An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever - 06/10/17

Doi : 10.1016/j.jinf.2017.05.007

Nga Tran Vu Thieu ^a, Tan Trinh Van ^a, Anh Tran Tuan ^a, Elizabeth J. Klemm ^b, Chau Nguyen Ngoc Minh ^a, Phat Voong Vinh ^a, Duy Pham Thanh ^a, Thanh Ho Ngoc Dan ^a, Trung Pham Duc ^a, Pinky Langat ^b, Laura B. Martin ^c, Jorge Galan ^d, Li Liang ^e, Philip L. Felgner ^e, D. Huw Davies ^e, Hanna K. de Jong ^f, Rapeephan R. Maude ^g,^h, Masako Fukushima ⁱ, Lalith Wijedoru ^g, Aniruddha Ghose ^j, Rasheda Samad ^j, Arjen M. Dondorp ^g,^k, Abul Faiz ^k, Thomas C. Darton ^a,^l, Andrew J. Pollard ^m, Guy E. Thwaites ^a,^h, Gordon Dougan ^b,ⁿ, Christopher M. Parry ^m,^{^{1
Joint senior authors.}}, Stephen Baker ^a,^h,^n,^⁎,^{^{1
Joint senior authors.}}
^a The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam
^b The Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom
^c Sclavo Berhing Vaccines Institute for Global Health, Siena, Italy
^d Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA
^e Department of Medicine, Division of Infectious Diseases, University of California, Irvine, CA, USA
^f 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
^g Mahidol-Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
^h Centre for Tropical Medicine and Global Health, Oxford University, Oxford, United Kingdom
ⁱ Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
^j Chittagong Medical College Hospital, Chittagong, Bangladesh
^k Malaria Research Group and Dev Care Foundation, Bangladesh
^l Sheffield Teaching Hospitals NHS Trust Foundation and the University of Sheffield, Sheffield, United Kingdom
^m Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom
ⁿ The Department of Medicine, University of Cambridge, Cambridge, United Kingdom

^∗Corresponding author. The Hospital for Tropical Diseases, 764 Vo Van Kiet, Quan 5, Ho Chi Minh City, Viet Nam. Fax: +84 89238904.The Hospital for Tropical Diseases764 Vo Van KietQuan 5Ho Chi Minh CityViet Nam

Summary

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.

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Keywords : Typhoid fever, Enteric fever, Salmonella Typhi, Diagnostics, Bangladesh, Vi polysaccharide, IgM, Febrile disease

Plan

Introduction

Materials and methods

Ethical approval

Study site, population and study design

PCR amplification, gene expression and protein purification

ELISAs using S. Typhi protein antigens

Statistical analysis

Results

Acute IgM antibody responses against Salmonella Typhi antigens

The diagnostic potential of IgM against Salmonella Typhi antigens

Sensitivity and specificity of the serodiagnostic antigens

Identifying typhoid cases in patients with undiagnosed febrile disease

Discussion

Conflict of interest

Funding sources

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Vol 75 - N° 2

P. 104-114 - août 2017 Retour au numéro

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An evaluation of purified Salmonella Typhi protein antigens for the serological diagnosis of acute typhoid fever - 06/10/17

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