survival, particularly in rural areas. [ABSTRACT FROM AUTHOR]

Background Diarrhea is the second leading cause of death in children under 5 years old worldwide. Known diarrhea risk factors include sanitation, water sources, and pathogens but do not fully explain the heterogeneity in frequency and duration of diarrhea in young children. We evaluated the role of host genetics in diarrhea. Methods Using 3 well-characterized birth cohorts from an impoverished area of Dhaka, Bangladesh, we compared infants with no diarrhea in the first year of life to those with an abundance, measured by either frequency or duration. We performed a genome-wide association analysis for each cohort under an additive model and then meta-analyzed across the studies. Results For diarrhea frequency, we identified 2 genome-wide significant loci associated with not having any diarrhea, on chromosome 21 within the noncoding RNA AP000959 (C allele odds ratio [OR] = 0.31, P = 4.01 × 10−8), and on chromosome 8 within SAMD12 (T allele OR = 0.35, P = 4.74 × 10−7). For duration of diarrhea, we identified 2 loci associated with no diarrhea, including the same locus on chromosome 21 (C allele OR = 0.31, P = 1.59 × 10−8) and another locus on chromosome 17 near WSCD1 (C allele OR = 0.35, P = 1.09 × 10−7). Conclusions These loci are in or near genes involved in enteric nervous system development and intestinal inflammation and may be potential targets for diarrhea therapeutics. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Populations that are reliant on subsistence farming are particularly vulnerable to climatic effects on crop yields. However, empirical evidence on the role of the timing of exposure to crop yield deficits in early-life development is limited. We examined the relationship between child survival and annual crop yield reductions at different stages of early-life development in a subsistence farming population in Burkina Faso. Using shared frailty Cox proportional hazards models adjusting for confounders, we analyzed 57,288 children under 5 years of age followed by the Nouna Health and Demographic Surveillance System (1994–2016) in relation to provincial food-crop yield levels experienced in 5 nonoverlapping time windows (12 months before conception, gestation, birth–age 5.9 months, ages 6.0 months–1.9 years, and ages 2.0–4.9 years) and their aggregates (birth–1.9 years, first 1,000 days from conception, and birth–4.9 years). Of the nonoverlapping windows, point estimates were largest for child survival related to food-crop yields for the time window of 6.0 months–1.9 years: The adjusted mortality hazard ratio was 1.10 (95% confidence interval: 1.03, 1.19) for a 90th-to-10th percentile yield reduction. These findings suggest that child survival in this setting is particularly vulnerable to cereal-crop yield reductions during the period of nonexclusive breastfeeding. [ABSTRACT FROM AUTHOR]

Background Drowning is the leading cause of death for children under the age of 15 years in Guangdong Province, China. This serious public health issue also exists in low- and middle-income countries (LMICs), which have few value-integrated intervention programs. The current study presents an integrated intervention project that aims to explore an effective pattern of prevention for child drowning in rural areas and feasibility to perform in other LMICs. Methods We conducted a cluster randomized controlled trial by comparing the incidence of non-fatal drowning among children in two groups in rural areas of southern China. We recruited the participants in two phases and reached a total of 10 687 students from 23 schools at two towns in Guangdong Province, China. At the first and second phases, 8966 and 1721 students were recruited, respectively. Results The final evaluation questionnaires were collected after 18 months of integrated intervention, where we obtained 9791 data from Grades 3–9. The incidence of non-fatal drowning between the intervention and control groups after intervention did not differ significantly from the baseline according to the total number of students, male students, female students and Grades 6–9 [0.81; 95% confidence interval (CI): [0.66, 1.00]; p  =   0.05, 1.17; 95% CI: [0.90, 1.51]; p  =   0.25, 1.40; 95% CI: [0.97, 2.02]; p  =   0.07 and 0.97; 95% CI: [0.70, 1.34]; p  =   0.86], except for Grades 3–5 (1.36; 95% CI: [1.02, 1.82]; p  =   0.037). The study observed a significantly positive benefit of awareness and risk behaviours of non-fatal drowning between the intervention and control groups (0.27, 95% CI: [0.21, 0.33]; p  =   0.00, −0.16; 95% CI: [−0.24, −0.08]; p  =   0.00). Conclusions The integrated intervention exerted a significant impact on the prevention and management of child non-fatal drowning, especially in rural areas. [ABSTRACT FROM AUTHOR]

Background Changing causes of deaths in the mortality transition in Papua New Guinea (PNG) are poorly understood. This study analysed community-level data to identify leading causes of death in the population and variations across age groups and sexes, urban-rural sectors and provinces. Method Mortality surveillance data were collected from 2018–20 as part of the Comprehensive Health and Epidemiological Surveillance System (CHESS), using the World Health Organization 2016 verbal autopsy (VA) instrument. Data from 926 VA interviews were analysed, using the InterVA-5 cause of death analytical tool to assign specific causes of death among children (0–14 years), those of working age (15–64 years) and the elderly (65+ years). Result Nearly 50% of the total deaths were attributed to non-communicable diseases (NCDs), followed by infectious and parasitic diseases (35%), injuries and external causes (11%) and maternal and neonatal deaths (4%). Leading causes of death among children were acute respiratory tract infections (ARTIs) and diarrhoeal diseases, each contributing to 13% of total deaths. Among the working population, tuberculosis (TB) contributed to 12% of total deaths, followed by HIV/AIDS (11%). TB- and HIV/AIDS-attributed deaths were highest in the age group 25–34 years, at 20% and 18%, respectively. These diseases killed more females of working age (n  = 79, 15%) than males (n  = 52, 8%). Among the elderly, the leading causes of death were ARTIs (13%) followed by digestive neoplasms (10%) and acute cardiac diseases (9%). Conclusion The variations in leading causes of death across the populations in PNG suggest diversity in mortality transition. This requires different strategies to address specific causes of death in particular populations. [ABSTRACT FROM AUTHOR]

Background: Statistical modeling suggests that decreasing diarrhea-associated mortality rates in recent decades are largely attributed to improved case management, rotavirus vaccine, and economic development. Methods: We examined data collected in 2 multisite population-based diarrhea case-control studies, both conducted in The Gambia, Kenya, and Mali: the Global Enteric Multicenter Study (GEMS; 2008–2011) and Vaccine Impact on Diarrhea in Africa (VIDA; 2015–2018). Population-level diarrhea mortality and risk factor prevalence, estimated using these study data, were used to calculate the attribution of risk factors and interventions for diarrhea mortality using a counterfactual framework. We performed a decomposition of the effects of the changes in exposure to each risk factor between GEMS and VIDA on diarrhea mortality for each site. Results: Diarrhea mortality among children under 5 in our African sites decreased by 65.3% (95% confidence interval [CI]: –80.0%, −45.0%) from GEMS to VIDA. Kenya and Mali had large relative declines in diarrhea mortality between the 2 periods with 85.9% (95% CI: −95.1%, −71.5%) and 78.0% (95% CI: −96.0%, 36.3%) reductions, respectively. Among the risk factors considered, the largest declines in diarrhea mortality between the 2 study periods were attributed to reduction in childhood wasting (27.2%; 95% CI: −39.3%, −16.8%) and an increased rotavirus vaccine coverage (23.1%; 95% CI: −28.4%, −19.4%), zinc for diarrhea treatment (12.1%; 95% CI: −16.0%, −8.9%), and oral rehydration salts (ORS) for diarrhea treatment (10.2%). Conclusions: The VIDA study sites demonstrated exceptional reduction in diarrhea mortality over the last decade. Site-specific differences highlight an opportunity for implementation science in collaboration with policymakers to improve the equitable coverage of these interventions globally. We demonstrated exceptional reduction in diarrhea mortality over a decade. Among the risk factors considered, the largest declines in diarrhea mortality were attributed to reduction in childhood wasting and an increased rotavirus vaccine coverage, zinc, and oral rehydration salts for diarrhea treatment. [ABSTRACT FROM AUTHOR]

