Background document: The diagnosis,treatment and ...

1 World Health OrganizationWHOB ackground document: The diagnosis,treatment andprevention of typhoid feverWHO/V& : ENGLISHC ommunicable Disease Surveillance and ResponseVaccines and BiologicalsWHO/V& : ENGLISHWHOB ackground document: The diagnosis,treatment andprevention of typhoid feverWorld Health OrganizationCommunicable Disease Surveillance and ResponseVaccines and Biologicals The Department of Vaccines and Biologicalsthanks the donors whose unspecified financial supporthas made the production of this publication document contains general Background information on the epidemiology, infection,diagnosis, treatment and prevention of typhoid fever . It is targeted at public healthprofessionals, clinicians and laboratory specialists. A second document to be publishedlater, targeting health professionals in the field, will focus on the practical aspects ofepidemic preparedness and the treatment of the disease. 2 2 2 2 2 s 2 2 2 2 2 2h 2 2 2 2f 2 2 2i 2h 2g 2 2h 2 2g 2h 2 2 2 Ordering code: WHO/V& : May 2003 This publication is available on the Internet may be requested from:World Health OrganizationDepartment of Vaccines and BiologicalsCH-1211 Geneva 27, Switzerland Fax: + 41 22 791 4227 Email: World Health Organization 2003 All rights reserved.

2 Publications of the World Health Organization can be obtained from Marketingand Dissemination, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland(tel.: +41 22 791 2476; fax: +41 22 791 4857; email: Requests for permission toreproduce or translate WHO publications whether for sale or for noncommercial distribution shouldbe addressed to Publications, at the above address (fax: +41 22 791 4806; email: designations employed and the presentation of the material in this publication do not imply theexpression of any opinion whatsoever on the part of the World Health Organization concerning the legalstatus of any country, territory, city or area or of its authorities, or concerning the delimitation of itsfrontiers or boundaries. Dotted lines on maps represent approximate border lines for which there maynot yet be full mention of specific companies or of certain manufacturers products does not imply that they areendorsed or recommended by the World Health Organization in preference to others of a similar naturethat are not mentioned.))

3 Errors and omissions excepted, the names of proprietary products are distinguishedby initial capital World Health Organization does not warrant that the information contained in this publication iscomplete and correct and shall not be liable for any damages incurred as a result of its use. viiChapter 1: The organism, the disease and transmission .. The The Contamination and transmission .. 4 Chapter 2: Diagnosis of typhoid fever .. Microbiological Serological 1 Antimicrobial susceptibility test for typhoid fever organisms .. 1 Storage of typhoid fever organisms .. 1 Quality control .. 1 7 Chapter 3: Treatment of typhoid fever .. 1 General 1 Antimicrobial 1 Management of complications .. 2 Management of 2 3 Chapter 4: Prevention of typhoid fever .. 2 Safe 2 Food safety .. 2 2 Health education .. 2 2 6 Conclusions.

4 3 1 Igimmunoglobulin (IgG, IgM) resistantMpmacrophagesNARST nalidixic-acid-resistant Salmonella typhiVivirulent (antigen)Abbreviations We would like to thank the following for their participation in the preparation ofthis document: Dr Camilo Acosta, International Vaccine Institute, Seoul, Republic of KoreaDr M. John Albert, Faculty of Medicine, Kuwait University, KuwaitDr Bhan, All India Institute of Medical Sciences, New Delhi, IndiaDr Zulfiqar Bhutta, Aga Khan University, Karachi, PakistanDr Robert Breiman, International Centre for Diarrhoeal Diseases Research, Dhaka,BangladeshDr John Clemens, International Vaccine Institute, Seoul, Republic of KoreaDr Jeremy Farrar, Oxford University and the Hospital for Tropical Diseases,Ho Chi Minh City, Viet NamDr Asma Ismail, Universiti Sains Malaysia, Kelantan, MalaysiaDr Keith Klugman, Emory University, Atlanta, USADr Claudio F.

5 Lanata, Instituto de Investigaci n Nutricional, Lima, PeruDr Myron M. Levine, University of Maryland School of Medicine, Baltimore, USADr Pakleong Lim, Clinical Immunology Unit, The Prince of Wales Hospital, Shatin,Hong Kong, People s Republic of ChinaDr Maria Neira, Department of Communicable Disease Prevention, Control andEradication, World Health Organization, Geneva, SwitzerlandDr Henk L. Smits, KIT Biomedical Research, Royal Tropical Institute/KoninklijkInstituut voor de Tropen, Amsterdam, NetherlandsDr Tikki Pang, Department of Evidence and Information for Policy, World HealthOrganization, Geneva, SwitzerlandDr Christopher Parry, Department of Medical Microbiology University of Liverpool,United KingdomAcknowledgements Dr Narain Punjabi, US NAMRU-2, Jakarta, IndonesiaDr Philippe Sansonetti, Institut Pasteur, Paris, FranceDr Shosun Szu, NIH, Bethesda, USADr John Wain, Imperial College Medical School, London, United Kingdomunder the coordination ofDr Bernard Ivanoff, Department of Vaccines and BiologicalsandDr Claire Lise Chaignat, Department of Communicable Disease Surveillanceand Response1 WHO/V& 1:The organism, the diseaseand The organismTyphoid fever is caused by Salmonella typhi, a Gram-negative bacterium.

