IL-1B-511 Allele T and IL-1RN-L/L play a pathologcal role in helicobacter pylori (H. pylori) disease outcome in the African population

BACKGROUND: Many of the pathogenic effects of Helicobacter pylori infection are related to chronic active inflammation, which is controlled and maintained by the complex interplay of pro-inflammatory and anti-inflammatory mediators. Pro-inflammatory genetic polymorphisms tend to increase the risk of development of gastric cancer. In Africa, the data are scarce regarding the effects of these polymorphisms on gastric pathology. The objective of this study is therefore to investigate the pro-inflammatory genetic polymorphisms and their role in H. pylori-related gastric disorders in a select African population. METHODS: This cross-sectional prospective study recruited six hundred and ninety six adult subjects with a history of uninvestigated dyspepsia. The H. pylori status was determined by tissue Giemsa staining, Rapid Urease Test (RUT), H. pylori stool antigen test (HpSAT), and PCR using the 16s-rRNA gene. The polymorphisms in IL-1B (511 C/T), TNF-A (_308 G/A) and IL-1RN were assessed by the PCR-restricted fragment length polymorphism (RFLP). RESULTS: H. pylori was significantly associated with gastric pathologies investigated (P ═ 0.0000). Heterozygous allele TC of IL-1 β -511 was significantly associated with H. pylori infection (p = 0.003815). Similarly, allele IL-1 RN*2/2 and allele IL-1 RN-L/L were associated with H. pylori infection (p = 0.0025 and p = 0.0203). Allele T of IL-1 β -511 and IL-1 RN-L/L are more frequent in H. pylori associated gastric pathologies in this series. CONCLUSION: Allele T of IL-1 β -511 and long allele IL-1 RN-L/L play a role in H. pylori disease in this population.Keywords: Pro-inflammatory cytokines, Helicobacter pylori, Pathologies, AfricaEthiopian Journal of Health Sciences vol 22 (3) 201

A Situational Analysis of Antimicrobial Drug Resistance in Africa: Are we Losing the Battle?

Background: The first arrival of a sizable shipment of penicillin at the North African Theatre of Operations for USA military use in 1943 was a landmark that turned a new chapter of antibiotic use in Africa. Over the past decade the expansion of resources and the technological advances have meant that much larger quantities of drugs are available in developing countries than ever before. As a result, many more individuals are receiving necessary treatment or therapy than just ten years ago. This very welcome event is accompanied by the terrible irony that increases in drug availability and use can promote drug resistance and render the same life-saving drugs ineffective.Methods: The study focused on bacterial pathogens. One hundred and three relevant literatures were identified from the PubMed online database. The coverage included research articles concerning antimicrobial resistance involving subjects of an African country.Results: Resistant bacteria are on a war path and evidently have acquired an edge over us. Our actions are evidently fuelling the resistance. The indiscriminate use of antibiotics in humans and livestock, wrong and substandard prescriptions by unqualified ‘medical personnel’ together with poor diagnosis or lack of it are all adding fuel to the already fired train of resistant microbes.Conclusion: To win the war and turn tables as we did with the discovery of penicillin and other antimicrobials in the 1940s, then we must all act now. Antimicrobial stewardship programs-Education, training of laboratory personnel and investment in laboratory infrastructure development are desirable in these situationsKeywords: Antibiotics, Resistance, BacteriaEthiop J Health Sci. Vol. 22, No. 2 July 201

Co-occurrence of Helicobacter pylori with faecal bacteria in Nairobi river basin: public health implications

Introduction: Overwhelming evidence implicates Helicobacter pylori (H. pylori) as an etiologic agent of gastrointestinal diseases including gastric cancer. The mode of transmission of this pathogen remains poorly understood.Objective: This investigation is to establish the presence of H. pylori in the waters of the Nairobi river basin and the predictive value the presence of fecal indicator bacteria would have for H. pylori.Methodology: Physical, chemical and biological assessment of water quality of rivers in Nairobi were carried out using standard methods. H. pylori DNA in water was detected using highly specific primers of glmM gene (294pb).Results: There was high presence of faecal bacteria in the waters sampled. H. pylori DNA was detected in two domestic wells and one river. The wells were located in two different regions of the water basin but influenced by similar human activities.Conclusion: The high presence of faecal bacteria in the waters sampled did not parallel the H. pylori detection in the same waters. H. pylori was detected in the Nairobi river basin, but there was no relationship between the numerical levels of fecal bacteria and H. pylori.Keywords: H. pylori, environment, water, coliform

Safety and analgesic properties of ethanolic extracts of Toddalia asiatica (L) Lam. (rutaceae) used for central and peripheral pain management among the east african ethnic communities

