Guidance for the gastrointestinal evaluation and management of iron deficiency in Sub-Saharan Africa.

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.

Prevalence of Helicobacter pylori in children less than three years of age in health facilities in Nairobi Province.

OBJECTIVES: To determine the prevalence of Helicobacter pylori in children less than three years of age and to determine socio-demographic correlates of Helicobacter pylori infection in these children. DESIGN: Cross sectional study. SETTING: The "well baby clinics", in Nairobi Province. SUBJECTS: Children less than three years of age. RESULTS: A total of 195 children were analysed in the study. There were 103 (52.8%) males and 92(47.2%) females giving a male to female ratio of 1.1:1. The mean age was 17.7 months and the median age was 16 months (range 2 weeks to 36 months). H. pylori antigen was found in stool of 89(45.6%) of the children. Low socio-economic status, crowding in the homes and poor sanitation were associated with H. pylori infection. CONCLUSION: There is a high prevalence rate of H. pylori infection in children less than three years as found in this study which is in agreement with studies done in other developing countries. Family income is associated with H. pylori infection and families with low income are at higher predisposition to H. pylori infection when compared to families with high income.

Drug susceptibility pattern of Helicobacter pylori in patients with dyspepsia at the Kenyatta National Hospital, Nairobi.

OBJECTIVE: To determine drug susceptibility pattern of Helicobacter pylori to metronidazole, clarithromycin, amoxicillin and tetracycline in patients presenting with dyspepsia at the Kenyatta National Hospital. DESIGN: Cross-sectional descriptive study. SETTING: Kenyatta National Hospital, Nairobi. SUBJECTS: Two hundred and sixty-seven patients aged 15 to 85 years, presenting with dyspepsia and referred for upper gastro-intestinal endoscopy were recruited into the study. RESULTS: Between October 2003 and April 2004, 138 male and 129 female patients aged 15-85 years, with a mean age of 45.4 years were studied. Gastritis was the most common endoscopic finding, occurring in 55%, followed by normal-looking mucosa in 27% and peptic ulcer disease in 16% of the patients. The rapid urease test was positive in 184 patients (69%). The culture yield was 62% of these CLO (Campylobacter like organisms) positive biopsies. The MIC90 (minimum inhibitory concentration) was 256 mg/l for metronidazole, 1.5 mg/l for clarithromycin, 1.5 mg/l for tetracycline and 0.75 mg/l for amoxicillin. The MIC values for amoxicillin were significantly higher in the female patients (p = 0.02) but showed no significant variation for age. The MIC values for metronidazole, tetracycline and clarithromycin showed no significant difference for age or gender. MIC values for tetracycline were significantly higher for patients with duodenitis and duodenal ulcer p = 0.009 and 0.02, respectively. CONCLUSION: All isolated H. pylori organisms were resistant to metronidazole. The susceptibility of the H. pylori isolates was 93.6% for clarithromycin, 95.4% for amoxicillin and 98.1% for tetracycline. The MIC90 for amoxicillin and clarithromycin were found to be close to the upper limit of the susceptibility range. There was a rising MIC90 for tetracycline and metronidazole compared to that found in a previous study in 1991.

Prevalence of hepatitis A, B, C and human immunodeficiency virus seropositivity among patients with acute icteric hepatitis at the Kenyatta National Hospital, Nairobi.

OBJECTIVE: To determine the prevalence of hepatitis A, B, C and HIV seropositivity among patients with acute icteric hepatitis. DESIGN: Cross-sectional descriptive survey. SETTING: Kenyatta National Hospital, Nairobi. SUBJECTS: Eighty four patients aged above six months with a history of jaundice not exceeding six months were recruited. There were 47 males and 17 females with an age range of eight months to 67 years and a median age of 25 years. METHODS: History was obtained physical examination done and blood taken for determination of bilirubin, ALT, AST and ALP levels. Sera that had disproportionately greater transaminase than ALP elevation were assayed for IgM anti-HAV, IgM anti-HBc, HbsAg, anti-HCV and anti-HIV antibodies. RESULTS: Evidence of hepatitis A, B, and C was round in 41.7%, 26.2%, and 7.1% of the patients respectively, 13.1% of the patients were HBsAg carriers while 30.1% of all patients were HIV positive. Thirty two patients did not have evidence of hepatitis A, B, or C infection and this group was significantly associated with HIV infection (p = 0.003). CONCLUSION: Hepatitis A was the commonest overall type of acute icteric hepatitis seen at the KNH, and among patients aged 15 years and below. Hepatitis B was the leading identified cause of acute hepatitis among those aged over 15 years. Hepatitis C accounted for 7.1% of acute icteric hepatitis 30.1% of all patients and 50% of those admitted with acute hepatitis were also HIV positive.

