Validation of malaria-attributed deaths using verbal autopsy studies: a systematic review.

BACKGROUND: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. METHODS: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990-March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. RESULTS: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. CONCLUSIONS: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible.

Antioxidant and Antibacterial Activities Evaluation, Phytochemical Characterisation of Rhizome from Angiopteris helferiana and Barks from Saurauia fasciculata in Nepal.

Ethnomedicinally, more than 2000 plants were found to be used in Nepal. Among them, the red colored rhizome of Angiopteris helferiana and the bark of Saurauia fasciculata have been used widely to treat muscle fatigue, bone pain, fever, postpartum hemorrhage, and thirst by healers in Kaski and Tanahun districts, Nepal. However, scientific evidence towards their traditional uses is lacking till December, 2023. Therefore, we report the phytochemicals, total phenolic content (TPC), total flavonoid content (TFC), total carbohydrate content (TCC), antioxidant and antibacterial activities of A. helferiana and S. fasciculata extracts. Phytochemical analysis indicated that A. helferiana and S. fasciculata extracts were potential sources of chemicals such as phenols, flavonoids, tannins, terpenoids, saponins, and carbohydrates. The TPC, TFC, and TCC of extracts were determined by using an ultraviolet visible spectrophotometer. Among the extracts tested, A. helferiana extracts showed the highest phenolic and carbohydrate contents of 208.33 ± 12.96 mg of gallic acid equivalent/g and 564.16 ± 2.92 mg of D-glucose equivalent/g of dry extract, respectively. Similarly, S. fasciculata revealed the highest flavonoid content of 30.35 ± 0.1 mg quercetin equivalent/g of dry extract. The extract of A. helferiana and S. fasciculata exhibited potent antioxidant activity by scavenging 2,2-diphenyl-1-picrylhydrazyl radicals with an IC50 of 25.9 µg/ml and 31.07 µg/ml, respectively. The antibacterial activity of the A. helferiana and S. fasciculata extract against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was determined using an agar-well diffusion protocol that revealed the potential antibacterial activity of A. helferiana against E. coli. The present study will help validate the traditional uses of A. helferiana rhizomes and S. fasciculata barks as a healing medicine and inspire the researcher towards further research, development, and formulation.

Characterizing the type 6 secretion system (T6SS) of E. cloacae SBP-8 and its role in pathogenesis and bacterial competition.

Despite the relevance of E. cloacae as an opportunistic pathogen, very little is known about its pathogenicity mechanism and the factors influencing its virulence. The mechanism of E. cloacae pathogenicity appears to be complex and multifactorial, with the presence of different putative virulence factors whose role is still not clear in the development of the disease. In this study, we systematically investigated the role of T6SS (type six secretion system) of E. cloacae SBP-8, an environmental isolate, in eukaryotic and bacterial cell interaction. Analysis of the genome sequence of E. cloacae SBP-8 revealed the presence of sets of genes coding for the expression of one complete T6SS cluster, which is similar to T6SS-1 cluster of E. cloacae ATCC 13047 (clinical isolates). In addition, an Hcp effector protein was detected in the secretome, and this secretion depended on ClpV, an Atpase of T6SS, confirming that strain SBP-8 produces functional T6SS. Deletion of T6SS-associated gene clpV did not induce any significant change in the life span and rate of colonization in C. elegans. No major significant change was observed in the expression profiling of antimicrobial genes (clec-60, clec-85, clec-87 and lys-1) and toll-like receptor (toll-1) gene, involved in stimulating an immune response against the pathogen. No difference in the ability to invade and proliferate in intestinal cells and phagocytosis by macrophages was observed. In addition, we demonstrated that the ability of E. cloacae SBP-8 to out-compete Escherichia coli was reliant upon its T6SS in contact-dependent manner. Our results show that T6SS of the environmental isolates is required for interbacterial competition but not for invasion and proliferation inside host cells.

Could vaccinating adults against malaria materially reduce adult mortality in high-transmission areas?

