Sareth Rith

Institut Pasteur du Cambodge

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Philippe Buchy

Institut Pasteur du Laos

Paul F. Horwood

James Cook University

Sirenda Vong

Tampere University

Srey Viseth Horm

Institut Pasteur du Cambodge

Sovann Ly

Ministry of Health

Philippe Dussart

Institut Pasteur du Cambodge

Arnaud Tarantola

Santé Publique France

Sowath Ly

Institut Pasteur du Cambodge

Sok Touch

Ministry of Health

Y Phalla

Institut Pasteur du Cambodge

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Institut Pasteur du Cambodge

Centers for Disease Control and Prevention

Institut Pasteur

Ministry of Health

Armed Forces Research Institute of Medical Science

Inserm

Cambodia-Oxford Medical Research Unit

Centre National de la Recherche Scientifique

National Center for Immunization and Respiratory Diseases

Cambodia National Malaria Center

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Epidemiological and Virological Characteristics of Influenza Viruses Circulating in Cambodia from 2009 to 2011

PLoS ONE (2014)

Srey Viseth Horm Sek Mardy Sareth Rith Sovann Ly Heng Seng

Background The Cambodian National Influenza Center (NIC) monitored and characterized circulating influenza strains from 2009 to 2011. Methodology/Principal Findings Sentinel and study sites collected nasopharyngeal specimens for diagnostic detection, virus isolation, antigenic characterization, sequencing and antiviral susceptibility analysis from patients who fulfilled case definitions for influenza-like illness, acute lower respiratory infections and event-based surveillance. Each year in Cambodia, influenza viruses were detected mainly from June to November, during the rainy season. Antigenic analysis show that A/H1N1pdm09 isolates belonged to the A/California/7/2009-like group. Circulating A/H3N2 strains were A/Brisbane/10/2007-like in 2009 before drifting to A/Perth/16/2009-like in 2010 and 2011. The Cambodian influenza B isolates from 2009 to 2011 all belonged to the B/Victoria lineage represented by the vaccine strains B/Brisbane/60/2008 and B/Malaysia/2506/2004. Sequences of the M2 gene obtained from representative 2009–2011 A/H3N2 and A/H1N1pdm09 strains all contained the S31N mutation associated with adamantanes resistance except for one A/H1N1pdm09 strain isolated in 2011 that lacked this mutation. No reduction in the susceptibility to neuraminidase inhibitors was observed among the influenza viruses circulating from 2009 to 2011. Phylogenetic analysis revealed that A/H3N2 strains clustered each year to a distinct group while most A/H1N1pdm09 isolates belonged to the S203T clade. Conclusions/Significance In Cambodia, from 2009 to 2011, influenza activity occurred throughout the year with peak seasonality during the rainy season from June to November. Seasonal influenza epidemics were due to multiple genetically distinct viruses, even though all of the isolates were antigenically similar to the reference vaccine strains. The drug susceptibility profile of Cambodian influenza strains revealed that neuraminidase inhibitors would be the drug of choice for influenza treatment and chemoprophylaxis in Cambodia, as adamantanes are no longer expected to be effective.

H5N1 genetic structure

10.1371/journal.pone.0110713

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Citations (37)

Genetic variability of human metapneumovirus amongst an all ages population in Cambodia between 2007 and 2009

Infection Genetics and Evolution (2011)

Alicia Arnott Sirenda Vong Sek Mardy Monica Naughtin Julien Beauté

Metapneumovirus

10.1016/j.meegid.2011.01.016

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Citations (57)

Human bocavirus amongst an all‐ages population hospitalised with acute lower respiratory infections in Cambodia

Influenza and Other Respiratory Viruses (2012)

Alicia Arnott Sirenda Vong Sareth Rith Monica Naughtin Sowath Ly

Please cite this paper as: Arnott et al. (2013) Human bocavirus amongst an all‐ages population hospitalised with acute lower respiratory infections in Cambodia. Influenza and Other Respiratory Viruses 7(2) 201–210. Background Human bocavirus (HBoV) is a novel parvovirus that is associated with respiratory and gastrointestinal tract disease. Objectives To investigate the prevalence and genetic diversity of HBoV amongst hospitalized patients with acute lower respiratory infection (ALRI) in Cambodia. Study Design Samples were collected from 2773 patients of all ages hospitalised with symptoms of ALRI between 2007 and 2009. All samples were screened by multiplex RT‐PCR/PCR for 18 respiratory viruses. All samples positive for HBoV were sequenced and included in this study. Results Of the samples tested, 43 (1·5%) were positive for HBoV. The incidence of HBoV did not vary between the consecutive seasons investigated, and HBoV infections were detected year‐round. The incidence of HBoV infection was highest in patients aged <2 years, with pneumonia or bronchopneumonia the most common clinical diagnosis, regardless of age. A total of 19 patients (44%) were co‐infected with HBoV and an additional respiratory pathogen. All isolates were classified as HBoV type 1 (HBoV‐1). High conservation between Cambodian NP1 and V1V2 gene sequences was observed. Conclusions Human bocavirus infection can result in serious illness, however is frequently detected in the context of viral co‐infection. Specific studies are required to further understand the true pathogenesis of HBoV in the context of severe respiratory illness.

