The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos
Identifieur interne : 002968 ( Istex/Corpus ); précédent : 002967; suivant : 002969The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos
Auteurs : Bounkong Syhavong ; Bouachanh Rasachack ; Lee Smythe ; Jean-Marc Rolain ; Anne-Marie Roque-Afonso ; Kemajittra Jenjaroen ; Vimone Soukkhaserm ; Simmaly Phongmany ; Rattanaphone Phetsouvanh ; Sune Soukkhaserm ; Te Thammavong ; Mayfong Mayxay ; Stuart D. Blacksell ; Eleanor Barnes ; Philippe Parola ; Elisabeth Dussaix ; Didier Raoult ; Isla Humphreys ; Paul Klenerman ; Nicholas J. White ; Paul N. NewtonSource :
- Transactions of The Royal Society of Tropical Medicine and Hygiene [ 0035-9203 ] ; 2010-07.
English descriptors
- KwdEn :
Abstract
There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (≥ × 3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis.
Url:
DOI: 10.1016/j.trstmh.2010.03.002
Links to Exploration step
ISTEX:DEC1F87054742B503CEF494BE7745DBFB1A60E95Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</title><author><name sortKey="Syhavong, Bounkong" sort="Syhavong, Bounkong" uniqKey="Syhavong B" first="Bounkong" last="Syhavong">Bounkong Syhavong</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Rasachack, Bouachanh" sort="Rasachack, Bouachanh" uniqKey="Rasachack B" first="Bouachanh" last="Rasachack">Bouachanh Rasachack</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Smythe, Lee" sort="Smythe, Lee" uniqKey="Smythe L" first="Lee" last="Smythe">Lee Smythe</name><affiliation><mods:affiliation>WHO/AO/OIE Collaborating Centre for Reference & Research on Leptospirosis, Queensland Health Forensic and Scientific Services, Coopers Plains, Queensland, 4108, Australia</mods:affiliation></affiliation></author><author><name sortKey="Rolain, Jean Marc" sort="Rolain, Jean Marc" uniqKey="Rolain J" first="Jean-Marc" last="Rolain">Jean-Marc Rolain</name><affiliation><mods:affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Roque Afonso, Anne Marie" sort="Roque Afonso, Anne Marie" uniqKey="Roque Afonso A" first="Anne-Marie" last="Roque-Afonso">Anne-Marie Roque-Afonso</name><affiliation><mods:affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</mods:affiliation></affiliation></author><author><name sortKey="Jenjaroen, Kemajittra" sort="Jenjaroen, Kemajittra" uniqKey="Jenjaroen K" first="Kemajittra" last="Jenjaroen">Kemajittra Jenjaroen</name><affiliation><mods:affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</mods:affiliation></affiliation></author><author><name sortKey="Soukkhaserm, Vimone" sort="Soukkhaserm, Vimone" uniqKey="Soukkhaserm V" first="Vimone" last="Soukkhaserm">Vimone Soukkhaserm</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Phongmany, Simmaly" sort="Phongmany, Simmaly" uniqKey="Phongmany S" first="Simmaly" last="Phongmany">Simmaly Phongmany</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Phetsouvanh, Rattanaphone" sort="Phetsouvanh, Rattanaphone" uniqKey="Phetsouvanh R" first="Rattanaphone" last="Phetsouvanh">Rattanaphone Phetsouvanh</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Soukkhaserm, Sune" sort="Soukkhaserm, Sune" uniqKey="Soukkhaserm S" first="Sune" last="Soukkhaserm">Sune Soukkhaserm</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Thammavong, Te" sort="Thammavong, Te" uniqKey="Thammavong T" first="Te" last="Thammavong">Te Thammavong</name><affiliation><mods:affiliation>National Blood Transfusion Centre, Lao Red Cross, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Mayxay, Mayfong" sort="Mayxay, Mayfong" uniqKey="Mayxay M" first="Mayfong" last="Mayxay">Mayfong Mayxay</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>Faculty of Post Graduate Studies, University of Health Sciences, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Blacksell, Stuart D" sort="Blacksell, Stuart D" uniqKey="Blacksell S" first="Stuart D." last="Blacksell">Stuart D. Blacksell</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Barnes, Eleanor" sort="Barnes, Eleanor" uniqKey="Barnes E" first="Eleanor" last="Barnes">Eleanor Barnes</name><affiliation><mods:affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Parola, Philippe" sort="Parola, Philippe" uniqKey="Parola P" first="Philippe" last="Parola">Philippe Parola</name><affiliation><mods:affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Dussaix, Elisabeth" sort="Dussaix, Elisabeth" uniqKey="Dussaix E" first="Elisabeth" last="Dussaix">Elisabeth Dussaix</name><affiliation><mods:affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</mods:affiliation></affiliation></author><author><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><affiliation><mods:affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Humphreys, Isla" sort="Humphreys, Isla" uniqKey="Humphreys I" first="Isla" last="Humphreys">Isla Humphreys</name><affiliation><mods:affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Klenerman, Paul" sort="Klenerman, Paul" uniqKey="Klenerman P" first="Paul" last="Klenerman">Paul Klenerman</name><affiliation><mods:affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="White, Nicholas J" sort="White, Nicholas J" uniqKey="White N" first="Nicholas J." last="White">Nicholas J. White</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Newton, Paul N" sort="Newton, Paul N" uniqKey="Newton P" first="Paul N." last="Newton">Paul N. Newton</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: paul@tropmedres.ac</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel.: +856 21 242168; fax: +856 21 242168. E-mail address: paul@tropmedres.ac</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: paul@tropmedres.ac</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:DEC1F87054742B503CEF494BE7745DBFB1A60E95</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1016/j.trstmh.2010.03.002</idno><idno type="url">https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">002968</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002968</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</title><author><name sortKey="Syhavong, Bounkong" sort="Syhavong, Bounkong" uniqKey="Syhavong B" first="Bounkong" last="Syhavong">Bounkong Syhavong</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Rasachack, Bouachanh" sort="Rasachack, Bouachanh" uniqKey="Rasachack B" first="Bouachanh" last="Rasachack">Bouachanh Rasachack</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Smythe, Lee" sort="Smythe, Lee" uniqKey="Smythe L" first="Lee" last="Smythe">Lee Smythe</name><affiliation><mods:affiliation>WHO/AO/OIE Collaborating Centre for Reference & Research on Leptospirosis, Queensland Health Forensic and Scientific Services, Coopers Plains, Queensland, 4108, Australia</mods:affiliation></affiliation></author><author><name sortKey="Rolain, Jean Marc" sort="Rolain, Jean Marc" uniqKey="Rolain J" first="Jean-Marc" last="Rolain">Jean-Marc Rolain</name><affiliation><mods:affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Roque Afonso, Anne Marie" sort="Roque Afonso, Anne Marie" uniqKey="Roque Afonso A" first="Anne-Marie" last="Roque-Afonso">Anne-Marie Roque-Afonso</name><affiliation><mods:affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</mods:affiliation></affiliation></author><author><name sortKey="Jenjaroen, Kemajittra" sort="Jenjaroen, Kemajittra" uniqKey="Jenjaroen K" first="Kemajittra" last="Jenjaroen">Kemajittra Jenjaroen</name><affiliation><mods:affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</mods:affiliation></affiliation></author><author><name sortKey="Soukkhaserm, Vimone" sort="Soukkhaserm, Vimone" uniqKey="Soukkhaserm V" first="Vimone" last="Soukkhaserm">Vimone Soukkhaserm</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Phongmany, Simmaly" sort="Phongmany, Simmaly" uniqKey="Phongmany S" first="Simmaly" last="Phongmany">Simmaly Phongmany</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Phetsouvanh, Rattanaphone" sort="Phetsouvanh, Rattanaphone" uniqKey="Phetsouvanh R" first="Rattanaphone" last="Phetsouvanh">Rattanaphone Phetsouvanh</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Soukkhaserm, Sune" sort="Soukkhaserm, Sune" uniqKey="Soukkhaserm S" first="Sune" last="Soukkhaserm">Sune Soukkhaserm</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Thammavong, Te" sort="Thammavong, Te" uniqKey="Thammavong T" first="Te" last="Thammavong">Te Thammavong</name><affiliation><mods:affiliation>National Blood Transfusion Centre, Lao Red Cross, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Mayxay, Mayfong" sort="Mayxay, Mayfong" uniqKey="Mayxay M" first="Mayfong" last="Mayxay">Mayfong Mayxay</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>Faculty of Post Graduate Studies, University of Health Sciences, Vientiane, Lao PDR</mods:affiliation></affiliation></author><author><name sortKey="Blacksell, Stuart D" sort="Blacksell, Stuart D" uniqKey="Blacksell S" first="Stuart D." last="Blacksell">Stuart D. Blacksell</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Barnes, Eleanor" sort="Barnes, Eleanor" uniqKey="Barnes E" first="Eleanor" last="Barnes">Eleanor Barnes</name><affiliation><mods:affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Parola, Philippe" sort="Parola, Philippe" uniqKey="Parola P" first="Philippe" last="Parola">Philippe Parola</name><affiliation><mods:affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Dussaix, Elisabeth" sort="Dussaix, Elisabeth" uniqKey="Dussaix E" first="Elisabeth" last="Dussaix">Elisabeth Dussaix</name><affiliation><mods:affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</mods:affiliation></affiliation></author><author><name sortKey="Raoult, Didier" sort="Raoult, Didier" uniqKey="Raoult D" first="Didier" last="Raoult">Didier Raoult</name><affiliation><mods:affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</mods:affiliation></affiliation></author><author><name sortKey="Humphreys, Isla" sort="Humphreys, Isla" uniqKey="Humphreys I" first="Isla" last="Humphreys">Isla Humphreys</name><affiliation><mods:affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Klenerman, Paul" sort="Klenerman, Paul" uniqKey="Klenerman P" first="Paul" last="Klenerman">Paul Klenerman</name><affiliation><mods:affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="White, Nicholas J" sort="White, Nicholas J" uniqKey="White N" first="Nicholas J." last="White">Nicholas J. White</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation></author><author><name sortKey="Newton, Paul N" sort="Newton, Paul N" uniqKey="Newton P" first="Paul N." last="Newton">Paul N. Newton</name><affiliation><mods:affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</mods:affiliation></affiliation><affiliation><mods:affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: paul@tropmedres.ac</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel.: +856 21 242168; fax: +856 21 242168. E-mail address: paul@tropmedres.ac</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: paul@tropmedres.ac</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Transactions of The Royal Society of Tropical Medicine and Hygiene</title><title level="j" type="abbrev">Trans R Soc Trop Med Hyg</title><idno type="ISSN">0035-9203</idno><idno type="eISSN">1878-3503</idno><imprint><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><date type="published" when="2010-07">2010-07</date><biblScope unit="volume">104</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="475">475</biblScope><biblScope unit="page" to="483">483</biblScope></imprint><idno type="ISSN">0035-9203</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0035-9203</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Hepatitis E virus</term><term>Jaundice</term><term>Laos</term><term>Leptospirosis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract">There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (≥ × 3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis.</div></front></TEI><istex><corpusName>oup</corpusName><author><json:item><name>Bounkong Syhavong</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string></affiliations></json:item><json:item><name>Bouachanh Rasachack</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string></affiliations></json:item><json:item><name>Lee Smythe</name><affiliations><json:string>WHO/AO/OIE Collaborating Centre for Reference & Research on Leptospirosis, Queensland Health Forensic and Scientific Services, Coopers Plains, Queensland, 4108, Australia</json:string></affiliations></json:item><json:item><name>Jean-Marc Rolain</name><affiliations><json:string>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</json:string></affiliations></json:item><json:item><name>Anne-Marie Roque-Afonso</name><affiliations><json:string>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</json:string></affiliations></json:item><json:item><name>Kemajittra Jenjaroen</name><affiliations><json:string>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</json:string></affiliations></json:item><json:item><name>Vimone Soukkhaserm</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string></affiliations></json:item><json:item><name>Simmaly Phongmany</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string></affiliations></json:item><json:item><name>Rattanaphone Phetsouvanh</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string><json:string>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</json:string></affiliations></json:item><json:item><name>Sune Soukkhaserm</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string></affiliations></json:item><json:item><name>Te Thammavong</name><affiliations><json:string>National Blood Transfusion Centre, Lao Red Cross, Vientiane, Lao PDR</json:string></affiliations></json:item><json:item><name>Mayfong Mayxay</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string><json:string>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</json:string><json:string>Faculty of Post Graduate Studies, University of Health Sciences, Vientiane, Lao PDR</json:string></affiliations></json:item><json:item><name>Stuart D. Blacksell</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string><json:string>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</json:string><json:string>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</json:string></affiliations></json:item><json:item><name>Eleanor Barnes</name><affiliations><json:string>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</json:string></affiliations></json:item><json:item><name>Philippe Parola</name><affiliations><json:string>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</json:string></affiliations></json:item><json:item><name>Elisabeth Dussaix</name><affiliations><json:string>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</json:string></affiliations></json:item><json:item><name>Didier Raoult</name><affiliations><json:string>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</json:string></affiliations></json:item><json:item><name>Isla Humphreys</name><affiliations><json:string>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</json:string></affiliations></json:item><json:item><name>Paul Klenerman</name><affiliations><json:string>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</json:string></affiliations></json:item><json:item><name>Nicholas J. White</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string><json:string>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</json:string><json:string>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</json:string></affiliations></json:item><json:item><name>Paul N. Newton</name><affiliations><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</json:string><json:string>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</json:string><json:string>E-mail: paul@tropmedres.ac</json:string><json:string>Corresponding author. Tel.: +856 21 242168; fax: +856 21 242168. E-mail address: paul@tropmedres.ac</json:string><json:string>E-mail: paul@tropmedres.ac</json:string></affiliations></json:item></author><subject><json:item><value>Jaundice</value></json:item><json:item><value>Hepatitis E virus</value></json:item><json:item><value>Leptospirosis</value></json:item><json:item><value>Laos</value></json:item></subject><arkIstex>ark:/67375/HXZ-3P65FQLM-4</arkIstex><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (≥ × 3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis.</abstract><qualityIndicators><score>9.124</score><pdfWordCount>5086</pdfWordCount><pdfCharCount>32065</pdfCharCount><pdfVersion>1.4</pdfVersion><pdfPageCount>9</pdfPageCount><pdfPageSize>544.3 x 742.7 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>177</abstractWordCount><abstractCharCount>1252</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</title><pmid><json:string>20378138</json:string></pmid><genre><json:string>research-article</json:string></genre><host><title>Transactions of The Royal Society of Tropical Medicine and Hygiene</title><language><json:string>unknown</json:string></language><issn><json:string>0035-9203</json:string></issn><eissn><json:string>1878-3503</json:string></eissn><publisherId><json:string>trstmh</json:string></publisherId><volume>104</volume><issue>7</issue><pages><first>475</first><last>483</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>the 21st Century</json:string><json:string>2001</json:string><json:string>1999</json:string><json:string>1210</json:string><json:string>2010</json:string><json:string>2004</json:string></date><geogName></geogName><orgName><json:string>Stata Corp.</json:string><json:string>Pathogen Research, University of Oxford, Oxford, UK</json:string><json:string>Ethical Review Committee of the Faculty of Medical Sciences, National University of Laos, Vientiane, Lao PDR</json:string><json:string>National Blood Transfusion Centre, Lao Red Cross, Vientiane, Lao PDR</json:string><json:string>University of Oxford</json:string><json:string>Panama, Shermani</json:string><json:string>Mahidol University</json:string><json:string>Elsevier Ltd.</json:string><json:string>University of Health Sciences</json:string><json:string>Mahosot Hospital, Vientiane</json:string><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration</json:string><json:string>Churchill Hospital, Oxford, UK</json:string><json:string>Biomedical Research Centre Programme</json:string><json:string>Mahosot Hospital, Vientiane, Laos</json:string><json:string>Curative Department, Ministry of Health, Professor Sommone Phounsavath</json:string><json:string>Serology and Microbiology Laboratories</json:string><json:string>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR WHO/AO/OIE Collaborating Centre for Reference</json:string><json:string>Thailand, HCV</json:string><json:string>Abbott Laboratories</json:string><json:string>Laos/Thai</json:string><json:string>Research on Leptospirosis, Queensland, Australia</json:string><json:string>Research on Leptospirosis, Queensland Health Forensic</json:string><json:string>National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif</json:string><json:string>Wellcome Trust of Great Britain</json:string></orgName><orgName_funder><json:string>Wellcome Trust of Great Britain</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Ponmek Dalaloy</json:string><json:string>P.J. Day</json:string><json:string>Walter Reed</json:string><json:string>P.N. Newton</json:string><json:string>Sue Lee</json:string><json:string>Bertrand Martinez-Aussel</json:string><json:string>Michel Strobel</json:string><json:string>C. Sera</json:string><json:string>Dr Khin</json:string><json:string>Keith Feldon</json:string><json:string>Michael Dohnt</json:string><json:string>Martin School</json:string><json:string>Elisabeth Dussaix</json:string></persName><placeName><json:string>TX</json:string><json:string>College Station</json:string><json:string>Switzerland</json:string><json:string>Vietnam</json:string><json:string>Thailand</json:string><json:string>Australia</json:string><json:string>Bangkok</json:string><json:string>Vientiane City</json:string><json:string>Laos</json:string><json:string>USA</json:string><json:string>Japan</json:string><json:string>Kawasaki</json:string><json:string>Basel</json:string><json:string>Vientiane</json:string><json:string>France</json:string><json:string>Marseille</json:string></placeName><ref_url><json:string>http://www.elsevier.com/locate/trstmh</json:string></ref_url><ref_bibl><json:string>Bounlu et al.</json:string><json:string>B. Syhavong et al.</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/HXZ-3P65FQLM-4</json:string></ark><categories><wos><json:string>social science</json:string><json:string>public, environmental & occupational health</json:string><json:string>science</json:string><json:string>tropical medicine</json:string></wos><scienceMetrix><json:string>health sciences</json:string><json:string>clinical medicine</json:string><json:string>tropical medicine</json:string></scienceMetrix><scopus><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Infectious Diseases</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Public Health, Environmental and Occupational Health</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - General Medicine</json:string><json:string>1 - Life Sciences</json:string><json:string>2 - Immunology and Microbiology</json:string><json:string>3 - Parasitology</json:string></scopus></categories><publicationDate>2010</publicationDate><copyrightDate>2010</copyrightDate><doi><json:string>10.1016/j.trstmh.2010.03.002</json:string></doi><id>DEC1F87054742B503CEF494BE7745DBFB1A60E95</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://publisher-list.data.istex.fr">Royal Society of Tropical Medicine and Hygiene</publisher><availability><licence><p>oup</p></licence></availability><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M"></p><date>2010</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</title><author xml:id="author-0000"><persName><forename type="first">Bounkong</forename><surname>Syhavong</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Bouachanh</forename><surname>Rasachack</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Lee</forename><surname>Smythe</surname></persName><affiliation>WHO/AO/OIE Collaborating Centre for Reference & Research on Leptospirosis, Queensland Health Forensic and Scientific Services, Coopers Plains, Queensland, 4108, Australia</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Jean-Marc</forename><surname>Rolain</surname></persName><affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Anne-Marie</forename><surname>Roque-Afonso</surname></persName><affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Kemajittra</forename><surname>Jenjaroen</surname></persName><affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Vimone</forename><surname>Soukkhaserm</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Simmaly</forename><surname>Phongmany</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Rattanaphone</forename><surname>Phetsouvanh</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation></author><author xml:id="author-0009"><persName><forename type="first">Sune</forename><surname>Soukkhaserm</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation></author><author xml:id="author-0010"><persName><forename type="first">Te</forename><surname>Thammavong</surname></persName><affiliation>National Blood Transfusion Centre, Lao Red Cross, Vientiane, Lao PDR</affiliation></author><author xml:id="author-0011"><persName><forename type="first">Mayfong</forename><surname>Mayxay</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation><affiliation>Faculty of Post Graduate Studies, University of Health Sciences, Vientiane, Lao PDR</affiliation></author><author xml:id="author-0012"><persName><forename type="first">Stuart D.