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Introduction\ud The beta EQ-5D-Y-5L is a new patient-reported outcome measure (PROM) for children aged 8–15 years that is currently under development by the EuroQol Group. The EQ-5D-Y-5L is similar to the EQ-5D-Y but has five levels of severity per dimension rather than three. The increased number of levels increases the granularity of the responses but possibly has also increased the difficulty of distinguishing between levels. The EuroQoL’s Version Management Committee (VMC) required a robust method to determine how well children distinguish between the five EQ-5D-Y-5L ordinal severity qualifiers (i.e. ‘no problems’ through to ‘extreme problems’), which are a critical aspect of both health measurement and the valuation of health states.\ud \ud Objective\ud This paper describes the development, testing, selection, and piloting of such a method.\ud \ud Methods\ud Following a literature review and consultation with the wider VMC and a Language Support Services agency, a range of exercises were developed to assess the ordering and comprehension of the five severity qualifiers. Three exercises were pre-tested with children in Spain and New Zealand. One exercise, preferred and understood by children, was then piloted.\ud \ud Results\ud Five children in Spain and 11 in New Zealand tested the three exercises. In both countries, all children found the three exercises easy to understand and complete. Of the 12 children who expressed a preference, nine said they preferred the card ranking. Card ranking also allowed the interviewer to observe difficult choices being made as the children physically rearranged the card order until they settled on their final order. Following rigorous assessment of translatability and cultural portability by an independent Language Support Service, card ranking was piloted in South Africa (n = 9) and in Indonesia (n = 10), where it highlighted severity qualifier order inversions that would otherwise not have been detected.\ud \ud Conclusion\ud The card ranking exercise was found to be a preferred and acceptable means of testing the ordering of translations of severity qualifiers among children. Additional formal testing of the exercise in other countries and languages is now underway. The approach developed and tested by the VMC for cognitive debriefing of beta EQ-5D-Y-5L language/country versions may also be useful in determining the adequacy of translated qualifiers in debriefing of adult EQ-5D-5L versions and other PROMs.

BackgroundShortages of clinical staff make chronic asthma care challenging in low-income countries. We evaluated an outpatient asthma care package for children, including task-shifting of asthma management roles.MethodsWe conducted a non-blinded individually randomised controlled trial at a tertiary-level government hospital in Blantyre, Malawi. Children aged 6–15 years diagnosed with asthma were recruited from outpatient clinic, stratified by Childhood Asthma Control Test (cACT) score and allocated 1:1 from a concealed file, accessed during electronic questionnaire completion. The intervention, delivered by non-physicians, comprised clinical assessment, optimisation of inhaled treatment, individualised asthma education. The control group received standard care from outpatient physicians. Primary outcome for intention-to-treat analysis was change in cACT score at 3 months. Secondary outcomes included asthma exacerbations requiring emergency healthcare and school absence.FindingsBetween September 2018 and December 2019, 120 children (59 intervention; 61 control) were recruited; 65.8% males, with mean (SD) age 9.8 (2.8) years, mean (SD) baseline cACT 20.3 (2.6). At 3 months, intervention children (n=56) had a greater mean (SD) change in cACT score from baseline (2.7 (2.8) vs 0.6 (2.8)) compared with standard care participants (n=59); a difference of 2.1 points (95% CI: 1.1 to 3.1, pInterpretationThe intervention resulted in decreased asthma symptoms and exacerbations. Wider scale-up could present substantial benefits for asthmatic patients in resource-limited settings.Trial registration numberPACTR201807211617031.

A special-care neonatal unit from a large public hospital in Malawi was noted as having more frequent, difficult-to-treat infections, and a suspected outbreak of multi-drug-resistant Klebsiella pneumoniae was investigated using genomic characterisation. All K. pneumoniae bloodstream infections (BSIs) from patients in the neonatal ward (n=62), and a subset of K. pneumoniae BSI isolates (n=38) from other paediatric wards in the hospital, collected over a 4 year period were studied. After whole genome sequencing, the strain sequence types (STs), plasmid types, virulence and resistance genes were identified. One ST340 clone, part of clonal complex 258 (CC258) and an ST that drives hospital outbreaks worldwide, harbouring numerous resistance genes and plasmids, was implicated as the likely cause of the outbreak. This study contributes molecular information necessary for tracking and characterizing this important hospital pathogen in sub-Saharan Africa.

Using a matched case control design conducted at MRC Gambia in 2015, we measured vitamin D levels in pairs of asymptomatic children with discordant tuberculin skin test status despite the same sleeping proximity to the same adult TB index case. Median ages of groups (infected; 10.0 years, uninfected 8.8 years) were not significantly different (p = 0.13). Mean vitamin D levels were 2.05 ng/mL (95% CI - 0.288 to 4.38) higher in 24 highly TB-exposed uninfected children compared with 24 matched highly TB-exposed infected children (p = 0.08). The findings warrant further investigation in larger studies to understand the implications and significance. Conclusion: Vitamin D levels were higher in TB-uninfected children compared with TB-infected despite equal high exposure to a TB case.

Background Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring. Methods and findings Between April 2014 and April 2015, we followed 421 Malawian mother–baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur–Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], −7.53 [−13.04, −2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], −8.57 [−13.09, −4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies. Conclusions This mother–baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children., Andrea Weckman and co-workers study associations between children’s neurodevelopmental outcomes and malaria in pregnancy., Author summary Why was this study done? Large human cohorts have linked maternal infection during pregnancy (without congenital infection) to an increased risk for neurocognitive deficits and neuropsychiatric disease in exposed children. Excessive maternal immune activation, irrespective of pathogen, is thought to mediate this effect. Millions of pregnant women are at risk for malaria infection each year. To our knowledge, the impact of malaria during pregnancy on child neurodevelopment has not been systematically studied in a clinical setting. What did the researchers do and find? We conducted an observational cohort follow-up study nested within a larger randomized controlled trial with detailed records of malaria in pregnancy to examine the impact of malaria in pregnancy on neurocognitive development in exposed children. To our knowledge, our data provide the first indication in a clinical cohort that malaria in pregnancy may be a previously unrecognized risk factor for neurodevelopmental delay. Furthermore, the association of systemic inflammation with reduced neurocognitive scores highlights a potential mechanistic pathway through which malaria in pregnancy could be affecting fetal neurodevelopment. What do these findings mean? There are millions of children in malaria-endemic regions who are not currently meeting their developmental potential. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental delay in children exposed in utero. Our findings suggest that scaling up efforts to prevent malaria infection could be an effective strategy to protect mother–baby dyads from poor developmental outcomes. Larger trials powered to address potential residual confounding, with a longer follow-up period and more diverse neurocognitive and neuropsychiatric tests, are required to confirm and extend these findings.

BACKGROUND\ud Typhoid fever caused by multidrug-resistant H58 Salmonella Typhi is an increasing public health threat in sub-Saharan Africa.\ud \ud METHODS\ud We conducted a phase 3, double-blind trial in Blantyre, Malawi, to assess the efficacy of Vi polysaccharide typhoid conjugate vaccine (Vi-TCV). We randomly assigned children who were between 9 months and 12 years of age, in a 1:1 ratio, to receive a single dose of Vi-TCV or meningococcal capsular group A conjugate (MenA) vaccine. The primary outcome was typhoid fever confirmed by blood culture. We report vaccine efficacy and safety outcomes after 18 to 24 months of follow-up.\ud \ud RESULTS\ud The intention-to-treat analysis included 28,130 children, of whom 14,069 were assigned to receive Vi-TCV and 14,061 were assigned to receive the MenA vaccine. Blood culture–confirmed typhoid fever occurred in 12 children in the Vi-TCV group (46.9 cases per 100,000 person-years) and in 62 children in the MenA group (243.2 cases per 100,000 person-years). Overall, the efficacy of Vi-TCV was 80.7% (95% confidence interval [CI], 64.2 to 89.6) in the intention-to-treat analysis and 83.7% (95% CI, 68.1 to 91.6) in the per-protocol analysis. In total, 130 serious adverse events occurred in the first 6 months after vaccination (52 in the Vi-TCV group and 78 in the MenA group), including 6 deaths (all in the MenA group). No serious adverse events were considered by the investigators to be related to vaccination.\ud \ud CONCLUSIONS\ud Among Malawian children 9 months to 12 years of age, administration of Vi-TCV resulted in a lower incidence of blood culture–confirmed typhoid fever than the MenA vaccine. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT03299426)

