Declining eradication rates of Helicobacter pylori with standard triple therapy in Addis Ababa, Ethiopia

Abstract

BACKGROUND

Standard triple therapy is an effective treatment for eradicating Helicobacter pylori infection, but it is encountered with drug resistance. The stool antigen test is a cost-effective and easy-to-perform test to confirm the eradication of H. pylori, 4-8 weeks post-therapy, with 86% sensitivity and 92% specificity.

AIM

To assess the H. pylori eradication rate of standard triple therapy and factors affecting the eradication rate.

METHODS

We conducted a prospective, multicenter follow-up study in Addis Ababa, Ethiopia, at selected healthcare facilities among dyspeptic patients with positive stool H. pylori antigen tests from June 1, 2023 to October 30, 2023 to assess the H. pylori eradication rate. After completing the standard triple therapy, the eradication was confirmed using a stool antigen test 4 weeks later. The data were analyzed using bivariate and multivariate logistic regression methods.

RESULTS

The H. pylori eradication rate was 85.4%. Patients with a previous diagnosis of H. pylori infection, smokers, and local alcohol consumption were associated with a lower H. pylori eradication rate, with adjusted odds ratio (AORs) of 0.159 [95% confidence interval (CI): 0.050-0.511], 0.206 (95%CI: 0.052-0.822), and 0.228 (95%CI: 0.052-0.997), respectively. Patients with complete symptom resolution were 5.383 times more likely to achieve eradication than patients without symptom improvement, AOR = 5.383, 95%CI: 1.74-21.089.

CONCLUSION

H. pylori eradication rate was lower than expected. Post-treatment testing is crucial to confirm eradication and guide further management, such as susceptibility testing.

Key Words: Helicobacter pylori; Triple therapy; dyspepsia; Proton pump inhibitor; Stool antigen test

Core Tip: Standard triple therapy for Helicobacter pylori eradication showed a lower success rate (85.4%) in Addis Ababa, Ethiopia, compared to previous studies. Patients with prior H. pylori diagnosis, smoking, and local alcohol consumption had a lower eradication rate. Complete symptom resolution was associated with higher eradication success. This suggests the need for routine eradication confirmation tests and monitoring for symptom improvement.

INTRODUCTION

Helicobacter pylori is a notable human pathogen affecting about 50% of the global population, primarily in developing nations. Hundreds of millions of people develop peptic ulceration during their lifetime, and tens of millions might develop gastric cancer[1,2]. The global prevalence of H. pylori infection varies significantly, with developing countries disproportionately affected. Africa, in particular, exhibits a notably high prevalence, often exceeding 70%[3]. A study by Bounder et al[4] showed that the prevalence of H. pylori infection varies in different geographic regions of Africa. The prevalence of H. pylori infection was examined in a Moroccan population; both symptomatic and asymptomatic individuals were included, and they found that 89.6% of those with gastrointestinal symptoms and 92.6% without symptoms were seropositive for H. pylori. In a systematic review and meta-analysis by Melese et al[5], the overall pooled prevalence of H. pylori infection in Ethiopia was 52.2%.

Developing countries, including those in Africa, face significant challenges in treating H. pylori infections due to the high prevalence of resistance to commonly used antibiotics such as metronidazole, clarithromycin, and amoxicillin. A systematic review and meta-analysis revealed high levels of antibiotic resistance among H. pylori strains in Africa. Specifically, resistance rates were 17.4% for quinolones, 29.2% for clarithromycin, 48.7% for tetracycline, 75.8% for metronidazole, and 72.6% for amoxicillin. Another systematic review and meta-analysis of 176 articles from 24 countries by Jaka et al[6] revealed high rates of primary H. pylori resistance. Specifically, the mean prevalence of resistance was 17% for clarithromycin, 44% for metronidazole, 18% for levofloxacin, 3% for amoxicillin, and 4% for tetracycline.

The growing antibiotic resistance poses a significant danger to human health despite the existing treatment options. Since 2017, the World Health Organization (WHO) has identified H. pylori as one of the top 20 pathogens with the most severe impact on human health due to its medication resistance[7].

Despite variations in rates and characteristics of antibiotic resistance of H. pylori across different regions, there has been a worldwide increase over the last 20 years, leading to a consistent decline in the effectiveness of eradication treatments[8]. Resistance rates to clarithromycin, metronidazole, and levofloxacin were reported to be ≥ 15% across all WHO regions, with a few exceptions such as primary clarithromycin resistance in the Americas and Southeast Asia and primary levofloxacin resistance in Europe[9]. These failures have created a challenge in treating patients who do not respond to multiple drug regimens, leaving no clear empirical third-line treatment option[10].

