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Editors

AnuKantele
SakariJokiranta

Prolonged Abdominal Complaints in Travellers

Essentials

  • Definitions vary; duration over 2 weeks or over 2 months.
  • If infectious, usually caused by intestinal parasites (protozoans in particular), more rarely bacteria or viruses
  • Other than infectious causes must always also be kept in mind.

Aetiology

Prolonged abdominal complaints caused by intestinal pathogens

  • Bacterial pathogens
    • The most common cause of acute diarrhoea (in travellers about 80% bacterial; see Acute Diarrhoeal Disease in a Traveller)
    • Long-term carriers may exist but are not common (most significant in practice in salmonellosis)
    • In 1-3% of patients with acute gastroenteritis abdominal symptoms become prolonged.
    • EPEC and EAEC (enteropathogenic and enteroaggregative E. coli) may sometimes be associated with prolonged symptoms.
  • Viruses
    • Cause acute disease; prolonged symptoms are rare.
    • Asymptomatic excretion of viruses may continue for several weeks or even several months after the acute infection (particularly in those with immunodeficiencies).
  • Intestinal protozoans
    • The longer the symptoms continue, the more probably they are caused by protozoans.
    • In the beginning, the infection is often either asymptomatic or produces few symptoms.
    • The most common causes are Dientamoeba fragilis Dientamoebiasis in Adults and Giardia lamblia Giardiasis.
    • Entamoeba histolyticaAmoebiasis usually causes more severe diarrhoea than the above and symptoms often include blood in stools and sometimes also fever.
    • In prolonged Cryptosporidium Cryptosporidiosis, Cyclospora Introduction to Intestinal Protozoal Diseases and Cystoisospora infections Introduction to Intestinal Protozoal Diseases and microsporidiosis, there is often immunodeficiency as a predisposing factor, such as advanced HIV infection or immunosuppressive medication. Also rarer pathogens are seen in patients with immunodeficiencies.
  • Intestinal worms
    • The infection is often either asymptomatic or produces few symptoms.
    • Strongyloides stercoralisStrongyloidiasis (the most common cause of symptomatic worm infections in travellers), Ascaris lumbricoides, or roundworm Ascariasis, hookworms Hookworm Disease and Trichuris trichiura Trichuriasis cause the most symptoms.
    • Other worms cause symptoms only at a high worm load; in practice these are seen only in people who have lived very long in endemic areas.

Antibiotic-associated diarrhoea (symptoms related to the use of antimicrobial drugs)

  • Occurs in 5-25% of patients on antimicrobial drugs.
  • In some, symptoms occur already a few hours, in others as long as several weeks after the initiation of the medication.
  • Antimicrobial drugs destroy the patient's own intestinal microbes, broad-spectrum antimicrobials more so than narrow-spectrum antimicrobials.
  • Microbial imbalance may appear as overgrowth of Clostridium difficile bacteria, for example.
  • Clostridioides difficileClostridioides Difficile Diarrhoea
    • Only toxin-producing strains cause diarrhoea.
    • May present as asymptomatic colonization.
    • Life-threatening pseudomembranous colitis is the most severe form of the disease.

Non-infectious abdominal complaints triggered by microbes

  • Microbes may sometimes trigger a non-infectious disease even if the causative agent can no longer be shown after prolonged symptoms. Acute gastroenteritis, for example, may trigger a chronic inflammatory bowel disease, such as Crohn's disease Crohn's Disease or ulcerative colitis Ulcerative Colitis.
  • Symptoms may persist for as long as several months.
  • Secondary malabsorption in some protozoal diseases, such as giardiasis
    • May be due to damaged intestinal villi.
    • The most common form of secondary malabsorption is secondary lactose intolerance, a state of disease sometimes resembling coeliac disease.
    • The symptoms will subside as the intestinal villi recover.
  • Postinfectious irritable bowel syndrome, PI-IBS Functional Bowel Disorders and the Irritable Bowel Syndrome (IBS)
    • The diagnosis is made by excluding other causes of prolonged abdominal complaints.
  • Postinfectious malabsorption syndrome, PI-MAS, or tropical sprue
    • Seen in people who have stayed a long time in tropical areas.
    • May present as severe malabsorption; the patient may lose a significant amount of weight.
    • May continue for several months.
    • Very rare in travellers
    • The diagnosis is made by excluding other causes.