</forename><surname>Blacksell</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation></author><author xml:id="author-0013"><persName><forename type="first">Eleanor</forename><surname>Barnes</surname></persName><affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</affiliation></author><author xml:id="author-0014"><persName><forename type="first">Philippe</forename><surname>Parola</surname></persName><affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</affiliation></author><author xml:id="author-0015"><persName><forename type="first">Elisabeth</forename><surname>Dussaix</surname></persName><affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</affiliation></author><author xml:id="author-0016"><persName><forename type="first">Didier</forename><surname>Raoult</surname></persName><affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</affiliation></author><author xml:id="author-0017"><persName><forename type="first">Isla</forename><surname>Humphreys</surname></persName><affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</affiliation></author><author xml:id="author-0018"><persName><forename type="first">Paul</forename><surname>Klenerman</surname></persName><affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</affiliation></author><author xml:id="author-0019"><persName><forename type="first">Nicholas J.</forename><surname>White</surname></persName><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation></author><author xml:id="author-0020" corresp="yes"><persName><forename type="first">Paul N.</forename><surname>Newton</surname></persName><email>paul@tropmedres.ac</email><email>paul@tropmedres.ac</email><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation><affiliation>Corresponding author. Tel.: +856 21 242168; fax: +856 21 242168. E-mail address: paul@tropmedres.ac</affiliation></author><idno type="istex">DEC1F87054742B503CEF494BE7745DBFB1A60E95</idno><idno type="ark">ark:/67375/HXZ-3P65FQLM-4</idno><idno type="DOI">10.1016/j.trstmh.2010.03.002</idno></analytic><monogr><title level="j">Transactions of The Royal Society of Tropical Medicine and Hygiene</title><title level="j" type="abbrev">Trans R Soc Trop Med Hyg</title><idno type="pISSN">0035-9203</idno><idno type="eISSN">1878-3503</idno><idno type="publisher-id">trstmh</idno><idno type="PublisherID-hwp">trstmh</idno><imprint><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><date type="published" when="2010-07"></date><biblScope unit="volume">104</biblScope><biblScope unit="issue">7</biblScope><biblScope unit="page" from="475">475</biblScope><biblScope unit="page" to="483">483</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2010</date></creation><abstract><p>There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (≥ × 3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Jaundice</term></item><item><term>Hepatitis E virus</term></item><item><term>Leptospirosis</term></item><item><term>Laos</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2010-07">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup, element #text not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0"</istex:xmlDeclaration><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article">
<front>
<journal-meta>
<journal-id journal-id-type="hwp">trstmh</journal-id>
<journal-id journal-id-type="publisher-id">trstmh</journal-id>
<journal-title>Transactions of The Royal Society of Tropical Medicine and Hygiene</journal-title>
<abbrev-journal-title>Trans R Soc Trop Med Hyg</abbrev-journal-title>
<issn pub-type="ppub">0035-9203</issn>
<issn pub-type="epub">1878-3503</issn>
<publisher>
<publisher-name>Royal Society of Tropical Medicine and Hygiene</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1016/j.trstmh.2010.03.002</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Articles</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Syhavong</surname><given-names>Bounkong</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Rasachack</surname><given-names>Bouachanh</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Smythe</surname><given-names>Lee</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Rolain</surname><given-names>Jean-Marc</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Roque-Afonso</surname><given-names>Anne-Marie</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Jenjaroen</surname><given-names>Kemajittra</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Soukkhaserm</surname><given-names>Vimone</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Phongmany</surname><given-names>Simmaly</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Phetsouvanh</surname><given-names>Rattanaphone</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Soukkhaserm</surname><given-names>Sune</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Thammavong</surname><given-names>Te</given-names></name><xref ref-type="aff" rid="aff7"><sup>g</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Mayxay</surname><given-names>Mayfong</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref><xref ref-type="aff" rid="aff8"><sup>h</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Blacksell</surname><given-names>Stuart D.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Barnes</surname><given-names>Eleanor</given-names></name><xref ref-type="aff" rid="aff9"><sup>i</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Parola</surname><given-names>Philippe</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Dussaix</surname><given-names>Elisabeth</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Raoult</surname><given-names>Didier</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Humphreys</surname><given-names>Isla</given-names></name><xref ref-type="aff" rid="aff9"><sup>i</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Klenerman</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff9"><sup>i</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>White</surname><given-names>Nicholas J.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff5"><sup>e</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Newton</surname><given-names>Paul N.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff6"><sup>f</sup></xref><xref ref-type="corresp" rid="cor1"><sup>⁎</sup></xref>
</contrib>
<aff id="aff1">
<label>a</label>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</aff>
<aff id="aff2">
<label>b</label>WHO/AO/OIE Collaborating Centre for Reference & Research on Leptospirosis, Queensland Health Forensic and Scientific Services, Coopers Plains, Queensland, 4108, Australia</aff>
<aff id="aff3">
<label>c</label>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</aff>
<aff id="aff4">
<label>d</label>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</aff>
<aff id="aff5">
<label>e</label>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</aff>
<aff id="aff6">
<label>f</label>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</aff>
<aff id="aff7">
<label>g</label>National Blood Transfusion Centre, Lao Red Cross, Vientiane, Lao PDR</aff>
<aff id="aff8">
<label>h</label>Faculty of Post Graduate Studies, University of Health Sciences, Vientiane, Lao PDR</aff>
<aff id="aff9">
<label>i</label>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">
<label>⁎</label>Corresponding author. Tel.: +856 21 242168; fax: +856 21 242168. <italic>E-mail address:</italic> <email>paul@tropmedres.ac</email> (P.N. Newton).</corresp>
</author-notes>
<pub-date pub-type="ppub">
<month>7</month>
<year>2010</year>
</pub-date>
<volume>104</volume>
<issue>7</issue>
<fpage>475</fpage>
<lpage>483</lpage>
<history>
<date date-type="received">
<day>12</day>
<month>7</month>
<year>2009</year></date>
<date date-type="rev-recd">
<day>4</day>
<month>3</month>
<year>2010</year></date>
<date date-type="accepted">
<day>5</day>
<month>3</month>
<year>2010</year></date>
</history>
<permissions>
<copyright-year>2010</copyright-year>
<copyright-holder>Royal Society of Tropical Medicine and Hygiene</copyright-holder>
</permissions>
<abstract>
<title>Summary</title>
<p>There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (≥ × 3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis.</p>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Jaundice</kwd>
<kwd>Hepatitis E virus</kwd>
<kwd><italic>Orientia tsutsugamushi</italic></kwd>
<kwd><italic>Rickettsia typhi</italic></kwd>
<kwd>Leptospirosis</kwd>
<kwd>Laos</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>Patients with biochemical liver impairment and an infective aetiology are commonly admitted to hospital in the tropics with a multitude of causes that may be difficult to distinguish. In Southeast Asia the aetiology includes pathogens such as hepatitis A, B, C and E, dengue, leptospirosis, typhus and those causing septicaemia.<sup><xref ref-type="bibr" rid="bib1">1</xref>,<xref ref-type="bibr" rid="bib2">2</xref></sup> Recent work in Vientiane, Lao PDR (Laos), has emphasised the importance of <italic>Salmonella enterica</italic> serovar typhi, scrub typhus (<italic>Orientia tsutsugamushi</italic>) and murine typhus (<italic>Rickettsia typhi</italic>) as causes of fever.<sup><xref ref-type="bibr" rid="bib3">3</xref>,<xref ref-type="bibr" rid="bib4">4</xref></sup> A study of the aetiology of jaundice and dark urine among 280 patients admitted to Vientiane hospitals gave evidence of acute hepatitis A virus (HAV) and B virus (HBV) infection in 14% and 10% of cases, respectively.<xref ref-type="bibr" rid="bib1"><sup>1</sup></xref> Among Vientiane blood donors the prevalences of hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) antibody were 8.7% and 1.1%, respectively.<xref ref-type="bibr" rid="bib5"><sup>5</sup></xref></p>
<p>Whilst investigating the causes of fever among hospitalized patients in Vientiane a substantial proportion were jaundiced or had raised transaminases. Most studies of the causes of jaundice or hepatitis have concentrated on a narrow range of pathogens, for example the hepatitis viruses, in one population and not cast the diagnostic net broad to include viruses, rickettsia, leptospires and conventionally culturable bacteria. We therefore investigated the aetiology amongst inpatients to try to capture the diversity of organisms responsible. As serological tests may not be sufficiently specific in populations with multiple potential etiologies because of the persistence of antibody, we endeavored to determine the aetiology using specific tests based on rises in antibody titre between acute and convalescent samples and antigen and PCR assays.</p>