Significant variability in antibiotic resistance rates among countries led to notable heterogeneity in the findings. Most WHO regions saw a noticeable upward trend in antibiotic resistance levels. Particularly concerning was the strong correlation between clarithromycin resistance and treatment failure when using clarithromycin-based therapies. The increasing levels of antibiotic-resistant H. pylori present a substantial obstacle to effective treatment globally. The WHO has highlighted clarithromycin-resistant H. pylori as a critical priority for further research and development of antibiotics[9].

The increasing prevalence of antimicrobial resistance jeopardizes the success of therapeutic regimens aimed at eradicating infection. Currently, the frequent use of empirical and repeated treatments to eliminate H. pylori is prevalent in clinical settings. This practice is likely to contribute to a rise in antibiotic resistance, leading to the inefficient use of medical resources, heightened stress for patients, disease advancement, and a negative impact on their quality of life[11].

Eradication failure is more problematic in Africa, which is already grappling with a massive burden of H. pylori infection occasioned by poor sanitation, overcrowding, low antimicrobial stewardship, poverty, and sparse endoscopic services[8].

Since retreatment is complex, choosing the best available first-line regimen based on pretreatment antimicrobial susceptibility testing, and in the cases where these cannot be done or are not available, at least as per the regional resistance pattern, may significantly decrease treatment failure and improve the eradication rate[11]. Numerous natural products have been shown to inhibit the growth of H. pylori[12]. Syzygium aromaticum, commonly known as clove, is a Myrtaceae plant with a wide range of pharmacological activities including antimicrobial, antioxidant, antiviral, anticancer, anti-inflammatory, and analgesic effects[12-14]. A study by El-Shouny et al[12] demonstrated that the methanol extract of S. aromaticum possesses significant antibacterial activity against drug-resistant H. pylori, suggesting its potential for biomedical applications. The presence of eugenol as the primary phenolic compound may contribute to the extract’s efficacy[12]. Another study by Peng et al[15] showed that aqueous and hydroalcoholic extracts of S. aromaticum were effective against drug-sensitive and drug-resistant H. pylori strains. The MICs ranged from 160 to 320 μg/mL. Aqueous extract displayed bactericidal activity, while hydroalcoholic extract exhibited bacteriostatic activity. No drug resistance was observed, and the extracts showed synergistic effects with standard antibiotics. Moreover, the extracts induced morphological and ultrastructural changes in H. pylori and downregulated the expression of virulent genes[15]. By inhibiting the adhesion of H. pylori to host cells, a key step in infection, chebulinic acid acts as an anti-adhesive agent. Additionally, it suppresses the expression of the cytotoxin-associated gene A (CagA) protein[16]. 1,3,6-Trigalloylglucose is a potent inhibitor of H. pylori, effectively inhibiting the growth of H. pylori strain ATCC 700392 and suppressing the expression of the CagA protein. Significantly, it does not damage GES-1 normal epithelial cells, demonstrating its selective antimicrobial activity[17].

In Ethiopia, data regarding antimicrobial therapy efficacy, national antibiotic resistance, and susceptibility patterns are scarce. This study assessed the effectiveness of standard H. pylori eradication therapy and possible associated factors. It will also serve as an entry point for further research and development of local antibiotic sensitivity and resistance patterns.

MATERIALS AND METHODS

Study design

A prospective follow-up study was carried out in Addis Ababa, the capital city of Ethiopia, from June 1 to October 30, 2023, at selected healthcare facilities. These include Tikur Anbessa Hospital, Adera Medical Center, Tekle Haimanot General Hospital, and three Health centers in the Kolfe Keranyo sub-city (Woreda 9, Woreda 3, and Woreda 5).

Tikur Anbessa Specialized Hospital is the largest referral and teaching hospital in Addis Ababa, Ethiopia with a monthly average 500 gastroenterology outpatient clinic visits. Adera medical center is a private hospital in Addis Ababa, Ethiopia with an average 70 per day gastroenterology outpatient clinic visits.

Study population

All dyspeptic stool H. pylori antigen-positive patients attending the selected health facility during the study period and fulfilling the inclusion criteria were included in the study population.

Eligibility criteria

All adult patients (age > 18 years) with dyspepsia who tested positive for H. pylori stool antigen and were willing to undergo post-treatment eradication tests after 4 weeks were included in the study. Those unwilling to undergo post-treatment eradication tests, patients with gastrointestinal bleeding, or patients who were critically ill were excluded from the study (gastrointestinal bleeding decreases the sensitivity of the H. pylori stool antigen test).