After a period of unprecedented progress against malaria in the 2000s, halving the global disease burden by 2015, gains overall in sub-Saharan Africa have slowed and even reversed in some places, beginning well before the COVID-19 pandemic. The highly effective drugs, treated nets, and diagnostics that fueled the initial progress all face some threats to their effectiveness, and global funding to maintain and increase their use over the long term is not guaranteed. Malaria vaccines are among the most promising new interventions that could accelerate the elimination of malaria. Vaccines are still in early stages of rollout in children, the age group (along with pregnant women) that has been the focus of malaria strategies for a century. At the same time, over the past decade, a case has been made, based largely on evidence from verbal autopsies in at least a few high-transmission areas, that the malaria death rate among adults has been greatly underestimated. Could vaccinating adults help to bring down the adult malaria mortality rate, contribute to reduced transmission, or both? A randomized trial of a malaria vaccine is proposed in Sierra Leone, a highly endemic setting, to shed light on this proposition.

The evolution of SARS-CoV-2 seroprevalence in Canada: a time-series study, 2020-2023.

BACKGROUND: During the first year of the COVID-19 pandemic, the proportion of reported cases of COVID-19 among Canadians was under 6%. Although high vaccine coverage was achieved in Canada by fall 2021, the Omicron variant caused unprecedented numbers of infections, overwhelming testing capacity and making it difficult to quantify the trajectory of population immunity. METHODS: Using a time-series approach and data from more than 900 000 samples collected by 7 research studies collaborating with the COVID-19 Immunity Task Force (CITF), we estimated trends in SARS-CoV-2 seroprevalence owing to infection and vaccination for the Canadian population over 3 intervals: prevaccination (March to November 2020), vaccine roll-out (December 2020 to November 2021), and the arrival of the Omicron variant (December 2021 to March 2023). We also estimated seroprevalence by geographical region and age. RESULTS: By November 2021, 9.0% (95% credible interval [CrI] 7.3%-11%) of people in Canada had humoral immunity to SARS-CoV-2 from an infection. Seroprevalence increased rapidly after the arrival of the Omicron variant - by Mar. 15, 2023, 76% (95% CrI 74%-79%) of the population had detectable antibodies from infections. The rapid rise in infection-induced antibodies occurred across Canada and was most pronounced in younger age groups and in the Western provinces: Manitoba, Saskatchewan, Alberta and British Columbia. INTERPRETATION: Data up to March 2023 indicate that most people in Canada had acquired antibodies against SARS-CoV-2 through natural infection and vaccination. However, given variations in population seropositivity by age and geography, the potential for waning antibody levels, and new variants that may escape immunity, public health policy and clinical decisions should be tailored to local patterns of population immunity.

Characterization of functional amyloid curli in biofilm formation of an environmental isolate Enterobacter cloacae SBP-8.

The biofilm formation by bacteria is a complex process that is strongly mediated by various genetic and environmental factors. Biofilms contribute to disease infestation, especially in chronic infections. It is, therefore important to understand the factors affecting biofilm formation. This study reports the role of a functional amyloid curli in biofilm formation at various abiotic surfaces, including medical devices, by an environmental isolate of Enterobacter cloacae (SBP-8) which has been known for its pathogenic potential. A knockout mutant of csgA, the gene encoding the major structural unit of curli, was created to study the effect of curli on biofilm formation by E. cloacae SBP-8. Our findings confirm the production of curli at 25 °C and 37 °C in the wild-type strain. We further investigated the role of curli in the attachment of E. cloacae SBP-8 to glass, enteral feeding tube, and foley latex catheter. Contrary to the previous studies reporting the curli production below 30 °C in the majority of biofilm-forming bacterial species, we observed its production in E. cloacae SBP-8 at 37 °C. The formation of more intense biofilm in wild-type strain on various surfaces compared to curli-deficient strain (ΔcsgA) at both 25 °C and 37 °C suggested a prominent role of curli in biofilm formation. Further, electron and confocal microscopy studies demonstrated the formation of diffused monolayers of microbial cells on the abiotic surfaces by ΔcsgA strain as compared to the thick biofilm by respective wild-type strain, indicating the involvement of curli in biofilm formation by E. cloacae SBP-8. Overall, our findings provide insight into biofilm formation mediated by curli in E. cloacae SBP-8. Further, we show that it can be expressed at a physiological temperature on all surfaces, thereby indicating the potential role of curli in pathogenesis.

Spatio-temporal modelling of malaria mortality in India from 2004 to 2013 from the Million Death Study.