Background\ud Previous studies have found mixed evidence for an effect of malaria on stunting, but have suffered from concerns about confounding and/or power. Currently, an effect of malaria on stunting is not included in the Lives Saved Tool (LiST) model.\ud \ud Methods\ud We used instrumental variables regression with the sickle cell trait and random assignment to bednets as instruments in the analysis of data on children aged 0–2 y from a bednet trial in western Kenya.\ud \ud Results\ud We estimated that one additional clinical malaria episode per year increases the odds of a child being stunted by 6% (OR estimate: 1.06, 95% CI 1.01 to 1.11).\ud \ud Conclusions\ud Our finding that malaria affects stunting suggests that an effect of malaria on stunting in young children should be considered in the LiST model.

Objectives: Consideration of health status in children and adolescents now includes broader concepts such as health-related\ud quality-of-life (HRQoL). Globally, there is a need for relevant preference-based HRQoL measures (PBMs) for use in children\ud and adolescents, yet measurement of HRQoL in these groups presents particular challenges. This article systematically\ud reviews the available generic childhood PBMs and their application and cross-cultural validation in sub-Saharan African (sSA).\ud Methods: A systematic review of published literature from January 1, 1990, to February 8, 2017, was conducted using MEDLINE\ud (through OvidSP), EMBASE (OvidSP), EconLit (EBSCOhost), PsycINFO, Web of Science, and PubMed.\ud Results: A total of 220 full-text articles were included in a qualitative synthesis. Ten generic childhood PBMs were identified,\ud of which 9 were adapted from adult versions and only 1 was developed specifically for children. None of the measures were\ud originally developed in sSA or other resource-constrained settings. The Health Utilities Index Mark 3 (HUI3) and the EQ-5D-Y\ud were the only measures that had been applied in sSA settings. Further, the HUI3 and the EQ-5D-Y were the only generic\ud childhood PBM that attempted to establish cross-cultural validation in sSA. Five of the 6 of these validation studies were\ud conducted using the EQ-5D-Y in a single country, South Africa.\ud Conclusions: The findings show that application of generic childhood PBMs in sSA settings has hitherto been limited to the\ud HUI3 and EQ-5D-Y. Most adaptations of existing measures take an absolutist approach, which assumes that measures can be\ud used across cultures. Nevertheless, there is also need to ensure linguistic and conceptual equivalence and undertake\ud validation across a range of sSA cultural contexts.

Objectives\ud This is a protocol for a Cochrane Review (intervention). The objectives are as follows:\ud \ud To evaluate the role of child growth monitoring and promotion (GMP) in identifying and addressing faltering growth, improving infant and child feeding practices, and promoting contact and use of health services in children under five years of age living in the community in low‐ and middle‐income countries.

ObjectiveTo determine whether Rojiroti microfinance, for poor Indian women, improves child nutrition.DesignCluster randomised trial.SettingTolas (village communities) in Bihar State.ParticipantsWomen and children under 5 years.InterventionsWith Rojiroti microfinance, women form self-help groups and save their money to provide loans to group members. After 6 months, they receive larger external loans. Tolas were randomised to receive Rojiroti immediately or after 18 months.Outcome measuresThe primary analysis compared the mean weight for height Z score (WHZ) of children under 5 years in the intervention versus control tolas who attended for weight and height measurement 18 months after randomisation. Secondary outcomes were weight for age Z score (WAZ), height for age Z score, mid-upper arm circumference (MUAC), wasting, underweight and stunting.ResultsWe randomised 28 tolas to each arm and collected data from 2469 children (1560 mothers) at baseline and 2064 children (1326 mothers) at follow-up. WHZ was calculated for 1718 children at baseline and 1377 (674 intervention and 703 control) at follow-up. At 18 months, mean WHZ was significantly higher for intervention (−1.02) versus controls (−1.37; regression coefficient adjusted for clustering β=0.38, 95% CI 0.16 to 0.61, p=0.001). Significantly fewer children were wasted in the intervention group (122, 18%) versus control (200, 29%; OR=0.46, 95% CI 0.28 to 0.74, p=0.002). Mean WAZ was better in the intervention group (−2.13 vs −2.37; β=0.27, 95% CI 0.11 to 0.43, p=0.001) as was MUAC (13.6 cm vs 13.4 cm; β=0.22, 95% CI 0.03 to 0.40, p=0.02). In an analysis adjusting for baseline nutritional measures (259 intervention children and 300 control), only WAZ and % underweight showed significant differences in favour of the intervention.ConclusionIn marginalised communities in rural India, child nutrition was better in those who received Rojiroti microfinance, compared with controls.Trial registration numberNCT01845545.

Background: There is paucity of data on objectively measured lung function abnormalities in Nigerian children using diagnostic testing methods such as spirometry. Such assessments could prompt early diagnosis and therapeutic interventions. Methods: This was a cross sectional study among children aged 6 to 12 years in South-Eastern Nigeria. We selected participants from one school using a multistage stratified random sampling technique. A structured respiratory questionnaire was administered to obtain necessary data. The lung functions of the children were measured by spirometry. We used Lower Limits of Normal (LLN) based on GLI reference equations for African-American and mixed ethnicities to define abnormal spirometry. We studied the association between the exposures and lung function using logistic regression/chi-squared tests. Results: A total of 145 children performed acceptable and repeatable tests. There were 73 males (50.3%), mean age of 9.13 years (+1.5) and age range 6 to 12 years. Frequency of respiratory symptoms was cough- 64 (44.1%) and wheeze in 19 (13.1%). Using GLI for African-Americans, fifty-five (37.9%) children had abnormal spirometryobstructive pattern in 40 (27.6%) and restrictive pattern in 15 (10.3%). The two references showed significant differences in interpretation of abnormality (χ2 = 72.86; P Conclusion: There is a high burden of respiratory symptoms and abnormal spirometry among these children. The need for objective evaluation of lung function especially for children with respiratory symptoms is evident.

Background\ud Despite health centres being the first point of contact of care, there are challenges faced in providing care to patients at this level. In Malawi, service provision barriers reported at this level included long waiting times, high numbers of patients and erratic consultation systems which lead to mis-diagnosis and delayed referrals. Proper case management at this level of care is critical to prevent severe disease and deaths in children. We aimed to adopt Emergency, Triage, Assessment and Treatment algorithm (ETAT) to improve ability to identify severe illness in children at primary health centre (PHC) through comparison with secondary level diagnoses.\ud \ud Methods\ud We implemented ETAT mobile Health (mHealth) at eight urban PHCs in Blantyre, Malawi between April 2017 and September 2018. Health workers and support staff were trained in mHealth ETAT. Stabilisation rooms were established and equipped with emergency equipment. All PHCs used an electronic tracking system to triage and track sick children on referral to secondary care, facilitated by a unique barcode. Support staff at PHC triaged sick children using ETAT Emergency (E), Priority (P) and Queue (Q) symptoms and clinician gave clinical diagnosis. The secondary level diagnosis was considered as a gold standard. We used statistical computing software R (v3.5.1) and used exact 95% binomial confidence intervals when estimating diagnosis agreement proportions.\ud \ud Results\ud Eight-five percentage of all cases where assigned to E (9.0%) and P (75.5%) groups. Pneumonia was the most common PHC level diagnosis across all three triage groups (E, P, Q). The PHC level diagnosis of trauma was the most commonly confirmed diagnosis at secondary level facility (85.0%), while a PHC diagnosis of pneumonia was least likely to be confirmed at secondary level (39.6%). The secondary level diagnosis least likely to have been identified at PHC level was bronchiolitis 3 (5.2%). The majority of bronchiolitis cases (n = 50; (86.2%) were classified as pneumonia at the PHC level facility.\ud \ud Conclusions\ud Implementing a sustainable and consistent ETAT approach with stabilisation and treatment capacity at PHC level reinforce staff capacity to diagnose and has the potential to reduce other health system costs through fewer, timely and appropriate referrals.

