TY - JOUR
AU - MD, Eli Schwartz,
AB - Abstract Background Persistent abdominal symptoms (PAS) are common among returning-travellers. In the absence of sensitive tests to identify intestinal parasites, gastrointestinal (GI) symptoms often remain a diagnostic challenge. In this study we examined the effectiveness of empirical anti-parasitic treatment in returning-travellers with PAS despite no positive stool-test. Methods A retrospective study among returning travellers who approached the clinic between the years 2014 and 2016 with GI complaints without a positive stool-test. The empirical treatment included broad-spectrum anti-parasitic agents—oral Tinidazole and Albendazole. A follow-up questionnaire was performed at least 6 months post-treatment. Results A total of 102 patients responded the questionnaire—50% women; average age 31.14 (±12.20) years. The average duration of complaints before treatment was 16.52 (±30.06) months. Common GI symptoms included abdominal pain (83.3%) and diarrhoea (78.4%); 67.6% of the patients complained of extreme fatigue. Overall, 69% of the patients reported an improvement in GI symptoms, 37% of them reported full recovery within a few weeks post-treatment. Furthermore, there was an improvement in the energy level and general well-being in 68% and 70% of the patients, respectively. Only 33% of the patients reported minor side effects related to the treatment. Conclusions The improvement in GI symptoms, energy level and general well-being shortly after anti-parasitic treatment justifies this empirical approach in returning-travellers with PAS despite negative stool-tests. The association between fatigue and PAS post-travel and the improvement in both as a response to treatment defines fatigue as part of a new syndrome—‘Post-travel fatigue and abdominal symptoms’. IBS, fatigue, post travel, persistent abdominal symptoms, giardia Introduction Over the past decades there is a significant increase in the number of travellers to developing countries, with an estimation that 533 million travellers crossed the borders of emerging economies in 2015.1 Traveller’s diarrhoea (TD) is common among travellers to developing countries with an incidence of 30–70% of travellers depending on travel destination, travel season, and the country of origin of the traveller.2 In 80–90% of TD cases, where pathogen was found, the symptoms are caused by bacterial pathogens that usually present with a sudden onset and tend to be self-limiting.2,3 TD is defined as the passing of three or more unformed stool per day in association with one or more other enteric symptoms such as nausea, vomiting, cramps, bloating, fecal urgency or tenesmus. Symptoms such as headache, joint pains and extreme fatigue may also be present.4 A small percentage of the travellers (1–3%) experience prolonged symptoms of more than 2 weeks, which may persist also after the travel, and are therefore defined as persistent TD.5–7 Since diarrhoea does not always exist but rather several other abdominal symptoms, persistent abdominal symptoms (PAS) is a more accurate term8 and it is a major reason for seeking medical care among returning travellers.9–11 The etiology of PAS can be divided into three major categories: a post-infectious phenomenon, unmasking a previously undiagnosed gastrointestinal (GI) disease such as celiac or inflammatory bowel disease or a chronic infectious cause.4,10 A temporary post-infectious phenomena such as disaccharidase deficiency, as a result of GI damage due to acute gastroenteritis. In these cases, the symptoms usually resolve within a few weeks after resolution of the initial diarrhoea. In a certain percentage of travellers, no specific etiology is identified and a permanent change in bowel function is assumed to be the cause of those prolonged symptoms. A new onset of IBS (according to ROME III criteria) following an episode of gastroenteritis is defined as post-infectious irritable syndrome (PI-IBS).12 The risk of developing IBS is increased by 6-fold after acute gastroenteritis13 and the incidence following acute TD is reported to be between 3% and 14%.14,15 The prognosis of PI-IBS is better compared to IBS without an infectious origin, but less than a half of cases recovered at 5–6 