Noninfectious causes

Diagnostic work-up

  • Abdominal complaints after travelling for less than one week do not usually require more detailed examination.
  • If symptoms continue (for more than 2 weeks), infectious causes should be sought, and also noninfectious causes, as necessary.

Bacterial causes

  • If aetiological investigations are needed, the basic study is either faecal bacterial culture or a more extensive combination of nucleic acid detection and culture.
  • Bacteria identified by both of these tests:
    • Salmonella
    • Shigella
    • Yersinia
    • Campylobacter
  • Detection of nucleic acids of faecal pathogens using a gene amplification method is more sensitive and faster than culture. In addition to the afore-mentioned bacteria, it can detect the following:.
    • Escherichia coli strains causing diarrhoea:
      • enteroaggregative (EAEC)
      • enteropathogenic (EPEC)
      • enterotoxigenic (ETEC)
      • enteroinvasive (EIEC)
      • enterohemorrhagic (EHEC) E. coli.
    • For any sample for which the nucleic acid detection method gives a positive result for Salmonella, Shigella, Yersinia, Campylobacter or EHEC, a culture and, if needed, sensitivity testing, are done without separate request.
  • Serological methods (Salmonella, Campylobacter and Yersinia antibodies) are used
    • when the symptoms have continued for more than 2 weeks and the aetiology is still not known
    • when reactive arthritis is suspected
    • when investigating prolonged unclear episodes of fever
    • when general symptoms occur.
  • In patients who have taken antimicrobials, nucleic acid detection test for Clostridium difficile is also performed. Nucleic acid detection is a sensitive test and should not be used in persons with no symptoms. In children below 2 years of age, C. difficile is a part of normal intestinal flora.

Biphasic diagnosis of parasitic infections

In Finnish patient samples protozoans are the most common parasites. Dientamoeba is clearly more common than Giardia. Since the introduction of nucleic acid detection tests, also Cryptosporidium findings have increased significantly, but especially the increased number of findings in 2018-2019 is suggestive of an increase in the number of infections (in 2019 almost 500 cases per year in a population of 5.5 million). Intestinal worms are clearly more rare findings than protozoans. In biphasic diagnosis, protozoans are first looked for and intestinal worms only in the second phase.

Phase one

  • Detection of the nucleic acids of intestinal protozoans in faeces is excellent for the investigation of prolonged abdominal complaints. The test can also detect Dientamoeba and Cryptosporidium.
  • As a secondary option, intestinal protozoans can also be detected by a less sensitive method in a formalin sample.
    • Three separate samples taken on different days at intervals of, preferably, a couple of days should be investigated.
    • The formalin sample does not detect Dientamoeba and Cryptosporidium and neither does it differentiate between the pathogenic Entamoeba histolytica and the apathogenic E. dispar.
    • If no pathogen is found in phase 1 studies, move on to phase 2.
    • Other investigations depending on the clinical picture (basic investigations include e.g. CRP, basic blood count with platelets, plasma sodium, potassium, creatinine and ALT).

