Showing papers by "International Centre for Diarrhoeal Disease Research, Bangladesh published in 2020"

COVID-19-Related Infodemic and Its Impact on Public Health: A Global Social Media Analysis.

Abstract: Infodemics, often including rumors, stigma, and conspiracy theories, have been common during the COVID-19 pandemic. Monitoring social media data has been identified as the best method for tracking rumors in real time and as a possible way to dispel misinformation and reduce stigma. However, the detection, assessment, and response to rumors, stigma, and conspiracy theories in real time are a challenge. Therefore, we followed and examined COVID-19-related rumors, stigma, and conspiracy theories circulating on online platforms, including fact-checking agency websites, Facebook, Twitter, and online newspapers, and their impacts on public health. Information was extracted between December 31, 2019 and April 5, 2020, and descriptively analyzed. We performed a content analysis of the news articles to compare and contrast data collected from other sources. We identified 2,311 reports of rumors, stigma, and conspiracy theories in 25 languages from 87 countries. Claims were related to illness, transmission and mortality (24%), control measures (21%), treatment and cure (19%), cause of disease including the origin (15%), violence (1%), and miscellaneous (20%). Of the 2,276 reports for which text ratings were available, 1,856 claims were false (82%). Misinformation fueled by rumors, stigma, and conspiracy theories can have potentially serious implications on the individual and community if prioritized over evidence-based guidelines. Health agencies must track misinformation associated with the COVID-19 in real time, and engage local communities and government stakeholders to debunk misinformation.

Dynamic interventions to control COVID-19 pandemic: a multivariate prediction modelling study comparing 16 worldwide countries.

Abstract: To date, non-pharmacological interventions (NPI) have been the mainstay for controlling the coronavirus disease-2019 (COVID-19) pandemic. While NPIs are effective in preventing health systems overload, these long-term measures are likely to have significant adverse economic consequences. Therefore, many countries are currently considering to lift the NPIs-increasing the likelihood of disease resurgence. In this regard, dynamic NPIs, with intervals of relaxed social distancing, may provide a more suitable alternative. However, the ideal frequency and duration of intermittent NPIs, and the ideal "break" when interventions can be temporarily relaxed, remain uncertain, especially in resource-poor settings. We employed a multivariate prediction model, based on up-to-date transmission and clinical parameters, to simulate outbreak trajectories in 16 countries, from diverse regions and economic categories. In each country, we then modelled the impacts on intensive care unit (ICU) admissions and deaths over an 18-month period for following scenarios: (1) no intervention, (2) consecutive cycles of mitigation measures followed by a relaxation period, and (3) consecutive cycles of suppression measures followed by a relaxation period. We defined these dynamic interventions based on reduction of the mean reproduction number during each cycle, assuming a basic reproduction number (R0) of 2.2 for no intervention, and subsequent effective reproduction numbers (R) of 0.8 and 0.5 for illustrative dynamic mitigation and suppression interventions, respectively. We found that dynamic cycles of 50-day mitigation followed by a 30-day relaxation reduced transmission, however, were unsuccessful in lowering ICU hospitalizations below manageable limits. By contrast, dynamic cycles of 50-day suppression followed by a 30-day relaxation kept the ICU demands below the national capacities. Additionally, we estimated that a significant number of new infections and deaths, especially in resource-poor countries, would be averted if these dynamic suppression measures were kept in place over an 18-month period. This multi-country analysis demonstrates that intermittent reductions of R below 1 through a potential combination of suppression interventions and relaxation can be an effective strategy for COVID-19 pandemic control. Such a "schedule" of social distancing might be particularly relevant to low-income countries, where a single, prolonged suppression intervention is unsustainable. Efficient implementation of dynamic suppression interventions, therefore, confers a pragmatic option to: (1) prevent critical care overload and deaths, (2) gain time to develop preventive and clinical measures, and (3) reduce economic hardship globally.

Urinary tract infections in pregnancy in a rural population of Bangladesh: population-based prevalence, risk factors, etiology, and antibiotic resistance.

