Uncovering the Burden of Dengue in Africa: Considerations on Magnitude, Misdiagnosis, and Ancestry

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Abstract

Dengue is a re-emerging neglected disease of major public health importance. This review highlights important considerations for dengue disease in Africa, including epidemiology and underestimation of disease burden in African countries, issues with malaria misdiagnosis and co-infections, and potential evidence of genetic protection from severe dengue disease in populations of African descent. The findings indicate that dengue virus prevalence in African countries and populations may be more widespread than reported data suggests, and that the Aedes mosquito vectors appear to be increasing in dissemination and number. Changes in climate, population, and plastic pollution are expected to worsen the dengue situation in Africa. Dengue misdiagnosis is also a problem in Africa, especially due to the typical non-specific clinical presentation of dengue leading to misdiagnosis as malaria. Finally, research suggests that a protective genetic component against severe dengue exists in African descent populations, but further studies should be conducted to strengthen this association in various populations, taking into consideration socioeconomic factors that may contribute to these findings. The main takeaway is that Africa should not be overlooked when it comes to dengue, and more attention and resources should be devoted to this disease in Africa.

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The global distribution and burden of dengue

Samir Bhatt, Peter W. Gething, Oliver J Brady … (2013)

Dengue is a systemic viral infection transmitted between humans by Aedes mosquitoes 1 . For some patients dengue is a life-threatening illness 2 . There are currently no licensed vaccines or specific therapeutics, and substantial vector control efforts have not stopped its rapid emergence and global spread 3 . The contemporary worldwide distribution of the risk of dengue virus infection 4 and its public health burden are poorly known 2,5 . Here we undertake an exhaustive assembly of known records of dengue occurrence worldwide, and use a formal modelling framework to map the global distribution of dengue risk. We then pair the resulting risk map with detailed longitudinal information from dengue cohort studies and population surfaces to infer the public health burden of dengue in 2010. We predict dengue to be ubiquitous throughout the tropics, with local spatial variations in risk influenced strongly by rainfall, temperature and the degree of urbanisation. Using cartographic approaches, we estimate there to be 390 million (95 percent credible interval 284-528) dengue infections per year, of which 96 million (67-136) manifest apparently (any level of clinical or sub-clinical severity). This infection total is more than three times the dengue burden estimate of the World Health Organization 2 . Stratification of our estimates by country allows comparison with national dengue reporting, after taking into account the probability of an apparent infection being formally reported. The most notable differences are discussed. These new risk maps and infection estimates provide novel insights into the global, regional and national public health burden imposed by dengue. We anticipate that they will provide a starting point for a wider discussion about the global impact of this disease and will help guide improvements in disease control strategies using vaccine, drug and vector control methods and in their economic evaluation. [285]

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Epidemiology of dengue: past, present and future prospects

Natasha Evelyn Anne Murray, Mikkel Quam, Annelies Wilder-Smith (2013)

Dengue is currently regarded globally as the most important mosquito-borne viral disease. A history of symptoms compatible with dengue can be traced back to the Chin Dynasty of 265–420 AD. The virus and its vectors have now become widely distributed throughout tropical and subtropical regions of the world, particularly over the last half-century. Significant geographic expansion has been coupled with rapid increases in incident cases, epidemics, and hyperendemicity, leading to the more severe forms of dengue. Transmission of dengue is now present in every World Health Organization (WHO) region of the world and more than 125 countries are known to be dengue endemic. The true impact of dengue globally is difficult to ascertain due to factors such as inadequate disease surveillance, misdiagnosis, and low levels of reporting. Currently available data likely grossly underestimates the social, economic, and disease burden. Estimates of the global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. The expansion of dengue is expected to increase due to factors such as the modern dynamics of climate change, globalization, travel, trade, socioeconomics, settlement and also viral evolution. No vaccine or specific antiviral therapy currently exists to address the growing threat of dengue. Prompt case detection and appropriate clinical management can reduce the mortality from severe dengue. Effective vector control is the mainstay of dengue prevention and control. Surveillance and improved reporting of dengue cases is also essential to gauge the true global situation as indicated in the objectives of the WHO Global Strategy for Dengue Prevention and Control, 2012–2020. More accurate data will inform the prioritization of research, health policy, and financial resources toward reducing this poorly controlled disease. The objective of this paper is to review historical and current epidemiology of dengue worldwide and, additionally, reflect on some potential reasons for expansion of dengue into the future.

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Antibody-dependent enhancement of severe dengue disease in humans

Leah C Katzelnick, Lionel Gresh, M. Halloran … (2017)

For dengue viruses 1 to 4 (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of preexisting anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.