BackgroundNon-urgent emergency department (ED) attendances are common among children. Primary care management may not only be more clinically appropriate, but may also improve patient experience and be more cost-effective.AimTo determine the impact on admissions, waiting times, antibiotic prescribing, and treatment costs of integrating a GP into a paediatric ED.Design and settingRetrospective cohort study explored non-urgent ED presentations in a paediatric ED in north-west England.MethodFrom 1 October 2015 to 30 September 2017, a GP was situated in the ED from 2.00 pm until 10.00 pm, 7 days a week. All children triaged as ‘green’ using the Manchester Triage System (non-urgent) were considered to be ‘GP appropriate’. In cases of GP non-availability, children considered non-urgent were managed by ED staff. Clinical and operational outcomes, as well as the healthcare costs of children managed by GPs and ED staff across the same timeframe over a 2-year period were compared.ResultsOf 115 000 children attending the ED over the study period, a complete set of data were available for 13 099 categorised as ‘GP appropriate’; of these, 8404 (64.2%) were managed by GPs and 4695 (35.8%) by ED staff. Median duration of ED stay was 39 min (interquartile range [IQR] 16–108 min) in the GP group and 165 min (IQR 104–222 min) in the ED group (P4 hours before being admitted or discharged (OR 0.11; 95% CI = 0.08 to 0.13), but were more likely to receive antibiotics (OR 1.42; 95% CI = 1.27 to 1.58). Treatment costs were 18.4% lower in the group managed by the GP (PConclusionGiven the rising demand for children’s emergency services, GP in ED care models may improve the management of non-urgent ED presentations. However, further research that incorporates causative study designs is required.

To describe COVID-19 deaths among children and adolescents in Sergipe, Brazil.Ecological study of all COVID-19 reported cases and deaths occurring in children and adolescents 19 years of age in Sergipe reported by the health surveillance and mortality information systems of Sergipe's Health Secretary and hospital records.Of 37 deaths of children 19 years old were reported up to 30 September 2020, corresponding to 4.87 deaths for 100 000 population 19 years old. Most deaths occurred among infants (44.1/100 000), and this age group had the highest case fatality rate (15.3 %). Most children had comorbidities such as chronic neurological diseases (n = 7; 19%) and prematurity (n = 4; 11%). Most children who died (n = 18; 49%) were not admitted to intensive care units (ICUs).COVID-19 mortality in children and adolescents in Sergipe was higher than in other Brazilian states and in high-income countries. A large proportion of the deaths occurred among children with comorbidities and a minority of children were admitted to ICU, reflecting the limited provision of such beds in the State. Newborns and infants are a high-risk group that must have priority in health public policy.Décrire les décès par COVID-19 chez les enfants et adolescents à Sergipe, au Brésil. MÉTHODES: Etude écologique de tous les cas et décès par COVID-19 signalés chez des enfants et des adolescents19 ans à Sergipe rapportés par les systèmes de surveillance de la santé et d’information sur la mortalité du Secrétariat de la Santé et les dossiers hospitaliers de Sergipe. RÉSULTATS: 37 décès d'enfants19 ans ont été signalés au 30 septembre 2020, correspondant à 4,87 décès pour 100.000 habitants de19 ans. La plupart des décès sont survenus chez des nourrissons (44,1/100.000) et ce groupe d'âge avait le taux de létalité le plus élevé (15,3%). La plupart des enfants présentaient des comorbidités telles que des maladies neurologiques chroniques (n = 7; 19%) et une prématurité (n = 4; 11%). La plupart des enfants décédés (n = 18; 49%) n'avaient pas été admis dans des unités de soins intensifs.La mortalité par COVID-19 chez les enfants et les adolescents de Sergipe était plus élevée que dans les autres Etats brésiliens et dans les pays à revenu élevé. Une grande partie des décès est survenue chez des enfants souffrant de comorbidités et une minorité d’enfants avaient été admis aux soins intensifs, ce qui reflète la disponibilité limitée de ce type de lits dans l’Etat. Les nouveau-nés et les nourrissons constituent un groupe à haut risque qui doit avoir la priorité dans les politiques de santé publiques.

BACKGROUND Children who have been hospitalized with severe anemia in areas of Africa in which malaria is endemic have a high risk of readmission and death within 6 months after discharge. No prevention strategy specifically addresses this period. METHODS We conducted a multicenter, two-group, randomized, placebo-controlled trial in nine hospitals in Kenya and Uganda to determine whether 3 months of malaria chemoprevention could reduce morbidity and mortality after hospital discharge in children younger than 5 years of age who had been admitted with severe anemia. All children received standard in-hospital care for severe anemia and a 3-day course of artemether–lumefantrine at discharge. Two weeks after discharge, children were randomly assigned to receive dihydroartemisinin–piperaquine (chemoprevention group) or placebo, administered as 3-day courses at 2, 6, and 10 weeks after discharge. Children were followed for 26 weeks after discharge. The primary outcome was one or more hospital readmissions for any reason or death from the time of randomization to 6 months after discharge. Conditional risk-set modeling for recurrent events was used to calculate hazard ratios with the use of the Prentice–Williams–Peterson total-time approach. RESULTS From May 2016 through May 2018, a total of 1049 children underwent randomization; 524 were assigned to the chemoprevention group and 525 to the placebo group. From week 3 through week 26, a total of 184 events of readmission or death occurred in the chemoprevention group and 316 occurred in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.54 to 0.78; P

appears in Infection Prevention & Control / International Journal of Infectious Diseases 101(S1) (2021) 300–335\ud \ud the organizers of the 19th International Congress on Infectious Diseases (ICID) made the decision to cancel the Congress scheduled for September 10-13, 2020 in Kuala Lumpur, Malaysia

Purpose\ud Patients treated with cytotoxic chemotherapy are at risk of neutropenia, neutropenic fever and neutropenic sepsis. We hypothesised that pre-existing neutrophil function dysfunction may increase susceptibility to neutropenic fever in paediatric patients receiving cytotoxic chemotherapy.\ud \ud Methods\ud Prospective cohort study recruited patients at Alder Hey Children’s NHS Foundation Trust, United Kingdom. We measured neutrophil phagocytic function using a validated flow cytometric whole blood phagocytosis assay in paediatric patients (n = 16) with oncological disease before and after chemotherapy in a prospective cohort study. We recruited healthy children as a control comparator (n = 10).\ud \ud Results\ud We found significantly decreased phagocytic function in oncology patients compared to healthy participants. In five patients who developed neutropenic fever, we observed increased pre-dose neutrophil respiratory burst.\ud \ud Conclusion\ud With further validation, measurement of neutrophil function could potentially be used to personalise appropriate prophylactic antimicrobial administration for patients receiving cytotoxic chemotherapy.

