[Show abstract][Hide abstract] ABSTRACT: Environmental factors during childhood are thought to play a role in the aetiolgy of Crohn's Disease (CD). However the association between age at time of exposure and the subsequent development of CD in South Africa is unknown.
A case control study of all consecutive CD patients seen at 2 large inflammatory bowel disease (IBD) referral centers in the Western Cape, South Africa between September 2011 and January 2013 was performed. Numerous environmental exposures during 3 age intervals; 0-5, 6-10 and 11-18 years were extracted using an investigator administered questionnaire. An agreement analysis was performed to determine the reliability of questionnaire data for all the relevant variables.
This study included 194 CD patients and 213 controls. On multiple logistic regression analysis, a number of childhood environmental exposures during the 3 age interval were significantly associated with the risk of developing CD. During the age interval 6-10 years, never having had consumed unpasteurized milk (OR = 5.84; 95% CI, 2.73-13.53) and never having a donkey, horse, sheep or cow on the property (OR = 2.48; 95% CI, 1.09-5.98) significantly increased the risk of developing future CD. During the age interval 11-18 years, an independent risk-association was identified for; never having consumed unpasteurized milk (OR = 2.60; 95% CI, 1.17-6.10) and second-hand cigarette smoke exposure (OR = 1.93; 95% CI, 1.13-3.35).
This study demonstrates that both limited microbial exposures and exposure to second-hand cigarette smoke during childhood is associated with future development of CD.
PLoS ONE 12/2014; 9(12):e115492. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inter-racial differences in disease characteristics and in the management of Crohn's disease (CD) have been described in African American and Asian subjects, however for the racial groups in South Africa, no such recent literature exists.
PLoS ONE 08/2014; 9(8):e104859. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and objectives. The aim of this study is to report the incidence of Clostridium difficile-associated disease (CDAD) in a tertiary-care hospital in South Africa and to identify risk factors, assess patient outcomes and determine the impact of the hypervirulent strain of the organism referred to as North American pulsed-field type 1 (NAP1). Methods. Adults who presented with diarrhoea over a period of 15 months were prospectively evaluated for CDAD using stool toxin enzyme immunoassay (EIA). Positive specimens were evaluated by PCR. Patient demographics, laboratory parameters and outcomes were analysed. Results. CDAD was diagnosed in 59 (9.2%) of 643 patients (median age 39 years, IQR 30 - 55). Thirty-four (58%) were female. Recent antibiotic exposure was reported in 39 (66%), 27 (46%) had been hospitalised within 3 months, and 14 (24%) had concomitant inflammatory bowel disease (IBD). Nineteen (32%) had community-acquired CDAD (CA-CDAD). The annual incidence of hospital-acquired CDAD (HA-CDAD) was 8.7 cases/10 000 hospitalisations. Two cases of the hypervirulent strain NAP1 were identified. Seven (12%) patients underwent colectomy (OR 6.83; 95% CI 2.41 - 19.3). On logistic regression, only antibiotic exposure independently predicted for CDAD (OR 2.9; 95% CI 1.6 - 5.1). Three (16%) cases of CA-CDAD reported antibiotic exposure (v. 90% of HA-CDAD, p<0.0001). Twelve (86%) patients had concomitant IBD (p<0.0001 v. HA-CDAD). CA-CDAD was significantly associated with antibiotic exposure (OR 0.04, 95% CI 0.01 - 0.24) and IBD (OR 9.6, 95% CI 1.15 - 79.8). Conclusion. The incidence of HA-CDAD in the South African setting is far lower than that reported in the West. While antibiotic use was a major risk factor for HA-CDAD, CA-CDAD was not associated with antibiotic therapy. Concurrent IBD was a predictor of CA-CDAD.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 03/2013; 103(3):168-72. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: Inflammatory bowel disease (IBD) is more common in countries with improved hygiene, suggesting that environmental exposures may be associated with its development. The primary objective of this study was to examine the association between self-reported childhood helminth infection and the development of IBD in South Africa. METHODS:: Unmatched case-control study. Logistic regression was used to model associations with IBD. RESULTS:: There were 88 patients with Crohn's disease (CD), 63 with ulcerative colitis (UC), and 219 control subjects. Of the 151, 93 (61.6%) IBD subjects (35 of 63 [55.6%] had UC and 58 of 88 [65.9%] had CD) reported childhood helminth exposure compared with 200 of 219 (91.3%) non-IBD subjects (P < 0.001). Helminth infection (adjusted odds ratio [AOR] = 0.2; 95% confidence interval [CI], 0.1-0.4), shared housing (AOR = 0.1; 95% CI, 0.04-0.4), and raw beef consumption (AOR = 0.2; 95% CI, 0.1-0.6) were protective, whereas urban dwelling (AOR = 4.2; 95% CI, 2.0-8.8) and parental tertiary education (AOR = 18.2; 95% CI, 3.2-103.7) were associated with CD. Helminth infection (AOR = 0.2; 95% CI, 0.1-0.6), mixed race (AOR = 0.1; 95% CI, 0.03-0.5), smoking (AOR = 0.2; 95% CI, 0.07-0.5), shared housing (AOR = 0.1; 95% CI, 0.01-0.4), and raw beef consumption (AOR = 0.1; 95% CI 0.04-0.5) were protective against UC, whereas parental tertiary education (AOR = 12.7; 95% CI, 1.0-157.4) was associated with UC. CONCLUSION:: This study demonstrates a protective association of childhood helminth infection against the development of IBD and supports the "hygiene hypothesis" that improved living conditions may increase the incidence of IBD. Our epidemiologic conclusions provide support that helminths may have immunomodulatory effects which provides protection against the development of IBD later in life.
