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0000-0003-1372-3008
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GSK Vaccines
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Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.MEEGID.2017.05.023
Abstract: The circulation of mammarenaviruses in rodent populations of the Mekong region has recently been established, with a genetic variant of Wēnzhōu virus, Cardamones virus, detected in two Rattus species. This study tests the potential teratogenic effects of Wēnzhōu infection on the development of a Murid rodent, Rattus exulans. Using direct virus detection, morphological records and comparative analyses, a link was demonstrated between host infection status and host morphologies (the spleen irrespective of weight, the skull shape and the cranial cavity volume) at the level of the in idual (females only). This study demonstrates that mammarenavirus infections can impact natural host physiology and/or affect developmental processes. The presence of an infecting micro-parasite during the development of the rat may lead to a physiological trade-off between immunity and brain size. Alternatively, replication of virus in specialized organs can result in selective morphologic abnormalities and lesions.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.SSTE.2016.04.002
Abstract: To establish how the conversion of natural habitats for agricultural purposes may impact the distribution of hantaviruses in Southeast Asia, we tested how habitat structure affects hantavirus infection prevalence of common murine rodents that inhabit human-dominated landscapes in this region. For this, we used geo-referenced data of rodents analysed for hantavirus infection and land cover maps produced for the seven study sites in Thailand, Cambodia and Lao PDR where they were collected. Rodents were tested by serological methods that detect several hantaviruses, including pathogenic ones. Rodents with a seropositive status were more likely to be found near to agriculture on steep land, and also in environments with a high proportion of agriculture on steep land. These results suggest that in Southeast Asia, hantaviruses, which are often associated with generalist rodent species with a preference for agricultural land, may benefit from land conversion to agriculture.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2017
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-2017
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.MEEGID.2011.01.004
Abstract: Scrub typhus is an acute infectious disease caused by an obligate intracellular bacterium Orientia tsutsugamushi following the bite of infected trombiculid mites of the genus Leptotrombidium. This zoonotic disease is a major cause of febrile illness in the Asia-Pacific region, with a large spectrum of clinical manifestations from unapparent or mild disease to fatal disease. O. tsutsugamushi is characterized by a very high genomic plasticity and a large number of antigenic variants amongst strains. The 56-kDa type specific antigen (TSA) gene, encoding the major antigenic protein, was used as reference to investigate the genetic relationships between the strains and to genotype O. tsutsugamushi isolates. The open reading frame of the 56-kDa TSA gene of 41 sequences (28 Cambodian and 13 Vietnamese strains) from patient s les were sequenced and used for genotyping. The 28 Cambodian isolates clustered into 5 major groups, including Karp (43.5%), JG-v (25%), Kato/TA716 (21.5%), TA763 (3.5%) and Gilliam (3.5%). Karp (77%), TA763 (15.5%) and JG-v (7.5%) strains were identified amongst the 13 Vietnamese isolates. This is the first countrywide genotyping description in Cambodia and in Central Vietnam. These results demonstrate the considerable ersity of genotypes in co-circulation in both countries. The genotyping result might raise awareness amongst Cambodian and Vietnamese clinicians of the high genetic ersity of circulating O. tsutsugamushi strains and provides unique and beneficial data for serological and molecular diagnosis of scrub typhus infections as well as raw materials for future studies and vaccine development.
