The case i shows how previous symptoms can contribute to the diagnosis of this illness, and ii elucidates current recommended diagnostic and therapeutic approaches to whipples disease. Apr 01, 2009 tropheryma whipplei is a grampositive bacterium responsible for whipples disease wd, a rare and chronic infection resulting in several heterogeneous clinical characteristics with or without gastrointestinal symptoms. This test allows the rapid and sensitive detection of tropheryma whipplei dna from. Genotypic analysis of tropheryma whipplei from patients with. Its clinical manifestations generally include diarrhea, preceded in most cases by articular symptoms. Intrafamilial circulation of tropheryma whipplei, france. We report the case of a 61yearold male patient who presented to emergency room complaining of asthenia, arthralgia, anorexia, articular complaints intermittent diarrhea, and a 10kg weight loss in one year. Whipples disease is a rare, systemic infectious disease caused by the bacterium tropheryma whipplei. Tropheryma whipplei is the causal agent of whipples disease a systemic chronic infection affecting predominantly caucasian middleaged men and involving multiple organ systems. Clinical manifestations, treatment, and diagnosis of. Tropheryma whipplei, the agent of whipples disease, is a grampositive rodshaped bacterium that belongs to the group of actinobacteria. Tropheryma whipplei, formerly called tropheryma whippelii, is a bacterium and the causative organism of whipples disease and, rarely, of endocarditis while t.
In the past decade, the responsible organism tropheryma whipplei has been cultivated, its genome sequenced and its antibiotic susceptibility defined. Whipple limbic encephalitis infectious diseases jama. Whipples disease, a systemic, chronic infectious disease caused by tropheryma whipplei, is extremely rare in asian populations. Whipples disease was first described in 1907, the genomic composition of the causative organism, tropheryma whipplei, was unravelled in 2003 and its in vitro susceptibility to antibiotics started. Cases of tw infection diagnosed from 1995 to 2010 were identified in three us referral centers and from 1995 to 2015 in one. Immunohistochemistry in the diagnosis of whipples disease. Recent advances in medical microbiology, epidemiology, cellular biology, and the availability of an expanded set of diagnostic methods such as histopathology, immunohistochemistry, pcr, and bacterial culture have improved our understanding of the clinical range and natural course of tropheryma whipplei infection and whipples disease. Tropheryma whipplei in culturenegative endocarditis.
Whipples disease, caused by the bacterium tropheryma whipplei, is a rare chronic multisystem illness commonly affecting the gastrointestinal gi tract and presenting with a triad of diarrhoea. Whipple disease causes weight loss, incomplete breakdown of carbohydrates or fats, and problems with the immune system. Tropheryma whipplei glycosylation in the pathophysiologic profile. Tropheryma whipplei laboratoire information genomique et. Summary whipples disease is a rare infectious disease that can be fatal if left untreated. Pdf tropheryma whipplei glycosylation in the pathophysiologic. Whipple disease genetic and rare diseases information. Tropheryma whipplei infection and whipples disease the. Tropheryma whipplei infection and whipples disease thomas marth, verena moos, christian muller, federico biagi, thomas schneider recent advances in medical microbiology, epidemiology, cellular biology, and the availability of an expanded set of. Data from this series and the literature 2224 were included.
Aug 16, 2016 chronic infection with tropheryma whipplei. Tropheryma whipplei infection should be considered in patients with suspected infective endocarditis with negative blood cultures. The role of t cells in the pathogenesis of classical. A correct diagnosis is necessary due to its high mortality rate. The bacterium tropheryma whipplei, which causes whipple disease in humans, is commonly detected in the feces of persons in africa.
