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      A Model for a Chikungunya Outbreak in a Rural Cambodian Setting: Implications for Disease Control in Uninfected Areas

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          Abstract

          Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It subsequently spread to the islands of the Indian Ocean, reaching Southeast Asia in 2006. The virus was first detected in Cambodia in 2011 and a large outbreak occurred in the village of Trapeang Roka Kampong Speu Province in March 2012, in which 44% of the villagers had a recent infection biologically confirmed. The epidemic curve was constructed from the number of biologically-confirmed CHIKV cases per day determined from the date of fever onset, which was self-reported during a data collection campaign conducted in the village after the outbreak. All individuals participating in the campaign had infections confirmed by laboratory analysis, allowing for the identification of asymptomatic cases and those with an unreported date of fever onset. We develop a stochastic model explicitly including such cases, all of whom do not appear on the epidemic curve. We estimate the basic reproduction number of the outbreak to be 6.46 (95% C.I. [6.24, 6.78]). We show that this estimate is particularly sensitive to changes in the biting rate and mosquito longevity. Our model also indicates that the infection was more widespread within the population on the reported epidemic start date. We show that the exclusion of asymptomatic cases and cases with undocumented onset dates can lead to an underestimation of the reproduction number which, in turn, could negatively impact control strategies implemented by public health authorities. We highlight the need for properly documenting newly emerging pathogens in immunologically naive populations and the importance of identifying the route of disease introduction.

          Author Summary

          During the recent resurgence of chikungunya, the scale of imported cases into previously unaffected countries has caused great concern due to the presence of a competent vector ( Aedes albopictus) in many of these regions. This study describes a mathematical model for a chikungunya outbreak in the rural Cambodian village of Trapeang Roka, where a chikungunya epidemic was recorded and documented in March 2012. The outbreak data is unique, in that all infections were confirmed by laboratory analysis, enabling the identification of asymptomatic individuals, in addition to individuals who failed to report details of their infection. A stochastic model, partitioning the infectious population into three distinct classes, is implemented using Gillespie's algorithm. We show that the incorporation of both biologically-confirmed symptomatic cases undocumented by date of fever onset and asymptomatic cases yields a higher estimate of the reproduction number. Our results highlight how reproduction numbers could be underestimated by limiting analysis to the epidemic curve. Carefully documenting cases and performing laboratory testing in cluster regions, such as the village considered here, could provide a more comprehensive insight into the true infection dynamics.

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          Most cited references59

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          Changing patterns of chikungunya virus: re-emergence of a zoonotic arbovirus.

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            Two Chikungunya Isolates from the Outbreak of La Reunion (Indian Ocean) Exhibit Different Patterns of Infection in the Mosquito, Aedes albopictus

            Background A Chikungunya (CHIK) outbreak hit La Réunion Island in 2005–2006. The implicated vector was Aedes albopictus. Here, we present the first study on the susceptibility of Ae. albopictus populations to sympatric CHIKV isolates from La Réunion Island and compare it to other virus/vector combinations. Methodology and Findings We orally infected 8 Ae. albopictus collections from La Réunion and 3 from Mayotte collected in March 2006 with two Chikungunya virus (CHIKV) from La Réunion: (i) strain 05.115 collected in June 2005 with an Alanine at the position 226 of the glycoprotein E1 and (ii) strain 06.21 collected in November 2005 with a substitution A226V. Two other CHIKV isolates and four additional mosquito strains/species were also tested. The viral titer of the infectious blood-meal was 107 plaque forming units (pfu)/mL. Dissemination rates were assessed by immunofluorescent staining on head squashes of surviving females 14 days after infection. Rates were at least two times higher with CHIKV 06.21 compared to CHIKV 05.115. In addition, 10 individuals were analyzed every day by quantitative RT-PCR. Viral RNA was quantified on (i) whole females and (ii) midguts and salivary glands of infected females. When comparing profiles, CHIKV 06.21 produced nearly 2 log more viral RNA copies than CHIKV 05.115. Furthermore, females infected with CHIKV 05.115 could be divided in two categories: weakly susceptible or strongly susceptible, comparable to those infected by CHIKV 06.21. Histological analysis detected the presence of CHIKV in salivary glands two days after infection. In addition, Ae. albopictus from La Réunion was as efficient vector as Ae. aegypti and Ae. albopictus from Vietnam when infected with the CHIKV 06.21. Conclusions Our findings support the hypothesis that the CHIK outbreak in La Réunion Island was due to a highly competent vector Ae. albopictus which allowed an efficient replication and dissemination of CHIKV 06.21.
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              Dispersal of the dengue vector Aedes aegypti within and between rural communities.

              Knowledge of mosquito dispersal is critical for vector-borne disease control and prevention strategies and for understanding population structure and pathogen dissemination. We determined Aedes aegypti flight range and dispersal patterns from 21 mark-release-recapture experiments conducted over 11 years (1991-2002) in Puerto Rico and Thailand. Dispersal was compared by release location, sex, age, season, and village. For all experiments, the majority of mosquitoes were collected from their release house or adjacent house. Inter-village movement was detected rarely, with a few mosquitoes moving a maximum of 512 meters from one Thai village to the next. Average dispersal distances were similar for males and females and females released indoors versus outdoors. The movement of Ae. aegypti was not influenced by season or age, but differed by village. Results demonstrate that adult Ae. aegypti disperse relatively short distances, suggesting that people rather than mosquitoes are the primary mode of dengue virus dissemination within and among communities.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, USA )
                1935-2727
                1935-2735
                September 2014
                11 September 2014
                : 8
                : 9
                : e3120
                Affiliations
                [1 ]Institut Català de Ciències del Clima, Barcelona, Spain
                [2 ]Institut Pasteur du Cambodge, Phnom Penh, Cambodia
                [3 ]National Dengue Control Program, Ministry of Health, Phnom Penh, Cambodia
                [4 ]Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
                United States Army Medical Research Institute of Infectious Diseases, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MR AC XR AT. Performed the experiments: MR AC. Analyzed the data: MR AC VD SL CN PB AT. Contributed reagents/materials/analysis tools: MR AC. Wrote the paper: MR AC XR. Collected data: AC VD SL CN PB AT.

                ¶ AT and XR also contributed equally to this work.

                Article
                PNTD-D-13-01438
                10.1371/journal.pntd.0003120
                4161325
                25210729
                83c8bcce-3c7d-4762-ada3-e7eb832c4bae
                Copyright @ 2014

                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
                : 19 September 2013
                : 15 July 2014
                Page count
                Pages: 15
                Funding
                Work undertaken in Cambodia was directly funded by the Institut Pasteur du Cambodge, Monivong Boulevard, 12201 Phnom Penh, Cambodia. The European researchers were funded under the EU project DENFREE ( http://www.denfree.eu/); Dengue Research Framework for Resisting Epidemics in Europe (grant agreement: 282 378), funded by the European Commission's Seventh Framework Research Programme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Biology and Life Sciences
                Population Biology

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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