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.JCV.2010.02.021
Abstract: Since 2005, eight patients with H5N1 infection were laboratory confirmed in Cambodia. Despite the widespread of highly pathogenic avian influenza H5N1 virus and the intense exposure to poultry, there is growing evidence that H5N1 viruses may not be easily transmitted to human. To evaluate the frequency of H5N1 transmission in rural Cambodia, to identify potential risk factors for H5N1 in humans and to explore the extent of asymptomatic and clinically mild illness among humans. A seroepidemiologic survey was conducted, 9 weeks after the recognition that H5N1 infection caused the death of a 13 years old female in April 2007. Blood specimens were collected from 700 participants for H5N1 serological testing. All participants were interviewed with standardized questionnaire to collect information about poultry exposure. Eighteen (2.6%) of the 700 villagers were tested positive cases for H5N1 antibodies. These 18 in iduals were more likely than seronegative participants to report bathing or swimming in the community pond (p=0.04). The seroprevalence of H5N1 antibodies was higher than previously reported in the other investigations conducted in Cambodia and Thailand. This finding reinforces the overwhelming evidence that the virus continues to circulate widely in settings where human have high exposure to poultry. Our results, provides additional evidence suggesting that bathing or swimming in the community ponds, remains important potential risk factor for H5N1 infection. Both wild birds and domestic poultry have free access to these ponds which are also used for aquaculture through the dumping of poultry feces for fish feeding.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.JCV.2007.02.005
Abstract: Highly pathogenic avian influenza (HPAI) H5N1 has spread globally in birds and infected over 270 humans with an apparently high mortality rate. Serologic studies to determine the extent of asymptomatic H5N1 infection in humans and other mammals and to investigate the immunogenicity of current H5N1 vaccine candidates have been h ered by the biosafety requirements needed for H5N1 micro-neutralization tests. Development of a serodiagnostic tool for highly pathogenic influenza that reproduces H5N1 biology but can be used with less biohazard. We have generated and evaluated H5 hemagglutinin pseudotyped lentiviral particles encoding the luciferase reporter (H5pp). H5pp entry into target cells depends on alpha2-3 cell surface sialic acids and requires low pH for membrane fusion. H5pp infectivity is specifically neutralized by sera from patients and animals infected with H5N1 and correlates well with conventional microneutralization test. H5pp reproduce H5N1 influenza virus entry into target cells and potentially provides a high-throughput and safe method for sero-epidemiology.
Publisher: Springer Science and Business Media LLC
Date: 29-11-2011
DOI: 10.1007/S10393-011-0725-7
Abstract: In order to evaluate the circulation of hantaviruses present in southeast Asia, a large scale survey of small mammal species was carried out at seven main sites in the region (Cambodia, Lao People's Democratic Republic, and Thailand). Small scale opportunistic trapping was also performed at an eighth site (Cambodia). Using a standard IFA test, IgG antibodies reacting to Hantaan virus antigens were detected at six sites. Antibody prevalence at each site varied from 0 to 5.6% with antibodies detected in several rodent species (Bandicota indica, B. savilei, Maxomys surifer, Mus caroli, M. cookii, Rattus exulans, R. nitidius, R. norvegicus, and R. tanezumi). When site seroprevalence was compared with site species richness, seropositive animals were found more frequently at sites with lower species richness. In order to confirm which hantavirus species were present, a subset of s les was also subjected to RT-PCR. Hantaviral RNA was detected at a single site from each country. Sequencing confirmed the presence of two hantavirus species, Thailand and Seoul viruses, including one s le (from Lao PDR) representing a highly ergent strain of Seoul virus. This is the first molecular evidence of hantavirus in Lao PDR and the first reported L segment sequence data for Thailand virus.
Publisher: Public Library of Science (PLoS)
Date: 23-10-2014
Publisher: Elsevier BV
Date: 12-2015
Publisher: O.I.E (World Organisation for Animal Health)
Date: 08-2015
Abstract: Chikungunya is an acute viral disease characterised by fever and painful arthralgia. The arthritic symptoms associated with chikungunya can be debilitating and may persist for months or even years in some patients. Severe neurological complications such as encephalitis have also been reported during recent large outbreaks. The disease is caused by chikungunya virus (CHIKV), a mosquito-borne alphavirus from the Togaviridae family, which has recently emerged to become one of the most important exotic viral threats worldwide. Chikungunya is endemic throughout Africa, and over the past decade, it has also spread throughout the Indian Ocean, Asia, the South Pacific, southern Europe, the Caribbean and Central America. The rapid emergence of CHIKV has been linked to expansion of the mosquito vector species, Aedes aegypti and Ae. albopictus, throughout most tropical and subtropical regions of the world. Furthermore, mutations in some strains of CHIKV have been associated with increased transmissibility of the virus. The lack of a commercial vaccine and the failure of vector control strategies to limit the expansion of chikungunya have prompted the need for further options to prevent the spread of this disease.
