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The article discusses the report from the U.S. Centers for Disease Control and Prevention about the worldwide polio eradication during the years 2009 and 2010. It investigates the quality of polio control and the timeliness of poliovirus isolation reporting and characterization by the World Health Organization-coordinated Global Polio Laboratory Network (GPLN). It also details how polio eradication can be achieved through strengthening acute flaccid paralysis (AFP) surveillance, implementation of environmental surveillance and maintenance of GPLN quality. INSET: What is already known on this topic?.

Abstract Background Susceptibility to atopy originates from effects of the environment on genes. Birth order has been identified as a risk factor for atopy and evidence for some candidate genes has been accumulated; however no study has yet assessed a birth order-gene interaction. Objective To investigate the interaction of IL13 polymorphisms with birth order on allergic sensitization at ages 4, 10 and 18 years. Methods Mother-infant dyads were recruited antenatally and followed prospectively to age 18 years. Questionnaire data (at birth, age 4, 10, 18); skin prick test (SPT) at ages 4, 10, 18; total serum IgE and specific inhalant screen at age 10; and genotyping for IL13 were collected. Three SNPs were selected from IL13: rs20541 (exon 4, nonsynonymous SNP), rs1800925 (promoter region) and rs2066960 (intron 1). Analysis included multivariable log-linear regression analyses using repeated measurements to estimate prevalence ratios (PRs). Results Of the 1456 participants, birth order information was available for 83.2% (1212/1456); SPT was performed on 67.4% at age 4, 71.2% at age 10 and 58.0% at age 18. The prevalence of atopy (sensitization to one or more food or aeroallergens) increased from 19.7% at age 4, to 26.7% at 10 and 41.1% at age 18. Repeated measurement analysis indicated interaction between rs20541 and birth order on SPT. The stratified analyses demonstrated that the effect of IL13 on SPT was restricted only to first-born children (p = 0.007; adjusted PR = 1.35; 95%CI = 1.09, 1.69). Similar findings were noted for firstborns regarding elevated total serum IgE at age 10 (p = 0.007; PR = 1.73; 1.16, 2.57) and specific inhalant screen (p = 0.034; PR = 1.48; 1.03, 2.13). Conclusions This is the first study to show an interaction between birth order and IL13 polymorphisms on allergic sensitization. Future functional genetic research need to determine whether or not birth order is related to altered expression and methylation of the IL13 gene.

Abstract Introduction Instrumental variable (IV) methods have been used in econometrics for several decades now, but have only recently been introduced into the epidemiologic research frameworks. Similarly, Mendelian randomization studies, which use the IV methodology for analysis and inference in epidemiology, were introduced into the epidemiologist's toolbox only in the last decade. Analysis Mendelian randomization studies using instrumental variables (IVs) have the potential to avoid some of the limitations of observational epidemiology (confounding, reverse causality, regression dilution bias) for making causal inferences. Certain limitations of randomized controlled trials, such as problems with generalizability, feasibility and ethics for some exposures, and high costs, also make the use of Mendelian randomization in observational studies attractive. Unlike conventional randomized controlled trials (RCTs), Mendelian randomization studies can be conducted in a representative sample without imposing any exclusion criteria or requiring volunteers to be amenable to random treatment allocation. Within the last decade, epigenetics has gained recognition as an independent field of study, and appears to be the new direction for future research into the genetics of complex diseases. Although previous articles have addressed some of the limitations of Mendelian randomization (such as the lack of suitable genetic variants, unreliable associations, population stratification, linkage disequilibrium (LD), pleiotropy, developmental canalization, the need for large sample sizes and some potential problems with binary outcomes), none has directly characterized the impact of epigenetics on Mendelian randomization. The possibility of epigenetic effects (non-Mendelian, heritable changes in gene expression not accompanied by alterations in DNA sequence) could alter the core instrumental variable assumptions of Mendelian randomization. This paper applies conceptual considerations, algebraic derivations and data simulations to question the appropriateness of Mendelian randomization methods when epigenetic modifications are present. Conclusion Given an inheritance of gene expression from parents, Mendelian randomization studies not only need to assume a random distribution of alleles in the offspring, but also a random distribution of epigenetic changes (e.g. gene expression) at conception, in order for the core assumptions of the Mendelian randomization methodology to remain valid. As an increasing number of epidemiologists employ Mendelian randomization methods in their research, caution is therefore needed in drawing conclusions from these studies if these assumptions are not met.