Background Rotavirus vaccine performance appears worse in countries with high rotavirus genotype diversity. Evidence suggests diminished vaccine efficacy (VE) against G2P[4], which is heterotypic with existing monovalent rotavirus vaccine formulations. Most studies assessing genotype-specific VE have been underpowered and inconclusive. Methods We pooled individual-level data from 10 Phase II and III clinical trials of rotavirus vaccine containing G1 and P[8] antigens (RV1) conducted between 2000 and 2012. We estimated VE against both any-severity and severe (Vesikari score ≥11) rotavirus gastroenteritis (RVGE) using binomial and multinomial logistic regression models for non-specific VE against any RVGE, genotype-specific VE, and RV1-typic VE against genotypes homotypic, partially heterotypic, or fully heterotypic with RV1 antigens. We adjusted models for concomitant oral poliovirus and RV1 vaccination and the country's designated child mortality stratum. Results Analysis included 87 644 infants from 22 countries in the Americas, Europe, Africa, and Asia. For VE against severe RVGE, non-specific VE was 91% (95% confidence interval [CI]: 87–94%). Genotype-specific VE ranged from 96% (95% CI: 89–98%) against G1P[8] to 71% (43–85%) against G2P[4]. RV1-typic VE was 92% (95% CI: 84–96%) against partially heterotypic genotypes but 83% (67–91%) against fully heterotypic genotypes. For VE against any-severity RVGE, non-specific VE was 82% (95% CI: 75–87%). Genotype-specific VE ranged from 94% (95% CI: 86–97%) against G1P[8] to 63% (41–77%) against G2P[4]. RV1-typic VE was 83% (95% CI: 72–90%) against partially heterotypic genotypes but 63% (40–77%) against fully heterotypic genotypes. Conclusions RV1 VE is comparatively diminished against fully heterotypic genotypes including G2P[4]. [ABSTRACT FROM AUTHOR]

Background Current malaria diagnostic tests do not reliably identify children at risk of severe and fatal infection. Host immune and endothelial activation contribute to malaria pathogenesis. Soluble urokinase-type plasminogen activator receptor (suPAR) is a marker of these pathways. We hypothesized that measuring suPAR at presentation could risk-stratify children with malaria. Methods Plasma suPAR levels were determined in consecutive febrile children with malaria at presentation to hospital in Jinja, Uganda. We evaluated the accuracy of suPAR in predicting in-hospital mortality, and whether suPAR could improve a validated clinical scoring system (Lambaréné Organ Dysfunction Score [LODS]). Results Of the 1226 children with malaria, 39 (3.2%) died. suPAR concentrations at presentation were significantly higher in children who went on to die than in those who survived (P <.0001). suPAR levels were associated with disease severity (LODS: 0 vs 1, P =.001; 1 vs 2, P <.001; 2 vs 3, 0 vs 2, 1 vs 3, and 0 vs 3, P <.0001). suPAR concentrations were excellent predictors of in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.92 [95% confidence interval {CI},.91–.94]). The prognostic accuracy of LODS (AUROC, 0.93 [95% CI,.91–.94]) was improved when suPAR was added (AUROC, 0.97 [95% CI,.96–.98]; P <.0001). Conclusions Measuring suPAR at presentation can identify children at risk of severe and fatal malaria. Adding suPAR to clinical scores could improve the recognition and triage of children at risk of death. suPAR can be detected with a point-of-care test and can now be evaluated in prospective trials. [ABSTRACT FROM AUTHOR]

Background Parental substance abuse (SA) of alcohol and drugs is associated with offspring mortality, including sudden infant death syndrome (SIDS), in infancy, but research on cause-specific mortality and mortality in later childhood is scarce. Methods Using population-based register data on all births in Sweden in 1973–2013 (N  = 4.2 million) and Cox regressions, we examined the associations of mother's and father's SA registered between 2 years before and 12 years after the child birth with offspring all-cause and cause-specific mortality in infancy and childhood. Results Parental SA was associated with increased offspring all-cause and natural-cause mortality in infancy, but not in the neonatal period, and with external-cause mortality in ages 1–9. Risk of SIDS was 130–280% higher in infants with parental SA compared to infants with no parental SA. Adjusting for parental socioeconomic and immigrant status and severe psychiatric disorders, paternal SA was associated with 66% higher mortality due to communicable diseases and infections in infancy, and both maternal and paternal SA were associated with 40–174% higher mortality due to accidents in infancy and in ages 1–9. The associations between parental SA and offspring mortality were similar for male and female offspring. Conclusions Child mortality is rare in contemporary Sweden, and parental SA has variable associations with elevated offspring mortality throughout the first 10 years of life, excluding the neonatal period, which is indicative of insufficient recognition of children at risk. Preventive measures should be long-term and targeted to both parental and offspring behaviour. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) viremia is associated with mortality in severely ill immunocompetent adults and hospitalized children with HIV (CWH). We measured CMV viremia in HIV-exposed and -unexposed Kenyan children aged 1-59 months discharged from hospital and determined its relationship with postdischarge mortality.Methods: CMV DNA levels were measured in plasma from 1024 children (97 of which were HIV exposed uninfected [HEU], and 15 CWH). Poisson and Cox proportional hazards regression models were used to identify correlates of CMV viremia ≥ 1000 IU/mL 
and estimate associations with 6-month mortality, respectively.Results: CMV viremia was detected in 31% of children, with levels ≥ 1000 IU/mL in 5.8%. HIV infection, age < 2 years, breastfeeding, and midupper arm circumference < 12.5 cm were associated with CMV viremia ≥ 1000 IU/mL. Among HEU children, CMV ≥ 1000 IU/mL (hazard ratio [HR] = 32.0; 95% confidence interval [CI], 2.9-354.0; P = .005) and each 1-log increase in CMV viral load (HR = 5.04; 95% CI, 1.7-14.6; P = .003) were associated with increased risk of mortality. CMV viremia was not significantly associated with mortality in HIV-unexposed children.Conclusions: CMV levels at hospital postdischarge predict increased risk of 6-month mortality in Kenyan HEU children. CMV suppression may be a novel target to reduce mortality in HEU children.Clinical Trial Registration: NCT02414399. [ABSTRACT FROM AUTHOR]

Objective To evaluate the cost-effectiveness and economic impact of changing childhood vaccination from the 10-valent pneumococcal conjugate vaccine (PCV10) to the 13-valent pneumococcal conjugate vaccine (PCV13) in the context of the Ecuadorian health system. Methods A Markov model was developed based on a hypothetical cohort of children <1 year old with a 2 + 1 vaccination schedule. The model incorporates the most impactful chronic sequelae of invasive pneumococcal disease: bilateral hearing loss, spasticity, neurological deficit, hydrocephalus and epilepsy. At the end of each annual Markov cycle, the children heal with/without sequelae or die. A time horizon of 5 years was considered. The analysis was done from the perspective of the Ministry of Health. Key findings Vaccination with PCV13 is cost-saving (US$ −2940/QALY) in relation to PCV10 considering indirect effects ('herd effect') of childhood vaccination over adult population (>65 years). So, PCV13 reduces incident cases of IPD in this adult population by 27.8% compared to PCV10. Simulation of the model in a cohort of 100 000 children <1 year old showed an incidence of 25 cases of IPD with PCV13 versus 40 cases with PCV10, that is, a reduction of 37.5%. A reduction compared to PCV10 in the incidence of pneumonia and meningitis of 30.2 and 57.1%, respectively, was demonstrated. PCV13 decreased mortality by 32% compared to PCV10. Conclusions Vaccination with PCV13 is cost-saving in the Ecuadorian health context and significantly reduces morbidity and mortality in children <5 years and in adults >65 years due to the herd effect. The probabilistic analysis showed consistency in the results. [ABSTRACT FROM AUTHOR]