BACKGROUND: India has a substantial burden of malaria, concentrated in specific areas and population groups. Spatio-temporal modelling of deaths due to malaria in India is a critical tool for identifying high-risk groups for effective resource allocation and disease control policy-making, and subsequently for the country's progress towards United Nations 2030 Sustainable Development Goals. METHODS: In this study, a spatio-temporal model with the objective of understanding the spatial distribution of malaria mortality rates and the rate of temporal decline, across the country, has been constructed. A spatio-temporal "random slope" model was used, with malaria risk depending on a spatial relative risk surface and a linear time effect with a spatially-varying coefficient. The models were adjusted for urban/rural status (residence of the deceased) and Normalized Difference Vegetation Index (NDVI), using 2004-13 data from the Million Death Study (MDS) (the most recent data available), with nationwide geographic coverage. Previous studies based on MDS had focused only on aggregated analyses. RESULTS: The rural population had twice the risk of death due to malaria compared to the urban population. Malaria mortality in some of the highest-risk regions, namely the states of Odisha and Jharkhand, are declining faster than other areas; however, the rate of decline was not uniformly correlated with the level of risk. The overall decline was faster after 2010. CONCLUSION: The results suggest a need for increased attention in high-risk rural populations, which already face challenges like inadequate infrastructure, inaccessibility to health care facilities, awareness, and education around malaria mortality and prevalence. It also points to the urgent need to restart the MDS to document changes since 2013, to develop appropriate malaria control measures.

The distributional effects of tobacco tax increases across regions in Mexico: an extended cost-effectiveness analysis.

BACKGROUND: Several studies have shown the beneficial effects of tobacco fiscal policy, but distributional effects have been less examined, especially at the subnational level. The objective of this study is to analyse the distributional effects of a one-peso tobacco tax increase (roughly equivalent to tripling the current excise tax) on health, poverty, and financial outcomes at the subnational level in Mexico. METHODS: We employ an extended cost-effectiveness analysis that estimates life-years gained, smoking attributable deaths averted, treatment costs averted, number of persons avoiding poverty and catastrophic health expenditures, and additional tax revenues by income group across five regions. RESULTS: With the one-peso tax increase (or 44% price increase), about 1.5 million smokers would quit smoking across the five regions, resulting in nearly 630 thousand premature deaths averted and 12.6 million life years gained. The bottom income quintile would gain three times more life years gains than the top quintile (ratio 3:1), and the largest gain for the most deprived would occur in the South (ratio 19:1), the region with the highest poverty incidence. Costs averted and additional tax revenues would reach 44.6 and 16.2 billion pesos, respectively. Moreover, 251 thousand individuals would avoid falling into poverty, including 53.2 in the lowest income quintile, and 563.9 thousand would avoid catastrophic health expenditures. Overall, the bottom income group would obtain 26% of the life years gained and 24% of the cost averted, while only paying 3% of the additional tax revenue. CONCLUSIONS: The most significant gains from a substantial cigarette price increase would be for the poorest 20%, especially in the South, the most impoverished region of Mexico. Therefore, tobacco taxes are an opportunity for governments to advance in equity and towards the achievement of sustainable development goals on non-communicable diseases.

Comparison of mortality hazard ratios associated with health behaviours in Canada and the United States: a population-based linked health survey study.

BACKGROUND: Modern health surveillance and planning requires an understanding of how preventable risk factors impact population health, and how these effects vary between populations. In this study, we compare how smoking, alcohol consumption, diet and physical activity are associated with all-cause mortality in Canada and the United States using comparable individual-level, linked population health survey data and identical model specifications. METHODS: The Canadian Community Health Survey (CCHS) (2003-2007) and the United States National Health Interview Survey (NHIS) (2000, 2005) linked to individual-level mortality outcomes with follow up to December 31, 2011 were used. Consistent variable definitions were used to estimate country-specific mortality hazard ratios with sex-specific Cox proportional hazard models, including smoking, alcohol, diet and physical activity, sociodemographic indicators and proximal factors including disease history. RESULTS: A total of 296,407 respondents and 1,813,884 million person-years of follow-up from the CCHS and 58,232 respondents and 497,909 person-years from the NHIS were included. Absolute mortality risk among those with a 'healthy profile' was higher in the United States compared to Canada, especially among women. Adjusted mortality hazard ratios associated with health behaviours were generally of similar magnitude and direction but often stronger in Canada. CONCLUSION: Even when methodological and population differences are minimal, the association of health behaviours and mortality can vary across populations. It is therefore important to be cautious of between-study variation when aggregating relative effect estimates from differing populations, and when using external effect estimates for population health research and policy development.