</sec>
<sec sec-type="subjects|methods">
<label>2</label>
<title>Patients and methods</title>
<sec>
<label>2.1</label>
<title>Study site and patients</title>
<p>The study was conducted at Mahosot Hospital, Vientiane, a 400-bed primary-tertiary hospital with approximately 1200 admissions/month. This, along with four other major hospitals of 1210 beds, and local hospitals, serves a population of approximately 900 000 people, including the urban population of Vientiane City and surrounding farming communities of Vientiane Province, and, less frequently, outlying provinces.</p>
<p>Patients of any age admitted to Mahosot Hospital with acute jaundice or elevated AST or ALT (by ≥3 times the upper limit of the reference range) who gave informed verbal consent were recruited (May 2001–May 2004) on eight adult and paediatric wards (192 beds). Blood samples were taken for admission and convalescent sera and, if community-acquired septicaemia was suspected, for a pair of blood cultures.<xref ref-type="bibr" rid="bib3"><sup>3</sup></xref> If the patient came from an area of Laos with endemic malaria, Giemsa-stained malaria thick and thin films were examined.</p>
</sec>
<sec>
<label>2.2</label>
<title>Laboratory procedures</title>
<p>Blood cultures were processed<xref ref-type="bibr" rid="bib3"><sup>3</sup></xref> and full blood counts (<italic>n</italic> = 252) and serum biochemistry (<italic>n</italic> = 375) determined on Abx MICROS<italic>OT</italic> (Abx Hematologie) and Cobas Integra (Roche, Basel, Switzerland) analyzers, respectively. In order to provide a clinical service, all sera were tested with Vidas immunoassay tests for anti-HAV IgM immunoglobulin (bioMérieux, Marcy l’Etoile, France), HBsAg, anti-HBsAg (Serodia-HBs, Serodia-Anti-HBs; Fujirebio, Japan) and HCV antibody tests (Serodia-HCV; Fujirebio, Japan). Serum samples were stored at −80 °C. Sera from a subset of 51 patients with anti-HAV IgM were analysed by anti-HAV IgG avidity assays and HAV PCR.<sup><xref ref-type="bibr" rid="bib6">6</xref>,<xref ref-type="bibr" rid="bib7">7</xref></sup> The AFRIMS ELISA was used to detect IgM and total antibody (Ig) to HEV.<sup><xref ref-type="bibr" rid="bib8">8</xref>,<xref ref-type="bibr" rid="bib9">9</xref></sup> Acute HEV infection was defined as anti-HEV IgM≥100 Walter Reed (WR) U/ml or anti-HEV Ig ≥500 WR U/ml. Sera from all patients with definite or probable acute HEV were tested by HEV PCR.<xref ref-type="bibr" rid="bib10"><sup>10</sup></xref> Patients positive for HBsAg or anti-HBsAg were tested using the Murex Anti-HB IgM ELISA kit (Abbott Laboratories, Abbott Park, IO, USA) for IgM anti-core antigen (HBcAb). Samples from patients with HCV antibodies were tested by HCV RNA 5′UTR PCR using the Superscript II RT (Invitrogen) and viruses genotyped.<xref ref-type="bibr" rid="bib11"><sup>11</sup></xref> Micro-immunofluorescence (IFA) assays for <italic>Orientia</italic>, <italic>Rickettsia</italic>, <italic>Coxiella</italic> species and <italic>Neorickettsia sennetsu</italic> (<xref ref-type="fig" rid="tbl1">Table 1</xref>
<fig id="tbl1">
<label>Table 1</label>
<caption>
<p>Serology, antigen and gene detection markers of acute jaundice/hepatitis among 392 Lao patients at Mahosot Hospital 2001–2004</p>
</caption>
<graphic mimetype="image" xlink:href="104-7-475-tbl001.tif"></graphic>
</fig>) were considered positive if (1) positive antibody titers were > 1/128 for IgG and > 1/64 for IgM, or (2) seroconversion, or (3) four-fold or greater increase in titers between the acute and the convalescent serum.<sup><xref ref-type="bibr" rid="bib4">4</xref>,<xref ref-type="bibr" rid="bib12">12</xref></sup> In microscopic agglutination tests (MAT) for <italic>Leptospira</italic> antibodies, a patient was considered to have a current or recent <italic>Leptospira</italic> infection if serum showed a titer of ≥1:400, or if paired sera demonstrated a four-fold rise (<xref ref-type="fig" rid="tbl1">Table 1</xref>).<xref ref-type="bibr" rid="bib13"><sup>13</sup></xref> Serum anti-dengue IgM/IgG antibodies and dengue NS1 antigen were assayed using ELISA kits (IgM/IgG Duo, Early Dengue, PanBio, Australia) for 189 patients without a confirmed diagnosis.</p>
</sec>
<sec>
<label>2.3</label>
<title>Statistical analysis</title>
<p>Analysis was performed using STATA v.10 (Stata Corp., College Station, TX, USA). Categorical variables were compared with Fisher's exact test and continuous variables by Student's <italic>t</italic>-test and Mann-Whitney <italic>U</italic> test as appropriate. Multiple logistic regression was used to identify predictor variable effects. A <italic>P</italic> value <0.02 was regarded as statistically significant.</p>
</sec>
</sec>
<sec sec-type="results">
<label>3</label>
<title>Results</title>
<sec>
<label>3.1</label>
<title>Patients</title>
<p>During the three years of the study 403 patients were recruited; 11 were included in error (without jaundice or transaminases three times the reference upper range). Patients came predominantly from Vientiane City (69.4%) and Vientiane Province (16.3%). The most frequent occupations (<italic>n</italic> = 391) recorded were housewife (16.9%), unemployed (16.1%), student (15.9%), government official (15.6%), building worker (14.3%) and rice farmer (8.7%). Three hundred and seven (78.3%) patients had a history of fever in the previous week or fever (≥37.5 °C) recorded on admission. Jaundice, or a history of jaundice in the presenting illness, were present in 334/390 (85.6%) and 199/385 (52%) had AST and/or ALT three times or above the upper limit of the local reference range (<37 IU/l and < 40 IU/l, respectively). Jaundice and transaminases raised at least threefold were both present in 174/385 (45.2%) of patients. A convalescent serum was taken from 204 (52%) patients a median (range) of 6 (1–43) days after the admission sample.</p>
<p>The serological, antigen-detection based and PCR-based assays of samples from 392 patients suggested, conservatively, the following diagnoses (<xref ref-type="fig" rid="tbl1">Table 1</xref>): hepatitis B 19/389 (4.9%, IgM HBcAb positive among those HBsAg or anti-HBsAg positive), hepatitis C 19/389 (4.9%. HCV PCR and anti-HCV positive), dengue 33/189 (17.5% or 8.4% of all 392 patients) (NS1 antigen positive and/or anti-dengue IgM/IgG positive), rickettsioses 28/382 (7.3%) (IgM/IgG positive), leptospirosis 26/385 (6.8%) (MAT positive), hepatitis E 6/378 (1.6%. HEV IgM or Ig positive and/or PCR positive), and 13/166 (7.8% or 3.3% of all 392 patients) with community-acquired septicaemia. Dengue, rickettsial infections, leptopirosis and HAV tended to be more common in the monsoon and post-monsoon months whilst septicaemia, HBV and HCV occurred throughout the year.</p>
<p>Anti-HAV IgM was positive in 136 (35.8%) patients but the age distribution (<xref ref-type="fig" rid="fig1">Figure 1</xref>
<fig id="fig1" position="float">
<label>Figure 1</label>
<caption>
<p>(A) Number of patients recruited per age category and percent age distribution of patients with anti-HAV IgM antibodies; (B) percent age distribution of patients with anti-HBV core IgM antibodies; (C) percent age distribution of patients HCV PCR positive; (D) percent age distribution of patients anti-leptospire MAT positive; (E) percent age distribution of patients dengue positive (IgM, IgG and/or NS1).</p>
</caption>
<graphic mimetype="image" xlink:href="104-7-475-fig001.jpg"></graphic>
</fig>) indicated a surprisingly high proportion of older positive patients — 35% of those positive were ≥40 years old. Given the prior probability of high rates of exposure and childhood infection, IgG anti-HAV avidity assays were performed on sera from 51 anti-HAV IgM positive patients; 42 (82%) patients had IgG anti-HAV avidity >70%, suggesting polyclonal activation and not acute HAV.<sup><xref ref-type="bibr" rid="bib6">6</xref>,<xref ref-type="bibr" rid="bib7">7</xref></sup> Of the 10 patients with low IgG avidity 8 were HAV PCR positive, whilst none of those with avidity index >70% (42 patients) were HAV PCR positive. The HAV in all eight PCR positive patients was genotype 1A.</p>
<p>Using conservative definitions of disease and excluding HAV, 130/392 (33.2%) of patients had an aetiological diagnosis. Serology gave evidence for murine typhus in 14/382 (3.7%), scrub typhus in 8/382 (2.1%) and spotted fever group in 6/382 (1.6%) patients. Those with community-acquired septicaemia grew <italic>S</italic>. Typhi in five (1.6%), <italic>E. coli</italic> in five (1.6%), <italic>Staphylococcus aureus</italic> in two (0.6%) and <italic>Burkholderia pseudomallei</italic> in one (0.3%). Blood smears from the 68 patients originating from malaria endemic areas were all negative for <italic>Plasmodium</italic> spp. Four patients had evidence of previous infection with <italic>C. burnetti</italic> but no evidence was found for acute or chronic Q fever infection. No evidence for acute <italic>N. sennetsu</italic> was found.</p>
<p>Using the conservative criteria for diagnosis of mixed infections, 44 (11.2%) patients had evidence of mixed infections but the majority (61%) were HAV IgM positive (see Discussion). Of 136 patients with anti-HAV IgM, 20% had other diagnoses (<xref ref-type="fig" rid="tbl2">Table 2</xref>
<fig id="tbl2">
<label>Table 2</label>
<caption>
<p>Evidence for dual positivity among serology, antigen and gene detection markers of acute jaundice/hepatitis among 392 Lao patients at Mahosot Hospital, 2001–2004. SFG = spotted fever group.</p>
</caption>
<graphic mimetype="image" xlink:href="104-7-475-tbl002.tif"></graphic>
</fig>). The remaining apparent mixed infections were mostly between leptospirosis/typhus and dengue/typhus.</p>
<p>Past HBV infection was inferred in 61/388 (15.7%) patients by the presence of anti-HBsAg antibodies. Past HEV infection was inferred in 15.9% by the presence of anti-HEV total immunoglobulin without evidence of acute infection. Of the 119 patients with anti-HBsAg antibodies or HBsAg tested for HBc IgM, the peak age group with HBc IgM was the 25–29 year group (31%), declining to 9% in those over 60 years of age (<xref ref-type="fig" rid="fig1">Figure 1</xref>B). HCV antibody and PCR positive patients tended to be older: 74% of HCV PCR positive patients were >40 years old (<xref ref-type="fig" rid="fig1">Figure 1</xref>C). The frequency of patients with leptospirosis (<xref ref-type="fig" rid="fig1">Figure 1</xref>D) and rickettsia differed little across age groups but those positive for dengue infection were mostly younger: 67% were aged <30 years (<xref ref-type="fig" rid="fig1">Figure 1</xref>E).</p>
<p>The seroprevalence among 399 blood bank controls [mean (95% CI) age 22.3 (21.6–23.0) years; 80% male] of anti-HBsAg and anti-HCV antibodies were 6.5 and 0.25%, respectively. Of a subset of 198 controls [mean (95% CI) age 24.3 (23.3–25.4) years] anti-HEV antibodies were detected in 18.2%. Of a subset of 162 controls [mean (95% CI) age 20.2 (19.2–21.2) years] IgM anti-HAV was detected in none.</p>
