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Abstract

  1. Top of page
  2. Abstract
  3. Reactive Arthritis
  4. Guillain-Barré Syndrome
  5. Post-Infectious Irritable Bowel Syndrome
  6. Disclaimer
  7. Declaration of Interests
  8. References

Background

Travelers' diarrhea (TD) has generally been considered a self-limited disorder which resolves more quickly with expeditious and appropriate antibiotic therapy given bacteria are the most frequently identified cause. However, epidemiological, clinical, and basic science evidence identifying a number of chronic health conditions related to these infections has recently emerged which challenges this current paradigm. These include serious and potentially disabling enteric and extra-intestinal long-term complications. Among these are rheumatologic, neurologic, gastrointestinal, renal, and endocrine disorders. This review aims to examine and summarize the current literature pertaining to three of these post-infectious disorders: reactive arthritis, Guillain-Barré syndrome, and post-infectious irritable bowel syndrome and the relationship of these conditions to diarrhea associated with travel as well as to diarrhea associated with gastroenteritis which may not be specifically travel related but relevant by shared microbial pathogens. It is hoped this review will allow clinicians who see travelers to be aware of these post-infectious sequelae thus adding to our body of knowledge in travel medicine.

Methods

Data for this article were identified by searches of PubMed and MEDLINE, and references from relevant articles using search terms “travelers' diarrhea” “reactive arthritis” “Guillain-Barré syndrome” “Post-Infectious Irritable Bowel Syndrome.” Abstracts were included when related to previously published work.

Results and Conclusions

A review of the published literature reveals that potential consequences of travelers' diarrhea may extend beyond the acute illness and these post-infectious complications may be more common than currently recognized. In addition since TD is such a common occurrence it would be helpful to be able to identify those who might be at greater risk of post-infectious sequelae in order to target more aggressive prophylactic or therapeutic approaches to such individuals. It is hoped this review will allow clinicians who see travelers to be aware of these post-infectious sequelae thus adding to our body of knowledge in travel medicine.

Travelers' diarrhea (TD) is a common and predictable illness in people traveling to developing countries.[1, 2] The incidence of TD has been reported to be between 30 and 70% depending on travel destination and season of travel.[2] TD is caused by the ingestion of contaminated food or water.[3] The majority (80%–90%) of TD cases are caused by bacterial pathogens,[2] although protozoal and viral pathogens are also identified. Microbial pathogens which cause TD can vary with geography,[3, 4] but generally speaking, enterotoxigenic Escherichia coli (ETEC), enteroaggregative E coli (EAEC), and norovirus appear to be the most important pathogens worldwide.[5] TD is typically an acute self-limited illness with symptoms resolving within 1 to 5 days but there has been increasing recognition of serious and potentially disabling enteric and extra-intestinal long-term complications of acute TD. This review will discuss three of these complications, reactive arthritis (ReA), Guillain-Barré syndrome (GBS), and post-infectious irritable bowel syndrome (PI-IBS), with a particular focus on their relationship with enteric infection. Although this review will highlight the relationship of these conditions with diarrhea associated with travel, much of the data are drawn from outbreaks of gastroenteritis which may not be specifically travel related. However, as the microbial pathogens are those commonly seen in TD it is hoped this review will allow clinicians who see travelers to be aware of these post-infectious sequelae thus adding to our body of knowledge in travel medicine.

