Irritable bowel syndrome: A review on the role of intestinal protozoa and the importance of their detection and diagnosis

Abstract

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder in which abdominal pain is associated with a defect or a change in bowel habits. Gut inflammation is one of the proposed mechanisms of pathogenesis. Recent studies have described a possible role for protozoan parasites, such as Blastocystis hominis and Dientamoeba fragilis, in the etiology of IBS. Dientamoeba fragilis is known to cause IBS-like symptoms and has a propensity to cause chronic infections but its diagnosis relies on microscopy of stained smears, which many laboratories do not perform, thereby leading to the misdiagnosis of dientamoebiasis as IBS. The role of B. hominis as an etiological agent of IBS is inconclusive, due to contradictory reports and the controversial nature of B. hominis as a human pathogen. Although Entamoeba histolytica infections occur predominately in developing regions of the world, clinical diagnosis of amebiasis is often difficult because symptoms of patients with IBS may closely mimic those patients with non-dysenteric amoebic colitis. Clinical manifestations of Giardia intestinalis infection also vary from asymptomatic carriage to acute and chronic diarrhoea with abdominal pain. These IBS-like symptoms can be continuous, intermittent, sporadic or recurrent, sometimes lasting years without correct diagnosis. It is essential that all patients with IBS undergo routine parasitological investigations in order to rule out the presence of protozoan parasites as the causative agents of the clinical signs.

Introduction

Irritable bowel syndrome (IBS) is defined as a functional group of bowel disorders in which abdominal pain is associated with defecation or alterations in bowel habit in the absence of an organic cause (Brandt et al., 2002). It is one of the most commonly diagnosed gastrointestinal illnesses with prevalence rates of 10–15% in North America and Europe (Brandt et al., 2002, Mertz, 2003 ) leading to an estimated cost to the United States of 1.7 billion dollars in 2000 (Mertz, 2003). Similar rates have been documented in developing countries; although it is difficult to know how aggressively alternative diagnoses were excluded in these populations (Olubuyide et al., 1995, Curioso et al., 2002, Lule and Amayo, 2002, Gwee, 2005, Kang, 2005, OKeke et al., 2005). Irritable bowel syndrome affects all ages and all sexes with a 2:1 female predominance.

The pathophysiology of IBS remains elusive and no mechanism is unique to, or characterises, IBS. There are probably several interconnected factors which occur to varying degrees in patients that account for the clinical symptoms of IBS. These include altered gut reactivity (colonic and/or small bowel motility) in response to luminal or psychological stimuli, visceral afferent hypersensitivity, and a hypersensitive gut with enhanced visceral perception and pain (Thompson et al., 2000, Mertz, 2003). It is unclear whether this hypersensitivity is mediated via the local or central nervous system or a dysregulation of the brain–gut axis. In addition, hereditary, environmental and dietary factors probably play a role (Levy et al., 2001, Brandt et al., 2002).

Persistent low-grade inflammation may play a role in IBS. It is estimated that 7–31% of patients with infectious gastroenteritis go on to develop IBS (post-infectious IBS) (McKendrick and Read, 1994, Neal et al., 1997, Rodriguez and Ruigomez, 1999). This translates into a 14-fold increase in the overall risk of developing IBS following acute diarrhoea compared with the general population. Risk factors include longer duration of symptoms, young age and being female. The immune activation is characterised by increased intra-epithelial and lamina propria lymphocytes. These changes have been documented to persist for more than a year following the resolution of the infectious agent (McKendrick and Read, 1994, Neal et al., 1997, Rodriguez and Ruigomez, 1999). Inflammation may also occur in deeper layers of the gut. In a small IBS cohort, full-thickness biopsies revealed normal mucosa but intra- and peri-ganglionic lymphocytic infiltration at the region of the myenteric plexus (Tornblom et al., 2002). Furthermore, a correlation was revealed with the numbers of mast cells in close proximity to enteric nerves and the intensity of symptoms (Barbara et al., 2004). Most patients recover. However, in a subset of patients, persistent immune activation results in ongoing symptoms. Possible mechanisms include a genetic predisposition, continuous antigenic exposure (bacterial, parasitic or dietary) or molecular mimicry.

As there are no biological markers for IBS, diagnosis is based on a cluster of clinical symptoms (Rome II criteria; Saito et al., 2000) which include abdominal pain or discomfort with associated changes in bowel frequency and/or stool form. Symptoms may be relieved by defecation. A central feature that supports IBS is the presence of continuous or recurrent symptoms for a minimum of 3 months. Passage of mucous and bloating or sensation of abdominal distension may also occur.

There are no firm recommendations about the extent and type of testing required to exclude other organic pathology. Investigation of stool for ova, cyst and parasites is generally recommended when diarrhoea is the major manifestation of IBS. The intestinal protozoa associated with IBS-like symptoms are shown in Table 1. The role that protozoan parasites may play in this complex disease has not been fully investigated.