High Child Mortality Research Articles

BIOL-05. IDENTIFICATION AND VALIDATION OF PA2G4 AS A POTENTIAL THERAPEUTIC TARGET IN PEDIATRIC DIFFUSE GLIOMAS

Abstract Brain tumors are the second most common pediatric malignancy after leukemia. High grade gliomas have a significantly high morbidity and mortality in children, with a 5-year survival rate under 20%. This study aims to identify important biological mechanisms and proteins as prognostic biomarkers and novel therapeutic targets. We hypothesize that higher grade pediatric diffuse gliomas can be effectively targeted by knocking down expression of the proliferation associated protein 2G4 (PA2G4) that binds to MYCN and prevents its ubiquitination. LC-MS/MS proteomic profiling was performed on 28 formalin-fixed paraffin embedded primary diffuse glioma samples from Nationwide Children’s Hospital (Columbus, OH). Cox proportional hazard models were used to correlate individual proteins with progression-free survival (PFS) and overall survival (OS). Differences in fold change were calculated for each protein between low grade (LGG, grade 2) and high-grade glioma (HGG, grades 3-4) patients. Ingenuity Pathway Analysis was performed considering only proteins with p-values <0.05. In vitro studies were performed to evaluate the roles of PA2G4 in the SF188 glioma cell line. In comparing high- and low-grade tumors, 471 proteins were found to be significantly differentially expressed. Eighty-six and 121 proteins were significantly associated with OS and PFS, respectively. PA2G4 was expressed 2.0-fold higher in HGG vs LGG (p=0.015). Additionally, high expression of PA2G4 protein was associated with significantly worse PFS (p=0.041) and OS (p=0.035) and selected for further studies. Preliminary in vitro results showed that knocking-down PA2G4 decreased AKT phosphorylation/activation and levels of MYCN protein. Given that activated MYCN plays critical oncogenic roles in patients with poor survival PA2G4 may serve as a novel therapeutic target in higher grade pediatric diffuse gliomas. Studies are underway to unfold how PA2G4 affects treatment resistance and tumor recurrence in pediatric patients.

Analisis Asuhan Keperawatan Bersihan Jalan Napas Tidak Efektif pada Anak Bronkopneumonia Dengan Tindakan Kolaborasi Pemberian Nebulizer di Ruang Picu Rsud Prof. Dr. H. Aloei Saboe

Background: Because of the very high mortality in children and children under the age of five, bronchopneumonia is the leading cause of death in children under the age of five worldwide. When viruses, bacteria, microbes and fungi enter the lungs through the respiratory system, they infect the lung parenchyma and cause pneumonia.
 Objective: Analyzing ineffective airway clearance nursing care in children with bronchopneumonia by collaborative action of administering a nebulizer in the Picu Room of Prof. Hospital. Dr. H Aloei Saboe
 Methods: Participants in this study, which used a quasi-experimental design, received treatment or intervention before measuring and analyzing the impacts. The pre-post-test group design method served as the basis for the research design. In children with bronchopneumonia, this strategy is used to check the results before and after administration of the nebulizer. Two young people who fight against crime become samples.
 Results: The results of the study show the overall evaluation results after nursing actions, namely: Based on the results before being given a nebulizer to patients the problem was not resolved in 2 patients and after being given a nebulizer to patients the problem was resolved in 2 patients
 Conclusion: Based on the description above, inhalation therapy to reduce symptoms of shortness of breath in children with bronchopneumonia is effective where inhalation therapy or steam inhalation therapy using drugs can widen the bronchial airways resulting in complaints such as shortness of breath and disappearance of breath sounds.

BOHEMIA a cluster randomized trial to assess the impact of an endectocide-based one health approach to malaria in Mozambique: baseline demographics and key malaria indicators

BackgroundMany geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission.MethodsThe demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study.Results25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district. The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age.ConclusionsThe study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (< 15 years) and there is a high childhood mortality. The results of this survey were crucial as they provided the household and population profiles and allowed the design and implementation of the cluster randomized clinical trial.Trial registration NCT04966702.

Antiviral effect of Favipiravir against Chandipura virus in vitro and in vivo.