Reactive Arthritis

  1. Top of page
  2. Abstract
  3. Reactive Arthritis
  4. Guillain-Barré Syndrome
  5. Post-Infectious Irritable Bowel Syndrome
  6. Disclaimer
  7. Declaration of Interests
  8. References

Symptoms

ReA was first described following gastrointestinal and genitourinary infections several decades ago. Review of the literature suggests variable attack rates following gastroenteritis and TD. Much of this variability is due in part to a lack of standardization of the definition of ReA with some studies using only the ReA triad (eg, arthritis associated with urethritis and conjunctivitis) to make the definition and others using only certain microorganisms as triggers in order to calculate rates of ReA.[5]

The onset of joint symptoms is typically 1 to 4 weeks (most commonly 2 weeks) post-enteric infection with a reported range of 4 to 35 days. The joint disease may be monoarticular but is more commonly polyarticular and the clinical spectrum varies from slight transient arthralgias to long-standing debilitating arthritis. There is a predilection for joints of the lower extremities: knees and ankles, although small joints may be involved. Tenosynovitis may occur and the elbow, wrists, low back, and shoulder may be affected as well. Extra-articular manifestations of ReA may be mucosal, urethral, and cutaneous. Ocular manifestations include conjunctivitis, episcleritis, and uveitis.

The duration of arthritic symptoms is variable as well. Fifty percent of patients with ReA after enteric infection recovered in approximately 30 weeks in one study,[6] while in another study of an outbreak of Salmonella typhimurium infection, 60% had joint pains 4 to 5 months later.[7] Another study showed that the majority of patients with Salmonella-associated ReA were symptomatic 5 years after enteric infection.[8] In a review of Campylobacter infections, 5% of those with ReA had chronic or relapsing symptoms 5 years later.[9]

Incidence Associated With Enteric Infection

ReA has been reported to occur in 1%[10] to 62%[11] of people following an enteric infection caused by any one of a variety of microbes. The enteric bacterial species most often associated with ReA are Salmonella enteritidis, Shigella spp., Campylobacter spp., and Yersinia spp.[5] Salmonella spp. or Yersinia spp. were identified in 52% of patients with enteric ReA in one study.[9] Case reports linking ReA to Cyclospora,[12] Giardia,[13] Clostridium difficile,[14] and TD with unspecified etiology[15] have been reported, although no well-controlled studies implicating these pathogens have been published to date. Notably all of these organisms, with the exception of C difficile, are also common pathogens associated with TD. A recent report utilizing a case–control study design from data obtained from the Department of Defense Medical Encounter Database also highlights that the burden of post-infectious ReA may be underestimated in high risk populations such as travelers and deployed military service members.[16] In this study, not only was increased risk of ReA by at least two separate ICD-9 medical encounter visits (as measured by ReA triad or post-dysenteric arthritis) following an acute gastroenteritis episode identified (OR: 4.42, 95% CI: 2.24, 8.73), but other incidental acute ICD-9 visits related to non-specific arthalgia/arthritis (undifferentiated ReA) were also found to be increased following an episode of gastroenteritis (OR: 1.76, 95% CI: 1.49, 2.07). Interestingly, medical care visits for these ICD-9 codes persisted in approximately 40 and 12% of specific ReA and undifferentiated ReA, respectively.

Risk Factors

Predicting who is at risk is problematic but it is believed that host factors, pathogen factors, and host–pathogen interaction all play a role. ReA is frequently, but not always associated with HLA-B27. Whereas HLA-B27 is found in 6% of the general population, it is found in approximately 50% of patients with ReA related to enteric infection[5] and 70% of patients with the ReA triad.

The risk of ReA after enteric infection in HLA-B27-positive patients may depend on the pathogenetic organism; the risk of ReA was significantly associated with infection by Salmonella, Shigella, or Yersinia, but not with Campylobacter or E coli.[17] Despite the significant association of HLA-B27 with the development of ReA following Salmonella infection, HLA-B27-independent ReA after Salmonella infection has been reported.[18, 19] However, some of the patients with HLA-B27-independent ReA expressed other class I major histocompatibility complex genes including the HLA-B27 crossreacting antigens B7, B22, and B40.[18] Two other studies have reported the presence of the related antigens B7 and further demonstrated the presence of HLA-Bw60 in a subset of patients with ReA.[19, 20] Thus, the members of the HLA-27 cross-reacting antigen group may also be risk factors for ReA.

