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J Infect. 2017 Aug;75(2):104-114. doi: 10.1016/j.jinf.2017.05.007. Epub 2017 May 25.

An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever.

Author information

1
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam.
2
The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
3
Sclavo Berhing Vaccines Institute for Global Health, Siena, Italy.
4
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
5
Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA, USA.
6
Department of Internal Medicine, Division of Infectious Diseases and Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
7
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom.
8
Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
9
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
10
Chittagong Medical College Hospital, Chittagong, Bangladesh.
11
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Malaria Research Group and Dev Care Foundation, Bangladesh.
12
Malaria Research Group and Dev Care Foundation, Bangladesh.
13
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Sheffield Teaching Hospitals NHS Trust Foundation and the University of Sheffield, Sheffield, United Kingdom.
14
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
15
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom.
16
The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom; The Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
17
The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom; The Department of Medicine, University of Cambridge, Cambridge, United Kingdom. Electronic address: sbaker@oucru.org.

Abstract

OBJECTIVES:

The diagnosis of typhoid fever is a challenge. Aiming to develop a typhoid diagnostic we measured antibody responses against Salmonella Typhi (S. Typhi) protein antigens and the Vi polysaccharide in a cohort of Bangladeshi febrile patients.

METHODS:

IgM against 12 purified antigens and the Vi polysaccharide was measured by ELISA in plasma from patients with confirmed typhoid fever (n = 32), other confirmed infections (n = 17), and healthy controls (n = 40). ELISAs with the most specific antigens were performed on plasma from 243 patients with undiagnosed febrile disease.

RESULTS:

IgM against the S. Typhi protein antigens correlated with each other (rho > 0.8), but not against Vi (rho < 0.6). Typhoid patients exhibited higher IgM against 11/12 protein antigens and Vi than healthy controls and those with other infections. Vi, PilL, and CdtB exhibited the greatest sensitivity and specificity. Specificity and sensitivity was improved when Vi was combined with a protein antigen, generating sensitivities and specificities of 0.80 and >0.85, respectively. Applying a dynamic cut-off to patients with undiagnosed febrile disease suggested that 34-58% had an IgM response indicative of typhoid.

CONCLUSIONS:

We evaluated the diagnostic potential of several S. Typhi antigens; our assays give good sensitivity and specificity, but require further assessment in differing patient populations.

KEYWORDS:

Bangladesh; Diagnostics; Enteric fever; Febrile disease; IgM; Salmonella Typhi; Typhoid fever; Vi polysaccharide

PMID:
28551371
PMCID:
PMC5522525
DOI:
10.1016/j.jinf.2017.05.007
[Indexed for MEDLINE]
Free PMC Article

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