LSHTM Research Online

    Surveillance of viral infections

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    Antioxidant vitamins and mortality in older persons: findings from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community.

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    BACKGROUND: Older persons are at risk of both poor nutrition and increased oxidative stress. Plasma ascorbate concentrations fall with increasing age, and concentrations of other antioxidants may also be reduced. OBJECTIVE: The goal was to examine the association between antioxidants and mortality in older persons. DESIGN: We randomly selected persons aged 75-84 y from the lists of 51 British family practitioners taking part in a randomized trial of assessment of older persons. A total of 1214 participants provided a blood sample and were interviewed about their usual diet with the use of a food-frequency questionnaire. Statistical analyses were based on deaths after a median of 4.4 y of follow-up, and hazard ratios were estimated for quintiles of dietary or blood antioxidants. RESULTS: We found strong inverse trends for blood ascorbate concentrations with all-cause and cardiovascular disease mortality, which were only marginally reduced after adjustment for confounders or supplement use. Those in the lowest fifth ( 66 micromol/L) had a mortality risk nearly half that (hazard ratio = 0.54; 95% CI: 0.34, 0.84). Similar results were found after the exclusion of those subjects with cardiovascular disease or cancer at baseline (hazard ratio = 0.51; 0.28, 0.93). In fully adjusted models, there was no evidence for an influence of alpha-tocopherol, beta-carotene, or retinol on total mortality. Dietary antioxidants measured by the food-frequency questionnaire were not associated with all-cause or cardiovascular disease mortality. CONCLUSION: Low blood vitamin C concentrations in the older British population are strongly predictive of mortality

    Domains of transmission and association of community, school, and household sanitation with soil-transmitted helminth infections among children in coastal Kenya.

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    INTRODUCTION: Few studies have simultaneously examined the role of sanitation conditions at the home, school, and community on soil-transmitted helminth (STH) infection. We examined the contribution of each domain that children inhabit (home, village, and school) to STH infection and estimated the association of STH infection with sanitation in each domain. METHODS: Using data from 4,104 children from Kwale County, Kenya, who reported attending school, we used logistic regression models with cross-classified random effects to calculate measures of general contextual effects and estimate associations of village sanitation coverage (percentage of households with reported access to sanitation), school sanitation coverage (number of usable toilets per enrolled pupil), and sanitation access at home with STH infection. FINDINGS: We found reported use of a sanitation facility by households was associated with reduced prevalence of hookworm infection but not with reduced prevalence of T. trichiura infection. School sanitation coverage > 3 toilets per 100 pupils was associated with lower prevalence of hookworm infection. School sanitation was not associated with T. trichiura infection. Village sanitation coverage > 81% was associated with reduced prevalence of T. trichiura infection, but no protective association was detected for hookworm infection. General contextual effects represented by residual heterogeneity between village and school domains had comparable impact upon likelihood of hookworm and T. trichiura infection as sanitation coverage in either of these domains. CONCLUSION: Findings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children

    Defining the Roles of Data Manager and Epidemiologist in Emergency Medical Teams.

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    Medical and epidemiological documentation in disasters is pivotal: the former for recording patient care and the latter for providing real-time information to the host country. Furthermore, documentation informs post-hoc analysis to improve the effectiveness of future deployments.Although documentation is considered important and indeed integral to health care response, there are many barriers and challenges. Some of these challenges include: working without well-established standards for medical documentation; and working with international guidelines which provide minimal guidance as to how health data should be managed practically to ensure accuracy and completion. Furthermore, there is a shift in mindset in disaster contexts wherein most health care focus shifts to direct clinical care and diverts almost all attention from quality documentation.This report distinguishes between the tasks of the epidemiologist and the data manager (DM) in an emergency medical team (EMT) and discusses the importance of data collection in the specific case of an EMT deployment. While combining these roles is sometimes possible if resources are limited, it is better to separate them, as the two are quite distinct. Although there is overlap, to achieve the goals of either role, preferentially they should be carried out by two people working closely together with complementary skill sets. The main objective of this report is to provide guidance and task descriptions to EMTs and field hospitals when training, recruiting, and preparing DMs and epidemiologists to work within their teams. Clear delineation of tasks will lead to better quality data, as it commits DMs to being concerned with the provision of real-time documentation from patient arrival through to compiling daily reports. It also commits epidemiologists to providing enhanced disease surveillance; outbreak investigation; and a source of reliable and actionable information for decision makers and stakeholders in the disaster management cycle

    Characterization of Breakfast Cereals Available in the Mexican Market: Sodium and Sugar Content.