Publisher: Elsevier BV
Date: 09-2017
Publisher: Public Library of Science (PLoS)
Date: 20-07-2010
Publisher: American Society of Tropical Medicine and Hygiene
Date: 06-2012
Publisher: American Association for the Advancement of Science (AAAS)
Date: 18-09-2015
Abstract: Along with their mosquito vectors, dengue viruses are spreading worldwide to infect millions of people. For a few, subsequent infection results in lethal hemorrhagic disease. Katzelnick et al. used antibody-binding data to map structural ergence and antigenic variation among dengue viruses. Comparing results in monkeys and humans, the viruses approximately clustered into the four known groups. However, the four virus groups showed as much antigenic distance within a group as between groups. This finding helps explain why immune responses to dengue are highly variable, and it has complex implications for epidemiology, disease, and vaccine deployment. Science , this issue p. 1338
Publisher: Wiley
Date: 30-05-2012
Publisher: Informa UK Limited
Date: 2014
DOI: 10.1038/EMI.2014.60
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 10-2009
Publisher: Springer Science and Business Media LLC
Date: 12-2010
DOI: 10.1038/NRMICRO2460
Publisher: American Society for Microbiology
Date: 2010
DOI: 10.1128/JCM.01687-09
Abstract: The analysis of A/H1N1 and A/H3N2 influenza viruses collected between 2005 and 2008 in Cambodia detected strains resistant to oseltamivir and confirmed widespread resistance to adamantanes. Phylogenetic analyses revealed intrasubtype reassortment, probable reemergence of A/H3N2 viruses in two consecutive seasons, and cocirculation of different lineages in each subtype.
Publisher: eLife Sciences Publications, Ltd
Date: 09-06-2016
DOI: 10.7554/ELIFE.13135
Abstract: Southeastern Asia is a recognised hotspot for emerging infectious diseases, many of which have an animal origin. Mammarenavirus infections contribute significantly to the human disease burden in both Africa and the Americas, but little data exists for Asia. To date only two mammarenaviruses, the widely spread lymphocytic choriomeningitis virus and the recently described Wēnzhōu virus have been identified in this region, but the zoonotic impact in Asia remains unknown. Here we report the presence of a novel mammarenavirus and of a genetic variant of the Wēnzhōu virus and provide evidence of mammarenavirus-associated human infection in Asia. The association of these viruses with widely distributed mammals of erse species, commonly found in human dwellings and in peridomestic habitats, illustrates the potential for widespread zoonotic transmission and adds to the known aetiologies of infectious diseases for this region.
Publisher: Informa UK Limited
Date: 2016
DOI: 10.1038/EMI.2016.69
Publisher: Informa UK Limited
Date: 2017
DOI: 10.1038/EMI.2017.15
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.IJID.2016.12.022
Abstract: This study aimed to investigate proteinuria occurring during dengue disease in children and assess if measurement of this parameter can help physicians in the clinical management of patients. Proteinuria was assessed by dipstick and quantified by urine protein:creatinine ratio (UPCR) in s les from patients hospitalized with a confirmed dengue infection and in healthy controls. The dipstick tested positive in 42.9% of the patients presenting at hospital with dengue versus 20.0% in healthy controls. UPCR increased during the critical phase of the disease peaking one week after fever onset then decreasing as the patients recovered. Patients with warnings signs or severe dengue were more likely to present with proteinuria detected by UPCR at the time of hospital admission compared to patients without warning signs. The sensitivity of this marker, however, was limited as only 16.1% of the patients with warning signs had proteinuria. Urine dipstick and UPCR do not seem to be very valuable for the triage of the patients at the time of the initial consultation but the observation of a decrease of the UPCR during the course of the illness appears to indicate an evolution towards recovery.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.IJID.2017.04.005
Abstract: In this study, we document the clinical characteristics and investigated risk factors for uncomplicated and severe forms of EV-A71 disease in Cambodian children. From March to July 2014 inclusive, all patients with suspicion of EV-A71 infection presenting to Kantha Bopha Hospitals in Phnom Penh and Siem Reap and confirmed by the Virology Unit at the Institut Pasteur du Cambodge were prospectively enrolled in this study. Throat swabs, rectal swabs and serum s les were collected from all consecutive patients with suspected EV-A71 infection. In addition, CSF was also collected from patients with suspected EV-A71 associated encephalitis. A total of 122 patients (29 with uncomplicated disease and 93 with severe disease) with confirmed EV-A71 infection with all available demographic and clinical data for clinical classification and further analysis were included in the study. In this prospective EV-A71 study in Cambodia, we confirmed the previously reported association of male gender and absence of mouth or skin lesions with severe disease. We also highlighted the strong association of neutrophils in blood, but also in CSF in patients with pulmonary oedema. More importantly, we identified new putative nutrition-related risk factors for severe disease. EV-A71 is an important cause of encephalitis in the Asia-Pacific region. Further studies to determine the risk factors associated with severe EV-A71 disease are needed.