The genetic risk of contracting ReA is not limited to HLA genotypes. A genetic variant of the Toll-like receptor (TLR)-2 was recently shown to be associated with ReA after infection with Salmonella.[21] This TLR-2 polymorphism appeared to be specifically related to the development of ReA because it was not detected in controls infected with Salmonella but who had not developed ReA.

Pathophysiology

One model for the pathogenic mechanism leading to ReA associated with enteric infection is depicted in Figure 1.[5, 22] During active infection, enteric bacteria invade the intestinal mucosa, enter the systemic circulation, and are transported to the joint. Transport to the joint may be mediated by monocytes (or other blood cells) that can carry the bacteria[22] and bacterial antigens [eg, lipopolysaccharide (LPS), heat shock protein].[23-25] Indeed, bacterial antigens[23, 26-30] and evidence of direct synovial bacterial infection (ie, bacterial DNA or RNA)[26, 31, 32] have been detected in synovial fluid from joints of patients with ReA. Salmonella LPS appears to be an important virulence factor and may assist the organism in breaching the intestinal mucosa inciting this variety of immune and inflammatory events. LPS has been demonstrated in synovial cells and ReA joints.

image

Figure 1. Proposed mechanism for molecular mimicry in the pathophysiology of reactive arthritis.[5, 22]

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Once in the synovial fluid of the joint, the bacterial antigens invoke a local and persistent immune response leading to the inflammation associated with ReA. This may occur via two possible mechanisms: (1) the immune system may be directly activated by recurrent infection or bacterial antigen delivery to the joint or (2) the immune response to the initial infection may result in production of antibody epitopes with cross-reactivity with bacterial and human antigens.[5] The latter of these two processes, known as molecular mimicry, may result in the activation of cytotoxic T lymphocytes with reactivity against HLA-B27, which contains protein sequences homologous to those detected in proteins of bacteria associated with ReA.[33-36] Indeed, antibodies with reactivity toward HLA-B27 have been detected in patients with ReA.[33, 34, 36] In addition, the novel finding of a variant TLR-2 in patients with ReA suggests that this receptor may also have a role in ReA pathogenesis.

An outcome of ReA following TD is more likely with a more severe enteric infection. ReA is more commonly associated with prolonged diarrhea (symptoms greater than 7 days), and there is a positive correlation with an emergency room visit or hospital admission for diarrhea. Antibiotics did not appear to decrease the risk for patients treated with fluoroquinolones for S enteritidis and ReA may be slightly increased in those treated with antibiotics.[37] Postulated reasons for this include: antibiotic-induced alteration of the microbe, prolongation in carriage of the microorganism, or it may simply be a marker of more severe disease. However in another study of patients who developed ReA after infection with Salmonella hadar, antibiotic therapy seemed to be protective.[38]

Guillain-Barré Syndrome

  1. Top of page
  2. Abstract
  3. Reactive Arthritis
  4. Guillain-Barré Syndrome
  5. Post-Infectious Irritable Bowel Syndrome
  6. Disclaimer
  7. Declaration of Interests
  8. References

Guillain-Barré syndrome (GBS) is a group of conditions in which an autoimmune response is mounted against the peripheral nerves,[39] leading to peripheral neuropathy and acute neuromuscular failure.[40] GBS is the most common cause of acute neuromuscular paralysis worldwide. There are three types of GBS: acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN).[39, 40] The overall incidence of GBS is approximately 1–2 per 100,000[41] The incidence of each type of GBS varies with geography, with AIDP being most common, occurring in 95% of GBS patients in the United States and Europe while 5% have the axonal form, which is more common among patients in Japan, northern China, and Central and South America.[41] Although all age groups are affected, peak incidence occurs in young adults and in the elderly and most, if not all, cases appear to have an infectious trigger.