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    Preschool Mexican children consume 7% of their total energy intake from processed breakfast cereals. This study characterized the nutritional quality and labelling (claims and Guideline Daily Amount (GDA)) of the packaged breakfast cereals available in the Mexican market. Photographs of all breakfast cereals available in the 9 main food retail chains in the country were taken. The nutrition quality of cereals was assessed using the United Kingdom Nutrient Profiling Model (UKNPM). Claims were classified using the International Network for Food and Obesity/non-communicable Diseases Research, Monitoring and Action Support (INFORMAS) taxonomy and the GDA was defined according to the Mexican regulation, NOM-051. Overall, a total of 371 different breakfast cereals were analysed. The nutritional profile showed that 68.7% were classified as "less healthy". GDAs and claims were displayed more frequently on the "less healthy" cereals. Breakfast cereals within the "less healthy" category had significantly higher content of energy, sugar and sodium (p < 0.001). Most of the claims were displayed in the "less healthy" cereals (n = 313). This study has shown that there is a lack of consistency between the labelling on the front of the pack and the nutritional quality of breakfast cereals

    The effects of dual-therapy intensification with insulin or dipeptidylpeptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: A retrospective cohort study.

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    PURPOSE: To compare time to a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke or all-cause mortality in patients with type 2 diabetes mellitus who had their treatment intensified with a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy (metformin plus sulfonylurea) failure. METHODS: A retrospective cohort study was conducted on 5238 patients newly treated with either a dipeptidylpeptidase-4 inhibitor or insulin following dual-therapy failure (2007-2014). Data were sourced from UK General Practices. The risk of the composite outcome was compared between two treatment groups: metformin + sulfonylurea + insulin ( n = 1584) and metformin + sulfonylurea + dipeptidylpeptidase-4 inhibitor ( n = 3654), while adjusting for baseline covariates. Follow-up was for up to 5 years. Propensity score matching analysis and Cox proportional hazard models were employed. RESULTS: Overall, 123 and 171 composite outcome events occurred among patients who added insulin versus dipeptidylpeptidase-4 inhibitor, respectively (44.5 vs 14.6 events per 1000 person-years). Addition of insulin was associated with a significantly higher hazard ratio versus the addition of a dipeptidylpeptidase-4 inhibitor (adjusted hazard ratio = 2.6, 95% confidence interval: 1.9-3.4; p < 0.01), an effect that was more pronounced in obese (body mass index: 30-34.9 kg/m2) patients (corresponding adjusted hazard ratio 3.6, 95% confidence interval: 2.3-5.6; p < 0.01). CONCLUSION: In routine clinical practice, intensification of metformin + sulfonylurea therapy by adding insulin is associated with increased risk of cardiovascular events and death compared with adding a dipeptidylpeptidase-4 inhibitor. These findings are in line with suggestions from previous studies regarding the cardiovascular safety of insulin in type 2 diabetes mellitus, but should be interpreted with caution

    The effect of daily co-trimoxazole prophylaxis on natural development of antibody-mediated immunity against P. falciparum malaria infection in HIV-exposed uninfected Malawian children.

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    BACKGROUND AND OBJECTIVES: Co-trimoxazole prophylaxis, currently recommended in HIV-exposed, uninfected (HEU) children as protection against opportunistic infections, also has some anti-malarial efficacy. We determined whether daily co-trimoxazole prophylaxis affects the natural development of antibody-mediated immunity to blood-stage Plasmodium falciparum malaria infection. METHODS: Using an enzyme-linked immunosorbent assay, we measured antibodies to 8 Plasmodium falciparum antigens (AMA-1, MSP-119, MSP-3, PfSE, EBA-175RII, GLURP R0, GLURP R2 and CSP) in serum samples from 33 HEU children and 31 HIV-unexposed, uninfected (HUU) children, collected at 6, 12 and 18 months of age. RESULTS: Compared to HIV-uninfected children, HEU children had significantly lower levels of specific IgG against AMA-1 at 6 months (p = 0.001), MSP-119 at 12 months (p = 0.041) and PfSE at 6 months (p = 0.038), 12 months (p = 0.0012) and 18 months (p = 0.0097). No differences in the IgG antibody responses against the rest of the antigens were observed between the two groups at all time points. The breadth of specificity of IgG response was reduced in HEU children compared to HUU children during the follow up period. CONCLUSIONS: Co-trimoxazole prophylaxis seems to reduce IgG antibody responses to P. falciparum blood stage antigens, which could be as a result of a reduction in exposure of those children under this regime. Although antibody responses were regarded as markers of exposure in this study, further studies are required to establish whether these responses are correlated in any way to clinical immunity to malaria

    Shotgun sequencing analysis of Trypanosoma cruzi I Sylvio X10/1 and comparison with T. cruzi VI CL Brener.