Background Non-traumatic coma is a common acute childhood presentation to healthcare facilities in Africa and is associated with high morbidity and mortality. Historically, the majority of cases were attributed to cerebral malaria (CM). With the recent drastic reduction in malaria incidence, non-malarial coma is becoming a larger proportion of cases and determining the aetiology is diagnostically challenging, particularly in resource-limited settings. The purpose of this study will be to evaluate the aetiology and prognosis of non-traumatic coma in African children. Methods With no date restrictions, systematic searches of MEDLINE, Embase, and Scopus will identify prospective and retrospective studies (including randomised controlled trials, cluster randomised trials, cohort studies, cross-sectional, and case-control studies) recruiting children (1 month–16 years) with non-traumatic coma (defined by Blantyre Coma Score ≤ 2 or comparable alternative) from any African country. Disease-specific studies will be included if coma is associated and reported. The primary outcome is to determine the aetiology (infectious and non-infectious) of non-traumatic coma in African children, with pooled prevalence estimates of causes (e.g., malaria). Secondary outcomes are to determine overall estimates of morbidity and mortality of all-cause non-traumatic coma and disease-specific states of non-traumatic coma, where available. Random effects meta-analysis will summarise aetiology data and in-hospital and post-discharge mortality. Heterogeneity will be quantified with τ2, I2, and Cochran’s Q test. Discussion This systematic review will provide a summary of the best available evidence on the aetiology and outcome of non-traumatic coma in African children. Systematic review registration PROSPERO CRD42020141937

BackgroundFever among children is a leading cause of emergency department (ED) attendance and a diagnostic conundrum; yet robust quantitative evidence regarding the preferences of parents and healthcare providers (HCPs) for managing fever is scarce.ObjectiveTo determine parental and HCP preferences for the management of paediatric febrile illness in the ED.SettingTen children’s centres and a children’s ED in England from June 2018 to January 2019.Participants98 parents of children aged 0–11 years, and 99 HCPs took part.MethodsNine focus-groups and coin-ranking exercises were conducted with parents, and a discrete-choice experiment (DCE) was conducted with both parents and HCPs, which asked respondents to choose their preferred option of several hypothetical management scenarios for paediatric febrile illness, with differing levels of visit time, out-of-pocket costs, antibiotic prescribing, HCP grade and pain/discomfort from investigations.ResultsThe mean focus-group size was 4.4 participants (range 3–7), with a mean duration of 27.4 min (range 18–46 min). Response rates to the DCE among parents and HCPs were 94.2% and 98.2%, respectively. Avoiding pain from diagnostics, receiving a faster diagnosis and minimising wait times were major concerns for both parents and HCPs, with parents willing-to-pay £16.89 for every 1 hour reduction in waiting times. Both groups preferred treatment by consultants and nurse practitioners to treatment by doctors in postgraduate training. Parents were willing to trade-off considerable increases in waiting times (24.1 min) to be seen by consultants and to avoid additional pain from diagnostics (45.6 min). Reducing antibiotic prescribing was important to HCPs but not parents.ConclusionsBoth parents and HCPs care strongly about reducing visit time, avoiding pain from invasive investigations and receiving diagnostic insights faster when managing paediatric febrile illness. As such, overdue advances in diagnostic capabilities should improve child and carer experience and HCP satisfaction considerably in managing paediatric febrile illness.

Background: The emergence of multidrug-resistant (MDR) and extended-spectrum beta-lactamase (ESBL)-producing uropathogens has ]complicated the treatment of urinary tract infections (UTI). Paediatric UTI is a common illness, which if not treated properly, may lead to acute and long-term complications, such as renal abscess, septicaemia, and renal scarring. This study aimed to determine the prevalence of MDR and ESBL-producing uropathogens among children. Methods: During the study period (April 2017-April 2018), midstream urine samples were collected following aseptic procedures from children < 16 years in Siddhi Memorial Hospital. Standard culture and biochemical tests were performed to identify uropathogens and antimicrobial susceptibility test was done by modified Kirby-Bauer disc diffusion method following Clinical and Laboratory Standard Institute (CLSI) guidelines. ESBL-producing uropathogens were screened by ceftazidime (30 μg) and cefotaxime (30 μg) discs, and confirmed by the combination disc tests: ceftazidime + clavulanic acid (30/10 μg) or cefotaxime + clavulanic acid (30/10 μg) as recommended by CLSI. Results: We processed 5545 non-repeated urine samples from the children with symptoms of UTI. A significant growth of uropathogens was observed in 203 samples (3.7%). The median age of the children was 24 months (interquartile range (IQR), 12-53 months). Escherichia coli (n = 158, 77.8%) and Klebsiella pneumoniae (n = 30, 14.8%) were common among the uropathogens. Among them, 80.3% were resistant to amoxycillin and 51.2% were resistant to cotrimoxazole. Most of them were susceptible to amikacin,nitrofurantoin, and ofloxacin. MDR was detected in 34.5% (n = 70/203) and ESBL producers in 24.6% (n = 50/203) of them. The proportion of MDR isolates was higher in children < 5 years (n = 59/153, 38.6%) than children ? 5 years (n = 11/50, 22%) (P = 0.03). Conclusions:Nitrofurantoin, ofloxacin, and amikacin can be used for the empirical treatment for UTI in children in Bhaktapur, Nepal.MDR and ESBL-producing uropathogens are prevalent; this warrants a continuous surveillance of antimicrobial resistance., Tropical Medicine and Health, 48(1), art.no.65; 2020

Background Intestinal schistosomiasis was not considered endemic in Lake Malawi until November 2017 when populations of Biomphalaria pfeifferi were first reported; in May 2018, emergence of intestinal schistosomiasis was confirmed. This emergence was in spite of ongoing control of urogenital schistosomiasis by preventive chemotherapy. Our current study sought to ascertain whether intestinal schistosomiasis is transitioning from emergence to outbreak, to judge if stepped-up control interventions are needed. Methods During late-May 2019, three cross-sectional surveys of primary school children for schistosomiasis were conducted using a combination of rapid diagnostic tests, parasitological examinations and applied morbidity-markers; 1) schistosomiasis dynamics were assessed at Samama (n = 80) and Mchoka (n = 80) schools, where Schistosoma mansoni was first reported, 2) occurrence of S. mansoni was investigated at two non-sampled schools, Mangochi Orphan Education and Training (MOET) (n = 60) and Koche (n = 60) schools, where B. pfeifferi was nearby, and 3) rapid mapping of schistosomiasis, and B. pfeifferi, conducted across a further 8 shoreline schools (n = 240). After data collection, univariate analyses and Chi-square testing were performed, followed by binary logistic regression using generalized linear models, to investigate epidemiological associations. Results In total, 520 children from 12 lakeshore primary schools were examined, mean prevalence of S. mansoni by ‘positive’ urine circulating cathodic antigen (CCA)-dipsticks was 31.5% (95% confidence interval [CI]: 27.5–35.5). Upon comparisons of infection prevalence in May 2018, significant increases at Samama (relative risk [RR] = 1.7, 95% CI: 1.4–2.2) and Mchoka (RR = 2.7, 95% CI: 1.7–4.3) schools were observed. Intestinal schistosomiasis was confirmed at MOET (18.3%) and Koche (35.0%) schools, and in all rapid mapping schools, ranging from 10.0 to 56.7%. Several populations of B. pfeifferi were confirmed, with two new eastern shoreline locations noted. Mean prevalence of urogenital schistosomiasis was 24.0% (95% CI: 20.3–27.7). Conclusions We notify that intestinal schistosomiasis, once considered non-endemic in Lake Malawi, is now transitioning from emergence to outbreak. Once control interventions can resume after coronavirus disease 2019 (COVID-19) suspensions, we recommend stepped-up preventive chemotherapy, with increased community-access to treatments, alongside renewed efforts in appropriate environmental control.

BackgroundThere is a scarcity of information regarding the most important outcomes for research in neonatal units in low-resource settings. Identification of important outcomes by different stakeholder groups would inform the development of a core outcome set (COS) for use in neonatal research.ObjectiveTo determine the perceptions and opinions of parents of newborn babies regarding what outcomes were most important to them in order to contribute towards development of a COS for neonatal research in sub-Saharan Africa.MethodsSemistructured interviews were undertaken with parents, mostly mothers, of babies admitted to one neonatal unit in North central and one in Southwest Nigeria. Participants were purposively sampled to include parents of babies with common neonatal problems such as prematurity.ResultsWe conducted 31 interviews. The most frequently raised outcomes were breast feeding, good health outcomes for their baby, education, growth and financial cost. Parents placed more emphasis on quality of life and functional status than health complications.ConclusionsThe opinions of parents need to be considered in developing a COS for neonatal research in low-resource settings. Further research should assess the opinions of families in other low-resource settings and also engage a broader range of stakeholders.

