M
I
S
T
143
Correspondence
Response to Both Letters: We thank Mutsch and colleagues for pointing out and summarizing a travelers’ diarrhea (TD) study that we failed to include in our recent review.1 The omission was inadvertent and the authors are familiar with the study. While the rates of irritable bowel syndrome (IBS) and post-infectious irritable bowel syndrome (PI-IBS) were lower in this prospective study, the differential J Travel Med 2014; 21: 141–145
144
rate was suggestive of an association between TD and incident PI-IBS at 6 months follow-up with an adjusted odds ratio of 3.61 (95% CI, 1.74–7.51).2 This is consistent with the effect estimate described in a systematic review of all-setting PI-IBS by Thabane and colleagues [odds ratio (OR) 5.18; 95% CI: 3.24–8.26].3 The heterogeneity in absolute risk of PI-IBS among travelers experiencing TD and relative risk compared to non-exposed controls is important to be highlighted. Mutsch and colleagues reiterate many of the factors related to study setting, populations, case definition, and surveillance methods, which differ across studies and thus likely contribute to the observed heterogeneity. However, the consistency of effect found with TD and PI-IBS, including this study, lend support to the observed association across the five studies reported thus far. In addition to the noted reasons explaining their observed results, other explanatory factors could include lack of data on pathogen etiology by which some pathogens may seem to induce PI-IBS and others may not. It is possible that the majority of pathogens that travelers experienced in this cohort may have been ‘‘non-inducing’’ pathogens, although it is interesting in univariate analysis that those reporting a dysentery TD episode (eg, Salmonella, Shigella, and Campylobacter) had increased risk estimates for PI-IBS in their study and limited numbers precluded multivariate adjustment. Furthermore, the authors are correct to point out that they used strict exclusion criteria that identified and excluded a significant proportion of travelers who had preexisting IBS. This is a valid design consideration. However, it is plausible that combining an older age population with exclusion of all subjects with a history of functional gastrointestinal disorder resulted in a population of travelers who were not ‘‘susceptible’’ to developing PI-IBS. While this explanation is theoretical, we do know from specific studies that document confirmed gastrointestinal infectious exposures that not all individuals go on to develop IBS. Thus, it is possible that the study design reduced the population which is ‘‘at risk’’ for developing IBS, ‘‘idiopathic,’’ or otherwise. We also feel that it is important to put these studies focused on TD-associated PI-IBS into the context of the larger body of epidemiological evidence that is accruing, which identifies consistency of post-infectious risk of IBS and other functional gastrointestinal disorders attributed to specific pathogen exposures such as Campylobacter, Salmonella, and Shigella—all pathogens associated with TD. In addition, as evidenced by the growing scientific inquiry in this field, two additional studies, one among a well-characterized medical encounter database in the Netherlands and another following UK service members returning from Iraq, have been reported since the time of this published review and both demonstrate clear increased risk among acute enteric infections/illnesses and increased risk for PI-IBS.4,5 These studies, in addition to important mechanistic studies, which are also being reported, provide for an increased certainty that this observed J Travel Med 2014; 21: 141–145
Correspondence
phenomenon is not exaggerated.6 A coordinated and funded research agenda is needed to understand the heterogeneity in observed risk and disease outcomes based on host, agent, and environmental differences, patho-etiological mechanisms, and more urgently how to mitigate these burdensome consequences that are known to impact medical care costs and quality of life among the millions of travelers and deployed military personnel at high risk for these infections. Such a research agenda has recently been put forward and should serve as a starting point for future efforts.7 Regarding the comments of Wakerley and Yuki about Guillain–Barr´e syndrome (GBS) and Campylobacter, their statement is not supported by the literature. A recent review suggests that Campylobacter jejuni infections can elicit both axonal and demyelinating subtypes of the disease.8 In one study, the seropositivity of C. jejuni infection in GBS patients ranges from 24% to 76% among which the highest has been reported from China in acute motor axonal neuropathy (AMAN) and 42% in acute inflammatory demyelinating polyneuropathy (AIDP) patients,9 suggesting that C. jejuni infection elicits AMAN more frequently than AIDP, but a considerable number of AIDP cases also occur after C. jejuni infection. In a large study conducted in North America and Europe involving 229 GBS patients, 52 (22.7%) patients had positive serology for C. jejuni and 56% showed demyelinating neurophysiology.10 Another study from Japan investigating 86 GBS patients showed that of the 20 (23.3%) C. jejuni-positive patients, 70% had AMAN and 15% had AIDP.11 Clearly there is still a lot we do not understand about the mechanism whereby C. jejuni infections cause GBS but the evidence to date supports at least two subtypes of the disease in those afflicted.
