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Seasonal trends in tuberculosis (TB) notifications have been observed in several countries but are poorly understood. Explanatory factors may include weather, indoor crowding, seasonal respiratory infections and migration. Using enhanced citywide TB surveillance data collected over nine years in Blantyre, Malawi, we set out to investigate how weather and seasonality affect temporal trends in TB case notification rates (CNRs) across different demographic groups. We used data from prospective enhanced surveillance between April 2011 and December 2018, which systematically collected age, HIV status, sex and case notification dates for all registering TB cases in Blantyre. We retrieved temperature and rainfall data from the Global Surface Summary of the Day weather station database. We calculated weekly trends in TB CNRs, rainfall and temperature, and calculated 10-week moving averages. To investigate the associations between rainfall, temperature and TB CNRs, we fitted generalized linear models using a distributed lag nonlinear framework. The estimated Blantyre population increased from 1,068,151 in April 2011 to 1,264,304 in December 2018, with 15,908 TB cases recorded. Overall annual TB CNRs declined from 222 to 145 per 100,000 between 2012 and 2018, with the largest declines seen in HIV-positive people and adults aged over 20 years old. TB CNRs peaks occurred with increasing temperature in September and October before the onset of increased rainfall, and later in the rainy season during January-March, after sustained rainfall. When lag between a change in weather and TB case notifications was accounted for, higher average rainfall was associated with an equivalent six weeks of relatively lower TB notification rates, whereas there were no changes in TB CNR associated with change in average temperatures. TB CNRs in Blantyre have a seasonal pattern of two cyclical peaks per year, coinciding with the start and end of the rainy season. These trends may be explained by increased transmission at certain times of the year, by limited healthcare access, by patterns of seasonal respiratory infections precipitating cough and care-seeking, or by migratory patterns related to planting and harvesting during the rainy season.

IntroductionChildhood malnutrition is widespread in low-income and middle-income countries (LMICs) and increases the frequency and severity of infections such as pneumonia. We aimed to identify studies investigating pneumonia deaths in malnourished children and estimate mortality risk by malnutrition severity.MethodsWe conducted a systematic review of MEDLINE, EMBASE and Global Health databases to identify relevant studies. We used a network meta-analysis to derive ORs of death from pneumonia for moderately and severely underweight children using low weight-for-age, the most reported measure of malnutrition. We compared meta-estimates of studies conducted before and after 2000 to assess changes in mortality risk over time. We estimated the prevalence of underweight hospitalised children from hospital-based cohort studies and calculated the population attributable fraction of in-hospital pneumonia deaths from being underweight using our results.ResultsOur network meta-analysis included 33 544 underweight children from 23 studies. The estimated OR of death from pneumonia was 2.0 (95% CI 1.6 to 2.6) and 4.6 (95% CI 3.7 to 5.9) for children moderately and severely underweight, respectively. The OR of death from pneumonia for those severely underweight was 5.3 (95% CI 3.9 to 7.4) pre-2000 and remained high post-2000 at 4.1 (95% CI 3.0 to 6.0). Prevalence of underweight children hospitalised with pneumonia varied (median 40.2%, range 19.6–66.3) but was high across many LMIC settings. We estimated a median 18.3% (range 10.8–34.6) and 40.9% (range 14.7–69.9) of in-hospital pneumonia deaths were attributable to being moderately and severely underweight, respectively.ConclusionsThe risk of death from childhood pneumonia dramatically increases with malnutrition severity. This risk has remained high in recent years with an estimated over half of in-hospital pneumonia deaths attributable to child malnutrition. Prevention and treatment of all child malnutrition must be prioritised to maintain progress on reducing pneumonia deaths.

