A proof of concept study establishing Necator americanus in Crohn's patients and reservoir donors.
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Biomedical subjects
Publications and source records attributed to J Croese.
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OBJECTIVE: To evaluate whether colonoscopy protects against subsequent colorectal cancer (CRC). DESIGN: Case and population survey. SETTING: Townsville region in northern Queensland, between mid 1985 and January 1998. SUBJECTS: All 8430 patients who underwent 11,148 colonoscopies performed by the author at the Mater Private Hospital (a community-based open-access colonoscopy service) between July 1985 and December 1996; those who were subsequently diagnosed with CRC, to January 1998; and all 476 residents diagnosed with colorectal cancer between 1994 and 1997. MAIN OUTCOME MEASURES: Age-standardised CRC incidence for 1994-1997 for patients who had had a previous colonoscopy and for the remaining community; Dukes' grade of CRCs. RESULTS: For people aged 50 years and over, the incidence of CRC was significantly lower among those who had had a previous colonoscopy than in the remaining community (1.14 versus 2.31 per 1000 patient-years; P = 0.0046). For people aged 35-49 years, the incidence was 0.35 versus 0.31 per 1000 patient-years (P = 0.86). Thirty-one CRCs developed in 29 people who had had previous colonoscopy; only five of these CRCs were graded Dukes C, with none graded Dukes D. In contrast, almost half the CRCs in the rest of the community were graded Dukes C or D (P < 0.001). All but one of those diagnosed with CRC on repeat colonoscopy had risk factors (personal or family history), and 23 of the CRCs were subclinical, with 20 being diagnosed during surveillance colonoscopy. CONCLUSIONS: Patients aged over 50 years who had previously undergone a colonoscopy and ensuing treatment were less likely to be diagnosed with CRC than otherwise expected. Surveillance colonoscopy led to diagnosis of CRCs with lower Dukes grades.
The existence of the canine hookworm Ancylostoma caninum in the human gut seems to be curtailed by an effective IgE-mediated inflammatory response against the helminth's feeding secretions, which, by damaging the host, compromises the parasite's feeding opportunities. In contrast, immunity does not develop against adapted, anthropophilic hookworm species, and it is suggested this relates to modulation of the inflammatory response by hookworm secretions. Here, John Croese discusses this hypothesis and its implications for the development of drugs to suppress allergy.
Recent studies in northeastern Australia indicate that enteric infection with Ancylostoma caninum is a leading cause of human eosinophilic enteritis. Much more frequent accompaniments of this infection are obscure abdominal pain with or without blood eosinophilia, while a large part of the population is probably infected asymptomatically. These conclusions are based on extensive serological investigations in patients and control subjects, as well as 15 cases in which single, adult hookworms were identified in situ in patients. In no case has more than one worm been identified, and none has been fully mature, so the infections have never been patent. Aphthous ulcers of the terminal ileum, caecum and colon have been seen in association with this infection and have also been observed in almost 5% of patients who are colonoscoped in north Queensland. Serodiagnosis has relied on an IgG and IgE ELISA using excretory-secretory antigens from adult A. caninum, but Western blot using these antigens to identify IgG4 antibodies to a protein of molecular weight 68 kDa (Ac68) promises to be more specific and sensitive. However, identical antigens appear to be secreted by the anthropophilic hookworms as well. The clinical, public health and biological significance of these findings are discussed in detail.
Ileal ulceration is diagnosed commonly at colonoscopy in northeastern Australia. This observation has occurred contemporaneously with the description of a painful enteritis caused through supposedly rare infections by Ancylostoma caninum, the cosmopolitan dog hookworm. In this study, we describe the morphology and prevalence of ileal ulcers and investigate their cause. There were 182 patients with a distinctive aphthous ileitis highlighted by haemorrhage into the tips of surrounding villi. The annual rate reached 4.7% of ileal examinations. Eosinophilic enteritis was the characteristic, but inconsistent, histological appearance. Ulceration was linked to infection by A. caninum through serological testing and, in three patients, by the retrieval of single hookworms. Affected patients were also more likely to own a dog (53%) than the total colonoscopic population (43%; P < 0.02). The monthly rates of diagnosis were related to climate with fewest recordings during winter. Pain was the chief indication for colonoscopy (49%), proportionally higher than in controls (28%; P < 0.0001). Patients with ulcers had increased blood eosinophil, immunoglobulin E and serological values. These results were higher still in the subset with pain compared with the rest. Most patients, however, had colonoscopy performed for unrelated reasons, such as bowel cancer surveillance, and were identified as having subclinical ulceration (rate 3.2%). The findings establish a distinctive aphthous ileitis characterized by tissue eosinophilia. The cause has been tentatively linked to canine hookworms. It is proposed that infection in this geographic region is common and only rarely does a painful enteritis develop as a consequence of hypersensitization.