Background In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling, and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling. Methods We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain magnatic resonance imaging (MRI), and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria. Results Three types of retinal leakage were seen: large focal leak (LFL), punctate leak (PL), and vessel leak. The LFL and PL were associated with death (odds ratio [OR] = 13.20, 95% confidence interval [CI] = 5.21–33.78 and OR = 8.58, 95% CI = 2.56–29.08, respectively) and brain swelling (P Conclusions Blood-retina barrier breakdown occurs in 3 patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak, from barrier dysfunction, and nonperfusion were not associated with severe brain swelling but with neurological deficits, suggesting hypoxic injury in survivors.

Supplemental Digital Content is available in the text, Objective: To investigate differences in viral shedding in respiratory and fecal samples from children with COVID-19. Methods: We searched PubMed, SCOPUS, Embase and Web of Science databases to identify pediatric studies comparing the pattern of fecal and respiratory shedding of SARS-CoV-2 RNA. Summary estimates were calculated using random-effects models. Results: Four studies reporting data from 36 children were included. A higher proportion of children had viral shedding in stools after 14 days of symptoms onset compared to respiratory samples (RR= 3.2, 95%CI 1.2 to 8.9, I2 = 51%). Viral RNA shedding was longer in fecal samples with a mean difference of approximately 9 days (Mean Difference = 8.6, 95%CI 1.7 to 15.4, I2 = 77%) compared with respiratory samples. Conclusion: SARS-CoV-2 shedding seems to be present in feces for a longer time than in the respiratory tract of children. Although fecal SARS-CoV-2 presence in feces do not confirm its transmissibility, the high and fast spread of the COVID-19 disease worldwide indicate other transmission routes are also plausible.

This paper aimed to assess the impact of maternal common mental disorders (CMD) among caregivers living with HIV on the cognitive functioning of their child. Data were collected at baseline and 12 months follow-up from mother–child dyads recruited as part of an ongoing trial in Zimbabwe. Symptoms of CMD were assessed using the Shona Symptom Questionnaire. Mixed-effects linear regression was used to assess child cognitive scores at follow-up (using the Mullen Scales of Early Learning) in relation to caregiver CMD prevalence over 12 months. At baseline, caregivers reporting CMD (n = 230; 40.1%) were less likely to have completed higher education (46.9% vs. 56.9%; p = 0.02), more likely to be unmarried (27.8% vs. 16.0%; p

Background Progress in controlling malaria has stalled in recent years. Today the malaria burden is increasingly concentrated in a few countries, including Burkina Faso, where malaria is not declining. A cohort study was conducted to identify risk factors for malaria infection in children in southwest Burkina Faso, an area with high insecticide-treated net (ITN) coverage and insecticide-resistant vectors. Methods Incidence of Plasmodium falciparum infection was measured in 252 children aged 5 to 15 years, using active and passive detection, during the 2017 transmission season, following clearance of infection. Demographic, socio-economic, environmental, and entomological risk factors, including use of ITNs and insecticide resistance were monitored. Results During the six-month follow-up period, the overall incidence of P. falciparum infection was 2.78 episodes per child (95% CI = 2.66–2.91) by microscopy, and 3.11 (95% CI = 2.95–3.28) by polymerase chain reaction (PCR). The entomological inoculation rate (EIR) was 80.4 infective bites per child over the six-month malaria transmission season. At baseline, 80.6% of children were reported as sleeping under an ITN the previous night, although at the last survey, 23.3% of nets were in poor condition and considered no longer protective. No association was found between the rate of P. falciparum infection and either EIR (incidence rate ratio (IRR): 1.00, 95% CI: 1.00–1.00, p = 0.08) or mortality in WHO tube tests when vectors were exposed to 0.05% deltamethrin (IRR: 1.05, 95% CI: 0.73–1.50, p = 0.79). Travel history (IRR: 1.52, 95% CI: 1.45–1.59, p P. falciparum infection (IRR: 1.05, 95% CI: 1.00–1.11, p = 0.04). Conclusions Incidence of P. falciparum infection remains overwhelmingly high in the study area. The study findings suggest that because of the exceptionally high levels of malaria transmission in the study area, malaria elimination cannot be achieved solely by mass deployment of ITNs and additional control measures are needed.

Objective: The purpose of this study is to estimate the effect of parent migration on intellectual and physical development of early school-aged children in rural China. Design: setting and participants: The present cross-sectional study participants were a subset from a controlled, cluster-randomized, double-blind trial. From October 2012 to September 2013, the offspring of women who participated in a large trial were examined in the present study. Wechsler intelligence scale for children (WISC-IV) in which validity and reliability were shown to be satisfactory was used to measure the intellectual function and trained anthropometrists measured weight and height of children using standard procedures. Results: The mean difference of FSIQ scores between non-migration and both-parent migration groups was &minus, 3.68 (95%CI: &minus, 5.49, &minus, 1.87). After adjusting for the confounders, the mean difference of full-scale IQ between non-migration and both-parent migration group was &minus, 1.97 (95%CI: &minus, 3.92, &minus, 0.01), the mean differences of perceptual reasoning index and processing speed index were &minus, 2.41 (95%CI: &minus, 4.50, &minus, 0.31) and &minus, 2.39 (95%CI: &minus, 4.42, &minus, 0.35) between two groups respectively. Conclusion: Our results emphasized the impairment of both-parental migration in intellectual function (FSIQ, PRI, PSI) of children. These findings have important policy implications for the Chinese government to prevent the impairment of left-behind children. Further research is required to clarify the mechanisms by which both-parental migration influence the impairment in intellectual function of children.

BACKGROUND: \ud The Griffiths Mental Development Scales (GMDS) are used in many countries to assess the development of children from birth to 8 years. There is a need for accurate and culturally appropriate developmental assessment tools for Chinese children. Here, we adapted the GMDS for use in Chinese children and compare the developmental trajectories between Chinese and British children.\ud METHODS: \ud Children with typical development were recruited from 7 urban cities in China between 2009 and 2013. The Griffiths Mental Development Scales-Chinese (GDS-C) were adapted and used to assess the development of urban Chinese children. Developmental curves were computed for 6 subscales using learning management system methods and compare against the British curves from the Griffiths Mental Development Scales-Extended Revised (GMDS-ER).\ud RESULTS: \ud The GDS-C were used to assess the developmental status of 815 Chinese children. Plots of the 1st, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 99th percentiles, and full percentile tables were obtained, which showed similar trends to data from the British GMDS-ER.\ud CONCLUSIONS: \ud The Chinese developmental curves obtained from the GDS-C showed similarities and differences to the developmental curves from the British GMDS-ER. The development of urban Chinese children should be assessed with the culturally appropriate GDS-C.

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations., A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

ObjectiveTo determine the magnitude of relationships of early life factors with child development in low/middle-income countries (LMICs).DesignMeta-analyses of standardised mean differences (SMDs) estimated from published and unpublished data.Data sourcesWe searched Medline, bibliographies of key articles and reviews, and grey literature to identify studies from LMICs that collected data on early life exposures and child development. The most recent search was done on 4 November 2014. We then invited the first authors of the publications and investigators of unpublished studies to participate in the study.Eligibility criteria for selecting studiesStudies that assessed at least one domain of child development in at least 100 children under 7 years of age and collected at least one early life factor of interest were included in the study.AnalysesLinear regression models were used to assess SMDs in child development by parental and child factors within each study. We then produced pooled estimates across studies using random effects meta-analyses.ResultsWe retrieved data from 21 studies including 20 882 children across 13 LMICs, to assess the associations of exposure to 14 major risk factors with child development. Children of mothers with secondary schooling had 0.14 SD (95% CI 0.05 to 0.25) higher cognitive scores compared with children whose mothers had primary education. Preterm birth was associated with 0.14 SD (–0.24 to –0.05) and 0.23 SD (–0.42 to –0.03) reductions in cognitive and motor scores, respectively. Maternal short stature, anaemia in infancy and lack of access to clean water and sanitation had significant negative associations with cognitive and motor development with effects ranging from −0.18 to −0.10 SDs.ConclusionsDifferential parental, environmental and nutritional factors contribute to disparities in child development across LMICs. Targeting these factors from prepregnancy through childhood may improve health and development of children.