[Benefits of the cigarette tax in Mexico, by sex and income quintileBenefícios do imposto sobre cigarros no México: análise por sexo e quintil de renda]. / Beneficios del impuesto a los cigarros en México: análisis por sexo y quintil de ingreso.

Objective: Estimate economic and health benefits, by sex and income quintile, of tax-based cigarette price increases in Mexico. Methods: An extended cost-effectiveness analysis (ECEA) model was used to estimate distributional benefits for women and men in the scenario of a 44% increase in the price of cigarettes (from 56.4 Mexican pesos [MX$] to MX$81.2 per pack), as a result of tripling the current specific excise tax (from MX$0.49/cigarette to MX$1.49/cigarette). The model was calibrated with official national information sources. Results: With a tax increase of one peso per cigarette, about 1.5 million smokers would quit (351 300 women and 1.1 million men). This would prevent approximately 630 000 smoking-attributable premature deaths. Reducing the burden of disease would save the health sector close to MX$42.8 billion and prevent more than 250 000 people (including 50 200 women smokers) from falling into poverty. It would also result in an additional MX$16.2 billion in revenue per year, of which the lowest income quintile would contribute less than 3% (1% for low-income women). Conclusions: The tobacco epidemic has clearly differentiated patterns between women and men, reflecting a gender component. While the tobacco tax in Mexico would have great benefits with respect to the current state of the epidemic, this could also contribute to the broader goal of social justice by reducing gender inequities.

Objetivo: Estimar os benefícios econômicos e de saúde, por sexo e quintil de renda, do aumento dos preços dos cigarros por meio de impostos no México. Métodos: Com um modelo de análise ampliada de custo-efetividade (ECEA, na sigla em inglês), foram estimados os benefícios distributivos em mulheres e homens com um cenário de aumento de 44% no preço dos cigarros (de 56,4 pesos mexicanos [MX$] para MX$ 81,2 por maço), como resultado da triplicação do imposto específico atual (de MX$ 0,49/cigarro para MX$ 1,49/cigarro). O modelo foi calibrado com fontes oficiais de informação nacional. Resultados: Com o aumento do imposto de um MX$ por cigarro, cerca de 1,5 milhão de fumantes abandonariam o consumo (351.300 mulheres e 1,1 milhão de homens). Assim, seriam evitadas aproximadamente 630.000 mortes prematuras atribuíveis ao tabaco. A redução da carga de doenças permitiria uma economia para o setor da saúde de cerca de MX$ 42,8 bilhões e evitaria que mais de 250.000 pessoas (incluindo 50.200 mulheres fumantes) caíssem na pobreza. Além disso, seriam arrecadados MX$ 16,2 bilhões adicionais por ano, dos quais o quintil mais baixo contribuiria com menos de 3% (1% no caso de mulheres de baixa renda). Conclusões: A epidemia de tabagismo tem padrões claramente diferenciados entre mulheres e homens e reflete um componente de gênero. Embora os benefícios do imposto sobre o tabaco no México tenham importância relativa no atual estado da epidemia em cada caso, poderiam contribuir para um objetivo mais amplo de justiça social ao reduzir as desigualdades de gênero.

Fluorescent glutamine and asparagine as promising probes for chemical biology.

Fluorescent probes have become valuable tools in chemical biology, providing interesting inferences for unfolding the complexities of natural biochemical processes. In this study, we report the synthesis and characterization of fluorescent labelled glutamine (Gln) and asparagine (Asn) derivatives via traceless Staudinger ligation, which exhibited high fluorescence quantum yields, excellent photostabilities and emission of blue fluorescence in the visible region. The successful permeation of these fluorescent amino acids into cellular components proved their potential as fluorescent probes for chemical biology.

Comparison of machine learning algorithms applied to symptoms to determine infectious causes of death in children: national survey of 18,000 verbal autopsies in the Million Death Study in India.