years.16–18 Parasites (protozoa and helminths) are the most likely infectious cause of PAS in travellers.3,19 Unlike the acute TD, bacterial infectious rarely cause persistent symptoms, although Clostridium difficile associated diarrhoea may follow antibiotic treatment.20,21 The diagnosis of intestinal parasites is traditionally relied on stool microscopic examination (O&P) that is associated with a poor sensitivity. Three stool specimens further increase the test yield by 10–30%22 and molecular assays (such EIAs and multiplex PCR assays) increase the sensitivity by 20–90% but require a laboratory with proficiency in molecular testing, which limits their use to major academic hospitals and reference laboratories.23 However, there is no ‘Gold standard’ test which is known to capture all pathogens and therefore in the absence of sufficient sensitive tests to identify intestinal parasites, a false-negative test cannot be excluded and PAS often remains a diagnostic challenge.5,24 In this study we examined the effectiveness of the existing approach in our clinic of empirical anti-parasitic treatment in returning travellers with persistent abdominal complaints despite negative stool tests, patients that usually are already diagnosed as PI-IBS. Methods A retrospective questionnaire-based study among returning travellers who approached the Chaim Sheba Medical Center and the Shaare-Zedek Medical Center post-travel clinics with PAS between 1 January 2014 and 30 January 2016. Patients with persistent post-travel abdominal symptoms were retrieved by diagnosis from both clinics databases. Data regarding the initial visit at the clinics was collected from the medical records. Exclusion criteria—patients with a pathogen found in a stool test (not including Blastocystis hominis), or patients who did not give an oral consent to participate in the study. The diagnosis of intestinal parasites relied on stool microscopic examination (O&P) that included direct microscopic examination with saline and Lugol’s iodine, on fresh stool and concentration of the stool by Formal Ether Sedimenation technique. Giardia EIA on stool and multiplex PCR are still uncommon in Israel for clinical use, and therefore were not routinely performed. The empiric anti-parasitic treatment protocol was composed of oral Tinidazole, an anti-protozoa agent, 1000 mg twice a day for 2 days followed by oral Albendazole 400 mg twice a day for 5 days. Adding Albendazole to the regimen seems to be highly important due to its broad-spectrum anti-parasitic activity, including helminths as well as protozoa. Resistant giardia seems to be an emerging problem in which the combination of Tinidazole and Albendazole may overcome it.25 A follow-up clinical questionnaire was completed by a telephone interview at least 6 months post treatment. All patients participating in this part of the study gave an informed consent to the interview. The patients were asked to assess their treatment response—substantial improvement, slight improvement or no change. In addition to assessing the overall response, improvement to treatment was measured by scorning the GI symptoms (on scale of 1–5, while 5 represents severe symptoms), general well-being (on scale of 1–5, 5 represents good health) and energy level (on scale of 1–10) before treatment and at follow-up time post treatment. The study was approved by the ethical committee of the Sheba Medical Center and the Shaare-Zedek Medical Center. Statistical Methods: In order to test the association between two categorical variables the Chi-square test as well as the Fisher’s exact test were used. The comparison of quantitative variables between two independent groups was performed by applying the Mann–Whitney non-parametric test. Testing the change in quantitative and ordinal variables was carried out using the Wilcoxon signed ranks test. Non-parametric tests were applied to quantitative variables if they were not normally distributed. ROC analysis was applied to find an optimal cutoff point (for a quantitative variable) for yielding the best sensitivity and specificity. All tests applied were two-tailed, and a P-value of 5% or less was considered statistically significant. Results Between the years 2014–2016, 283 patients