Phase two

  • Repeat examination for faecal parasites in a formalin sample from three different stool samples to exclude intestinal worms.
  • Nucleic acid detection test for intestinal protozoans using 1-2 samples taken on different days
  • Blood eosinophil count or automated differential plasma leucocyte count
    • Eosinophilia may be associated with a worm infection (e.g. Strongyloides stercoralis Strongyloidiasis).
    • If the patient has clear eosinophilia without other diseases explaining it (e.g. asthma or symptomatic allergy), ask a physician specialized in infectious diseases or gastroenterology for assessment.
    • If parasite tests give negative results and the patient has no eosinophilia, worm infections are unlikely (but pinworm is still possible).
  • Other tests include e.g. HIV antigen and antibody, TSH, CRP, ESR, sodium, potassium, creatinine, ALT, GT, blood lactose intolerance (DNA test), tissue transglutaminase antibodies, faecal calproctetin.
  • A serum worm antibody test is in certain cases requested after consulting a specialist in infectious diseases. It is used to seek antibodies to seven worms often found in patients with eosinophilia (e.g. Strongyloides, Toxocara and Schistosoma). Toxocara cannot be detected in faecal samples. It is a canine and feline parasite that in humans remains migrating in the larval stage in the intestine (visceral larva migrans) and may cause abdominal complaints continuing several months without diarrhoea.

Treatment

  • If a specific causative agent is found, proceed accordingly.
    • Clostridioides difficile (formerly Clostridium difficile)
      • For detailed instructions on dosage, see Clostridioides Difficile Diarrhoea
      • First-line
        • In very mild disease, discontinuing antimicrobial medication suffices.
        • In mild or moderately severe disease, the first line drug therapy is oral metronidazole, alternatively vancomycin
        • In severe clinical picture vancomycin
      • Second line
      • When deciding on the treatment, the high differences in prices should be taken into account. (In Finland in March 2020, the prices of vancomycin and fidaxomicin were about 17 and 120 times that of metronidazole, respectively.)
      • Faecal transfusion has given good results in the treatment of repeated infections.
    • Dientamoeba fragilisDientamoebiasis in Adults
      • Metronidazole - first-line choice in outpatient care (moderately effective)
      • Secnidazole and tinidazole - possibly under special license (less effective than paromomycin)
      • Paromomycin - possibly under special license (highly effective)
    • Giardia lambliaGiardiasisDrugs for Treating Giardiasis
    • Blastocystis hominis
      • Common faecal finding
      • Usually considered apathogenic, medication not necessary
      • Shows previous contact with faecally contaminated water or food; more samples need to be collected to find the pathogenic parasite.
      • If the organism is detected repeatedly in large amounts and without other explanation for the abdominal complaints, treatment with metronidazole, for example, should be considered.A therapeutic trial may in some cases reduce symptoms because the drug may be effective against pathogenic protozoans not detected in tests or otherwise changes the microbial balance in the intestine.
  • Even if the symptoms of protozoan disease are alleviated or cease during treatment, they may recur after the end of the treatment. In that case new samples should be collected. The reason may be:
    • drug resistance
      • Giardia may be resistant to metronidazole but this is not common.
      • Other intestinal parasites are hardly resistant.
    • re-infestation at home or amongst the close family (e.g. Dientamoeba)
    • relapse caused by surviving parasites sensitive to the drug
      • In giardiasis, a 5-10% risk
      • In Entamoeba histolytica infections relapses are common unless specially licensed drugs effective against cysts are used
    • insufficient patient compliance.
  • Empirical pharmacotherapy
    • As suggested by a physician specialized in infections if there is a strong suspicion of a parasite infection
  • Symptoms of malabsorption secondary to damage to intestinal villi associated with parasite infections (particularly giardiasis) can be alleviated by a lactose-free diet rich in fibre, sometimes also by a gluten-free (i.e. coeliac) diet.

    References

    • van Lieshout L, Roestenberg M. Clinical consequences of new diagnostic tools for intestinal parasites. Clin Microbiol Infect 2015;21(6):520-8. [PubMed]
    • Pietilä JP, Meri T, Siikamäki H, et al. Dientamoeba fragilis - the most common intestinal protozoan in the Helsinki Metropolitan Area, Finland, 2007 to 2017. Euro Surveill 2019;24(29):. [PubMed]