BACKGROUND: Machine learning (ML) algorithms have been successfully employed for prediction of outcomes in clinical research. In this study, we have explored the application of ML-based algorithms to predict cause of death (CoD) from verbal autopsy records available through the Million Death Study (MDS). METHODS: From MDS, 18826 unique childhood deaths at ages 1-59 months during the time period 2004-13 were selected for generating the prediction models of which over 70% of deaths were caused by six infectious diseases (pneumonia, diarrhoeal diseases, malaria, fever of unknown origin, meningitis/encephalitis, and measles). Six popular ML-based algorithms such as support vector machine, gradient boosting modeling, C5.0, artificial neural network, k-nearest neighbor, classification and regression tree were used for building the CoD prediction models. RESULTS: SVM algorithm was the best performer with a prediction accuracy of over 0.8. The highest accuracy was found for diarrhoeal diseases (accuracy = 0.97) and the lowest was for meningitis/encephalitis (accuracy = 0.80). The top signs/symptoms for classification of these CoDs were also extracted for each of the diseases. A combination of signs/symptoms presented by the deceased individual can effectively lead to the CoD diagnosis. CONCLUSIONS: Overall, this study affirms that verbal autopsy tools are efficient in CoD diagnosis and that automated classification parameters captured through ML could be added to verbal autopsies to improve classification of causes of death.

Trends in cause-specific mortality among children aged 5-14 years from 2005 to 2016 in India, China, Brazil, and Mexico: an analysis of nationally representative mortality studies.

BACKGROUND: With global survival increasing for children younger than 5 years of age, attention is required to reduce the approximately 1 million deaths of children aged 5-14 years occurring every year. Causes of death at these ages remain poorly documented. We aimed to explore trends in mortality by causes of death in India, China, Brazil, and Mexico, which are home to about 40% of the world's children aged 5-14 years and experience more than 200 000 deaths annually at these ages. METHODS: We examined data on 244 401 deaths in children aged 5-14 years from four nationally representative data sources that obtained direct distributions of causes of death: the Indian Million Death Study, the Chinese Disease Surveillance Points, mortality data from the Mexican Instituto Nacional de Estadística y Geografía, and mortality data from the Brazilian Institute of Geography and Statistics. We present data on 12 main disease groups in all countries, with breakdown by communicable and nutritional diseases, non-communicable diseases, injuries, and ill-defined causes. To calculate age-specific and sex-specific death rates for each cause, we applied the national cause of death distribution to the UN mortality envelopes for 2005-16 for each country. FINDINGS: Unlike Brazil, China, and Mexico, communicable diseases still account for nearly half of deaths in India in children aged 5-14 years (73 920 [46·1%] of 160 330 estimated deaths in 2016). In 2016, India had the highest death rates in nearly every category, including from communicable diseases. Fast declines among girls in communicable disease mortality narrowed the gap by 2016 with boys in India (32·6 deaths per 100 000 girls vs 26·2 per 100 000 boys) and China (1·7 vs 1·5). In China, injuries accounted for the greatest proportions of deaths (20 970 [53·2%] of 39 430 estimated deaths, in which drowning was a leading cause). The homicide death rate at ages 10-14 years was higher for boys than for girls in Brazil, increasing annually by an average of 0·7% (0·3-1·1). In India and China, the suicide death rates were higher for girls than for boys at ages 10-14 years. By contrast, in Mexico it was higher for boys than for girls, increasing annually by an average of 2·8% (2·0-3·6). Deaths from transport injuries, drowning, and cancer are common in all four countries, with transport accidents among the top three causes of death for both sexes in all countries, except for Indian girls, and cancer in the top three causes for both sexes in Mexico, Brazil, and China. INTERPRETATION: Most of the deaths that occurred between 2005 and 2016 in children aged 5-14 years in India, China, Brazil, and Mexico arose from preventable or treatable conditions. This age group is important for extending some of the global disease-specific targets developed for children younger than 5 years of age. Interventions to control non-communicable diseases and injuries and to strengthen cause of death reporting systems are also required. FUNDING: WHO and the University of Toronto Connaught Global Challenge.

Elucidating the pathogenic potential of Enterobacter cloacae SBP-8 using Caenorhabditis elegans as a model host.

