Genetic characterization of rotavirus strains in Mozambique, 2012-2018: identification of rotavirus genotypes and full genome sequencing by next generation sequencing

Os rotavirus do grupo A são uma das principais causas de diarreia aguda grave em crianças menores de 5 anos de idade em todo o mundo. Os vírus também causam infecção em animais jovens de variadas espécies de mamíferos e aves. Existem vários genótipos de rotavirus que causam infecção em crianças, por isso, as pesquisas sobre a circulação e prevalência de estirpes de genótipos de rotavirus circulantes e o sequenciamento do genoma completo são importantes para caracterizacção genética do vírus no país, auxiliando assim na avaliação do impacto da vacina contra rotavirus introduzida no programa alargado de vacinação em Setembro de 2015. Neste contexto, o principal objetivo deste projeto foi caracterizar geneticamente as estirpes de rotavirus circulantes entre 2012 e 2018 em Moçambique, incluindo uma comparação antes e após a introdução da vacina contra rotavirus no país. As estirpes de rotavirus foram detectadas em crianças menores de cinco anos de idade que apresentaram diarreia aguda grave. A caracterização genética de rotavirus foi realizada utilizando RT-PCR, sequenciação de moléculas de DNA pelo método de paragem da polimerização por incorporação de didesoxirribonucleótidos (método de Sanger) e sequenciação do genoma completo da segunda geração (Next Generation Sequencing). Os resultados de RT-PCR mostraram a alta diversidade de genótipos circulantes com variações anuais no período pré e após a introdução da vacina, conforme reportado anteriormente por vários estudos a nível mundial. Antes da introdução da vacina (2012-2013), os genótipos de rotavirus mais frequentes foram G2P[4] e G12P[6] e durante 2014-2015 foram G1P[8] e G9P[8]. Após a introdução da vacina (2016-2018), observou-se o surgimento dos genótipos emergentes como G9P[4], G3P[4] e G3P[8] que não tinham sido detectados antes. O surgimento de novos genótipos de rotavirus no período pós-vacinal reforça a necessidade de uma vigilância contínua em todo o país para monitorizar se o aparecimento de outros genótipos foi devido a vacina. A análise do genoma completo das estirpes dos genótipos G1P[8] e G9P[8] de 2014 e 2016 revelou a circulação de estirpes com um backbone Wa-like típico. Com as análises do genoma completo, foi possível fornecer evidências da diversidade genética do genótipo P[8] em Moçambique ao longo dos anos e foram observadas várias substituições nas regiões antigénicas de rotavirus, sendo importante continuar a vigilância das genótipos para monitorizar o efeito dessas mutações. A análise do genoma completo das estirpes dos genótipos G2P[6] circulantes em 2015 e 2016 revelou um backbone DS1-like típico com alta identidade com estirpes moçambicanas que circularam em 2012 e 2013, entretanto, foram detectados possíveis eventos de reassortments. No presente estudo, apesar da análise do genoma completo de rotavirus ter sido efectuada em estirpes provenientes de diferentes locais de Moçambique, os resultados ilustraram que no país estão em circulação estirpes com o mesmo genetic makeup. Esta tese caracterizou estirpes de rotavirus do grupo A em crianças menores de 5 anos de idade e mostrou a existência de alta diversidade de estirpes circulantes no país. A análise do genoma completo evidenciou que estirpes G1P[8] e G9P[8] têm um backone Wa-like típico e estirpes G2P[6] têm um backbone DS1-like típico. No entanto, é importante a vigilância contínua, como forma de monitorizar os possíveis eventos de reassortment que derivam da pressão da vacina.Rotavirus group A were confirmed as a major cause of life-threatening diarrhoea in infants and children <5 years of age worldwide and in the young of many mammalian and avian species. The virus is known to have several rotavirus strains causing infection in children, due to that, the assessment of information on the prevalence of circulating rotavirus strains as well the complete genetic makeup is important in the assessment of the likely impact of vaccine. In this context the main aim of this project was to genetically characterize the rotavirus strains circulating between 2012-2018 in Mozambique, including a comparison before and after rotavirus vaccine implementation in the country. The strains were from children under five years of age and suffering from moderate-to-severe acute diarrhoea. The genetic characterization was done using RT-PCR, dideoxynucleotide chain termination sequencing (Sanger method) and next generation sequencing of rotavirus genome. The results by RT-PCR showed diversity of genotypes with yearly fluctuations of strains, prior and post vaccine introduction. Prior to vaccine introduction, during 2012-2013, the most frequent rotavirus genotypes were G2P[4] and G12P[6] and during 2014-2015 were G1P[8] and G9P[8]. Post vaccine-introduction (2016-2018) was observed emergence of genotypes G9P[4], G3P[4] and G3P[8]. The emergence of other rotavirus strains in the post-vaccination period supports the need for continuous surveillance across the country to understand if the emergence of the strains is vaccine derived and their impact in human health. The full genome analysis of G1P[8] and G9P[8] strains from 2014 and 2016 revealed circulation of strains with typical Wa-like genome backbone. With full genome analyses, it was possible to provide evidence of genetic diversity within genotype P[8] in Mozambique throughout the years and several substitutions in rotavirus antigenic regions were observed. It is, thus, important to continue surveillance of rotavirus strains to monitor the implication of these mutations. The full genome analysis of G2P[6] strains from 2015 and 2016 revealed a DS1-like typical genome backbone with high identity with Mozambican strains from 2012-2013, however, with possible occurrence of reassortment events.The rotavirus genome of strains from different sites from Mozambique analysed in the present study showed, in general, the same genetic makeup of rotavirus strains in the country. This thesis characterized the RVA strains from children less than five years of age and showed high diversity of strains in Mozambique. The full genome analyses showed Wa-like with typical genome backbone in strains G1P[8] and G9P[8], and DS1-like with typical genome backbone in G2P[6] strains. There is a need to continue the surveillance in order to monitor possible reassortment events derived from vaccine pressure