Background: Better understanding of SARS-CoV-2 transmission risks is needed to support decision-making around mitigation measures for COVID-19 in schools.Methods: We updated a living systematic review and meta-analysis to investigate the extent of SARS-CoV-2 transmission in schools. In this update we modified our inclusion criteria to include: 1) cohort studies; 2) cross-sectional studies that investigated and cross-assessed SARS-COV-2 positivity rates in schools and communities; and 3) pre-post studies. We performed risk of bias evaluation for all included studies using the Newcastle-Ottawa Scale (NOS).Results: 6270 articles were retrieved and six new studies were added in this update. In total from the two updates and using the new inclusion criteria, we identified 11 cohort studies (1st update: n = 5; 2nd update: n = 6) and one cross-sectional study (1st update: n = 1; 2nd update: n = 0). We performed a meta-analysis on nine of the 11 cohort studies investigating IAR in schools. Nine cohort studies reported a total of 91 student and 52 staff index cases that exposed 5698 contacts with 101 secondary infections (overall infection attack rate (IAR) = 1.45%, 95% CI = 0.31%-3.26%). IARs for students and school staff were 1.66% (95% CI = 0.08%-4.78%) and 1.18% (95% CI = 0.00%-4.43%) respectively. The risk of bias was found to be high for most studies identified, limiting the confidence in results.Conclusions: There is limited high-quality evidence available to quantify the extent of SARS-CoV-2 transmission in schools or to compare it to community transmission. Emerging evidence suggests the overall IAR and SARS-CoV-2 positivity rate in school settings are low. Higher IAR were found in students, compared to staff.Note: This article is a living systematic review that will be updated to reflect emerging evidence. This is the second version of the original article published on 23 December 2020 (J Glob Health 2020;11:021104), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

BackgroundSevere childhood malnutrition impairs growth and development short-term, but current understanding of long-term outcomes is limited. We aimed to identify studies assessing neurodevelopmental, cognitive, behavioural and mental health outcomes following childhood malnutrition.MethodsWe systematically searched MEDLINE, EMBASE, Global Health and PsychINFO for studies assessing these outcomes in those exposed to childhood malnutrition in low- and middle-income settings. We included studies assessing undernutrition measured by low mid-upper arm circumference, weight-for-height, weight-for-age or nutritional oedema. We used guidelines for synthesis of results without meta-analysis to analyse three outcome areas: neurodevelopment, cognition/academic achievement, behaviour/mental health.ResultsWe identified 30 studies, including some long-term cohorts reporting outcomes through to adulthood. There is strong evidence that malnutrition in childhood negatively impacts neurodevelopment based on high-quality studies using validated neurodevelopmental assessment tools. There is also strong evidence that malnutrition impairs academic achievement with agreement across seven studies investigating this outcome. 8 of 11 studies showed association between childhood malnutrition and impaired cognition. This moderate evidence is limited by some studies failing to measure important confounders such as socioeconomic status. 5 of 7 studies found a difference in behavioural assessment scores in those exposed to childhood malnutrition compared to controls but this moderate evidence is similarly limited by unmeasured confounders. Mental health impacts were difficult to ascertain due to few studies with mixed results.ConclusionsChildhood malnutrition is associated with impaired neurodevelopment, academic achievement, cognition and behavioural problems but evidence regarding possible mental health impacts is inconclusive. Future research should explore the interplay of childhood and later-life adversities on these outcomes. Whilst evidence on improving nutritional and clinical therapies to reduce long-term risks is also needed, preventing and eliminating child malnutrition is likely to be the best way of preventing long-term neurocognitive harms.PROSPERO registration numberCRD42021260498KEY QUESTIONSWhat is already known?– High mortality risk and impaired growth are well-recognised short-term risks of childhood malnutrition– Whilst there is increasing appreciation of longer-term risks for survivors, notably adult cardiometabolic non-communicable disease, other longer-term risks have been poorly described.What are the new findings?– There is strong evidence that malnutrition impairs neurodevelopment and academic achievement in childhood which has significant implications for future wellbeing and prospects of those affected– Childhood malnutrition is associated with impaired cognition and behavioural problems with evidence of effects through to adolescence and adulthood but the effect of nutritional treatment and interplay with childhood adversity, co-existing illness such as HIV and environmental factors in influencing these outcomes is unclearWhat do the new findings imply?– Study findings imply that there are likely to be long-term effects of childhood malnutrition on cognition and wellbeing lasting through adolescence and adulthood– Long-term needs of malnutrition survivors need to be carefully considered in treatment programmes. Further research is needed on the effects of nutritional therapy, adversity and environmental factors to tailor future interventions, particularly with regards to mental health which has been little researched