IntroductionHIV-exposed children show signs of developmental delay. We assessed the impact of a pragmatic multicomponent intervention for caregivers of HIV-exposed children aged 0–2 years in Zimbabwe.MethodsWe conducted a cluster-randomised trial from 2016 to 2018. Clusters were catchments surrounding clinics, allocated (1:1) to either National HIV guidelines standard of care or standard care plus an 18-session group intervention comprising i) early childhood stimulation (ECS) and parenting training with home visits to reinforce skills and retention in HIV care; ii) economic strengthening. Primary outcomes measured 12 months after baseline (4.5 months postintervention completion) included: i) global child development measured using the Mullen early learning composite score; ii) retention in HIV care. Analysis used mixed effects regression to account for clustering and adjusted minimally for baseline prognostic factors and was by intention to treat.ResultsThirty clusters, 15 in each arm, were randomised. 574 dyads were recruited with 89.5% retained at follow-up. Ninety one of 281 (32.4%) were recorded as having received the complete intervention package, with 161/281 (57.3%) attending ≥14 ECS sessions. There was no evidence of an intervention effect on global child development (intervention mean 88.1 vs standard of care mean 87.6; adjusted mean difference=0.06; 95% CI −2.68 to 2.80; p=0.97) or infant retention in care (proportion of children who had missed their most recent HIV test: intervention 21.8% vs standard of care 16.9%, p=0.18). There was weak evidence that the proportion of caregivers with parental stress was reduced in the intervention arm (adjusted OR (aOR)=0.69; 95% CI 0.45 to 1.05; p=0.08) and stronger evidence that parental distress specifically was reduced (intervention arm 17.4% vs standard of care 29.1% scoring above the cut-off; aOR=0.56; 95% CI 0.35 to 0.89; p=0.01).ConclusionThis multicomponent intervention had no impact on child development outcomes within 4.5 months of completion, but had an impact on parental distress. Maternal mental health remains a high priority.Trial registration numberPACTR201701001387209.

Background: Owing to inadequate supplies of donor blood for transfusion in sub-Saharan Africa (sSA) World Health Organization paediatric guidelines recommend restrictive transfusion practices, based on expert opinion. We examined whether survival amongst hospitalised children by admission haemoglobin and whether this was influenced by malaria infection and/or transfusion. Methods: A retrospective analysis of standardised clinical digital records in an unselected population of children admitted to a rural hospital in Kenya over an 8-year period. We describe baseline parameters with respect to categories of anaemia and outcome (in-hospital death) by haemoglobin (Hb), malaria and transfusion status. Results: Among 29,226 children, 1,143 (3.9%) had profound anaemia (Hb Conclusion: Although severe anaemia is common among children admitted to hospital in sSA (~16%), our data do not indicate that outcome is improved by transfusion irrespective of malaria status. Given the limitations of observational studies, clinical trials investigating the role of transfusion in outcomes in children with severe anaemia are warranted.

CD8+ T cells have been shown to play a critical role in the pathogenesis of experimental cerebral malaria (ECM) in mice, but their role in development of human cerebral malaria (HCM) remains unclear. Thus, in this study we have provided the first direct contrast of the accumulation of CD8+ T cells in the brain during HCM and ECM. HCM cases were from children who died of Plasmodium falciparum cerebral malaria at Queen Elizabeth Central Hospital (Malawi) between 2003 and 2010. ECM was induced by infecting C57BL/6J mice with P. berghei ANKA. We demonstrate similarities in the intracerebral CD8+ T cell responses in ECM and HCM, in particular an apparent shared choroid plexus—meningeal route of CD8+ T cell accumulation in the brain. Nevertheless, we also reveal some potentially important differences in compartmentalization of CD8+ T cells within the cerebrovascular bed in HCM and ECM.

Objectives: To evaluate the clinical outcomes and costs of managing pneumonia and severe malnutrition in a day clinic management (DC) model (outpatient) compared to hospital care (inpatient).\ud Methods: A randomized clinical trial where children aged 2 months to 5 years with pneumonia and severe malnutrition were randomly allocated to DC or inpatient hospital care. We used block randomization of variable length from 8-20 and produced\ud computer-generated random numbers that were assigned to one of the two interventions. Successful management was defined as resolution of clinical signs of pneumonia and being discharged from the model of care (DC or hospital) without need for referral to a hospital (DC), or referral to another hospital. All the children in both DC and hospital received intramuscular ceftriaxone, daily nutrition support and micronutrients.\ud Results: 470 children were randomly assigned to either DC or hospital care. Successful management was achieved for 184 of 235 (78.3%) by DC alone, compared to 201 of 235 (85.5%) by hospital inpatient care [RR (95% CI) = 0.79 (0.65 – 0.97), p=0.02]. During 6-months of follow-up, 30/235 (12.8%) and 36/235 (15.3%) required\ud readmission to hospital in the DC and hospital care groups respectively [RR (95% CI) = 0.89 (0.67 – 1.18), p=0.21]. The average overall health care and societal cost was 34% lower in DC (US$ 188±11.7) compared to hospital (US$ 285±13.6) (p

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: \ud Primary objectives\ud \ud To determine the diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for a) PTB in children presumed to have tuberculosis; b) lymph node tuberculosis in children presumed to have tuberculosis; c) tuberculous meningitis in children presumed to have tuberculosis; and d) rifampicin resistance in children presumed to have tuberculosis. \ud For tuberculosis detection, the role of the index tests would be a replacement for standard practice. \ud For rifampicin resistance detection, the role of the index tests would be an initial replacement test for culture‐based drug susceptibility testing.

Background\ud Stimulating home environments that have children's books, pictures and play toys facilitate caregiver-child interactions and enhance children's development. Although this has been demonstrated in small-scale intervention studies, it is important to document whether book ownership is beneficial at large scale in low and middle-income settings.\ud Methods\ud We conducted a secondary analysis using data from the multiple-indicator cluster survey, covering 100 012 children aged 36-59 months, from 35 countries. The outcome was children being on-track for a literacy-numeracy index (LNI) constructed from three questions assessing children's ability to identify/name at least 10 letters of the alphabet, read at least four simple popular words and know the names and symbols of all numbers from 1-10. The main exposure was availability of children's book to the child within household. Analysis considered the survey design, assessed and ranked risk ratios of being on track, adjusting for potential confounders such as child's age (in months), maternal education, household wealth index quintile and area of residence (rural/urban). Ecological analysis was performed using meta-regression after grouping countries by World Bank income groups (low- to high-income).\ud Results\ud Only half (51.8%) of children from all the countries analysed have at least one children's book at home and less than one-third (29.9%; 95% confidence interval (CI) = 23.5%, 36.3%) are on track for literacy-numeracy. After adjusting for confounders, the likelihood of being on track in literacy-numeracy almost doubled if at least one book was available at home compared to when there was none: RR = 1.89 (95% CI = 1.75, 2.03). There was an economic gradient showing that the likelihood of children being on track for LNI decreased with the country's income group: adjusted-RR ranged from 1.65 in upper middle income to 2.23 in LIC (F-test -value

An estimated 26% of current global child deaths can be attributed to various and modifiable environmental factors, which are addressed under multiple Sustainable Development Goals (SDGs). This study assesses future reductions in child mortality in relation to the achievement of environment-related SDG targets. It uses projections of health risk factors from the IMAGE 3.0 Integrated Assessment Model, based on the Shared Socioeconomic Pathways (SSPs), linked to a standard multi-state health model (GISMO), distinguishing risk factors, disease occurrence and cause-specific death. The study concludes that, on a global level, the SDG target on child mortality will not be achieved in any of the three SSP scenarios analysed, mainly due to persistent high mortality rates in Sub-Saharan Africa and South Asia. By 2030, environmental health risk factors – including childhood undernutrition, no access to improved drinking water and sanitation, no access to modern fuels and exposure to malaria – will still be responsible for 14% to 16% of total global child deaths (8% to 10% when excluding nutrition-related mortality). Under the middle-of-the-road SSP2 baseline scenario, achievement of the SDG targets on hunger, drinking water and sanitation and modern energy services, would avoid 433 thousand child deaths by 2030. If, in addition, also higher standards would be achieved for access to water and energy, as well as universal secondary female education and advanced malaria control, a total of 733 thousand child deaths is projected to be avoided by 2030 (444 thousand child deaths, when excluding nutrition-related mortality), which would reduce projected global child mortality by 13%. Overall, more than 25% of the child mortality reduction that is needed to achieve the SDG target in Sub-Saharan Africa can be achieved through SDG-related policies on food, water and energy. This requires integrated and intersectoral approaches to environmental health.