in the two post-travel clinics were diagnosed with either ‘Diarrhoea, chronic unspecified’; ‘abdominal pain, unspecified etiology’; or ‘intestinal parasite, Probable’ (Figure 1). We excluded 85 of them due to missing data, irrelevant diagnosis or a positive stool test. Out of the remaining 198 patients, we were able to make phone contact with 119 patients, 102 (86%) of them gave oral consent and completed the follow-up questionnaire (Figure 1). Figure 1. View largeDownload slide A flow chart of study participants Figure 1. View largeDownload slide A flow chart of study participants Table 1 summarizes the demographic and epidemiologic data of the 102 patients who gave consent to participate in the follow-up questionnaire. Fifty percent of them were women and the average age was 31.14 (±12.20) years. The main reason for travel was tourism (85.3%). The three most common travel destinations were East-Asia (56.9%), South and Central America (25.5%) and Africa (6.9%), yet, there were cases imported from Europe (5.9%) and North America (2.9%). The average travel length was 3.38 (±3.99) months, 66 (64.7%) patients were long term travellers, with a travel duration of more than a month, while the rest were travellers for 1 month period or shorter. The average follow-up time post-treatment was 18.18 (±8.08) months. Table 1. Epidemiological data of returning travellers with chronic GI symptoms who completed the follow-up questionnaire after empirical anti-parasitic treatment   All patients (n = 102)  Age  31.14 ± 12.20 (13–67)  Gender     Male  51 (50%)   Female  51 (50%)  Travel destination     East-Asia  58 (56.9%)   South and Central America  26 (25.5%)   Africa  7 (6.9%)   Europe  6 (5.9%)   North America  3 (2.9%)  Travel duration (months)  3.38 ± 3.99 (0.13–25)  Follow-up time (months)  18.18 ± 8.08 (6.9–42.9)  Purpose of travel     Tourism  87 (85.3%)   Business  12 (11.8%)   Visiting relatives  1 (1%)   Volunteer  2 (2%)  Vaccines before travelling  77 (75.5%)    All patients (n = 102)  Age  31.14 ± 12.20 (13–67)  Gender     Male  51 (50%)   Female  51 (50%)  Travel destination     East-Asia  58 (56.9%)   South and Central America  26 (25.5%)   Africa  7 (6.9%)   Europe  6 (5.9%)   North America  3 (2.9%)  Travel duration (months)  3.38 ± 3.99 (0.13–25)  Follow-up time (months)  18.18 ± 8.08 (6.9–42.9)  Purpose of travel     Tourism  87 (85.3%)   Business  12 (11.8%)   Visiting relatives  1 (1%)   Volunteer  2 (2%)  Vaccines before travelling  77 (75.5%)  Table 2 describes the clinical characteristics of the patients. The average duration of complaints before approaching our clinic was 16.52 (±30.06) months. For most patients the symptoms appeared during their travels (69.6%), with an event of acute diarrhoea preceding the chronic symptoms (63.7%). Forty percent of all patients took an antibiotic treatment following the acute diarrhoea. Seventeen percent of the patients had GI complaints before travelling and complained of worsening of the symptoms during the journey. Table 2. Characteristics of complaint, symptoms and laboratory tests of returning travellers with chronic GI symptoms at presentation in our clinic   All patients (n = 102)  Complaint duration (months)  16.52 ± 30.06 (0.5–180)  Symptoms before travelling  17 (16.7%)  Beginning of symptoms     During travel  71 (69.6%)   First week after  9 (8.8%)   Later then first week  6 (5.9%)  Acute diarrhoea during travel  65 (63.7%)   With antibiotic treatment  41 (40.0%)  Symptoms     Intestinal      Discomfort or abdominal pain  85 (83.3%)    Diarrhoea  80 (78.4%)    Constipation  15 (14.7%)    Nausea or vomiting  17 (16.7%)    Flatulence  69 (67.6%)    Abdominal bloating  58 (56.9%)    Stomach rumble  53 (52%)    Weight loss  41 (40.2%)    Decreased appetite  29 (28.4%)   Extra-intestinal      Headache  2 (2.0%)    Muscles pain  1 (1.0%)    Fatigue  69 (67.6%)  Investigation before approaching the clinic   Abdominal ultrasound  16 (15.7%)   Abdominal CT scan  7 (6.9%)   Colonoscopy  21 (20.6%)   Gastroscopy  13 (12/7%)  Laboratory findings     Mild eosinophilia  6 (5.9%)   Low B12  10 (9.8%)  Stool tests     Negative  58 (56.9%)   Insignificant finding  23 (22.5%)   Not tested  21 (20.6%)    All patients (n = 102)  Complaint duration (months)  16.52 ± 30.06 (0.5–180)  Symptoms before travelling  17 (16.7%)  Beginning of symptoms     During travel  71 (69.6%)   First week after  9 (8.8%)   Later then first week  6 (5.9%)  Acute diarrhoea during travel  65 (63.7%)   With antibiotic treatment  41 (40.0%)  Symptoms     Intestinal      Discomfort or abdominal pain  85 (83.3%)    Diarrhoea  80 (78.4%)    Constipation  15 (14.7%)    Nausea or vomiting  17 (16.7%)    Flatulence  69 (67.6%)    Abdominal bloating  58 (56.9%)    Stomach rumble  53 (52%)    Weight loss  41 (40.2%)    Decreased appetite  29 (28.4%)   Extra-intestinal      Headache  2 (2.0%)    Muscles pain  1 (1.0%)    Fatigue  69 (67.6%)  Investigation before approaching the clinic   Abdominal ultrasound  16 (15.7%)   Abdominal CT scan  7 (6.9%)   Colonoscopy  21 (20.6%)   Gastroscopy  13 (12/7%)  Laboratory findings     Mild eosinophilia  6 (5.9%)   Low B12  10 (9.8%)  Stool tests     Negative  58 (56.9%)   Insignificant finding  23 (22.5%)   Not tested  21 (20.6%)  Common symptoms included discomfort or abdominal pain (83.3%), diarrhoea (78.4%), flatulence (67.6%), abdominal bloating (56.9%), stomach rumble (52%), weight loss (40.2%) and decreased appetite (28.4%). In addition to GI symptoms, the majority of the patients complained of fatigue and lack of energy (67.6%). Basic laboratory tests were normal in most patients. Eosinophilia was found in 5.9% of patients (range absolute count: 500–1200/ul). Low B12 level were found in 9.8% of patients. Some of the patients underwent imaging and invasive investigation before approaching the clinic. Sixteen patients did an abdominal sonography imaging and 7 patients went through a CT imaging. Twenty one patients performed a colonoscopy test and 13 patients performed a gastroscopy test. Fifty-seven percent of the patients had a negative stool test and 22.5% had nonpathogenic protozoa such as B. hominis, while the remaining patients did not perform a stool test before treatment. Thirty-three percent of the patients complained of minor side effects following the recommended treatment such as nausea and vomiting, worsening in abdominal pain, metallic taste, headaches and dizziness, dark urine, dry mouth and fatigue. Response to treatment Seventy patients out of 102 patients (68.6%) reported an improvement in GI symptoms following the empirical anti-parasitic treatment, in 88.6% of them the improvement occurred within a few weeks after treatment. Among the responders 34% of reported full recovery, 33% reported a substantial improvement and 33% a slight improvement. The remaining 32 patients did not experience any improvement—nine patients reported improvement following dietary change or alternative medicine; 23 patients had persistent GI symptoms during the follow-up time, 12 of them (11.8% of all patients) met the Rome III criteria for IBS. In addition to assessing the overall improvement following treatment, the patients were asked to rate their GI symptoms severity, energy level and general well-being before and after treatment. A decline in the GI symptoms severity scale from 4.25 (±0.90) to 2.53 (±1.23) at follow-up time was recorded (P < 0.001) (Table 3a). Table 3. Scoring of improvement before and after treatment. GI symptoms on scale of 1–5 (5 represents severe symptoms), general well-being on scale of 1–5 (5 represents good health) and energy level on scale of 1–10   Before treatment  After treatment  P value  A. All patients   GI symptoms  4.25 ± 0.90  2.53 ± 1.23  <0.001   Well-being  2.58 ± 1.12  3.95 ± 0.99  <0.001   Energy level  4.51 ± 2.41  7.27 ± 2.17  <0.001  B. Improved patients   GI symptoms  4.45 ± 0.60  2.00 ± 0.90  <0.001   Well-being  2.20 ± 0.87  4.25 ± 0.75  <0.001   Energy level  3.67 ± 1.87  8.04 ± 1.27  <0.001    Before treatment  After treatment  P value  A. All patients   GI symptoms  4.25 ± 0.90  2.53 ± 1.23  <0.001   Well-being  2.58 ± 1.12  3.95 ± 0.99  <0.001   Energy level  4.51 ± 2.41  7.27 ± 2.17  <0.001  B. Improved patients   GI symptoms  4.45 ± 0.60  2.00 ± 0.90  <0.001   Well-being  2.20 ± 0.87  4.25 ± 0.75  <0.001   Energy level  3.67 ± 1.87  8.04 ± 1.27  <0.001  Assessing the changes in symptoms score among the responders group (68% of the cohort) the decline in the severity of symptoms