Chandipura virus (CHPV) is an emerging encephalitic virus with outbreak potential in a pediatric population. It causes acute encephalitis, with clinical symptoms leading to death within 48-72 h and an alarmingly high case fatality rate up to 55%-78%. Despite the high mortality rate in children, no vaccines or antivirals are currently available; thus, repurposing licensed drugs seems to be one of the attractive therapeutic approaches. Among the various options available, Favipiravir emerged as a promising candidate, and its unique characteristics and clinical efficacy have garnered significant attention and demonstrated considerable potential in the fight against viral diseases. In the current study, we have evaluated the antiviral effect of Favipiravir against CHPV by Plaque reduction assay and viral growth kinetics assay in Vero cells and in vivo effect of drug treatment against lethal viral challenge was analysed in 10-day-old CD1 mice. A dose-dependent reduction in CHPV plaque size and number was observed in Vero cells treated with Favipiravir, with an EC50 of 92.26 μM. Complete inhibition of CHPV replication was observed at 320 μM drug concentration and 50% cytotoxicity (CC50 ) at 4774 μM, indicating a high selectivity index 51.24. In vivo, studies in mice showed 100% survival with 300 mg/kg/day of Favipiravir given orally till seventh-day postinfection. The study provides evidence of the antiviral activity of Favipiravir against CHPV infection, and further clinical evaluation may alleviate the associated mortality.

Real-world vaccination status of children with hematologic tumors before and after chemotherapy

ABSTRACTBackgroundThere is a high incidence and mortality rate in children with hematologic tumors (CHT), who are more prone to various infectious diseases. This study aims to clarify the real-world National Immunization Program (NIP) vaccination status of CHT before and after chemotherapy.MethodsMedical records, NIP vaccination data, and the Adverse Event Following Immunization (AEFI) of CHT who were admitted to the Children’s Hospital, Zhejiang University School of Medicine, from 1 January 2011 to 1 December 2021 were completely collected.ResultsA total of 2,874 CHT were included, and 1975 (68.7%) had vaccination records. Among the enrolled patients, the vaccination rate of all NIP vaccines was lower than 90% before diagnosis. Only 24.29% of CHT (410/1688) resumed vaccination after chemotherapy, and 69.02% (283/410) resumed vaccination more than 12 months after chemotherapy. No uncommon or serious side effects were reported.ConclusionThe vaccination rate of CHT after chemotherapy was lower than that before the disease was diagnosed. It is necessary to provide more evidence-based support and formulate specific regimens to perfect the vaccination procedure after chemotherapy so as to improve the quality of life of CHT.

METTL1/WDR4-mediated tRNA m7G modification and mRNA translation control promote oncogenesis and doxorubicin resistance.

Osteosarcoma is the most common bone tumor that leads to high mortality in adolescents and children. The tRNA N7-methylguanosine methyltransferase METTL1 is located in chromosome 12q14.1, a region that is frequently amplified in osteosarcoma patients, while its functions and underlying mechanisms in regulation of osteosarcoma remain unknown. Herein we show that METTL1 and WDR4 are overexpressed in osteosarcoma and associated with poor patient prognosis. Knockdown of METTL1 or WDR4 causes decreased tRNA m7G modification level and impairs osteosarcoma progression in vitro and in vivo. Conversely, METTL1/WDR4 overexpression promotes osteosarcoma proliferation, migration and invasion capacities. tRNA methylation and mRNA translation profiling indicate that METTL1/WDR4 modified tRNAs enhance translation of mRNAs with more m7G tRNA-decoded codons, including extracellular matrix (ECM) remodeling effectors, which facilitates osteosarcoma progression and chemoresistance to doxorubicin. Our study demonstrates METTL1/WDR4 mediated tRNA m7G modification plays crucial oncogenic functions to enhance osteosarcoma progression and chemoresistance to doxorubicin via alteration of oncogenic mRNA translation, suggesting METTL1 inhibition combined with chemotherapy is a promising strategy for treatment of osteosarcoma patients.

