Prevalence, diagnosis and treatment of Helicobacter pylori infection in Nigeria

Stella I Smith; Abraham Ajayi; Tolulope F Jolaiya; Utibeima Essiet

doi:10.4103/njgh.njgh_10_22

REVIEW ARTICLES

Year : 2022 | Volume : 14 | Issue : 1 | Page : 2-10

Prevalence, diagnosis and treatment of Helicobacter pylori infection in Nigeria

Stella I Smith¹, Abraham Ajayi¹, Tolulope F Jolaiya², Utibeima Essiet¹
¹ Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Yaba, Nigeria
² Lagos State, Ministry of Health, Lagos, Nigeria

Date of Submission	19-May-2022
Date of Acceptance	17-Jun-2022
Date of Web Publication	21-Jul-2022

Correspondence Address:
Stella I Smith
Department of Molecular Biology and Biotechnology, Nigerian Institute of Medical Research, Yaba, Lagos
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njgh.njgh_10_22

Abstract

Helicobacter pylori infection remains a major health concern around the world as untreated infection can lead to gastric cancer. The burden of H. pylori infection in Nigeria is high (87.7%) with the northern part of the country having a higher prevalence compared to other regions of the country. Methods comprising invasive and non-invasive approach are widely used around the country for the diagnosis of H. pylori infection. However, data on use of culture which gives the advantage of antimicrobial susceptibility testing is limited. Treatment and management of H. pylori in Nigeria is becoming difficult as the rate of resistance to antibiotics is on the rise. This review highlights key findings on the incidence, diagnosis and treatment of H. pylori infection in Nigeria.

Keywords: Diagnosis, Helicobacter pylori, Nigeria, prevalence, treatment

How to cite this article:
Smith SI, Ajayi A, Jolaiya TF, Essiet U. Prevalence, diagnosis and treatment of Helicobacter pylori infection in Nigeria. Niger J Gastroenterol Hepatol 2022;14:2-10

How to cite this URL:
Smith SI, Ajayi A, Jolaiya TF, Essiet U. Prevalence, diagnosis and treatment of Helicobacter pylori infection in Nigeria. Niger J Gastroenterol Hepatol [serial online] 2022 [cited 2023 Mar 21];14:2-10. Available from: https://www.njghonweb.org/text.asp?2022/14/1/2/351550

Key Messages: Helicobacter pylori diagnosis in Nigeria started with serology tests and progressed to culture technique (although culture technique is not commonly done in Nigeria) and finally Urea Breath Test (UBT) which is a more current technique for H. pylori diagnosis. Treatment failure/lack of appropriate drugs for H. pylori eradication is a problem and therefore randomized control trials and other means of H. pylori eradication through the use of should be investigated.

Introduction

The burden of Helicobacter pylori infection globally estimated at 50% of the world’s population undoubtedly makes the organism a pathogen of concern coupled with its classification as group I carcinogen by the World Health Organization (WHO).^[1],[2]Helicobacter pylori is a gram-negative, helical, microaerophilic bacterium that colonizes the gut.^[1]Helicobacter pylori has been implicated in various gastric disorders including peptic ulcer disease (PUD), gastritis, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma.^[3] In Nigeria, the prevalence of H. pylori is high with an estimated 87.7% prevalence rate. Most infected individuals (>80%) have asymptomatic chronic gastritis and only a minority eventually develop PUD or gastric malignancies.^[4] In the study of Palamides et al.,^[5] gastric erosion and ulcers were found in 43.6% and 15.4% of Nigerian patients compared to 4% and 9.3% of South African patients, respectively. In the same study, 2.6% of Nigerian patients were reported to have gastric cancer resulting from H. pylori infection. Beyond the high prevalence of H. pylori infection and its associated clinical outcomes, emerging high antimicrobial resistance in Nigeria poses grave danger to the effective treatment and eradication of the pathogen.^[6] There is therefore need to aggregate data on incidence, diagnosis, and treatment of H. pylori in Nigeria with the view to highlighting areas for which focus is needed in terms of research, policy formulation, treatment, and management of H. pylori infection in the country.

PREVALENCE OF HELICOBACTER PYLORI IN NIGERIA

Several studies have reported the prevalence of H. pylori infection in Nigeria over time with differences in demography, age groups, occupation, gender, marital status, level of education, and disease condition across the country. The Northern part of the country is shown to have the highest prevalence of H. pylori infection. A study conducted by Ishaleku and Ihiabe,^[7] and Oti et al.^[8] in Keffi, Nasarawa State, North Central Nigeria, reported high prevalence ((56.3%) and (56.3%), respectively, and found association of H. pylori infection with gender, age, type of infection (symptomatic or asymptomatic seropositive infection) age and alcohol consumption among patients. However, Kolawole et al.^[9] in their study conducted on students of Bingham University, Karu in North-Central Nigeria observed a very low (5.5%) seroprevalence of H. pylori infection of which 5.5% comprised female students. Their study had no association of H. pylori infection between age and gender but attributed the low prevalence of H. pylori infection to good knowledge of H. pylori infection as well as a good standard of living among the studied subjects.

