Success of 14-day triple and quadruple therapy for the control of Helicobacter pylori infections in Kohat district

Introduction

Helicobacter pylori is a Gram negative, microaerophilic bacteria that is very common, infecting more than half of the world’s population (1). H. pylori infection can cause gastric inflammation, peptic ulcer, intestinal metaplasia and can lead to gastric cancer (2,3). Its urease activity, flagella mobility, adhesive proteins and S-shape help to colonize the human stomach and initiate infection (4). Besides these, the cagA and vacA genes are the major virulence factors in H. pylori, responsible for the gastric pathology. The cagA gene is responsible for peptic ulcer disease and adenocarcinoma, while the vagA gene causes injury to gastric epithelium (5,6). Its invasiveness in the human stomach instigates mucosal and systemic immune responses in the infected host but it has acquired some mechanism that can evade host responses (7).

H. pylori infection rates vary by geographic location, age, ethnicity and socioeconomic status of population (8). It has been documented that infection rates are higher in poor socioeconomic conditions, particularly in developing countries (9). Its transmission takes place in different ways. Most common routes of transmission are iatrogenic, feco-oral and person-to-person contact (10,11). Along with this, contaminated food and water may be a source of infection (12).

Different strategies have been adopted for its treatment. Commonly and most acceptable treatment therapies are triple and quadruple therapy (13,14). In recent era due to the emergence of antibiotic resistance, its success has declined. Antibiotic resistance to H. pylori is considered the major cause of the eradication failure (15,16). One of the most enduring debates in the world is the optimal duration of therapy for its eradication (17).

The incidence of H. pylori eradication failure and antibiotic resistance has been documented worldwide. In Pakistan, the rate of H. pylori is very high due to lack of proper diagnosis of dyspepsia and the over-the-counter use of inappropriate doses of proton pump inhibitors (PPIs). In our population of the District of Kohat, the rate of H. pylori infection is increasing day by day, and it is yet to find factors that lead to eruption of resistance. Therefore, keeping in view the existence data regarding its resistance and treatment failure of H. pylori infection, the study was conducted to determine the incidence of H. pylori infection and its response to different regimen of eradication in Kohat district. The aim of the study was to recognize the best treatment regimen for the eradication of H. pylori.

Methods

This study was conducted at the District Headquarters Hospital Kohat and Kohat University of Science and Technology, from April 2021 to December 2021. It was approved by the University Ethical Committee and written consent was taken from all patients. Only positive cases were considered in this study for further analysis.

Results

In total there were 178 patients positive for H. pylori infection; there were 38.76% (n = 69) female and 61.23% (n = 109) male positive cases. Among the total, there were high numbers of positivity (n = 82; 46.06%) in patients aged below 30 years, while the number of positive patients in group aged 30-50 years is 38.76% (n = 69) and in that of above 50 years is 15.16% (n = 27). Of the 178 patients, 71.91% (n = 128) were living in the rural area while 28.08% (n = 50) were living in the urban area. According to the above results, high numbers of the patients were living in the rural area and only a small number of patients were living in the urban areas. The demographic information and characteristic of the suspected patients are shown in Table I.

Gastrointestinal symptoms were almost similar in all the patients, but there were high numbers of patients who complained of epigastric pain and recurrent abdominal pain; all the patients showed more than one symptom as mentioned in Table II.

The hematological parameters of H. pylori patients included (n = 52) H. pylori positive patients whose hematological values were compared with H. pylori negative control group (n = 52). It showed that the hemoglobin level was low in the positive patients. Comparing platelets and neutrophile, it was increased in the infected patients as shown in Table III.

The above results show the eradication percentage of each given regimen in which 100 patients were given MEL, out of whom 88 (88%) patients showed successful eradication (Fig. 1). MRL was given to 53 patients, of whom 40 patients recovered, exhibiting 75.47% eradication percentage. The bismuth-based quadruple therapy (MELB) was given to 25 patients, of whom 21 (84%) patients showed successful eradication after 14 days of therapy, as shown in Table IV.