Abstract: Urinary tract infection (UTI) in pregnancy, including asymptomatic bacteriuria, is associated with maternal morbidity and adverse pregnancy outcomes, including preterm birth and low birthweight. In low-middle income countries (LMICs), the capacity for screening and treatment of UTIs is limited. The objective of this study was to describe the population-based prevalence, risk factors, etiology and antimicrobial resistance patterns of UTIs in pregnancy in Bangladesh. In a community-based cohort in Sylhet district, Bangladesh, urine specimens were collected at the household level in 4242 pregnant women (< 20 weeks gestation) for culture and antibiotic susceptibility testing. Basic descriptive analysis was performed, as well as logistic regression to calculate adjusted odds ratios (aOR) for UTI risk factors. The prevalence of UTI was 8.9% (4.4% symptomatic UTI, 4.5% asymptomatic bacteriuria). Risk factors for UTI in this population included maternal undernutrition (mid-upper arm circumference <23 cm: aOR= 1.29, 95% CI: 1.03–1.61), primiparity (aOR= 1.45, 95% CI: 1.15–1.84), and low paternal education (no education: aOR= 1.56, 95% CI: 1.09–2.22). The predominant uro-pathogens were E. coli (38% of isolates), Klebsiella (12%), and staphyloccocal species (23%). Group B streptococcus accounted for 5.3% of uro-pathogens. Rates of antibiotic resistance were high, with only two-thirds of E. coli susceptible to 3rd generation cephalosporins. In Sylhet, Bangladesh, one in 11 women had a UTI in pregnancy, and approximately half of cases were asymptomatic. There is a need for low-cost and accurate methods for UTI screening in pregnancy and efforts to address increasing rates of antibiotic resistance in LMIC.

The impact of the COVID-19 pandemic on the mental health of the adult population in Bangladesh: a nationwide cross-sectional study.

Abstract: The recent COVID-19 pandemic has imposed threats on both physical and mental health since its outbreak. This study aimed to explore the impact of the COVID-19 pandemic on mental health among a representative sample of home-quarantined Bangladeshi adults. A cross-sectional design was used with an online survey completed by a convenience sample recruited via social media. A total of 1,427 respondents were recruited, and their mental health was assessed by the DASS-21 measure. The prevalence of anxiety symptoms and depressive symptoms was 33.7% and 57.9%, respectively, and 59.7% reported mild to extremely severe levels of stress. Perceptions that the pandemic disrupted life events, affected mental health, jobs, the economy and education, predictions of a worsening situation, and uncertainty of the health care system capacities were significantly associated with poor mental health outcomes. Multivariate logistic regressions showed that sociodemographic factors and perceptions of COVID-19 significantly predict mental health outcomes. These findings warrant the consideration of easily accessible low-intensity mental health interventions during and beyond this pandemic.

Current knowledge of COVID-19 and infection prevention and control strategies in healthcare settings: A global analysis.

Abstract: OBJECTIVE: In the current absence of a vaccine for COVID-19, public health responses aim to break the chain of infection by focusing on the mode of transmission. We reviewed the current evidence on the transmission dynamics and on pathogenic and clinical features of COVID-19 to critically identify any gaps in the current infection prevention and control (IPC) guidelines. METHODS: In this study, we reviewed global COVID-19 IPC guidelines by organizations such as the World Health Organization (WHO), the US Centers for Disease Control and Prevention (CDC), and the European Centre for Disease Prevention and Control (ECDC). Guidelines from 2 high-income countries (Australia and United Kingdom) and from 1 middle-income country (China) were also reviewed. We searched publications in English on 'PubMed' and Google Scholar. We extracted information related to COVID-19 transmission dynamics, clinical presentations, and exposures that may facilitate transmission. We then compared these findings with the recommended IPC measures. RESULTS: Nosocomial transmission of SARS-CoV-2 in healthcare settings occurs through droplets, aerosols, and the oral-fecal or fecal-droplet route. However, the IPC guidelines fail to cover all transmission modes, and the recommendations also conflict with each other. Most guidelines recommend surgical masks for healthcare providers during routine care and N95 respirators for aerosol-generating procedures. However, recommendations regarding the type of face mask varied, and the CDC recommends cloth masks when surgical masks are unavailable. CONCLUSION: IPC strategies should consider all the possible routes of transmission and should target all patient care activities involving risk of person-to-person transmission. This review may assist international health agencies in updating their guidelines.