Investing in Infants: Child Protection and Nationalism in Transylvania during Dualism and the Interwar Period

AbstractThe high infant mortality rate of illegitimate children in Dualist Hungary urged politicians to create a modern state child welfare system for the protection of abandoned children whose upbringing became a national matter. Their main concern was providing adequate nutrition for infants and increase their chances of survival. The article examines how demographical concerns and national-political ideals influenced the evolution of the child welfare system in multi-ethnic Transylvania, first as part of the dual monarchy and after the First World War as a province of Romania. The Hungarian state children’s asylums offered a variety of nursing programs for abandoned infants, where the foster-care system often resulted in their Magyarization at a later age. During the First World War, the new objective was the protection of infants together with mothers and the promotion of breastfeeding in order to ensure the viability of the Hungarian nation. National arguments were used in both time periods to support infant protection initiatives. In interwar Transylvania, the urban-rural ethnic distribution influenced the development of infant protection facilities: all state investments were channeled toward the “authentic” Romanian countryside, while in the “foreign” urban environment ethnic minorities focused on their own institutions.

SOCIAL DETERMINANTS OF INFANT AND CHILD MORTALITY

Infant and child mortality rate are significant phenomenon closely related to the healthy status of a society. They are major indicators of development. The secondary analysis methodology was adopted in this study while the major source of data was NDHS 2013 report. The ex post-facto research design was used in describing the NDHS 2013 qualitative data. The collected data is centered on Nigeria while empirical studies are not limited to Nigeria.to classify various social determinants of infant and child mortality either as individual and community factors or endogenous and exogenous factors. These social determinants were ex-rayed in relationship to their socio-economic implication. At the macro level, high rate of infant and child mortality are clear indices of poor health care facility and system, unhygienic environment, chronic poverty, enduring illiteracy and intense insecurity. At the micro level, it shows skewed income distribution, ignorance, poor exposure and food insufficiency. The study shows that social exclusion of mothers from decision making, inadequate knowledge about care for pregnancies, attitude toward accessibility of quality and affordable health care and insecurity have influence on morality growth. While there was an inverse relationship between income, residence, education, occupation, age of mothers, mother’s experience and infant and child mortality, there was a positive relationship between choice of contraceptives, male preference, mother’s non-freedom of choice, attitude toward place of delivery, inaccessibility of antenatal and post-natal care, perception toward acceptance of anti-tetanus treatment during pregnancies, incompetency of health workers and infant and child mortality. The study also shows that increase in per capital GDP is associated with decrease in infant and child mortality.

5610785 THE EFFICACY OF HEALTH EDUCATION INTERVENTION AND MATERNAL SCREENING ON KNOWLEDGE AND INFANT SCREENING FOR SICKLE CELL DISEASE AMONG PREGNANT WOMEN ATTENDING ANTENATAL CLINICS IN DAR-ES-SALAAM, TANZANIA

Background: Globally, Sickle cell disease (SCD) is one of the most common genetic disease with high childhood mortality 1. Early identification of babies with SCD through newborn screening (NBS) and linking them to care are among the recommended interventions 2. For these to be effective, it is important for pregnant women to have the right knowledge on SCD and motivation to screen their babies. Aim: To assess the efficacy of health education (HE) intervention and maternal screening for SCD on knowledge and the uptake of infant screening for SCD among pregnant women attending antenatal clinics (ANC) in Dar-Es-Salaam, Tanzania. Methods: This was a quasi-experimental study, involved pregnant women attending ANC at Buguruni health center, Mbagala hospital and Sinza hospital in Dar Es Salaam between August 2020 to April 2022. A structured questionnaire was used in data collection. Knowledge on SCD (poor if score <7; good if score 7-10) was assessed to all participants before and after two sessions of HE3, and participants in Buruguni and Mbagala were also screened for SCD using Sickle SCAN point-of-care test (BioMedomics Inc, USA). We computed effectiveness of HE intervention as the post-intervention minus baseline knowledge score. Two-sample test of proportions, univariate and multivariate logistic regression were used to analyze the efficacy of HE intervention and also predictors of infant diagnosis. Before enrollment, written informed consent was obtained from participants, parents/guardian of participants <18 years of age. Results: A total of 467 pregnant women completed two sessions of HE intervention where 221 (47.3 %) participants were screened for SCD; Out of 221 screened participants, 203 (91.9%) remembered their sickle cell status 3 to 4 months after screening. The proportion of participants with good knowledge on SCD had significantly increased from 12.4% at baseline to 85.9% following the education intervention p-value <0.0001. HE provided was effective to 85.3% of participants, and was 2.45 times higher among those who shared the received education with others than those who did not share (AOR = 2.45; 95% CI = 1.38 to 4.36). The uptake of infant diagnosis was 5.39 higher in infants whose mothers shared the received education than those who did not share (AOR = 5.39; 95% CI = 1.18 to 24.67). 5.4% of babies (26/170 babies) were screened post-delivery, and 3 of them had Hb SS. Mothers who were employed had 6.49 higher odds of screening their infants than housewives (AOR = 6.49; 95% CI =1.52 to 27.79). Maternal status was also seen to associate with infant diagnosis whereby those with hemoglobin S (AS or SS) had 13.28 times higher odds of screening their infants than those who did not know their SCD status (AOR = 13.28; 95% CI = 4.11 to 42.86). There was no difference in odds of the baby being screened for SCD between mothers who had Hemoglobin AA as compared to mothers who were not screened for SCD (AOR = 1.62; 95% CI = 0.56 to 4.84). Conclusion: This study has demonstrated that maternal HE and maternal screening for SCD are feasible and effective interventions in increasing knowledge as well as improving the uptake of infant screening for SCD. These interventions are strongly recommended to be included in the comprehensive care package for pregnant women attending antenatal clinics, particularly in areas with a high burden of SCD.