Symptoms

GBS is characterized by global weakness affecting both proximal and distal limbs.[40, 41] Numbness, pain, and paresthesias are also typically present.[41] Hyporeflexia may occur early on,[40, 41] but 33% to 48% of patients with AMAN may have hyperreflexia.[42, 43] The cranial nerves are often affected as manifested by facial weakness, bulbar palsy, and eye movement disorder.[40, 41] Respiration may be weakened, requiring ventilation[40, 41]; in one report, 33% of patients required ventilation.[44] Autonomic signs are commonly present and may include tachycardia, hypertension, orthostatic hypotension, urinary retention, and ileus.[40, 41]

The symptoms of GBS usually begin between 1 and 3 weeks following an acute viral or bacterial infection,[39] and are acutely progressive, with the neuropathy peaking within 4 weeks.[41] After a plateau phase of variable duration, symptoms will begin to regress during a period of weeks to months. Most patients recover from GBS, but up to 20% may remain disabled, and 4% to 15% will die from GBS.[41] Symptoms of GBS reappear in 8% to 16% of patients after initial treatment,[41] with some patients eventually being diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy.[45]

Incidence Associated With Enteric Infection

Up to 72% of patients report having an infection preceding the onset of GBS.[46] GBS has been associated with preceding infection by several bacterial and viral pathogens (Table 1). The most common enteric pathogen associated with GBS is Campylobacter with approximately one case of GBS for every 1,000 cases of Campylobacteriosis.[47] Campylobacter is one of the most prevalent bacterial causes of food-borne disease in the United States with over 2.4 million cases a year[48] and it is a common cause of TD especially among travelers to Asia. Evidence for other enteric pathogens in GBS has also been reported. Yersinia infection was detected in stool samples in 1% of patients with GBS in one study[46] and there was a case report of a patient with Cyclospora-triggered GBS.[49]

Table 1. Incidence of Guillain-Barré syndrome by pathogena
PathogenRange of reported incidence, %
  1. a

    Based on data from studies examining the incidence of multiple pathogens by serology only.

Campylobacter jejuni[46, 58, 59]14–32
Cytomegalovirus[46, 58, 59]7–18
Mycoplasma pneumoniae[46, 59]1–9
Epstein-Barr Virus[46, 58, 59]1–7
Parvovirus[59]4

Although Campylobacter is the single most common pathogen associated with GBS, the link was only first recognized in 1982,[50] and since then most epidemiologic studies have confirmed this association with up to 40% of GBS resulting from recent Campylobacter infections.[51] In a case–control study in the UK of 103 patients with GBS, 26% had evidence of recent Campylobacter jejuni infection compared with 2% of household and 1% non-matched controls.[52] The estimated risk of GBS from symptomatic C jejuni infections is 100 times that of the general population.[53]

Risk Factors

Unlike the association of ReA with HLA-B27, no strong link between HLA antigens has been reported for GBS.[39, 40] Further, no strong link has been made between GBS and human immunosusceptibility genes in general, although some potential genetic factors have been identified.[39-41] However, other pathogen and host factors may impact the risk of development of GBS. Infection with the C jejuni strains with the HS:19 serotype and cstII polymorphism Thr51 may increase the risk for production of autoantibodies and development of GBS compared with infection by other enteritis-associated strains of C jejuni.[54] Increasing age and male sex also increased the risk of GBS in patients in one study.[55] Another study showed a bimodal distribution for increased incidence of GBS by age with peaks between 20 and 24 years and 70 and 74 years.[56]

A variety of factors may also influence the course of GBS. Infection by C jejuni is associated with significantly longer recovery time,[52] greater disability after 8 weeks, 6 months,[57] and 1 year,[52] and poorer outcome after 1 year[58] compared with infection by other organisms. Other factors significantly associated with poorer outcomes for patients with GBS include older age (≥50 years),[57, 59] rapid onset of weakness,[57] being bedbound or on a ventilator,[57] severe arm weakness,[58] and diarrhea.[56, 59]

