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

Cooperative Institutions

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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Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011

Eurosurveillance (2014)

Nora Chea Shaoqiong Yi Sareth Rith Heng Seng Vannra Ieng

Binary file ES_Abstracts_Final_ECDC.txt matches

Christian ministry

Throat

10.2807/1560-7917.es2014.19.25.20839

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Citations (12)

A Study of the Genetic Variability of Human Respiratory Syncytial Virus (HRSV) in Cambodia Reveals the Existence of a New HRSV Group B Genotype

Journal of Clinical Microbiology (2011)

Alicia Arnott Sirenda Vong Sek Mardy Simon Chu Monica Naughtin

Human respiratory syncytial virus (HRSV) is the leading cause of hospitalization of children aged <5 years due to respiratory illness in industrialized countries, and pneumonia is the leading cause of mortality among children aged <5 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 diversity 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 <5 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.

Group A

10.1128/jcm.01131-11

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Citations (104)

Acute lower respiratory infections on lung sequelae in Cambodia, a neglected disease in highly tuberculosis-endemic country

Respiratory Medicine (2013)

Blandine Rammaert Sophie Goyet Arnaud Tarantola Sopheak Hem Sareth Rith

Endemic diseases

10.1016/j.rmed.2013.07.018

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Citations (6)

Acute lower respiratory infections in ≥5 year -old hospitalized patients in Cambodia, a low-income tropical country: clinical characteristics and pathogenic etiology

BMC Infectious Diseases (2013)

Sirenda Vong Bertrand Guillard Laurence Borand Blandine Rammaert Sophie Goyet

Few data exist on viral and bacterial etiology of acute lower respiratory infections (ALRI) in ≥5 year –old persons in the tropics. We conducted active surveillance of community-acquired ALRI in two hospitals in Cambodia, a low-income tropical country. Patients were tested for acid-fast bacilli (AFB) by direct sputum examination, other bacteria by blood and/or sputum cultures, and respiratory viruses using molecular techniques on nasopharyngeal/throat swabs. Pulmonologists reviewed clinical/laboratory data and interpreted chest X-rays (CXR) to confirm ALRI. Between April 2007 - December 2009, 1,904 patients aged ≥5 years were admitted with acute pneumonia (50.4%), lung sequelae-associated ALRI (24.3%), isolated pleural effusions (8.9%) or normal CXR-related ALRI (17.1%); 61 (3.2%) died during hospitalization. The two former diagnoses were predominantly due to bacterial etiologies while viral detection was more frequent in the two latter diagnoses. AFB-positive accounted for 25.6% of acute pneumonia. Of the positive cultures (16.8%), abscess-prone Gram-negative bacteria (39.6%) and Haemophilus influenzae (38.0%) were most frequent, followed by Streptococcus pneumoniae (17.7%). Of the identified viruses, the three most common viruses included rhinoviruses (49.5%), respiratory syncytial virus (17.7%) and influenza viruses (12.1%) regardless of the diagnostic groups. Wheezing was associated with viral identification (31.9% vs. 13.8%, p < 0.001) independent of age and time-to-admission. High frequency of H. influenzae and S. pneumoniae infections support the need for introduction of the respective vaccines in the national immunization program. Tuberculosis was frequent in patients with acute pneumonia, requiring further investigation. The relationship between respiratory viruses and wheezing merits further studies.

Medical microbiology

Etiology

Rhinovirus

10.1186/1471-2334-13-97

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Citations (32)

Environmental contamination and risk factors for transmission of highly pathogenic avian influenza A(H5N1) to humans, Cambodia, 2006-2010

BMC Infectious Diseases (2016)

Sowath Ly Sirenda Vong Philippe Cavailler Elizabeth Mumford Channa Mey

Highly pathogenic avian influenza A (H5N1) virus has been of public health concern since 2003. Probable risk factors for A(H5N1) transmission to human have been demonstrated in several studies or epidemiological reports. However, transmission patterns may differ according to demographic characteristics of the population and local practices. This article aggregates these data from three studies with data collected in the previous surveys in 2006 and 2007 to further examine the risks factors associated with presence of anti-A(H5) antibodies among villagers residing within outbreak areas. We aggregated 5-year data (2006–2010) from serology survey and matched case-control studies in Cambodia to further examine the risks factors associated with A(H5N1) infection among villagers in the outbreak areas. Serotesting among villagers detected 35 (1.5 % [0–2.6]) positive cases suggesting recent exposure to A(H5N1) virus. Practices associated with A(H5N1) infection among all ages were: having poultry cage or nesting area under or adjacent to the house (OR: 6.7 [1.6–28.3]; p = 0.010) and transporting poultry to market (OR: 17.6 [1.6–193.7]; p = 0.019). Practices found as risk factors for the infection among age under 20 years were swimming/bathing in ponds also accessed by domestic poultry (OR: 4.6 [1.1–19.1]; p = 0.038). Association with consuming wild birds reached borderline significance (p = 0.066). Our results suggest that swimming/bathing in contaminated pond water and close contact with poultry may present a risk of A(H5N1) transmission to human.

Bathing

Medical microbiology

10.1186/s12879-016-1950-z

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Citations (13)

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

bioRxiv (Cold Spring Harbor Laboratory) (2019)

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

Abstract 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. Author summary H5N1 avian influenza viruses can cross species barriers and cause severe disease in humans. H5N1 viruses currently cannot replicate and transmit efficiently among humans, but animal infection studies and modeling experiments have suggested that human adaptation may require only a few mutations. However, data from natural spillover infection has been limited, posing a challenge for risk assessment. Here, we analyze a unique dataset of deep sequence data from H5N1 virus-infected humans and domestic ducks in Cambodia. We find that well-known markers of human receptor binding and replication arise in multiple, independent humans. We also find that 3 mutations detected within-host are enriched along phylogenetic branches leading to human infections, suggesting that they are likely human-adapting. However, we also show that within-host evolution in both humans and ducks are shaped heavily by purifying selection and genetic drift, and that a large fraction of within-host variation is never detected on the H5N1 phylogeny. Taken together, our data show that H5N1 viruses do generate human-adapting mutations during natural infection. However, short infection times, purifying selection, and genetic drift may severely limit how much H5N1 viruses can evolve during the course of a single infection.

Viral evolution

Host adaptation

Natural reservoir

10.1101/683151

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Citations (1)

Identification of Molecular Markers Associated with Alteration of Receptor-Binding Specificity in a Novel Genotype of Highly Pathogenic Avian Influenza A(H5N1) Viruses Detected in Cambodia in 2013

Journal of Virology (2014)

Sareth Rith C. Todd Davis Veasna Duong Borann Sar Srey Viseth Horm

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 samples, suggested that the mutations occurred during human infection and did not transmit further.

Identification

Highly pathogenic

10.1128/jvi.01887-14

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Citations (39)

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

Figshare (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.

Highly pathogenic

10.6084/m9.figshare.12853610

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Citations (0)

Dynamic of H5N1 virus in Cambodia and emergence of a novel endemic sub-clade

Infection Genetics and Evolution (2012)

San Sorn Sok Touch Sovann Ly Sareth Rith Nguyen Tung

Lineage (genetic)

10.1016/j.meegid.2012.05.013

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Citations (26)

Genetic diversity of human rhinoviruses in Cambodia during a three-year period reveals novel genetic types