Differential coverage for vaccines in the expanded program on immunization (EPI) among children in rural Pakistan.

Pakistan has a well-established Expanded Program on Immunization (EPI) however vaccine-preventable diseases still account for high infant and child mortality rates. This study describes the differential vaccine coverage and determinants of vaccine uptake in rural Pakistan. From October 2014 to September 2018, we enrolled children younger than 2years of age from the Matiari Demographic Surveillance System in Sindh, Pakistan. Socio-demographic and vaccination history were collected from all participants. Vaccine coverage rates and timeliness were reported. Socio-demographic variables for missed and untimely vaccination were studied in multivariable logistic regression. Of the 3140 enrolled children, 48.4% received all EPI recommended vaccines. Only 21.2% of these were age appropriate. Around 45.4% of the children were partially vaccinated, and 6.2% were unvaccinated. Highest coverage was seen for the first dose of pentavalent (72.8%), 10-valent Pneumococcal Conjugate Vaccine (PCV10) (70.4%) and Oral Polio Vaccine (OPV) (69.2%) and the lowest coverage was for measles (29.3%) and rotavirus (1.8%) vaccines. Primary caretakers and wage earners with a higher level of education were protective against missed and untimely vaccination. Enrollment in the 2nd, 3rd and 4th study year was negatively associated with being unvaccinated whereas distance from a major road was positively associated with non-adherence to schedule. Vaccine coverage was low among children in Matiari, Pakistan, and majority received delayed doses. Parents' education status and year of study enrollment was protective against vaccine dropout and delayed vaccination whereas geographical distance from a major road was a predictor. Vaccine promotion and outreach efforts may have had a beneficial impact on vaccine coverage and timeliness.

Clinical and epidemiological features of pediatric population hospitalized with COVID-19: a multicenter longitudinal study (March 2020-December 2021) from Pakistan.

We aimed to explore the epidemiological, clinical, and phenotypic parameters of pediatric patients hospitalized with COVID-19 in Pakistan. This longitudinal cohort study was conducted in five tertiary care hospitals in Pakistan from March 2020 to December 2021. Data on various epidemiological and clinical variables were collected using Case Report Forms (CRFs) adapted from the WHO COVID-19 clinical data platform at baseline and at monthly follow-ups for 3 months. A total of 1090 children were included. The median age was 5 years (Interquartile range 1-10), and the majority presented due to new signs/symptoms associated with COVID-19 (57.8%; n=631), the most common being general and respiratory symptoms. Comorbidities were present in 417 (38.3%) children. Acute COVID-19 alone was found in 932 (85.5%) children, 81 (7.4%) had multisystem inflammatory syndrome (MIS-C), 77 (7.0%) had overlapping features of acute COVID-19 and MIS-C, and severe disease was found in 775/1086 (71.4%). Steroids were given to 351 (32.2%) patients while 77 (7.1%) children received intravenous immunoglobulins. Intensive care unit (ICU) care was required in 334 (31.6%) patients, and 203 (18.3%) deaths were reported during the study period. The largest spike in cases and mortality was from July to September 2021 when the Delta variant first emerged. During the first and second follow-ups, 37 and 10 children expired respectively, and medical care after discharge was required in 204 (25.4%), 94 (16.6%), and 70 (13.7%) children respectively during each monthly follow-up. Our study highlights that acute COVID-19 was the major phenotype associated with high severity and mortality in children in Pakistan in contrast to what has been observed globally. The study was supported by the World Health Organization (WHO), which was involved in the study design but played no role in its analysis, writeup, or publication.