Clinical and laboratory predictors of cholelithiasis in patients with sickle cell anaemia.

Cholelithiasis is a common clinical condition in patients with sickle cell disease and there are conflicting reports on laboratory indices useful in predicting those patients who are likely to have gallstones. There is however lack of similar studies from Kenya. We therefore studied the role of clinical (Body Mass Index), haematological (reticulocyte count, haemoglobin level), and biochemical (serum bilirubin: direct and indirect, serum alkaline phosphatase, serum transaminase) indices in predicting sickle cell anaemia patients likely to develop gallstones. A cross sectional descriptive study was conducted from October 1993 to December 1994 on consecutive male and female patients of all ages with homozygous sickle cell disease (HbSS) confirmed by cellulose acetate paper electrophoresis. A total of 64 patients aged between three and 37 years were recruited into the study. They were classified into two groups: stone formers and non-formers. The difference in the two groups with respect to clinical, haematological and biochemical indices were determined by Chi-square contingency test. Body mass index (BMI), reticulocyte count and alkaline phosphatase were found to have a significant positive association with increased likelihood of gallstone formation at p values of 0.004, 0.007 and 0.007, respectively. The rest of the study indices had no association. The cut-off points were reticulocyte counts above ten per cent and alkaline phosphatase levels above 13 K.A. units. Though sickle cell anaemia patients with BMI > 20 had significant increased likelihood of cholelithiasis, we could not determine its cut-off value.

Upper gastrointestinal mucosal lesions in dyspeptic patients with homozygous sickle cell disease in Kenya.

A case controlled study comprising 51 patients with homozygous sickle cell (HbSS) disease who complained of dyspepsia and 41 age and sex matched non-HbSS control dyspeptic patients was carried out, to look at upper gastrointestinal mucosal lesions associated with dyspepsia. Upper gastrointestinal tract (UGIT) endoscopy was performed with gastric control biopsy taken for histology. Thirty two (62.3%) of the HbSS or sickle cell anaemia (SCA) patients had upper gastrointestinal pathology at endoscopy as compared to 17 (41.5%) of controls. The difference was significant at p = 0.042. Bile reflux (47%) was the predominant abnormal morphological finding in SCA patients while duodenal ulcer was the most common morphological finding in dyspeptic controls. The prevalence of duodenal ulcer in controls (22%) though higher than in SCA patients (9.8%), was not statistically significant p = 0.18. Gastric ulcer was not found in SCA patients. Duodenal ulcer was commoner in males than females in both cases and controls with a ratio of 4:1 and 3.5:1 respectively. Only four (7.8%) SCA patients and one (2.4%) of controls had normal mucosa at histology, the rest had evidence of histological gastritis. We could not draw any correlation between non-steroidal anti-inflammatory drugs (NSAIDS) use and UGIT findings. Since the proportion of SCA cases with UGIT abnormalities was significantly high, we recommend that dyspeptic SCA patients undergo UGIT investigations including endoscopy to maximise their clinical care.

Endoscopic findings and prevalence of Helicobacter pylori in Kenyan patients with dyspepsia.

One hundred and twenty consecutive patients above 12 years of age with dyspepsia were studied from June 1993 to September 1994. They underwent upper gastrointestinal endoscopy to find the mucosal lesions which were associated with their dyspeptic symptoms. At endoscopy gastric mucosal biopsies were taken in order to identify Helicobacter pylori (H. pylori) using three different techniques: culture, histology and the rapid urease test. Normal looking mucosa was the commonest single endoscopic finding, accounting for 34.2%, followed by gastritis 31.7% and duodenal ulcer 29.2%. However, when duodenal ulcers and gastric ulcers were put together, then peptic ulcer was the most prevalent finding accounting for 38.4%. Peptic ulcer was the most prevalent pathological finding in both young (less than 50 years) and older patients (50 years and above). Duodenal ulcer was more prevalent than gastric ulcer in the younger age group with a ratio of 5.8:1, however, the ratio in the older age group was 1:1. Gastric cancer was only found in patients aged 50 years and above, accounting for 17.4% of dyspeptic symptoms in this age group. Females were found to have more normal endoscopic findings than males (59.6%, versus 17.8% respectively). The difference being statistically significant (p < 0.001). All our cases of peptic ulcer disease had evidence of H. pylori infection while dyspeptic patients with normal endoscopic mucosal findings had H. pylori in 80.5% of cases. The difference in prevalence of H. pylori in the two groups was statistically significant (p < 0.001). Surprisingly, evidence of H. pylori in gastric cancer cases was very low in this study, being found in only 25% of patients.