Most patients with proven or suspected enteric infection with the common hookworm of dogs, Ancylostoma caninum, produce immunoglobulin G (IgG) and IgE antibodies to an immunodominant excretory/secretory antigen (Ac68) of the parasite. These antibodies were detected in both enzyme-linked immunosorbent assay (ELISA) and Western blots; the Western blot to detect IgG antibodies to Ac68 was the most specific and sensitive. The subclasses of IgG of the antibody response to the parasite were analyzed using Western blots with anti-IgG subclass-specific monoclonal antibodies as marker systems in an attempt to further improve the specificity of the assay. Eight patients with confirmed enteric infections with A. caninum (positive controls) were tested; six had antibodies in all IgG subclasses against Ac68. Twenty sera from patients with suspected enteric infection with A. caninum (manifested as eosinophilic enteritis or unexplained abdominal pain with peripheral eosinophilia) were tested; 16 had total IgG antibodies to Ac68, while IgG1, IgG2, IgG3, and IgG4 responses were found in 11, 10, 9, and 12 of these sera, respectively. Small numbers of sera from groups of patients infected with other helminths and from healthy blood donors had various combinations of IgG, IgG1, IgG2, and IgG3 antibodies to Ac68, but none of these sera had IgG4 antibodies to Ac68. Sera from all nine patients with human hookworm infection had IgG, IgG1, IgG2, and IgG3 antibodies to Ac68 and eight of the nine were also positive for IgG4 antibodies. These results indicate the Western blot to detect IgG4 antibodies to Ac68 is the most reliable immunodiagnostic test yet described for enteric infection with A. caninum, although this test does not discriminate between infections with human and canine hookworms.
While eosinophilic gastroenteritis is considered a rare condition, eosinophilic enteritis without gastric involvement is quite common in northeastern Australia. We present 79 patients with biopsy-proven eosinophilic enteritis, 70 seen since 1987. In 10 patients, eosinophilic enteritis was associated with infection by single, sexually immature, adult hookworms, most positively identified as the common dog hookworm Ancylostoma caninum. An additional 22 patients (of 34 tested) had serological evidence of A. caninum exposure. The essential pathology, i.e., edema and eosinophilic infiltration of the gut wall, ascites, and regional lymphadenopathy, was identical to that seen in eosinophilic gastroenteritis. Additional, more specific features included pathological reactions centered on attached worms, mucosal alterations and ulcers considered to be hookworm bite sites, and submucosal and lymph node granulomas with central eosinophil degranulation and degradation products. Since A. caninum has an almost worldwide distribution, it is probable that A. caninum-induced eosinophilic enteritis occurs outside Australia. We show that the worm is easily overlooked in pathological specimens and that care is required to preserve worms intact for specific parasitological identification. The clinical and pathological features were similar to those seen in another human enteric helminthic zoonosis, anisakiasis. The possibility that there are yet other undiscovered intestinal zoonoses remains.
Ancylostoma caninum, the cosmopolitan canine hookworm prevalent in domestic pets throughout northeastern Australia, has been identified as a cause of obscure abdominal pain. To investigate the influence of climate on putative and confirmed human infections, a retrospective study of patients with eosinophilic enteritis and established infections was undertaken to identify the monthly and seasonal rates. The numbers seen each month were maintained throughout most of the year but decreased in June and remained low during winter. An increased rate of enteritis occurred during spring, which preceded the wet season. It is concluded that climate directly influences the rate of human enteric infection by canine hookworms. The increase in prevalence before the monsoon season was unexpected and suggests other influences, such as extraneous infection promoted by the irrigation of domestic gardens and possibly endogenous reinfection of the gut by hypobiotic larvae.