Environmental changes related to agricultural practices and activities can impact malaria transmission. In the objective to evaluate this impact on the human-vector contact, the level of human exposure to Anopheles vector bites was assess by an immuno-epidemiological indicator based on the assessment of the human IgG antibody response to the Anopheles gambiae gSG6-P1 salivary peptide, previously validated as a pertinent biomarker.Two cross-sectional surveys were carried out in the dry and rainy season in three villages with intensive agricultural plantations (N'Zikro with rubber cultivation, Ehania-V5 and Ehania-V1 with palm oil exploitation) and in a control village without plantations (Ayébo). Overall, 775 blood samples were collected in filter papers from children aged 1 to 14 years-old for immunological analysis by ELISA. The IgG levels to the gSG6-P1 salivary peptide significantly differed between studied villages both in the dry and the rainy seasons (P

RATIONALE\ud Pooling data from multiple cohorts and extending the time-frame across childhood should minimize study-specific effects, enabling better characterization of the childhood wheezing.\ud OBJECTIVE\ud To analyze wheezing patterns from early childhood to adolescence using combined data from five birth cohorts.\ud METHODS\ud We used latent class analysis to derive wheeze phenotypes among 7719 participants from five birth cohorts with complete report of wheeze at five time-periods. We tested the association of derived phenotypes with late asthma outcomes and lung function, and investigated the uncertainty in phenotype assignment.\ud RESULTS\ud We identified five phenotypes: Never/Infrequent wheeze (52.1%), Early-onset pre-school remitting (23.9%), Early-onset mid-childhood remitting (9%), Persistent (7.9%) and Late-onset wheeze (7.1%). Compared to the Never/infrequent wheeze, all phenotypes had higher odds of asthma and lower FEV1 and FEV1/FVC in adolescence. The association with asthma was strongest for Persistent wheeze (adjusted odds ratio 56.54, 95%CI 43.75-73.06). We observed considerable within-class heterogeneity at individual level, with 913 (12%) children having low membership probability (

Wilson L Mandala,1–3 Esther N Gondwe,1,† Tonney S Nyirenda,1,4 Mark Drayson,5 Malcolm E Molyneux,1,6 Calman A MacLennan1,7 1Malawi Liverpool Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; 2Biomedical Sciences Department, College of Medicine, Blantyre, Malawi; 3Academy of Medical Sciences, Malawi University of Science and Technology, Thyolo, Malawi; 4Pathology Department, College of Medicine, Blantyre, Malawi; 5Institute of Immunology and Immunotherapy, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, UK; 6Liverpool School of Tropical Medicine, Liverpool, UK; 7Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK †Esther N Gondwe passed away on April 5, 2018 Aim: Cerebral malaria (CM), unlike severe malarial anemia (SMA), has previously been characterized by pan-lymphopenia that normalizes in convalescence, while HIV infection is associated with depletion of CD4+ T cells. In this study, we investigate whether HIV infection in Malawian children exacerbates the pan-lymphopenia associated with CM. Methods: We investigated the absolute and percentage lymphocyte-subset counts and their activation and memory status in Malawian children presenting with either CM who were HIV-uninfected (n=29), HIV-infected (n=9), or SMA who were HIV-uninfected (n=30) and HIV-infected (n=5) in comparison with HIV-uninfected children without malaria (n=42) and HIV-infected children without malaria (n=4). Results: HIV-infected CM cases had significantly lower absolute counts of T cells (P=0.006), CD4+ T cells (P=0.0008), and B cells (P=0.0014) than HIV-uninfected CM cases, and significantly lower percentages of CD4+ T cells than HIV-uninfected CM cases (P=0.005). HIV-infected SMA cases had significantly lower percentages of CD4+ T cells (P=0.001) and higher CD8+ T cells (P=0.003) in comparison with HIV-uninfected SMA cases. HIV-infected SMA cases had higher proportions of activated T cells (P=0.003) expressing CD69 than HIV-uninfected SMA cases. Conclusion: HIV infection compounds the perturbation of acute CM and SMA on lymphocytes, exacerbating subset-specific lymphopenia in CM and increasing activation status in SMA, potentially exacerbating host immunocompromise. Keywords: HIV, cerebral malaria, severe malarial anemia, Malawian children

Early infant growth and development has attracted worldwide attention. Although numerous studies have demonstrated that maternal syphilis increases the risk of adverse pregnancy outcomes and congenital syphilis, the subsequent growth pattern and morbidity of syphilis-exposed uninfected infants are less understood. We conducted a longitudinal study to compare the growth pattern and disease distribution of syphilis-exposed and syphilis-unexposed uninfected children, and World Health Organization (WHO) reference standards from birth to 18 months of age. We obtained data from a prospective cohort study in three representative regions of Zhejiang Province in China. A total of 333 syphilis-uninfected children born to women with syphilis were recruited at birth and matched with 333 syphilis-uninfected children born to women without syphilis during pregnancy. Children were followed-up by medical staff every 3 months until 18 months of age. The mixed-effects model was used to compare changes in growth patterns and influencing factors between the two groups. Mean weight, length, and head circumference of children, as well as disease prevalence, were similar between the groups. Multilevel analysis indicated that, after controlling confounders, growth velocities were comparable in both weight and length measures from birth to 18 months old between the two groups; however, low birth weight had a negative impact on weight gain in both groups. There was no significant negative association between syphilis exposure and early growth and health in children, under 18 months in a setting with universal coverage of therapeutic interventions for maternal syphilis. These findings may contribute to improving prevention efforts for mother-to-child transmission of syphilis, such as early screening for syphilis in pregnant women, universal coverage of treatment, and interventions for exposed children. Children with low birth weight should be given priority as this is a risk factor for weight gain.

\ud Background: Paediatric fever is a common cause of emergency department (ED) attendance. A lack of prompt and\ud definitive diagnostics makes it difficult to distinguish viral from potentially life-threatening bacterial causes, necessitating a\ud cautious approach. This may result in extended periods of observation, additional radiography, and the precautionary use\ud of antibiotics (ABs) prior to evidence of bacterial foci. This study examines resource use, service costs, and health\ud outcomes.\ud Methods: We studied an all-year prospective, comprehensive, and representative cohort of 6518 febrile children\ud (aged < 16 years), attending Alder Hey Children’s Hospital, an NHS-affiliated paediatric care provider in the North\ud West of England, over a 1-year period. Performing a time-driven and activity-based micro-costing, we estimated\ud the economic impact of managing paediatric febrile illness, with focus on nurse/clinician time, investigations,\ud radiography, and inpatient stay. Using bootstrapped generalised linear modelling (GLM, gamma, log), we identified the\ud patient and healthcare provider characteristics associated with increased resource use, applying retrospective case-note\ud identification to determine rates of potentially avoidable AB prescribing.\ud Results: Infants aged less than 3 months incurred significantly higher resource use than any other age group, at £1000.28\ud [95% CI £82.39–£2993.37] per child, (p < 0.001), while lesser experienced doctors exhibited 3.2-fold [95% CI 2.0–5.1-fold]\ud higher resource use than consultants (p < 0.001). Approximately 32.4% of febrile children received antibiotics, and 7.1%\ud were diagnosed with bacterial infections. Children with viral illnesses for whom antibiotic prescription was potentially\ud avoidable incurred 9.9-fold [95% CI 6.5–13.2-fold] cost increases compared to those not receiving antibiotics, equal to an\ud additional £1352.10 per child, predominantly resulting from a 53.9-h increase in observation and inpatient stay\ud (57.1 vs. 3.2 h). Bootstrapped GLM suggested that infants aged below 3 months and those prompting a respiratory rate\ud ‘red flag’, treatment by lesser experienced doctors, and Manchester Triage System (MTS) yellow or higher were statistically\ud significant predictors of higher resource use in 100% of bootstrap simulations.