Human bocavirus

10.1111/j.1750-2659.2012.00369.x

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Citations (21)

Seroprevalence and Transmission of Human Influenza A(H5N1) Virus before and after Virus Reassortment, Cambodia, 2006–2014

Emerging infectious diseases (2017)

Sowath Ly Paul F. Horwood Malen Chan Sareth Rith Sopheak Sorn

Abstract Thirty-five human influenza A(H5N1) cases were reported in Cambodia during 2013–2014 after emergence of a clade 1.1.2 reassortant virus. We tested 881 villagers and found 2 cases of pauci- or asymptomatic infection. Seroprevalence after emergence of the reassortant strain (0.2%) was lower than the aggregate seroprevalence of 1.3% reported in earlier studies.

Seroprevalence

Reassortment

10.3201/eid2302.161232

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Citations (14)

Transmission experiments support clade-level differences in the transmission and pathogenicity of Cambodian influenza A/H5N1 viruses

Emerging Microbes & Infections (2020)

Paul F. Horwood Thomas Fabrizio Srey Viseth Horm Artem Metlin Sopheaktra Ros

Influenza A/H5N1 has circulated in Asia since 2003 and is now enzootic in many countries in that region. In Cambodia, the virus has circulated since 2004 and has intermittently infected humans. During this period, we have noted differences in the rate of infections in humans, potentially associated with the circulation of different viral clades. In particular, a reassortant clade 1.1.2 virus emerged in early 2013 and was associated with a dramatic increase in infections of humans (34 cases) until it was replaced by a clade 2.3.2.1c virus in early 2014. In contrast, only one infection of a human has been reported in the 6 years since the clade 2.3.2.1c virus became the dominant circulating virus. We selected three viruses to represent the main viral clades that have circulated in Cambodia (clade 1.1.2, clade 1.1.2 reassortant, and clade 2.3.2.1c), and we conducted experiments to assess the virulence and transmissibility of these viruses in avian (chicken, duck) and mammalian (ferret) models. Our results suggest that the clade 2.3.2.1c virus is more "avian-like," with high virulence in both ducks and chickens, but there is no evidence of aerosol transmission of the virus from ducks to ferrets. In contrast, the two clade 1 viruses were less virulent in experimentally infected and contact ducks. However, evidence of chicken-to-ferret aerosol transmission was observed for both clade 1 viruses. The transmission experiments provide insights into clade-level differences that might explain the variation in A/H5N1 infections of humans observed in Cambodia and other settings.

Enzootic

Viral evolution

Reassortment

10.1080/22221751.2020.1792353

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Citations (7)

Serologic evidence of human influenza virus infections in swine populations, Cambodia

Influenza and Other Respiratory Viruses (2012)

Sareth Rith Punnaporn Netrabukkana San Sorn Elizabeth Mumford Channa Mey

Background This study was conducted from 2006 to 2010 and investigated the seroprevalence of influenza A viruses in Cambodian pigs, including human H1N1, H3N2, 2009 pandemic H1N1 (A(H1N1)pdm09), and highly pathogenic avian H5N1 influenza A viruses. Methods A total of 1147 sera obtained from pigs in Cambodia were tested by haemagglutination inhibition (HI) assays for antibody to human influenza A viruses along with both HI and microneutralization (MN) tests to assess immunological responses to H5N1 virus. The results were compared by year, age, and province. Results Antibodies against a human influenza A virus were detected in 14·9% of samples. A(H1N1)pdm09 virus were dominant over the study period (23·1%), followed by those to human H1N1 (17·3%) and H3N2 subtypes (9·9%). No pigs were serologically positive for avian H5 influenza viruses. The seroprevalence of human H1N1 and H3N2 influenza viruses peaked in 2008, while that of A(H1N1)pdm09 reached a peak in 2010. No significant differences in seroprevalence to human influenza subtypes were observed in different age groups. Conclusions Cambodian pigs were exposed to human strains of influenza A viruses either prior to or during this study. The implications of these high prevalence rates imply human-to-swine influenza virus transmission in Cambodia. Although pigs are mostly raised in small non-commercial farms, our preliminary results provide evidence of sustained human influenza virus circulation in pig populations in Cambodia.