OBJECTIVE: To describe a zoonotic ancylostomiasis (canine), acquired from domestic pets by patients living in developed, urban communities. DESIGN: An 8-year, retrospective case study. SETTING: A clinical gastroenterologic practice in Townsville and a university parasitology department in Brisbane, Australia. PATIENTS: Nine patients, each with enteric hookworm infection diagnosed by finding a single organism in situ; five were treated by us, and the rest were referred to us for parasite identification. MEASUREMENTS: Clinical and demographic data, complete blood examinations, total serum immunoglobulin E assay, and serologic testing with enzyme-linked immunosorbent assay and Western blot using excretory-secretory antigens of Ancylostoma caninum. Gut biopsy specimens were examined histologically, and hookworms were identified using morphologic criteria. RESULTS: The infections in three of the patients were diagnosed during the initial 6 years and six in the last 2 years. All owned a dog and described activity potentially exposing them to infection with canine hookworm larvae. Three patients had a laparotomy for acute abdominal pain, and six had colonoscopies (five with pain and one without symptoms). Six of the nine had blood eosinophilia (mean, 0.97 x 10(9)/L), and five of eight had elevated immunoglobulin E levels (mean level, 756 micrograms/L); six of eight had eosinophilic inflammation of the gut. In six patients, the worm was identified as A. caninum, whereas in three, damage to the specimen did not allow specific identification; however, they were unlikely to be human parasite species. Although all parasites were in the adult stage, none were sexually mature. Positive serologic findings in seven of the eight patients tested confirmed presence of antibody to the parasite. CONCLUSIONS: Human enteric infections with A. caninum are being diagnosed more frequently in northeastern Australia. Although infection may be subclinical, the chief symptom is abdominal pain, sometimes sudden and severe. The pathologic finding is focal or diffuse eosinophilic inflammation caused by a type 1 hypersensitivity response to secreted antigens. Infection by sexually immature worms is scant and nonpatent, indicating poor adaptation to the human host. Serologic testing assists in identification of occult infection. Advanced hygiene and sanitation afford little protection because the parasite reservoir is a large and growing pool of infected domestic pets.
BACKGROUND/AIMS: Human disease caused by the canine hookworm Ancylostoma caninum and a high incidence of eosinophilic enteritis have been reported from northern Queensland, Australia. The aim of this study was to evaluate patients with unexplained abdominal pain and a possible association with cryptic infections by A. caninum. METHODS: The clinical and demographic features of patients from this region with eosinophilic enteritis (group A1, n = 42), obscure abdominal pain associated with (group A2, n = 105) and without (group A3, n = 84) blood eosinophilia were reviewed and sera were tested against A. caninum excretory-secretory antigens by enzyme-linked immunosorbent assay (ELISA) and Western blot. Four additional patients, two with confirmed A. caninum, had hookworm infection. RESULTS: The level of dog ownership in these four groups was 79%-100%, higher than in the local population (P < 0.001). The ELISA tested positive in 71% of A1, 67% of A2, and 30% of A3, versus 8% in controls (P < 0.002). All cases tested were positive on Western blot versus 10% of controls (P < 0.0001). The ELISA values increased with chronicity and decreased during convalescence. CONCLUSIONS: We conclude occult human A. caninum infections are common and are characterized by eosinophilic enteritis and obscure abdominal pain with or without blood eosinophilia. The diagnosis can be confirmed by serology.
In northeastern Australia, the incidence of human eosinophilic enteritis (EE) and unexplained abdominal pain with peripheral blood eosinophilia (PE) appear to be exceptionally high. Because adults of the common dog hookworm, Ancylostoma caninum, were found in situ in several cases, we compared specific antibody responses in patients with EE or PE with those of individuals from various control groups. Sera were obtained from three patients with confirmed dog hookworm infection, 25 patients with EE/PE, 42 with other diagnosed gastrointestinal disorders, eight with human hookworm infection, 27 with other diagnosed parasitic infections, and 100 blood donors from the State of Tasmania, where A. caninum does not occur. They were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blot for IgG and IgE antibodies to excretory-secretory (ES) antigens from adult A. caninum. In the ELISA, sera from 88% of EE/PE patients were positive for IgG and IgE antibodies to ES antigen. All eight patients infected with human hookworm (identified as A. duodenale in three) were also seropositive, while most of those with other parasitic infections, as well the blood donors, those with diagnosed gastrointestinal diseases, and the control subjects, were seronegative. In Western blots, sera from 92% of EE/PE patients demonstrated IgG and IgE antibodies to a component of ES antigen with a molecular weight of approximately 68 kD (Ac68), as did all sera from cases infected with human hookworms. Among the patients with other gastrointestinal disorders and parasitic infections, four of 42 (10%) and three of 27 (11%), respectively, reacted positively.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To describe the clinical presentation, diagnosis and management of strongyloidiasis in northern Queensland, and to identify predisposing factors for this infection. DESIGN: A five-year retrospective study of medical records of all cases diagnosed in a regional hospital microbiology laboratory, with follow-up by interview where possible. SETTING: The Townsville General Hospital. PATIENTS: A total of 14 cases of strongyloidiasis were identified, with patients ranging in age from 7 months to 59 years. RESULTS: Infected patients included nine Aborigines and two Vietnamese refugees, both high-risk groups. Of three Caucasians diagnosed, one was a war veteran, but the other two did not have significant travel histories; all three had lived or worked under insanitary conditions. In only one case was strongyloidiasis suspected; in most, it was diagnosed because of diarrhoea or blood eosinophilia which could not be related to the presenting illness. Thiabendazole treatment was effective in most cases. CONCLUSION: In northern Australia, strongyloidiasis can be acquired locally by Caucasians who live in unhygienic circumstances. It should be suspected in any person with unexplained abdominal pain, diarrhoea, cutaneous symptoms or blood eosinophilia, and the laboratory must be informed of the provisional diagnosis.
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Eosinophilic enteritis is now commonly diagnosed in northern Queensland, and cases have been seen elsewhere. The patients present with acute abdominal symptoms, which may mimic appendicitis, and many cases are managed by surgery. To facilitate the diagnosis of this unusual syndrome, six surgically treated cases are reported here. Blood eosinophilia may be a helpful diagnostic feature, but in some cases it does not develop until after the acute abdominal episode. Most cases resolve satisfactorily with conservative management.
An epidemic of eosinophilic enteritis (93 cases) has occurred in Townsville, northern Queensland, Australia. A hookworm was found attached to a resected, inflamed ileal segment from 1 patient but the species could not be identified. An adult hookworm of species Ancylostoma caninum was recovered at colonoscopy from the terminal ileum of a later patient. All of 38 patients interviewed in an epidemiological survey described behaviour which could have exposed them to infective larvae of this widespread dog parasite.
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During a 12-month period, feces from 780 persons from the Townsville region were evaluated by the Kinyoun acid-fast strain, and 36 (4.6%) immunocompetent patients were found to have Cryptosporidium oocysts. Twenty-five index cases were identified; 13 (8.6%) cases from 151 patients were from Palm Island, an isolated Aboriginal community in the wet tropics and 12 (1.9%) cases from 629 patients were from the dry tropics of Townsville. All 11 secondary cases were associated with a person-to-person outbreak in the nursery of a Townsville day-care centre. Infection occurred mainly in two distinct age groups: the under five-year-old (27 cases), and the 25 to 35-year-old (six cases). A prodrome of dry cough, rhinorrhea and vomiting often preceded symptoms of fever, weight loss, abdominal pain, persistent cough and vomiting, and acute diarrhea with frequent, non-bloodstained, watery, mucous stools. Although 13 patients were hospitalised because of their illness, the infection was self-limiting and all 36 patients recovered with symptomatic treatment. Cryptosporidium was the third most commonly identified enteric pathogen after Rotavirus and Giardia. Infection did not appear to depend on seasonal variation and no animal or environmental sources of infection were identified. Cryptosporidiosis in immunocompetent persons is endemic and common in North Queensland and routine investigations for this parasite in symptomatic patients are warranted.
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