Sampling procedure

All eligible patients during the study period were included. Therefore, sample size calculation and sampling techniques were not used. We opted not to calculate the sample size for the following reasons: (1) Feasibility and Resource Constraints: Conducting a large-scale clinical trial with a predefined sample size is resource-intensive, especially in resource-limited settings such as in ours; and (2) Exploratory nature of the study: This study has an exploratory nature, aiming to investigate the prevalence of H. pylori infection and the effectiveness of standard triple therapy in a specific population. So, we opted to collect data until we found a sufficient number of participants. The lack of a calculated sample size could limit the generalizability of the findings to the larger Ethiopian population. It may also reduce the precision of the estimates of the eradication rate and the factors associated with it. Additionally, the study may lack the statistical power to detect smaller but potentially important effects.

Data collection tool and procedures

Data were collected from study participants through face-to-face interviews using a pre-tested structured questionnaire adopted from previous literature and similar studies, with modifications to fit the local context. The questionnaire is divided into five parts assessing sociodemographic profile, clinical manifestations, comorbidities, alcohol and medication use, and treatment profile, including side effects. Study participants were treated with standard triple therapy (twice daily proton pump inhibitors [PPIs] standard dose, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily) for a 14-day duration. The success of the therapy was determined by a negative stool antigen test result after 4 weeks of eradication treatment, with a positive result indicating treatment failure. The primary diagnosis and confirmation of eradication after 4 weeks of standard triple therapy were conducted using a stool antigen test (Guangzhou Wondfo Test Kit, manufactured by Guangzhou Wondfo Biotech co.,Ltd, China). Drug adherence was defined using Morisky’s medication adherence scale -8 (good adherence score of 8, medium adherence score of 6-8, and poor adherence < 8). Morisky’s medication adherence scale was administered after therapy.

Data quality assurance

Every day after data collection, the collected data were reviewed for completeness and accuracy to ensure data integrity. Before the actual data collection, the questionnaire was pre-tested. The data collectors were closely monitored, and the collected data were inspected and double-checked for accuracy.

Data processing and analysis

After verifying, cleaning, and checking data for quality, it was entered into SPSS version 26 (SPSS Inc., Chicago, IL, USA) and then analyzed. Results were summarized using tables and figures. Categorical variables are expressed as the frequencies and percentages. Means, standard deviations, and minimum and maximum values were used to express continuous variables. Bivariate and multivariable logistic regression analyses were employed to identify predictors associated with the successful eradication of the target condition. In the first phase of the analysis, bivariable analysis was conducted to examine individual variables and their significant associations with the eradication rate. This initial screening helped to identify potential predictors worthy of further investigation. Following this, multiple logistic regression was utilized to assess the combined effects of these predictors while controlling for potential confounding variables. This comprehensive approach allowed a deeper understanding of the factors influencing eradication rates. Multivariate logistic regression analysis was used to assess the independent association of various factors, including prior H. pylori diagnosis, alcohol consumption, smoking status, and symptom resolution, with successful H. pylori eradication. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify the strength of these associations. Statistical significance was determined at P < 0.05 level.

The fitness model was checked using the Hosmer-Lemeshow test. The degree of association between dependent and independent variables was described using crude OR and adjusted OR (AOR), with 95%CI as an indicator of the strength of association.

RESULTS

Of the 172 consenting patients, 152 (88.4%) returned to the healthcare facility for the follow-up stool antigen test after completing eradication therapy, as shown in Figure 1. Efforts were made to maximize participation; patients who missed their appointments received reminder phone calls to encourage their return.

Figure 1 Enrollment of study participants attending selected healthcare institutions at Addis Ababa, Ethiopia, June 2023 to October 2023.

Socio-demographic characteristics of study subjects

The study cohort included 152 patients with a nearly even sex distribution (72 males, 47.4%; 80 females, 52.6%). The participants' average age was 39.2 years old (± 13.35), ranging from 18 to 72 years. A significant majority (82.2%) of participants reside in urban areas (Table 1).

Table 1 Sociodemographic characteristics of study subjects.

