scholarly journals A Paradoxical Screening Serological Assay for the Diagnosis of Whipple’s Disease (infection with Tropheryma whipplei)

2021 ◽  
Author(s):  
K.C. Liew ◽  
Chelsea Nguyen ◽  
Nilakshi T Waidyatillake ◽  
John Stenos ◽  
Aaron Walton ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Characteristic Curve ◽  
Tropheryma Whipplei ◽  
Whipple’S Disease ◽  
Igg Antibody ◽  
Whipple's Disease ◽  
Serological Assay ◽  
Igm Antibody ◽  
Antibody Titers

ABSTRACTWhipple’s disease (WD) is a rare infection due to Tropheryma whipplei. Following in-vitro cultivation of T. whipplei, an indirect-immunofluorescence serological assay (IFA) was developed. We tested the hypothesis that this assay could be used to either identify WD patients, or rule out WD, in patients in whom the diagnosis is being considered, based on the antibody titers of their IgM and IgG antibody responses. In this small study fourteen WD patients and 22 healthy volunteers’ sera were obtained from across Australia. All specimens were coded and de-identified before testing. A patient with an IgG antibody titer of ≤1:16 may have WD [sensitivity 57% (8/14) and specificity close to 100% (22/22)]. High IgM antibody titers (≥1:256) were more common in WD patients [sensitivity 50% (7/14) and specificity 86% (19/22)] than in controls. The area under Receiver-Operator-Characteristic curve for IgG in the IFA assay was 0.84 (95% CI 0.69-1.00). At an IgG antibody titer of ≤1:16 the Youden’s index was 0.57. WD patients’ under-produce IgG antibody to T.whipplei but are more likely to over-produce IgM antibodies. This screening IFA serological assay may be clinically useful in detecting those with a possible diagnosis of WD. Patients with an IgG antibody titer of ≤1:16 and an IgM antibody titer of ≥1:256 may have WD and should proceed to a tissue biopsy and PCR for confirmation. Further validation of this assay, by increasing the sample size, by testing it in patients with non-WD disease and trialing in other countries should be undertaken.

Tropheryma whipplei, Immunosuppression and Whipple's Disease: From a Low-Pathogenic, Environmental Infectious Organism to a Rare, Multifaceted Inflammatory Complex

2015 ◽  
Vol 33 (2) ◽  
pp. 190-199 ◽  
Author(s):  
Thomas Marth
Keyword(s):  
Heart Valves ◽  
Clinical Manifestations ◽  
Systemic Infection ◽  
Tropheryma Whipplei ◽  
Molecular Techniques ◽  
Whipple’S Disease ◽  
Whipple's Disease ◽  
New Findings ◽  
The Central Nervous System ◽  
Body Compartments

Background: The actinobacterium Tropheryma whipplei was detected 20 years ago by molecular techniques, and following its culture has been characterized as the cause of a systemic infection known as Whipple's disease (WD). T. whipplei occurs in the environment, is prevalent only in humans, is believed to be transmitted via oral routes and to be host dependent. Key Messages: The classical form of T. whipplei infection, i.e. classical WD (CWD), is rare. It is well defined as slowly progressing chronic infection with arthralgia, diarrhea and weight loss, mostly in middle-aged men. However, current research revealed a much broader spectrum of clinical features associated with T. whipplei infection. Thus, T. whipplei may cause acute and transient infections (observed primarily in children) and the bacterium, which is found in soil and water, occurs in asymptomatic carriers as well as in CWD patients in clinical remission. In addition, T. whipplei affects isolated and localized body compartments such as heart valves or the central nervous system. Subtle immune defects and HLA associations have been described. New findings indicate that the progression of asymptomatic T. whipplei infection to clinical WD may be associated with medical immunosuppression and with immunomodulatory conditions. This explains that there is a discrepancy between the widespread occurrence of T. whipplei and the rareness of WD, and that T. whipplei infection triggered by immunosuppression presents with protean clinical manifestations. Conclusions: This review highlights recent findings and the clinical spectrum of infection with T. whipplei and WD, focusing specifically on the role of host immunity and immunosuppression. Current concepts of the pathogenesis, diagnosis and therapy are discussed.

scholarly journals Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway

2010 ◽  
Vol 1 (4) ◽  
pp. e34-e34 ◽  
Author(s):  
L Gorvel ◽  
K Al Moussawi ◽  
E Ghigo ◽  
C Capo ◽  
J-L Mege ◽  
...  
Keyword(s):  
Tropheryma Whipplei ◽  
Whipple’S Disease ◽  
Extrinsic Pathway ◽  
Whipple's Disease ◽  
Macrophage Apoptosis

scholarly journals Tropheryma whippleiCrystalline Keratopathy: Report of a Case and Updated Review of the Literature

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Scott D. Schoenberger ◽  
Sumeer Thinda ◽  
Stephen J. Kim
Keyword(s):  
Signs And Symptoms ◽  
Tropheryma Whipplei ◽  
Extensive Literature ◽  
Whipple’S Disease ◽  
Whipple's Disease ◽  
Case Presentation ◽  
Search Terms ◽  
Crystalline Keratopathy ◽  
Extensive Literature Search ◽  
English Articles

Purpose. To report a case ofTropheryma whippleiinfection with crystalline keratopathy and review the recent literature on the presentation, diagnosis, and management of Whipple's disease.Methods. Detailed case presentation and extensive literature search of Pubmed for all years through February 2012 using the following search terms:Whipple's disease, Tropheryma whipplei, corneal deposits, crystalline keratopathy, and uveitis. Relevant articles were retrieved and analyzed. English abstracts were used for non-English articles. Cross-referencing was employed and reference lists from selected articles were used to identify additional pertinent articles.Results. Diagnosis of Whipple's disease remains challenging and untreated infection can result in mortality. Ocular signs and symptoms are usually nonspecific, but several independent cases have reported the presence of intraocular crystals or crystalline-like deposits.Conclusions. The presence of intraocular crystals or crystalline-like deposits may be an identifying feature of ocular Whipple’s disease.