Background The world is set on the eradication of measles. Continuation of the measles vaccine (MV) after eradication could still reduce morbidity because the MV has so-called beneficial nonspecific effects. We evaluated the effect of a "booster" dose of the MV on overall severe morbidity. Methods We conducted a randomized controlled trial among children aged 17.5 to 48 months in Guinea-Bissau, where the MV is recommended only at 9 months of age. At the time of this interim analysis, 3164 children had been allocated 1:1 to a second dose of measles vaccine (MV2) at 18 months of age or to no vaccine. Severe morbidity (a composite outcome of nonaccidental deaths and hospital admissions) rate ratios (SMRRs) were calculated by Cox regression analysis censored for national oral polio vaccine (OPV) campaigns. Results There were no measles cases during the trial period. There were 43 nonaccidental deaths or hospital admissions during follow-up. Severe morbidity was 2.6 per 100 person-years in the MV2 group and 3.6 per 100 person-years among controls; hence, the estimated effect of MV2 on severe morbidity was 28% (SMRR, 0.72; 95% confidence interval [CI],.38–1.38). At 12 months of follow-up, the number needed to treat to prevent 1 severe morbidity event was 137 children. After OPV campaigns, the estimated effect of MV2 was reduced to 9% (SMRR, 0.91; 95% CI,.46–1.81). Conclusions MV2 may reduce nonmeasles severe morbidity by 28% (−38% to 62%), although this did not achieve statistical significance in this study. If significant in higher powered studies, this has major implications for child health, even after measles eradication. Clinical Trials Registration NCT02943681. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is considered an important contributing factor to child mortality, and the mid-upper arm circumference (MUAC) is regarded as one of the better anthropometric predictors of child mortality. We explored whether the decline in child mortality over recent decades could be explained by changes in children's MUAC.Methods: This prospective study analysed individual-level data from 47 731 children from the capital of Guinea-Bissau followed from 3 months until 36 months of age over 2003 to 2016. We used standardization to compare the mortality rate as if only the MUAC distribution had changed between an early period (2003-05) and a late period (2014-16). We adjusted the analyses for age, sex, socioeconomic-related possessions and maternal education.Results: A total of 949 deaths were included in the analysis. The adjusted mortality rate was 18.9 [95% confidence interval (CI) 14.3-23.3] deaths per 1000 person-years (pyrs) in the early period and declined to 4.4 (95% CI 2.9-6.0) deaths per 1000 pyrs in the late period, a 77% (95% CI 71-83%) reduction in the mortality rate. At all calendar years, the MUAC distribution in the population was close to the WHO reference population. MUAC below -1 z-score was associated with increased child mortality. The change in MUAC distribution from the early period to the late period (in the early period mortality standardization) corresponded to 1.5 (95% CI 1.0-2.2) fewer deaths per 1000 pyrs, equivalent to 11% (95% CI 7-14%) of the observed change in child mortality.Conclusions: From 2003 to 2016, child mortality in urban Guinea-Bissau declined considerably but, though a low MUAC was associated with increased mortality, changes in the MUAC distribution in the population explained little of the decline. Understanding the driving factors of child mortality decline can help scope tomorrow's interventions. [ABSTRACT FROM AUTHOR]

Background Dietary diversity (DD) is a key component of diet quality, and malnutrition due to poor diet quality leads to child morbidity and mortality. However, in Bangladesh, there is a lack of information on childhood DD (for children aged 6–59 mo) amid the coronavirus disease 2019 (COVID-19) pandemic. Objectives The purpose of this study was to assess the minimum DD and its associated factors among children aged 6–59 mo during the COVID-19 pandemic in Bangladesh. Methods A cross-sectional study was carried out in 6 districts of Bangladesh. A total of 1190 respondents were included using cluster random sampling. The Individual Dietary Diversity Score (IDDS) for children was used to assess the children's DD. Factors associated with DD of children were identified using a multilevel binary logistics regression model. Results About 70% of the children aged 6–59 mo had minimum DD during the COVID-19 pandemic in Bangladesh. Children who belonged to slum areas [adjusted odds ratio (AOR): 0.45; 95% CI: 0.24, 0.83], family income 12,000–15,000 Bangladeshi taka (BDT) (AOR: 1.79; 95% CI: 1.06, 3.05) and >15,000 BDT (AOR: 2.59; 95% CI: 1.47, 4.57), mothers aged 26–30 y (AOR: 0.35; 95% CI: 0.20, 0.62) and >30 y (AOR: 0.43; 95% CI: 0.22, 0.85), respondents who had 2 children <5 y old (AOR: 0.43; 95% CI: 0.28, 0.66), and children aged 12–23 mo (AOR: 1.89; 95% CI: 1.14, 3.20) were significantly associated with DD among children aged 6–59 mo. Conclusions The findings of this study highlight the need for food and nutrition-related intervention, particularly targeting mothers of younger age and with >2 children <5 y old, mothers from slum regions, and fathers who were unemployed, to improve children's DD practices. [ABSTRACT FROM AUTHOR]

Background The live vaccines bacille Calmette-Guérin (BCG) and measles vaccine have beneficial nonspecific effects (NSEs) reducing mortality, more than can be explained by prevention of tuberculosis or measles infection. Live oral polio vaccine (OPV) will be stopped after polio eradication; we therefore reviewed the potential NSEs of OPV. Methods OPV has been provided in 3 contexts: (1) coadministration of OPV and diphtheria-tetanus-pertussis (DTP) vaccine at 6, 10, and 14 weeks of age; (2) at birth (OPV0) with BCG; and (3) in OPV campaigns (C-OPVs) initiated to eradicate polio infection. We searched PubMed and Embase for studies of OPV with mortality as an outcome. We used meta-analysis to obtain the combined relative risk (RR) of mortality associated with different uses of OPV. Results First, in natural experiments when DTP was missing, OPV-only compared with DTP + OPV was associated with 3-fold lower mortality in community studies (RR, 0.33 [95% confidence interval {CI},.14–.75]) and a hospital study (RR, 0.29 [95% CI,.11–.77]). Conversely, when OPV was missing, DTP-only was associated with 3-fold higher mortality than DTP + OPV (RR, 3.23 [95% CI, 1.27–8.21]). Second, in a randomized controlled trial, BCG + OPV0 vs BCG + no OPV0 was associated with 32% (95% CI, 0–55%) lower infant mortality. Beneficial NSEs were stronger with early use of OPV0. Third, in 5 population-based studies from Guinea-Bissau and Bangladesh, the mortality rate was 24% (95% CI, 17%–31%) lower after C-OPVs than before C-OPVs. Conclusions There have been few clinical polio cases reported in this century, and no confounding factors or bias would explain all these patterns. The only consistent interpretation is that OPV has beneficial NSEs, reducing nonpolio child mortality. [ABSTRACT FROM AUTHOR]

