Abstract:

Background and aim: Rates of H. pylori infections are significantly high in developing countries. In East Africa, the prevalence of H. pylori has been found to range from 46% to 75% with a prevalence of 45.7% to 65% being reported in Tanzania. H. pylori infection can by symptomatic or asymptomatic and is associated with erosions, ulceration and gastric cancers. Eradication of the infection using standard first-line regimen is declining in different parts of the world and has been found to be than 80%. H. pylori antibiotic resistance has been found to be the most common cause of treatment failure. This study aimed at determining the helicobacter pylori sero-prevalence, active infection, treatment outcomes and mutations conferring resistance to quinolones and clarithromycin, among patients presenting with dyspeptic symptoms at Bugando medical centre, northwestern Tanzania.

Methods: This study was conducted between October 2015 and July 2019. The first part was a cross-sectional study which included dyspeptic individuals planned for esophagogastroduodenoscopy (EGD) at Bugando medical centre gastroenterology unit and asymptomatic individuals in Mwanza. The second part was a cohort study that involved H. pylori immunoglobulin G (IgG) antibodies were detected using rapid immunochromatographic kits while the H. pylori antigen from stool tested positive on stool antigen test were put on ten days of standard therapy. In addition, two biopsies were taken from the antrum and fundus for polymerase chain reaction (PCR) and sequencing to detect mutations known to confer resistance of quinolones and clarithromycin. A follow up assessed the cure rate and level of adherence. Stool antigen testing was performed within seven days and 5 weeks after completion of the treatment to establish treatment failure. Data were analysed by STATA-13 software as per study objectives.

Results: H. pylori specific IgG antibodies were detected in 39.1% (95% CI: 32.2 – 45.7) of 202 patients with dyspepsia. It was observed that, as the age increased, the likelihood of H. pylori infection also increased (OR: 1.02 95% CI: 1.04, P=0.02). Furthermore, it was observed that the prevalence of active H. pylori infection was significantly higher in dyspeptic patients than in asymptomatic individuals [213/353 (60.3% vs. 154/349 (44.1%), p<0.001]. Out of 208 non-repetitive biopsies examined, specific PCR for H. pylori was positive in 188/208 (92.2%) of biopsies. Mutations conferring resistance to clarithromycin were detected in 54/188 (28.7%) of the biopsies while mutations conferring quinolones resistance were detected in 77/131 (58.8%) of biopsies. Common clarithromycin mutations detected were A2143G (32) and A2142G (22) while common quinolones mutations were N871 (20) and D91N (15) samples having a new mutation at A92T and 20 having both clarithromycin and fluoroquinolones.

Among 210 patients followed, 75 (35.7%) tested positive immediately after completion of treatment with 65/210 (30.9%, 95% CI; 24.6 – 37.2) testing positive 5 weeks post completion of treatment, implying first-line treatment failure. Independent predictors of first-line treatment failure were the presence of clarithromycin resistance mutations (OR: 23.1, 95% CI: 9.4 – 56.9, p<0.001) and poor adherence (OR: 7.39, 95% CI: 3.25 – 16.77, p<0.0001). The sensitivity of immediately testing in detecting treatment failure was 100% with a specificity of 93.2% and positive and negative predictive values of 86.7% and 100% respectively.

Conclusion and recommendations: About two-thirds of the dyspeptic patients were infected with H. pylori, about twenty percent of these patients are infected by H. pylori strains harbouring mutations conferring resistance to clarithromycin and quinolones. Presence of clarithromycin mutations and poor adherence were found to significantly predict first-line treatment failure. There is a need to conduct surveillance of H. pylori susceptibility patterns to commonly used drugs in order to provide data that can be used to establish local H. pylori treatment guidelines. Stool antigen testing within seven days after completion has good sensitivity and specificity; therefore, it can be practiced to evaluate H. pylori treatment in order to initiate second line treatment early to prevent associated morbidities. Further studies to establish the role of new mutation (A92T) in H. pylori phenotypic resistance are warranted.