In resource-limited settings where vital registration and medical death certificates are unavailable or incomplete, verbal autopsy (VA) is often used to attribute causes of death (CoD) and prioritize resource allocation and interventions. We aimed to determine the CoD concordance between InterVA and CHAMPS's method. The causes of death (CoDs) of children <5 were determined by two methods using data from seven low- and middle-income countries (LMICs) enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) network. The first CoD method was from the DeCoDe panel using data from Minimally Invasive Tissue Sampling (MITS), whereas the second method used Verbal Autopsy (VA), which utilizes the InterVA software. This analysis evaluated the agreement between the two using Lin's concordance correlation coefficient. The overall concordance of InterVA4 and DeCoDe in assigning causes of death across surveillance sites, age groups, and causes of death was poor (0.75 with 95% CI: 0.73-0.76) and lacked precision. We found substantial differences in agreement by surveillance site, with Mali showing the lowest and Mozambique and Ethiopia the highest concordance. The InterVA4 assigned CoD agrees poorly in assigning causes of death for U5s and stillbirths. Because VA methods are relatively easy to implement, such systems could be more useful if algorithms were improved to more accurately reflect causes of death, for example, by calibrating algorithms to information from programs that used detailed diagnostic testing to improve the accuracy of COD determination., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network programme undertakes post-mortem minimally invasive tissue sampling (MITS), together with collection of ante-mortem clinical information, to investigate causes of childhood deaths across multiple countries. We aimed to evaluate the overall contribution of pneumonia in the causal pathway to death and the causative pathogens of fatal pneumonia in children aged 1-59 months enrolled in the CHAMPS Network., Methods: In this observational study we analysed deaths occurring between Dec 16, 2016, and Dec 31, 2022, in the CHAMPS Network across six countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and one in South Asia (Bangladesh). A standardised approach of MITS was undertaken on decedents within 24-72 h of death. Diagnostic tests included blood culture, multi-organism targeted nucleic acid amplifications tests (NAATs) of blood and lung tissue, and histopathology examination of various organ tissue samples. An interdisciplinary expert panel at each site reviewed case data to attribute the cause of death and pathogenesis thereof on the basis of WHO-recommended reporting standards., Findings: Pneumonia was attributed in the causal pathway of death in 455 (40·6%) of 1120 decedents, with a median age at death of 9 (IQR 4-19) months. Causative pathogens were identified in 377 (82·9%) of 455 pneumonia deaths, and multiple pathogens were implicated in 218 (57·8%) of 377 deaths. 306 (67·3%) of 455 deaths occurred in the community or within 72 h of hospital admission (presumed to be community-acquired pneumonia), with the leading bacterial pathogens being Streptococcus pneumoniae (108 [35·3%]), Klebsiella pneumoniae (78 [25·5%]), and non-typeable Haemophilus influenzae (37 [12·1%]). 149 (32·7%) deaths occurred 72 h or more after hospital admission (presumed to be hospital-acquired pneumonia), with the most common pathogens being K pneumoniae (64 [43·0%]), Acinetobacter baumannii (19 [12·8%]), S pneumoniae (15 [10·1%]), and Pseudomonas aeruginosa (15 [10·1%]). Overall, viruses were implicated in 145 (31·9%) of 455 pneumonia-related deaths, including 54 (11·9%) of 455 attributed to cytomegalovirus and 29 (6·4%) of 455 attributed to respiratory syncytial virus., Interpretation: Pneumonia contributed to 40·6% of all childhood deaths in this analysis. The use of post-mortem MITS enabled biological ascertainment of the cause of death in the majority (82·9%) of childhood deaths attributed to pneumonia, with more than one pathogen being commonly implicated in the same case. The prominent role of K pneumoniae, non-typable H influenzae, and S pneumoniae highlight the need to