<p>Two patients had serological evidence for acute HEV infection with HEV PCR confirmation. The first patient was a 27 year-old non-pregnant housewife from Xaysetta District, Vientiane City, with 6 days of fever and jaundice. She had left upper quadrant tenderness, total serum bilirubin 14.3 μmol/l, AST 55 IU/l and ALT 41 IU/l. The second patient was a 32 year-old construction worker from Sikkotabong District, Vientiane City, with four days of fever, jaundice, and right upper quadrant pain, a history of excessive alcohol intake, total serum bilirubin 530 μmol/l, AST 568 IU/l and ALT 321 IU/l. He was febrile, with spider naevi and hepatomegaly. Both were discharged well with supportive therapy. An additional four patients had significant antibodies against HEV but were HEV PCR negative.</p>
<p>The 26 leptospirosis serovars as determined by MAT were Pomona (1), Autumnalis (5), Bataviae (4), Javanica (3), Copenhageni (6), Grippotypphosa (3), Celledoni (1), Hardjo (1) and Mwalok (2). Some patients showed low level reactions against multiple serovars but determination of the infecting serovars could not be resolved.</p>
</sec>
<sec>
<label>3.2</label>
<title>Clinical features</title>
<p>Of all 392 patients the median (range) age was 34 (0.4–83) years, 259 (66%) were male and 381 (97%) were 15 years or older (Supplementary Table 1). Five patients with scrub typhus (Kato; admission IgG 1:512, IgM 1:1024 to IgG 1:1024, IgM 1:512, 5 days later), primary dengue (anti-dengue IgM positive), hepatitis B (admission anti-HBV core IgM), hepatitis A (admission anti-HAV IgM) and leptospirosis (MAT 1/1600 against Autumnalis) were pregnant. One patient had no aetiological diagnosis and none had acute HEV infection. All survived to discharge with intact pregnancies but the patient with HBV was discharged moribund.</p>
<p>Of 389 (99%) patients with discharge information 13 (3.3%) died in hospital; six (46%) had aetiological diagnoses of HCV infection (2), HAV infection (1), HBV infection (1), leptospirosis (1) and scrub typhus (1).</p>
<p>All viral A, B, C and E hepatitis patients’ data were combined and compared with those with leptospirosis, typhus, community-acquired septicaemia and dengue. Grossly raised transaminases was more common in the dengue and hepatitis A, B, C and E patients whilst high bilirubin was common for all disease categories except septicaemia (<xref ref-type="fig" rid="fig2">Figure 2</xref> A-E
<fig id="fig2" position="float">
<label>Figure 2</label>
<caption>
<p>Box plots (median, 25th and 75th percentiles and whiskers to range) for serum AST (A), ALT (B), total bilirubin (C) concentrations and total bilirubin:AST (D) and total bilirubin:ALT (E) ratios for patients with laboratory evidence for leptospirosis, typhus (scrub typhus, murine typhus and spotted fever group combined), community-acquired septicaemia, dengue and viral hepatitis A,B,C and E. Patients with mixed infections have been excluded.</p>
</caption>
<graphic mimetype="image" xlink:href="104-7-475-fig002.jpg"></graphic>
</fig>). The total birirubin:AST ratio and total bilirubin:ALT ratios were higher for patients with leptospirosis and typhus than those with septicaemia, dengue and hepatitis A, B, C and E (<xref ref-type="fig" rid="fig2">Figure 2</xref>D and 2E). The clinical features of the 50 (12.8%, including mixed infections) patients with an infection expected to respond to doxycycline [leptospirosis and typhus-‘doxycycline responsive illness’ (DRI)] were similar to those with other causes of jaundice and raised transaminases, expect that those with DRI were more likely to have meningism (5/49, 10.2%) than those without (6/332, 1.8%) (<italic>P</italic> = 0.007). The median (range) AST was lower in those with DRI [88 (25–337) IU/l] than in those without [113 (2–1679) IU/l] and median (range) ALT was lower in those with DRI [23 (4–164) IU/l] than in those without [31 (2–1305) IU/l] (<italic>P</italic> = 0.008 and <italic>P</italic> = 0.003, respectively). The median (range) total bilirubin:AST and bilirubin:ALT ratios were significantly higher in those with DRI [0.818 (0.018–9.10) and 2.16 (0.116–39.48)] than in those without [0.507 (0.027–26.41) and 1.651 (0.067–66.58)] (<italic>P</italic> = 0.008 and <italic>P</italic> = 0.007, respectively). Applying multiple logistic regression to the 373 patients with data on meningism and serum AST and ALT, the odds ratios (95% CI) for DRI (against all without known DRI) were 5.3 (1.5–18.4, <italic>P</italic> = 0.009), 0.99 (0.99–1.00, <italic>P</italic> = 0.15) and 0.99 (0.98–1.00, <italic>P</italic> = 0.223), respectively. Inclusion of the bilirubin:AST/ALT ratios did not improve the models (<italic>P</italic> = 0.9 and <italic>P</italic> = 0.2, respectively). Considering those with and without leptospirosis, the median (range) AST was lower in those with this disease [85 (25–309) IU/l] than in those without [108 (2–1679) IU/l] (<italic>P</italic> = 0.01), median (range) ALT was lower in those with [15 (4–164) IU/l] than in those without [31 (2–1305) IU/l] (<italic>P</italic> = 0.003), the bilirubin:AST ratio was higher in those with [1.163 (0.018-9.095)] than in those without [0.513 (0.027–26.41] (<italic>P</italic> = 0.004) and the bilirubin:ALT ratio was higher in those with [3.433 (0.171–38.048)] than in those without leptospirosis [1.659 (0.067–66.58)] (P = 0.002).</p>
<p>None of the potential risks factors for jaundice/hepatitis (source of water, night soil use, past blood transfusions, intravenous drug misuse, sexually transmitted diseases, presence of rats, cats or pigs at home) were associated with any of the diseases tested for, except that those with rickettsial disease were less likely to have drunk from piped tap water (6/28) than those with other diseases (56/120) (<italic>P</italic> = 0.01).</p>
</sec>
</sec>
<sec sec-type="discussion">
<label>4</label>
<title>Discussion</title>
<p>This study investigated the importance of nine viral and bacterial diseases/syndromes in the aetiology of patients presenting with jaundice and/or raised transaminases in Laos. As expected HAV, HBV, HCV and leptospirosis were identified as important causes. HBV immunization at birth and after has been introduced in Laos. Dengue was also common, emphasising the importance of considering dengue and appropriate specific fluid management.<xref ref-type="bibr" rid="bib14"><sup>14</sup></xref> That 7.8% of patients who had blood cultures drawn had community-acquired bacteraemia, emphasises the importance of taking blood cultures in patients with biochemical liver derangement. In a series of patients at Mahosot Hospital with murine and scrub typhus, 34.6% had abnormal liver biochemistry<xref ref-type="bibr" rid="bib4"><sup>4</sup></xref> and among 462 Japanese patients with scrub typhus elevated serum AST and ALT were also common (87% and 77%, respectively).<xref ref-type="bibr" rid="bib15"><sup>15</sup></xref> The association of not drinking tap water with rickettsial disease presumably reflects that poorer people, without taps, are at greater risk.</p>
<p>The limitations of the study include that, as it was hospital based, it will tend to underestimate the incidence of disease in the community, that the median interval between acute and convalescent sera was relatively short at 6 days, that 48% of patients did not have a convalescent sample and that we did not investigate for HGV (GBV-C), parvovirus B19, syphilis, hantavirus, autoimmune diseases, medicine adverse effects and alcohol, and few children were included.<sup><xref ref-type="bibr" rid="bib1">1</xref>,<xref ref-type="bibr" rid="bib16">16</xref></sup> This study differs from that of Bounlu et al.<xref ref-type="bibr" rid="bib1"><sup>1</sup></xref> which was a case–control study and included patients with <24 days of jaundice and dark urine, from three hospitals in Vientiane (including Mahosot Hospital). Falciparum malaria is likely to be more important as a cause of jaundice than suggested here in southern Laos where malaria remains common. We included patients with both jaundice and raised transaminases as reflecting abnormal biochemical liver function. However, raised bilirubin and transaminases can reflect pathology in other organs, potentially confounding the results.</p>
<p>We used conservative definitions of disease, which are appropriate for rickettsial disease, leptospirosis, septicaemia, dengue and HEV. However, we may have missed patients with acute HBV during the core window as we only performed HBcAb assays on patients who were HBsAg or anti-HBsAg positive. The only method to diagnose acute HCV infection conclusively is to document seroconversion and some of our HCV PCR positive patients may have had chronic, and not acute, HCV infection.<xref ref-type="bibr" rid="bib17"><sup>17</sup></xref></p>
<p>An important finding is the description of diagnostic problems for HAV for the first time in the tropics.<sup><xref ref-type="bibr" rid="bib6">6</xref>,<xref ref-type="bibr" rid="bib7">7</xref></sup> Anti-HAV IgM, conventionally considered the gold standard for the diagnosis of acute HAV, persists for 3 months–5 years.<xref ref-type="bibr" rid="bib18"><sup>18</sup></xref> However, HAV IgM can result from nonspecific polyclonal activation of memory cells and positive results not reflecting acute HAV infection may be more common than previously appreciated.<sup><xref ref-type="bibr" rid="bib6">6</xref>,<xref ref-type="bibr" rid="bib7">7</xref>,<xref ref-type="bibr" rid="bib19">19</xref></sup> The HAV IgG avidity and PCR analysis suggest that the majority of positive anti-HAV IgM results did not represent acute HAV infection but polyclonal activation. This is supported by the relatively low median transaminases in those with apparent HAV (Supplementary Table 1, <xref ref-type="fig" rid="fig2">Figure 2A</xref> and <xref ref-type="fig" rid="fig2">2B</xref>) and the absence of anti-HAV IgM in blood donors. Hence, we are unable to provide a secure estimate of the incidence of acute HAV in this cohort. The diagnosis of HAV using IgM antibodies needs review and investigation of the causes of polyclonal activation. The predominant subgenotype in adjacent Thailand is also 1A.<xref ref-type="bibr" rid="bib20"><sup>20</sup></xref></p>
<p>HEV has been described from adjacent countries<xref ref-type="bibr" rid="bib21"><sup>21</sup></xref> and the six patients described here are the first confirmed from Laos. HEV infections are common in Lao domestic pigs<xref ref-type="bibr" rid="bib22"><sup>22</sup></xref> and, if human HEV infections are contracted from pigs, HEV is likely to be a more important disease in rural Laos.</p>