Variables		Helicobacter pylori stool antigen test after treatment
		Negative	Positive
		Negative	Positive
Sex	Male	60	12
	Female	70	10
Age	18-30	41	12
	31-40	39	2
	41-51	25	5
	51-60	16	2
	Above 61	9	1
Body mass index	Less than 18.5	4	1
	18.5-24.9	85	15
	25-29.9	33	5
	30-34.9	6	1
	35-39.9	2	0
	Above 40	0	0
Educational level	Unable to read and write	14	2
	Grade 1-8	23	1
	Grade 9-12	34	11
	Diploma	28	3
	Degree and above	31	5
Residency	Rural	20	7
	Urban	110	15
Average monthly family income in Ethiopian Birr	Less than 1000 birr	5	2
	1000-5000 birr	21	4
	5000-10000 birr	38	7
	Above 10000 birr	66	9

Clinical information and H. pylori eradication rate of the study subjects

Among the 152 patients interviewed (Table 1), 45 (29.6%) had a previous diagnosis of H. pylori infection, and 23 (15.1%) had received prior triple therapy with unknown treatment outcomes. Over half (71.2%) of the patients reported chronic gastrointestinal symptoms lasting over 3 months. These symptoms typically worsened after meals (48.0%) or persisted throughout the day (21.0%). Notably, 27 (17.8%) of the patients used over-the-counter medications (cimetidine and omeprazole) to manage these symptoms before their H. pylori diagnosis. More than half of the patients (54.6%) used traditional homemade remedies for symptomatic relief. Telba and milk (19.1%) was the most common remedy, followed by Abesh (13.8%).

Nearly half (44.7%) of the patients consumed alcohol, with beer (25.0%) being the most common type, followed by local beverages (16.4%). While over half (69.7%) reported no chronic medical conditions, 46 (30.3%) had self-reported comorbidities. Hypertension (9.2%) and diabetes mellitus (5.3%) were the most frequent chronic illnesses. Additionally, 16 (10.5%) of the participants were active smokers.

The overall eradication rate (treatment success) for H. pylori was 85.5% (130 patients). Among those successfully eradicated, more than half (58.6%) reported symptomatic improvement with triple therapy. Conversely, only 5.9% of patients with failed eradication showed improvement, while 22.7% still experienced some symptoms. This eradication rate is higher compared to eradication rates seen in other neighboring countries, such as Kenya 68%, Tanzania 69%, and Egypt 82%[18].

Adherence to triple therapy was good for 86.2% (131 patients) and moderate for 13.8% (21 patients). Adherence was higher in failed eradication groups (90.9%) than successful eradication (85.4%). Non-severe side effects were reported by 15.1% of patients. These were primarily gastrointestinal and included nausea and vomiting (5.3%), watery diarrhea (6.6%), myalgia (2%), and taste changes (1.3%). A total of 10.5% of patients used homemade remedies during the treatment course (Table 2).

Table 2 Clinical information and Helicobacter pylori eradication rate of standard triple therapy.

Variables		Frequency	Percent (%)
Previous diagnosis of Helicobacter pylori		45	29.6
Previous treatment with standard triple therapy		23	15.1
Duration of gastrointestinal symptoms	One week	3	2.0
	Two weeks	15	9.9
	One month	26	17.1
	Three months	22	14.5
	3-6 months	25	16.4
	Six months to 1 year	39	25.7
	One to Two years	8	5.3
	≥ 3 years	14	9.2
Pain worsens	After meal	73	48.0
	Before meal	31	20.4
	During night	15	9.9
	Always present	33	21.7
Intake of PPI in the past 2 weeks to control symptoms		27	17.8
History of chronic medical illness	Liver disease	5	3.3
	Kidney disease	7	4.6
	Diabetes mellitus	8	5.3
	Hypertension	14	9.2
	Cardiac	7	4.6
	Pulmonary disease	2	1.3
	Neurologic	3	2.0
Alcohol consumption	Local beverage (Tella, Tej, Areke)	25	16.4
	Beer	38	25.0
	Wine	5	3.3
	Whisky	2	1.3
	Other	2	1.3
Smoking		18	11.8
Use of homemade remedy during triple therapy		16	10.5
Use of traditional homemade remedy	Telba	29	19.1
	Abesh	21	13.8
	Milk	29	19.1
	Hot water	0	0.0
	Other	4	2.6
Adherence to treatment	Good adherence	131	86.2
	Medium adherence	21	13.8
	Poor adherence	0	0.0
Adverse side effects of triple therapy		23	15.1
Outcome of treatment	Helicobacter pylori eradication achieved	130	85.5
	Helicobacter pylori eradication failed	22	14.5

PPI: Proton pump inhibitor.

