Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It s... more 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.
Chikungunya virus (CHIKV), probably Asian genotype, was rst detected in Cambodia in 1961. Despite... more Chikungunya virus (CHIKV), probably Asian genotype, was rst detected in Cambodia in 1961. Despite no evidence of acute or recent CHIKV infections since 2000, real-time reverse transcription PCR of serum collected in 2011 detected CHIKV, East Central South African genotype. Spatiotemporal patterns and phylogenetic clustering indicate that the virus probably originated in Thailand.
MMWR. Morbidity and mortality weekly report, Jan 21, 2012
Chikungunya virus (CHIKV) is an alphavirus transmitted to humans through the bite of infected Aed... more Chikungunya virus (CHIKV) is an alphavirus transmitted to humans through the bite of infected Aedes mosquitoes. CHIKV causes fever and usually is not fatal, but can cause debilitating joint pains or, in rare instances, severe illness. The East/Central/South African strain of chikungunya has been emerging in Asia since 2006, first in the Indian subcontinent, then Thailand. This report describes the characteristics of a local outbreak linked with chikungunya reemergence in a rural Asian setting. Sporadic cases of chikungunya were identified in Cambodia in 2011. Antibodies to CHIKV have been detected in serum collected in Cambodia in 2007, but the strain could not be identified for those cases (U.S. Naval Medical Research Unit 2, unpublished data, 2012). On March 7, 2012, several cases of rash with fever were reported among village residents of Trapeang Roka in Kampong Speu Province, Cambodia. Subsequent field investigation revealed that four of six blood samples from affected persons ...
Dengue is a major contributor to morbidity in children aged twelve and below throughout Cambodia;... more Dengue is a major contributor to morbidity in children aged twelve and below throughout Cambodia; the 2012 epidemic season was the most severe in the country since 2007, with more than 42,000 reported (suspect or confirmed) cases.
Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It s... more 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.
Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecula... more Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further.
On the cover: The evolution of arthropod-borne viruses, such as dengue or chikungunya, is thought... more On the cover: The evolution of arthropod-borne viruses, such as dengue or chikungunya, is thought to be strongly in uenced by their mosquito hosts. Thus, the ability to follow the host-speci c evolutionary trajectories of these viruses is essential to predict and prevent epidemics. In this issue, examine the evolution of chikungunya virus in mosquitoes and show that the emergence of previous and potentially future epidemic strains can be detected by monitoring saliva samples. They identify mutations that increase virion stability and fusion activity and show their potential to replace a currently circulating strain in natural transmission experiments. The cover image illustrates the ominous threat posed by mosquitoes and the evolving viruses that they harbor. Cover art designed by Stephanie Welter of Celery Design Collaborative.
Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of febrile illness i... more Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of febrile illness in rural area of Asia-Pacific region. A multi-locus sequence typing (MLST) analysis was performed on strains isolated from human patients from 3 countries in Southeast Asia: Cambodia, Vietnam and Thailand. The phylogeny of the 56-kDa protein encoding gene was analyzed on the same strains and showed a structured topology with genetically distinct clusters. MLST analysis did not lead to the same conclusion. DNA polymorphism and phylogeny of individual gene loci indicated a significant level of recombination and genetic diversity whereas the ST distribution indicated the presence of isolated patches. No correlation was found with the geographic origin. This work suggests that weak divergence in core genome and ancestral haplotypes are maintained by permanent recombination in mites while the 56-kDa protein gene is diverging in higher speed due to selection by the mammalian immune system.
Background: Dengue diagnosis is complex and until recently only specialized laboratories were abl... more Background: Dengue diagnosis is complex and until recently only specialized laboratories were able to definitively confirm dengue infection. Rapid tests are now available commercially making biological diagnosis possible in the field. The aim of this study was to evaluate a combined dengue rapid test for the detection of NS1 and IgM/IgG antibodies. The evaluation was made prospectively in the field conditions and included the study of the impact of its use as a point-of-care test for case management as well as retrospectively against a panel of well-characterized samples in a reference laboratory.
During the 2012 epidemic of dengue in Vientiane capital, Lao PDR, a major serotype switch from de... more During the 2012 epidemic of dengue in Vientiane capital, Lao PDR, a major serotype switch from dengue 1 to 3 was observed. A molecular epidemiology study demonstrated that dengue 3 remained the predominant serotype in 2013, but also revealed the co-circulation of two genotypes, supporting the hypothesis of multiple geographic origins of dengue 3 strains circulating in Vientiane capital.
Background: Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes vira... more Background: Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described.
Background: Deciphering host responses contributing to dengue shock syndrome (DSS), the life-thre... more Background: Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians.