Background It is of paramount importance to understand the transmission of SARS-CoV-2 in schools, which could support the decision-making about educational facilities closure or re-opening with effective prevention and control measures in place. Methods We conducted a systematic review and meta-analysis to investigate the extent of SARS-CoV-2 transmission in schools. We performed risk of bias evaluation of all included studies using the Newcastle-Ottawa Scale (NOS). Results 2178 articles were retrieved and 11 studies were included. Five cohort studies reported a combined 22 student and 21 staff index cases that exposed 3345 contacts with 18 transmissions (overall infection attack rate (IAR): 0.08%, 95% confidence interval (CI) = 0.00%-0.86%). IARs for students and school staff were 0.15% (95% CI = 0.00%-0.93%) and 0.70% (95% CI = 0.00%-3.56%) respectively. Six cross-sectional studies reported 639 SARS-CoV-2 positive cases in 6682 study participants tested [overall SARS-CoV-2 positivity rate: 8.00% (95% CI = 2.17%-16.95%). SARS-CoV-2 positivity rate was estimated to be 8.74% (95% CI = 2.34%-18.53%) among students, compared to 13.68% (95% CI = 1.68%-33.89%) among school staff. Gender differences were not found for secondary infection (OR = 1.44, 95% CI = 0.50-4.14, P = 0.49) and SARS-CoV-2 positivity (OR = 0.90, 95% CI = 0.72-1.13, P = 0.36) in schools. Fever, cough, dyspnea, ageusia, anosmia, rhinitis, sore throat, headache, myalgia, asthenia, and diarrhoea were all associated with the detection of SARS-CoV-2 antibodies (based on two studies). Overall, study quality was judged to be poor with risk of performance and attrition bias, limiting the confidence in the results. Conclusions There is limited high-quality evidence available to quantify the extent of SARS-CoV-2 transmission in schools or to compare it to community transmission. Emerging evidence suggests lower IAR and SARS-CoV-2 positivity rate in students compared to school staff. Future prospective and adequately controlled cohort studies are necessary to confirm this finding.

BackgroundPeople affected by homelessness, imprisonment, substance use, sex work or severe mental illness experience substantial excess ill health and premature death. Though these experiences often co-occur, health outcomes associated with their overlap have not previously been reviewed. We synthesised existing evidence on mortality, morbidity, self-rated health and quality of life among people affected by more than one of these experiences.MethodsIn this systematic review and meta-analysis, we searched Medline, Embase, and PsycINFO for peer-reviewed English-language observational studies from high-income countries published between 1 January 1998 and 11 June 2018. Two authors undertook independent screening, with risk of bias assessed using a modified Newcastle-Ottawa Scale. Findings were summarised by narrative synthesis and random-effect meta-analysis.ResultsFrom 15 976 citations, 2517 studies underwent full-text screening, and 444 were included. The most common exposure combinations were imprisonment/substance use (31% of data points) and severe mental illness/substance use (27%); only 1% reported outcomes associated with more than two exposures. Infections were the most common outcomes studied, with blood-borne viruses accounting for 31% of all data points. Multiple exposures were associated with poorer outcomes in 80% of data points included (sign test for effect direction, pConclusionPeople affected by multiple exclusionary processes experience profound health inequalities, though there are important gaps in the research landscape. Addressing the health needs of these populations is likely to require co-ordinated action across multiple sectors, such as healthcare, criminal justice, drug treatment, housing and social security.PROSPERO registration numberCRD42018097189.

Background: Understanding carriage and transmission potential of SARS-CoV-2 in children is of paramount importance to understand the spread of virus in school and community settings.Methods: We performed an updated rapid review to investigate the role of children in the transmission of SARS-CoV-2. We synthesized evidence for five categories and results are reported narratively.Results: A total of 33 new studies were included for this review. We did not identify additional studies that reported documented cases of SARS-CoV-2 transmission by children. We identified 15 new studies that demonstrate children's susceptibility and transmission risk of SARS-CoV-2 with evidence provided on the chance of being index or secondary cases, the potential of faecal-oral transmission, and the possibility of asymptomatic transmission. There is little data on the transmission of SARS-CoV-2 in schools. There were three studies reporting COVID-19 school outbreaks in France (Oise), Australia (New South Wales) and Israel. The remaining four studies found that all reported cases did not infect any other pupils or staff. With data from seven studies and governmental websites, the proportion of children among all confirmed COVID-19 patients was estimated for 29 countries, varying from 0.3% (lowest in Spain) up to 13.8% (highest in Argentina). Lastly, we identified seven studies reporting on PIMS-TS linked to COVID-19 among paediatric patients.Conclusions: There is somewhat limited evidence available for quantifying the extent to which children may contribute to overall transmission, but the balance of evidence so far suggests that children and schools play only a limited role in overall transmission.