Facilitators and barriers associated with breastfeeding among mothers attending primary healthcare facilities in Mpumalanga, South Africa.

Despite the health benefits of breastfeeding for both the mother and the child, early cessation of breastfeeding remains a public health problem in South Africa, attributed to contextual barriers and facilitators. Within the context of Mpumalanga province, which is characterized by low breastfeeding rates and high infant mortality rates in children under 5 years, we explored the facilitators and barriers to breastfeeding among mothers attending the three primary health facilities in Ermelo. Using a semi-structured interview guide suggested by the socio-ecological model, three focus group discussions and 12 in-depth interviews were conducted among mothers selected using a purposive sampling. Transcripts from audiotaped and transcribed verbatim interviews were assessed through thematic analysis using NVivo version 10. Mothers were aged between 18 and 42 years and from poor sociodemographic backgrounds. At the individual level, mothers valued breastfeeding facilitated by their commitment, maintaining it, eating healthy foods, and having sufficient breast milk. However, returning to work, insufficient breast milk, misconceptions about breastfeeding, and interference with social life were the barriers for mothers to breastfeed continuously. At the interpersonal level, the family was identified as the main form of support to breastfeeding mothers; however, family interference was also identified as a barrier. At the community level, mothers shared some family beliefs and practices but were still split between societal and cultural norms and traditional beliefs as facilitators or barriers to breastfeeding. At the organizational level, most mothers valued the support provided by healthcare workers on childcare and techniques for breastfeeding at the health facilities. They did however articulate concerns on the miscommunication some healthcare workers offered regarding breastfeeding, which negatively influenced their infant feeding practices. Intervention efforts should focus on behaviour change to educate and equip mothers to overcome the barriers that are within their control. Such interventions should further focus on family-centered education and strengthening the proficiency of healthcare workers on advising breastfeeding mothers.

Neural tube defects: a review of global prevalence, causes, and primary prevention.

Neural tube defects (NTDs) are common birth defects and contribute to life-long disabilities, high medical care costs, and perinatal and child mortality. This review is a primer on prevalence, causes, and evidence-based prevention strategies for NTDs. The estimated average global prevalence of NTDs is two cases per 1000 births, amounting toapproximately 214,000-322,000 affected pregnancies worldwide annually. Prevalence and associated adverse outcomes are disproportionately high in developing countries. NTDs have multiple risk factors including genetic and non-genetic (i.e., maternal nutritional status, pre-pregnancy diabetes, early pregnancy exposure to valproic acid (anti-epileptic medication), and a previous pregnancy affected by aNTD) factors. Maternal folate insufficiency before and during early pregnancy is the most common risk factor and is preventable. Folic acid (vitamin B9) is required for formation of the neural tube early in pregnancy, around 28days after conception, when most women are unaware of their pregnancies. Current guidelines recommend that all women planning or capable of pregnancy take a daily supplement containing 400-800μg of folic acid. Mandatory folic acid fortification of staple foods (e.g., wheat flour, maize flour, rice) is safe, economical, and the effective intervention for primary prevention of NTDs. Currently, about 60 countries are implementing mandatory folic acid fortification of staple foods, preventing just a quarter of all preventable NTD cases worldwide. There is an urgent need for active champions, including neurosurgeons and other healthcare providers, to generate political will and promote effective mandatory food fortification with folic acid, and reach equitable primary prevention of NTDs in all countries.

Ten-year survival of children with trisomy 13 or trisomy 18: a multi-registry European cohort study

ObjectiveTo investigate the survival to 10 years of age of children with trisomy 13 (T13) and children with trisomy 18 (T18), born 1995–2014.DesignPopulation-based cohort study that linked mortality data to...