Motivation Sepsis is a leading cause of death and disability in children globally, accounting for ∼3 million childhood deaths per year. In pediatric sepsis patients, the multiple organ dysfunction syndrome (MODS) is considered a significant risk factor for adverse clinical outcomes characterized by high mortality and morbidity in the pediatric intensive care unit. The recent rapidly growing availability of electronic health records (EHRs) has allowed researchers to vastly develop data-driven approaches like machine learning in healthcare and achieved great successes. However, effective machine learning models which could make the accurate early prediction of the recovery in pediatric sepsis patients from MODS to a mild state and thus assist the clinicians in the decision-making process is still lacking. Results This study develops a machine learning-based approach to predict the recovery from MODS to zero or single organ dysfunction by 1 week in advance in the Swiss Pediatric Sepsis Study cohort of children with blood-culture confirmed bacteremia. Our model achieves internal validation performance on the SPSS cohort with an area under the receiver operating characteristic (AUROC) of 79.1% and area under the precision-recall curve (AUPRC) of 73.6%, and it was also externally validated on another pediatric sepsis patients cohort collected in the USA, yielding an AUROC of 76.4% and AUPRC of 72.4%. These results indicate that our model has the potential to be included into the EHRs system and contribute to patient assessment and triage in pediatric sepsis patient care. Availability and implementation Code available at https://github.com/BorgwardtLab/MODS-recovery. The data underlying this article is not publicly available for the privacy of individuals that participated in the study. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background: Since the beginning of the ongoing conflict in Yemen, >23 000 air strikes and >100 000 fatalities have been recorded. Data from Yemen Data Project linked >1300 child fatalities and >900 child injuries to air raids. However, there is little literature on the effect of the protracted armed conflict on the pattern of child mortality using data from small-scale surveys. We aimed to identify the pattern of the death rate for children aged <5 years ('under-5') and its relationship with human insecurity in Yemen.Methods: We created a human insecurity index (i.e. severely insecure vs insecure) for the 22 governorates in Yemen from 2015 to 2019, using data from the Armed Conflict Location and Event Database. We matched this insecurity index with the corresponding under-5 mortality data from the Complex Emergency Database. We analysed the relationship between the under-5 death rate (U5DR) and the insecurity level using a Bayesian finite mixture model in order to account for unobserved heterogeneity in clustered finite subsets of a population.Results: We extracted 72 surveys and 77.8% (n = 56) were included in this study. The mean of the recall period for mortality was 106 days with a standard deviation of 93 days. We identified two subpopulations: Subpopulation I-high average number of child deaths and Subpopulation II-low average number of child deaths. The log posterior mean of the U5DR is 1.10 (95% credible intervals: 0.36, 1.82) in the severely insecure group in Subpopulation I and 3-fold the estimate in Subpopulation II. However, in Subpopulation II, we found no association between the insecurity level and the U5DR.Conclusion: The pattern of child deaths is crucial in understanding the relationship between human insecurity and the U5DR. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries.Methods: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths.Results: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality.Conclusions: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between smoke haze (hereafter 'haze') and adverse health effects have increased in recent years due to extreme weather conditions and the increased occurrence of vegetation fires. The possible adverse health effects on under-five children (U5Y) is especially worrying due to their vulnerable condition. Despite continuous repetition of serious haze occurrence in Southeast Asia, epidemiological studies in this region remained scarce. Furthermore, no study had examined the association accounting for three important aspects (time lag, duration and intensity) concurrently.Objective: This study aimed to examine the association between haze and U5Y mortality in Malaysia, considering time lag, duration and intensity of exposure.Methods: We performed a time-stratified case-crossover study using a generalized additive model to examine the U5Y mortality related to haze in 12 districts in Malaysia, spanning from 2014 to 2016. A 'haze day' was characterized by intensity [based on concentrations of particulate matter (PM)] and duration (continuity of haze occurrence, up to 3 days).Results: We observed the highest but non-significant odds ratios (ORs) of U5Y mortality at lag 4 of Intensity-3. Lag patterns revealed the possibility of higher acuteness at prolonged and intensified haze. Stratifying the districts by the 95th-percentile of PM distribution, the 'low' category demonstrated marginal positive association at Intensity-2 Duration-3 [OR: 1.210 (95% confidence interval: 1.000, 1.464)].Conclusions: We found a null association between haze and U5Y mortality. The different lag patterns of the association observed over different duration and intensity suggest consideration of these aspects in future studies. [ABSTRACT FROM AUTHOR]

Background Trials of mass drug administration (MDA) of azithromycin (AZM) report reductions in child mortality in sub-Saharan Africa. AZM targeted to high-risk children may preserve benefit while minimizing antibiotic exposure. We modeled the cost-effectiveness of MDA to children 1–59 months of age, MDA to children 1–5 months of age, AZM administered at hospital discharge, and the combination of MDA and postdischarge AZM. Methods Cost-effectiveness was modeled from a payer perspective with a 1-year time horizon, and was presented as cost per disability-adjusted life-year (DALY) averted and death averted, with probabilistic sensitivity analyses. The model included parameters for macrolide resistance, adverse events, hospitalization, and mortality sourced from published data. Results Assuming a base-case 1.64% mortality risk among children 1–59 months old, 3.1% among children 1–5 months old, 4.4% mortality risk postdischarge, and 13.5% mortality reduction per trial data, MDA would avert ~267 000 deaths at a cost of $14.26/DALY averted (95% uncertainty interval [UI], 8.72–27.08). MDA to only children 1–5 months old would avert ~186 000 deaths at a cost of $4.89/DALY averted (95% UI, 2.88–11.42), and postdischarge AZM would avert ~45 000 deaths, at a cost of $2.84/DALY (95% UI, 1.71–5.57) averted. Cost-effectiveness decreased with presumed diminished efficacy due to macrolide resistance. Conclusions Targeting AZM to children at highest risk of death may be an antibiotic-sparing and highly cost-effective, or even cost-saving, strategy to reduce child mortality. However, targeted AZM averts fewer absolute deaths and may not reach all children who would benefit. Any AZM administration decision must consider implications for antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. Methods Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. Results Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02–0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. Conclusions Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors. [ABSTRACT FROM AUTHOR]

Background Mass drug administration (MDA) with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear. To better understand the nature and extent of protection provided by AZ, we explored the profile of protection by time since administration, using data from a household-randomized, placebo-controlled trial in Burkina Faso and Mali. Methods Between 2014 and 2016, 30 977 children aged 3–59 months received seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine and either AZ or placebo monthly, on 4 occasions each year. Poisson regression with gamma-distributed random effects, accounting for the household randomization and within-individual clustering of illness episodes, was used to compare incidence of prespecified outcomes between SMC+AZ versus SMC+placebo groups in fixed time strata post-treatment. The likelihood ratio test was used to assess evidence for a time-treatment group interaction. Results Relative to SMC+placebo, there was no evidence of protection from SMC+AZ against hospital admissions and deaths. Additional protection from SMC+AZ against malaria was confined to the first 2 weeks post-administration (protective efficacy (PE): 24.2% [95% CI: 17.8%, 30.1%]). Gastroenteritis and pneumonia were reduced by 29.9% [21.7; 37.3%], and 34.3% [14.9; 49.3%], respectively, in the first 2 weeks postadministration. Protection against nonmalaria fevers with a skin condition persisted up to 28 days: PE: 46.3% [35.1; 55.6%]. Conclusions The benefits of AZ-MDA are broad-ranging but short-lived. To maximize impact, timing of AZ-MDA must address the challenge of targeting asynchronous morbidity and mortality peaks from different causes. [ABSTRACT FROM AUTHOR]

Background Lower respiratory tract infections are a leading cause of death in young children, but few studies have collected the specimens needed to define the role of specific causes. The Child Health and Mortality Prevention Surveillance (CHAMPS) platform aims to investigate causes of death in children aged <5 years in high–mortality rate settings, using postmortem minimally invasive tissue sampling and other advanced diagnostic techniques. We examined findings for deaths identified in CHAMPS sites in 7 countries in sub-Saharan Africa and south Asia to evaluate the role of respiratory syncytial virus (RSV). Methods We included deaths that occurred between December 2016 and December 2019. Panels determined causes of deaths by reviewing all available data including pathological results from minimally invasive tissue sampling, polymerase chain reaction screening for multiple infectious pathogens in lung tissue, nasopharyngeal swab, blood, and cerebrospinal fluid samples, clinical information from medical records, and verbal autopsies. Results We evaluated 1213 deaths, including 695 in neonates (aged <28 days), 283 in infants (28 days to <12 months), and 235 in children (12–59 months). RSV was detected in postmortem specimens in 67 of 1213 deaths (5.5%); in 24 deaths (2.0% of total), RSV was determined to be a cause of death, and it contributed to 5 other deaths. Younger infants (28 days to <6 months of age) accounted for half of all deaths attributed to RSV; 6.5% of all deaths in younger infants were attributed to RSV. RSV was the underlying and only cause in 4 deaths; the remainder (n = 20) had a median of 2 (range, 1–5) other conditions in the causal chain. Birth defects (n = 8) and infections with other pathogens (n = 17) were common comorbid conditions. Conclusions RSV is an important cause of child deaths, particularly in young infants. These findings add to the substantial body of literature calling for better treatment and prevention options for RSV in high–mortality rate settings. [ABSTRACT FROM AUTHOR]