Factors associated with H. pylori eradication rate

Several factors were analyzed using bivariate logistic regression to assess their association with H. pylori eradication: Previous diagnosis of H. pylori infection, alcohol consumption, smoking, complete symptom resolution, sex, age, religion, body mass index, marital status, residence, occupation, income, educational status, duration of symptoms, use of traditional/modern medications, adverse drug side effects, adherence, and presence of chronic medical illnesses. However, only previous diagnoses of H. pylori infection, alcohol consumption, smoking, and complete symptom resolution showed potential associations with eradication. On multivariate analysis, patients with a prior diagnosis of H. pylori infection, smokers, and local alcohol consumption were associated with a lower H. pylori eradication rate with an AOR of 0.159, 95%CI: 0.050-0.511; 0.206, 95%CI: 0.052-0.822; and 0.228, 95%CI: 0.052-0.997, respectively. Patients with complete symptom resolution were more likely to achieve eradication than patients without symptom improvement, with an AOR of 5.383, 95%CI: 1.74-21.089 (Table 3).

Table 3 Factors affecting Helicobacter pylori eradication in selected healthcare institutions Addis Ababa, n (%).

Variable	Post-treatment Helicobacter pylori stool antigen test		Odds ratio (95%CI)		P value
	Successful eradication	Failed eradication	Crude	Adjusted
Prior diagnosis of Helicobacter pylori					< 0.001
Yes	30 (23.1)	15(68.2)	0.140 (0.052-0.375)	0.159 (0.050-0.511)
No	100 (76.9)	7 (31.8)		1
Alcohol intake					0.001
Local	13 (10.0)	12 (5.5)	0.164 (0.048-0.559)	0.228 (0.052-0.997)
Beer	33 (25.4)	5 (22.7)	0.271 (0.026-2.777)	0.122 (0.007-2.224)
Wine	4 (3.1)	1 (4.5)	0	0
Whisky	2 (1.5)	0	1.083 (0.061-19.313)	0.666 (0.27-16.692)
Other	1 (0.8)	1 (4.5)	0.042 (0.010-0.170)	0.065 (0.013-0.317)
No	77 (59.2)	3 (13.6)		1
Smoking					0.01
Yes	10 (7.7)	8 (36.4)	0.146 (0.049-0.43)	0.206 (0.052-0.822)
No	120 (92.3)	14 (63.6)		1
Symptom resolution					0.006
Feeling better	81 (62.3)	5 (22.7)	5.786 (1.968-17.012)	5.383 (1.374-21.089)
Improved, but still had a Feeling	42 (32.3)	15 (68.2)	6.629 (0.756-28.354)	1.885 (0.185-19.242)
No improvement	7 (5.4)	2 (9.1)		1

CI: Confidence interval

DISCUSSION

This study assessed the eradication rate of standard triple therapy for H. pylori infection in Addis Ababa, Ethiopia, and investigated factors influencing this rate. We found an eradication rate of 85.4% with standard treatment, and factors such as previous H. pylori infection, alcohol consumption, and smoking were associated with lower eradication rates. Conversely, complete symptom control was associated with a favorable eradication outcome. Still, it should be noted that symptomatic relief might not always correlate with the eradication rate, and follow-up and testing for eradication are necessary for all patients, including those with symptomatic relief.

The average patient age in our study was 36.5 years, consistent with the mean age reported in a previous study (30.63 years)[19]. Similar to other studies[20,21], we observed a slight predominance of female patients (52.6%) in our study. Similar to previous studies, there was no significant correlation between age, sex, and the success of eradication therapy[22].

Our study found a higher eradication rate of H. pylori infection than a previous pooled meta-analysis in Africa (85.4% vs 79%). In subgroup analysis, the highest eradication rate (90%) was in a study done in Bahirdar, Northwest Ethiopia, which was higher than ours[19]. By contrast, a study in Ankara, Turkey, reported significantly lower eradication rates (58%-63%), likely due to a higher prevalence of resistant H. pylori strains. Compared to the prevailing local antibiotic resistance patterns, resistance to clarithromycin, metronidazole, and levofloxacin in that study was 26.7%, 28.4%, and 19.6%, respectively[23]. An earlier study in Addis Ababa (2004) showed susceptibility to some antibiotics (clarithromycin, erythromycin, tetracycline, amoxicillin) but concerningly high resistance to metronidazole (76%)[24]. No further studies on local resistance patterns have been conducted since then. However, a 2018 meta-analysis and systematic review by Jaka et al[6] to assess the magnitude of antimicrobial resistance to H. pylori in Africa, which included neighborhood countries, found that metronidazole resistance varied widely across studies, ranging from 4.6% in Kenya to 100% in Egypt and Nigeria among 2085 isolates tested and overall resistance of 75.8%. Clarithromycin, a potent first-line H. pylori treatment, showed significant regional variation in resistance rates, ranging from 0% in Gambia, Kenya, and Ethiopia to 100% in Egypt and Nigeria. A high resistance rate of 72.6% was observed among 1530 amoxicillin-tested isolates. Similarly, 48.7% of 1277 isolates were resistant to tetracycline. For quinolones, resistance varied from 0% to 32% among 823 isolates, with an overall resistance of 17.4%. While rifampicin resistance was high at 87.1%, no resistance was detected for rifamycin[6].