Background\ud Continuous Positive Airway Pressure (CPAP) is a form of non-invasive ventilatory support which is increasingly used in low- and middle-income countries to treat neonates with acute respiratory distress. However, it may be harmful if used incorrectly. We aimed to explore the experiences of doctors and nurses using CPAP in neonatal units in India and their views on enablers and barriers to implementation of CPAP.\ud Methods\ud Participants from 15 neonatal units across Andhra Pradesh were identified through purposive sampling. Eighteen in-depth interviews (IDI) with doctors and eight focus group discussions (FGD) with 51 nurses were conducted. Data were analysed thematically using the framework approach.\ud Results\ud Common structural factors that limit the use of CPAP include shortages of staff, consumables and equipment, and problems with regard to the organisation of neonatal units in both district hospitals and medical colleges. This meant that CPAP was often not available for babies who were identified to need CPAP, or that CPAP use was not perceived to be of the highest quality. Providing care under constrained circumstances left staff feeling powerless to provide good quality care for neonates with acute respiratory distress. Despite this, staff were enthusiastic about the use of CPAP and its potential to save lives. CPAP use was mostly perceived as technically easier to provide than ventilation and allowed nurses to provide advanced neonatal care, independently of doctors.\ud Conclusions\ud Doctors and nurses embraced CPAP use but identified barriers to implementation which will need to be addressed in order not to impact on safety and quality of care. Ensuring a supportive and enabling environment is in place will be crucial if CPAP is to be scaled-up more widely.

Background\ud Asthma attacks are common and have significant physical, psychological, and financial consequences. Improving the assessment of a child's risk of subsequent asthma attacks could support front‐line clinicians’ decisions on augmenting chronic treatment or specialist referral. We aimed to identify predictors for emergency department (ED) or hospital readmission for asthma from the published literature. \ud \ud Methods\ud We searched MEDLINE, EMBASE, AMED, PsycINFO, and CINAHL with no language, location, or time restrictions. We retrieved observational studies and randomized controlled trials (RCT) assessing factors (personal and family history, and biomarkers) associated with the risk of ED re‐attendance or hospital readmission for acute childhood asthma. \ud \ud Results\ud Three RCTs and 33 observational studies were included, 31 from Anglophone countries and none from Asia or Africa. There was an unclear or high risk of bias in 14 of the studies, including 2 of the RCTs. Previous history of emergency or hospital admissions for asthma, younger age, African‐American ethnicity, and low socioeconomic status increased risk of subsequent ED and hospital readmissions for acute asthma. Female sex and concomitant allergic diseases also predicted hospital readmission. \ud \ud Conclusion\ud Despite the global importance of this issue, there are relatively few high quality studies or studies from outside North America. Factors other than symptoms are associated with the risk of emergency re‐attendance for acute asthma among children. Further research is required to better quantify the risk of future attacks and to assess the role of commonly used biomarkers.

The aim of this study was to assess the effect of low maternal weight at pre-pregnancy and the average gestational weight gain on undernourished children and their intellectual development. From October 2012 to September 2013, we followed 1744 offspring of women who participated in a trial conducted from 2002 to 2006. Pregnant women recruited in the original trial could receive three prenatal health checks for free, at which maternal weight and height were measured. WISC-IV was used to estimate the intellectual development of children. Weight and height of both pregnant women and children were measured by trained anthropometrists using standard procedures. Having low maternal weight at pre-pregnancy was associated with an increased risk of undernutrition amongst children (underweight: OR = 2.02, 95%CI: 1.14-3.56, thinness: OR = 2.79, 95%CI: 1.50-5.17) and a decrease in verbal comprehension index (-2.70 points, 95%CI: -4.95-0.44) of children. The effect of average gestational weight gain on occurrences of underweight children (OR = 0.08, 95%CI: 0.01-0.55) was also found. We identified the effect of maternal pre-pregnancy underweight on impairment of the separate intellectual domains (verbal comprehension index) and increasing occurrence of undernourished children. Average gestational weight gain was positively associated with a decreased prevalence of underweight children but not with the intellectual development of children in rural China.

Situation\ud Malnutrition plays a significant role in under-five mortality rates following disasters. Older people play an important role in childcare in non-Western societies, which often increases in displacement contexts. Until now, policy, in general, and nutrition programmes, in particular, have focused on the mother-child dyad.\ud \ud Aim\ud To gather information on possible barriers to older carers accessing nutritional services for the children they care for and explore ways to overcome these obstacles.\ud \ud Method\ud A qualitative approach was taken to explore the experiences of the carers themselves. Focus group discussions provided data, which were analysed using grounded theory.\ud \ud Results\ud Data collected showed older people have similar needs to other caregivers in emergency settings, needs that are often amplified by age. Moreover, many barriers to accessing services were elicited, including targeting and advertising of nutritional programmes, alongside physical and psychosocial barriers to assessing existing support. Participants generated potential solutions to each identified barrier.\ud \ud Conclusion\ud As older people in Haiti were often the sole carers of under-fives, there is a need to recognise their importance in this role and support them within. More generally, in any emergency setting, organisations need take into account all stakeholders in child nutrition when planning and implementing programmes.

Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 pediatric and 386 adult patients were analyzed using nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if needed, to propose an optimized dosing regimen for children under 5 years of age. The population pharmacokinetics of sulfadoxine and pyrimethamine were both best described by a one-compartment disposition model with first-order absorption and elimination. Body weight, age, and nutritional status (measured as the weight-for-age Z-score) were found to be significant covariates. Allometric scaling with total body weight and the maturation of clearance in children by postgestational age improved the model fit. Underweight-for-age children were found to have 15.3% and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively, for each Z-score unit below −2. Under current dosing recommendations, simulation predicted that the median day 7 concentration was below the 25th percentile for a typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of 8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing regimen was constructed that would achieve sulfadoxine and pyrimethamine exposures in young children and underweight-for-age young children that were similar to those currently seen in a typical adult.

Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n=817, OR, 95% CI: 2.90, 1.96-4.30; 3.4, 1.8-6.3, both p

Background Rural infant growth failure has been highlighted as a priority for action in China’s national nutrition and child development policies. The aim of this paper was to evaluate the effect of community-based intervention project on child feeding, child health care and child growth. Methods From 2001 to 2005, UNICEF and China’s Ministry of Health worked together to develop holistic strategies for child health care. All the interventions were implemented through the three-tier (county-township-village) rural health care network.In this study, 34 counties were included in both surveys in 2001 and 2005. Among these 34 counties, nine were subjected to the intervention and 25 counties were used as controls. In nine intervention counties, leaflets containing information of supplemental feeding of infants and young children were printed and distributed to women during hospital delivery or visit to newborn by village doctors. Two cross-sectional surveys were both conducted from July to early September in 2001 and 2005. We calculated Z-scores of height-for-age (HAZ), weight-for-age (WAZ) and weight-for-height (WHZ), with the new WHO growth standard. HAZ

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:\ud \ud To assess the impact and cost-effectiveness of different types of death review in reducing maternal, perinatal and child mortality.