[Show abstract][Hide abstract] ABSTRACT: Intestinal tuberculosis occurs mainly in the terminal ileum and caecum, where the concentration of bile acids is lowest, and rarely in the upper digestive tract.
We examined the effect of physiological concentrations of bile acids on the in vitro growth of Mycobacterium tuberculosis (MTB).
The 4 major bile acids, lithocolic acid, cholic acid, deoxycholic acid and chenodeoxycholic acid, were added to individual Lowenstein-Jensen (LJ) culture media at physiological concentrations. A combined LJ medium was also prepared using all 4 bile acids. These were double-diluted 4 times by the addition of LJ media. Each culture medium was inoculated with the H37Rv strain of MTB and incubated at 37°C for 8 weeks. MTB growth was measured at 2 and 8 weeks in a semiquantitative fashion using cut-offs of >5, >10, >20, >100 colony-forming units.
All lithocolic acid cultures showed uninhibited TB growth at 2 and 8 weeks. Chenodeoxycholic acid, deoxycholic acid and cholic acid alone, and in combination, showed concentration-dependent inhibition of MTB growth at 2 and 8 weeks. Four cultures were lost to contamination.
Certain bile acids alone and in combination, at physiological concentrations, inhibit the growth of MTB in vitro. This might explain why intestinal TB occurs in the ileocaecum in the majority of cases and why gallbladder TB is very rare.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 06/2012; 102(6):522-4. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While disorders such as gastro-oesophageal reflux disease, gastrointestinal (GI) cancers and inflammatory bowel disease are prevalent among all racial groups in the Western Cape, there is little knowledge of local GI service provision. The state of equipment, facilities and staffing is largely unrecorded and to date unknown. The aim of this study was to audit the availability of GI facilities in the provincial sector, which provides care for the majority of people in the Western Cape.
All hospitals in the Western Cape providing endoscopy were evaluated by means of a hands-on audit, to identify available organisational infrastructure. Data including staffing, details and utilisation of existing equipment, maintenance and disinfection techniques and delays in service provision were collected.
Over a period of 12 months, 17 Western Cape hospitals were visited: 3 tertiary, 5 regional and 9 district-level institutions. There are currently 89 GI endoscopes in state service, with an average age of 6.1 years (range 1-23 years). While most institutions utilise video endoscopy, in many instances equipment is near the end of its economic life. A total of 26,434 endoscopic procedures were performed over a 12-month period. Overall at least 60% of all adult endoscopy was undertaken at tertiary institutions. The mean delay from consultation until gastroscopy or colonoscopy was 9.25 weeks (range 0.5-28 weeks) and 8 weeks (range 1-20 weeks), respectively. Only 1 tertiary and 1 regional hospital employed fully trained, registered nurses, and the majority of institutions did not conform to internationally accepted standards for the maintenance and disinfection of endoscopic equipment.
While endoscopy equipment is widely distributed throughout the province, it is evident from this study that services in the Western Cape fall short of international standards, with delays in endoscopic provision, lack of adequate equipment, inadequate scope maintenance and disinfection and a shortage of trained staff. As such, much of the population reliant on state facilities has poor access to GI health care. These deficiencies need to be addressed.
South African journal of surgery. Suid-Afrikaanse tydskrif vir chirurgie 09/2008; 46(3):68-72. · 0.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The rapid urease test (RUT) is used at Groote Schuur Hospital for diagnosing Helicobacter pylori infection. This is an in-house method, which has not been validated.
To validate our practice of reading the RUT immediately after endoscopy (RUT(0)), by comparing this with a reading at 24 hours (RUT(24)) and with histological analysis.
Ninety consecutive patients undergoing upper endoscopy over a 6-week period from October 2005 to November 2005, and in whom rapid urease testing was indicated, were included in the study. Patients with recent exposure (within 2 weeks of endoscopy) to proton pump inhibitors (PPIs), histamine receptor antagonists (H2RAs) and antibiotics (confounders) were noted and included in the cohort. Two antral and two body biopsies were taken for histological examination and a third antral biopsy was placed in the RUT bottle. Both haematoxylin and eosin and modified Giemsa staining methods were used to identify H. pylori. The RUT was read immediately (within 5 minutes of upper endoscopy) (RUT(0)), as per our current practice, and each specimen was re-read at 24 hours (RUT(24)). Sensitivity, specificity, positive and negative predictive values and the impact of confounders were calculated.
Of the 90 patients undergoing rapid urease testing, 39% were male and 61% were female, with a mean age of 55 years (range 22-79 years). Histological examination revealed H. pylori in 67.8% (N=61) of the biopsy specimens. In the 65 patients without confounders, the sensitivity and specificity of the RUT(0) were 65.9% and 100% respectively, and 90.9% and 100% for RUT(24). After including the 25 patients with confounders, the sensitivity and specificity were 68.8% and 100% for RUT(0), and 90.1% and 100% for RUT(24) respectively. Thirteen RUT(0) specimens (30.9%) that were initially negative became positive at the RUT(24) reading. There were 6 (9.8%) RUT(0)- and RUT(24)-negative but histology-positive specimens. Four of these 6 false-negative RUT(24) results could be accounted for by a low H. pylori density on histological analysis (2 patients were taking PPIs). Confounders did not alter the sensitivity and specificity outcomes or impact on the number of false-negative RUTs.
Our locally prepared RUT is a specific test for the detection of H. pylori infection. The sensitivity is greatly enhanced by reading the test at 24 hours. The use of PPIs, H(2)RAs and antibiotics preceding endoscopy did not impact significantly on the results.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 01/2008; 97(12):1281-4. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Distinguishing Crohn's disease from intestinal tuberculosis in endemic areas is challenging as both conditions have overlapping clinical, radiological, endoscopic and histological characteristics. Furthermore, high rates of latent tuberculosis confer a considerable risk of reactivation once therapy for established Crohn's disease is started.
To review current strategies in differentiating these two conditions, and in managing Crohn's disease, in populations with high rates of tuberculosis.
Literature review and clinical experience.
While various clinical, radiological, endoscopic and histological parameters may aid in differentiating Crohn's disease from intestinal tuberculosis, these remain imperfect and as treatment options differ misdiagnosis has grave consequences. We propose a diagnostic algorithm, based on currently available evidence and experience, to aid in this dilemma. We also discuss approaches to the management of Crohn's disease, including agents targeting tumour necrosis factor-alpha, in patients at risk of developing tuberculosis.
A diagnosis of Crohn's disease in individuals at risk for tuberculosis should only be made after careful interpretation of clinical signs, abdominal imaging and systematic endoscopic and histological assessment. Newer techniques for the diagnosis of latent tuberculosis still need to be validated in this environment, and guidelines on the treatment of latent tuberculosis in this setting require clarification.
[Show abstract][Hide abstract] ABSTRACT: The histological differential diagnosis of Crohn's disease and intestinal tuberculosis can be very challenging, as both are chronic granulomatous disorders with overlapping histological features.
To evaluate selected clinical and histological parameters in colonic biopsy specimens for their ability to discriminate between Crohn's disease and intestinal tuberculosis.
25 patients with Crohn's disease and 18 patients with intestinal tuberculosis were selected for this study on the basis of established clinical, radiological and histological criteria. Clinical data and selected histological parameters in colonoscopic biopsy specimens were assessed retrospectively. A total of 103 and 41 biopsy sites were evaluated in patients with Crohn's disease and intestinal tuberculosis, respectively.
Clinical parameters helpful in differentiating intestinal tuberculosis from Crohn's disease included chest radiographic features of tuberculosis (56% v 0%), perianal fistulae (0% v 40%) and extraintestinal manifestations of Crohn's disease (0% v 40%). Histopathological features that seemed to reliably differentiate between intestinal tuberculosis and Crohn's disease included confluent granulomas, > or =10 granulomas per biopsy site and caseous necrosis (in biopsy samples of 50%, 33% and 22% of patients with intestinal tuberculosis, respectively, v 0% of patients with Crohn's disease). Features that were observed more often in patients with intestinal tuberculosis than in those with Crohn's disease included granulomas exceeding 0.05 mm(2) (67% v 8%), ulcers lined by conglomerate epithelioid histiocytes (61% v 8%) and disproportionate submucosal inflammation (67% v 10%).
Clinical features and selected histological parameters in colonoscopic biopsy specimens can help in differentiating between Crohn's disease and intestinal tuberculosis.
Journal of Clinical Pathology 08/2006; 59(8):840-4. · 2.55 Impact Factor