Nipah virus dynamics in bats and implications for spillover to humans

Abstract: Nipah virus (NiV) is an emerging bat-borne zoonotic virus that causes near-annual outbreaks of fatal encephalitis in South Asia-one of the most populous regions on Earth. In Bangladesh, infection occurs when people drink date-palm sap contaminated with bat excreta. Outbreaks are sporadic, and the influence of viral dynamics in bats on their temporal and spatial distribution is poorly understood. We analyzed data on host ecology, molecular epidemiology, serological dynamics, and viral genetics to characterize spatiotemporal patterns of NiV dynamics in its wildlife reservoir, Pteropus medius bats, in Bangladesh. We found that NiV transmission occurred throughout the country and throughout the year. Model results indicated that local transmission dynamics were modulated by density-dependent transmission, acquired immunity that is lost over time, and recrudescence. Increased transmission followed multiyear periods of declining seroprevalence due to bat-population turnover and individual loss of humoral immunity. Individual bats had smaller host ranges than other Pteropus species (spp.), although movement data and the discovery of a Malaysia-clade NiV strain in eastern Bangladesh suggest connectivity with bats east of Bangladesh. These data suggest that discrete multiannual local epizootics in bat populations contribute to the sporadic nature of NiV outbreaks in South Asia. At the same time, the broad spatial and temporal extent of NiV transmission, including the recent outbreak in Kerala, India, highlights the continued risk of spillover to humans wherever they may interact with pteropid bats and the importance of limiting opportunities for spillover throughout Pteropus's range.

Improving the impact of non-pharmaceutical interventions during COVID-19: examining the factors that influence engagement and the impact on individuals.

Abstract: During an evolving outbreak or pandemic, non-pharmaceutical interventions (NPIs) including physical distancing, isolation, and mask use may flatten the peak in communities. However, these strategies rely on community understanding and motivation to engage to ensure appropriate compliance and impact. To support current activities for COVID-19, the objectives of this narrative review was to identify the key determinants impacting on engagement. An integrative narrative literature review focused on NPIs. We aimed to identify published peer-reviewed articles that focused on the general community (excluding healthcare workers), NPIs (including school closure, quarantine, isolation, physical distancing and hygiene behaviours), and factors/characteristics (including social, physical, psychological, capacity, motivation, economic and demographic) that impact on engagement. The results revealed that there are a range of demographic, social and psychological factors underpinning engagement with quarantine, school closures, and personal protective behaviours. Aside from the factors impacting on acceptance and compliance, there are several key community concerns about their use that need to be addressed including the potential for economic consequences. It is important that we acknowledge that these strategies will have an impact on an individual and the community. By understanding the barriers, we can identify what strategies need to be adopted to motivate individuals and improve community compliance. Using a behavioural framework to plan interventions based on these key barriers, will also ensure countries implement appropriate and targeted responses.

Urban informal settlements as hotspots of antimicrobial resistance and the need to curb environmental transmission.

Abstract: Antimicrobial resistance (AMR) is a growing public health challenge that is expected to disproportionately burden lower- and middle-income countries (LMICs) in the coming decades. Although the contributions of human and veterinary antibiotic misuse to this crisis are well-recognized, environmental transmission (via water, soil or food contaminated with human and animal faeces) has been given less attention as a global driver of AMR, especially in urban informal settlements in LMICs-commonly known as 'shanty towns' or 'slums'. These settlements may be unique hotspots for environmental AMR transmission given: (1) the high density of humans, livestock and vermin living in close proximity; (2) frequent antibiotic misuse; and (3) insufficient drinking water, drainage and sanitation infrastructure. Here, we highlight the need for strategies to disrupt environmental AMR transmission in urban informal settlements. We propose that water and waste infrastructure improvements tailored to these settings should be evaluated for their effectiveness in limiting environmental AMR dissemination, lowering the community-level burden of antimicrobial-resistant infections and preventing antibiotic misuse. We also suggest that additional research is directed towards developing economic and legal incentives for evaluating and implementing water and waste infrastructure in these settings. Given that almost 90% of urban population growth will occur in regions predicted to be most burdened by the AMR crisis, there is an urgent need to build effective, evidence-based policies that could influence massive investments in the built urban environment in LMICs over the next few decades.