Pathophysiology

Like the proposed mechanism for ReA (Figure 1), molecular mimicry is believed to be the mechanism for the pathophysiology of GBS[39-41] (Figures 2 and 3). In the case of AIDP, an inflammatory condition, activation of autoreactive T cells and production of autoreactive antibodies leads to attack on the myelin sheath and on Schwann cells leading to disruption of nerve transmission. In AMAN and ASMAN, both noninflammatory conditions, T cells are not involved, and autoreactive antibodies targeting the nerve axolemmal membrane lead to disruption of nerve conduction or axonal damage. Additional evidence for an immunologic rather than a toxic basis for disease production is the fact that the median interval from onset of diarrhea to neuropathic symptoms is approximately 9 days. This is more consistent with GBS as a consequence of an immune response rather than a direct effect of the organism or toxin.

image

Figure 2. Proposed mechanism for molecular mimicry in the pathophysiology of AIDP (acute inflammatory demyelinating polyradiculoneuropathy).

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image

Figure 3. Proposed mechanism for molecular mimicry in the pathophysiology of AMAN and AMSAN.[39-41] AMAN = acute motor axonal neuropathy; AMSAN = acute motor and sensory axonal neuropathy; LPS = lipopolysaccharide.

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Post-Infectious Irritable Bowel Syndrome

  1. Top of page
  2. Abstract
  3. Reactive Arthritis
  4. Guillain-Barré Syndrome
  5. Post-Infectious Irritable Bowel Syndrome
  6. Disclaimer
  7. Declaration of Interests
  8. References

In most cases, the gastrointestinal effects of TD are self-limiting. In a subset of patients, however, persistent changes in GI function may occur following the infection.[60] These enteric changes, which often result in persistent diarrhea, may be related to several conditions including but not limited to persistent infection, co-infection with a second organism that was not targeted by initial therapy for TD, an underlying previously undiagnosed gastrointestinal illness, or PI-IBS.

Persistent diarrhea, chronic abdominal discomfort, and changes in bowel function in returned travelers have been commonly noted by clinicians who frequently see returned travelers. It was studies done in the past two decades, however, mainly follow-up of community-wide outbreaks of gastroenteritis, which showed that a percentage of those afflicted with acute enteric infection continued to have symptoms for months or even years after the inciting infection, a condition which has come to be known as PI-IBS. There is increasing evidence to support PI-IBS as a specific diagnosis. This requires a paradigm shift: a peripheral event, in this case an infection, leads to prolonged and permanent changes in GI function.

PI-IBS has been defined as the new onset of IBS symptoms as defined by Rome III Criteria for IBS (Table 2) following an episode of gastroenteritis or TD where the workup for chronic enteric infection and underlying organic gastrointestinal disease is negative.[60] In most cases, PI-IBS is characterized by diarrhea-predominant IBS but constipation-predominant IBS and mixed IBS have also been reported in PI-IBS.[61]

Table 2. Post-infectious IBS (PI-IBS)
  1. Following an episode of gastroenteritis or travelers' diarrhea where work-up for microbial pathogens and underlying gastrointestinal disease is negative.

New IBS symptoms by Rome III criteria:
At least 3 months, with onset at least 6 months previously of recurrent abdominal pain or discomfort associated with 2 or more of the following features:
• improvement with defecation and/or
• onset associated with a change in frequency of stool and/or
• onset associated with a change in form (appearance) of stool

To put this in historical perspective, however, requires review of medical literature from more than a half century ago when it was observed that post-dysenteric gastrointestinal symptoms occurred in British troops following successful treatment for amebic dysentery.[61] A common finding was functional non-ulcerative “colitis” with continued symptoms, but no obvious pathology. In more recent studies of IBS patients 20% retrospectively recalled diarrhea, vomiting, and fever at the onset of their symptoms and in other studies, 6% to 17% of IBS sufferers recalled acute diarrhea as a herald of IBS.[62]

Incidence

The incidence of IBS after any enteric infection has been reported to range from 4%[63] to 32%.[60, 64, 65] This wide range may be related to differences across studies in the definition of PI-IBS, the time between infection and follow-up, geography, and methods used for diagnosing IBS.[60] Further, most studies are retrospective, lack control groups, and rely on patients' recollection of previous gastroenteritis and on patients accurately reporting the severity of symptoms before and after their acute infections.[60] These limitations notwithstanding, PI-IBS appears to be a complication of enteric infection.