Prevalence of intestinal parasites in Kenyans with dyspepsia.

Dyspepsia and intestinal worm infestation are both common clinical conditions in a developing country like Kenya and thus this study was designed to look at the correlation between the two in a referral gastroenterology clinic at Kenyatta National Hospital. One hundred and twenty five patients with dyspepsia had their stool, duodenal aspirate and duodenal biopsy analysed for evidence of intestinal parasites. Seven (5.6%) were found to have various types of intestinal parasites with giardia lamblia comprising 42.8% of worms isolated. 71.4% of patients with dyspepsia and worm infestation had their symptoms improved after deworming, but the low prevalence of intestinal parasite in dyspeptic patients makes routine deworming not cost effective. Stool examination had the best yield for intestinal parasites.

Colonoscopic findings in Kenyan African patients.

OBJECTIVE: To determine the types and prevalence of colonic diseases in Kenyan African patients referred for colonoscopy with lower gastrointestinal tract symptoms. DESIGN: A cross sectional survey conducted over a two year period. SETTING: Major private hospitals in Nairobi. PATIENTS: Two hundred forty seven consecutive patients of both sexes and all ages referred for colonoscopy between January 1996 and December 1997. Only Kenyans of African origin were included. Patients were referred from all over the country though the majority of cases were from Nairobi and its surrounding districts. RESULTS: The major indications for colonoscopy were lower abdominal pain (35.6%), non-bloody diarrhoea (22.3%), constipation (21.4%) and rectal bleeding (19.8%). Nearly 53% of patients colonoscoped had abnormal mucosal findings, with the main abnormalities being: proctocolitis (20.2%), colorectal cancers (12.1%), haemorrhoids (7.3%), colorectal polyps (6.5%) and diverticulosis (5.3%). The main histological diagnosis among patients whose colonic biopsy were done included normal colonic mucosa (29%), non-specific colitis (28.5%), adenocarcinoma (18.2%), benign colonic polyp (9.7%) and ulcerative colitis (7.3%). There was one case of Crohn's colitis and five cases (3%) of infective colitis. CONCLUSION: The study shows that the African colon has a number of pathological lesions contrary to previous reported literature.

Role of 5-hydroxytryptamine type 3 receptors in rat intestinal fluid and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.

Cholera toxin and Escherichia coli heat labile toxin (LT) induced intestinal secretion has in the past been attributed exclusively to an increase in intracellular cAMP whereas E coli heat stable toxin (ST) induced secretion is mediated through cGMP. Evidence is accumulating on the importance of 5-hydroxytryptamine (5-HT) in cholera toxin induced secretion, but its role in LT and ST is not well established. This study therefore investigated in vivo the effect of 5-HT3 receptor antagonist, granisetron, on intestinal fluid and electrolyte secretion induced by cholera toxin, LT, and ST. Granisetron (30, 75, 150, or 300 micrograms/kg) was given subcutaneously to adult male Wistar rats 90 minutes before instillation of 75 micrograms cholera toxin or 50 micrograms LT in isolated whole small intestine. In situ small intestinal perfusion was performed with an iso-osmotic plasma electrolyte solution (PES) to assess fluid movement. In a second group of animals, granisetron (300 micrograms/kg) was given subcutaneously and two hours later small intestinal perfusion with PES containing 200 micrograms/l ST was performed. Cholera toxin induced net fluid secretion (median -50.1 microliters/min/g (interquartile range -59.5 to -29.8)) was found to be dose dependently decreased or abolished by granisetron (plateau effect at 75 micrograms/kg: 18 (-7.8 to 28), p < 0.01). Granisetron in high dose (300 micrograms/kg), however, failed to prevent LT or ST induced secretion (-52 (-121 to -71) v -31 (-44 to -18), and (-39 (-49 to 17) v (-22 (-39 to -3)), respectively). Sodium and chloride movement paralleled that of fluid. In conclusion, these data show that 5-HT and 5-HT3 receptors play an important part in cholera toxin induced secretion but are not involved in E coli heat stable or heat labile toxin induced secretion.