the decrease in the severity was even more substantial from 4.54 (±0.60) to 2.00 (±0.90). Sixty-eight percent of the patients reported a higher energy level after treatment, from an average of 4.51 (±2.41) to 7.27 (±2.17) (P < 0.001) [from 3.67 (±1.87) to 8.04 (±1.27)]. General well-being improved from 2.58 (±1.12) to 3.95 (±0.99) post-treatment (P < 0.001) [from 2.20 (±0.87) to 4.25 (±0.75)] (Table 3B). Correlation with improvement Comparing the patients who improved post treatment to those who did not (Table 4), shows that those who improved were significantly younger (30.06 ± 12.90 vs 33.50 ± 10.32, P = 0.004), were predominantly females compared to males (57.14% vs 42.86%, P = 0.033) and had a higher prevalence of travel destination to South and Central America (32.86% in the improved patients vs 9.38% in those who did not improve, P = 0.005). An acute diarrhoeal episode during the trip or antibiotic treatment following acute TD was not associated with treatment response (Table 4). We could not find a correlation between any of the symptoms or laboratory tests at presentation to the treatment response. However the duration of complaints before receiving treatment was significantly shorter for the patients who improved following treatment 8.08 ± 14.90 months vs 34.97 ± 44.01 in those who did not improve (P < 0.001). Furthermore, the Kaplan–Mayer curve shows that 7 month duration of complaints was relatively a good cutoff to estimate a positive treatment response (Figure 2). Table 4. Clinical and epidemiological characteristics of patients who reported improvement following treatment compared with the rest of patients   Improved patients  Unimproved patients  P value  (n = 70)  (n = 32)  Age  30.06 ± 12.90  33.50 ± 10.32  0.004  Gender         Male  30 (42.86%)  21 (65.63%)  0.033   Female  40 (57.14%)  11 (34.38%)  Travel destination         East-Asia  35 (50.00%)  23 (71.88%)  0.005   South and Central America  23 (32.86%)  3 (9.38%)   Africa  6 (8.57%)  1 (3.13%)   Europe  4 (5.71%)  2 (6.25%)   North America  –  3 (9.38%)  Travel duration (months)  3.42 ± 4.01  3.29 ± 4.03  0.619  Complaint duration (months)  8.08 ± 14.90  34.97 ± 44.01  <0.001  Follow-up time (months)  18.98 ± 8.31  16.43 ± 7.38  0.141  Symptoms before travelling  11 (15.71%)  6 (18.75%)  0.703  Acute diarrhoea during travel  46 (65.71%)  18 (56.25%)  0.359   antibiotic treatment  30 (42.86%)  11 (34.38%)  0.418  Symptoms         Discomfort or abdominal pain  62 (88.57%)  23 (71.88%)  0.036   Diarrhoea  58 (82.86%)  22 (8.75%)  0.108   Flatulence  44 (62.86%)  25 (78.13%)  0.126   Abdominal bloating  37 (52.86%)  21 (65.63%)  0.227   Stomach rumble  36 (51.43%)  17 (53.13%)  0.874   Weight loss  32 (45.71%)  9 (28.13%)  0.286   Decreased appetite  24 (34.29%)  5 (15.63%)  0.053   Fatigue  51 (72.86%)  18 (56.25%)  0.096  Stool tests         Negative  41 (58.57%)  17 (53.13%)  0.659   Insignificant finding  14 (20.00%)  9 (28.13%)   Not tested  15 (21.43%)  6 (18.75%)    Improved patients  Unimproved patients  P value  (n = 70)  (n = 32)  Age  30.06 ± 12.90  33.50 ± 10.32  0.004  Gender         Male  30 (42.86%)  21 (65.63%)  0.033   Female  40 (57.14%)  11 (34.38%)  Travel destination         East-Asia  35 (50.00%)  23 (71.88%)  0.005   South and Central America  23 (32.86%)  3 (9.38%)   Africa  6 (8.57%)  1 (3.13%)   Europe  4 (5.71%)  2 (6.25%)   North America  –  3 (9.38%)  Travel duration (months)  3.42 ± 4.01  3.29 ± 4.03  0.619  Complaint duration (months)  8.08 ± 14.90  34.97 ± 44.01  <0.001  Follow-up time (months)  18.98 ± 8.31  16.43 ± 7.38  0.141  Symptoms before travelling  11 (15.71%)  6 (18.75%)  0.703  Acute diarrhoea during travel  46 (65.71%)  18 (56.25%)  0.359   antibiotic treatment  30 (42.86%)  11 (34.38%)  0.418  Symptoms         Discomfort or abdominal pain  62 (88.57%)  23 (71.88%)  0.036   Diarrhoea  58 (82.86%)  22 (8.75%)  0.108   Flatulence  44 (62.86%)  25 (78.13%)  0.126   Abdominal bloating  37 (52.86%)  21 (65.63%)  0.227   Stomach rumble  36 (51.43%)  17 (53.13%)  0.874   Weight loss  32 (45.71%)  9 (28.13%)  0.286   Decreased appetite  24 (34.29%)  5 (15.63%)  0.053   Fatigue  51 (72.86%)  18 (56.25%)  0.096  Stool tests         Negative  41 (58.57%)  17 (53.13%)  0.659   