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      Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults: A Prospective Cohort and Parallel Case-Control Study

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          Abstract

          Human immunodeficiency virus (HIV)–related immunosuppression is a major risk factor for influenza illness and severity in Malawian adults. Household crowding, food insecurity, and poor sanitation are additional risk factors. Influenza preventive strategies should target HIV-infected adults in Africa.

          Abstract

          Background

          The impact of human immunodeficiency virus (HIV) infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings but is rarely implemented in Africa.

          Methods

          We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized) lower respiratory tract infection, and mild influenza (influenza-like illness [ILI]).

          Results

          The cohort study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April 2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119 (4.2%) in HIV-uninfected adults were positive for influenza by means of polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years; incidence rate ratio, 2.75; 95% confidence interval, 1.02–7.44; P = .03; adjusted for age, sex, household crowding, and food security). In the case-control study, influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence was 69.6% and 29.6%, respectively, among influenza-positive case patients and controls. HIV was a significant risk factor for severe influenza (odds ratio, 4.98; 95% confidence interval, 2.09–11.88; P < .001; population-attributable fraction, 57%; adjusted for season, sanitation facility, and food security).

          Conclusions

          HIV is an important risk factor for influenza-associated ILI and severe presentation in this high–HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be reevaluated, and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined.

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          Most cited references34

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          A simulation study of the number of events per variable in logistic regression analysis

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            A simulation study of the number of events per variable in logistic regression analysis.

            We performed a Monte Carlo study to evaluate the effect of the number of events per variable (EPV) analyzed in logistic regression analysis. The simulations were based on data from a cardiac trial of 673 patients in which 252 deaths occurred and seven variables were cogent predictors of mortality; the number of events per predictive variable was (252/7 =) 36 for the full sample. For the simulations, at values of EPV = 2, 5, 10, 15, 20, and 25, we randomly generated 500 samples of the 673 patients, chosen with replacement, according to a logistic model derived from the full sample. Simulation results for the regression coefficients for each variable in each group of 500 samples were compared for bias, precision, and significance testing against the results of the model fitted to the original sample. For EPV values of 10 or greater, no major problems occurred. For EPV values less than 10, however, the regression coefficients were biased in both positive and negative directions; the large sample variance estimates from the logistic model both overestimated and underestimated the sample variance of the regression coefficients; the 90% confidence limits about the estimated values did not have proper coverage; the Wald statistic was conservative under the null hypothesis; and paradoxical associations (significance in the wrong direction) were increased. Although other factors (such as the total number of events, or sample size) may influence the validity of the logistic model, our findings indicate that low EPV can lead to major problems.
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              What are we assessing when we measure food security? A compendium and review of current metrics.

              The appropriate measurement of food security is critical for targeting food and economic aid; supporting early famine warning and global monitoring systems; evaluating nutrition, health, and development programs; and informing government policy across many sectors. This important work is complicated by the multiple approaches and tools for assessing food security. In response, we have prepared a compendium and review of food security assessment tools in which we review issues of terminology, measurement, and validation. We begin by describing the evolving definition of food security and use this discussion to frame a review of the current landscape of measurement tools available for assessing food security. We critically assess the purpose/s of these tools, the domains of food security assessed by each, the conceptualizations of food security that underpin each metric, as well as the approaches that have been used to validate these metrics. Specifically, we describe measurement tools that 1) provide national-level estimates of food security, 2) inform global monitoring and early warning systems, 3) assess household food access and acquisition, and 4) measure food consumption and utilization. After describing a number of outstanding measurement challenges that might be addressed in future research, we conclude by offering suggestions to guide the selection of appropriate food security metrics.
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                Author and article information

                Journal
                Clin Infect Dis
                Clin. Infect. Dis
                cid
                Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
                Oxford University Press (US )
                1058-4838
                1537-6591
                15 March 2018
                16 October 2017
                16 October 2017
                : 66
                : 6
                : 865-876
                Affiliations
                [1 ]Institute of Infection and Global Health, University of Liverpool, United Kingdom
                [2 ]Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi
                [3 ]Liverpool School of Tropical of Medicine, United Kingdom
                [4 ]Queen Elizabeth Central Hospital, Blantyre, Malawi
                [5 ]College of Medicine, University of Malawi, Blantyre, Malawi
                [6 ]University College London, United Kingdom
                Author notes

                R. S. H. and N. F. contributed equally to this work.

                Correspondence: A. Ho, Institute of Infection and Global Health, University of Liverpool, Liverpool, L69 7BE, United Kingdom ( toniho@ 123456doctors.org.uk ).
                Article
                cix903
                10.1093/cid/cix903
                5850564
                29045699
                1a31d082-b1a1-4c1c-8c50-fe54c51c8fd3
                © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 June 2017
                : 14 October 2017
                Page count
                Pages: 12
                Funding
                Funded by: Wellcome Trust 10.13039/100004440
                Award ID: 097464/Z/11/A
                Categories
                Articles and Commentaries

                Infectious disease & Microbiology
                hiv,influenza,malawi
                Infectious disease & Microbiology
                hiv, influenza, malawi

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