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    Trypanosoma cruzi is the causative agent of Chagas disease, which affects more than 9 million people in Latin America. We have generated a draft genome sequence of the TcI strain Sylvio X10/1 and compared it to the TcVI reference strain CL Brener to identify lineage-specific features. We found virtually no differences in the core gene content of CL Brener and Sylvio X10/1 by presence/absence analysis, but 6 open reading frames from CL Brener were missing in Sylvio X10/1. Several multicopy gene families, including DGF, mucin, MASP and GP63 were found to contain substantially fewer genes in Sylvio X10/1, based on sequence read estimations. 1,861 small insertion-deletion events and 77,349 nucleotide differences, 23% of which were non-synonymous and associated with radical amino acid changes, further distinguish these two genomes. There were 336 genes indicated as under positive selection, 145 unique to T. cruzi in comparison to T. brucei and Leishmania. This study provides a framework for further comparative analyses of two major T. cruzi lineages and also highlights the need for sequencing more strains to understand fully the genomic composition of this parasite

    Physical assault in the previous year and total and cause-specific mortality in Russia: a case-control study of men aged 25-54 years.

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    Background: Violence has important health effects. The results of exposure to physical violence include, but may not be limited to, death from suicide and homicide. The connection between the experience of assault and risk of death from causes other than homicide and suicide has rarely been examined. Methods: We analysed data from the first Izhevsk Family Study (IFS-1), a population-based case-control study of premature mortality in Russian men. Structural equation models were used to obtain odds ratios (ORs) for the association between the proxy report of physical attack in the previous year and mortality. Results: The estimate of the all-cause mortality OR for assault, after adjusting for alcohol use and socio-demographic confounders, was 1.96 (95% confidence interval: 1.71, 3.31). Strong cause-specific associations were found for external causes, but associations were also found for deaths from cardiovascular and alcohol-related deaths. Conclusions: We found that, in our population of working-aged Russian men, there was a strong association between physical assault and mortality from a wide range of causes. Other than direct effects of physical assault on mortality, residual confounding is an important possibility. The association between assault and mortality, particularly from cardiovascular and alcohol-related causes requires replication and further investigation

    Using Data from Macaques To Predict Gamma Interferon Responses after Mycobacterium bovis BCG Vaccination in Humans: a Proof-of-Concept Study of Immunostimulation/Immunodynamic Modeling Methods.

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    Macaques play a central role in the development of human tuberculosis (TB) vaccines. Immune and challenge responses differ across macaque and human subpopulations. We used novel immunostimulation/immunodynamic modeling methods in a proof-of-concept study to determine which macaque subpopulations best predicted immune responses in different human subpopulations. Data on gamma interferon (IFN-γ)-secreting CD4+ T cells over time after recent Mycobacterium bovis BCG vaccination were available for 55 humans and 81 macaques. Human population covariates were baseline BCG vaccination status, time since BCG vaccination, gender, and the monocyte/lymphocyte cell count ratio. The macaque population covariate was the colony of origin. A two-compartment mathematical model describing the dynamics of the IFN-γ T cell response after BCG vaccination was calibrated to these data using nonlinear mixed-effects methods. The model was calibrated to macaque and human data separately. The association between subpopulations and the BCG immune response in each species was assessed. The macaque subpopulations that best predicted immune responses in different human subpopulations were identified using Bayesian information criteria. We found that the macaque colony and the human baseline BCG status were significantly (P < 0.05) associated with the BCG-induced immune response. For humans who were BCG naïve at baseline, Indonesian cynomolgus macaques and Indian rhesus macaques best predicted the immune response. For humans who had already been BCG vaccinated at baseline, Mauritian cynomolgus macaques best predicted the immune response. This work suggests that the immune responses of different human populations may be best modeled by different macaque colonies, and it demonstrates the potential utility of immunostimulation/immunodynamic modeling to accelerate TB vaccine development
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