Protein-losing enteropathy and trichuriasis - abstract

The phenomenon of protein-losing enteropathy (PLE) is defined as the abnormal loss of serum proteins into the gastrointestinal tract resulting from a variety of gastrointestinal abnormalities. Infestation of the large bowel and terminal ileum by adult Trichuris trichiura results in inflammatory reactions surrounding the sites of attachment. This study establishes Trichuris dysentery syndrome as one of the clinical disorders characterized by PLE. The clearance by the gut alpha-1-antitrypsin (OAT), a serum protein that resists proteolysis by digestive enzymes, was assessed in (i) subjects infected by the parasitic nematode and presenting with the Trichuris dysentery syndrome, and (ii) subjects manifesting no gastrointestinal diseases nor having conditions or receiving drugs likely to cause PLE. All subjects were within the age range 3 through 11 years, inclusive. A linear regression analysis showed a significant correlation between clearance of O AT and adult worm count (r = 0.4, p<0.05). The daily loss of this amount of serum protein is likely to be a considerable part of the cost to the host of this chronic parasitic infection (AU)

Tissue histamine release in rectal mucosa from trichuris dysentery syndrome children: infected, after worm expulsion, and during the recovery growth spurt - abstract

There is clearly some form of inflammatory response to the heavy load of epithelially invasive whipworms in the colonic and rectal mucosa in the fully developed trichuris dysentery syndrome (TDS). We have shown by extensive immunohistochemical studies of caecal biopsies that there is no evidence that this is "immunologically medicated" (essentially, T-cell-controlled) inflammation with mucosal structural damage. One major difference between infected and control children shown by immunohistochemistry, however, was a 10-fold increase in lamina propria cells with surface IgE, presumably mast-cells (MacDonald et al, CCMRC, 1989). Children with TDS were studied before treatment, 3 days after the completion of worm-expulsive chemotherapy, and 3 or 6 weeks later when they had shown a height gain of >0.7 percent over a 3-week interval. On each of these 3 occasions rectal mucosa was placed in ice-cold Tyrode's buffer for in vitro histamine release studies, either spontaneous (at 37§C) or following challenge with rabbit anti-human IgE or T.trichiura excretory-secretory (ES) product. Residual tissue histamine concentration was also assayed. Spontaneous histamine release tended to be high on the first biopsy (maximum 81 percent of total in 20 mn), and was not then capable of being boosted by anti-IgE or Trichuris ES. However, following worm expulsion (max 16 percent) and on the third biopsy (max 6 percent) there was a clear trend for spontaneous histamine release to be diminishing. In some specimens at the 2nd and 3rd stages Trichuris ES antigen could then provoke a massive discharge of intracellular histamine into the supernatant. These studies of cell histamine release have advanced our understanding of the inflammatory mechanism of this disease (Type I hypersensitivity) and have shown in some children a persisting worm-sensitive state of the rectal mucosa (AU)

Trichuriasis: the clinical picture - abstract

Human trichuriasis is a disease of clinical importance. This study reaffirms its status as such, highlighting the spectrum of manifestations presenting in individuals with Trichuris dysentery syndrome. Individuals with and without the syndrome, having in common a history of bloody, mucoid diarrhoea, were compared. Thirty-one patients (age range 2-10 years) were admitted to the Tropical Metabolism Research Unit. Anthropometry was preceded by full history and physical examination. The cause of dysenteric symptoms in each case was determined by stool analyses and colonscopy. Twenty-six of the patients had colitis secondary to massive Trichuris trichuriura infection. Worm burden was assessed by antihelminthic expulsion following colonoscopy. We present data (Table) from which an index of the diagnostic likelihood of Trichuris dysentery syndrome can be derived. When one or more of the symptoms are present in a child with over 3 months' history of diarrhoea, a diagnosis of the disease, confirmable by stool examination, and suitable antihelminthic treatment are indicated (AU)

Plasma protein response in children with trichuris dysentry syndrome - abstract

In Trichuris Dysentry Syndrome (TDS), we have elsewhere shown an IgE-mediated mucosal mast cell inflammatory response and infiltration of the colonic lamina propria by macrophages with evidence of the cellular production to TNF O. There is an increased concentration of this cytokine in the systemic circulation: both this and the correlation of finger-clubbing with worm load are evidence of an inflammatory response which is systemic as well as local to the intestine. We therefore assayed the plasmas of 53 TDS children, 16 "disease control" (DC) and 20 "normal control" (NC) children for plasma protein changes. DC children were Trichuris negative patients who had clinical indications for colonoscopy, mainly chronic diarrhoea; NC were trichuris-negative asymptomatic children of similar background to the TDS patients who were subjected to venepuncture and non-invasive tests of intestinal permeability and intestinal protein clearance (normal). There was a significant increase (p<0.05) in the means of C-Reactive protein (CRP) and antitrypsin in the TDS compared with the NC group. The mean increase in the DC group was significantly differernt from the NC. The reduction in the mean albumin concentration in TDS compared with NC children was not quite significant (p=0.05). Caeruloplasmin showed a significant difference only between the DC and NC children (p < 0.05). The other plasma proteins assayed, transferrin and fibrinogen, showed no significant difference in their means among the three groups. These changes in plasma protein concentrations are indicative of a generalized sytemic response to Trichuris trichuria and correspond to a continuous, mile "acute phase response" to this chronic infection (AU)

Immediate hypersensitivity in colon of children with chronic Trichuris trichiura dysentery

There are few data on mucosal immune responses to intestinal helminths in human beings, especially those involving the IgE system, which is thought to be important in parasite expulsion. We sought evidence of an immediate hypersensitivity reaction in the colon of children with chronic dysentery due to Trichuris trichiura. 28 children with Trichuris dysentery syndrome (TDS) were compared with 16 control children (with no TDS or worms visible on colonoscopy). All children were aged 1-11 years. Rectal biopsy samples were taken before and after expulsion of the worms by means of mebendazole treatment. Children wtih TDS had significantly greater numbers than controls of mast cells (mean [SD] 10.9 [1.3] vs 3.9 [0.6] percent of all cells; p<0.0003) and of cells with surface IgE (median [range] 11.1 [7.5-11.6] vs 1.0 [0-1.5] percent; p<0.001) in the subepithelial region of the mucosa. On electronmicroscopy, degranulating mast cells were prominent in parasitised children. In culture, rectal biopsy samples from parasitised children showed high rates of spontaneous histamine release, but only low rates of antigen-specific release. After treatment, spontaneous histamine release was significantly reduced and antigen-specific histamine release could be provoked. Thus, an IgE-mediated immune mucosal response to a helminth infection does occur in human beings but is not sufficient to cause appreciable parasite expulsion. (Summary)