Seroprevalence

Pandemic

Human influenza

H5N1 genetic structure

10.1111/j.1750-2659.2012.00382.x

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Citations (18)

Identification of viruses in Acute Lower Respiratory Infections (ALRI) in Lao People's Democratic Republic

BMC Proceedings (2011)

Anne‐Charlotte Sentilhes Vimatha Xaysitthideth Sareth Rith Somvay Ongkhamme Thongchanh Sisouk

Results Between 2009 and 2010, Multiplex PCR / RT-PCR detected respiratory viruses in 111 (54.7%) of 203 samples. Single virus was detected in 44.8% (91/203) and virus co-infections were observed in 9.9% (20/203). Rhinovirus (40.5%), human Respiratory Syncytial virus (hRSV; 27.9%), and Influenza A virus (9.0%) were the most frequently detected viruses. Adenovirus and human Metapneumovirus were detected in 8.1% and 6.3% of ALRI specimen, respectively. Influenza C virus and SARS-coronavirus were not detected during the study period. Children < 5 years represented 50% of patients identified.

Identification

10.1186/1753-6561-5-s1-p74

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Citations (1)

Quantifying within-host diversity of H5N1 influenza viruses in humans and poultry in Cambodia

PLoS Pathogens (2020)

Louise H. Moncla Trevor Bedford Philippe Dussart Srey Viseth Horm Sareth Rith

Avian influenza viruses (AIVs) periodically cross species barriers and infect humans. The likelihood that an AIV will evolve mammalian transmissibility depends on acquiring and selecting mutations during spillover, but data from natural infection is limited. We analyze deep sequencing data from infected humans and domestic ducks in Cambodia to examine how H5N1 viruses evolve during spillover. Overall, viral populations in both species are predominated by low-frequency (<10%) variation shaped by purifying selection and genetic drift, and half of the variants detected within-host are never detected on the H5N1 virus phylogeny. However, we do detect a subset of mutations linked to human receptor binding and replication (PB2 E627K, HA A150V, and HA Q238L) that arose in multiple, independent humans. PB2 E627K and HA A150V were also enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adaptive. Our data show that H5N1 viruses generate putative human-adapting mutations during natural spillover infection, many of which are detected at >5% frequency within-host. However, short infection times, genetic drift, and purifying selection likely restrict their ability to evolve extensively during a single infection. Applying evolutionary methods to sequence data, we reveal a detailed view of H5N1 virus adaptive potential, and develop a foundation for studying host-adaptation in other zoonotic viruses.

Viral evolution

10.1371/journal.ppat.1008191

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Citations (28)

Aerosol exposure of live bird market workers to viable influenza A/H5N1 and A/H9N2 viruses, Cambodia

Zoonoses and Public Health (2022)

Paul F. Horwood Srey Viseth Horm Sokhoun Yann Songha Tok Malen Chan

Abstract Live bird markets (LBMs) have been identified as key factors in the spread, persistence and evolution of avian influenza viruses (AIVs). In addition, these settings have been associated with human infections with AIVs of pandemic concern. Exposure to aerosolised AIVs by workers in a Cambodian LBM was assessed using aerosol impact samplers. LBM vendors were asked to wear an air sampler for 30 min per day for 1 week while continuing their usual activities in the LBM during a period of high AIV circulation (February) and a period of low circulation (May). During the period of high circulation, AIV RNA was detected from 100% of the air samplers using molecular methods and viable AIV (A/H5N1 and/or A/H9N2) was isolated from 50% of air samplers following inoculation into embryonated chicken eggs. In contrast, AIV was not detected by molecular methods or successfully isolated during the period of low circulation. This study demonstrates the increased risk of aerosol exposure of LBM workers to AIVs during periods of high circulation and highlights the need for interventions during these high‐risk periods. Novel approaches, such as environmental sampling, should be further explored at key high‐risk interfaces as a potentially cost‐effective alternative for monitoring pandemic threats.

Embryonated

Pandemic

10.1111/zph.13009

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Citations (11)

1482Sentinel Surveillance of Respiratory Viral Pathogens in Border Areas of Western Cambodia

Open Forum Infectious Diseases (2014)

Ilin Chuang Ans Timmermans Melanie C. Melendrez Youry Se Samon Nou

Pathogenic organism

10.1093/ofid/ofu052.1028

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