Background: Understanding the role of children in the transmission of SARS-CoV-2 is urgently required given its policy implications in relation to the reopening of schools and intergenerational contacts.Methods: We conducted a rapid review of studies that investigated the role of children in the transmission of SARS-CoV-2. We synthesized evidence for four categories: 1) studies reporting documented cases of SARS-CoV-2 transmission by infected children; 2) studies presenting indirect evidence on the potential of SARS-CoV-2 transmission by (both symptomatic and asymptomatic) children; 3) studies reporting cluster outbreaks of COVID-19 in schools; 4) studies estimating the proportions of children infected by SARS-CoV-2, and reported results narratively.Results: A total of 16 unique studies were included for narrative synthesis. There is limited evidence detailing transmission of SARS-CoV-2 from infected children. We found two studies that reported a 3-month-old whose parents developed symptomatic COVID-19 seven days after caring for the infant and two children who may have contracted COVID-19 from the initial cases at a school in New South Wales. In addition, we identified six studies presenting indirect evidence on the potential for SARS-CoV-2 transmission by children, three of which found prolonged virus shedding in stools. There is little data on the transmission of SARS-CoV-2 in schools. We identified only two studies reporting outbreaks of COVID-19 in school settings and one case report of a child attending classes but not infecting any other pupils or staff. Lastly, we identified six studies estimating the proportion of children infected; data from population-based studies in Iceland, Italy, South Korea, Netherlands, California and a hospital-based study in the UK suggest children may be less likely to be infected.Conclusions: Preliminary results from population-based and school-based studies suggest that children may be less frequently infected or infect others, however current evidence is limited. Prolonged faecal shedding observed in studies highlights the potentially increased risk of faeco-oral transmission in children. Further seroprevalence studies (powered adequately for the paediatric population) are urgently required to establish whether children are in fact less likely to be infected compared to adults.Note: We plan to update this rapid review as new data becomes available. These updates are available at https://www.ed.ac.uk/usher/uncover/completed-uncover-reviews.

During October and November 2016, over 1,000 customers and staff reported gastroenteritis after eating at all 23 branches of a restaurant group in the United Kingdom. The outbreak coincided with a new menu launch and norovirus was identified as the causative agent. We conducted four retrospective cohort studies; one among all restaurant staff and three in customers at four branches. We investigated the dishes consumed, reviewed recipes, interviewed chefs and inspected restaurants to identify common ingredients and preparation methods for implicated dishes. Investigations were complicated by three public health agencies concurrently conducting multiple analytical studies, the complex menu with many shared constituent ingredients and the high media attention. The likely source was a contaminated batch of a nationally distributed ingredient, but analytical studies were unable to implicate a single ingredient. The most likely vehicle was a new chipotle chilli product imported from outside the European Union, that was used uncooked in the implicated dishes. This outbreak exemplifies the possibility of rapid spread of infectious agents within a restaurant supply chain, following introduction of a contaminated ingredient. It underlines the importance of appropriate risk assessments and control measures being in place, particularly for new ingredients and ready-to-eat foods.

Background: The high disease burden of respiratory syncytial virus (RSV) infection and renewed focus on developing a vaccine has led to sustained interest in published RSV-related research. The majority of this research comes from Europe and North/Central America and this landscape review aimed to identify and characterize RSV-related research published during 2011-2015 in these geographical areas.Methods: We conducted a literature review on electronic databases Scopus and Web of Science to identify published studies investigating RSV throughout Europe and North/Central America. We stratified RSV-related publications between 2011-2015 by study type, country, research institution and funding body.Results: The annual published output of RSV-related research has increased by 29% over the period 2011-2015. Eighty seven percent (13/15) of the most highly cited papers on RSV during this period were from North America. US universities with the highest number of RSV-related publications included Emory (n = 23), Vanderbilt (n = 23), University of Michigan (n = 21) and Ohio State (n = 20). The UK (n = 125), Netherlands (n = 97) and Spain (n = 76) were major European contributors to RSV-related publications. University Medical Centre Utrecht (n = 40) and Imperial College London (n = 28) were the European universities with the largest number of RSV-related publications. The National Institutes of Health provided funding for one quarter of all RSV-related publications. However, few countries in Eastern Europe, Central America and the Caribbean published RSV-related research. Few epidemiological studies focused on adult populations over 18 years old (n = 28, 7%) with only five publications specifically investigating elderly populations over 65.Conclusions: This review identifies key regions and research institutions which contributed to RSV-related research during 2011-2015 as well as the donor agencies which supported this research. Further research investment is required in a number of countries. More research in the elderly and in high-risk adults is required given the lack of studies pertaining to these populations. Researchers and those commissioning research can use the data from this review to identify productive research institutions and geographical gaps in RSV research.