May 04, 2019 tropheryma whipplei is a topic covered in the johns hopkins abx guide to view the entire topic, please sign in or purchase a subscription official website of the johns hopkins antibiotic abx, hiv, diabetes, and psychiatry guides, powered by unbound medicine. Changing paradigms in whipples disease and infection with. Tropheryma whipplei associated with diarrhoea in young. Moreover, besides classical whipples disease, there are newly recognized infections with t. Here we describe a case of infective endocarditis caused by tropheryma whipplei in a patient with no other symptoms of whipples disease. Tropheryma whipplei is the bacterial agent of whipples disease, a spectacular. Risk factors related to the host whipple the safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Whipple disease wd is an infection caused by the bacterium tropheryma whipplei tw. Keywords whipple disease intestinal lipodystrophy tropheryma malabsorption syndromes. Malabsorption syndrome due to tropheryma whipplei severe infection in a patient thirteen years after kidney transplantation abdellaoui i1, sahtout w1, ben mansour i2, mokni m3, azzabi a 1, mrabet s, guedri y 1, zellama d, toumi s1, sabri f 1, amor s, achour a1 and jmaa a 2 1nephrology, dialysis and transplantation ward, sahloul hospital, france 2gastrology ward, sahloul hospital, france. Oct 24, 2019 whipple disease is a systemic disease most likely caused by a grampositive bacterium, tropheryma whippelii. During june 2010march 2012, we collected wholeblood fingerprick samples from 786 febrile and 385 healthy villagers. Whipple disease celiac disease center columbia university. Very little is known about the epidemiology of whipples disease. Nov 18, 2015 tropheryma whipplei infection should be considered in patients with suspected infective endocarditis with negative blood cultures. J clin microbiol 2012 feb this organism was the most frequently identified pathogen among patients with culturenegative endocarditis and rarely caused the gastrointestinal symptoms typical of whipple disease. Does tropheryma whipplei contribute to travelers diarrhea a pcr analysis of paired stool samples in french travelers to senegal. Pdf tropheryma whipplei is the bacterial agent of the wellknown and rare whipples disease, mainly observed among caucasians. Tropheryma whipplei glycosylation in the pathophysiologic. Tropheryma whippelii an overview sciencedirect topics. The classical form of tropheryma whipplei infection, i.
Apr 06, 2017 tropheryma whipplei, the agent of whipple disease, causes a rare bacterial disease that may be fatal if not treated. Newly recognised clinical spectrum of tropheryma whipplei infection. Nov 01, 20 tropheryma whipplei endocarditis differs from classic whipple disease, which primarily affects the gastrointestinal system. Tropheryma whipplei infection and whipples disease. Whipple disease is a chronic, systemic illness that in the majority of cases involves the small intestine and its lymphatic drainage.
The name tropheryma whippelii was proposed for this bacterium. A new study performed by a swiss team has shown the presence of t. Update on whipples disease and tropheryma whipplei. These represent macrophages filled with tropheryma whipplei. Tropheryma whipplei formerly tropheryma whippelii is a grampositive bacterium that causes a rare, chronic infectious systemic disease, predominantly in middleaged caucasian men. The goal of this activity is to describe the epidemiology, laboratory findings, and clinical presentation of tropheryma whipplei gastroenteritis in children. Whipples disease is a rare, multisystemic, chronic infectious disease caused by tropheryma whipplei, a grampositive bacterium from the actinomycetes clade with a genome rich in guanine and cytosine gc nucleotides. Tropheryma whipplei realtime pcr great ormond street. In order to produce monoclonal antibodies mabs against this bacterium, we inoculated mice with two different strains, slow2 and endo5. Tropheryma whipplei in culturenegative endocarditis larry m. Tropheryma whippelii whipples disease infectious disease. Tropheryma whipplei is a grampositive bacterium with a reduced genome closely related to mycobacteria and actinomycetes 1.
Whipples disease is a systemic infectious disease associated with the bacterium tropheryma whipplei. Clinical findings may include malabsorption, chronic diarrhea, abdominal pain, arthralgia, fever, and central nervous system symptoms. Tropheryma whipplei infective endocarditis as the only. Whipples disease wd is a systemic disease that predominantly affects the intestine and is associated with the presence of tropheryma whipplei in macrophages 1,2. Tropheryma whipplei wikipedia, a enciclopedia livre. The disease primarily affects middleaged individuals, with a peak incidence in the third and fourth decades. Tropheryma whipplei and gastroenteritis until recently, t. The case was diagnosed using broadrange pcr and confirmed by specific pcrs. Tropheryma whipplei is the bacterial agent of whipples disease. Specimens were analyzed mostly by molecular and histologic techniques.