Role of 5-hydroxytryptamine in intestinal water and electrolyte movement during gut anaphylaxis.

Exposure of sensitised intestine to specific allergen is known to produce appreciable reduction in water and electrolyte absorption. The mediators participating in this process have not been fully characterised. The effects of the 5-hydroxytryptamine2 (5-HT2) and 5-HT3 receptor antagonists, ketanserin and granisetron, respectively, on water movement during intestinal anaphylaxis were studied. Hooded Lister rats (120-150 g) were sensitised to ovalbumen and 14 days later, intestinal water and electrolyte movement was assessed at 10 minute intervals by in situ jejunal perfusion with a plasma electrolyte solution (PES) or PES containing 20 mg/l ovalbumen. Within 20 minutes of exposure to PES+ovalbumen, net water secretion that could be completely prevented by the mast cell stabilising agent doxantrazole occurred compared with absorption with PES alone (median -20 microliters/min/g (interquartile range -43 to -5), n = 11), v (107 (86 to 113), n = 10; p < 0.01). Pre-treatment with subcutaneous ketanserin 200 micrograms/kg (n = 7) or granisetron 300 micrograms/kg (n = 8) partially inhibited the secretory response to PES+ovalbumen (18 (11 to 48) and 13 (6 to 32) respectively; both p < 0.01 compared with PES+ovalbumen control). After 40 minutes perfusion with PES+ovalbumen, the changes in water movement were less pronounced 24 (-3 to 43) and neither ketanserin or granisetron had any effect (ketanserin: 48 (28 to 87), granisetron: 41 (32 to 83); NS). In all experiments, sodium and chloride movement paralleled that of water. Thus, the profound water secretion that occurs in the early stages of intestinal anaphylaxis is partly 5-HT dependent because it can be reversed by 5-HT2 and 5-HT3 receptor antagonists. Other mediators must also be involved, especially in the late phase of anaphylaxis.

Structural and functional analysis of HLA-DR beta-promoter polymorphism and isomorphism.

Evolutionary relatedness among the highly polymorphic DR beta genes has been established based on shared nucleotide sequences and structural organization of DR beta loci. The evolution of promoter regions of the B1*0701, B1*0101, B1*1501, B5*0101 genes was analyzed by cloning and sequencing. This shows that the polymorphism and isomorphism of HLA DR beta genes extend into the 5' flanking promoter region of the genes and that evolutionary relatedness also exists among the DR beta gene promoters. This suggests that DR beta gene promoters and coding regions coevolved. The effect of the naturally occurring nucleotide substitutions in the polymorphic and isomorphic DR beta promoters on transcriptional activity has been determined in a transient expression system. The transcriptional activity of two polymorphic DR beta promoters, B1*1501 and B1*0701, and two isomorphic DR2 promoters, B1*1501 and B5*0101, is the same for these promoters. Together these data suggest that naturally occurring substitutions do not significantly affect the transcriptional activity of these promoters.

Factors that influence the short term outcome of upper gastrointestinal bleeding at Kenyatta National Hospital.

Between April 1990 to January 1991, a prospective study of 97 consecutive patients admitted to the medical wards of Kenyatta National Hospital with upper gastrointestinal haemorrhage was done. All the patients studied under went upper gastrointestinal endoscopy within 24 hours of presentation and a positive endoscopic diagnosis was possible in 90 (93%) of the patients studied. The leading causes of bleeding were oesophageal varices in 34 (35%) patients, duodenal ulceration in 17 (17.5%) patients, and superficial inflammatory lesions in 17 (17.5%) patients. 17 (17.5%) patients had multiple lesions with superficial inflammation and oesophageal varices as the commonest combination. In 86 (88%) patients, bleeding settled on simple conservative measures which included intravenous fluids, blood transfusion and antacids. Further haemorrhage was observed in 11 (11.3%) patients. Tachycardia (> 100/minute), hypotension (systolic BP < 100mm Hg) and low haemoglobin (< 8 g/dl) at admission were all correlated with a poor outcome. Variceal bleeding had the worst prognosis and the overall mortality rate was 5%.

Famotidine in the management of gastro-oesophageal reflux.

