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      Heritable strategies for controlling insect vectors of disease

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          Abstract

          Mosquito-borne diseases are causing a substantial burden of mortality, morbidity and economic loss in many parts of the world, despite current control efforts, and new complementary approaches to controlling these diseases are needed. One promising class of new interventions under development involves the heritable modification of the mosquito by insertion of novel genes into the nucleus or of Wolbachia endosymbionts into the cytoplasm. Once released into a target population, these modifications can act to reduce one or more components of the mosquito population's vectorial capacity (e.g. the number of female mosquitoes, their longevity or their ability to support development and transmission of the pathogen). Some of the modifications under development are designed to be self-limiting, in that they will tend to disappear over time in the absence of recurrent releases (and hence are similar to the sterile insect technique, SIT), whereas other modifications are designed to be self-sustaining, spreading through populations even after releases stop (and hence are similar to traditional biological control). Several successful field trials have now been performed with Aedes mosquitoes, and such trials are helping to define the appropriate developmental pathway for this new class of intervention.

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          Wolbachia: master manipulators of invertebrate biology.

          Wolbachia are common intracellular bacteria that are found in arthropods and nematodes. These alphaproteobacteria endosymbionts are transmitted vertically through host eggs and alter host biology in diverse ways, including the induction of reproductive manipulations, such as feminization, parthenogenesis, male killing and sperm-egg incompatibility. They can also move horizontally across species boundaries, resulting in a widespread and global distribution in diverse invertebrate hosts. Here, we review the basic biology of Wolbachia, with emphasis on recent advances in our understanding of these fascinating endosymbionts.
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            Global Spread and Persistence of Dengue

            Dengue is a spectrum of disease caused by four serotypes of the most prevalent arthropod-borne virus affecting humans today, and its incidence has increased dramatically in the past 50 years. Due in part to population growth and uncontrolled urbanization in tropical and subtropical countries, breeding sites for the mosquitoes that transmit dengue virus have proliferated, and successful vector control has proven problematic. Dengue viruses have evolved rapidly as they have spread worldwide, and genotypes associated with increased virulence have expanded from South and Southeast Asia into the Pacific and the Americas. This review explores the human, mosquito, and viral factors that contribute to the global spread and persistence of dengue, as well as the interaction between the three spheres, in the context of ecological and climate changes. What is known, as well as gaps in knowledge, is emphasized in light of future prospects for control and prevention of this pandemic disease.
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              Effect of a fall in malaria transmission on morbidity and mortality in Kilifi, Kenya

              Summary Background As efforts to control malaria are expanded across the world, understanding the role of transmission intensity in determining the burden of clinical malaria is crucial to the prediction and measurement of the effectiveness of interventions to reduce transmission. Furthermore, studies comparing several endemic sites led to speculation that as transmission decreases morbidity and mortality caused by severe malaria might increase. We aimed to assess the epidemiological characteristics of malaria in Kilifi, Kenya, during a period of decreasing transmission intensity. Methods We analyse 18 years (1990–2007) of surveillance data from a paediatric ward in a malaria-endemic region of Kenya. The hospital has a catchment area of 250 000 people. Clinical data and blood-film results for more than 61 000 admissions are reported. Findings Hospital admissions for malaria decreased from 18·43 per 1000 children in 2003 to 3·42 in 2007. Over 18 years of surveillance, the incidence of cerebral malaria initially increased; however, malaria mortality decreased overall because of a decrease in incidence of severe malarial anaemia since 1997 (4·75 to 0·37 per 1000 children) and improved survival among children admitted with non-severe malaria. Parasite prevalence, the mean age of children admitted with malaria, and the proportion of children with cerebral malaria began to change 10 years before hospitalisation for malaria started to fall. Interpretation Sustained reduction in exposure to infection leads to changes in mean age and presentation of disease similar to those described in multisite studies. Changes in transmission might not lead to immediate reductions in incidence of clinical disease. However, longitudinal data do not indicate that reductions in transmission intensity lead to transient increases in morbidity and mortality. Funding Wellcome Trust, Kenya Medical Research Institute.
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                Author and article information

                Journal
                Philos Trans R Soc Lond B Biol Sci
                Philos. Trans. R. Soc. Lond., B, Biol. Sci
                RSTB
                royptb
                Philosophical Transactions of the Royal Society B: Biological Sciences
                The Royal Society
                0962-8436
                1471-2970
                19 June 2014
                19 June 2014
                : 369
                : 1645 , Theme Issue ‘After 2015: infectious diseases in a new era of health and development’ compiled and edited by Christopher Dye and Anne O'Garra
                : 20130432
                Affiliations
                Department of Life Sciences, Imperial College London , Silwood Park, Ascot, Berks SL5 7PY, UK
                Author notes
                Article
                rstb20130432
                10.1098/rstb.2013.0432
                4024225
                24821918
                b5cea36c-10fa-49c4-8d7a-833448e497a5

                © 2014 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.

                History
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                Review Article
                Custom metadata
                June 19, 2014

                Philosophy of science
                malaria,dengue,population genetic engineering,wolbachia,ridl,homing endonuclease genes

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