BACKGROUND: Although herbs are often perceived as “natural” and therefore safe, many different side effects have been reported. Additionally, there is limited scientific evidence to establish the safety and efficacy of most herbal products. The aim of this study was to evaluate the biochemical and  haematological effects of Toddaliaasiatica (L) Lam. (Rutaceae) (T. asiatica (L.) in albino Wistar rats.MATERIALS AND METHODS: The phytochemicals present in the plant were determined. The analgesic activity was determined using the hot plate technique. The whole blood with anticoagulant was used for assay of the haematological parameters using the COULTERAc•T5diff AL Hematology Analyzer (Fullerton, CA, USA). The biochemical parameters determined with HumaLyzer 2000, a semi-automatic, microprocessor-controlled photometer fromchem-labs, Nairobi.RESULTS: The effect of extract on serum biochemical parameters after 14 days treatment with the crude ethanolic extract of T. asiatica (L.) revealed significant difference in the Cholesterol (P = 0.041), alanine transaminase (P = 0.007), gamma-glutamyl transferase (P = 0.045). There was no significance in the alkaline phosphatase (ALP), aspartate transaminase (AST) levels compared to the untreated controls. Peripheral blood films (PBFs) of the treated animals were performed and stained with leishman’s stain. Major morphological changes were observed including anisocytosis, burr cells, anisochromia, hypochromia and reactive lymphocytes among others.CONCLUSION: The crude extract of T. asiatica (L.) showed better analgesic effect (28.2±13.16) than Acetylsalicylate used as control (4±0.31). The potential of T. asiatica (L.) asananalgesic was  remarkable. However, the crude extract of T. asiatica (L.) induced nephrotoxicity and liver enzymes  modulation and elevated total cholesterol in the test organisms compared to the untreated negative  controls.KEYWORDS: Biochemical, Haematological, Toxicity, Phytochemical

Helicobacter pylori: prevalence and antibiotic susceptibility among Kenyans

Background. Helicobacter pylori infection in Kenya is staggeringly high. Evidence links infection of the gastric mucosa by H. pylori with subsequent development of gastric pathologies. Aim. We investigated the prevalence of H. pylori in dyspeptic patients, its relationship with gastric pathologies, and associated antibiotic susceptibility profiles, and compared two media to find the appropriate medium that enhances growth and expedites culture and isolation. Methods. Rapid urease and histological tests were used to screen for H. pylori. Culture was performed to test sensitivity and evaluate media. Selective and nutritional supplements were added to culture media (Colombia blood agar and brainheart infusion agar) for growth enhancement. E-test strips for metronidazole, amoxicillin and clarithromycin were used for susceptibility testing. Results. The prevalence of H. pylori infection in children was 73.3%, and 54.8% in adults. All the H. pylori investigated in this study were largely sensitive to clarithromycin (100%, minimum inhibiting concentration (MIC)μg/ml), amoxicillin (100%, MICμg/ml) and metronidazole (95.4%, MICμg/ml). There was, however, occasional resistance to metronidazole (4.6%, MIC \u3e8 μg/ml). Both Colombia blood and brain-heart infusion agar, with the supplements, effectively supported H. pylori growth. Growth was achieved in an average of 36 hours for primary isolations and 24 hours for subcultures. Conclusion. The media described here reduce the time required to culture and isolate bacteria and perform susceptibility testing. Despite the high prevalence of H. pylori infection, the associated pathology is low and does not parallel H. pylori prevalence in the population

Glucose-6-phosphate dehydrogenase deficiency allelic variants and their prevalence in malaria patients in Eritrea

Introduction: glucose 6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy with a relatively high frequency in malaria-endemic regions. In Eritrea, there is scanty knowledge of G6PD deficiency. The aim of the study was to characterize and determine the prevalence of four common G6PD allelic variants. Methods: three hundred and fourteen dried blood spot samples from unrelated microscopically diagnosed malaria patient Eritrean ethnic groups living in five zobas (regions) of Eritrea were analysed by PCR-RFLP method to identify the G6PD B, G6PD A (A376G), G6PD A-(G202A), and G6PD Mediterranean (C563T) variants. To confirm the RFLP results, samples positive for A376G but negative for G202A variants were subjected to Sanger sequencing and a subset of PCR products (exon 5) directly sequenced to identify A376G and other mutations. Results: for G6PD genotyping, G6PD B was detected in 87.5% and A376G detected in 12.5% of malaria patients, whereas G202A and C563T were absent. Bivariate statistical analysis showed a statistically significant association between G6PD genotypes and zoba (P < 0.004 < 0.05). Sequencing revealed the expected A376G variant. In exon 5, four common (A376G) mutations, three uncommon mutations rs782669677 (535G→A) and one potentially new mutation (451G→C), relative to the reference, mRNA NM_001042351 were detected. Bioinformatic analysis of these mutations' potential functional impact suggests minimal effect on protein function. Conclusion: this is the first report indicating that G6PD B and G6PD A genotypes are prevalent in Eritrea. Similar findings were reported in neighboring countries. Further studies including phenotype analysis are needed to corroborate the observed results