This activity is intended for pediatricians, infectious disease specialists, and other physicians who care for patients at risk for infection with tropheryma whipplei. A paradoxical tropheryma whipplei western blot differentiates patients with whipple disease from asymptomatic carriers. Tropheryma whipplei is rod shaped, a grampostive bacterium 5. T ropheryma whipplei is known mainly as the bacterial pathogen responsible for. High frequency of tropheryma whipplei in culturenegative. Tropheryma whipplei in children with gastroenteritis. Specific genome features include deficiencies in amino acid metabolisms, the lack of clear thioredoxin. Tropheryma whipplei genome genome biology full text. Tropheryma whipplei in children with gastroenteritis volume. Gastroenteritis in children and tropheryma whipplei. Whipples disease is a systemic disease that affects many organ systems, producing. Tropheryma whipplei endocarditis pubmed central pmc. Duke criteria were ineffective for diagnosis before heart valve. T whipplei is frequently detected in stool and saliva samples from patients with whipples disease and, to a small degree, in asymptomatic carriers roughly 24%.
Polymerase chain reaction assay for the diagnosis of whipple disease. Most patients present with nonspecific symptoms, and as routine cultivation of the bacterium is not feasible, it is difficult to diagnose this infection. Whipples disease wd is a chronic infectious disorder in which almost all organ systems can be invaded by the rodshaped bacterium tropheryma whipplei. Western blotting was performed for samples from children with diarrhea who had positive or negative results for t. Pcrbased methods for diagnosis of wd have been developed. Quantitative pcr determined a doubling time of approximately 28. Tropheryma whipplei is a bacterium commonly found in people with whipples. Small intestine tissue duodenum, ileum, or jejunum, lymph node, other visceral tissue, synovial tissue. The diagnosis of this disease is often carried out by a duodenoscopy with histological examination, including periodic acidschiff pas staining in conjunction with pcr and immunochemistry. Production of monoclonal antibodies to tropheryma whipplei.
In revealing its genetic blueprint we learn a great deal about the particular strategy chosen by t. Tropheryma whipplei as a cause of epidemic fever, senegal. Now, this appearance is nonspecific the main differentials are xanthelasma macrophages filled with fat and atypical mycobacterial infection macrophages filled with mycobacterium avium complex bacteria, both of which are more common than whipples disease. Tropheryma whipplei also has a mutation in the dna gyrase, which relates to the fact that it is resistant to quinolone antibiotic.
Deglycosylation of tropheryma whipplei biofilm and discrepancies between diagnostic results during whipples disease progression article pdf available in scientific reports 6. Yardley and hendrix described the characteristic electron microscopic finding of a trilaminar bacterial cell wall both within macrophages and extracellularly. The fact that the disease is more frequently diagnosed in older individuals might at least in part be related to the usually significant. This means that this pathogen is the smallest known within its class. It was finally isolated in eukaryotic cells in the year 2000 and propagated in culture at thirtyseven degrees celsius, but was believed to resist culturing for a long time 3. In 2000, tropheryma whipplei was finally identified as the cause of whipples disease, a chronic condition with protean manifestations that was first described in 1907. Tropheryma whipplei endocarditis volume 19, number 11.
Tropheryma whipplei is the etiologic pathogenic agent of whipple disease wd, characterized by various clinical signs, such as diarrhea, weight loss, lymphadenopathy, and polyarthritis. Numerous reports have presented puzzling discrepancies between diagnosis methods. Mar 23, 2018 whipple disease wd is an infection caused by the bacterium tropheryma whipplei tw. Deglycosylation of tropheryma whipplei biofilm and discrepancies. When recognized and treated, whipple disease can usually be cured. Whipple himself probably observed the organisms as rodshaped. According to the data published by dobbins, it predominantly affects caucasian males, with a maletofemale ratio of approximately 8. The disease was first described by george hoyt whipple in 1907 as intestinal lipodystrophy due to the accumulation of large masses of neutral fats and fatty acids. The relationship of whipples disease with the johns hopkins hospital continued, and in 1961, drs. Unique genotypes were associated with this bacterium.