review empirical management guidelines for management of very severe pneumonia in low-income and middle-income settings, and the need for research into new or improved vaccines against these pathogens., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests CGW received honoraria from the University of St Andrews for speaking to alumni about CHAMPS and global health work. SAM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Merck, Providence, Gritstone, and ImmunityBio. SAM has received honoraria from GSK for lecturing. GR has received grants from Fleming Fund Kenya Country, Deutsche Forschungsgemeinschaft, and bioMerieux. SA and JAGS have received support for attending meetings or travels, or both, for WHO, Bill & Melinda Gates Foundation (SA) and the International Society of Pneumonia & Pneumococcal Diseases (JAGS). CGW, JAGS, and SAM report serving on data safety monitoring boards for Safety Platform for Emergency VACcines (SPEAC; CGW), PATH (SAM), Centre for the AIDS Programme of Research in South Africa (CAPRISA; SAM), MRC The Gambia (JAGS) and ILiAD Biotechnologies (JAGS). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CGW received honoraria from the University of St. Andrews for speaking to alumni about CHAMPS and global health work. JAGS reports receiving funding from the Wellcome Trust, UK FCDO, European Union, and the National Institute for Health Research. SM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Providence, Gritstone, and ImmunityBio. SM has received honoraria from GSK for lecturing. CGW and SM report serving on data safety monitoring boards for SPEAC (CGW) and PATH and CAPRISA (SM). DT-F reports having received the support of a fellowship from “La Caixa” Foundation (ID 100010434, “LCF/BQ/DR21/11880018”). All other investigators declare no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children., Methods: We conducted a retrospective, descriptive study examining clinical data for children aged 1-59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016-June 2021. Catchment areas included: Baliakandi and Faridpur, Bangladesh; Kersa, Haramaya, and Harar, Ethiopia; Kisumu and Siaya, Kenya; Bamako, Mali; Manhiça and Quelimane, Mozambique; Makeni, Sierra Leone; Soweto, South Africa. We reviewed medical records of those who died from lower respiratory tract infections, sepsis, malnutrition, malaria, and diarrheal diseases to determine the proportion who received recommended treatments and compared adherence by hospitalization duration., Findings: CHAMPS enrolled 460 hospitalized children who died from the leading causes (median age 12 months, 53.0% male). Median hospital admission was 31 h. There were 51.0% (n = 127/249) of children who died from lower respiratory tract infections received supplemental oxygen. Administration of intravenous fluids for sepsis (15.9%, n = 36/226) and supplemental feeds for malnutrition (14.0%, n = 18/129) were uncommon. There were 51.4% (n = 55/107) of those who died from malaria received antimalarials. Of the 80 children who died from diarrheal diseases, 76.2% received intravenous fluids. Those admitted for ≥24 h more commonly received antibiotics for lower respiratory tract infections and sepsis, supplemental feeds for malnutrition, and intravenous fluids for sepsis than those admitted <24 h., Interpretation: Provision of recommended clinical care for leading causes of death among young children was suboptimal. Further studies are needed to understand the reasons for deficits in clinical care recommendation adherence., Funding: Bill & Melinda Gates Foundation., Competing Interests: CGW received honoraria from the University of St. Andrews for speaking to alumni about CHAMPS and global health work. JAGS reports receiving funding from the Wellcome Trust, UK FCDO, European Union, and the National Institute for Health Research. SM has received grants from the Bill & Melinda Gates Foundation, GSK, Pfizer, Minervax, Novavax, Providence, Gritstone, and ImmunityBio. SM has received honoraria from GSK for lecturing. CGW and SM report serving on data safety monitoring boards for SPEAC (CGW) and PATH and CAPRISA (SM). All other investigators declare no competing interests., (© 2023 The Author(s).)