The incidence of PI-IBS specifically associated with TD has only been examined in four studies. The most recent study was reported among 121 US military travelers returning from routine deployment (>6 month follow-up) to the Middle East where it was reported that there was an over fivefold increase in incident IBS among those who experienced an episode of TD during travel compared to those that did not (17.2% vs 3.7%, p = 0.12).[66] Another study among travelers from Israel reported that significantly more people (14%) who had TD developed IBS after 6 to 7 months compared with only 2% of those who did not have diarrhea.[67] A third study reported an incidence of PI-IBS of 10% in patients who had acquired TD in Mexico.[68] The fourth study reported only a 4% incidence of PI-IBS after TD which was not statistically different compared with those who developed IBS who did not have diarrhea (2%).[69] However, this study may have been underpowered and unable to detect a statistical significance for such a small difference in incidence.

Risk Factors

The risk factors for PI-IBS are only now beginning to be understood, but host factors, genetic factors, pathogen factors, and host–pathogen interaction are felt to serve as a basis for risk of PI-IBS. In a study of unselected patients with IBS versus controls, fewer patients with IBS were noted to have anti-inflammatory cytokines, IL-10, and TGF-b implying more susceptibility to prolonged and severe inflammation.[70] This is consistent with the increase in inflammatory cells such as enterochromaffin cells and T lymphocytes in the lamina propria in rectal biopsies of patients with PI-IBS. In addition, PI-IBS patients have increased post-prandial 5HT release compared to controls and those with standard constipation predominant IBS (IBS-C). PI-IBS patients also have an increased IL-1b both during and after infection compared to controls.[71]

Host risk factors for the development of PI-IBS have also been described. Psychological factors such as stress and anxiety have been shown to be associated with the development of PI-IBS in several studies.[72-75] Younger age has been shown to be a risk factor in some studies,[75, 76] but not in another.[77] Host genetics may also be an important risk factor in PI-IBS; however, no studies to date have reported any relevant genes. Several studies suggest that individuals with a genetic background that results in the high production of the pro-inflammatory TNF-a and low production of the anti-inflammatory IL-10 may be more susceptible to prolonged inflammation following gastroenteritis, which may be important in the pathophysiology of PI-IBS.[78, 79]

Pathophysiology

Similar to that of ReA and GBS, the pathophysiology of PI-IBS appears to be related to dysregulation of an immune/inflammatory response (Figure 4). In contrast to the other two conditions, however, there is no compelling evidence to suggest PI-IBS is an autoimmune condition resulting from molecular mimicry. Instead, as described above, patients may be unable to downregulate intestinal inflammation caused by enteric infection.[60] The chronic intestinal immune activation in PI-IBS may be caused by low-grade inflammation and increased intestinal permeability, which leads to disrupted intestinal barrier function, altered neuromuscular function, chronic inflammation, and ultimately to the symptoms of PI-IBS.[80] The mechanistic significance of this is that once mucosal inflammation begins, an alteration of function of the enteric nervous system occurs leading to changes and excitability of muscle and nerves. A cascade starts in the mucosa and involves a series of mediators leading to activation of the visceral sensory system with visceral hypersensitivity and alteration in GI transit times with disturbed motor function. As a result of altered motility specifically decreased interdigestive Phase III waves, small intestinal bacterial overgrowth may occur resulting in changes in the intestinal microflora. Interestingly, recent data have emerged from an animal model which appears to link C jejuni infections with gut motor dysfunction, chronic inflammation, and small intestinal bacterial overgrowth.[81] A purported mechanism has been put forward which describes changes in the density of Interstitial Cells of Cajal (ICC) in the intestinal mucosa and subsequent aberrations in dysmotility.[82] While a number of questions regarding the potential patho-etiology and relevance to human PI-IBS exist, this finding, if confirmed, may prove to be an initial understanding of the mechanism by which acute enteric infections may trigger functional gastrointestinal disorders and be of great value in advancing our understanding of the genetics, immunology, and microbiomics behind this disease mechanism, as well as potentially evaluating mitigative host susceptibility factors and potential preventive interventions (eg, chemoprophylaxis, vaccination).

