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

Antimicrobial resistance patterns in extended-spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae isolates in a private tertiary hospital, Kenya

Background: Extended-Spectrum β-Lactamase (ESBL) producing Enterobacteriaceae have become widespread in hospitals and are increasing in community settings where they cause a variety of infections. In addition to hydrolyzing most beta-lactam agents, bacteria harboring these enzymes display resistance to other unrelated antimicrobial agents and thus often pose a therapeutic dilemma. Though these resistance patterns have been studied elsewhere within Africa, such data from hospitals in Kenya are scanty. We therefore undertook to determine these patterns at the Aga Khan University hospital by studying multidrug resistant Escherichia coli and Klebsiella pneumoniae isolates from patients\u27 samples. Findings: A total of 159 isolates (109 E. coli and 50 K. pneumoniae) were confirmed as ESBL producers and tested against eighteen antimicrobials. The proportion of resistant isolates was high (\u3e80%) for the antimicrobials tested with the exception of the carbapenems (\u3c1%), nitrofurantoin (23%) and gentamicin (63%). Klebsiella pneumoniae had a higher proportion of isolates resistant to ceftazidime, gentamicin and nitrofurantoin (P \u3c 0.05) than E. coli which had a higher proportion of isolates resistant to ciprofloxacin, levofloxacin and tetracycline (P \u3c 0.05). Conclusions: In our study, antimicrobial coresistance is common in ESBL producers; however resistance to carbapenems is low and these drugs would be the appropriate empiric therapy for serious or life threatening systemic infections. Nitrofurantoin retains good activity among the multidrug resistant isolates and can be the drug of choice for non-complicated urinary tract infections due to ESBL producing E. coli

Performance of TUBEX® TF IgM Antibody Test Against Culture to Detect Typhoid Fever Among Hospitalized Patients in Nairobi County

Typhoid fever has remained endemic and a major health problem in developing countries like Kenya due to poor sanitation, overcrowding and limited access to diagnostic services. The main aim of this study was to determine the diagnostic value of TUBEX® TF IGM antibody tests for early diagnosis of typhoid fever among hospitalized patients in Nairobi County. TUBEX® TF is a competitive immunoassay which detects presence of anti-09 IgM Salmonella Typhi antibodies in a patient’s serum. We studied TUBEX® TF a rapid sera diagnostic test for its usefulness in early diagnosis of typhoid fever and we compared its sensitivity and specificity to that of Widal test. The study was conducted on 92 (Gp-I) febrile patients who had clinically suggestive signs and symptoms of typhoid fever. Two groups of controls were created; 45 (Gp-II) and 15 (Gp-III) age and sex matched febrile and healthy controls, respectively.  Blood culture was performed in all cases while TUBEX® TF and Widal tests were performed in both cases and controls. The sample size was based on convenience at the two health facilities of our study. Gp-I had 9 (9.78%) blood culture positives for S.Typhi, 11(11.99%) were positive for TUBEX® TF while 17 (18.48%) were positive for Widal test. 3 (6.67%) Gp-II were positive on both TUBEX® TF and Widal test while none of the two tests tested positive on Gp-III. Among 9 culture positive cases, TUBEX® TF was positive in 8 cases same as Widal test with sensitivity, specificity, PPV and NPV values of 88.9% (95% CI: 51.18-99.7), 97.6% (95% CI: 91.6-99.7), 80.0 %(95% CI: 44.4-97.5), 98.8 %(95% CI: 93.4-100), respectively. Widal test had 88.89% (95% CI: 51.8-99.7), 90.4% (95% CI: 81.9-95.7), 50.00% (95% CI: 24.7-75.3), 98.7% (95% CI: 92.9-100) respectively. This study demonstrated better results with TUBEX® TF test compared to Widal test when blood culture was used as a gold standard. However, these results should be further confirmed by using multiple gold standard tests such as molecular and enzyme-linked immunosorbent assays and carried out on large scale cross-sectional studies with varied prevalence of typhoid fever in the population. Keywords: Typhoid fever, TUBEX® TF, Widal, Cases and Controls. DOI: 10.7176/JBAH/9-4-0

Phenotypic and Genotypic Characterization of Antibiotics Resistance Klebsiella pneumoniae Isolated from Clinical Samples at The Nairobi Hospital, Kenya.

