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      Allergies and Diabetes as Risk Factors for Dengue Hemorrhagic Fever: Results of a Case Control Study

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          Abstract

          Background

          The physiopathology of dengue hemorrhagic fever (DHF), a severe form of Dengue Fever, is poorly understood. We are unable to identify patients likely to progress to DHF for closer monitoring and early intervention during epidemics, so most cases are sent home. This study explored whether patients with selected co-morbidities are at higher risk of developing DHF.

          Methods

          A matched case-control study was conducted in a dengue sero-positive population in two Brazilian cities. For each case of DHF, 7 sero-positive controls were selected. Cases and controls were interviewed and information collected on demographic and socio-economic status, reported co-morbidities (diabetes, hypertension, allergy) and use of medication. Conditional logistic regression was used to calculate the strength of the association between the co-morbidities and occurrence of DHF.

          Results

          170 cases of DHF and 1,175 controls were included. Significant associations were found between DHF and white ethnicity (OR = 4.70; 2.17–10.20), high income (OR = 6.84; 4.09–11.43), high education (OR = 4.67; 2.35–9.27), reported diabetes (OR = 2.75; 1.12–6.73) and reported allergy treated with steroids (OR = 2.94; 1.01–8.54). Black individuals who reported being treated for hypertension had 13 times higher risk of DHF then black individuals reporting no hypertension.

          Conclusions

          This is the first study to find an association between DHF and diabetes, allergy and hypertension. Given the high case fatality rate of DHF (1–5%), we believe that the evidence produced in this study, when confirmed in other studies, suggests that screening criteria might be used to identify adult patients at a greater risk of developing DHF with a recommendation that they remain under observation and monitoring in hospital.

          Author Summary

          Dengue is an arboviral disease that affects large areas of countries in tropical and subtropical regions of the world. Around 500,000 cases and 22,000 deaths of dengue hemorrhagic fever (DHF)/Dengue Shock Syndrome (DSS), the most severe presentations of this disease, occur annually. It is unclear why some cases of dengue fever (0.5% to 4%) progress to DHF/DSS. There is weak evidence that some diseases could have a role in this process, such as diabetes, hypertension, and allergies. In epidemics most dengue fever cases are sent home as there are too many to be kept in observation, but if it were possible to identify those with a higher risk of progression to DHF, they could be kept for observation, for early detection of signs, symptoms and alterations in laboratory tests suggestive of DHF, to enable timely and effective clinical management and early intervention. We study this issue and we believe that the evidence produced in this study, when confirmed in other studies, suggests that screening criteria might be used to identify adult patients at a greater risk of developing DHF with a recommendation that they remain under observation and monitoring in a hospital.

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          Most cited references14

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          Dengue: an update.

          This review is an update of dengue and dengue haemorrhagic fever (DHF) based on international and Cuban experience. We describe the virus characteristics and risk factors for dengue and DHF, and compare incidence and the case fatality rates in endemic regions (southeast Asia, western Pacific, and the Americas). The clinical picture and the pathogenesis of the severe disease are explained. We also discuss the viral, individual, and environmental factors that determine severe disease. Much more research is necessary to clarify these mechanisms. Also reviewed are methods for viral isolation and the serological, immunohistochemical, and molecular methods applied in the diagnosis of the disease. We describe the status of vaccine development and emphasise that the only alternative that we have today to control the disease is through control of its vector Aedes aegypti.
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            Dengue in the Americas and Southeast Asia: do they differ?

            The populations of Southeast Asia (SE Asia) and tropical America are similar, and all four dengue viruses of Asian origin are endemic in both regions. Yet, during comparable 5-year periods, SE Asia experienced 1.16 million cases of dengue hemorrhagic fever (DHF), principally in children, whereas in the Americas there were 2.8 million dengue fever (DF) cases, principally in adults, and only 65,000 DHF cases. This review aims to explain these regional differences. In SE Asia, World War II amplified Aedes aegypti populations and the spread of dengue viruses. In the Americas, efforts to eradicate A. aegypti in the 1940s and 1950s contained dengue epidemics mainly to the Caribbean Basin. Cuba escaped infections with the American genotype dengue-2 and an Asian dengue-3 endemic in the 1960s and 1970s. Successive infections with dengue-1 and an Asian genotype dengue-2 resulted in the 1981 DHF epidemic. When this dengue-2 virus was introduced in other Caribbean countries, it encountered populations highly immune to the American genotype dengue-2. During the 1980s and 1990s, rapidly expanding populations of A. aegypti in Brazil permitted successive epidemics of dengue-1, -2, and -3. These exposures, however, resulted mainly in DF, with surprisingly few cases of DHF. The absence of high rates of severe dengue disease in Brazil, as elsewhere in the Americas, may be partly explained by the widespread prevalence of human dengue resistance genes. Understanding the nature and distribution of these genes holds promise for containing severe dengue. Future research on dengue infections should emphasize population-based designs.
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              The many faces of the hygiene hypothesis.

              About 15 years have gone by since Strachan first proposed the idea that infections and unhygienic contact might confer protection against the development of allergic illnesses. The so-called hygiene hypothesis has ever since undergone numerous more or less subtle modifications by various researchers in the fields of epidemiology, clinical science, and immunology. Three major tracts have developed exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and the effect of both on underlying responses of the innate and adaptive immunity. To date, a truly unifying concept has not yet emerged, but various pieces of a complex interplay between immune responses of the host, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures becomes apparent. These influences are discussed as determinants for a number of complex allergic illnesses in this review, while we attempt to pay attention to the importance of different phenotypes, namely of the asthma syndrome. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                June 2010
                1 June 2010
                : 4
                : 6
                : e699
                Affiliations
                [1 ]State University of Bahia, Salvador, Brazil
                [2 ]London School of Hygiene & Tropical Medicine, London, United Kingdom
                [3 ]Federal University of Bahia, Salvador, Brazil
                [4 ]State University of Ceará, Fortaleza, Brazil
                [5 ]Case Western Reserve University, Cleveland, Ohio, United States of America
                [6 ]Evandro Chagas Institute, Pará, Brazil
                Pediatric Dengue Vaccine Initiative, United States of America
                Author notes

                Conceived and designed the experiments: MAAF MLB JWOL MCNC RB MGT. Performed the experiments: MAAF LCR JWOL VM RB PFCV MGT. Analyzed the data: MAAF LCR MLB JWOL MCNC VM PFCV MRTN MGT. Contributed reagents/materials/analysis tools: RB PFCV MRTN. Wrote the paper: MAAF LCR MLB JWOL MCNC VM RB PFCV MRTN MGT.

                Article
                09-PNTD-RA-0387R5
                10.1371/journal.pntd.0000699
                2879373
                20532230
                c2bd457b-4a04-4412-9e57-5be2f6604cc8
                Figueiredo 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.
                History
                : 4 August 2009
                : 8 April 2010
                Page count
                Pages: 6
                Categories
                Research Article
                Infectious Diseases
                Infectious Diseases/Epidemiology and Control of Infectious Diseases
                Infectious Diseases/Neglected Tropical Diseases
                Infectious Diseases/Viral Infections

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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