The 30 Years' War and Violent Crime in the Late 19th Century

We introduce a unique data set of estimated population losses in Germany as a result of the 30 Years’ War (30 YW), fought between 1618 and 1648, which we match to German counties as defined in 1900. We find that counties with larger population losses experience significantly more youth assault crimes in 1900. To support a more causal interpretation of our results, we identify a set of counterfactual counties via propensity score matching. On this matched sample, we find that a county’s 30 YW population losses are largely unrelated to a wide range of pre-30 YW social, economic, geographic and religious characteristics, indicating that our result is driven by differential exposure to the violence of the war and not by pre-existing county differences. Although, owing to the historical nature of our data, it is difficult to uncover precise mechanisms, we present additional evidence that suggests 30 YW population losses lead to a general deterioration of county social and economic conditions over time: Differential exposure to the violence of the war led otherwise similar counties to experience more conflict following the 30 YW as well as higher rates of child mortality, less welfare expenditure, and increases in suicides some 250 years later. (JEL: N33, N43, D74, Z10)

Public health determinants of child malaria mortality: a surveillance study within Siaya County, Western Kenya

BackgroundMalaria deaths among children have been declining worldwide during the last two decades. Despite preventive, epidemiologic and therapy-development work, mortality rate decline has stagnated in western Kenya resulting in persistently high child malaria morbidity and mortality. The aim of this study was to identify public health determinants influencing the high burden of malaria deaths among children in this region.MethodsA total of 221,929 children, 111,488 females and 110,441 males, under the age of 5 years were enrolled in the Kenya Medical Research Institute/Center for Disease Control Health and Demographic Surveillance System (KEMRI/CDC HDSS) study area in Siaya County during the period 2003–2013. Cause of death was determined by use of verbal autopsy.Age-specific mortality rates were computed, and cox proportional hazard regression was used to model time to malaria death controlling for the socio-demographic factors. A variety of demographic, social and epidemiologic factors were examined.ResultsIn total 8,696 (3.9%) children died during the study period. Malaria was the most prevalent cause of death and constituted 33.2% of all causes of death, followed by acute respiratory infections (26.7%) and HIV/AIDS related deaths (18.6%). There was a marked decrease in overall mortality rate from 2003 to 2013, except for a spike in the rates in 2008. The hazard of death differed between age groups with the youngest having the highest hazard of death HR 6.07 (95% CI 5.10–7.22). Overall, the risk attenuated with age and mortality risks were limited beyond 4 years of age. Longer distance to healthcare HR of 1.44 (95% CI 1.29–1.60), l ow maternal education HR 3.91 (95% CI 1.86–8.22), and low socioeconomic status HR 1.44 (95% CI 1.26–1.64) were all significantly associated with increased hazard of malaria death among children.ConclusionsWhile child mortality due to malaria in the study area in Western Kenya, has been decreasing, a final step toward significant risk reduction is yet to be accomplished. This study highlights residual proximal determinants of risk which can further inform preventive actions.

Generating enhanced mucosal immunity against Bordetella pertussis: current challenges and new directions.

Bordetella pertussis (Bp) is the highly transmissible etiologic agent of pertussis, a severe respiratory disease that causes particularly high morbidity and mortality in infants and young children. Commonly known as "whooping cough," pertussis is one of the least controlled vaccine-preventable diseases worldwide with several countries experiencing recent periods of resurgence despite broad immunization coverage. While current acellular vaccines prevent severe disease in most cases, the immunity they confer wanes rapidly and does not prevent sub clinical infection or transmission of the bacterium to new and vulnerable hosts. The recent resurgence has prompted new efforts to generate robust immunity to Bp in the upper respiratory mucosa, from which colonization and transmission originate. Problematically, these initiatives have been partially hindered by research limitations in both human and animal models as well as potent immunomodulation by Bp. Here, we consider our incomplete understanding of the complex host-pathogen dynamics occurring in the upper airway to propose new directions and methods that may address critical gaps in research. We also consider recent evidence that supports the development of novel vaccines specifically designed to generate robust mucosal immune responses capable of limiting upper respiratory colonization to finally halt the ongoing circulation of Bordetella pertussis.

Increased nuchal translucency in children with congenital heart defects and normal karyotype-is there a correlation with mortality?