Famotidine has been used for the treatment of peptic ulcers and Zollinger Ellison syndrome and is also useful in reflux and erosive oesophagitis. To evaluate the effects of Famotidine 20 mg given twice daily in the symptomatic relief of gastro-oesophageal reflux disease with normal oesophagus or mild endoscopic oesophagitis, patients were followed over a period of six weeks. 70% of the patients had complete day-time heartburn relief during the study and 75% had complete night-time heartburn relief during the study. Famotidine was found to be safe and there were no serious clinical or laboratory adverse experiences.

Ambient-temperature-stable molecular biology reagents.

We have processed biological materials to generate several reagents that are ambient temperature stable and ready to use. Stabilized biomolecules in a glassy matrix of carbohydrate polymers offer water-soluble reagents for complex molecular biology applications. This approach is particularly useful for reagent systems composed of enzymes, nucleotides and other components dispensed in single-use aliquots. Reconstitution of the glassy matrix delivers buffered enzymes and/or nucleotides for restriction, modification, sequencing and/or amplification of nucleic acids. These ambient-temperature-stable reagents allow a high level of reproducibility as they minimize the potential for pipetting errors. They also provide advantages in shipping, storage and subsequent handling. Added convenience includes elimination of setup time, cross contamination and refrigeration. Applications of ambient-temperature-stable biological reagents for routine molecular biology methods are presented.

Evaluation of culture media and antimicrobial susceptibility of Helicobacter pylori.

Isolation of Helicobacter pylori on artificial culture is hampered by the lack of reliable and cheap media. In this study, three different types of culture media were evaluated for isolation of H. pylori from clinical specimens. These media included: Modified Thayer-Martin (MTM), Skirrow's campylobacter agar and chocolate agar. Modified Thayer-Martin agar was superior in isolation to others with an isolation rate of 47% (31/66). The size of colonies on this media were larger and clearly defined. Growth was detectable after 4 days of incubation, with a maximum growth after 7 days. Thirty one strains of H. pylori isolated from cases were tested against ten antibiotics (ampicillin, tetracycline, gentamicin, erythromycin, chloramphenicol, nalidixic acid, colistin, kanamycin, sulpharazole and metronidazole) in Mueller-Hinton agar, to determine the minimum inhibitory concentration (MIC). H. pylori was very susceptible to most drugs but resistant to nalidixic acid.

Helicobacter pylori in peptic ulcer disease in Kenya.

Sixty six patients with dyspeptic symptoms underwent upper gastrointestinal endoscopy and biopsies for Helicobacter pylori culture. The number of H. pylori isolated increased with age reaching a peak at 51 to 60 years of age. Antral gastritis closely followed by duodenitis accounted for the highest number of H. pylori isolated, (87.5% and 85.7% respectively). In patients with duodenal ulceration only, 57% had H. pylori isolated from their antral biopsies, a result that was just slightly higher than that where no endoscopic diagnosis was made (50%).

Gastric carcinoma in the Kenyan African population.

Fifty three consecutive patients with histological evidence of gastric carcinoma were studied between June 1987 and June 1989 at Kenyatta National Hospital (KNH). The male to female ration was 3.4:1 and the peak age of occurrence was in the 7th decade with 62.3% of gastric carcinoma being at the gastric antrum. Poorly differentiated adenocarcinoma was found in 68.2% of patients while well differentiated adenocarcinoma in 4.5% of cases. Intestinal metaplasia was a rare finding. If Lauren's classification of gastric carcinoma is considered then diffuse type of gastric cancer is by far the commoner type in our environment.

Adult polycystic liver disease.

Characteristics of 14 patients above 12 years of age with congenital polycystic liver disease attending liver clinic at KNH were analysed. The diagnosis was mainly based on ultrasonographic findings. The disease was found predominantly among the Kikuyu ethnic group with a female/male ratio of 6:1 and the peak age at presentation was in the 5th decade. The liver function tests were essentially normal in all cases with no complication directly relating to liver disease. Hypertension was found in 78.6% of cases and chronic renal failure in 35.7% of cases. There was an associated polycystic disease in at least one other abdominal organ in all cases.

Cholelithiasis in the Kenyan African.

A prospective and retrospective review of 20 cases of cholelithiasis diagnosed at Kenyatta National Hospital (KNH) between June 1987 and June 1989 was done. Females were more often affected (6 times) than their male counterparts. 94% of the females were parous with a mean parity of 5.6. Most patients were in the 4th decade at the time of diagnosis. Qualitative analysis for gall-stones showed evidence of cholesterol in all stones analysed with calcium being detected in only one female patient.