<p>In adjacent northeast Thailand, HCV antibodies were detected in 6.5% of male (0.9% of female) blood donors and the prevalence of HBsAg was 4.9%. Of HCV antibody positive blood donors 80.4% were viraemic.<xref ref-type="bibr" rid="bib23"><sup>23</sup></xref> In adjacent northern Vietnam, of 188 patients with clinical hepatitis, there was serological evidence for HAV in 29%, HBV in 24%, HCV in 10% with no evidence for acute HEV.<xref ref-type="bibr" rid="bib24"><sup>24</sup></xref> Of HCV from 18 Lao patients in this study all were genotype 6, which has also been recorded in east and Southeast Asia.<xref ref-type="bibr" rid="bib11"><sup>11</sup></xref> Although we found no evidence for acute <italic>C. burnetii</italic> infection, this has been recently described in northeast Thailand.<xref ref-type="bibr" rid="bib25"><sup>25</sup></xref> In 1999–2003 a large epidemic of leptospirosis afflicted northeast Thailand, caused by Serotype 34 <italic>Leptospira interrogans</italic> serovar Autumnalis.<xref ref-type="bibr" rid="bib26"><sup>26</sup></xref> However, only 5/26 (19%) of leptospira isolates from patients in Vientiane, 70 km from the study site of Thaipadungpanit,<xref ref-type="bibr" rid="bib26"><sup>26</sup></xref> were Autumnalis. No epidemics of undifferentiated fever, such as occurred in adjacent areas of northeast Thailand, appear to have occurred in/around Vientiane. The Mekong River, which forms the Laos/Thai border in central Laos with only one bridge at the time of the study, may therefore have acted as an effective barrier preventing the significant spread of rats and the epidemic <italic>Leptospira</italic> clone into Laos.</p>
<p>The interpretation of apparent mixed infections, especially when based on serology for clinically similar diseases, is difficult. Given the difficulties demonstrated in the diagnosis of acute HAV, the apparent mixed infections with HAV may represent false HAV positivity. Those between leptospirosis and typhus and between dengue and typhus may represent serial infections with persistence of antibody, false positivity or genuine mixed infections. More research is required, using culture and antigen and gene detection tests, to tease out the relative frequency of these explanations in the Asiatic tropics.</p>
<p>Of the diagnoses entertained here, only leptospirosis, typhus and septicaemia, or 62 (15.8%, including mixed infections) patients, have specific affordable treatments available. In Thailand the current cost of treating HBV and HCV infections are approximately US$1000 and US$1250 a month, respectively. With a Laos per capita income of US$701 a year these are not affordable.<xref ref-type="bibr" rid="bib27"><sup>27</sup></xref> Therefore, in the absence of locally accessible diagnostic tests and antiviral therapy in the vast majority of Laos, empirical therapy with doxycycline may be a cost-effective treatment with significant public health benefits for the 12.8% of patients with a DRI; these are currently the only patients with a potentially treatable disease. Those with a DRI represent 39% of all patients with a diagnosis and, excluding those with septicaemia, for the remaining 52% patients with a diagnosis, therapy is unavailable or unaffordable. A DRI is suggested by meningism and relatively low ALT (none of the patients with DRI had an ALT >164 IU/l). However, as transaminases assays are rarely available in Laos and relatively expensive (US$3.5 a test), empirical therapy for febrile jaundice with doxycycline may be cost effective, as the cost of a 7 day oral course of doxycycline is only approximately US$0.9 and is available in rural Laos. The available data suggest that doxycycline is safe in liver impairment.<xref ref-type="bibr" rid="bib28"><sup>28</sup></xref> There is evidence that oral doxycycline, provided patients can swallow, is effective in severe leptospirosis and probably in severe typhus.<sup><xref ref-type="bibr" rid="bib29">29</xref>,<xref ref-type="bibr" rid="bib30">30</xref></sup> However, doxycycline adverse effects, especially to the upper gastrointestinal tract, are frequent and would reduce the positive public health impact of such an intervention.</p>
</sec>
<sec>
<title>Authors’ contributions</title>
<p>BS, BR, VS, SP, RP, SS, TT, MM, NJW and PNN designed the study; BS, BR, VS, SP, SS, TT, MM recruited patients to the study; LS, JMR, AMR-A, KJ, VS, RP, TT, SDB, EB, PP, ED, DR, IH, PK performed the laboratory assays; PNN analysed the data; PNN, JMR, MM, EB, NJW drafted the paper and all authors revised, read and approved the final manuscript. PNN is guarantor of the paper.</p>
</sec>
<sec>
<title>Funding</title>
<p>This study was funded by the Wellcome Trust of Great Britain. The work at the Peter Medawar Building for Pathogen Research was funded by the James Martin School for the 21st Century and the NIHR Biomedical Research Centre Programme.</p>
</sec>
<sec>
<title>Conflicts of interest</title>
<p>None declared.</p>
</sec>
<sec>
<title>Ethical approval</title>
<p>Ethical clearance was granted by the Ethical Review Committee of the Faculty of Medical Sciences, National University of Laos, Vientiane, Lao PDR.</p>
</sec>
</body>
<back>
<ack>
<title>Acknowledgements</title>
<p>We are grateful to Dr Khin Saw Aye Myint for her enormous help in performing assays for hepatitis E and B; all the patients who participated in this study; the doctors and nursing staff; the staff of the Serology and Microbiology Laboratories and medical wards, especially Amphay Phyaluanglath, Somphone Phannouvong, Pathila Inthepphavong, Suriyasak Thongpaseuth, Anisone Chanthongthip, Viengmone Davong, Olay Lattana, Manivanh Vongsouvath, Sengmani Symanivong, Sengkham Symanivong, Viengmala Sihalath, Kai-amporn Keopaseuth, Sue Lee, Kamolrat Silamut, Valy Keoluangkhot, Bertrand Martinez-Aussel, Keith Feldon, Michel Strobel, Nicholas P.J. Day and Michael Dohnt; Meegan Symonds and Andrew Slack of the WHO/FAO/OIE Collaborating Centre for Reference & Research on Leptospirosis, Queensland, Australia; the Minister of Health, His Excellency Dr Ponmek Dalaloy and the Director of the Curative Department, Ministry of Health, Professor Sommone Phounsavath for their support for this study, which was part of the Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration funded by the Wellcome Trust of Great Britain.</p>
</ack>
<ref-list>
<title>References</title>
<ref id="bib1">
<label>1</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Bounlu</surname><given-names>K.</given-names></name>
<name><surname>Insisiengmay</surname><given-names>S.</given-names></name>
<name><surname>Vanthanouvong</surname><given-names>K.</given-names></name>
<name><surname>Saykham</surname></name>
<name><surname>Widjaja</surname><given-names>S.</given-names></name>
<name><surname>Iinuma</surname><given-names>K.</given-names></name>
<etal></etal>
</person-group>
<article-title>Acute jaundice in Vientiane, Lao People's Democratic Republic</article-title>
<source>Clin Infect Dis</source>
<year>1998</year>
<volume>27</volume>
<fpage>717</fpage>
<lpage>721</lpage>
</nlm-citation>
</ref>
<ref id="bib2">
<label>2</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Laras</surname><given-names>K.</given-names></name>
<name><surname>Cao</surname><given-names>B.V.</given-names></name>
<name><surname>Bounlu</surname><given-names>K.</given-names></name>
<name><surname>Nguyen</surname><given-names>T.K.</given-names></name>
<name><surname>Olson</surname><given-names>J.G.</given-names></name>
<name><surname>Thongchanh</surname><given-names>S.</given-names></name>
<etal></etal>
</person-group>
<article-title>The importance of leptospirosis in Southeast Asia</article-title>
<source>Am J Trop Med Hyg</source>
<year>2002</year>
<volume>67</volume>
<fpage>278</fpage>
<lpage>286</lpage>
</nlm-citation>
</ref>
<ref id="bib3">
<label>3</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Phetsouvanh</surname><given-names>R.</given-names></name>
<name><surname>Phongmany</surname><given-names>S.</given-names></name>
<name><surname>Soukaloun</surname><given-names>D.</given-names></name>
<name><surname>Rasachak</surname><given-names>B.</given-names></name>
<name><surname>Soukhaseum</surname><given-names>V.</given-names></name>
<name><surname>Soukhaseum</surname><given-names>S.</given-names></name>
<etal></etal>
</person-group>
<article-title>Causes of community-acquired bacteremia and patterns of antimicrobial resistance in Vientiane, Laos</article-title>
<source>Am J Trop Med Hyg</source>
<year>2006</year>
<volume>75</volume>
<fpage>978</fpage>
<lpage>985</lpage>
</nlm-citation>
</ref>
<ref id="bib4">
<label>4</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Phongmany</surname><given-names>S.</given-names></name>
<name><surname>Rolain</surname><given-names>J.M.</given-names></name>
<name><surname>Phetsouvanh</surname><given-names>R.</given-names></name>
<name><surname>Blacksell</surname><given-names>S.D.</given-names></name>
<name><surname>Soukkhaseum</surname><given-names>V.</given-names></name>
<name><surname>Rasachack</surname><given-names>B.</given-names></name>
<etal></etal>
</person-group>
<article-title>Rickettsial infections and fever, Vientiane, Laos</article-title>
<source>Emerg Infect Dis</source>
<year>2006</year>
<volume>12</volume>
<fpage>256</fpage>
<lpage>262</lpage>
</nlm-citation>
</ref>
<ref id="bib5">
<label>5</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Jutavijittum</surname><given-names>P.</given-names></name>
<name><surname>Yousukh</surname><given-names>A.</given-names></name>
<name><surname>Samountry</surname><given-names>B.</given-names></name>
<name><surname>Samountry</surname><given-names>K.</given-names></name>
<name><surname>Ounavong</surname><given-names>A.</given-names></name>
<name><surname>Thammavong</surname><given-names>T.</given-names></name>
<etal></etal>
</person-group>
<article-title>Seroprevalence of hepatitis B and C virus infections among Lao blood donors</article-title>
<source>Southeast Asian J Trop Med Public Health</source>
<year>2007</year>
<volume>38</volume>
<fpage>674</fpage>
<lpage>679</lpage>
</nlm-citation>
</ref>
<ref id="bib6">
<label>6</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Roque-Afonso</surname><given-names>A.M.</given-names></name>
<name><surname>Grangeot-Keros</surname><given-names>L.</given-names></name>
<name><surname>Roquebert</surname><given-names>B.</given-names></name>
<name><surname>Desbois</surname><given-names>D.</given-names></name>
<name><surname>Poveda</surname><given-names>J.D.</given-names></name>
<name><surname>Mackiewicz</surname><given-names>V.</given-names></name>
<etal></etal>
</person-group>
<article-title>Diagnostic relevance of immunoglobulin G avidity for hepatitis A virus</article-title>
<source>J Clin Microbiol</source>
<year>2004</year>
<volume>42</volume>
<fpage>5121</fpage>
<lpage>5124</lpage>
</nlm-citation>
</ref>
<ref id="bib7">
<label>7</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Roque-Afonso</surname><given-names>A.M.</given-names></name>
<name><surname>Mackiewicz</surname><given-names>V.</given-names></name>
<name><surname>Dussaix</surname><given-names>E.</given-names></name>
</person-group>
<article-title>Detection of immunoglobulin M antibody to hepatitis A virus in patients without acute hepatitis A: the usefulness of specific immunoglobulin G avidity</article-title>
<source>Clin Infect Dis</source>
<year>2006</year>
<volume>42</volume>
<fpage>887</fpage>
<lpage>888</lpage>
</nlm-citation>
</ref>
<ref id="bib8">
<label>8</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Seriwatana</surname><given-names>J.</given-names></name>
<name><surname>Shrestha</surname><given-names>M.P.</given-names></name>
<name><surname>Scott</surname><given-names>R.M.</given-names></name>
<name><surname>Tsarev</surname><given-names>S.A.</given-names></name>
<name><surname>Vaughn</surname><given-names>D.W.</given-names></name>
<name><surname>Myint</surname><given-names>K.S.</given-names></name>
<etal></etal>
</person-group>
<article-title>Clinical and epidemiological relevance of quantitating hepatitis E virus-specific immunoglobulin M</article-title>
<source>Clin Diagn Lab Immunol</source>
<year>2002</year>