Background Globally, pneumonia is the leading cause of death among children. Few data exist regarding the effect of Haemophilus influenzae type b (Hib) vaccine and 13-valent pneumococcal conjugate vaccine (PCV-13) on the burden of childhood pneumonia in African settings. Methods We collected data on children aged 1 to 59 months at 3 hospitals in Botswana. Hib vaccine and PCV-13 were introduced in Botswana in November 2010 and July 2012, respectively. We compared pneumonia hospitalizations and deaths prevaccine (January 2009 to October 2010) with postvaccine (January 2013 to December 2017) using seasonally adjusted, interrupted time-series analyses. Results We identified 6943 pneumonia hospitalizations and 201 pneumonia deaths. In the prevaccine period, pneumonia hospitalizations and deaths increased by 24% (rate, 1.24; 95% CI,.94–1.64) and 59% (rate, 1.59; 95% CI,.87–2.90) per year, respectively. Vaccine introduction was associated with a 48% (95% CI, 29–62%) decrease in the number of pneumonia hospitalizations and a 50% (95% CI, 1–75%) decrease in the number of pneumonia deaths between the end of the prevaccine period (October 2010) and the beginning of the postvaccine period (January 2013). During the postvaccine period, pneumonia hospitalizations and deaths declined by 6% (rate,.94; 95% CI,.89–.99) and 22% (rate,.78; 95% CI,.67–.92) per year, respectively. Conclusions Pneumonia hospitalizations and deaths among children declined sharply following introduction of Hib vaccine and PCV-13 in Botswana. This effect was sustained for more than 5 years after vaccine introduction, supporting the long-term effectiveness of these vaccines in preventing childhood pneumonia in Botswana. [ABSTRACT FROM AUTHOR]

Background Pneumococcal conjugate vaccines (PCVs) are recommended for use in pediatric immunization programs worldwide. Few data are available on their effect against mortality. We present a multicountry evaluation of the population-level impact of PCVs against death due to pneumonia in children < 5 years of age. Methods We obtained national-level mortality data between 2000 and 2016 from 10 Latin American and Caribbean countries, using the standardized protocol. Time series models were used to evaluate the decline in all-cause pneumonia deaths during the postvaccination period while controlling for unrelated temporal trends using control causes of death. Results The estimated declines in pneumonia mortality following the introduction of PCVs ranged from 11% to 35% among children aged 2–59 months in 5 countries: Colombia (24% [95% credible interval {CrI}, 3%–35%]), Ecuador (25% [95% CrI, 4%–41%]), Mexico (11% [95% CrI, 3%–18%]), Nicaragua (19% [95% CrI, 0–34%]), and Peru (35% [95% CrI, 20%–47%]). In Argentina, Brazil, and the Dominican Republic, the declines were not detected in the aggregated age group but were detected in certain age strata. In Guyana and Honduras, the estimates had large uncertainty, and no declines were detected. Across the 10 countries, most of which have low to moderate incidence of pneumonia mortality, PCVs have prevented nearly 4500 all-cause pneumonia deaths in children 2–59 months since introduction. Conclusions Although the data quality was variable between countries, and the patterns varied across countries and age groups, the balance of evidence suggests that mortality due to all-cause pneumonia in children declined after PCV introduction. The impact could be greater in populations with a higher prevaccine burden of pneumonia. [ABSTRACT FROM AUTHOR]

Background: Scorpion envenomation is a common medical emergency in many countries, including Turkey. Severe systemic symptoms occur more easily in children and mortality rates are higher. The aim of this study is to describe the clinical effects and predictive factors affecting the clinical severity of scorpion envenomations in Western Turkey.Methods: Two hundred one children (138 mild cases, 34 moderate, and 29 severe) with scorpion envenomation aged between 1 month and -17 years were included in the study. The patients' demographic and laboratory characteristics were compared among clinical severity subgroups.Results: The patients' median age was 7 (4-11) years. The median age of the severe group was significantly lower than that of the mild and moderate groups (p < 0.001). Seventeen patients (8.5%) developed myocarditis, while no pulmonary edema was observed in any case. Leukocyte, neutrophil and platelet (PLT) counts, and plateletcrit (PCT) and glucose levels increased significantly with the severity of envenomation (p < 0.001). PLT counts and PCT levels exhibited positive correlation with leukocyte and neutrophil counts (p < 0.001, r = 0.781, r = 0.638, r = 0.772, and r = 0.629, respectively). Supraventricular tachycardia developed in 1 (5.9%) patient, and dilated cardiomyopathy in another (5.9%). No mortality occurred in any case.Conclusion: Increased PLT counts and PCT levels may be helpful in evaluating clinical severity in patients with scorpion sting envenomation. The possibility of myocarditis development in children should be remembered and cardiac enzymes should be checked, even if patients are asymptomatic and cardiac enzymes are normal on admission. [ABSTRACT FROM AUTHOR]

Background: Altered mental status (AMS) is a priority presenting sign that must be assessed in HIV-infected, febrile children, yet diagnosis is difficult in areas with limited diagnostic capacity. Malaria and bacterial meningitis have been reported as the most common causes of AMS in febrile children presenting to the hospital in sub-Saharan Africa. However, in an HIV-infected child, central nervous system manifestations are diverse.Methods: We conducted a clinical observational study of HIV-infected febrile children, aged 0-59 months, hospitalized in Mozambique and prospectively followed. Within this cohort, a nested study was designed to characterize children admitted with AMS and to assess factors associated with mortality. Univariate and multivariable analysis were performed comparing characteristics of the cohort by AMS status and evaluated demographic and clinical factors by in-hospital mortality outcome.Results: In total, 727 children were enrolled between April 2016 and February 2019, 16% had AMS at admission. HIV-infected, febrile children, who presented with AMS and who had a diagnosis of bacteremia, had a 4-fold increased relative odds of in-hospital mortality, and children who presented with neurologic symptoms on admission had a roughly 8-fold higher odds of in-hospital mortality relative to children without presenting neurologic findings.Conclusions: Mozambique has a pressing need to expand local diagnostic capacity. Our results highlight the critical need for clinicians to incorporate a broader differential into their potential causes of AMS, and to develop a Ministry of Health approved diagnostic and management algorithm, which is standardly used, to manage patients for whom reliable and relevant diagnostic services are not available. [ABSTRACT FROM AUTHOR]

Background: The third dose of diphtheria-tetanus-pertussis vaccine (DTP3) is used to monitor immunization programs. DTP has been associated with higher female mortality.Methods: We updated previous literature searches for DTP studies of mortality by sex. We examined the female/male (F/M) mortality rate ratio (MRR) with increasing number of doses of DTP and for subsequent doses of measles vaccine (MV) after DTP and of DTP after MV.Results: Eight studies had information on both DTP1 and DTP3. The F/M MRR was 1.17 (95% confidence interval [CI], .88-1.57) after DTP1 and increased to 1.66 (95% CI, 1.32-2.09) after DTP3. Following receipt of MV, the F/M MRR declined to 0.63 (95% CI, .42-.96). In 11 studies the F/M MRR increased to 1.73 (95% CI, 1.33-2.27) when DTP-containing vaccine was administered after MV.Conclusions: F/M MRR increased with increasing doses of DTP. After MV, girls had lower mortality than boys. With DTP after MV, mortality increased again for girls relative to boys. No bias can explain these changes in F/M MRR. DTP does not improve male survival substantially in situations with herd immunity to pertussis and higher F/M MRR after DTP may therefore reflects an absolute increase in female mortality. [ABSTRACT FROM AUTHOR]