∗
Bradley A. Connor∗ and Mark S. Riddle† Weill Medical College of Cornell University, New York, NY, USA; † Naval Medical Research Center, Silver Spring, MD, USA
References 1. Connor BA, Riddle MS. Post-infectious sequelae of travelers’ diarrhea. J Travel Med 2013; 20:303–312. 2. Pitzurra R, Fried M, Rogler G, et al. Irritable bowel syndrome among a cohort of European travelers to resource-limited destinations. J Travel Med 2011; 18:250–256. 3. Thabane M, Kottachchi DT, Marshall JK. Systematic review and meta-analysis: the incidence and prognosis of post-infectious irritable bowel syndrome. Aliment Pharmacol Ther 2007; 26:535–544. 4. Kowalcyk BK, Smeets HM, Succop PA, et al. Relative risk of irritable bowel syndrome following acute gastroenteritis and associated risk factors. Epidemiol Infect 2013:1–10. 5. Goodwin L, Bourke JH, Forbes H, et al. Irritable bowel syndrome in the UK military after deployment to Iraq: what are the risk factors? Soc Psychiatry Psychiatr Epidemiol 2013; 48:1755–1765.
Correspondence 6. Verdu EF, Riddle MS. Chronic gastrointestinal consequences of acute infectious diarrhea: evolving concepts in epidemiology and pathogenesis. Am J Gastroenterol 2012; 107:981–989. 7. Deising A, Gutierrez RL, Porter CK, et al. Postinfectious functional gastrointestinal disorders: a focus on epidemiology and research agendas. Gastroenterol Hepatol 2013; 9:145–157. 8. Nyati KK, Nyati R. Role of Campylobacter jejuni infection in the pathogenesis of Guillain-Barr´e syndrome: an update. Biomed Res Int 2013; 2013:852195.
145 9. Ho TW, Mishu B, Li CY, et al. Guillain-Barre syndrome in northern China. Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies. Brain 1995; 118:597–605. 10. Hadden RDM, Karch H, Hartung HP, et al. Preceding infections, immune factors, and outcome in Guillain-Barre syndrome. Neurology 2001; 56:758–765. 11. Ogawara K, Kuwabara S, Mori M, et al. Axonal GuillainBarre syndrome: relation to antiganglioside antibodies and Campylobacter jejuni infection in Japan. Ann Neurol 2000; 48:624–631.
This is a sign showing the way to the toilets in a temple in Luxor, Egypt. The temples standing along the shores of the Nile River are often visited through boat cruises. Travelers’ diarrhea may be a common event for travelers boarding some of these cruise ships, as well as in Egypt in general. Photo Credit: Eric Caumes.
J Travel Med 2014; 21: 141–145
I
S
T
143
Correspondence
Response to Both Letters: We thank Mutsch and colleagues for pointing out and summarizing a travelers’ diarrhea (TD) study that we failed to include in our recent review.1 The omission was inadvertent and the authors are familiar with the study. While the rates of irritable bowel syndrome (IBS) and post-infectious irritable bowel syndrome (PI-IBS) were lower in this prospective study, the differential J Travel Med 2014; 21: 141–145
144
rate was suggestive of an association between TD and incident PI-IBS at 6 months follow-up with an adjusted odds ratio of 3.61 (95% CI, 1.74–7.51).2 This is consistent with the effect estimate described in a systematic review of all-setting PI-IBS by Thabane and colleagues [odds ratio (OR) 5.18; 95% CI: 3.24–8.26].3 The heterogeneity in absolute risk of PI-IBS among travelers experiencing TD and relative risk compared to non-exposed controls is important to be highlighted. Mutsch and colleagues reiterate many of the factors related to study setting, populations, case definition, and surveillance methods, which differ across studies and thus likely contribute to the observed heterogeneity. However, the consistency of effect found with TD and PI-IBS, including this study, lend support to the observed association across the five studies reported thus far. In addition to the noted reasons explaining their observed results, other explanatory factors could include lack of data on pathogen etiology by which some pathogens may seem to induce PI-IBS and others may not. It is possible that the majority of pathogens that travelers experienced in this cohort may have been ‘‘non-inducing’’ pathogens, although it is interesting in univariate analysis that those reporting a dysentery TD episode (eg, Salmonella, Shigella, and Campylobacter) had increased risk estimates for PI-IBS in their study and limited numbers precluded multivariate adjustment. Furthermore, the authors are correct to point out that they used strict exclusion criteria that identified and excluded a significant proportion of travelers who had preexisting IBS. This is a valid design consideration. However, it is plausible that combining an older age population with exclusion of all subjects with a history of functional gastrointestinal disorder resulted in a population of travelers who were not ‘‘susceptible’’ to developing PI-IBS. While this explanation is theoretical, we do know from specific studies that document confirmed gastrointestinal infectious exposures that not all individuals go on to develop IBS. Thus, it is possible that the study design reduced the population which is ‘‘at risk’’ for developing IBS, ‘‘idiopathic,’’ or otherwise. We also feel that it is important to put these studies focused on