Enterobacter cloacae, an opportunistic nosocomial pathogen, is reported to possess different virulence factors that could potentially influence its pathogenesis. Generally, the E. cloacae infections are of endogenous origin occurring in immunocompromised patients. The mechanisms of pathogenicity remain elusive, possibly due to the absence of established model hosts. Thus, we explored the utility of Caenorhabditis elegans as a model host to test the pathogenicity of E. cloacae SBP-8, a soil isolate. E. cloacae SBP-8 progressively colonized the intestine of C. elegans. It induced cell death (as assessed through DNA damage), reproductive defect and reduction of lifespan, comparable to a clinical isolate, E. cloacae (MTCC 509). Observation with Nomarski microscopy revealed significant anterior pharyngeal distention, and altered egg arrangement with internal egg hatching in 70% infected worms. The internal egg hatching was observed as early as 48 h post infection. E. cloacae SBP-8 infection reduced the brood size by 16%. A 2',7'-dichlorodihydrofluorescein diacetate staining confirmed the 10-fold induction of reactive oxygen species implicating either mitochondrial damage or septic shock in infected worms. Expression analysis through RT-PCR indicated stimulation of immune response by E. cloacae SBP-8 in worms by upregulating tol-1, a Toll-like receptor, within 6 h of exposure. During the initial phase of infection (up to 24 h) the nematodes exhibited protective immune response by upregulating antimicrobial peptide genes, lys-1, clec-60, clec-85, and clec-87. However, these genes were downregulated at later hours (48 h), indicating the nematodes surrendered to the infection. A similar trend was observed for reproductive genes (lin-29 and let-23), suggesting a struggle to maintain functional reproduction by the nematodes. These results clearly demonstrate the pathogenic potential of E. cloacae SBP-8 and suggest the suitability of C. elegans as a model organism to study its pathogenesis. This is the first study indicating that E. cloacae infections could potentially originate from an exogenic source (here soil).

Health-care investments for the urban populations, Bangladesh and India.

OBJECTIVE: To estimate the costs and mortality reductions of a package of essential health interventions for urban populations in Bangladesh and India. METHODS: We used population data from the countries' censuses and United Nations Population Division. For causes of mortality in India, we used the Indian Million Death Study. We obtained cost estimates of each intervention from the third edition of Disease control priorities. For estimating the mortality reductions expected with the package, we used the Disease control priorities model. We calculated the benefit-cost ratio for investing in the package, using an analysis based on the Copenhagen Consensus method. FINDINGS: Per urban inhabitant, total costs for the package would be 75.1 United States dollars (US$) in Bangladesh and US$ 105.0 in India. Of this, prevention and treatment of noncommunicable diseases account for US$ 36.5 in Bangladesh and U$ 51.7 in India. The incremental cost per urban inhabitant for all interventions would be US$ 50 in Bangladesh and US$ 75 in India. In 2030, the averted deaths among people younger than 70 years would constitute 30.5% (1027/3362) and 21.2% (828/3913) of the estimated baseline deaths in Bangladesh and India, respectively. The health benefits of investing in the package would return US$ 1.2 per dollar spent in Bangladesh and US$ 1.8 per dollar spent in India. CONCLUSION: Investing in the package of essential health interventions, which address health-care needs of the growing urban population in Bangladesh and India, seems beneficial and could help the countries to achieve their 2030 sustainable development goals.

Development and validation of algorithms to classify type 1 and 2 diabetes according to age at diagnosis using electronic health records.

BACKGROUND: Validated algorithms to classify type 1 and 2 diabetes (T1D, T2D) are mostly limited to white pediatric populations. We conducted a large study in Hong Kong among children and adults with diabetes to develop and validate algorithms using electronic health records (EHRs) to classify diabetes type against clinical assessment as the reference standard, and to evaluate performance by age at diagnosis. METHODS: We included all people with diabetes (age at diagnosis 1.5-100 years during 2002-15) in the Hong Kong Diabetes Register and randomized them to derivation and validation cohorts. We developed candidate algorithms to identify diabetes types using encounter codes, prescriptions, and combinations of these criteria ("combination algorithms"). We identified 3 algorithms with the highest sensitivity, positive predictive value (PPV), and kappa coefficient, and evaluated performance by age at diagnosis in the validation cohort. RESULTS: There were 10,196 (T1D n = 60, T2D n = 10,136) and 5101 (T1D n = 43, T2D n = 5058) people in the derivation and validation cohorts (mean age at diagnosis 22.7, 55.9 years; 53.3, 43.9% female; for T1D and T2D respectively). Algorithms using codes or prescriptions classified T1D well for age at diagnosis < 20 years, but sensitivity and PPV dropped for older ages at diagnosis. Combination algorithms maximized sensitivity or PPV, but not both. The "high sensitivity for type 1" algorithm (ratio of type 1 to type 2 codes ≥ 4, or at least 1 insulin prescription within 90 days) had a sensitivity of 95.3% (95% confidence interval 84.2-99.4%; PPV 12.8%, 9.3-16.9%), while the "high PPV for type 1" algorithm (ratio of type 1 to type 2 codes ≥ 4, and multiple daily injections with no other glucose-lowering medication prescription) had a PPV of 100.0% (79.4-100.0%; sensitivity 37.2%, 23.0-53.3%), and the "optimized" algorithm (ratio of type 1 to type 2 codes ≥ 4, and at least 1 insulin prescription within 90 days) had a sensitivity of 65.1% (49.1-79.0%) and PPV of 75.7% (58.8-88.2%) across all ages. Accuracy of T2D classification was high for all algorithms. CONCLUSIONS: Our validated set of algorithms accurately classifies T1D and T2D using EHRs for Hong Kong residents enrolled in a diabetes register. The choice of algorithm should be tailored to the unique requirements of each study question.