6 A very similarbut often less severe disease is caused by Salmonella serotype paratyphi nomenclature for these bacteria is confused because the criteria for designatingbacteria as individual species are not clear. Two main views on the nomenclature of thegenus Salmonella have been discussed. Le Minor and Popoff suggested that two speciesshould be recognized: Salmonella bongori and Salmonella enterica. S. enterica includedsix subspecies, of which subspecies I (one) contained all the pathogens of warm-bloodedanimals. S. typhi was a serotype within subspecies I: Salmonella enterica subspecies Iserotype typhi. This proposal was rejected by the International Judicial Commissionbecause the name was not well known to clinicians and its use might cause accidentsendangering health or life. The original rules therefore remain in force. Ezaki andcolleagues have noted in the International Journal of Systematic and EvolutionaryMicrobiology that the correct nomenclature for the causal agent of typhoid fever isSalmonella typhi and have requested that the current subspecific status of serotypeparatyphi A should be raised to specific status, Salmonella paratyphi typhi has several unique features, the genetic basis of many of which is known asa result of early genetic studies and the recent sequencing of the whole many genes are shared with E.

7 Coli and at least 90% with S. typhimurium,there are several unique clusters of genes known as pathogenicity islands and manymore single genes that seem to have been acquired by S. typhi during typhi can be identified in the laboratory by several biochemical and serological tests(see Chapter 2). One of the most specific is that of polysaccharide capsule Vi, which ispresent in about 90% of all freshly isolated S. typhi and has a protective effect againstthe bactericidal action of the serum of infected patients. This capsule provides the basisfor one of the commercially available vaccines (see Chapter 4). Vi antigen is present insome other bacteria (Citrobacter freundii, Salmonella paratyphi C and Salmonelladublin) but not in exactly the same genetic context. The ratio of disease caused byS. typhi to that caused by S. paratyphi is about 10 to 1 in most of the countries wherethis matter has been The diseaseDuring an acute infection, S.

8 Typhi multiplies in mononuclear phagocytic cells beforebeing released into the bloodstream. After ingestion in food or water, typhoid organismspass through the pylorus and reach the small intestine. They rapidly penetrate themucosal epithelium via either microfold cells or enterocytes and arrive in the laminapropria, where they rapidly elicit an influx of macrophages (Mp) that ingest the bacillibut do not generally kill them. Some bacilli remain within Mp of the small intestinalThe diagnosis, treatment and prevention of typhoid fever2lymphoid tissue. Other typhoid bacilli are drained into mesenteric lymph nodes wherethere is further multiplication and ingestion by Mp. It is believed that typhoid bacillireach the bloodstream principally by lymph drainage from mesenteric nodes,after which they enter the thoracic duct and then the general circulation. As a result ofthis silent primary bacteraemia the pathogen reaches an intracellular haven within24 hours after ingestion throughout the organs of the reticuloendothelial system (spleen,liver, bone marrow, etc.)

9 , where it resides during the incubation period, usually of 8 to14 days. The incubation period in a particular individual depends on the quantity ofinoculum, it decreases as the quantity of inoculum increases, and on host periods ranging from 3 days to more than 60 days have been illness is accompanied by a fairly sustained but low level of secondarybacteraemia (~1E10 bacteria per ml of blood). SymptomsThe clinical presentation of typhoid fever varies from a mild illness with low-gradefever, malaise, and slight dry cough to a severe clinical picture with abdominal discomfortand multiple complications. Many factors influence the severity and overall clinicaloutcome of the infection. They include the duration of illness before the initiation ofappropriate therapy, the choice of antimicrobial treatment, age, the previous exposureor vaccination history, the virulence of the bacterial strain, the quantity of inoculumingested, host factors ( HLA type, AIDS or other immunosuppression) and whetherthe individual was taking other medications such as H2 blockers or antacids to diminishgastric acid.

10 Patients who are infected with HIV are at significantly increased risk ofclinical infection with S. typhi and S. paratyphi (1). Evidence of Helicobacter pyloriinfection also represents an increased risk of acquiring typhoid fever . Acute non-complicated disease: Acute typhoid fever is characterized by prolongedfever, disturbances of bowel function (constipation in adults, diarrhoea in children),headache, malaise and anorexia. Bronchitic cough is common in the early stage ofthe illness. During the period of fever , up to 25% of patients show exanthem (rosespots), on the chest, abdomen and back. Complicated disease: Acute typhoid fever may be severe. Depending on the clinicalsetting and the quality of available medical care, up to 10% of typhoid patientsmay develop serious complications. Since the gut-associated lymphoid tissueexhibits prominent pathology, the presence of occult blood is a common findingin the stool of 10-20% of patients, and up to 3% may have melena.