Publisher: Springer Science and Business Media LLC
Date: 16-05-2016
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.MEEGID.2011.06.019
Abstract: In Cambodia, dengue virus (DENV) was first isolated in 1963 and has become endemic with peak epidemic during raining season. Since 2000, the Dengue National Control Program has reported from 10,000 to 40,000 cases per year with fatality rates ranging from 0.7 to 1.7. All four dengue serotypes are found circulating in Cambodia with alternative predominance of serotypes DENV-2 and DENV-3. The DENV-1 represents from 5% to 20% of all circulating viruses, depending upon the year. In this work, 79 clinical strains of DENV-1 were isolated between 2000 and 2009 and their genome fully sequenced. Four distinct lineages with different dynamics were identified. The main evolutionary drive was negative selective pressure but each lineage was characterized by the presence of specific mutations acquired through evolution. Coexistence, extinction and replacement of lineages occurred over the 10-year period. Lineages 1, 2 and 3 were all detected since 2000-2002 and disappeared in 2003, 2004-2005 and 2007, respectively. Lineages 1 and 2 displayed different dynamics. Lineage 1 was very erse whereas lineage 2 was very homogeneous. Lineage 4 which derived from lineage 3 in 2003 remained the only one at the end of the s ling period in 2008-2009 owing to a selective sweep. The lineages dynamic of DENV-1 viruses and consequences for molecular epidemiology are discussed.
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 2016
Publisher: Informa UK Limited
Date: 2020
Publisher: Hindawi Limited
Date: 25-01-2014
DOI: 10.1111/TBED.12204
Abstract: This study analysed the available data of seroprevalence to human influenza viruses in pigs in Cambodia using generalized linear mixed models in order to improve understanding of factors underlying the spread of human influenza viruses in Cambodian pigs. The associations between seroprevalence against seasonal H1N1 influenza virus in pigs and the population density of humans and pigs were not significant. However, a positive association between anti-H3 antibodies in pigs and the human population density was identified. In contrast, there was a negative association between seroprevalence of H3N2 in pigs and the pig population density. Our study has highlighted the difficulty in identifying epidemiological risk factors when a limited data set is used for analyses. We therefore provide recommendations on data collection for future epidemiological analyses that could be improved by collecting metadata related to the animals s led. In addition, serosurveillance for influenza A viruses in pigs in high-risk areas or at slaughterhouses is recommended in resource-limited countries.
Publisher: Public Library of Science (PLoS)
Date: 25-09-0013
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.MEEGID.2012.05.012
Abstract: The Dengue National Control Program was established in Cambodia in 2000 and has reported between 10,000 and 40,000 dengue cases per year with a case fatality rate ranging from 0.7 to 1.7. In this study 39 DENV-2 and 57 DENV-3 viruses isolated from patients between 2000 and 2008 were fully sequenced. Five DENV2 and four DENV3 distinct lineages with different dynamics were identified. Each lineage was characterized by the presence of specific mutations with no evidence of recombination. In both DENV-2 and DENV-3 the lineages present prior to 2003 were replaced after that date by unrelated lineages. After 2003, DENV-2 lineages D2-3 and D2-4 cocirculated until 2007 when they were almost completely replaced by a lineage D2-5 which emerged from D2-3 Conversely, all DENV-3 lineages remained, ersified and cocirculated with novel lineages emerging. Years 2006 and 2007 were marked by a high prevalence of DENV-3 and 2007 with a large dengue outbreak and a high proportion of patients with severe disease. Selective sweeps in DENV-1 and DENV-2 were linked to immunological escape to a predominately DENV-3-driven immunological response. The complex dynamic of dengue in Cambodia in the last ten years has been associated with a combination of stochastic climatic events, cocirculation, coevolution, adaptation to different vector populations, and with the human population immunological landscape.