Indole-3-lactic acid associated with Bifidobacterium-dominated microbiota significantly decreases inflammation in intestinal epithelial cells

Abstract: Bifidobacterium longum subsp. infantis (B. infantis) is a commensal bacterium that colonizes the gastrointestinal tract of breast-fed infants. B. infantis can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence. We hypothesized that metabolites from B. infantis grown on HMO produce a beneficial effect on the host. In a previous study, we demonstrated that B. infantis routinely dominated the fecal microbiota of a breast fed Bangladeshi infant cohort (1). Characterization of the fecal metabolome of binned samples representing high and low B. infantis populations from this cohort revealed higher amounts of the tryptophan metabolite indole-3-lactic acid (ILA) in feces with high levels of B. infantis. Further in vitro analysis confirmed that B. infantis produced significantly greater quantities of the ILA when grown on HMO versus lactose, suggesting a growth substrate relationship to ILA production. The direct effects of ILA were assessed in a macrophage cell line and intestinal epithelial cell lines. ILA (1-10 mM) significantly attenuated lipopolysaccharide (LPS)-induced activation of NF-kB in macrophages. ILA significantly attenuated TNF-α- and LPS-induced increase in the pro-inflammatory cytokine IL-8 in intestinal epithelial cells. ILA increased mRNA expression of the aryl hydrogen receptor (AhR)-target gene CYP1A1 and nuclear factor erythroid 2–related factor 2 (Nrf2)-targeted genes glutathione reductase 2 (GPX2), superoxide dismutase 2 (SOD2), and NAD(P) H dehydrogenase (NQO1). Pretreatment with either the AhR antagonist or Nrf-2 antagonist inhibited the response of ILA on downstream effectors. These findings suggest that ILA, a predominant metabolite from B. infantis grown on HMO and elevated in infant stool high in B. infantis, and protects gut epithelial cells in culture via activation of the AhR and Nrf2 pathway.

Duodenal Microbiota in Stunted Undernourished Children with Enteropathy

Abstract: Background Environmental enteric dysfunction (EED) is an enigmatic disorder of the small intestine that is postulated to play a role in childhood undernutrition, a pressing global health p...

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Abstract: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been ass ...

Tackling antimicrobial resistance in Bangladesh: A scoping review of policy and practice in human, animal and environment sectors.

Abstract: Background Antimicrobial resistance (AMR) has become an emerging issue in the developing countries as well as in Bangladesh. AMR is aggravated by irrational use of antimicrobials in a largely unregulated pluralistic health system. This review presents a ‘snap shot’ of the current situation including existing policies and practices to address AMR, and the challenges and barriers associated with their implementation. Methods A systematic approach was adopted for identifying, screening, and selecting relevant literature on AMR situation in Bangladesh. We used Google Scholar, Pubmed, and Biomed Central databases for searching peer-reviewed literature in human, animal and environment sectors during January 2010-August 2019, and Google for grey materials from the institutional and journal websites. Two members of the study team independently reviewed these documents for inclusion in the analysis. We used a ‘mixed studies review’ method for synthesizing evidences from different studies. Result Of the final 47 articles, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Nineteen articles on human health dealt with prescribing and/or use of antimicrobials, five on self-medication, two on non-compliance of dosage, and 10 on the sensitivity and resistance patterns of antibiotics. Four papers focused on the use of antimicrobials in food animals and seven on environmental contamination. Findings reveal widespread availability of antimicrobials without prescription in the country including rise in its irrational use across sectors and consequent contamination of environment and spread of resistance. The development and transmission of AMR is deep-rooted in various supply and demand side factors. Implementation of existing policies and strategies remains a challenge due to poor awareness, inadequate resources and absence of national surveillance. Conclusion AMR is a multi-dimensional problem involving different sectors, disciplines and stakeholders requiring a One Health comprehensive approach for containment.

Drivers of Antibiotic Use in Poultry Production in Bangladesh: Dependencies and Dynamics of a Patron-Client Relationship

Abstract: Background: There is increasing concern around the use of antibiotics in animal food production and the risk of transmission of antimicrobial resistance within the food chain. In many low and middle-income countries, including Bangladesh, the commercial poultry sector comprises small-scale producers who are dependent on credit from poultry dealers to buy day-old chicks and poultry feed. The same dealers also supply and promote antibiotics. The credit system is reliant upon informal relationships among multiple actors as part of social capital. This paper aims to describe dependencies and relationships between different actors within unregulated broiler poultry production systems to understand the social and contextual determinants of antibiotic use in low-resource settings. Methods: We used a cross-sectional qualitative design including in-depth interviews among purposefully selected commercial poultry farmers (n = 10), poultry dealers (n = 5), sales representatives of livestock pharmaceutical companies (n = 3) and the local government livestock officer as a key-informant (n = 1). We describe the food production cycle and practices relating to credit purchases and sales using social capital theory. Findings: Poultry dealers provide credit and information for small-scale poultry farmers to initiate and operate their business. In return for credit, farmers are obliged to buy poultry feed and medicine from their dealer and sell their market-ready poultry to that same dealer. All farms applied multiple antibiotics to poultry throughout the production cycle, including banned antibiotics such as colistin sulfate. The relationship between dealers and poultry farmers is reciprocal but mostly regulated by the dealers. Dealers were the main influencers of decision-making by farmers, particularly around antibiotic use as an integral part of the production cycle risk management. Our findings suggest that strategies to improve antibiotic stewardship and responsible use should exploit the patron-client relationship which provides the social and information network for small-scale farmers. Conclusion: Social capital theory can be applied to the patron-client relationship observed among poultry farmers and dealers in Bangladesh to identify influences on decision making and antibiotic use. Within unregulated food production systems, strategies to promote the prudent use of antibiotics should target commercial feed producers and livestock pharmaceutical manufacturers as a first step in developing a sustainable poultry value chain.