This study was financially supported by the research grant from Government of BURUNDI. Abstract Antimicrobial resistance is a growing threat worldwide. The present study aimed to determine the molecular basis of antibiotics resistant characteristics of Klebsiella pneumoniae isolates. Identification of Clinical isolates and detection of Beta lactamase enzymes with their antibiotic susceptibility pattern was done by automated VITEK 2 system. The distribution of genes was assessed by PCR method. The resistance rate of Klebsiella pneumoniae isolates to antibiotics was 100% to Ampicillin. Among 272 isolates, ESBLs were seen in 81(29.8%) isolates, carbapenemases were seen in 19(7.0%) isolates, ESBL and carbapenemases co-existed in 14(5.1%) isolates, AmpC and carbapenemases co-occurred in a 5 isolates (1.8%), 7 (2.6%) isolates produced ESBL + AmpC+carbapenemases,2 (0.7%)showed ESBL +AmpC  producers. None of the isolates showed AmpC production alone. The occurrence of TEM, SHV and CTX-M was 5.77%, 1.92% and 2.88% respectively. The combination of TEM/CTX-M, SHV/CTX-M, TEM/SHV, TEM/SHV/CTX-M, TEM/SHV/CTX-M/OXA48 genes was carried by 4.81%, 8.65%, 13.46%, 52.88% and 9.62% respectively. The distribution of KPC and OXA-48 genes was 24.4% and 62.2% respectively. VIM and IMP were not detected. The presence of beta lactamases complicates treatment option; hence their prompt detection is critical to patient’s wellbeing. Keywords: Klebsiella pneumoniae, Resistance, Antibiotics, Beta lactamases, Co-existence, ESBLs genes, Carbapenemases genes

Molecular Characteristics of Archived Isolates of Escherichia coli from the Gut of Healthy Food Animals and Environmental Sources in Selected Counties in Kenya

E. coli is a reservoir of resistance genes encoding resistance enzymes including extended-spectrum beta-lactamases (ESBL) and carbapenemases. This study aims to determine the resistance pattern, the pathotypes, and the proportion of ESBL producers among archived E. coli isolates from healthy food animals and their immediate environments at the Center for Microbiology Research, Kenya Medical Research Institute. Of the 375 isolates, 78.4% isolates were resistant to at least one of the 13 tested antibiotics and 28.8% showed multidrug resistance. Resistance was higher to tetracycline (55.2%), co-trimoxazole (44%), trimethoprim (43.7%), and ampicillin (28.8%). The proportion of Enteroaggregative E. coli was 88.3% while other pathotypes were not found. The proportion of ESBL producers was 8.8% of which 100% harboured blaTEM, 18.1% harboured blaCTX-M; blaSHV was not found. E.coli isolates from healthy food animals were multidrug resistant and harboured virulence genes and ESBL genes. Risk assessment and management is necessary to protect farmers and the public in general. Keywords: Archived E. coli isolates, antimicrobial resistance, multidrug resistance, pathotypes, ESBLs

Molecular Characterization of Beta-lactams Resistance in Pseudomonas aeruginosa Isolated from Clinical Sources at the Nairobi Hospital

The increase of Beta-lactamases producing organisms can cause major therapeutic failure and poses a significant clinical challenge in healthcare settings.  A total of 185 clinical isolates of Pseudomonas aeruginosa strains were collected from in-and out-patients at The Nairobi Hospital, 74.1 % were inpatients and 25.9% were outpatients with the high prevalence of this bacterium among the male gender (61.1%) than female(38.9%); and preponderantly comprising the patients above 45 years old (64.3%). The highest numbers of P. aeruginosa were isolated from pus swab (39.5%), respiratory secretions (25.9%), and urine (18.9%). The resistance rate of P. aeruginosa against carbapenem was 31.5% among the isolates. The prevalence of MBL producing P. aeruginosa was 22.7% as compared to non-MBL isolates (77.3%). The MBL isolates were resistant to the examined antibiotics. There were two predominant genes VIM-2 (28.57%) and NDM-1 (66.67%) types among MBL P. aeruginosa, and more prevalent genes were isolated from Critical care nursing ward; Intensive Care Unit (45.2%) and High Dependency Unite (28.6%) at The Nairobi Hospital. These findings suggest that the early detection of   Metallo-Beta-Lactamases-producing isolates and the cooperation between medical professionals and infection control team may help in appropriate antimicrobial therapy and avoid further spread of these multidrug resistance strains. Keywords: Pseudomonas aeruginosa, Metallo-Beta-Lactamases, Resistance, Beta-lactams