Publisher: American Society for Microbiology
Date: 10-2011
DOI: 10.1128/JCM.01131-11
Abstract: Human respiratory syncytial virus (HRSV) is the leading cause of hospitalization of children aged years due to respiratory illness in industrialized countries, and pneumonia is the leading cause of mortality among children aged years worldwide. Although HRSV was first identified in 1956, a preventative vaccine has yet to be developed. Here we report the results of the first study to investigate the circulation and genetic ersity of HRSV in Cambodia among an all-ages population over 5 consecutive years. The incidences of HRSV infection among all-ages outpatient and hospitalized populations were equivalent, at 9.5% and 8.2%, respectively. Infection was most prevalent among children aged years, with bronchiolitis being the most frequently observed clinical syndrome in the same age group. Circulation of HRSV was seasonal, typically coinciding with the rainy season between July and November annually. Strains belonging to HRSV groups A and B were detected with equivalent frequencies however, we observed a potentially biennial shift in the predominant circulating HRSV genotype. The majority of HRSV group B strains belonged to the recently described BA genotype, with the exception of 10 strains classified as belonging to a novel HRSV group B genotype, SAB4, first reported here.
Publisher: American Society for Microbiology
Date: 12-2014
DOI: 10.1128/JVI.01887-14
Abstract: 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 s les, suggested that the mutations occurred during human infection and did not transmit further.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.MEEGID.2015.12.011
Abstract: This first extensive retrospective study of the molecular epidemiology of dog rabies in Cambodia included 149 rabies virus (RABV) entire nucleoprotein sequences obtained from 1998-2011. The sequences were analyzed in conjunction with RABVs from other Asian countries. Phylogenetic reconstruction confirmed the South-East Asian phylogenetic clade comprising viruses from Cambodia, Vietnam, Thailand, Laos and Myanmar. The present study represents the first attempt to classify the phylogenetic lineages inside this clade, resulting in the confirmation that all the Cambodian viruses belonged to the South-East Asian (SEA) clade. Three distinct phylogenetic lineages in the region were established with the majority of viruses from Cambodia closely related to viruses from Thailand, Laos and Vietnam, forming the geographically widespread phylogenetic lineage SEA1. A South-East Asian lineage SEA2 comprised two viruses from Cambodia was identified, which shared a common ancestor with RABVs originating from Laos. Viruses from Myanmar formed separate phylogenetic lineages within the major SEA clade. Bayesian molecular clock analysis suggested that the time to most recent common ancestor (TMRCA) of all Cambodian RABVs dated to around 1950. The TMRCA of the Cambodian SEA1 lineage was around 1964 and that of the SEA2 lineage was around 1953. The results identified three phylogenetically distinct and geographically separated lineages inside the earlier identified major SEA clade, covering at least five countries in the region. A greater understanding of the molecular epidemiology of rabies in South-East Asia is an important step to monitor progress on the efforts to control canine rabies in the region.
Publisher: Public Library of Science (PLoS)
Date: 27-05-2010
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.MEEGID.2010.08.015
Abstract: Orientia tsutsugamushi, the causative agent of scrub typhus in South East Asia and Pacific, is an obligate intracellular bacterium closely related to the Rickettsia. The pathogen is transmitted to humans through the bites of infected larvae of trombiculid mites of the genus Leptotrombidium in which is maintained trough vertical transmission mechanism. The infection in rodents has been described in over 20 species. Scrub typhus is commonly confused with other tropical fevers and late diagnosis and treatment can lead to severe organ failures and a strain-dependent mortality rate of up to 50%. A MLST scheme associating seven core function genes: adk, lepB, lipA, lipB, secY, sodB and sucA was developed and validated on seven Cambodian strains detected in patients and two complete reference genomes from Korea and Japan. Sequence data were analyzed both with respect to sequence type (ST) ersity and DNA polymorphism. Differing trends were revealed. DNA polymorphism and phylogeny of in idual gene loci indicated a significant level of recombination and genetic ersity. However, the ST distribution is clearly clonal and the clinical situation can be summarized by the formula: one patient, one strain, one ST. This contradiction is only apparent and is most likely the consequence of the unique life cycle of O. tsutsugamushi. The quasi exclusive vertical transmission mode in mites generates repeated bottlenecks and small-size populations and strongly limits genetic ersity. O. tsutsugamushi has developed specific mechanisms for generating genetic ersity which include recombination, duplication and conjugation. Recombination and other mechanisms for increasing genetic ersity are likely to occur in rodents which can act as maintenance hosts, although occurrence in mites cannot be excluded. Consequences for the epidemiology of scrub typhus are discussed.
No related grants have been discovered for Philippe BUCHY.