Current knowledge for the microbiological diagnosis of Tropheryma whipplei infection

ABSTRACT

Introduction

Whipple's disease is a rare clinical entity that is usually fatal if left untreated.Tropheryma whippleiwas first cultured 20 years ago, and has led to the development of diagnostic tools that have greatly improved knowledge of the disease. T. whipplei is actually more common than initially described with the description of common asymptomatic carriage.

Areas covered

We reviewed current knowledge of microbiological diagnosis and summarized the diagnostic strategy ofT. whipplei infection. Articles were selected from Medline and Google scholar using the keywords ‘Tropheryma whipplei’ OR ‘Whipple’s disease’ AND ‘diagnosis’.

Expert opinion

Definitive diagnosis of Whipple’s disease is challenging and continues to be based on immunohistochemical analysis or PAS staining combined with positive qPCR on duodenal biopsy. Initially, screening forT. whipplei was recommended on stool and saliva which are associated with a high positive predictive value of Whipple’s disease. However, given the presence of a large number of asymptomatic carriers, the specificity of a positive qPCR on these samples is likely to have decreased and their interests should be reevaluated. The development of new noninvasive tests may be useful for the diagnosis of Whipple’s disease and qPCR performed on urine could be a promising alternative.

KEYWORDS:

• Tropheryma whipplei
• Whipple’s disease
• qPCR
• fish
• diagnosis

Article highlights

• Classic Whipple’s disease and localized infections are rare clinical entities but T. whipplei is a common bacterium responsible for asymptomatic carriage in stool and/or saliva in humans.

• T. whipplei infection spectrum is still probably incompletely understood and diagnosis remained challenging. Definitive diagnosis of classic Whipple’s disease or localized infections required invasive specimens collected from affected site and continues to be based on the complementary of different techniques to ensure that the results supporting one another.

• An isolated positive qPCR on intestinal biopsy should be confirmed by alternative techniques (PAS, IHC) to reach a definitive diagnosis of classic Whipple’s disease.

• qPCR on urine samples currently present a higher positive predictive value (PPV) of Whipple’s disease than qPCR on stool or saliva samples when screening for T. whipplei on non-invasive samples.

• 18F-FDG-PET/CT could be used for patient diagnosis and follow-up.

• Associations between different immune-related genes and T. whipplei susceptibility have been established.

• Efforts should be made to investigate genetic predisposition and the role of the host’s immune system in both clearing the infection and developing chronic Whipple’s disease.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work received funding from the French government, through the Agence Nationale pour la Recherche, including the ‘Investissements d’Avenir’ programme under reference Méditerranée Infection 10-IAHU-03.