Study Question: How many twins are born in human populations and how has this changed over recent decades?Summary Answer: Since the 1980s, the global twinning rate has increased by a third, from 9.1 to 12.0 twin deliveries per 1000 deliveries, to about 1.6 million twin pairs each year.What Is Known Already: It was already known that in the 1980s natural twinning rates were low in (East) Asia and South America, at an intermediate level in Europe and North America, and high in many African countries. It was also known that in recent decades, twinning rates have been increasing in the wealthier parts of our world as a result of the rise in medically assisted reproduction (MAR) and delayed childbearing.Study Design, Size, Duration: We have brought together all information on national twinning rates available from statistical offices, demographic research institutes, individual survey data and the medical literature for the 1980-1985 and the 2010-2015 periods.Participants/materials, Setting, Methods: For 165 countries, covering over 99% of the global population, we were able to collect or estimate twinning rates for the 2010-2015 period. For 112 countries, we were also able to obtain twinning rates for 1980-1985.Main Results and the Role Of Chance: Substantial increases in twinning rates were observed in many countries in Europe, North America and Asia. For 74 out of 112 countries the increase was more than 10%. Africa is still the continent with highest twinning rates, but Europe, North America and Oceania are catching up rapidly. Asia and Africa are currently home to 80% of all twin deliveries in the world.Limitations, Reasons For Caution: For some countries, data were derived from reports and papers based on hospital registrations which are less representative for the country as a whole than data based on public administrations and national surveys.Wider Implications Of the Findings: The absolute and relative number of twins for the world as a whole is peaking at an unprecedented level. An important reason for this is the tremendous increase in medically assisted reproduction in recent decades. This is highly relevant, as twin deliveries are associated with higher infant and child mortality rates and increased complications for mother and child during pregnancy and during and after delivery.Study Funding/competing Interest(s): The contribution of CM was partially supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (grant No 681546, FAMSIZEMATTERS), Nuffield College, and the Leverhulme Trust. The contribution of GP was partially supported by the French Agence Nationale de la Recherche (grant No ANR-18-CE36-0007-07). The authors declare no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background Between 2002 and 2014, Guinea-Bissau had 17 national campaigns with oral polio vaccine (OPV) as well as campaigns with vitamin A supplementation (VAS), measles vaccine (MV), and H1N1 influenza vaccine. We examined the impact of these campaigns on child survival. Methods We examined the mortality rate between 1 day and 3 years of age of all children in the study area. We used Cox models with age as underlying time to calculate adjusted mortality rate ratios (MRRs) between "after-campaign" mortality and "before-campaign" mortality, adjusted for temporal change in mortality and stratified for season at risk. Results Mortality was lower after OPV-only campaigns than before, with an MRR for after-campaign vs before-campaign being 0.75 (95% confidence interval [CI],.67–.85). Other campaigns did not have similar effects, the MRR being 1.22 (95% CI, 1.04–1.44) for OPV + VAS campaigns, 1.39 (95% CI, 1.20–1.61) for VAS-only campaigns, 1.32 (95% CI, 1.09–1.60) for MV + VAS campaigns, and 1.13 (95% CI,.86–1.49) for the H1N1 campaign. Thus, all other campaigns differed significantly from the effect of OPV-only campaigns. Effects did not differ for trivalent, bivalent, or monovalent strains of OPV. With each additional campaign of OPV only, the mortality rate declined further (MRR, 0.86 [95% CI,.81–.92] per campaign). With follow-up to 3 years of age, the number needed to treat to save 1 life with the OPV-only campaign was 50 neonates. Conclusions OPV campaigns can have a much larger effect on child survival than otherwise assumed. Stopping OPV campaigns in low-income countries as part of the endgame for polio infection may increase child mortality. [ABSTRACT FROM AUTHOR]

Offspring desertion is often a plastic behavioral strategy that requires precise timing as the termination of parental care may have profound consequences for the fitness of parents and offspring. However, the decision process involved with termination of care is still poorly understood. Snowy Plovers Charadrius nivosus show highly flexible brood care with some females deserting the brood early and re-mate, whereas others provide extended care until the young are independent. Using a dynamic modeling framework, we investigated the effect of multiple factors on the decision-making process of female brood care in Ceuta, Mexico over a 7-year period. Females were more likely to stay with larger broods, while their probability of care was lower at the beginning of the season, when re-mating opportunities are higher than later in the season. Offspring condition at hatching did not influence the length of female care. Chick death and offspring desertion frequently coincided, suggesting that deteriorating offspring condition may trigger female desertion. Females deserted broods with high survival prospects when their absence did not impact negatively chick survival. Conversely, females deserted broods with low survival prospects when chick mortality despite female care reduced the value of the brood and re-mating was still possible. This suggests that female Snowy Plovers are sensitive to the needs and the value of their broods and adjust their parental care strategy accordingly. Taken together, we conclude that offspring desertion is a highly plastic behavior that allows females to maximize their reproductive success in a stochastic environment. [ABSTRACT FROM AUTHOR]

Background In informal settlements, the benefits of urban dwelling are diminished by conditions of poverty that exacerbate child undernutrition. The Child Health and Mortality Prevention Surveillance (CHAMPS) project has identified malnutrition as the leading underlying cause of death in children under 5 in the Manyatta urban informal settlement in Kisumu County, Kenya. Objective This qualitative study, nested within the CHAMPS project, aimed to understand community perspectives on complementary feeding practices in this settlement. Methods In-depth interviews were conducted with 20 mothers who lived in the urban informal settlement and had a child 6–23 months old. Two focus group discussions were conducted, 1 with mothers and 1 with community health workers (CHWs), to further explore themes related to complementary feeding. Results Mothers were knowledgeable about globally recommended feeding practices, but such practices were often not implemented due to 1) the community/household water and sanitation environment, 2) the community/household food environment, 3) a lack of income and employment opportunities for women, and 4) sociocultural factors. Together, these create an environment that is not conducive to optimal child feeding practices. Conclusions To improve complementary feeding practices and child nutritional outcomes in Kenya's informal urban settings, both community- and individual-level factors should be addressed. Possible interventions include investment in water infrastructure and social protection programs, such as cash transfers. [ABSTRACT FROM AUTHOR]

Objectives: Although glioblastoma (GBM) is rare in the pediatric population, it is the most common cause of death among children with central nervous system neoplasms. Recent molecular profiling of these neoplasms has demonstrated distinct differences in comparison to their adult counterparts. Moreover, many pediatric GBMs occur within the context of cancer predisposition syndromes, such as constitutional mismatch repair deficiency syndrome (CMMRD). Children with CMMRD who develop GBM exhibit a high tumor mutational burden and may benefit from treatment with immune checkpoint inhibitors.Methods: We performed next-generation sequencing and immunohistochemistry for mismatch repair proteins in our cohort of pediatric and adult GBMs to further characterize the molecular profiles of these groups.Results: We examined a total of 11 pediatric and 11 adult GBMs. Pediatric patients had a higher number of alterations compared to their adult counterparts. They also had a higher frequency of alterations in the mismatch repair genes, which can be detected by immunohistochemistry (IHC). We also identified one pediatric patient with CMMRD syndrome.Conclusions: Our study highlighted the distinct molecular differences between pediatric and adult GBM. We also demonstrated that pediatric patients have a higher frequency of alterations in the mismatch repair genes, which may render them susceptible to treatment with immune checkpoint inhibitors. These alterations can be detected using routine IHC and should be performed on all pediatric GBM. [ABSTRACT FROM AUTHOR]