Characterization of HIV-1 Integrase Gene and Resistance Associated Mutations Prior to Roll out of Integrase Inhibitors by Kenyan National HIV-Treatment Program in Kenya

BACKGROUND: Antiretroviral therapy containing an integrase strand transfer inhibitor plus two Nucleoside Reverse Transcriptase inhibitors has now been recommended for treatment of HIV-1-infected patients. This thus determined possible pre-existing integrase resistance associated mutations in the integrase gene prior to introduction of integrase inhibitors combination therapy in Kenya.METHODS: Drug experienced HIV patients were enrolled at Kisii Teaching and Referral in Kenya. Blood specimens from (33) patients were collected for direct sequencing of HIV-1 polintegrase genes. Drug resistance mutations were interpreted according to the Stanford algorithm and phylogenetically analysed using insilico tools.RESULTS: From pooled 188 Kenyan HIV integrase sequences that were analysed for drug resistance, no major mutations conferring resistance to integrase inhibitors were detected. However, polymorphic accessory mutations associated with reduced susceptibility of integrase inhibitors were observed in low frequency; M50I (12.2%), T97A (3.7%), S153YG, E92G (1.6%), G140S/A/C (1.1%) and E157Q (0.5%). Phylogenetic analysis (330 sequences revealed that HIV-1 subtype A1 accounted for majority of the infections, 26 (78.8%), followed by D, 5 (15.2%) and C, 2 (6%).CONCLUSION: The integrase inhibitors will be effective in Kenya where HIV-1 subtype A1 is still the most predominant. However, occurring polymorphisms may warrant further investigation among drug experienced individuals on dolutegravir combination or integrase inhibitor treatment.&nbsp

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

Displacement of hospital-acquired, methicillin-resistant Staphylococcus Aureus clones by heterogeneous community strains in Kenya over a 13-Year period

We determined antibiotic susceptibility and employed Oxford Nanopore whole-genome sequencing to explore strain diversity, resistance, and virulence gene carriage among methicillin-resistant Staphylococcus aureus (MRSA) strains from different infection sites and timepoints in a tertiary Kenyan hospital. Ninety-six nonduplicate clinical isolates recovered between 2010 and 2023, identified and tested for antibiotic susceptibility on the VITEK ID/AST platform, were sequenced. Molecular typing, antibiotic resistance, and virulence determinant screening were performed using the relevant bioinformatics tools. The strains, alongside those from previous studies, were stratified into two periods covering 2010–2017 and 2018–2023 and comparisons were made. Mirroring phenotypic profiles, aac(6′)-aph(2″) [aminoglycosides]; gyrA (S84L) and grlA (S80Y) [fluoroquinolones]; dfrG [anti-folates]; and tet(K) [tetracycline] resistance determinants dominated the collection. While the proportion of ST239/241-t037-SCCmec III among MRSA reduced from 37.7% to 0% over the investigated period, ST4803-t1476-SCCmec IV and ST152-t355-SCCmec IV were pre-eminent. The prevalence of Panton–Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) genes was 38% (33/87) and 6.8% (6/87), respectively. We observed the displacement of HA-MRSA ST239/241-t037-SCCmec III with the emergence of ST152-t355-SCCmec IV and a greater clonal heterogeneity. The occurrence of PVL+/ACME+ CA-MRSA in recent years warrants further investigations into their role in the CA-MRSA virulence landscape, in a setting of high PVL prevalence