Discussion

H. pylori infection is the most common bacterial infection in the world, infecting about half of the world’s population. This infection is more common in areas where there are poor hygienic conditions such as use of contaminated food and water. This bacterium is mainly transmitted by feco-oral route from the fecal contaminated water. The oral-oral route is also the leading cause of the infection, as few authentic studies have cultured H. pylori from the oral cavity (21); the oral-oral transmission has been examined in the eating of premasticated food, the use of the same spoon by mother and children (22). Various diagnostic methods have been identified for the detection of H. pylori but the choice usually depends on the sampling and condition of the patient. In this study, the stool antigen test has been used for the diagnosis of H. pylori as stool antigen test is noninvasive and rapid for the detection of H. pylori infection (23).

H. pylori analysis included 178 positive patients in this study in which most of the patients were less than 30 years of age. One of the studies in Egypt included 89 asymptomatic young patients, out of whom 78 were positive for H. pylori antigen, all aged below 30 years (24). A total of 128 patients out of 178 belonged to the rural areas, exhibiting high percentage because of the poor hygienic conditions of the people living in the rural areas. Most authentic studies have also shown that most of the H. pylori positive patients were from rural areas, where the environment was not hygienic. Similarly, one of the studies in Venezuela revealed that H. pylori in the rural population was found in 87.2% (34/39) of the patients (25). H. pylori is associated with a number of symptoms that are still in debate. In this study, all the patients complained of gastrointestinal symptoms, but there were high number of patients who complained about epigastric pain and recurrent abdominal pain. The main reason behind this is the hyperacidity during peptic ulcer. Primarily, gastrin and oxyntic gland are responsible for the production of more acid during H. pylori infection that can lead to epigastric pain (26).

In this study, we found abnormalities in some of the hematological parameters of H. pylori positive patients when compared to the control group. The hemoglobin level is quite lower than the control group, while the platelets and neutrophil level remarkably increased. This may be due to the inflammatory conditions and immune response to H. pylori.

Eradication of H. pylori needs combinations of drug treatment with adjuvant regimen that increase antibiotic activity and host responses. The duration of therapy also strongly affects the eradication of H. pylori. One of the studies in the United States was based on the duration of therapy of H. pylori, which shows that RAC (Rabeprazole, Amoxicillin, and Clarithromycin) treatment of 7 days and 10 days had a higher percentage of eradication than the 3-day treatment (27). Similarly, a study in Turkey based on levofloxacin triple therapy in which MEL was given to 92 patients showed 95.5% positive response toward MEL combination. In this study, each patient was given 14 days treatment of PPI base triple and quadruple therapy, which show that MEL had a high percentage of eradication (88/100; 88%) followed by MELB (21/25; 84%). MEL and MRL are the same triple therapy with two different PPIs (Tab. V). The reason for changing one PPI to another was that some of the patients in either group were already using that drug with the same name, so for patient satisfaction, psychologically, we changed the drug. Another reason is some of the studies showed better results with rabeprazole than esomeprazole (28).

Conclusion

This study concludes that there were high numbers of positive patients aged below 30 years in which many patients were from rural area, and according to this study MEL is the most effective treatment regimen for the eradication of H. pylori. This study recommends that clinicians may suggest MEL treatment for H. pylori positive patients for complete eradication of H. pylori.

Disclosures

Financial support: This study was part of the basic research with a focus on patients’ treatment and was mainly supported and conducted at District Headquarters Hospital Kohat, Pakistan. We extend our gratitude to the Department of Microbiology, Kohat University of Science and Technology, for providing lab facilities and supporting this research.

Conflict of interest: The authors declare that they have no conflict of interests.

Authors’ contribution: Syed Fahim Shah and Sohail Aziz Paracha conducted the experiments; Somaid iqbal helped in editing the manuscript and in conducting experimentations; Sadar Zaman, Mudassir Hussain, Hafeez Ullah and Iqbal Muhammad helped in sample collection; Aisha Gul helped in experimentations; and Waheed Ullah designed the project and wrote the manuscript.