Background: Nigeria has the largest number of global under-five deaths and almost half of these occur in the newborn period in an almost 50:50 ratio across hospital facilities and communities. We examine and describe risk factors for newborn mortality at a busy neonatal unit of a referral tertiary hospital in North-central Nigeria.Methods: We conducted a retrospective cohort analysis of all newborn admissions to the Dalhatu Araf Specialist Hospital between September 2018 and March 2020. We determined the newborn mortality rate (NMR) and case fatality rates (CFRs) for individual diagnostic categories and determined risk predictors for mortality using cox-proportional hazard models.Results: Of 1171 admitted newborn infants, 175 (14.9%) died with about half of these occurring within 24 h of admission. Extremely low birth weight infants and those with congenital anomalies had the highest CFRs. Identified risk factors for mortality were age at admission [adjusted hazard ratio (AHR): 0.996, 95% CI: 0.993-0.999], admitting weight (AHR: 0.9995, 95% CI: 0.9993-0.9997) and home delivery (AHR: 1.65, 95% CI: 1.11-to 2.46).Conclusions: Facility-based newborn mortality is high in North-central Nigeria. Majority of these deaths occur within the first 24 h of admission, signifying challenges in acute critical newborn care. To improve the current situation and urgently accelerate progress to meet the sustainable development goal NMR targets, there is an urgent need to develop human and material resources for acute critical newborn care while encouraging facility-based delivery and decentralizing existing newborn care. Lay summaryNigeria now has the greatest number of deaths in children below the age of five globally. Almost half of these occurred in the newborn period and these deaths occur within hospital facilities and also in communities in an almost 50:50 ratio. As such, the country might not attain global newborn mortality rates that were set as targets for the sustainable development goals (SDGs). In this article, we examine and describe the risk factors for newborn deaths occurring at a typical newborn unit in North-central Nigeria. During the period under review, we found that about 175 (14.9%) died and about half of these deaths occurred within 24 h of admission. Extremely small babies and those who were born with physical defects had the highest death rates. Older babies and those who weighed more at admission had decreased risks of dying while being delivered at home increased the risk of death. Hospital newborn deaths remain high in North-central Nigeria and the pattern of early admission deaths signifies challenges in stabilizing critically ill newborn infants. There is an urgent need to develop human and material resources for acute critical newborn care while encouraging institutional delivery and decentralizing of existing newborn care. [ABSTRACT FROM AUTHOR]

Introduction: Acute pneumonia is a leading infectious cause of death among children under 5 years globally and in Nigeria. Despite various existing strategies and interventions, pneumonia mortality remains unacceptably high. Novel interventions like improving vitamin D status may be needed as optimal vitamin D status may facilitate the ability of immune cells to fight against infections like pneumonia. We investigated the relationship between serum vitamin D [25(OH)D] levels and acute pneumonia in children younger than 5 years in Nigeria.Subjects and Methods: This cross-sectional study involved 135 children with pneumonia and 135 apparently healthy controls. Acute pneumonia was diagnosed using the revised World Health Organization criteria (2012) and chest radiological signs. Serum 25(OH)D concentrations were determined using a vitamin D ELISA kit. The mean serum 25(OH)D levels in both groups were compared and also determined odds ratio (OR) of pneumonia.Results: The mean serum 25(OH)D level of children with pneumonia (52.14 ± 21.87 nmol/l) was significantly lower than that of controls (60.91 ± 32.65 nmol/l), p = 0.010. The proportion of children with low serum vitamin D levels (≤75.0 nmol/l) was significantly higher in the pneumonia group (n = 123, 91.1%) than the control group (n = 97, 71.9%), p < 0.001. After adjusting for confounders, serum 25(OH)D levels of greater than 75 nmol/l was associated with decreased odds of acute pneumonia (adjusted OR = 0.33, p = 0.007).Conclusion: A low vitamin D level was associated with increased risk of acute pneumonia. Lay summary.Introduction: Chest infection (pneumonia) is a leading cause of death in children younger than 5 years of age globally and also in Nigeria. Pneumonia death is still very high despite all the existing efforts at reducing it. New methods may still be needed to drastically reduce this problem. One of these new methods may include improving the vitamin D status of an individual because optimal vitamin D levels may help the body to fight against infections like pneumonia. We investigated the relationship between blood levels of vitamin D and pneumonia in children younger than 5 years.Subjects and Methods: Vitamin D levels of 135 children with pneumonia were measured and compared with vitamin D levels of another 135 healthy children without pneumonia. We diagnosed pneumonia by using both revised World Health Organization criteria (2012) and chest X-rays signs. Blood levels of vitamin D were measured using a vitamin D ELISA kit.Results: The average blood vitamin D level of children with pneumonia (52.14 ± 21.87 nmol/l) was low compared with that of children without pneumonia (60.91 ± 32.65 nmol/l), p = 0.010. The number of children with low blood vitamin D levels (≤75.0 nmol/l) was more in the pneumonia group (n = 123, 91.1%) than in children without pneumonia (n = 97, 71.9%), p < 0.001. After adjusting for other potential risk factors, blood level of vitamin D >75 nmol/l was associated with lower risk of having pneumonia, (adjusted OR = 0.33, p = 0.007).Conclusion: A low vitamin D level was associated with increased risk of acute pneumonia. [ABSTRACT FROM AUTHOR]

13 Following the Sixty-Third World Health Assembly, and due to the absence of epidemiological data concerning incidence and burden of birth defects among several WHO regions, attention was directed to implementation of BD surveillance programmes. Whereas generally the highest BD prevalence rates are found among the world's poorest countries and lowest rates are found among the world's wealthiest countries, the exceptions are countries where recessive disorders and marriages between first cousins and other close relatives are common, as is the case in the EMR. 4 The March of Dimes foundation published in 2006 the first report providing global BD prevalence estimates, thus permitting broad comparison of specific BD across countries. Building on the experiences of other countries in the region and globally in terms of surveillance and data collection infrastructure materials, including BD manuals and collection sheets and implementation difficulties and solutions, is vital in achieving a functional BDSP with few complications in countries with limited resources. [Extracted from the article]

Background Cryptosporidium is a leading cause of diarrhea in Sub-Saharan Africa and is associated with substantial morbidity and mortality in young children. Methods   We analyzed data from children aged 6–71 months presenting to 2 public hospitals in Western Kenya with acute diarrhea and their primary caregivers, including detection of Cryptosporidium by quantitative polymerase chain reaction (PCR) and immunoassay analysis in stool samples from both children and their caregivers. Associations between potential transmission sources and child/caregiver Cryptosporidium infection were evaluated using prevalence ratios (PRs). Secondary analyses evaluated host and clinical risk factors of child/caregiver Cryptosporidium infection. Results Among 243 child–caregiver pairs enrolled, 77 children (32%) and 57 caregivers (23%) had Cryptosporidium identified by either immunoassay or PCR. Twenty-six of the 243 child–caregiver pairs (11%) had concordant detection of Cryptosporidium. Cryptosporidium infection in children was associated with detection of Cryptosporidium in caregivers (adjusted PR [aPR], 1.8; 95% CI, 1.2 to 2.6; P = .002) and unprotected water source (aPR, 2.0; 95% CI, 1.3 to 3.2; P = .003). Risk factors for Cryptosporidium detection in caregivers included child Cryptosporidium infection (aPR, 2.0; 95% CI, 1.3 to 3.0; P = .002) as well as cow (aPR, 3.1; 95% CI, 1.4 to 7.0; P = .02) and other livestock ownership (aPR, 2.6; 95% CI, 1.1 to 6.3; P = .03) vs no livestock ownership. Recent diarrhea in caregivers and children was independently associated with child and caregiver Cryptosporidium infections, respectively. Conclusions Our results are consistent with the hypothesis that Cryptosporidium transmission can occur directly between child–caregiver dyads as well as through other pathways involving water and livestock. Additional research into caregivers as a source of childhood Cryptosporidium infection is warranted. [ABSTRACT FROM AUTHOR]

