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Background. Over 30% of the world’s population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products. Method. Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group. Conclusion. The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

Background. Overlapping clinical, endoscopic, radiographic and histological features, coupled with poor microbiological yield, make differentiating Crohn’s disease (CD) from intestinal tuberculosis (ITB) challenging. Granulomas are present in both diseases; in CD they predict the need for immunosuppressive therapy that requires ITB to be excluded before initiation.Objectives. To compare granuloma-positive CD and ITB, to identify factors that may aid in diagnosis.Methods. This was a retrospective cohort study evaluating granuloma-positive CD and ITB identified from a pathology database.Results. Sixty-eight ITB and 48 CD cases were identified. Patients with ITB were more likely to be male, and to have HIV infection, isolated colitis, night sweats and tachycardia. ITB was also associated with lower serum albumin and haemoglobin and higher C-reactive protein levels, a chest radiograph showing active tuberculosis, and lymph nodes >1 cm on imaging. Extraintestinal manifestations (EIMs) were predictive of CD. There were no significant differences in smoking status, symptom duration or perianal disease. On multivariate analysis, HIV positivity (odds ratio (OR) 29.72, 95% confidence interval (CI) 2.15 - 410.96; p=0.01), isolated colitis (OR 6.17, 95% CI 1.17 - 32.52; p=0.03) and the absence of EIMs (OR 0.10, 95% CI 0.01 - 0.65; p=0.02) remained significant risk factors for ITB.Conclusion. This is the first study to identify clinical and biochemical factors to aid in differentiating granuloma-positive ITB from CD. EIMs support a diagnosis of CD, while isolated colitis and HIV are predictors of ITB.Â

Several new classes of drugs have recently been developed for the management of Inflammatory Bowel Disease (IBD). In response, updated international guidelines have been published providing recommendations on how to incorporate these agents into existing treatment algorithms. Recent approval of these new therapies in South Africa has however raised many questions on how they should best be used in a local setting. Since no formal guidance is available, the South African Gastroenterology Society (SAGES) has put forward, in the present position paper, guidance on the best use of both existing and novel drug therapies in the management of IBD in the South African setting. [ABSTRACT FROM AUTHOR]

There is a knowledge gap on the epidemiology of inflammatory bowel disease in Africa. To begin to address this issue we formed a case reporting network of practitioners with an interest in inflammatory bowel disease across sub-Saharan Africa. Here we report a series of 175 cases from 12 countries over 2 years., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Over 30% of the world's population is anaemic, with a significant proportion of these being iron deficient. As iron deficiency (ID) anaemia in men and post-menopausal women is mostly caused by gastrointestinal blood loss or malabsorption, the initial evaluation of a patient with ID anaemia involves referral to a gastroenterologist. The current drive towards patient blood management in sub-Saharan Africa (SSA)prescribes that we regulate not only the use of blood transfusion but also the management of patients in whom the cause of iron loss or inadequate iron absorption is sought. Recommendations have been developed to: (i) aid clinicians in the evaluation of suspected gastrointestinal iron loss and iron malabsorption, and often a combination of these; (ii) improve clinical outcomes for patients with gastrointestinal causes of ID; (iii) provide current, evidence-based, context-specific recommendations for use in the management of ID; and (iv) conserve resources by ensuring rational utilisation of blood and blood products., Method: Development of the guidance document was facilitated by the Gastroenterology Foundation of Sub-Saharan Africa and the South African Gastroenterology Society. The consensus recommendations are based on a rigorous process involving 21 experts in gastroenterology and haematology in SSA. Following discussion of the scope and purpose of the guidance document among the experts, an initial review of the literature and existing guidelines was undertaken. Thereafter, draft recommendation statements were produced to fulfil the outlined purpose of the guidance document. These were reviewed in a round-table discussion and were subjected to two rounds of anonymised consensus voting by the full committee in an electronic Delphi exercise during 2022 using the online platform, Research Electronic Data Capture. Recommendations were modified by considering feedback from the previous round, and those reaching a consensus of over 80% were incorporated into the final document. Finally, 44 statements in the document were read and approved by all members of the working group., Conclusion: The recommendations incorporate six areas, namely: general recommendations and practice, Helicobacter pylori, coeliac disease, suspected small bowel bleeding, inflammatory bowel disease, and preoperative care. Implementation of the recommendations is aimed at various levels from individual practitioners to healthcare institutions, departments and regional, district, provincial and national platforms. It is intended that the recommendations spur the development of centre-specific guidelines and that they are integrated with the relevant patient blood management protocols. Integration of the recommendations is intended to promote optimal evaluation and management of patients with ID, regardless of the presence of anaemia.

With the exception of South Africa, inflammatory bowel disease (IBD) has long been considered uncommon in sub-Saharan Africa (SSA) with a dearth of peer-reviewed publications from the subcontinent. This most likely reflects underreporting as some cases may be missed due to the high burden of infectious diseases which may closely mimic IBD. In addition, many countries in SSA have limited endoscopic capacity, inadequate access to diagnostic imaging and a notable scarcity of histopathologists, radiologists and gastroenterologists. Beyond these obstacles, which significantly impact patient care, there are many other challenges in SSA, particularly the unavailability of key IBD therapies. In this review, we discuss barriers in diagnosing and managing IBD in SSA, as well as some of the initiatives currently in place to address these short comings., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Gastric adenocarcinoma (GCA) is the 5th leading cancer globally with an estimated 1.1 million cases reported in 2020. Ninety percent of non-cardia GCAs are attributable to Helicobacter pylori ( H. pylori ), the most prevalent bacterial infection globally. Rates of H. pylori infection are highest in Sub-Saharan Africa (SSA), yet surprisingly low numbers of GCAs are reported in the region. A similar phenomenon is seen with the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. These disorders have risen dramatically over the past century in high income countries across the globe, with sharp increases noted more recently in newly industrialized regions. In contrast IBD is rare in most regions in SSA. For both diseases this may reflect under-reporting or limited access to diagnostic modalities, but an alternative explanation is the high burden of infection with gastrointestinal parasites endemic to SSA which may attenuate the risk of developing GCA and IBD. In this mini review we discuss the complex interplay between these microorganisms, GCA, and IBD, as well as a possible protective role of H. pylori and the development of IBD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Setshedi and Watermeyer.)

Over the past century, the incidence of inflammatory bowel disease (IBD) in high-income countries has shown a sharp rise that then plateaued, and a similar trend has been observed in newly industrialised countries. IBD has long been considered uncommon in sub-Saharan Africa, possibly reflecting low exposure to environmental risk factors described in high-income populations. Alternatively, individuals living in sub-Saharan Africa might have a different genetic disposition. However, some cases of IBD might remain undetected in sub-Saharan Africa because of a lack of awareness, deficiencies in diagnostic and clinical capacity, and a substantial rate of misdiagnosis due to the high burden of infectious diseases. There are few published data describing the natural history of IBD in sub-Saharan Africa, and the true burden of the disease remains largely unknown, although there is some evidence that the incidence of IBD is rising in this region. This Series paper summarises the present understanding of IBD and challenges facing clinicians when diagnosing this disease in sub-Saharan Africa., Competing Interests: Declaration of interests GW reports travel support from AbbVie and Janssen and speakers honoraria from Janssen, AbbVie, and Adcock Ingram. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Inflammatory bowel disease (IBD) is generally considered a disease of high-income countries and is regarded as rare in sub-Saharan Africa. However, this assumption is almost certainly an underestimate, and the high burden of communicable diseases makes IBD in sub-Saharan Africa difficult to detect. Furthermore, some gastrointestinal infections can closely mimic IBD, contributing to delays in diagnosis and complicating therapeutic decision making. Constraints in endoscopic capacity alongside a scarcity of qualified diagnostic pathologists add to the difficulties. Implementing evidence-based guidelines recommended by international societies is challenging, mostly due to high costs and unavailability of medication. However, cost-effective approaches can still be implemented to manage IBD in sub-Saharan Africa as the predominant disease phenotype is mild-to-moderate ulcerative colitis, which often responds to treatment with basic medication. In this Series paper, we summarise the current management of IBD in sub-Saharan Africa and propose how it can be tailored to suit the epidemiological and socioeconomic specificities of the region. We also discuss measures required to address existing challenges, such as educating health-care workers about the diagnosis and management of IBD or improving endoscopic capacity., Competing Interests: Declaration of interests GW reports travel support from AbbVie and Janssen and speakers honoraria from Janssen, AbbVie, and Adcock Ingram. DE reports travel support from Janssen, speakers fees from Cipla, Janssen, and Takeda, and declares directorship of Inflammatory Bowel Disease Africa. EF reports honoraria from Janssen. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-287/coif). CF has received honoraria for participation in Advisory Boards and Speaker’s Bureaus for MSD and Pfizer. CF reports that the development of this document and its recommendations was funded by an unrestricted educational grant from Pifzer to the Federation of Infectious Diseases Societies of Southern Africa. SD has received payment for Speaker’s Bureaus for the following organizations in the last 36 months, Pfizer, MSD, ABBVIE, and SANOFI. All these speaker activities were for educational meetings or conferences. In addition, SD has participated in Advisory Board for the following organizations, MSD, ViiV, Health/GSK, Adcock Ingram and Jansen. GAR has received honoraria for Speaker’s Bureaus from Pfizer and MSD-None recently however. MM has acted on the speaker’s bureaus of MSD, Pfizer, J&J, Aspen, Mylan and Cipla, and on the Advisory Boards of Pfizer, MSD, J&J and Mylan, has also received fully paid travel expenses to international conferences and advisory boards, and had leadership or fiduciary roles in SAHIVSOC and AVCS. MYSM has received consulting fees from Johnson & Johnson, Cipla, MSD, ViiV, 360 pharmaceuticals and Mylan, and participated on data safety monitoring boards or advisory boards for EnACT, NTZ versus SOF/DCV Study, and The CARES Study, and acts on the Southern African HIV Clinicians Society. JP has received speaker’s fees from Sanofi, Novartis and Janssen, and participated on the advisory board for Sanofi. CvV has acted on the Speaker’s Bureaus of Mylan and Viatris. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

While inflammatory bowel disease (IBD) has been well characterised in the West and other parts of the world, there are little data from sub-Saharan Africa (SSA). To throw light on the current status of IBD in SSA, we performed a systematic review of the literature, extracting relevant publications. We found only 210 documented IBD cases in SSA (excluding South Africa (SA)), which were reported in 34 publications until August 2019. The majority were cases of ulcerative colitis. Only three reports, all from SA, attempted to determine IBD incidence rates. The rest were mostly case reports or small case series; the largest from Nigeria comprised 32 patients. The paucity of documented cases possibly reflects under-diagnosis and under-reporting. Major deficiencies in diagnostic and clinical capacity were noted, which need to be addressed going forward.

The treatment of inflammatory bowel disease (IBD) is often challenging. It has a vexing and waning course with frequent relapses, despite adequate maintenance therapy. Biological  agents have been available for the treatment of IBD for the last two decades, with impressive results. However, these drugs are costly and often have significant side-effects. Therefore, the benefit of aggressive treatment must be carefully balanced against the risk of serious adverse events. Despite good clinical outcomes, patients often request to discontinue the drugs because of cost and detrimental effects, especially the risk of malignancy. This review focuses on the benefits of biological treatment, strategies to de-escalate therapy, risk of relapse when these agents are discontinued and success with retreatment with the same or a similar biological agent.

Background: Overlapping clinical, endoscopic, radiographic and histological features, coupled with poor microbiological yield, make differentiating Crohn's disease (CD) from intestinal tuberculosis (ITB) challenging. Granulomas are present in both diseases; in CD they predict the need for immunosuppressive therapy that requires ITB to be excluded before initiation., Objectives: To compare granuloma-positive CD and ITB, to identify factors that may aid in diagnosis., Methods: This was a retrospective cohort study evaluating granuloma-positive CD and ITB identified from a pathology database., Results: Sixty-eight ITB and 48 CD cases were identified. Patients with ITB were more likely to be male, and to have HIV infection, isolated colitis, night sweats and tachycardia. ITB was also associated with lower serum albumin and haemoglobin and higher C-reactive protein levels, a chest radiograph showing active tuberculosis, and lymph nodes &gt;1 cm on imaging. Extraintestinal manifestations (EIMs) were predictive of CD. There were no significant differences in smoking status, symptom duration or perianal disease. On multivariate analysis, HIV positivity (odds ratio (OR) 29.72, 95% confidence interval (CI) 2.15 - 410.96; p=0.01), isolated colitis (OR 6.17, 95% CI 1.17 - 32.52; p=0.03) and the absence of EIMs (OR 0.10, 95% CI 0.01 - 0.65; p=0.02) remained significant risk factors for ITB., Conclusion: This is the first study to identify clinical and biochemical factors to aid in differentiating granuloma-positive ITB from CD. EIMs support a diagnosis of CD, while isolated colitis and HIV are predictors of ITB.

[This corrects the article DOI: 10.1371/journal.pone.0139597.].

[This corrects the article DOI: 10.1371/journal.pone.0171742.].

Accurate diagnosis of Clostridium difficile infection is essential for disease management. A clinical and molecular analysis of C. difficile isolated from symptomatic patients at Groote Schuur Hospital, South Africa, was conducted to establish the most suitable clinical test for the diagnosis and characterization of locally prevalent strains. C. difficile was detected in stool samples using enzyme-based immunoassays (EIA) and nucleic acid amplification methods, and their performance was compared with that of C. difficile isolation using direct selective culture combined with specific PCR to detect the C. difficile tpi gene, toxin A and B genes and binary toxin genes. Toxigenic isolates were characterized further by ribotyping. Selective culture isolated 32 C. difficile strains from 145 patients (22 %). Of these, the most prevalent (50 %) were of ribotype 017 (toxin A -  B + ) while 15.6 % were ribotype 001 (toxin A + B + ). No ribotype 027 strains or binary toxin genes ( cdtA and cdtB ) were detected. The test sensitivities and specificities, respectively, of four commercial clinical diagnostic methods were as follows: Immuno Card Toxins A & B (40 % and 99.1 %), VIDAS C. difficile Toxin A & B (50 % and 99.1 %), GenoType CDiff (86.7 % and 88.3 %) and Xpert C. difficile (90 % and 97.3 %). Ribotype 001 and 017 strains had a 100 % detection rate by Xpert C. difficile , 100 % and 93.3 % by GenoType CDiff, 75 % and 53.3 % by Immuno Card and 75 % and 60 % by VIDAS, respectively. The overall poor performance of EIA suggests that a change to PCR-based testing would assist diagnosis and ensure reliable detection of locally prevalent C. difficile 017 strains.

Objective: Vitamin D has immunoregulatory properties and appears to influence disease outcomes in patients with Crohn's disease (CD). The primary aim of this study was to evaluate the association between vitamin D status and CD activity in South Africa., Methods: In a cross-sectional study performed between September 2011 and January 2013, serum 25-hydroxyvitamin D (25(OH)D) was measured in 186 consecutive patients with CD seen at 2 inflammatory bowel disease (IBD) centers and 199 healthy controls in the Western Cape, South Africa. Lifestyle and clinical variables were identified using an investigator-administered questionnaire, as well as clinical examination and patient case notes. Vitamin D status was evaluated in 2 ways: ≤ 20 ng/mL vs ≥ 21 ng/mL and ≤ 29 ng/mL vs ≥ 30 ng/mL. Disease activity was measured by the Harvey Bradshaw Index (HBI). Various 25(OH)D threshold concentrations for predicting a higher HBI score were also investigated., Results: On multiple log-binomial regression analysis, higher HBI scores and not having taken vitamin D supplementation in the 6 months prior to enrollment were identified as risk factors for vitamin D deficiency in patients with CD, defined either as ≤ 20 ng/mL or as ≤ 29 ng/mL (p < 0.03). Compared to patients with HBI < 5, those with HBI ≥ 8 were 2.5 times more likely to have 25(OH)D concentrations ≤ 21 ng/mL (prevalence risk [PR] = 2.5; 95% confidence interval [CI], 1.21-6.30). The risk was similar, though not as high, when defined as ≤ 29 ng/mL (PR = 2.0; 95% CI, 1.13-3.51). When vitamin D deficiency was defined as <20, <30, <40, and <50 ng/mL, the sensitivity and specificity obtained were 44.9% and 78.8%; 75.5% and 62.4%; 86.7% and 44.7%; and 92.9% and 23.5%, respectively (area under the curve = 0.71; p < 0.0001)., Conclusion: Low serum 25(OH)D was associated with increased CD activity in a South African cohort.

Background: Smoking may worsen the disease outcomes in patients with Crohn's disease (CD), however the effect of exposure to second-hand cigarette smoke during childhood is unclear. In South Africa, no such literature exists. The aim of this study was to investigate whether disease phenotype, at time of diagnosis of CD, was associated with exposure to second-hand cigarette during childhood and active cigarette smoking habits., Methods: A cross sectional examination of all consecutive CD patients seen during the period September 2011-January 2013 at 2 large inflammatory bowel disease centers in the Western Cape, South Africa was performed. Data were collected via review of patient case notes, interviewer-administered questionnaire and clinical examination by the attending gastroenterologist. Disease phenotype (behavior and location) was evaluated at time of diagnosis, according to the Montreal Classification scheme. In addition, disease behavior was stratified as 'complicated' or 'uncomplicated', using predefined definitions. Passive cigarette smoke exposure was evaluated during 3 age intervals: 0-5, 6-10, and 11-18 years., Results: One hundred and ninety four CD patients were identified. Cigarette smoking during the 6 months prior to, or at time of diagnosis was significantly associated with ileo-colonic (L3) disease (RRR = 3.63; 95% CI, 1.32-9.98, p = 0.012) and ileal (L1) disease (RRR = 3.54; 95% CI, 1.06-11.83, p = 0.040) compared with colonic disease. In smokers, childhood passive cigarette smoke exposure during the 0-5 years age interval was significantly associated with ileo-colonic CD location (RRR = 21.3; 95% CI, 1.16-391.55, p = 0.040). No significant association between smoking habits and disease behavior at diagnosis, whether defined by the Montreal scheme, or stratified as 'complicated' vs 'uncomplicated', was observed., Conclusion: Smoking habits were associated with ileo-colonic (L3) and ileal (L1) disease at time of diagnosis in a South African cohort.

Background: Over time, most patients with Crohn's disease (CD) develop strictures or fistulas, resulting in hospitalisations and surgery. Timely therapy with immunomodulators and biologicals may alter this natural history, but carries a significant risk of side-effects., Objective: To identify factors to predict poor-outcome severe CD at diagnosis, and thus patients who would benefit most from early, aggressive medical therapies., Methods: CD patients (n=101) with uncomplicated non-stricturing, non-penetrating disease at diagnosis, and with follow-up >5 years, were retrospectively analysed using a predefined definition of severe CD (SCD) over the disease course. Clinical, demographic, laboratory and histological factors at diagnosis associated with SCD and poor outcome were evaluated by univariate and multivariate analysis., Results: Overall 33.7% of the cohort developed SCD, and on multivariate Cox proportional hazard analysis the presence of granulomas on endoscopic biopsy at diagnosis was independently associated with development of SCD (hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.15 - 4.64; p=0.02). Simple perianal disease was also associated with this outcome (HR 2.49; 95% CI 1.14 - 5.41; p=0.02). The presence of these variables had a specificity of 99% and a positive predictive value of 88%., Conclusion: At diagnosis, factors predictive of SCD in our referral centre were endoscopic biopsy granulomas and perianal disease. Patients with these risk factors should be considered for early, aggressive medical therapy, as benefit will probably outweigh risk. To our knowledge, this is the first study to show that endoscopic biopsy granulomas in patients with uncomplicated (non-stricturing, non-penetrating) CD predict the subsequent development of SCD.

Background: 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., Methods: 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., Results: 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)., Conclusion: This study demonstrates that both limited microbial exposures and exposure to second-hand cigarette smoke during childhood is associated with future development of CD.

Pancreatitis occurs in approximately 4% of patients treated with the thiopurines azathioprine or mercaptopurine. Its development is unpredictable and almost always leads to drug withdrawal. We identified patients with inflammatory bowel disease (IBD) who had developed pancreatitis within 3 months of starting these drugs from 168 sites around the world. After detailed case adjudication, we performed a genome-wide association study on 172 cases and 2,035 controls with IBD. We identified strong evidence of association within the class II HLA region, with the most significant association identified at rs2647087 (odds ratio 2.59, 95% confidence interval 2.07-3.26, P = 2 × 10(-16)). We replicated these findings in an independent set of 78 cases and 472 controls with IBD matched for drug exposure. Fine mapping of the HLA region identified association with the HLA-DQA1*02:01-HLA-DRB1*07:01 haplotype. Patients heterozygous at rs2647087 have a 9% risk of developing pancreatitis after administration of a thiopurine, whereas homozygotes have a 17% risk.

Background: 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., Methods: A cross sectional 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 demographic and clinical variables at diagnosis and date of study enrolment were identified using an investigator administered questionnaire as well as clinical examination and patient case notes. Using predefined definitions, disease behavior was stratified as 'complicated' or 'uncomplicated'., Results: One hundred and ninety four CD subjects were identified; 35 (18%) were white, 152 (78%) were Cape Coloured and 7(4%) were black. On multiple logistic regression analysis Cape Coloureds were significantly more likely to develop 'complicated' CD (60% vs. 9%, p = 0.023) during the disease course when compared to white subjects. In addition, significantly more white subjects had successfully discontinued cigarette smoking at study enrolment (31% vs. 7% reduction, p = 0.02). No additional inter-racial differences were found. A low proportion of IBD family history was observed among the non-white subjects., Conclusions: Cape Coloured patients were significantly more likely to develop 'complicated' CD over time when compared to whites.

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.

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.

Background: 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., Objectives: We examined the effect of physiological concentrations of bile acids on the in vitro growth of Mycobacterium tuberculosis (MTB)., Methods: 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., Results: 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., Conclusions: 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.

Background and Aim: The thiopurines azathioprine and 6-mercaptopurine are effective in the management of patients with inflammatory bowel disease (IBD) in whom aminosalicylates, antibiotics and corticosteroids have failed to induce or maintain remission. Long-term use of these agents has been linked to a greatly increased risk of non-melanoma skin cancer and lymphatic cancer in organ transplant recipients. There is some evidence to suggest that IBD patients receiving thiopurines might be at increased risk of cancer. Our aim was to determine the incidence of cancer in a cohort of patients with IBD managed in our clinic, and to relate this to thiopurine exposure., Methods: We conducted a retrospective study based on the clinical and pathology records of patients attending a specialist IBD clinic at Groote Schuur Hospital, Cape Town, South Africa between 1960 and 2007., Results: We analyzed the records of 1084 patients. A total of 123 subjects (11.5%) had received thiopurine therapy. Cancer was identified in 51 patients (4.7%), including colorectal cancer (15 patients), melanoma (two patients), non-melanoma skin cancer (seven patients) and non-Hodgkin's lymphoma (five patients). A diagnosis of non-melanoma skin cancer was significantly associated with thiopurine exposure (odds ratio 5.0, 95% confidence interval 1.1-22.8). Six of seven non-melanoma skin cancers occurred in Caucasian patients, with a highly significant association with thiopurine use (odds ratio 12.4, 95% confidence interval 2.3-67.4)., Conclusions: Patients with IBD who receive thiopurines are at increased risk of non-melanoma skin cancer. The risk is highest in Caucasian patients, and is negligible in other groups., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world.

Background: 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., Method: 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., Results: 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., Conclusion: 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.

Background: 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., Objective: 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., Design: 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., Results: 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., Conclusions: 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.

Background: 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., Aim: To review current strategies in differentiating these two conditions, and in managing Crohn's disease, in populations with high rates of tuberculosis., Methods: Literature review and clinical experience., Results: 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., Conclusions: 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.

Background: 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., Aim: To evaluate selected clinical and histological parameters in colonic biopsy specimens for their ability to discriminate between Crohn's disease and intestinal tuberculosis., Methods: 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., Results: 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%)., Conclusion: Clinical features and selected histological parameters in colonoscopic biopsy specimens can help in differentiating between Crohn's disease and intestinal tuberculosis.

The ability of fecal bacteria to 7alpha-dehydroxylate primary bile acids was measured in vitro by incubating stool homogenates with labeled primary bile acids, and was compared to serum cholesterol levels in 4 South African groups: Rural Bantu (50 subjects), Urban White (20), Urban Bantu (17) and Urban Coloured (16). Mean serum cholesterol levels were 137 +/- 23, 213 +/- 51, 199 +/- 62 and 206 +/- 46 mg/100 ml, respectively. (Rural Bantu significantly different.) The in vitro conversion of cholic acid by stool homogenates of Rural Bantu was significantly slower than that of the Urban Whites or the Urban Bantu was significantly slower than that of the Urban Whites or the Urban Bantu in two-hour incubations. There was no difference of conversion rates in 24-hour incubations of cholic or chenodeoxycholic acids. Gas-liquid chromatographic analysis of stool homogenates showed little difference in the distribution pattern of fecal bile acids or neutral sterols. These data suggest that the activity of the intestinal bacterial flora to convert primary bile acids was significantly reduced in the Rural Bantu as compared to the other groups, corresponding with lower serum cholesterol levels. However, by the time the stools were excreted the degree of conversion was comparable in each group.