According to a previously established classification system based on eradication rates, the efficacy of our H. pylori eradication therapy falls within the “borderline” category (85%-89%)[25]. This classification suggests the treatment may be ineffective in our study population. Falling within the “borderline” efficacy category raises public health concerns for several reasons: (1) Increased risk of H. pylori infection persistence. A lower eradication rate means more individuals will continue harboring the H. pylori infection. This increases the risk of associated health complications, including peptic ulcer disease, gastric cancer, and mucosa-associated lymphoid tissue lymphoma; (2) Spread of antibiotic-resistant H. pylori: Ineffective treatment can contribute to the spread of antibiotic-resistant H. pylori strains. This makes it more difficult to treat the infection in the future, both for the individual and the wider population; and (3) Public Health Burden: The increased prevalence of H. pylori infection and antibiotic resistance can lead to a significant public health burden. This includes increased healthcare costs due to the treatment of H. pylori-related complications and lost productivity and mortality.

This trend could be linked to the rising prevalence of antibiotic resistance. Systematic reviews and meta-analyses conducted in Africa from studies done between 1986 and 2017 have conferred increased antibiotic resistance[6].

The success rate of H. pylori eradication has declined over time due to the increasing resistance of the bacteria to antibiotics[8,9,26-28]. The WHO has identified H. pylori as a major health concern due to its resistance to many common treatments[7]. H. pylori develops antibiotic resistance through various complex molecular mechanisms. These include genetic mutations within the bacteria themselves and physiological changes that boost the activity of efflux pumps, which expel antibiotics from the bacterial cells[29-34]. Another possible mechanism for antibiotic resistance is the formation of biofilms by the bacteria. These structures can shield the bacteria from the effects of antibiotics[35,36]. Even though H. pylori treatments combine multiple antibiotics, resistance to just one of these drugs can still lead to treatment failure[37].

Antibiotic resistance in H. pylori significantly reduces the effectiveness of eradication treatments. For instance, the success rate of clarithromycin-based treatments is significantly lower when the bacteria are resistant to clarithromycin[37-39]. Hence, Standard triple therapy containing clarithromycin is only recommended in regions where less than 15% of H. pylori strains are resistant to clarithromycin[40]. In contrast, metronidazole resistance has not led to a significant decline in eradication rates. Bismuth quadruple therapy, particularly with higher doses of metronidazole, has shown success even in cases of metronidazole resistance[37-39]. The poor correlation between metronidazole resistance and treatment outcomes may be due to the various mechanisms leading to resistance and its diverse mutations. The increasing number of H. pylori strains resistant to multiple drugs has made treatment increasingly difficult. Since initial treatments are typically chosen without testing for antibiotic resistance, treatment failures can contribute to the emergence of more drug-resistant strains[41-43].

Given the significant global decline in eradication rates and the increasing antibiotic resistance of H. pylori, a more targeted approach to treatment, such as antimicrobial stewardship, is necessary[42]. Many regions lack reliable data on the prevalence and nature of antibiotic resistance within their populations, hindering informed decisions about initial treatment choices.

Currently, bismuth quadruple therapy is recommended in areas where both clarithromycin and metronidazole resistance are widespread[40]. Adding bismuth to certain triple therapy regimens and extending treatment duration to 14 days can boost eradication rates by up to 30% or more, even in the face of antibiotic resistance in some strains[44]. We believe studies on local resistant patterns are recommended to determine the extent of the problem.

In our study, those with a previous diagnosis of H. pylori infection were associated with an 84.1% lower likelihood of successful eradication than those without a prior diagnosis AORs = 0.159, 95%CI: 0.050-0.511. This is similar to a previous study in Madrid, Spain, which suggests that recurrence of H. pylori infection is uncommon after successful eradication using effective therapies[45]. In developed countries, the annual recurrence rate is estimated to be around 3%. Many apparent recurrences may be reactivations of an inadequately treated prior infection, often due to an ineffective treatment regimen[46]. Since treatment adherence and eradication success were not monitored in the previous course of triple therapy for our study participants, concluding recurrence is challenging.

