Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods: We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings: The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation: By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health. Funding: Bill & Melinda Gates Foundation

Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000-17

Background Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2 center dot 5th and 97 center dot 5th percentiles of those 250 draws. Findings While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62 center dot 6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Copyright (c) 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

6-C-METHYLQUERCETIN-3, 3', 4'-TRIMETHYL ETHER FROM THE LEAVES EXTRACT OF PILIOSTIGMA RETICULATUM

From the leaves of Piliostigma reticulatum, three C-methylflavonols: 6-C-methylquercetin-3, 3', 4'-trimethyl ether, a new natural product; 6-C-methylkaempferol-3-methyl ether, 6,8-di-C-methylkaempferol-3,7-dimethyl ether and a 2-phenoxychromone ( Piliostigmin) and were isolated along with quercetin, quercetrin and quercetin-3-O-glucoside. The chemotaxonomic significance of the findings is briefly discussed. Key Words: Piliostigma reticulatum; Caesalpinaceae; leaves; 2-phenoxychromone; C- methylflavonols; chemotaxonomy. Nigerian Journal of Natural Products and Medicine Vol.7 2003: 37-3

Thermal isomerization of N-oxalyl derivatives of diamino acids.

The neurotoxic constituent of the legume Lathyrus sativus, beta-N-oxalyl-alpha,beta-diaminopropionic acid, was thermally isomerized to an equilibrium mixture (60/40) containing the non-toxic alpha-N-oxalyl-alpha,beta-diaminopropionic acid. The same equilibrium mixture was established by starting with the alpha-isomer but required longer time. alpha- and gamma-N-Oxalyl-alpha,gamma-diaminobutyric acids also underwent thermally induced isomerization with alpha-gamma, or gamma-alpha migration of the oxalyl group. Delta-N-Oxalylomithine and epsilon-N-oxalyllysine did not isomerize under these conditions. The observation that the higher homologues do not undergo isomerization suggests the intramolecular nature of the reaction.The neurotoxic constituent of the legume Lathyrus sativus, beta-N-oxalyl-alpha,beta-diaminopropionic acid, was thermally isomerized to an equilibrium mixture (60/40) containing the non-toxic alpha-N-oxalyl-alpha,beta-diaminopropionic acid. The same equilibrium mixture was established by starting with the alpha-isomer but required longer time. alpha- and gamma-N-Oxalyl-alpha,gamma-diaminobutyric acids also underwent thermally induced isomerization with alpha-gamma, or gamma-alpha migration of the oxalyl group. Delta-N-Oxalylomithine and epsilon-N-oxalyllysine did not isomerize under these conditions. The observation that the higher homologues do not undergo isomerization suggests the intramolecular nature of the reaction.A

A new prenylated dihydrochalcone from the leaves of Artocarpus lowii

A new prenylated dihydrochalcone, 2′,4′-dihydroxy-4-methoxy-3′-prenyldihydrochalcone (1), along with two known compounds, 2′,4′,4-trihydroxy-3′-prenylchalcone (2) and 2′,4-dihydroxy-3′,4′-(2,2-dimethylchromene)chalcone (3) were isolated from the leaves of Artocarpus lowii. The structures of 1-3 were elucidated by spectroscopic methods and by comparison with data reported in the literature. Compounds 1-3 showed strong free radical scavenging activity towards 2,2-diphenyl-1-picrylhydrazyl (DPPH) measured by electron spin resonance (ESR) spectrometry

Evaluation of cotrimoxazole use as a preventive therapy among patients living with HIV/AIDS in Gondar University Referral Hospital, northwestern Ethiopia: a retrospective cross-sectional study

Begashaw Melaku Gebresillassie,1 Minaleshewa Biruk Gebeyehum,1 Tadesse Melaku Abegaz,1 Daniel Asfaw Erku,2 Abebe Basazn Mekuria,3 Yokabd Dechassa Tadesse2 1Department of Clinical Pharmacy, 2Department of Pharmaceutical Chemistry, 3Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Purpose: Cotrimoxazole preventive therapy (CPT) is a feasible, inexpensive, and well-tolerated way of using cotrimoxazole intervention for patients living with HIV/AIDS to reduce HIV/AIDS-related morbidities and mortalities caused by various bacteria, fungi, and protozoa. The aim of this study was to evaluate the use of cotrimoxazole as a prophylaxis therapy among patients living with HIV/AIDS at Gondar University Referral Hospital (GURH), northwestern Ethiopia.Materials and methods: A retrospective cross-sectional study was used to evaluate the use of cotrimoxazole as a prophylaxis therapy among people living with HIV/AIDS at GURH, northwestern Ethiopia from September 2013 to October 2015. Medical records of 264 patients were selected by using systematic random sampling technique from the sampling frame list of all patients’ medical records. Data were collected from patients’ medical records using the structured checklist and evaluated against World Health Organization (WHO) guidelines on the use of cotrimoxazole prophylaxis. The quantitative data were analyzed using the statistical packages for social sciences Version 20. Descriptive and binary logistic regression analyses were used to describe and assess the association between different variables.Results: Approximately 95 (36.0%) patients were at WHO clinical stage III at the start of CPT. The use of CPT was consistent with the guidelines in the rationale for indication 200 (75.75%) and dose 263 (99.62%), despite the presence of contraindications in 24 (9.90%) patients. The occurrence of cotrimoxazole-associated side effects was higher in the first month of therapy. Problems regarding drug–drug interactions were identified in 63 (23.86%) patients, and 92 (34.84%) patients discontinued CPT due to different reasons.Conclusion: Although the practice of discontinuation of CPT and follow-up for adverse drug effects were not consistent with WHO guidelines on the rational use of cotrimoxazole prophylaxis, the use of CPT among people living with HIV/AIDS at GURH was appropriate. Health professionals who were working in the antiretroviral therapy units should update themselves and adhere to the available updated guidelines to reduce the occurrence of adverse effects and prophylaxis failure. Keywords: drug use evaluation, cotrimoxazole, HIV/AIDS, Gonda