Safety and immunogenicity of the oral, inactivated, enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi children and infants: a double-blind, randomised, placebo-controlled phase 1/2 trial

Abstract: Summary Background Enterotoxigenic Escherichia coli causes diarrhoea, leading to substantial mortality and morbidity in children, but no specific vaccine exists. This trial tested an oral, inactivated, enterotoxigenic E coli vaccine (ETVAX), which has been previously shown to be safe and highly immuongenic in Swedish and Bangladeshi adults. We tested the safety and immunogenicity of ETVAX, consisting of four E coli strains overexpressing the most prevalent colonisation factors (CFA/I, CS3, CS5, and CS6) and a toxoid (LCTBA) administered with or without a double-mutant heat-labile enterotoxin (dmLT) as an adjuvant, in Bangladeshi children. Methods We did a randomised, double-blind, placebo-controlled, dose-escalation, age-descending, phase 1/2 trial in Dhaka, Bangladesh. Healthy children in one of three age groups (24–59 months, 12–23 months, and 6–11 months) were eligible. Children were randomly assigned with block randomisation to receive either ETVAX, with or without dmLT, or placebo. ETVAX (half [5·5 × 1010 cells], quarter [2·5 × 1010 cells], or eighth [1·25 × 1010 cells] adult dose), with or without dmLT adjuvant (2·5 μg, 5·0 μg, or 10·0 μg), or placebo were administered orally in two doses 2 weeks apart. Investigators and participants were masked to treatment allocation. The primary endpoint was safety and tolerability, assessed in all children who received at least one dose of vaccine. Antibody responses to vaccine antigens, defined as at least a two-times increase in antibody levels between baseline and post-immunisation, were assessed as secondary endpoints. This trial is registered with ClinicalTrials.gov , NCT02531802 . Findings Between Dec 7, 2015, and Jan 10, 2017, we screened 1500 children across the three age groups, of whom 430 were enrolled and randomly assigned to the different treatment groups (130 aged 24–59 months, 100 aged 12–23 months, and 200 aged 6–11 months). All participants received at least one dose of vaccine. No solicited adverse events occurred that were greater than moderate in severity, and most were mild. The most common solicited event was vomiting (ten [8%] of 130 patients aged 24–59 months, 13 [13%] of 100 aged 12–23 months, and 29 [15%] of 200 aged 6–11 months; mostly of mild severity), which appeared related to dose and age. The addition of dmLT did not modify the safety profile. Three serious adverse events occurred but they were not considered related to the study drug. Mucosal IgA antibody responses in lymphocyte secretions were detected against all primary vaccine antigens (CFA/I, CS3, CS5, CS6, and the LCTBA toxoid) in most participants in the two older age groups, whereas such responses to four of the five antigens were less frequent and of lower magnitude in infants aged 6–11 months than in older children. Faecal secretory IgA immune responses were recorded against all vaccine antigens in infants aged 6–11 months. 78 (56%) of 139 infants aged 6–11 months who were vaccinated developed mucosal responses against at least three of the vaccine antigens versus 14 (29%) of 49 of the infants given placebo. Addition of the adjuvant dmLT enhanced the magnitude, breadth, and kinetics (based on number of responders after the first dose of vaccine) of immune responses in infants. Interpretation The encouraging safety and immunogenicity of ETVAX and benefit of dmLT adjuvant in young children support its further assessment for protective efficacy in children in enterotoxigenic E coli-endemic areas. Funding PATH (Bill & Melinda Gates Foundation and the UK's Department for International Development), the Swedish Research Council, and The Swedish Foundation for Strategic Research.