Alterations in the Endophyte-Enriched Root-Associated Microbiome of Rice Receiving Growth-Promoting Treatments of Urea Fertilizer and Rhizobium Biofertilizer.

We examined the bacterial endophyte-enriched root-associated microbiome within rice (Oryza sativa) 55 days after growth in soil with and without urea fertilizer and/or biofertilization with a growth-promotive bacterial strain (Rhizobium leguminosarum bv. trifolii E11). After treatment to deplete rhizosphere/rhizoplane communities, washed roots were macerated and their endophyte-enriched communities were analyzed by 16S ribosomal DNA 454 amplicon pyrosequencing. This analysis clustered 99,990 valid sequence reads into 1105 operational taxonomic units (OTUs) with 97% sequence identity, 133 of which represented a consolidated core assemblage representing 12.04% of the fully detected OTU richness. Taxonomic affiliations indicated Proteobacteria as the most abundant phylum (especially α- and γ-Proteobacteria classes), followed by Firmicutes, Bacteroidetes, Verrucomicrobia, Actinobacteria, and several other phyla. Dominant genera included Rheinheimera, unclassified Rhodospirillaceae, Pseudomonas, Asticcacaulis, Sphingomonas, and Rhizobium. Several OTUs had close taxonomic affiliation to genera of diazotrophic rhizobacteria, including Rhizobium, unclassified Rhizobiales, Azospirillum, Azoarcus, unclassified Rhizobiaceae, Bradyrhizobium, Azonexus, Mesorhizobium, Devosia, Azovibrio, Azospira, Azomonas, and Azotobacter. The endophyte-enriched microbiome was restructured within roots receiving growth-promoting treatments. Compared to the untreated control, endophyte-enriched communities receiving urea and/or biofertilizer treatments were significantly reduced in OTU richness and relative read abundances. Several unique OTUs were enriched in each of the treatment communities. These alterations in structure of root-associated communities suggest dynamic interactions in the host plant microbiome, some of which may influence the well-documented positive synergistic impact of rhizobial biofertilizer inoculation plus low doses of urea-N fertilizer on growth promotion of rice, considered as one of the world's most important food crops.

Extremes in water availability and suicide: Evidence from a nationally representative sample of rural Indian adults.

BACKGROUND: Extremes in water availability, either exceptionally wet or dry conditions, can damage crops and may detrimentally affect the livelihood and well-being of people engaged in agriculture. We estimated the effect of water availability on suicide in rural India, a context where the majority of households are dependent upon agriculture. METHODS: We used data from a nationally representative sample of 8.5 million people who were monitored for causes of death from 2001 to 2013. Water availability was measured with high-resolution precipitation and temperature data (i.e., the Standardized Precipitation Evapotranspiration Index). We used a fixed effects approach that modeled changes in water availability within districts (n = 569) over time (n = 13 years) to estimate the impact on suicide deaths. We restricted our analysis to rural areas and to deaths occurring during the growing season (June-March) among adults aged 15 or older, and controlled for sex, age, region, and year. We used Poisson regression with standard errors clustered at the district level and total deaths as the offset. RESULTS: There were 9456 suicides and 249,786 total deaths in our study population between 2001 and 2013. Compared to normal growing seasons, the percent of deaths due to suicide increased by 18.7% during extremely wet growing seasons (95% CI: 6.2, 31.2) and by 3.6% during extremely dry growing seasons (95% CI: -17.9, 25.0). We found that effects varied by age. CONCLUSIONS: We found extremes is water availability associated with an increase in suicide. Abnormally wet growing conditions may play an important, yet overlooked, role in suicide among rural Indian adults.