A prior study conducted in Barcelona, Spain, demonstrated a significant association between daily alcohol consumption and eradication rates in a dose-dependent manner. The likelihood of eradication failure was significantly higher in non-drinkers (29.9%) compared to drinkers (12.2%), with an AOR of 3.24 (95%CI: 1.12-9.20; P = 0.03)[45]. Interestingly, in our study, alcohol consumption was associated with a statistically significant decrease in eradication success. Patients who consumed local alcoholic beverages were 77.2% less likely to achieve H. pylori eradication than non-drinkers (AOR = 0.228; 95%CI: 0.052-0.997). Similarly, beer consumption was associated with a lower likelihood of eradication (AOR = 0.122; 95%CI: 0.007-2.224) compared to no alcohol consumption. However, a study from Bahirdar, Ethiopia, reported no significant influence of alcohol consumption on eradication rates[47]. These discrepancies might be due to variations in how alcohol consumption was defined in each study, and potential cultural differences in drinking patterns between the investigated populations. In our study, most participants consumed local drinks and beer with relatively low ethanol content. This could explain the observed difference compared to studies investigating beverages with higher alcohol content, which are hypothesized to enhance H. pylori eradication by increasing stomach acidity[45].

Various biological mechanisms explain the link between alcohol consumption and an increased risk of H. pylori eradication failure. First, Alcohol consumption can increase gastric acid secretion, lowering stomach pH. This acidic environment can degrade antibiotics, reducing their effectiveness against H. pylori[48]. Furthermore, alcohol consumption can significantly reduce the absorption rate of amoxicillin[49].

Second, alcohol can induce the liver enzyme cytochrome P450 family 2 subfamily C member 19 (CYP2C19), which can impact the metabolism of PPIs[50]. Studies have shown that individuals with rapid or intermediate CYP2C19 metabolizer genotypes have lower H. pylori eradication rates than poor metabolizer genotypes[51]. Thus, alcohol-induced CYP2C19 induction may contribute to reduced eradication rates. Finally, alcohol can also disrupt the gastric microenvironment, which may compromise the stability of antibiotics and subsequently reduce eradication rates[52].

In this study, active smoker patients were 79.4% less likely to achieve H. pylori eradication than non-smokers. Similarly, a meta-analysis of 22 articles showed smoking was associated with a reduced eradication rate (OR = 1.95; 95%CI: 1.552.45). The variance in eradication rates between individuals who smoke and those who do not smoke was found to be 8.4% (95%CI: 3.3-13.5%; P < 0.01). Moreover, another analysis of 39 studies indicates that smoking is linked to an increased likelihood of H. pylori eradication failure. The risk of failure rises with the number of cigarettes smoked per day (> 5 cigarettes/day) (OR = 2.59; 95%CI: 1.28-5.24), smoking during treatment (OR = 2.49; 95%CI: 1.52-4.06), and the presence of a peptic ulcer (OR = 2.14; 95%CI: 1.51-3.02)[53].

The mechanism contributing to treatment failure in smokers is the reduction in gastric mucosal blood flow and mucus secretion caused by smoking, which may hinder the effective delivery of antibiotics to the gastric mucosa[54,55]. Furthermore, smoking can increase gastric acid production, which can degrade acid-sensitive antibiotics like amoxicillin and clarithromycin, reducing their effectiveness[56]. These two mechanisms are supported by a study done by Ishioka et al[57].

Similar to the previous study, complete symptom resolution was associated with an increased likelihood of achieving H. pylori eradication compared to those without improvement following triple therapy (AOR = 5.383; 95%CI: 1.74-21.089)[47]. In our study, Telba (flaxseed) and milk emerged as the most commonly used home remedies alongside triple therapy. Specifically, 43.7% and 37.5% of participants reported using Telba and milk, respectively, followed by “Abesh” (18.75%).

While the incorporation of these traditional remedies did not significantly affect H. pylori eradication rates, they might be associated with a reduction in adverse drug side effects. Pearson's correlation analysis revealed a weak positive correlation (r = 0.214, P = 0.008) between traditional remedy use and reduced side effects. This finding aligns with a retrospective study conducted in Bahirdar[19]. Since Pearson's value shows a weak correlation, the recommendation of using traditional remedies to reduce adverse drug side effects can't be made.

There is a belief that chronic medical conditions can sometimes impact the effectiveness of H. pylori eradication therapy, resulting in diverse outcomes and being backed by limited evidence[58-61].

However, our study found that self-reported chronic medical conditions did not influence the eradication rate. Pearson's data analysis revealed a correlation coefficient of r = 0.112, with a P value of 0.170, which aligned with findings from a study in Bahirdar, Ethiopia[19].

This study found that 15.1% of patients reported mild side effects associated with triple therapy for H. pylori eradication. This rate was lower than that reported in a Cochrane review (33.5%) and a study conducted in Bahirdar, Ethiopia (26.1%)[19,62].