Insignificant finding  14 (20.00%)  9 (28.13%)   Not tested  15 (21.43%)  6 (18.75%)  Figure 2. View largeDownload slide The association between duration of complaints and treatment response in a Kaplan–Mayer curve. Every down step on this curve demonstrates improvement following treatment. A larger proportion of patients improved when received treatment within the first few months of the onset of symptoms. By applying ROC analysis, 7 months duration of complaints was found to be a relatively good cutoff to estimate a positive treatment response Figure 2. View largeDownload slide The association between duration of complaints and treatment response in a Kaplan–Mayer curve. Every down step on this curve demonstrates improvement following treatment. A larger proportion of patients improved when received treatment within the first few months of the onset of symptoms. By applying ROC analysis, 7 months duration of complaints was found to be a relatively good cutoff to estimate a positive treatment response Discussion PAS are a major reason for seeking medical care post travel.4,10 In travellers, there is a wide differential diagnosis for PAS including infectious and non-infectious causes,4 but in most cases the blood workup is normal, including a normal celiac serology; blood tests do not have any signs of inflammation and the stool tests are negative. Therefore, most clinicians relate this condition to IBS. Furthermore, upon considering the epidemiologic exposure and the history of a proceeding acute gastroenteritis, a per-exclusion diagnosis of PI-IBS is given. The per-exclusion diagnosis of PI-IBS is supported by the lack of a pathogen in a stool test. However, given the poor sensitivity of stool tests, a negative test cannot exclude parasitic infection, a diagnosis for which there is a relatively simple and safe treatment. Despite the fact that parasitic infection may be a leading etiology for PAS in travellers to developing countries, there is no previous study examining an empirical approach for this etiology. Furthermore, many researchers, as mentioned, attribute these PAS to PI-IBS and describe a slow improvement over the time without any treatment.26 The recovery rate in this set of patients is reported to be 25% at follow-up time of 2–3 years and 43–48% after 6–8 years, respectively.17,18,27 The main finding in our study, an improvement of 68.6% of patients with PAS (with 37% of them experiencing full recovery) shortly after receiving empirical anti-parasitic treatment, is an earlier and higher improvement than the recovery rate ever reported in PI-IBS. This high percentage of recovery justifies this empirical approach in returning-travellers with PAS and suggests that many of those PI-IBS patients may actually have a parasitic infection and therefore respond to empirical anti-parasitic treatment (although it is possible that the drugs have other unknown and non-specific beneficial effects). The duration of complaints before receiving treatment was found to be an important factor in estimating the chance for a positive treatment response, with response rate of 81% during the first 7 months of symptoms onset, yet even after 2 years of symptoms 32% of the patients reported improvement following the empirical treatment. Many of the patients at this stage have already gone through a thorough and sometimes expensive and/or invasive workup (such as colonoscopy, gastroscopy, capsular endoscopy, etc.). The empirical treatment has no significant side effects and in many regions of the world it is not expensive. Therefore we recommend that in travellers with PAS, a trial of empirical anti-parasitic treatment should be given prior to an extensive medical investigation and irrespectively of the duration of symptoms. Adding an empirical approach to the Rome 3 criteria28 is highly advisable as an approach of excluding a current infection. Although bacterial and viral pathogens are a major cause of acute TD, they are as a rule self-limited infections and are not responsible for the PAS reported by travellers. Therefore adding a broad-spectrum anti-parasitic treatment, as our protocol, for example, seems to be an important part of defining the Rome 3 criteria for PI-IBS. An additional interesting finding