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Clinical and Vaccine Immunology, November 2009, p. 1587-1594, Vol. 16, No. 11
1071-412X/09/$08.00+0 doi:10.1128/CVI.00311-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever
Alaullah Sheikh,1,
M. Saruar Bhuiyan,1,
Farhana Khanam,1
Fahima Chowdhury,2
Amit Saha,1
Dilruba Ahmed,1
K. M. A. Jamil,1
Regina C. LaRocque,2
Jason B. Harris,2
Mian Mashhud Ahmad,3
Richelle Charles,2
W. Abdullah Brooks,1
Stephen B. Calderwood,2,4,5
Alejandro Cravioto,1
Edward T. Ryan,2,4,6 and
Firdausi Qadri1*
International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh,1 Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts,2 Dhaka Medical College Hospital, Dhaka, Bangladesh,3 Department of Medicine, Harvard Medical School, Boston, Massachusetts,4 Department of Microbiology and Molecular Center, Harvard Medical School, Boston, Massachusetts,5 Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts6
Received 29 July 2009/ Returned for modification 28 August 2009/ Accepted 31 August 2009
Many currently available diagnostic tests for typhoid fever lack sensitivity and/or specificity, especially in areas of the world where the disease is endemic. In order to identify a diagnostic test that better correlates with typhoid fever, we evaluated immune responses to Salmonella enterica serovar Typhi (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh. We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We harvested peripheral blood lymphocytes and analyzed antibody levels in supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte-supernatant [ALS] assay), as well as in plasma on these days. We measured ALS reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever individuals into different groups (groups I to V) based on blood culture results, Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin A isotype were detectable at the time of presentation in the plasma of 81% of patients. The ALS assay, however, tested positive in all patients with documented or highly suspicious typhoid, suggesting that such a response could be the basis of improved diagnostic point-of-care-assay for serovar Typhi infection. It can be important for use in epidemiological studies, as well as in difficult cases involving fevers of unknown origin.
* Corresponding author. Mailing address: Immunology Unit, Laboratory Sciences Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh. Phone: 88-02-8860523-32, ext. 2431. Fax: 88-02-8823116. E-mail: fqadri{at}icddrb.org
Published ahead of print on 9 September 2009.
A.S. and M.S.B. contributed equally to this study.
Clinical and Vaccine Immunology, November 2009, p. 1587-1594, Vol. 16, No. 11
1071-412X/09/$08.00+0 doi:10.1128/CVI.00311-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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