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Clinical and Vaccine Immunology, October 2009, p. 1413-1419, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00245-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Kinetics of the Natural, Humoral Immune Response to Salmonella enterica Serovar Typhi in Kathmandu, Nepal{triangledown}

Anoop S. Pulickal,1* Samir Gautam,2 Elizabeth A. Clutterbuck,1 Stephen Thorson,2 Buddha Basynat,2 Neelam Adhikari,2 Katherine Makepeace,3 Sjoerd Rijpkema,4 Ray Borrow,5 Jeremy J. Farrar,6 and Andrew J. Pollard1

Oxford Vaccine Group, University Department of Paediatrics, University of Oxford, Oxford, United Kingdom,1 Departments of Paediatrics and Internal Medicine, Patan Hospital, Kathmandu, Nepal,2 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom,3 Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, United Kingdom,4 Vaccine Evaluation Unit, Health Protection Agency, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, United Kingdom,5 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam6

Received 18 June 2009/ Returned for modification 17 July 2009/ Accepted 17 August 2009

Typhoid fever is a major public health problem in developing countries, conservatively estimated to occur in 17 million cases and be responsible for 200,000 deaths annually. We investigated the acquisition of natural immunity to Salmonella enterica serovar Typhi in a region where typhoid is endemic by testing sera from an age-stratified sample of 210 healthy participants in Kathmandu, Nepal, for bactericidal activity toward S. Typhi and for anti-Vi capsular polysaccharide antibodies. Bactericidal titers in children were significantly lower than those in newborns and adults (P < 0.0001). Anti-S. Typhi bactericidal geometric mean titers were age dependent, increasing 10-fold during childhood. Anti-Vi polysaccharide antibody geometric mean concentrations were also lower in children than in adults. Data presented here indicate the possibility of a relationship between low levels of bactericidal activity toward S. Typhi in serum and susceptibility to disease, as observed for other polysaccharide-encapsulated bacteria. Bactericidal antibody may be a marker of protective immunity against S. Typhi.

* Corresponding author. Mailing address: Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, United Kingdom. Phone and fax: 44 (0)1865 857420. E-mail: anoopdoc{at}yahoo.com

{triangledown} Published ahead of print on 26 August 2009.

Clinical and Vaccine Immunology, October 2009, p. 1413-1419, Vol. 16, No. 10
1071-412X/09/$08.00+0     doi:10.1128/CVI.00245-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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