H. pylori is classified as a Group 1 carcinogen by the WHO and is associated with an elevated risk of gastric cancer[63,64]. H. pylori infection is a significant risk factor for gastric cancer, potentially contributing to over 80% of cases[65,66].

This highlights the importance of implementing effective public health measures to decrease the prevalence of this infection[67]. Clinical evidence indicates that H. pylori infection is associated with increased mortality in gastric cancer patients[68]. Conversely, eradicating H. pylori has been shown to reduce mortality rates in this population[69]. A study by Ou et al[70] found that H. pylori infection can induce gastric cancer cell migration by altering gene expression in cell movement, immune response, and drug resistance[70].

Numerous small single-arm trials and larger retrospective studies have investigated H. pylori eradication therapy for treating gastric extranodal marginal zone lymphoma. However, comparing these trials is challenging due to the lack of consensus on response evaluation criteria and the definition of complete response (CR). Nearly all patients succeeded in eradicating H. pylori infection; however, around 20% required a second course of H. pylori-directed therapy. Histologic CR was attained in 50% to 83% of patients. The median time from H. pylori eradication to CR was 15 months, with a range extending from 5 months to over 3 years[71-79]. We suggest the following methods to improve H. pylori eradication rates in resource-limited settings.

Patient education

Provide clear and concise information about the infection, treatment regimen, and potential side effects. Use simple language and visual aids to enhance understanding. Address concerns and misconceptions about the treatment.

Regular follow-up

Schedule regular follow-up visits to monitor adherence and address issues or concerns. Use mobile health technologies for remote monitoring and reminders.

Involving community health workers

Involve community health workers to support and educate patients, especially in rural areas. They can help with medication administration, symptom monitoring, and adherence counseling.

Addressing socioeconomic barriers

To reduce barriers to treatment, provide financial assistance or subsidies for medication costs. Implement programs to improve access to healthcare facilities, especially in rural areas.

Addressing lifestyle factors

Educate patients about the impact of smoking and alcohol consumption on H. pylori infection and treatment outcomes. Encourage lifestyle modifications to improve overall health.

This was a prospective study addressing public health problems. The other strength of this study is that it was conducted in multiple healthcare centers. However, there were some limitations. The sample size was relatively small, which might limit the generalizability of the findings. Additionally, the results of previous H. pylori treatment and alcohol consumption were not accessed in detail. Furthermore, the study did not assess antimicrobial susceptibility and resistance patterns due to financial constraints. The lack of antimicrobial susceptibility testing makes recommending appropriate regimens in this population difficult, leading to treatment failure and increased healthcare costs. We believe a study addressing local antimicrobial susceptibility patterns is needed to address eradication failure, especially considering the last study, which assessed H. pylori susceptibility, was conducted in 2004. The other limitation of this study is the study period is limited due to financial and manpower constraints, this might affect the study due to seasonal variations of H. pylori prevalence[80]. To address this matter, we recommend future research be conducted in a more extensive time frame.

CONCLUSION

This study found a lower eradication rate of H. pylori than previous studies, falling within a borderline range for clinical significance. This suggests that the therapy may not be as effective as expected. Prior diagnosis of H. pylori infection, alcohol consumption, and smoking habits were all associated with failure of H. pylori eradication. Conversely, post-treatment symptom resolution was significantly related to successful eradication. Interestingly, while the use of traditional homemade remedies during triple therapy did not improve eradication rates, it might be linked to a reduction in adverse drug side effects. We believe this study provides valuable insights that can guide the development of tailored first-line regimens for H. pylori eradication in Ethiopia using the following methods. Prioritize antibiotic susceptibility testing: Implementing routine antibiotic susceptibility testing (AST) for H. pylori isolates can help identify the most effective antibiotics and inform treatment decisions. This approach can optimize treatment outcomes and minimize the development of further resistance. Consider tailored treatment regimens: Based on AST results, tailored treatment regimens can be developed. For example, if clarithromycin resistance is prevalent, alternative regimens like bismuth-based quadruple therapy or levofloxacin-based triple therapy can be considered. This personalized approach can improve eradication rates and reduce the risk of treatment failure. Regular surveillance of H. pylori resistance: Continuous surveillance of H. pylori resistance patterns is essential to tracking changes over time and informing updates to treatment guidelines. This can help ensure the ongoing effectiveness of H. pylori eradication therapies. Tests for cure and monitoring for symptomatic improvement should be incorporated into routine care to confirm eradication. Incorporating this into routine practice will be important to decide on the next management step for those who didn’t achieve eradication, such as stepping up to quadruple therapy or testing for antimicrobial susceptibility.