Prevalence of gastric mucosal interleukin-1 polymorphisms in Kenyan patients with advanced gastric cancer

Helicobacter pylori is the main cause of peptic ulceration, distal gastric adenocarcinoma, and gastric lymphoma.1 Worldwide, gastric cancer is the second most common malignancy in men and women.1 According to data from the Nairobi Cancer Registry, gastric cancer is the fourth most common malignancy in adult males and the fifth most common in adult females. However, this may not represent the true situation because of under-reporting of cases. In the development of gastric cancer, environmental factors such as smoking, diet and, in particular, infection with H. pylori are significant.1 Based on epidemiological studies, the International Agency for Research on Cancer (IARC) identified H. pylori as a ‘group 1 agent (definite carcinogen)’.2 H. pylori infection can result in decreased acid secretion with subsequent mucosal atrophy and intestinal metaplasia.1 Another precondition for mucosal atrophy is autoimmunity against parietal cells, which can mimic classic autoimmune gastritis with the presence of various autoantibodies in up to 40% of H. pylori-infected individuals.1 The occurrence of intestinal metaplasia, for which a relationship with gastric cancer is strongly suggested, has been demonstrated in approximately 60% of patients with H. pylori infection.1 The metaplasia may then progress to gastric cancer, especially to tumours of the intestinal type.1 Findings by Uemura et al. support the importance of these histological findings as a precancerous condition in H. pyloriassociated gastritis.3 However, only a minority of H. pyloriinfected patients develop gastric cancer, which underscores the notion that the host genetic background could be of critical importance. Data strongly suggest that the susceptibility to infection from H. pylori is mainly conferred by genes involved in inflammatory processes following colonisation with H. pylori.1 Chronic gastritis is characterised by the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) or tumour-necrosis factor alpha (TNFα), which are potent inhibitors of gastric acid secretion.1 Advanced-stage gastric cancer has been repeatedly associated with polymorphisms of the IL-1 gene cluster on chromosome 2q, which contains 3 related genes within a 430 kb region (IL-1A, IL-1B, and IL-1RN), encoding for IL-1α , IL-1β, and the endogenous receptor antagonist IL-1ra, respectively. It was hypothesised that genetic differences within these genes could influence the immune response against pathogens such as H. pylori and the development of premalignant histological alterations in the gastric mucosa.1 In patients with advanced-stage gastric cancer, an increased frequency of the IL-1B-31C and IL-1B-511T alleles and the uncommon IL-1B-31C/IL-1B-511T haplotype was demonstrated. In addition, the IL-1RN*2 allele and the homozygous genotype IL-1RN*2/2 were found in increased prevalence in gastric cancers.1 Subsequent studies confirmed these genetic associations.1 El-Omar et al. genotyped patients with gastric cancer according to tumour localisation (cardia v. non-cardia) and oesophageal cancers (adenocarcinomas v. squamous cell carcinomas) for various polymorphisms of genes encoding for pro- and anti-inflammatory cytokines.4 They described an increased risk for non-cardia gastric cancer in carriers of the IL-1B-511T allele, IL-1RN*2 homozygotes, carriers of the TNF-A-308A allele and the haplotype IL-10- 1082A/-819T/-592A. The cumulative risk depends on the number of high-risk alleles or genotypes per patient.4 A previous study confirmed the risk increase for development of gastric carcinoma in carriers of multiple proinflammatory genotypes.1 The alleles IL-1RN*2 and IL-1B-511T are associated with increased synthesis of the proinflammatory cytokine IL-1ß, and the allele TNFA-308A results in an increased production of the proinflammatory cytokine TNF.

Whole Genome Sequencing Reveals Virulence Potentials of Helicobacter pylori Strain KE21 Isolated from a Kenyan Patient with Gastric Signet Ring Cell Carcinoma

Helicobacter pylori (H.pylori) infection is etiologically associated with severe diseases including gastric cancer; but its pathogenicity is deeply shaped by the exceptional genomic diversification and geographic variation of the species. The clinical relevance of strains colonizing Africa is still debated. This study aimed to explore genomic features and virulence potentials of H. pylori KE21, a typical African strain isolated from a native Kenyan patient diagnosed with a gastric cancer. A high-quality circular genome assembly of 1,648,327 bp (1590 genes) obtained as a hybrid of Illumina Miseq short reads and Oxford Nanopore MinION long reads, clustered within hpAfrica1 population. This genome revealed a virulome and a mobilome encoding more than hundred features potentiating a successful colonization, persistent infection, and enhanced disease pathogenesis. Furthermore, through an experimental infection of gastric epithelial cell lines, strain KE21 showed the ability to promote interleukin-8 production and to induce cellular alterations resulting from the injection of a functional CagA oncogene protein into the cells. This study shows that strain KE21 is potentially virulent and can trigger oncogenic pathways in gastric epithelial cells. Expended genomic and clinical explorations are required to evaluate the epidemiological importance of H. pylori infection and its putative complications in the study population