image

Figure 4. Proposed analytic framework for evaluating the pathogenesis of post-infectious irritable bowel syndromes and other functional disorders.

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There is substantial evidence for inflammation in the gut of patients with PI-IBS. Significantly greater numbers of chronic inflammatory cells were detected in rectal biopsies from patients with PI-IBS than those from patients who had enteritis but did not develop PI-IBS.[74] Several other studies have also reported evidence of immune activation and inflammation in the GI system of patients with PI-IBS (Table 3).[70-72, 83] Elevated levels of EC cells are relevant to the pathogenesis of PI-IBS because they produce serotonin, which can stimulate enteric secretions, activate visceral sensory nerves, and regulate peristalsis, thus playing a role in mediating the symptoms of PI-IBS.[60, 84] Interleukin-1b may also be important in PI-IBS as it can affect enteric nerve function and contribute to diarrhea.[85]

Table 3. Evidence for increased immune activation in intestines of patients with PI-IBS relative to controlsa
Biopsy comparisonsEC cellsCD3+ lymphocytesMast cellsIL-1b mRNA
  1. EC = enterochromaffin; IL-1b = interleukin 1 beta; ND = no difference; PI-IBS = post-infectious IBS.

  2. a

    Results shown if significantly different from all listed controls.

  3. b

    Results only significantly greater than non-infected controls.

Patients with PI-IBS vs healthy controls, rectal[71]++++
Patients with PI-IBS vs post-infection controls and healthy controls, rectal[70]+++
Patients with PI-IBS vs post-infectious and non-infected controls, rectal[72]++b
Patients with PI-IBS vs non-PI-IBS and non-infected family controls[83]
RectalND+
Ileal+b+

In summary, potential consequences of TD extend beyond the acute illness. There is an increasing recognition of serious disabling and permanent sequelae of TD. As a result, this begs the need to reconsider strategies for treatment and perhaps prophylaxis of TD. Since TD is such a common occurrence it would be helpful to be able to identify who might be at greater risk of post-infectious medical sequelae in order to target more aggressive prophylactic or therapeutic approaches to such individuals. To this end, utilizing existing databases of ill-returned travelers (eg, GeoSentinel) to look at potential risk factors for post-infectious complications of TD and designing prospective studies from a geographically diverse selection of travel clinics might enable a more informed approach.

Disclaimer

  1. Top of page
  2. Abstract
  3. Reactive Arthritis
  4. Guillain-Barré Syndrome
  5. Post-Infectious Irritable Bowel Syndrome
  6. Disclaimer
  7. Declaration of Interests
  8. References

The views expressed in this article by M. S. R. are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government. There are no restrictions on its use. There were no financial conflicts of interests among any of the authors. This work was not supported by any work unit number.

This work was prepared as part of official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the US Government.” Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties.

Declaration of Interests

  1. Top of page
  2. Abstract
  3. Reactive Arthritis
  4. Guillain-Barré Syndrome
  5. Post-Infectious Irritable Bowel Syndrome
  6. Disclaimer
  7. Declaration of Interests
  8. References

M. S. R. is an employee of the US Government or military service members. B. A. C. states he has no conflicts of interest to declare.

References

  1. Top of page
  2. Abstract
  3. Reactive Arthritis
  4. Guillain-Barré Syndrome
  5. Post-Infectious Irritable Bowel Syndrome
  6. Disclaimer
  7. Declaration of Interests
  8. References