Our objective was to investigate if an increased nuchal translucency (NT) was associated with higher mortality in chromosomally normal children with congenital heart defects (CHD). In a nationwide cohort using population-based registers, we identified 5,633 liveborn children in Denmark with a pre- or postnatal diagnosis of CHD from 2008 to 2018 (incidence of CHD 0.7%). Children with chromosomal abnormalities and non-singletons were excluded. The final cohort compromised 4,469 children. An increased NT was defined as NT > 95th-centile. Children with a NT > 95th-centile vs. NT < 95th-centile including subgroups of simple- and complex CHD were compared. Mortality was defined as death from natural causes, and mortalities were compared among groups. Survival analysis with Cox-regression was used to compare rates of mortality. Analyses were adjusted for mediators (possibly explanatory factors between increased NT and higher mortality): preeclampsia, preterm birth and small for gestational age. And for confounding effects of extracardiac anomalies and cardiac intervention, due to their close association to both the exposure and the outcome (i.e., confounders). Of the 4,469 children with CHD, 754 (17%) had complex CHD and 3,715 (83%) simple CHD. In the combined group of CHDs the mortality rate was not increased when comparing those with a NT > 95th-centile to those with a NT < 95th-centile [Hazard ratio (HR) 1.6, 95%CI 0.8;3.4, p = 0.2]. In simple CHD there was a significantly higher mortality rate with a HR of 3.2 (95%CI: 1.1;9.2, p = 0.03) when having a NT > 95th centile. Complex CHD had no differences in mortality rate between a NT > 95th-centile and NT < 95th-centile (HR 1.1, 95%CI: 0.4;3.2, p = 0.8). All analysis adjusted for severity of CHD, cardiac operation and extracardiac anomalies. Due to limited numbers the association to mortality for a NT > 99th centile (>3.5 mm) could not be assessed. Adjustment for mediating (preeclampsia, preterm birth, small for gestational age) and confounding variables (extracardiac anomalies, cardiac intervention) did not alter the associations significantly, except for extracardiac anomalies in simple CHD. An increased NT > 95th-centile is correlated with higher mortality in children with simple CHD, but the underlying cause is unknown and undetected abnormal genetics might explain the correlation rather than the increased NT itself, hence further research is warranted.

High Burden of Co-Infection with Multiple Enteric Pathogens in Children Suffering with Diarrhoea from Rural and Peri-Urban Communities in South Africa.

Infectious diarrhoea contributes to high morbidity and mortality in young children from sub-Saharan Africa. The aim of this study was to assess the prevalence of single and multiple diarrhoeal-causing pathogen combinations in children suffering from diarrhoea from rural and peri-urban communities in South Africa. A total of 275 diarrhoea stool specimens were collected between 2014 and 2016 from Hospitals and Primary Health Care clinics. The BioFire® FilmArray® Gastrointestinal panel was used to simultaneously detect 22 diarrhoea pathogens (viruses, bacteria, parasites) known to cause diarrhoea. A total of 82% (226/275) enteric pathogens were detected in the stool specimens. The two most detected bacterial, viral and parasitic pathogens each included: EAEC (42%), EPEC (32%), Adenovirus F40/41 (19%), Norovirus (15%), Giardia (8%) and Cryptosporidium (6%), respectively. Single enteric pathogen infections were recorded in 24% (65/275) specimens with EAEC, and Norovirus was found in 26% (17/65) and 14% (9/65) of the specimens, respectively. Multiple enteric pathogen combinations were recorded in 59% (161/275) of the stool specimens with 53% (85/161) containing two pathogens, 22% (35/161) containing three pathogens and 25% (41/161) containing four or more pathogens. The results from this study demonstrated the complex nature of pathogen co-infections in diarrhoeal episodes which could have an impact on treatment effectiveness.

Navigating the Health and Wellbeing Landscape in South Asia: Assessing Progress, Addressing Challenges, and Charting a Path Forward

This article aims to assess the current state of health and wellbeing in South Asia, identify the major challenges that are currently facing the region, and propose solutions for addressing these challenges and charting a path forward. The article begins by providing an overview of the current state of health and wellbeing in South Asia, highlighting the progress that has been made in recent years as well as the areas where progress has been slow. It then goes on to discuss the major challenges that are facing the region, such as inadequate healthcare infrastructure, lack of access to quality healthcare services, and high rates of maternal and child mortality. The article then proposes solutions for addressing these challenges, including increasing access to healthcare, improving maternal and child health, addressing non-communicable diseases, promoting universal access to sexual and reproductive health services and rights, strengthening health systems, increasing domestic resource allocation to health, and enhancing regional cooperation and coordination. Ultimately, this article serves as a call to action for policymakers, healthcare providers, and other stakeholders to work together to improve the health and wellbeing of the people of South Asia.