TD-associated PI-IBS into the context of the larger body of epidemiological evidence that is accruing, which identifies consistency of post-infectious risk of IBS and other functional gastrointestinal disorders attributed to specific pathogen exposures such as Campylobacter, Salmonella, and Shigella—all pathogens associated with TD. In addition, as evidenced by the growing scientific inquiry in this field, two additional studies, one among a well-characterized medical encounter database in the Netherlands and another following UK service members returning from Iraq, have been reported since the time of this published review and both demonstrate clear increased risk among acute enteric infections/illnesses and increased risk for PI-IBS.4,5 These studies, in addition to important mechanistic studies, which are also being reported, provide for an increased certainty that this observed J Travel Med 2014; 21: 141–145
Correspondence
phenomenon is not exaggerated.6 A coordinated and funded research agenda is needed to understand the heterogeneity in observed risk and disease outcomes based on host, agent, and environmental differences, patho-etiological mechanisms, and more urgently how to mitigate these burdensome consequences that are known to impact medical care costs and quality of life among the millions of travelers and deployed military personnel at high risk for these infections. Such a research agenda has recently been put forward and should serve as a starting point for future efforts.7 Regarding the comments of Wakerley and Yuki about Guillain–Barr´e syndrome (GBS) and Campylobacter, their statement is not supported by the literature. A recent review suggests that Campylobacter jejuni infections can elicit both axonal and demyelinating subtypes of the disease.8 In one study, the seropositivity of C. jejuni infection in GBS patients ranges from 24% to 76% among which the highest has been reported from China in acute motor axonal neuropathy (AMAN) and 42% in acute inflammatory demyelinating polyneuropathy (AIDP) patients,9 suggesting that C. jejuni infection elicits AMAN more frequently than AIDP, but a considerable number of AIDP cases also occur after C. jejuni infection. In a large study conducted in North America and Europe involving 229 GBS patients, 52 (22.7%) patients had positive serology for C. jejuni and 56% showed demyelinating neurophysiology.10 Another study from Japan investigating 86 GBS patients showed that of the 20 (23.3%) C. jejuni-positive patients, 70% had AMAN and 15% had AIDP.11 Clearly there is still a lot we do not understand about the mechanism whereby C. jejuni infections cause GBS but the evidence to date supports at least two subtypes of the disease in those afflicted.
∗
Bradley A. Connor∗ and Mark S. Riddle† Weill Medical College of Cornell University, New York, NY, USA; † Naval Medical Research Center, Silver Spring, MD, USA
References 1. Connor BA, Riddle MS. Post-infectious sequelae of travelers’ diarrhea. J Travel Med 2013; 20:303–312. 2. Pitzurra R, Fried M, Rogler G, et al. Irritable bowel syndrome among a cohort of European travelers to resource-limited destinations. J Travel Med 2011; 18:250–256. 3. Thabane M, Kottachchi DT, Marshall JK. Systematic review and meta-analysis: the incidence and prognosis of post-infectious irritable bowel syndrome. Aliment Pharmacol Ther 2007; 26:535–544. 4. Kowalcyk BK, Smeets HM, Succop PA, et al. Relative risk of irritable bowel syndrome following acute gastroenteritis and associated risk factors. Epidemiol Infect 2013:1–10. 5. Goodwin L, Bourke JH, Forbes H, et al. Irritable bowel syndrome in the UK military after deployment to Iraq: what are the risk factors? Soc Psychiatry Psychiatr Epidemiol 2013; 48:1755–1765.
Correspondence 6. Verdu EF, Riddle MS. Chronic gastrointestinal consequences of acute infectious diarrhea: evolving concepts in epidemiology and pathogenesis. Am J Gastroenterol 2012; 107:981–989. 7. Deising A, Gutierrez RL, Porter CK, et al. Postinfectious functional gastrointestinal disorders: a focus on epidemiology and research agendas. Gastroenterol Hepatol 2013; 9:145–157. 8. Nyati KK, Nyati R. Role of Campylobacter jejuni infection in the pathogenesis of Guillain-Barr´e syndrome: an update. Biomed Res Int 2013; 2013:852195.
145 9. Ho TW, Mishu B, Li CY, et al. Guillain-Barre syndrome in northern China. Relationship to Campylobacter jejuni infection and anti-glycolipid antibodies. Brain 1995; 118:597–605. 10. Hadden RDM, Karch H, Hartung HP, et al. Preceding infections, immune factors, and outcome in Guillain-Barre syndrome. Neurology 2001; 56:758–765. 11. Ogawara K, Kuwabara S, Mori M, et al. Axonal GuillainBarre syndrome: relation to antiganglioside antibodies and Campylobacter jejuni infection in Japan. Ann Neurol 2000; 48:624–631.
This is a sign showing the way to the toilets in a temple in Luxor, Egypt. The temples standing along the shores of the Nile River are often visited through boat cruises. Travelers’ diarrhea may be a common event for travelers boarding some of these cruise ships, as well as in Egypt in general. Photo Credit: Eric Caumes.
J Travel Med 2014; 21: 141–145