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., Competing Interests: Potential conflicts of interest. The authors have declared that no competing interests exist., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia., Methods: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site., Findings: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site., Interpretation: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SEA reports grants from Emory University, during the conduct of the study. JAGS reports grants from the Wellcome Trust, the National Institute for Health and Care Research, Gavi, the Foreign Commonwealth and Development Office (UK), the European and Developing Countries Clinical Trials Partnership, the Medical Research Council, and the Bill & Melinda Gates Foundation whose payments were direct to his institution. LM reports grants from the Bill & Melinda Gates Foundation via Emory, whose payments were made direct to her institution. KLK reports grants from the Bill & Melinda Gates Foundation, whose payments were made direct to her institution and support attending meetings. KLK, SOS, and AMK report the provision of study materials and funding to their institution for this study from the Bill & Melinda Gates Foundation. AW reports a stipend for participating in the CHAMPS research and payment for travel to the High Horizons meeting in Belgium from the University of Witwatersrand; honoraria for lectures from Sanofi; and being a council member of The South African Society of Obstetricians and Gynaecologists. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The high burden of stillbirths and neonatal deaths is driving global initiatives to improve birth outcomes. Discerning stillbirths from neonatal deaths can be difficult in some settings, yet this distinction is critical for understanding causes of perinatal deaths and improving resuscitation practices for live born babies., Methods: We evaluated data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network to compare the accuracy of determining stillbirths versus neonatal deaths from different data sources and to evaluate evidence of resuscitation at delivery in accordance with World Health Organization (WHO) guidelines. CHAMPS works to identify causes of stillbirth and death in children <5 years of age in Bangladesh and 6 countries in sub-Saharan Africa. Using CHAMPS data, we compared the final classification of a case as a stillbirth or neonatal death as certified by the CHAMPS Determining Cause of Death (DeCoDe) panel to both the initial report of the case by the family member or healthcare worker at CHAMPS enrollment and the birth outcome as stillbirth or livebirth documented in the maternal health record., Results: Of 1967 deaths ultimately classified as stillbirth, only 28 (1.4%) were initially reported as livebirths. Of 845 cases classified as very early neonatal death, 33 (4%) were initially reported as stillbirth. Of 367 cases with post-mortem examination showing delivery weight >1000g and no maceration, the maternal clinical record documented that resuscitation was not performed in 161 cases (44%), performed in 14 (3%), and unknown or data missing for 192 (52%)., Conclusion: This analysis found that CHAMPS cases assigned as stillbirth or neonatal death after DeCoDe expert panel review were generally consistent with the initial report of the case as a stillbirth or neonatal death. Our findings suggest that more frequent use of resuscitation at delivery and improvements in documentation around events at birth could help improve perinatal outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized., Methods: The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital., Results: We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8-3.3) was lower than in-hospital (2.4 months; IQR: 1.5-4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001)., Conclusions: We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: To inform the introduction of pneumococcal conjugate vaccine (PCV) and rotavirus vaccine, the World Health Organization (WHO) established the Global Invasive Bacterial Vaccine-Preventable Disease Surveillance Network (GISN) and the Global Rotavirus Surveillance Network (GRSN) in 2008. We investigated whether participation in these networks or other surveillance was associated with vaccine introduction., Methods: Between 2006 and 2018, among all WHO member states, we used multivariable models adjusting for economic status to assess (1) the association between surveillance for pneumococcal disease or rotavirus disease, including participation in GISN or GRSN and the introduction of the PCV or the rotavirus vaccine, respectively, and (2) the association between the rotavirus disease burden and the rotavirus vaccine introduction among 56 countries participating in GRSN from 2008 to 2018., Results: Countries that participated in or conducted surveillance for invasive pneumococcal disease or rotavirus disease were 3.5 (95% confidence interval [CI], 1.7-7.1) and 4.2 (95% CI, 2.1-8.6) times more likely to introduce PCV or rotavirus respectively, compared to those without surveillance. Among countries participating in GRSN, there was insufficient evidence to demonstrate an association between countries with higher rotavirus positivity and vaccine introduction., Conclusions: Surveillance should be incorporated into advocacy strategies to encourage the introduction of