Background: Since 2006, more than 100 countries have introduced rotavirus vaccine into their immunization programs. We reviewed published data on relative reductions of rotavirus hospitalizations, acute gastroenteritis (AGE) hospitalizations, and AGE deaths among children <5 years old.Methods: Articles published from January 1, 2006 to December 31, 2019 with at least 12 months of data before and after rotavirus vaccine introduction were included. Relative reductions were abstracted into a standardized form. Descriptive statistics are presented as medians and interquartile ranges (IQRs).Results: We reviewed 1827 total records and included 105 articles from 49 countries. Among children <5 years old, there was a median reduction of 59% (IQR, 46-74) in rotavirus hospitalizations, 36% (IQR, 23-47) in AGE hospitalizations, and 36% (IQR, 28-46) AGE mortality. Reductions were larger in countries with low child mortality, among younger age groups, and in countries with higher coverage. The median percentage of specimens that tested positive for rotavirus among children <5 years old hospitalized for diarrhea was 40% (IQR, 28-45) before rotavirus vaccine introduction and 20% (IQR, 20-20) 4 years after introduction.Conclusions: Overall, we found sustained impact on rotavirus and AGE hospitalizations and deaths. These results should encourage countries still considering rotavirus vaccine implementation. [ABSTRACT FROM AUTHOR]

OBJECTIVES Open in new tab Download slide Open in new tab Download slide Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden death in children and young adults. The most threatening anatomy is an interarterial and an intramural course, both probably involved in ischaemic phenomena and sudden death. The treatment of interarterial AAOCA remains controversial. Most of the published studies describe the results of the unroofing technique. Our study aims to evaluate the results of a different surgical approach. METHODS From 2005 to 2019, 61 patients were operated on for an interarterial AAOCA (median age 14.7 years). Forty patients had a right AAOCA, and 21 patients had a left AAOCA including 5 patients with intraseptal course. Seventy percent of patients were symptomatic. Five patients had an aborted sudden cardiac death. Two surgical techniques were used: an 'anatomical' repair for 35 patients (15 left and 22 right AAOCA) or a coronary translocation with creation of a neo-ostia in 19 patients (1 left and 18 right AAOCA). The 5 left AAOCA patients with an intra-septal course required a complete release of the coronary artery from the septum. RESULTS There was no early or late postoperative death. Three patients had an acute postoperative ischaemic event. Two patients required immediate angioplasty and stenting: 1 patient (7 years) with a hypoplastic right AAOCA and 1 patient (66 years) for inadequate tailoring after septal release. The third patient required an immediate surgical revision (H-2) for left AAOCA thrombosis at the level of the pericardial patch with full myocardial recovery at discharge. During follow-up, 1 patient with right AAOCA translocation and chronic chest pain required subsequent stenting and finally a coronary artery bypass grafting 2 years after initial surgery. One patient who had an asymptomatic mild right coronary stenosis 1 year after anatomical repair was successfully treated by angioplasty alone. All patients but 1 who underwent coronary translocation are totally asymptomatic. All patients with anatomical repair or septal release are free from ischaemic symptoms. CONCLUSIONS Anatomical repair might provide a better protective option for these patients. Unlike unroofing, it treats the entire intramural segment, relocates the ostium at the appropriate sinus level and corrects any acute take-off angle. [ABSTRACT FROM AUTHOR]

Congenital heart disease (CHD) is one of the major debilitating birth defects resulting in significant impact on neonatal and child mortality globally. The etiology of CHD is complex and multifactorial. Many causative genes responsible for CHDs have been identified from the familial forms previously. Still, the non-Mendelian inheritance and predominant sporadic cases have stimulated research to understand the epigenetic basis and environmental impact on the incidence of CHD. The fetal epigenetic programming affecting cardiac development is susceptible to the availability of key dietary factors during the crucial periconceptional period. This article highlights the need and importance of in-depth research in the new emerging area of maternal nutritional epigenetics and CHD. It summarizes the current research and underlines the limitations in these types of studies. This review will benefit the future research on nutrition as a modifiable environmental factor to decrease the incidence of CHD. [ABSTRACT FROM AUTHOR]

Objective: Snake envenomation has been poorly studied in developing countries. 'Early morning neuroparalytic syndrome' (EMNS), the classical clinical constellation caused by krait bites, refers to nighttime, indoor bites where nonspecific symptoms progress to neuroparalysis. Literature regarding EMNS in children is scarce. This study was planned to describe the clinical profile, intensive care needs and predictors of outcome in children with EMNS.Methods: It is a retrospective study of children below 12 years admitted with a clinical diagnosis of snake envenomation to the pediatric intensive care unit (PICU) of a tertiary care hospital in North India. Patient records were reviewed from the electronic patient database manager. Comparison was made between the EMNS group and the non-EMNS group and between survivors and nonsurvivors within the EMNS group.Results: Of the 111 children with snake envenomation, 76 had neuroparalysis (68%) and 51 had EMNS. In the EMNS cohort, 37 (72.5%) belonged to rural areas, 46 (90.2%) had indoor bites and 39 (76.5%) were witnessed. Patients with EMNS were more likely to have absent fang marks, hypoxemia at admission, bulbar palsy and need for PICU admission. Mortality rate was 13.7% in EMNS; predictors included younger age, presence of ptosis, cardiac arrest at admission and nonavailability of PICU bed (univariable analysis) but none of them independently predicted mortality.Conclusion: Younger age, presence of ptosis, cardiac arrest at admission and nonavailability of intensive care beds increase the risk of mortality in children with EMNS. Timely recognition and respiratory support may reduce mortality in these children. [ABSTRACT FROM AUTHOR]

Background Population data, such as mortality and morbidity statistics, are essential for many reasons, including giving context for research, supporting action on health determinants, formulation of evidence-based policy for health care and outcome evaluation. However, when considering children, it is difficult to find such data, despite children comprising one-fifth of the European population and being in a key formative life stage and dependent on societal support. Moreover, it would be expected that there should be confidence in the key child health data available, with little to no discrepancy between recognized health statistic databases. Methods This study explored the main health databases in or including Europe to collate child mortality data, for both all-cause and specific-cause mortality. Tables were constructed for comparison of values and rankings. Results The results show that there are major differences in reported mortality data between two prominent health statistic databases, difference in coding systems, and unannounced changes within one of the databases. Conclusions The lack of health data for children seems compounded by challenges to the trust and credibility, which are vital if these data are to have utility. Children and society are the losers, and resolution is needed as a priority. [ABSTRACT FROM AUTHOR]

Background: Bubble-continuous positive airway pressure (bCPAP) is a simple, low-cost ventilation therapy with the potential to lower morbidity and mortality in children in low- and middle-income countries (LMICs).Aim: To examine (i) whether bCPAP is a safe and effective treatment for children in all age-groups presenting with respiratory distress from any cause, (ii) LMIC-implemented bCPAP devices including their technical specifications and costs and (iii) the setting and level of health care bCPAP has been implemented in.Method: A systematic search was performed of Embase, PubMed and Web of Science. Inclusion criteria: bCPAP for children with respiratory distress in all age groups in LMICs. Database searches were performed up to 1 November 2018.Results: A total of 24 publications were eligible for the review. For neonates bCPAP was superior in improving survival and clinical progression compared with oxygen therapy and mechanical ventilation (MV). In two studies bCPAP was superior to low flow oxygen in reducing mortality in children 29 days to 13 months. Respiratory rate reductions were significant across all ages. Only three of six studies in children of all ages evaluated serious adverse events. In 12 studies comprising 1338 neonates treated with bCPAP, pneumothorax was reported 27 times. The majority of studies were carried out at tertiary hospitals in middle-income countries and 50% implemented the most expensive bCPAP-device.Conclusion: In neonates and children below 13 months bCPAP is a safe treatment improving clinical outcomes and reducing the need for MV, without an increase in mortality. High-quality studies from non-tertiary settings in low-income countries are needed. [ABSTRACT FROM AUTHOR]