scholarly journals Survival of Tropheryma whipplei, the Agent of Whipple's Disease, Requires Phagosome Acidification

2002 ◽  
Vol 70 (3) ◽  
pp. 1501-1506 ◽  
Author(s):  
Eric Ghigo ◽  
Christian Capo ◽  
Marianne Aurouze ◽  
Ching-Hsuan Tung ◽  
Jean-Pierre Gorvel ◽  
...  
Keyword(s):  
Hela Cells ◽  
Cathepsin D ◽  
Tropheryma Whipplei ◽  
Host Cells ◽  
Whipple’S Disease ◽  
Acidic Ph ◽  
Bafilomycin A1 ◽  
Phagosome Maturation ◽  
Whipple's Disease ◽  
New Approach

ABSTRACT Tropheryma whipplei was established as the agent of Whipple's disease in 2000, but the mechanisms by which it survives within host cells are still unknown. We show here that T. whipplei survives within HeLa cells by controlling the biogenesis of its phagosome. Indeed, T. whipplei colocalized with lysosome-associated membrane protein 1, a membrane marker of late endosomal and lysosomal compartments, but not with cathepsin D, a lysosomal hydrolase. This defect in phagosome maturation is specific to live organisms, since heat-killed bacilli colocalized with cathepsin D. In addition, T. whipplei survived within HeLa cells by adapting to acidic pH. The vacuoles containing T. whipplei were acidic (pH 4.7 ± 0.3) and acquired vacuolar ATPase, responsible for the acidic pH of late phagosomes. The treatment of HeLa cells with pH-neutralizing reagents, such as ammonium chloride, N-ethylmaleimide, bafilomycin A1, and chloroquine, increased the intravacuolar pH and promoted the killing of T. whipplei. The ability of T. whipplei to survive in an acidic environment and to interfere with phagosome-lysosome fusion is likely critical for its prolonged persistence in host cells during the course of Whipple's disease. Our results suggest that manipulating the intravacuolar pH may provide a new approach for the treatment of Whipple's disease.

scholarly journals Type I Interferon Induction Is Detrimental during Infection with the Whipple's Disease Bacterium, Tropheryma whipplei

2010 ◽  
Vol 6 (1) ◽  
pp. e1000722 ◽  
Author(s):  
Khatoun Al Moussawi ◽  
Eric Ghigo ◽  
Ulrich Kalinke ◽  
Lena Alexopoulou ◽  
Jean-Louis Mege ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Tropheryma Whipplei ◽  
Whipple’S Disease ◽  
Type I ◽  
Whipple's Disease ◽  
Interferon Induction

Tropheryma whipplei infection and Whipple's disease

2016 ◽  
Vol 16 (3) ◽  
pp. e13-e22 ◽  
Author(s):  
Thomas Marth ◽  
Verena Moos ◽  
Christian Müller ◽  
Federico Biagi ◽  
Thomas Schneider
Keyword(s):  
Tropheryma Whipplei ◽  
Whipple’S Disease ◽  
Whipple's Disease

scholarly journals Antibiotic Susceptibility of Tropheryma whipplei in MRC5 Cells

2004 ◽  
Vol 48 (3) ◽  
pp. 747-752 ◽  
Author(s):  
Areen Boulos ◽  
Jean-Marc Rolain ◽  
Didier Raoult
Keyword(s):  
Clinical Manifestations ◽  
Extensive Study ◽  
Tropheryma Whipplei ◽  
Whipple’S Disease ◽  
Chronic Infections ◽  
Pcr Assay ◽  
Whipple's Disease ◽  
Reference Treatment ◽  
Clinical Observations ◽  
Reference Strains

ABSTRACT Whipple's disease is considered a rare chronic disease with a broad spectrum of clinical manifestations. Several antibiotics have been used for the treatment of this disease, and the current reference treatment was determined empirically on the basis of only a few clinical observations. Patients should be treated for months, and many relapse after antibiotic withdrawal. We report here the first extensive study on the susceptibilities of three reference strains of Tropheryma whipplei to antibiotic in cell culture by using a real-time PCR assay as previously described. We found that doxycycline, macrolides, ketolides, aminoglygosides, penicillin, rifampin, teicoplanin, chloramphenicol, and trimethoprim-sulfamethoxazole were active, with MICs ranging from 0.25 to 2 μg/ml. Vancomycin was somewhat active at an MIC of 10 μg/ml. We found heterogeneity in the susceptibility to imipenem, with one strain being susceptible and the two other strains being resistant. Cephalosporins, colimycine, aztreonam, and fluoroquinolones were not active. We also demonstrated that a combination of doxycycline and hydroxychloroquine was bactericidal. This combination has been shown to be active in the treatment of patients suffering from chronic infections with Coxiella burnetii, a bacterium that is also found intracellularly in acidic vacuoles. We believe, then, that this combination therapy should be further evaluated in clinical trials for the treatment of Whipple's disease.

scholarly journals Back from the brink of obscurity

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Donald C Vinh
Keyword(s):  
Transcription Factor ◽  
Rare Condition ◽  
Tropheryma Whipplei ◽  
Whipple’S Disease ◽  
Whipple's Disease

A mutation in a transcription factor makes people susceptible to Tropheryma whipplei, the bacterium that causes a rare condition called Whipple's disease.

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