vaccines, with countries benefiting from data from, support for, and coordination of international disease surveillance networks., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Background: Missed opportunities for vaccination (MOVs), estimated to be about 32-47% of child healthcare clinic visits in various settings globally, contribute to unfulfilled childhood vaccination coverage targets in the African region., Objective: We assessed the extent of MOVs, identify local drivers and test interventions to reduce MOVs in Malawi., Methods: We conducted in-depth and key informant interviews with administrators of district hospitals and officers in charge of community health facilities. Focus group discussions were held with health workers and caregivers of children under 24 months of age who received services from study health facilities in Malawi. Coverage rates were collected from the health facility records., Results: Vaccination is appreciated in the communities, but coverage is generally below targets. In some facilities, reported coverage was less than 50%. Opportunities to provide up-to-date vaccination for children were missed due to lack of awareness and knowledge of health workers and caregivers, attitude and priority of health workers, long waiting time, poor coordination and referral of eligible children by clinicians and nurses and overall lack of a team approach to vaccination perceived as a responsibility of health surveillance assistants. Other notable issues included limited time of caregivers labouring on estate farms, unavailability of vaccines resulting from poorly functioning of cold chain equipment and limited transport and failure to appreciate the impact of MOV on poor immunization coverage., Conclusion: Simple, low-cost, pragmatic and community-driven interventions that may reduce MOVs and improve vaccine coverage., Competing Interests: Conflict of Interest None

Background: Delivering vaccination services during the second year of life (2YL) 1 provides countries with an opportunity to achieve greater coverage, to provide booster doses and vaccines missed during the first year of life, as well as contribute towards disease control and elimination goals., Methods: Using data from demographic health surveys (DHSs) conducted during 2010 to 2016, this paper explores the proportion of missed opportunities for vaccinations generally provided during routine immunization among children in their 2YL., Results: DHS data in 46 countries surveyed 478,737 children, from which 169,259 children were 12-23 months old and had vaccination/health cards viewed by surveyors. From this group, 69,489 children aged 12-23 months had contact with health services in their 2YL. Three scenarios for a missed opportunity for vaccinations were analysed: (1) a child received one vaccine in the immunization schedule and was eligible for another vaccine, but did not receive any further vaccination, (2) a child received a vitamin A supplementation (VAS) and was due for a vaccine, but did not receive vaccines that were due, and (3) a child was taken to a health facility for a sick visit and was due (and eligible) for a vaccine, but did not receive the vaccine. A total of 16,409 (24%) children had one or more missed opportunities for vaccinations., Conclusion: This analysis highlights the magnitude of the problem of missed opportunities in the 2YL. The global community needs to provide better streamlined guidance, policies and strategies to promote vaccination screenings at well-child and sick child visits in the 2YL. Where they do not exist, well-child visits in the 2YL should be established and strengthened., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In an essay, Paul Bloem and Ikechukwu Ogbuanu discuss the public health implications of HPV vaccination.

Introduction: Children are important transmitters of influenza in the community and a number of non-pharmaceutical interventions (NPIs), including hand washing and use of hand sanitizer, have been recommended to mitigate the transmission of influenza, but limited information is available regarding schools' ability to implement these NPIs during an influenza outbreak. We evaluated implementation of NPIs during fall 2009 in response to H1N1 pandemic influenza (pH1N1) by New York City (NYC) public schools., Methods: From January 25 through February 9, 2010, an online survey was sent to all the 1,632 NYC public schools and principals were asked to participate in the survey or to designate a school nurse or other school official with knowledge of school policies and characteristics to do so., Results: Of 1,633 schools, 376(23%) accessed and completed the survey. Nearly all respondents (99%) implemented at least two NPIs. Schools that had a Flu Response Team (FRT) as a part of school emergency preparedness plan were more likely to implement the NPI guidelines recommended by NYC public health officials than schools that did not have a FRT. Designation of a room for isolating ill students, for example, was more common in schools with a FRT (72%) than those without (53%) (p<0.001)., Conclusions: Implementing an NPI program in a large school system to mitigate the effects of an influenza outbreak is feasible, but there is potential need for additional resources in some schools to increase capacity and adherence to all recommendations. Public health influenza-preparedness plans should include school preparedness planning and FRTs.