Risk factors, genotypes distribution by vaccination status and age of children in Nampula Province, Northern Mozambique (2015-2019)

Publisher Copyright: © 2021 Chissaque et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Mozambique introduced the monovalent rotavirus vaccine (Rotarix®, GSK Biologicals, Rixensart, Belgium) in September 2015. Previous analysis, showed that Nampula province continues reporting a high frequency of Rotavirus A (RVA) infection and the emergence of G9P[6], G9P[4] and G3P[4] genotypes. This analysis aimed to determine the RVA frequency; risk factors; genotype distribution by vaccination status and age between pre- and post-vaccine periods in children under-five years old with diarrhea in Nampula. A cross-sectional, hospital-based surveillance study was conducted in the Hospital Central de Nampula in Mozambique. Socio-demographic and clinical data were collected to assess factors related to RVA infection in both periods. Stool specimens were screened to detect RVA by ELISA, and positive samples were genotyped. Between 2015 (pre-vaccine period) and 2016-2019 (post-vaccine period), 614 stool specimens were collected and tested for RVA in which 34.9% (67/192) were positive in pre-vaccine period and 21.8% (92/422) in post-vaccine (p = 0.001). In the post-vaccine period, age, year, and contact with different animal species (chicken, duck, or multiple animals) were associated with RVA infection. RVA infection was higher in children partially vaccinated (40.7%, 11/27) followed by the fully vaccinated (29.3%, 56/191) and the unvaccinated (15.3%, 21/137) (p = 0.002). G1P[8] and G9P[4] were common in vaccinated children less than 12 months. The present analysis showed that RVA infection reduced slightly in the post-vaccine period, with a high proportion of infection and genotype diversity in children, under 12 months of age, vaccinated. Further research on factors associated with RVA infection on vaccinated compared to unvaccinated children and vaccination optimization should be done.publishersversionpublishe

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20–27) for women and 18% (16–21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions