Challenges in the management of inflammatory bowel disease in sub-Saharan Africa.

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.

South African Society of Clinical Microbiology Clostridioides difficile infection diagnosis, management and infection prevention and control guideline.

Clostridioides difficile infection (CDI) is a problem in both developed and developing countries and is a common hospital-acquired infection. This guideline provides evidence-based practical recommendations for South Africa and other developing countries. The scope of the guideline includes CDI diagnostic approaches; adult, paediatric and special populations treatment options; and surveillance and infection prevention and control recommendations.

Short chain fatty acids and monocarboxylate transporters in irritable bowel syndrome.

BACKGROUND/AIMS: Gut microbiota ferments indigestible food that rests in the colon to produce short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. Colonic SCFA stimulate the synthesis of serotonin which is central in irritable bowel syndrome (IBS) pathophysiology. Reduced SCFA have been linked to specific IBS symptoms like colonic hyperalgesia and hypersensitivity. SCFA enter the colonocyte mainly via 2 energy-dependent monocarboxylate transporters, MCT1 (SLC16A1) and SMCT1 (SLC5A8). We investigated specific gut microbiota, SCFA concentrations, and monocarboxylate transporter mRNA expression in patients with IBS. MATERIAL AND METHODS: A total of 30 IBS patients-15 constipation-predominant (C-IBS) and 15 diarrhoea-predominant (D-IBS)-and 15 healthy controls were recruited. Bacteroidetes and Bifidobacterium species were analyzed using quantitative polymerase chain reaction (qPCR) on stool samples. SCFA concentrations were determined by gas chromatography/mass spectroscopy of stool samples. Monocarboxylate transporter mRNA was quantified by qPCR on colon biopsy specimens. RESULTS: Bacteroides was significantly increased in the D-IBS group compared with the C-IBS group and healthy controls. Bifidobacterium was significantly reduced in both IBS groups. SCFA ratios were altered in both IBS groups with a reduction of all 3 measured SCFA in C-IBS and acetic acid in D-IBS. MCT1 and SMCT1 were significantly reduced in C-IBS and D-IBS. CONCLUSION: In agreement with findings of previous studies, the microbiota assessed were significantly altered inferring dysbiosis in IBS. SCFA and their ratios were significantly altered in both IBS groups. SCFA transporters, MCT1 and SMCT1 were significantly reduced in both IBS groups, suggesting reduced colonocyte SCFA transfer. SCFA availability and transfer into the colonocytes may be important in IBS pathogenesis and should be prospectively studied.

ß-Catenin Regulation in Sporadic Colorectal Carcinogenesis: Not as Simple as APC.

Background: The wnt/APC/ß-catenin pathway is a critical initiator in colorectal carcinogenesis in both hereditary and sporadic colorectal cancer (CRC). The progression of this process remains incompletely understood, although inflammation is pivotal. Drivers of inflammation are elevated in malignant tissue and have been shown to regulate ß-catenin expression. Interleukin-17A (IL-17A) is protumorigenic at elevated levels via COX-2 stimulation. Elevated peroxisome proliferator-activated receptor γ (PPARγ) expression has reduced risk of carcinogenesis and good overall prognosis in established CRC. Activation of PPARγ has inhibitory effect on ß-catenin. Methods: Using qPCR and IHC, we compared ß-catenin, PPARγ, COX-2, and IL-17A in the colonic mucosa of patients with sporadic CRC, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS), against a normal control population. Results: ß-catenin mRNA and protein expression progressively increased from the Normal group, through IBS and IBD reaching statistical significance in CRC. COX-2 mRNA levels increased similarly with statistical significance in IBD and CRC. However, COX-2 protein expression was inverted with significant expression in the Normal and IBS groups and reduced levels in IBD and CRC. PPARγ mRNA expression was unchanged in IBD and CRC but was significantly elevated in the IBS. IL-17A mRNA was significantly reduced in IBS and CRC but unchanged in IBD. There were no differences in all parameters tested in the Normal and IBS groups. Conclusion: ß-catenin is confirmed as a major driver of colorectal carcinogenesis but is controlled by many more players other than APC. Elevated levels of PPARγ may have an anticarcinogenic effect. The role of COX-2 expression, especially its posttranscriptional regulation in colorectal cancer, needs further elucidation.

Inflammatory bowel disease: pathogenetic mechanisms

Abstract Significant progress has been made in the understanding of ulcerative colitis and Crohn's Disease over the last decades.Despite this, the pathogenesis of inflammatory bowel disease (IBD) remains obscure, especially at molecular level. Various contributing factors have been identified so far, but their respective contributions are not entirely clear cut. In this review, we focus on the genetic and environmental factors linked with IBD pathogenesis. We also explore the role of pro-inflammatory cytokines on the molecular pathophysiology of IBD

Treatment of refractory left sided ulcerative colitis : lessons from the sages IBD registry

Background: Left sided ulcerative colitis is often a severe disease which requires aggressive medical therapy. Rarely, it can result in colectomy. Moreover, it can progress and extent to involve the entire colon. Method: Retrospective analysis of patient data on the SAGES IBD database. Patient data with severe left sided ulcerative colitis requiring anti-TNF therapy for the period between September 2016 to August 2017. Patient consent was obtained. Results: A total of 149 requests for biologic therapy were received during this period of which 13 had left sided ulcerative colitis. Seven (53.4%) were male and the mean age at diagnosis 33.3 years. Mean age at commencement of biologic therapy was 40.9 years. There were no smokers. One (7.7%) had ulcerative proctitis, 7 (53.8%) had proctosigmoiditis and 5 (38.4%) had left sided colitis. No patient was receiving topical steroids and 2 (15.4%) patients had exposure to topical 5-aminosalicylic acid. All patients had exposure to oral 5-aminosalicylic acid and 9 (69.2%) were receiving ongoing treatment. Ten (76.9%) received azathioprine or 6-mercaptopurine and 5 (38.5%) received methotrexate. Of the 12 patients on immunomodulator therapy, 10 (76.9) were concurrently on 5-aminosalicylic acid. Seven (53.8%) patients received infliximab and 9 (69.2%) patients received adalimumab. No one received golimumab or vedolizumab. All patients received standard dose anti-TNF therapy except 1 (7.7%) patient who received double dose infliximab. Biologic therapy was well tolerated with good clinical outcome and no side-effects. Conclusion: The incidence of severe left sided ulcerative colitis was low in this cohort. Severe left sided disease is associated with a high medication burden and cost. Response to biologic therapy was excellent

Treatment of refractory left sided Ulcerative colitis: lessons from the Sages IBD registry

ABSTRACT Background: Left sided ulcerative colitis is often a severe disease which requires aggressive medical therapy. Rarely, it canresult in colectomy. Moreover, it can progress and extent to involve the entire colon. Method: Retrospective analysis of patient data on the SAGES IBD database. Patient data with severe left sided ulcerative colitis requiring anti-TNF therapy for the period between September 2016 to August 2017. Patient consent was obtained. Results: A total of 149 requests for biologic therapy were received during this period of which 13 had left sided ulcerative colitis. Seven (53.4%) were male and the mean age at diagnosis 33.3 years. Mean age at commencement of biologic therapy was 40.9 years. There were no smokers. One (7.7%) had ulcerative proctitis, 7 (53.8%) had proctosigmoiditis and 5 (38.4%) had left sided colitis. No patient was receiving topical steroids and 2 (15.4%) patients had exposure to topical 5-aminosalicylic acid. All patients had exposure to oral 5 aminosalicylic acid and 9 (69.2%) were receiving ongoing treatment. Ten (76.9%) received azathioprine or 6-mercaptopurine and 5 (38.5%) received methotrexate. Of the 12 patients on immunomodulator therapy, 10 (76.9) were concurrently on 5-aminosalicylic acid. Seven (53.8%) patients received infliximab and 9 (69.2%) patients received adalimumab. No one received golimumab or vedolizumab. All patients received standard dose anti-TNF therapy except 1 (7.7%) patient who received double dose infliximab. Biologic therapy was well tolerated with good clinical outcome and no side-effects. Conclusion: The incidence of severe left sided ulcerative colitis was low in this cohort. Severe left sided disease is associated with a high medication burden and cost. Response to biologic therapy was excellent

Golimumab treatment in South African IBD patients: A 2 year review

Background: Ulcerative colitis (UC) is a chronic relapsing inflammation of the colon that sometimes fails standard medicaltherapy. Escalation of treatment often requires introduction of anti-TNF therapy. Golimumab is a new anti-TNF agent launched in South Africa in 2015 for moderate-severe UC. It is not licensed for Crohn's disease (CD).Method: Retrospective analysis of patients with moderate-severe UC requiring golimumab therapy (induction and maintenance therapy) for a 2-year period from September 2016 to August 2018 on the SAGES IBD registry. Patients gave signed informed consent.Results: A total of 109 patients required induction therapy with biologics during this 2 year period of which 12 (11%) required golimumab. A further 4 patients were already receiving golimumab making it 16 patients in total. Fourteen (87.5%) patients had UC and 2 (12.5%) had CD. Ten (62.5%) of the 16 patients were female with a median age of 46. There was 1 current smoker. A small number (18.8%) were taking corticosteroids at the time of induction with golimumab but they all discontinued steroid therapy during golimumab treatment. All 14 patients with UC was currently or previously exposed to aminosalicylates.Four (28.5%) of them discontinued this treatment due to intolerance or lack of efficacy. None of the patients with CD received aminosalicylates. Fourteen (87.5%) of the 16 patients received immunomodulator therapy. Four (28.5%) patients discontinued this treatment because of side-effects or lack of effect. Eleven (68.8%) patients received both aminosalicylates and immunomodulatory therapy concurrently during the study period. Ten (62.5%) of the 16 patients were naïve to biologics and were commenced on golimumab as first line therapy. Nine (90%) of the 10 patients remained on golimumab for the entire duration of the study. Six (37.5%) patients were switched to golimumab after having failed other forms of biologic therapy. Two (12.5%) patients stopped treatment with golimumab altogether during the study period because of treatment failure. Golimumab was well tolerated with good clinical outcome and no side-effects.Conclusion: The use of golimumab for moderate-severe IBD remained low since its launch. Golimumab therapy was safe and effective in moderate-severe UC and CD, although patient numbers were low. Treatment failure rate was low

Randomized clinical trial: effect of Lactobacillus plantarum 299 v on symptoms of irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) is a common diagnosis in gastroenterology. Its etiology is unknown and therapeutic options limited. Trials suggest probiotics may be beneficial. The aim of this study was to assess the symptomatic efficacy of Lactobacillus plantarum 299 v (L. plantarum 299 v) for the relief of abdominal pain in patients with IBS fulfilling Rome II criteria. METHODS: This study was conducted in a referral hospital. Trial participants were randomized to receive either two capsules of L. plantarum 299 v at a dosage of 5 × 10(9) cfu per capsule or placebo daily for 8 wk. Severity of abdominal pain was assessed using a visual analog scale at each visit and a quality-of-life IBS (QoL-IBS) questionnaire was also completed. RESULTS: There was no significant difference in abdominal pain relief between the study and placebo groups (P = 0.800). There was also no difference in QoL- IBS scores between the groups (P = 0.687). Both groups had a significant improvement in abdominal pain scores over the study period, from an average of 251.55 to 197.90 (P < 0.0001) indicating a large placebo effect. CONCLUSION: An 8-wk treatment with L. plantarum 299 v did not provide symptomatic relief, particularly of abdominal pain and bloating, in patients fulfilling the Rome II criteria.