<volume>9</volume>
<fpage>1072</fpage>
<lpage>1078</lpage>
</nlm-citation>
</ref>
<ref id="bib9">
<label>9</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Innis</surname><given-names>B.L.</given-names></name>
<name><surname>Seriwatana</surname><given-names>J.</given-names></name>
<name><surname>Robinson</surname><given-names>R.A.</given-names></name>
<name><surname>Shrestha</surname><given-names>M.P.</given-names></name>
<name><surname>Yarbough</surname><given-names>P.O.</given-names></name>
<name><surname>Longer</surname><given-names>C.F.</given-names></name>
<etal></etal>
</person-group>
<article-title>Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay</article-title>
<source>Clin Diagn Lab Immunol</source>
<year>2002</year>
<volume>9</volume>
<fpage>639</fpage>
<lpage>648</lpage>
</nlm-citation>
</ref>
<ref id="bib10">
<label>10</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Tsarev</surname><given-names>S.A.</given-names></name>
<name><surname>Emerson</surname><given-names>S.U.</given-names></name>
<name><surname>Tsareva</surname><given-names>T.S.</given-names></name>
<name><surname>Yarbough</surname><given-names>P.O.</given-names></name>
<name><surname>Lewis</surname><given-names>M.</given-names></name>
<name><surname>Govindarajan</surname><given-names>S.</given-names></name>
<etal></etal>
</person-group>
<article-title>Variation in course of hepatitis E in experimentally infected cynomolgus monkeys</article-title>
<source>J Infect Dis</source>
<year>1993</year>
<volume>167</volume>
<fpage>1302</fpage>
<lpage>1306</lpage>
</nlm-citation>
</ref>
<ref id="bib11">
<label>11</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Pybus</surname><given-names>O.G.</given-names></name>
<name><surname>Barnes</surname><given-names>E.</given-names></name>
<name><surname>Taggart</surname><given-names>R.</given-names></name>
<name><surname>Lemey</surname><given-names>P.</given-names></name>
<name><surname>Markov</surname><given-names>P.V.</given-names></name>
<name><surname>Rasachak</surname><given-names>B.</given-names></name>
<etal></etal>
</person-group>
<article-title>The Genetic history of the hepatitis C virus in East Asia</article-title>
<source>J Virol</source>
<year>2009</year>
<volume>83</volume>
<fpage>1071</fpage>
<lpage>1082</lpage>
</nlm-citation>
</ref>
<ref id="bib12">
<label>12</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Newton</surname><given-names>P.N.</given-names></name>
<name><surname>Rolain</surname><given-names>J.M.</given-names></name>
<name><surname>Rasachak</surname><given-names>B.</given-names></name>
<name><surname>Mayxay</surname><given-names>M.</given-names></name>
<name><surname>Vathanatham</surname><given-names>K.</given-names></name>
<name><surname>Seng</surname><given-names>P.</given-names></name>
<etal></etal>
</person-group>
<article-title>Sennetsu neorickettsiosis <italic>–</italic> a probably fish borne cause of fever rediscovered in Laos</article-title>
<source>Am J Trop Med Hyg</source>
<year>2009</year>
<volume>81</volume>
<fpage>190</fpage>
<lpage>194</lpage>
</nlm-citation>
</ref>
<ref id="bib13">
<label>13</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Cole</surname><given-names>J.R.</given-names></name>
<name><surname>Sulzer</surname><given-names>C.R.</given-names></name>
<name><surname>Pursell</surname><given-names>A.R.</given-names></name>
</person-group>
<article-title>Improved microtechnique for the leptospiral microscopic agglutination test</article-title>
<source>Appl Microbiol</source>
<year>1973</year>
<volume>25</volume>
<fpage>976</fpage>
<lpage>980</lpage>
</nlm-citation>
</ref>
<ref id="bib14">
<label>14</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Wahid</surname><given-names>S.F.S.A.</given-names></name>
<name><surname>Sanusi</surname><given-names>S.</given-names></name>
<name><surname>Zawawi</surname><given-names>M.M.</given-names></name>
<name><surname>Ali</surname><given-names>R.A.</given-names></name>
</person-group>
<article-title>A comparison of the patterns of liver involvement in dengue hemorrhagic fever with classic dengue fever</article-title>
<source>Southeast Asian J Trop Med Public Health</source>
<year>2000</year>
<volume>31</volume>
<fpage>259</fpage>
<lpage>263</lpage>
</nlm-citation>
</ref>
<ref id="bib15">
<label>15</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Ogawa</surname><given-names>M.</given-names></name>
<name><surname>Hagiwara</surname><given-names>T.</given-names></name>
<name><surname>Kishimoto</surname><given-names>T.</given-names></name>
<name><surname>Shiga</surname><given-names>S.</given-names></name>
<name><surname>Yoshida</surname><given-names>Y.</given-names></name>
<name><surname>Furuya</surname><given-names>Y.</given-names></name>
<etal></etal>
</person-group>
<article-title>Scrub typhus in Japan: epidemiology and clinical features of cases reported in 1998</article-title>
<source>Am J Trop Med Hyg</source>
<year>2002</year>
<volume>67</volume>
<fpage>162</fpage>
<lpage>165</lpage>
</nlm-citation>
</ref>
<ref id="bib16">
<label>16</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Toan</surname><given-names>N.L.</given-names></name>
<name><surname>Song le</surname><given-names>H.</given-names></name>
<name><surname>Kremsner</surname><given-names>P.G.</given-names></name>
<name><surname>Duy</surname><given-names>D.N.</given-names></name>
<name><surname>Binh</surname><given-names>V.Q.</given-names></name>
<name><surname>Duechting</surname><given-names>A.</given-names></name>
<etal></etal>
</person-group>
<article-title>Co-infection of human parvovirus B19 in Vietnamese patients with hepatitis B virus infection</article-title>
<source>J Hepatol</source>
<year>2006</year>
<volume>45</volume>
<fpage>361</fpage>
<lpage>369</lpage>
</nlm-citation>
</ref>
<ref id="bib17">
<label>17</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Maheshwari</surname><given-names>A.</given-names></name>
<name><surname>Ray</surname><given-names>S.</given-names></name>
<name><surname>Paul</surname><given-names>J.</given-names></name>
<name><surname>Thuluvath</surname><given-names>P.J.</given-names></name>
</person-group>
<article-title>Acute hepatitis C</article-title>
<source>Lancet</source>
<year>2008</year>
<volume>372</volume>
<fpage>321</fpage>
<lpage>332</lpage>
</nlm-citation>
</ref>
<ref id="bib18">
<label>18</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Kurt</surname><given-names>M.</given-names></name>
<name><surname>Harmanci</surname><given-names>O.</given-names></name>
<name><surname>Dizdar</surname><given-names>O.</given-names></name>
<name><surname>Onal</surname><given-names>I.K.</given-names></name>
<name><surname>Bayraktar</surname><given-names>Y.</given-names></name>
</person-group>
<article-title>Prolonged anti-HAV IgM positivity in a pregnant woman</article-title>
<source>Indian J Gastroenterol</source>
<year>2005</year>
<volume>24</volume>
<fpage>181</fpage>
<lpage>182</lpage>
</nlm-citation>
</ref>
<ref id="bib19">
<label>19</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Castrodale</surname><given-names>L.</given-names></name>
<name><surname>Fiore</surname><given-names>A.</given-names></name>
<name><surname>Schmidt</surname><given-names>T.</given-names></name>
</person-group>
<article-title>Detection of immunoglobulin M antibody to hepatitis A virus in Alaska residents without other evidence of hepatitis</article-title>
<source>Clin Infect Dis</source>
<year>2005</year>
<volume>41</volume>
<fpage>e86</fpage>
<lpage>e88</lpage>
</nlm-citation>
</ref>
<ref id="bib20">
<label>20</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Barameechai</surname><given-names>K.</given-names></name>
<name><surname>Sa-Nguanmoo</surname><given-names>P.</given-names></name>
<name><surname>Suwannakarn</surname><given-names>K.</given-names></name>
<name><surname>Thongmee</surname><given-names>C.</given-names></name>
<name><surname>Payungporn</surname><given-names>S.</given-names></name>
<name><surname>Chongsrisawat</surname><given-names>V.</given-names></name>
<etal></etal>
</person-group>
<article-title>Molecular characterisation of the hepatitis A virus circulating in the 2001-2005 outbreaks in Thailand</article-title>
<source>Ann Trop Med Parasitol</source>
<year>2008</year>
<volume>102</volume>
<fpage>247</fpage>
<lpage>257</lpage>
</nlm-citation>
</ref>
<ref id="bib21">
<label>21</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Corwin</surname><given-names>A.L.</given-names></name>
<name><surname>Khiem</surname><given-names>H.B.</given-names></name>
<name><surname>Clayson</surname><given-names>E.T.</given-names></name>
<name><surname>Pham</surname><given-names>K.S.</given-names></name>
<name><surname>Vo</surname><given-names>T.T.</given-names></name>
<name><surname>Vu</surname><given-names>T.Y.</given-names></name>
<etal></etal>
</person-group>
<article-title>A waterborne outbreak of hepatitis E virus transmission in southwestern Viet Nam</article-title>
<source>Am J Trop Med Hyg</source>
<year>1996</year>
<volume>54</volume>
<fpage>559</fpage>
<lpage>562</lpage>
</nlm-citation>
</ref>
<ref id="bib22">
<label>22</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Blacksell</surname><given-names>S.B.</given-names></name>
<name><surname>Myint</surname><given-names>K.S.A.</given-names></name>
<name><surname>Khounsy</surname><given-names>S.</given-names></name>
<name><surname>Phruaravanh</surname><given-names>M.</given-names></name>
<name><surname>Mammen</surname><given-names>M.P.</given-names></name>
<name><surname>Day</surname><given-names>N.P.</given-names></name>
<etal></etal>
</person-group>
<article-title>Prevalence of hepatitis E virus antibodies in pigs: Implications for human infections in village-based subsistence pig farming in the Lao PDR</article-title>
<source>Trans R Soc Trop Med Hyg</source>
<year>2006</year>
<volume>101</volume>
<fpage>305</fpage>
<lpage>307</lpage>
</nlm-citation>
</ref>
<ref id="bib23">
<label>23</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Songsivilai</surname><given-names>S.</given-names></name>
<name><surname>Jinathongthai</surname><given-names>S.</given-names></name>
<name><surname>Wongsena</surname><given-names>W.</given-names></name>
<name><surname>Tiangpitayakorn</surname><given-names>C.</given-names></name>
<name><surname>Dharakul</surname><given-names>T.</given-names></name>
</person-group>
<article-title>High prevalence of hepatitis C infection among blood donors in northeastern Thailand</article-title>
<source>Am J Trop Med Hyg</source>
<year>1997</year>
<volume>57</volume>
<fpage>66</fpage>
<lpage>69</lpage>
</nlm-citation>
</ref>
<ref id="bib24">
<label>24</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Corwin</surname><given-names>A.L.</given-names></name>
<name><surname>Dai</surname><given-names>T.C.</given-names></name>
<name><surname>Duc</surname><given-names>D.D.</given-names></name>
<name><surname>Suu</surname><given-names>P.I.</given-names></name>
<name><surname>Van</surname><given-names>N.T.</given-names></name>
<name><surname>Ha</surname><given-names>L.D.</given-names></name>
<etal></etal>
</person-group>
<article-title>Acute viral hepatitis in Hanoi</article-title>
<source>Trans R Soc Trop Med Hyg</source>
<year>1996</year>
<volume>90</volume>
<fpage>647</fpage>
<lpage>648</lpage>
</nlm-citation>
</ref>
<ref id="bib25">