Background: Detection of dengue NS1 antigen in acute infection has been proposed for early diagno... more Background: Detection of dengue NS1 antigen in acute infection has been proposed for early diagnosis of dengue disease. The aim of this study was to evaluate the clinical and virological factors influencing the performance of the Platelia NS1 Ag kit (BioRad) and to assess the potential use of NS1 antigen and dengue viral loads as markers of dengue disease severity.
Background: Dengue vaccines are now in late-stage development, and evaluation and robust estimate... more Background: Dengue vaccines are now in late-stage development, and evaluation and robust estimates of dengue disease burden are needed to facilitate further development and introduction. In Cambodia, the national dengue case-definition only allows reporting of children less than 16 years of age, and little is known about dengue burden in rural areas and among older persons. To estimate the true burden of dengue in the largest province of Cambodia, Kampong Cham, we conducted community-based active dengue fever surveillance among the 0-to-19-year age group in rural villages and urban areas during 2006-2008. Methods and Findings: Active surveillance for febrile illness was conducted in 32 villages and 10 urban areas by mothers trained to use digital thermometers combined with weekly home visits to identify persons with fever. An investigation team visited families with febrile persons to obtain informed consent for participation in the follow-up study, which included collection of personal data and blood specimens. Dengue-related febrile illness was defined using molecular and serological testing of paired acute and convalescent blood samples. Over the three years of surveillance, 6,121 fever episodes were identified with 736 laboratory-confirmed dengue virus (DENV) infections for incidences of 13.4-57.8/1,000 person-seasons. Average incidence was highest among children less than 7 years of age (41.1/1,000 person-seasons) and lowest among the 16-to-19-year age group (11.3/1,000 person-seasons). The distribution of dengue was highly focal, with incidence rates in villages and urban areas ranging from 1.5-211.5/1,000 person-seasons (median 36.5). During a DENV-3 outbreak in 2007, rural areas were affected more than urban areas (incidence 71 vs. 17/1,000 person-seasons, p,0.001).
Background: Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an e... more Background: Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an estimated 21 million people are infected. Foci of ongoing transmission remain often unnoticed. We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foci and suspected paragonimiasis cases.
Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It s... more 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.
Chikungunya virus (CHIKV), probably Asian genotype, was rst detected in Cambodia in 1961. Despite... more Chikungunya virus (CHIKV), probably Asian genotype, was rst detected in Cambodia in 1961. Despite no evidence of acute or recent CHIKV infections since 2000, real-time reverse transcription PCR of serum collected in 2011 detected CHIKV, East Central South African genotype. Spatiotemporal patterns and phylogenetic clustering indicate that the virus probably originated in Thailand.
MMWR. Morbidity and mortality weekly report, Jan 21, 2012
Chikungunya virus (CHIKV) is an alphavirus transmitted to humans through the bite of infected Aed... more Chikungunya virus (CHIKV) is an alphavirus transmitted to humans through the bite of infected Aedes mosquitoes. CHIKV causes fever and usually is not fatal, but can cause debilitating joint pains or, in rare instances, severe illness. The East/Central/South African strain of chikungunya has been emerging in Asia since 2006, first in the Indian subcontinent, then Thailand. This report describes the characteristics of a local outbreak linked with chikungunya reemergence in a rural Asian setting. Sporadic cases of chikungunya were identified in Cambodia in 2011. Antibodies to CHIKV have been detected in serum collected in Cambodia in 2007, but the strain could not be identified for those cases (U.S. Naval Medical Research Unit 2, unpublished data, 2012). On March 7, 2012, several cases of rash with fever were reported among village residents of Trapeang Roka in Kampong Speu Province, Cambodia. Subsequent field investigation revealed that four of six blood samples from affected persons ...
Dengue is a major contributor to morbidity in children aged twelve and below throughout Cambodia;... more Dengue is a major contributor to morbidity in children aged twelve and below throughout Cambodia; the 2012 epidemic season was the most severe in the country since 2007, with more than 42,000 reported (suspect or confirmed) cases.
Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It s... more 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.
Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecula... more Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further.
On the cover: The evolution of arthropod-borne viruses, such as dengue or chikungunya, is thought... more On the cover: The evolution of arthropod-borne viruses, such as dengue or chikungunya, is thought to be strongly in uenced by their mosquito hosts. Thus, the ability to follow the host-speci c evolutionary trajectories of these viruses is essential to predict and prevent epidemics. In this issue, examine the evolution of chikungunya virus in mosquitoes and show that the emergence of previous and potentially future epidemic strains can be detected by monitoring saliva samples. They identify mutations that increase virion stability and fusion activity and show their potential to replace a currently circulating strain in natural transmission experiments. The cover image illustrates the ominous threat posed by mosquitoes and the evolving viruses that they harbor. Cover art designed by Stephanie Welter of Celery Design Collaborative.
Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of febrile illness i... more Orientia tsutsugamushi is the causative agent of scrub typhus, a major cause of febrile illness in rural area of Asia-Pacific region. A multi-locus sequence typing (MLST) analysis was performed on strains isolated from human patients from 3 countries in Southeast Asia: Cambodia, Vietnam and Thailand. The phylogeny of the 56-kDa protein encoding gene was analyzed on the same strains and showed a structured topology with genetically distinct clusters. MLST analysis did not lead to the same conclusion. DNA polymorphism and phylogeny of individual gene loci indicated a significant level of recombination and genetic diversity whereas the ST distribution indicated the presence of isolated patches. No correlation was found with the geographic origin. This work suggests that weak divergence in core genome and ancestral haplotypes are maintained by permanent recombination in mites while the 56-kDa protein gene is diverging in higher speed due to selection by the mammalian immune system.
Background: Dengue diagnosis is complex and until recently only specialized laboratories were abl... more Background: Dengue diagnosis is complex and until recently only specialized laboratories were able to definitively confirm dengue infection. Rapid tests are now available commercially making biological diagnosis possible in the field. The aim of this study was to evaluate a combined dengue rapid test for the detection of NS1 and IgM/IgG antibodies. The evaluation was made prospectively in the field conditions and included the study of the impact of its use as a point-of-care test for case management as well as retrospectively against a panel of well-characterized samples in a reference laboratory.
During the 2012 epidemic of dengue in Vientiane capital, Lao PDR, a major serotype switch from de... more During the 2012 epidemic of dengue in Vientiane capital, Lao PDR, a major serotype switch from dengue 1 to 3 was observed. A molecular epidemiology study demonstrated that dengue 3 remained the predominant serotype in 2013, but also revealed the co-circulation of two genotypes, supporting the hypothesis of multiple geographic origins of dengue 3 strains circulating in Vientiane capital.
Background: Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes vira... more Background: Japanese encephalitis virus (JEV) is a major mosquito-borne pathogen that causes viral encephalitis throughout Asia. Vaccination with an inactive JEV particle or attenuated virus is an efficient preventative measure for controlling infection. Flavivirus NS1 protein is a glycoprotein secreted during viral replication that plays multiple roles in the viral life cycle and pathogenesis. Utilizing JEV NS1 as an antigen in viral vectors induces a limited protective immune response against infection. Previous studies using E. coli-expressed JEV NS1 to immunize mice induced protection against lethal challenge; however, the protection mechanism through cellular and humoral immune responses was not described.
Background: Deciphering host responses contributing to dengue shock syndrome (DSS), the life-thre... more Background: Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians.
Background: Detection of dengue NS1 antigen in acute infection has been proposed for early diagno... more Background: Detection of dengue NS1 antigen in acute infection has been proposed for early diagnosis of dengue disease. The aim of this study was to evaluate the clinical and virological factors influencing the performance of the Platelia NS1 Ag kit (BioRad) and to assess the potential use of NS1 antigen and dengue viral loads as markers of dengue disease severity.
Background: Dengue vaccines are now in late-stage development, and evaluation and robust estimate... more Background: Dengue vaccines are now in late-stage development, and evaluation and robust estimates of dengue disease burden are needed to facilitate further development and introduction. In Cambodia, the national dengue case-definition only allows reporting of children less than 16 years of age, and little is known about dengue burden in rural areas and among older persons. To estimate the true burden of dengue in the largest province of Cambodia, Kampong Cham, we conducted community-based active dengue fever surveillance among the 0-to-19-year age group in rural villages and urban areas during 2006-2008. Methods and Findings: Active surveillance for febrile illness was conducted in 32 villages and 10 urban areas by mothers trained to use digital thermometers combined with weekly home visits to identify persons with fever. An investigation team visited families with febrile persons to obtain informed consent for participation in the follow-up study, which included collection of personal data and blood specimens. Dengue-related febrile illness was defined using molecular and serological testing of paired acute and convalescent blood samples. Over the three years of surveillance, 6,121 fever episodes were identified with 736 laboratory-confirmed dengue virus (DENV) infections for incidences of 13.4-57.8/1,000 person-seasons. Average incidence was highest among children less than 7 years of age (41.1/1,000 person-seasons) and lowest among the 16-to-19-year age group (11.3/1,000 person-seasons). The distribution of dengue was highly focal, with incidence rates in villages and urban areas ranging from 1.5-211.5/1,000 person-seasons (median 36.5). During a DENV-3 outbreak in 2007, rural areas were affected more than urban areas (incidence 71 vs. 17/1,000 person-seasons, p,0.001).
Background: Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an e... more Background: Paragonimiasis is a food-borne trematodiasis leading to lung disease. Worldwide, an estimated 21 million people are infected. Foci of ongoing transmission remain often unnoticed. We evaluated a simple questionnaire approach using lay-informants at the village level to identify paragonimiasis foci and suspected paragonimiasis cases.
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Papers by Veasna Duong