Survival of tropheryma whipplei, the agent of whipples disease. Tropheryma whipplei, which causes whipple disease, is found in human feces and may cause gastroenteritis. Duke criteria were ineffective for diagnosis before heart valve analysis. Pdf intrafamilial circulation of tropheryma whipplei. Fenollar and his coauthors have contributed greatly to our understanding of t. The human pathogen tropheryma whipplei is the only known reduced genome species whipplei twist strain, encoding 808 predicted proteincoding genes. Whipples disease symptoms, diagnosis and treatment. The high sensitivity of amplification by pcr requires the specimen to be processed in an environment in which contamination of the specimen by tropheryma whipplei dna is unlikely. Although the first descriptions of the disorder described a malabsorption syndrome with small intestine involvement, the disease also affects the joints, central nervous system, and cardiovascular system. From december 2009 to january 20, rectal swabs collected from 3796 children in the. The colocalization of the ph probe with intracellular bacteria was analyzed by merging the dmnerf and texas red fluorescence images. Deglycosylation of tropheryma whipplei biofilm and discrepancies between diagnostic results during.
Deglycosylation of tropheryma whipplei biofilm and. Because these clinical forms may lead to cwd under certain conditions, as. Dr whipple first described the laternamed whipples disease in a 36yearold clinician in 1907 with gradual loss of weight and strength, stools consistent chiefly of neutral fat and fatty acids, indefinite abdominal signs, and a peculiar multiple arthritis. Text is available under the creative commons attributionsharealike license. Tropheryma whipplei an overview sciencedirect topics. Pdf deglycosylation of tropheryma whipplei biofilm and. The disorder mainly affects white men of middleage. Whipple disease is a systemic bacterial infection due to tropheryma whipplei. Whipples disease is a rare systemic infectious disorder caused by the bacterium tropheryma whipplei. We produced and 10 mabs against slow2 and endo5, respectively. Since its identification, information concerning tropheryma whipplei, the causative agent of whipples disease wd, has increased. Pdf does tropheryma whipplei contribute to travelers. Research tropheryma whipplei in children with gastroenteritis. Because of its metabolic deficiencies, like the major energy producing system, which is the krebs or tca it must get the nutrients it needs from the environment, in this case, the stomach lining.
Pdf tropheryma whipplei is a bacterium commonly found in people with. Specific genome features include deficiencies in amino acid metabolisms, the lack of clear thioredoxin and. The disease is caused by infection with tropheryma whipplei, a bacterium that may be more common than was initially assumed. Pdf murine model of infection by tropheryma whipplei. Mar 30, 2016 whipples disease is a systemic infectious disease associated with the bacterium tropheryma whipplei. It is important for tropheryma whipplei to have its genome sequenced, because with a 0. Tropheryma whipplei and whipples disease request pdf. Listing a study does not mean it has been evaluated by the u. First described by george hoyt whipple in 1907 and commonly considered a gastrointestinal disorder, whipples disease primarily causes malabsorption but may affect any part of the body including the heart, brain, joints, skin, lungs and the eyes.
To report on the demographics, clinical manifestations, diagnostic findings, treatment, and outcomes of tw infection. Tropheryma whipplei endocarditis differs from classic whipple disease, which primarily affects the gastrointestinal system. Tropheryma whippelii definition of tropheryma whippelii by. Number of reported cases of tropheryma whipplei endocarditis per 1 million inhabitants in each area of france over 10 years. Tropheryma whipplei is an actinobacterium and the etiologic agent of whipple disease. The classical form of the disease includes diarrhoea, weight loss, arthritis, endocarditis and neurological manifestations. Tropheryma whipplei was detected in preliminary studies in faeces of young children with diarrhoea and also in faeces of asymptomatic persons, not only in europe but also in africa.
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