Enterovirus D68 (EV-D68) is an emerging infection associated with acute flaccid myelitis (AFM). Cases of AFM associated with EV-D68 infection have increased in recent years and the evidence for a causal link is growing. However, our understanding of the epidemiology, clinical features, prognosis, and neurological sequelae of EV-D68 requires ongoing surveillance and investigation. We report five cases of AFM in previously typically developing children (2-6y) from South East Scotland during September and October 2016 after infection with EV-D68 (all detected in the nasopharyngeal aspirates). All cases presented with significant neurological symptoms, which were severe in two cases requiring intensive care support because of respiratory paralysis. At 18-month follow-up, two cases remain ventilator-dependent with other cases requiring ongoing community rehabilitation. These cases represent one of the largest reported paediatric cluster of AFM associated with EV-D68 in Europe. The epidemiology and clinical information add to the knowledge base and the 18-month outcome will help clinicians to counsel families. WHAT THIS PAPER ADDS: Nasopharyngeal aspirate is more sensitive for viral isolation and isolated in all cases. Clinical outcome at 18 months after enterovirus D68 with acute flaccid myelitis provides information on extent of recovery and level of disability.

This study aimed to investigate the differences in reported care seeking behaviour and treatment between children with pneumonia and children without pneumonia with cough and/or difficult breathing.Three hundred and two children aged 0-59 months with fast breathing pneumonia were matched with 302 children seeking care for cough and/or difficult breathing at four outpatient clinics in Ibadan, Nigeria. After follow up at home, Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) questionnaires were administered in the community by trained field workers to gather information around care seeking delay, patterns of care seeking, appropriateness of care seeking and treatment provided once care was sought. Multivariable analysis was carried out to determine significant factors associated with care seeking delay.Children with pneumonia had a significantly longer delay (median = 3d) before seeking care than those without pneumonia (median = 2d;Given that children with pneumonia and cough/cold had similar patterns of reported care seeking information gathered on care seeking (type of provider visited) from DHS and MICS surveys on those with 'symptoms of acute respiratory infection' in this setting provide a reasonably valid indication of care seeking behaviours in children with pneumonia. There are high levels of antibiotic overuse for children with cough/cold in this setting which risks worsening antibiotic resistance.

Childhood pneumonia is the single largest infectious cause of death in children under five worldwide. Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS) provide health information on care sought for sick children in resource poor settings. Despite not being primarily designed to identify childhood pneumonia, there are concerns that reported episodes of "symptoms of acute respiratory infection" in DHS and MICS are often interpreted by other groups as a "proxy" for childhood pneumonia. Using DHS5 and MICS5 survey tools, this study aimed to assess how accurately caregivers report of "symptoms of acute respiratory infection" reflect pneumonia episodes and antibiotic use in children under five.Children aged 0 to 59 months presenting with cough and/or difficult breathing were recruited from four study hospitals in Ibadan, Nigeria from August 2015 to March 2017. Children were assessed using World Health Organization (WHO) standard criteria by study physicians to identify whether they had pneumonia. Three hundred and two matched children in each category of 'pneumonia' and "no pneumonia" were followed up at home, either two or eight weeks later, using questions from DHS5 and MICS5 surveys to assess the accuracy of caregiver recall of pneumonia.The specificity of DHS5 and MICS5 questions for identifying childhood pneumonia were 87.4 (95% confidence interval (CI) = 83.1-91.0) and 86.1 (95% CI = 81.7-89.8) respectively and the sensitivity of questions were 37.1 (95% CI = 31.6-42.8) and 37.1 (95% CI = 31.6-42.8). Correct recall of antibiotic treatment was poor (kappa statistic = 0.064) but improved with the use of medicine pill boards (kappa statistic = 0.235).DHS5 and MICS5 survey questions are not designed to identify childhood pneumonia and this study confirms that they do not accurately discern episodes of childhood pneumonia from cough/cold in children under five. The proportion of pneumonia episodes appropriately treated with antibiotics cannot be accurately assessed using current DHS and MICS surveys. If these results are used to guide programmatic decisions, it is likely to encourage overuse and inappropriate prescribing of antibiotics for episodes of cough/cold. International agencies who continue to use these household data to monitor the proportion of children with pneumonia who receive antibiotic treatment should be discouraged from doing this as these data are likely to mislead national and global programmes. Medicine pill boards are used in a number of DHS surveys and should be promoted for wider use in national population surveys to improve the accuracy of antibiotic recall.