<label>25</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Suputtamongkol</surname><given-names>Y.</given-names></name>
<name><surname>Rolain</surname><given-names>J.M.</given-names></name>
<name><surname>Losuwanaruk</surname><given-names>K.</given-names></name>
<name><surname>Niwatayakul</surname><given-names>K.</given-names></name>
<name><surname>Suttinont</surname><given-names>C.</given-names></name>
<name><surname>Chierakul</surname><given-names>W.</given-names></name>
<etal></etal>
</person-group>
<article-title>Q fever in Thailand</article-title>
<source>Emerg Infect Dis</source>
<year>2003</year>
<volume>9</volume>
<fpage>1186</fpage>
<lpage>1188</lpage>
</nlm-citation>
</ref>
<ref id="bib26">
<label>26</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Thaipadungpanit</surname><given-names>J.</given-names></name>
<name><surname>Wuthiekanun</surname><given-names>V.</given-names></name>
<name><surname>Chierakul</surname><given-names>W.</given-names></name>
<name><surname>Smythe</surname><given-names>L.D.</given-names></name>
<name><surname>Petkanchanapong</surname><given-names>W.</given-names></name>
<name><surname>Limpaiboon</surname><given-names>R.</given-names></name>
<etal></etal>
</person-group>
<article-title>Dominant clone of <italic>Leptospira interrogans</italic> associated with an outbreak of human leptospirosis in Thailand</article-title>
<source>PLoS Negl Trop Dis</source>
<year>2007</year>
<volume>1</volume>
<fpage>e56</fpage>
</nlm-citation>
</ref>
<ref id="bib27">
<label>27</label>
<nlm-citation citation-type="other">
<comment>UNDP. 2007/2008 Human Development Report – Lao People's Democratic Republic. <ext-link ext-link-type="uri" xlink:href="http://hdrstats.undp.org/en/countries/data_sheets/cty_ds_LAO.html">http://hdrstats.undp.org/en/countries/data_sheets/cty_ds_LAO.html</ext-link> [accessed 3 March 2010].</comment>
</nlm-citation>
</ref>
<ref id="bib28">
<label>28</label>
<nlm-citation citation-type="book">
<person-group person-group-type="author">
<name><surname>Chopra</surname><given-names>I.</given-names></name>
</person-group>
<person-group person-group-type="editor">
<name><surname>Finch</surname><given-names>R.G.</given-names></name>
<name><surname>Greenwood</surname><given-names>D.</given-names></name>
<name><surname>Norrby</surname><given-names>S.R.</given-names></name>
<name><surname>Whitely</surname><given-names>R.J.</given-names></name>
</person-group>
<article-title>Tetracyclines</article-title>
<source>Antibiotic chemotherapy</source>
<year>2003</year>
<publisher-loc>Edinburgh</publisher-loc>
<publisher-name>Churchill Livingstone</publisher-name>
<fpage>393</fpage>
<lpage>406</lpage>
</nlm-citation>
</ref>
<ref id="bib29">
<label>29</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Lee</surname><given-names>N.</given-names></name>
<name><surname>Ip</surname><given-names>M.</given-names></name>
<name><surname>Wong</surname><given-names>B.</given-names></name>
<name><surname>Lui</surname><given-names>G.</given-names></name>
<name><surname>Tsang</surname><given-names>O.T.</given-names></name>
<name><surname>Lai</surname><given-names>J.Y.</given-names></name>
<etal></etal>
</person-group>
<article-title>Risk factors associated with life-threatening rickettsial infections</article-title>
<source>Am J Trop Med Hyg</source>
<year>2008</year>
<volume>78</volume>
<fpage>973</fpage>
<lpage>978</lpage>
</nlm-citation>
</ref>
<ref id="bib30">
<label>30</label>
<nlm-citation citation-type="journal">
<person-group person-group-type="author">
<name><surname>Suputtamongkol</surname><given-names>Y.</given-names></name>
<name><surname>Niwattayakul</surname><given-names>K.</given-names></name>
<name><surname>Suttinont</surname><given-names>C.</given-names></name>
<name><surname>Losuwanaluk</surname><given-names>K.</given-names></name>
<name><surname>Limpaiboon</surname><given-names>R.</given-names></name>
<name><surname>Chierakul</surname><given-names>W.</given-names></name>
<etal></etal>
</person-group>
<article-title>An open, randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis</article-title>
<source>Clin Infect Dis</source>
<year>2004</year>
<volume>39</volume>
<fpage>1417</fpage>
<lpage>1424</lpage>
</nlm-citation>
</ref>
</ref-list>
</back>
</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos</title></titleInfo><name type="personal"><namePart type="given">Bounkong</namePart><namePart type="family">Syhavong</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Bouachanh</namePart><namePart type="family">Rasachack</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Lee</namePart><namePart type="family">Smythe</namePart><affiliation>WHO/AO/OIE Collaborating Centre for Reference & Research on Leptospirosis, Queensland Health Forensic and Scientific Services, Coopers Plains, Queensland, 4108, Australia</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-Marc</namePart><namePart type="family">Rolain</namePart><affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anne-Marie</namePart><namePart type="family">Roque-Afonso</namePart><affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kemajittra</namePart><namePart type="family">Jenjaroen</namePart><affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Vimone</namePart><namePart type="family">Soukkhaserm</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Simmaly</namePart><namePart type="family">Phongmany</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Rattanaphone</namePart><namePart type="family">Phetsouvanh</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sune</namePart><namePart type="family">Soukkhaserm</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Te</namePart><namePart type="family">Thammavong</namePart><affiliation>National Blood Transfusion Centre, Lao Red Cross, Vientiane, Lao PDR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Mayfong</namePart><namePart type="family">Mayxay</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation><affiliation>Faculty of Post Graduate Studies, University of Health Sciences, Vientiane, Lao PDR</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stuart D.</namePart><namePart type="family">Blacksell</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Eleanor</namePart><namePart type="family">Barnes</namePart><affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Philippe</namePart><namePart type="family">Parola</namePart><affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elisabeth</namePart><namePart type="family">Dussaix</namePart><affiliation>AP-HP, National Reference Centre for HAV, Hôpital Paul Brousse, Villejuif, 94804 France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Didier</namePart><namePart type="family">Raoult</namePart><affiliation>URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Isla</namePart><namePart type="family">Humphreys</namePart><affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Paul</namePart><namePart type="family">Klenerman</namePart><affiliation>The Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicholas J.</namePart><namePart type="family">White</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Paul N.</namePart><namePart type="family">Newton</namePart><affiliation>Wellcome Trust-Mahosot Hospital-Oxford Tropical Medicine Research Collaboration, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR</affiliation><affiliation>Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford, UK</affiliation><affiliation>E-mail: paul@tropmedres.ac</affiliation><affiliation>Corresponding author. Tel.: +856 21 242168; fax: +856 21 242168. E-mail address: paul@tropmedres.ac</affiliation><affiliation>E-mail: paul@tropmedres.ac</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Royal Society of Tropical Medicine and Hygiene</publisher><dateIssued encoding="w3cdtf">2010-07</dateIssued><copyrightDate encoding="w3cdtf">2010</copyrightDate></originInfo><abstract>There is little information on the diverse infectious causes of jaundice and hepatitis in the Asiatic tropics. Serology (hepatitis A, B, C and E, leptospirosis, dengue, rickettsia), antigen tests (dengue), PCR assays (hepatitis A, C and E) and blood cultures (septicaemia) were performed on samples from 392 patients admitted with jaundice or raised transaminases (≥ × 3) to Mahosot Hospital, Vientiane, Laos over 3 years. Conservative definitions suggested diagnoses of dengue (8.4%), rickettsioses (7.3%), leptospirosis (6.8%), hepatitis B (4.9%), hepatitis C (4.9%), community-acquired septicaemia (3.3%) and hepatitis E (1.6%). Although anti-hepatitis A virus (HAV) IgM antibody results suggested that 35.8% of patients had acute HAV infections, anti-HAV IgG antibody avidity and HAV PCR suggested that 82% had polyclonal activation and not acute HAV infections. Scrub typhus, murine typhus or leptospirosis were present in 12.8% of patients and were associated with meningism and relatively low AST and ALT elevation. These patients would be expected to respond to empirical doxycycline therapy which, in the absence of virological diagnosis and treatment, may be an appropriate cost-effective intervention in Lao patients with jaundice/hepatitis.</abstract><subject lang="en"><genre>Keywords</genre><topic>Jaundice</topic><topic>Hepatitis E virus</topic><topic>Leptospirosis</topic><topic>Laos</topic></subject><relatedItem type="host"><titleInfo><title>Transactions of The Royal Society of Tropical Medicine and Hygiene</title></titleInfo><titleInfo type="abbreviated"><title>Trans R Soc Trop Med Hyg</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><identifier type="ISSN">0035-9203</identifier><identifier type="eISSN">1878-3503</identifier><identifier type="PublisherID">trstmh</identifier><identifier type="PublisherID-hwp">trstmh</identifier><part><date>2010</date><detail type="volume"><caption>vol.</caption><number>104</number></detail><detail type="issue"><caption>no.</caption><number>7</number></detail><extent unit="pages"><start>475</start><end>483</end></extent></part></relatedItem><identifier type="istex">DEC1F87054742B503CEF494BE7745DBFB1A60E95</identifier><identifier type="DOI">10.1016/j.trstmh.2010.03.002</identifier><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</recordContentSource><recordOrigin>Royal Society of Tropical Medicine and Hygiene</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/metadata/json</uri></json:item></metadata><covers><json:item><extension>tiff</extension><original>true</original><mimetype>image/tiff</mimetype><uri>https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/covers/tiff</uri></json:item></covers><annexes><json:item><extension>jpeg</extension><original>true</original><mimetype>image/jpeg</mimetype><uri>https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/annexes/jpeg</uri></json:item><json:item><extension>gif</extension><original>true</original><mimetype>image/gif</mimetype><uri>https://api.istex.fr/document/DEC1F87054742B503CEF494BE7745DBFB1A60E95/annexes/gif</uri></json:item></annexes><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002968 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 002968 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Istex
|étape= Corpus
|type= RBID
|clé= ISTEX:DEC1F87054742B503CEF494BE7745DBFB1A60E95
|texte= The infective causes of hepatitis and jaundice amongst hospitalised patients in Vientiane, Laos
}}
| This area was generated with Dilib version V0.6.33. |  |