New learnings on drivers of men's physical and/or sexual violence against their female partners, and women's experiences of this, and the implications for prevention interventions.

Abstract: Background: Understanding the drivers of intimate partner violence (IPV), perpetrated by men and experienced by women, is a critical task for developing effective prevention programmes.Objectives: To provide a comprehensive assessment of the drivers of IPV.Methods: A comprehensive review of the drivers of IPV, at the end of a six-year programme of research through the What Works to Prevent Violence Against Women and Girls Global Programme with reference to other important research in the field.Results: Broadly, we argue that IPV is driven by poverty, patriarchal privilege, and the normative use of violence in interpersonal relationships. These factors also increase childhood trauma, poor mental health and substance misuse, and poor communication and conflict in relationships, which in turn impact on IPV. Disability status, and contexts of armed conflict, or post-conflict, further reinforce and exacerbate these risks. We move beyond describing associations towards describing the causal pathways through which these factors operate to increase IPV.Conclusions: Specific recommendations about the future of further research on drivers of IPV include a greater focus on understanding the causal pathways from drivers to IPV and clearly delineating association from causality in studies, particularly for women and girls with disabilities, in armed conflicts, and adolescent girls and young women. To achieve this, we recommend extensive in-depth qualitative research, and complex quantitative modeling studies. Understanding drivers and causal pathways better will enable the identification of points of entry for the development of more effective IPV prevention interventions.

Impact of early-onset persistent stunting on cognitive development at 5 years of age: Results from a multi-country cohort study.

Abstract: Background Globally more than 150 million children under age 5 years were stunted in 2018, primarily in low- and middle-income countries (LMICs), and the impact of early-onset, persistent stunting has not been well explored. To explore the association between early-onset persistent stunting in children and cognitive development at 5 years of age, and to identify the factors associated with early-onset stunting.

COVID-19 PICU guidelines: for high- and limited-resource settings.

Abstract: Background Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic co-morbidities are likely to develop critical illness. Recently, a multisystem inflammatory syndrome (MIS-C) has been described in children with some of these patients requiring care in the pediatric ICU. Methods An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. Results This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed anti-viral drugs, anti-inflammatory or anti-thrombotic therapies are also described. Conclusion Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing this data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. Impact At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2. Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae. These guidelines can be adapted to both high- and limited-resource settings.

Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

Abstract: Background The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. Methods and findings Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3–14.0) for the Trinity assay and 8.3 U/g Hb (6.8–15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%–94%) to 100% (95% CI: 96%–100%) and specificity from 96% (95% CI: 89%–99%) to 100% (100%–100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%–75%) and specificity to 35% (95% CI: 24%–46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies. Conclusions Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.

Determining a global mid-upper arm circumference cut-off to assess underweight in adults (men and non-pregnant women)

Abstract: Objective: To determine if a global mid-upper arm circumference (MUAC) cut-off can be established to classify underweight in adults (men and non-pregnant women). Design: We conducted an individual participant data meta-analysis (IPDMA) to explore the sensitivity (SENS) and specificity (SPEC) of various MUAC cut-offs for identifying underweight among adults (defined as BMI < 18·5 kg/m2). Measures of diagnostic accuracy were determined every 0·5 cm across MUAC values from 19·0 to 26·5 cm. A bivariate random effects model was used to jointly estimate SENS and SPEC while accounting for heterogeneity between studies. Various subgroup analyses were performed. Setting: Twenty datasets from Africa, South Asia, Southeast Asia, North America and South America were included. Participants: All eligible participants from the original datasets were included. Results: The total sample size was 13 835. Mean age was 32·6 years and 65 % of participants were female. Mean MUAC was 25·7 cm, and 28 % of all participants had low BMI (<18·5 kg/m2). The area under the receiver operating characteristic curve for the pooled dataset was 0·91 (range across studies 0·61–0·98). Results showed that MUAC cut-offs in the range of ≤23·5 to ≤25·0 cm could serve as an appropriate screening indicator for underweight. Conclusions: MUAC is highly discriminatory in its ability to distinguish adults with BMI above and below 18·5 kg/m2. This IPDMA is the first step towards determining a global MUAC cut-off for adults. Validation studies are needed to determine whether the proposed MUAC cut-off of 24 cm is associated with poor functional outcomes.