in our results is the remarkable fatigue accompanying the PAS. In our study, 67.6% of the travellers had significant fatigue. Furthermore, beyond the improvement in GI symptoms there was an impressive decline in the fatigue post treatment, and an incline in the energy level score. The association between fatigue and PAS post-travel and the improvement in both as a response to treatment defines fatigue as an important symptom for a new syndrome—‘Post-travel fatigue and abdominal symptoms’. Chronic fatigue syndrome or post-infectious fatigue state have been described following acute infectious illness with a diverse spectrum of pathogens.29,30 However, it is not a common finding neither a part of the definition of IBS.28 In our study among returning travellers, fatigue and lack of energy were found to be commonly associated with PAS. Similar fatigue has been described post giardiasis, as reported by Morch et al.31 after a large waterborne outbreak in Bergen. They reported a prevalence of 41% chronic fatigue symptoms during the 2 years post treatment with a spontaneous resolution in only 20.8% of the cases at a follow-up time of 5 years.31,32 Our results show a higher recovery rate following empirical treatment, with 68% of our patients reporting an improvement in energy level, a significant improvement compared to the 20.8% reported in the Bergen study. The main limitations of our study is the retrospective design with a lack of a control group, although based on our study might be ethically unjustified to withhold the empiric treatment in these cases (In our experience, many patients refuse to participate in a randomized control study as they do not want to postpone their treatment.). Moreover, many of the patients already had received several antibiotics courses, antacid and IBS treatments without relief. Another limitation is the possibility of memory bias, although the median time frame of the study was 1.3 years post treatment (0.6–3.6). In conclusion, the improvement in GI symptoms, energy level and general well-being, shortly after the empiric anti-parasitic treatment justifies this early empirical approach (before a wide clinical investigation is taken) in returning-travellers with post travel PAS. It is important to note that in our study the parasite diagnosis was done by stool microscopy, however further studies are needed to assess the effect of molecular testing on the diagnosis and treatment of intestinal parasites in returning travellers. The association between fatigue and persistent abdominal Syndrome post-travel and the improvement in both as a response to treatment defines fatigue as part of a new syndrome—‘Post-travel fatigue and abdominal symptoms’. Funding None. Acknowledgements This work was performed as part of the requirements of the Hebrew university medical school for Medical Degree. Thanks to Ms. Tali Bdolach Avram for her statistical analysis contribution. Conflict of interest: All authors declare no conflicts of interest. Authors' contributions All authors made substantial contributions to the following: the conception and design of the study (T.L., E.S., B.N.); data acquisition (B.N.,T.L.); analysis or interpretation (B.N., E.S., T.L.), the drafting of the article or its critical revision for important intellectual content (B.N., T.L., E.S.,); formatting and revising the final version of the article (T.L.). All the authors have approved the final article. References 1 Word Tourism Organization, UNWTO. UNWTO Tourism Highlights [online], 2016. http://mkt.unwto.org/publication/unwto-tourism-highlights-2016-edition (1 November 2016, date last accessed). 2 Connor BA. Travelers’ diarrhea. 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Google Scholar CrossRef Search ADS PubMed  Author notes The study was presented at the APTHC 2016, Nepal. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
TI - The effectiveness of empirical anti-parasitic treatment in returning travellers with persistent abdominal symptoms
JO - Journal of Travel Medicine
DO - 10.1093/jtm/tax083
DA - 2017-12-08
UR - https://www.deepdyve.com/lp/oxford-university-press/the-effectiveness-of-empirical-anti-parasitic-treatment-in-returning-eNJmb2e9RG
SP - tax083
VL - 25
IS - 1
DP - DeepDyve
ER -