Public health benefits of expanded HIV screening will be adequately realized only if an early diagnosis is followed by prompt linkage to care. We characterized rates and factors associated with failure to enter into medical care within three months of HIV diagnosis and assessed the predictors of time to enter care over a follow-up period of up to 60 months. The study cohort included 3697 South Carolina (SC) residents' ≥13 years who were newly HIV-diagnosed in 2004-2008. Date of first laboratory report of CD4(+) T-cell count or viral load (VL) test after 30 days of confirmatory HIV diagnosis was used to define time to linkage to care. Results showed that of the total 3697 persons, 1768 (48%) entered care within three months, 1115 (30%) in four-12 months after diagnosis, and 814 (22%) failed to initiate care within 12 months of HIV diagnosis. At the end of study follow-up period of up to 60 months from the date of HIV diagnosis, 472/3697 (13%) individuals remained out of care. Multivariable Cox proportional hazards analysis showed that compared with hospitals, time to enter care was shorter in those diagnosed at state mental health/correctional facilities (adjusted hazards ratio [aHR] 1.16; 95% confidence interval [CI] 1.02-1.34) and longer in those diagnosed at county health departments (aHR 0.87; 95% CI 0.80-0.96) and at "Other/unknown" facilities (aHR 0.79; 95% CI 0.70-0.89). Time to entry into care was longer for men (aHR 0.82; 95% CI 0.75-0.89) compared with women, blacks (aHR 0.91; 95% CI 0.83-0.98) compared with whites, and males who have sex with males (MSM) (aHR 0.89; 95% CI 0.80-0.98) compared with heterosexual exposure. Delayed entry into HIV care remains a challenge in controlling HIV transmission in SC. Better integration of testing and care facilities could improve the proportion of newly HIV-diagnosed persons who enter care in a timely manner.

The effect of breastfeeding on asthma is controversial, which may be explained by related and interacting early childhood risk factors. We assessed the joint effects of a risk-triad consisting of maternal smoking during pregnancy, breastfeeding for less than 3 months, and recurrent lower respiratory tract infections (RLRTI) on physician-diagnosed childhood asthma. The association was assessed in the Isle of Wight birth cohort study (1989-1990) using a repeated measurement approach with data collection at birth, and at ages 1, 2, 4, and 10 years. The population consists of 1,456 children recruited between January 1989 and February 1990. Prenatal smoking, breastfeeding for less than 3 months, and recurrent lower respiratory infections (RLRTI) were combined into eight risk-triads. Relative risks (RR) and 95% confidence intervals were estimated with a log-linear model. The risk-triad involving RLRTI in infancy, maternal smoking during pregnancy, and breastfeeding for less than 3 months showed a stronger association with asthma at ages 4 and 10 compared to other risk-triads (RR of 5.79 for any asthma at ages 1, 2, 4, and 10; and 3.1 for asthma at ages 4 and 10). Of the three individual risk factors, RLRTI appeared to be the major driver of the combined effects in the risk-triads. The effect of RLRTI on asthma was modified by breastfeeding. Breastfeeding for > or = 3 months also attenuated the effect of prenatal smoking on asthma in children without RLRTI. A high proportion of asthma cases in childhood can be prevented by promoting breastfeeding, by preventing smoking during pregnancy, and by avoidance of recurrent lower respiratory tract infections in early childhood.