Kumurya,^[10] in a study conducted on patients presenting with gastric symptom in Kano, Northwest, Nigeria, reported a markedly high infection rate (96%) in individuals between 40 and 50 years old but stated no significant difference between men and women in seropositivity to H. pylori. In Sokoto, North-West, Nigeria, Jadda et al.^[11] and Saidu et al.^[12] in their individual studies reported 78.9% and 56.8% prevalence rates of H. pylori infection among students of Sultan Abdurrahaman School of Health Technology Gwadabawa and adults in Sokoto Metropolis, respectively. They observed a higher frequency of infection in females compared to males and an even higher frequency in married subjects than singles. Association between abdominal pains and ulcers was found in H. pylori-infected subjects. A similar study was conducted among dyspeptic patients in Damaturu, Yobe, North East, Nigeria by Gide et al.^[13] revealed an overall high (51.96%) prevalence of H. pylori infection in studied subjects with the highest infection rate of 69.23% and 61.79% among patients between the ages of 50 and 59 years and male gender, respectively.

In South-South Nigeria, Omosor et al.^[14] reported a 52% H. pylori infection rate among asymptomatic patients in Delta State, and reported no association of H. pylori infection with age as well as gender. In contrast, Ayodele et al.^[15] reported a low (19.6%) prevalence of H. pylori infection among patients in Port Harcourt. Owowo et al.^[16] also reported low (29.7%) prevalence of H. pylori infection among internally displaced people between the ages of 5 to 75 years in Uyo, Akwa Ibom State with female subjects between the age group of 5 and 14 years having the highest (20%) and (17.6%) infection rates, respectively. Their study found an association of H. pylori infection with occupation and identified alcohol consumption and smoking as risk factors. On the contrary, studies conducted on students of Babcock University in Ogun State South-West, Nigeria by Enitan et al.^[17] reported a low (23.5%) prevalence rate of H. pylori infection and indicated an association of infection with gender and age. However, among patients presenting with duodenal ulcer-associated symptoms in Lagos, South West, Nigeria, a higher (80%) prevalence rate of H. pylori infection was reported by Ajayi et al.^[18] The variation in the prevalence of H. pylori infection could be attributed to low standard of living, poor personal hygiene, overcrowding, level of education attained, lifestyle, and poverty.

Among dyspeptic patients in Calabar, Cross River State, Kooffreh-Ada et al.^[19] reported a moderate (42.1%) prevalence of H. pylori infection. Their study revealed a high prevalence rate of H. pylori infection within the ages of 40 to 60 years but showed no relationship of H. pylori infection with the sex of the patients.

In a study at the Nnamdi Azikiwe University, Anambra, South-East Nigeria, the seroprevalence of H. pylori was 51.4% amongst peptic ulcer patients within the age group 24–35 years and predominantly female.^[20] Although there was no relationship between gender and source of drinking water in their study, age was found to be an associated risk factor for H. pylori infection among individuals with peptic ulceration. In a similar study conducted in Aba, Abia State, South East, Nigeria, Ibebuike et al.^[21] reported a relatively high (60.63%) and low (39.37%) prevalence of H. pylori infection among bleeding and non-bleeding peptic ulcer with poor personal hygiene and low standard of living attributed to observed prevalence.

The prevalence of H. pylori infection among the pediatric class (age one to 18) seen at a tertiary hospital in South-East, Nigeria, revealed a relatively high (36.3%) seroprevalence of H. pylori infection within the ages of 6–12 years with the concomitant association of age of the subjects, parental education, social class, ingestion of uncooked/ raw food materials and H. pylori infection (P < 0.05). In Uyo, Akwa Ibom State, similar findings of 30.9% seroprevalence of H. pylori infection were reported by Etukudo et al.^[22] among children within the age range of 0.5 to15 years with a peak prevalence of 40.7% for the 6 to 10 years age group. Their study showed an association of H. pylori infection with personal hygiene, source of drinking water, household overcrowding, and type of toilet used. However, the study of Olufemi et al.^[23] in Lagos, South-West Nigeria revealed a high (68.7%) seroprevalence of H. pylori in children, respectively, with high frequency of H. pylori infection within the ages 11 to 13 years. Their study established the association of H. pylori infection with overcrowding, water-borne infections and poor sanitary practices. In the study of Smith et al.,^[24] crowded living conditions among families with a history of ulcer/gastritis were significantly associated with H. pylori. However, other factors including level of education, occupation, drinking and smoking habits, and source of drinking water were not associated with H. pylori infection.

From the foregoing, Northern and Southwest Nigeria have a higher prevalence of H. pylori infection when compared to other regions with an increased infection rate in females. The prevalence rate of H. pylori infection in Nigeria has in some cases been associated with several risk factors including low socioeconomic status, poor personal hygiene, poor environmental hygiene, lack of availability of treated water, household overcrowding, alcoholic drink addiction, cigarette smoking, and poor knowledge of H. pylori infection. Obviously, the alleviation of poverty would help control the infection. The provision of basic amenities such as treated water supply, adequate waste disposal system as well as sensitization on the transmission of H. pylori infection and its long-term consequences will help to curb the increasing infection rate of H. pylori infection in Nigeria.

DIAGNOSIS OF HELICOBACTER PYLORI IN NIGERIA

Considering the high prevalence of H. pylori in Nigeria, the need for accurate primary diagnosis, management or monitoring of eradication process is apt.^[4],[25] Methods for the diagnosis of H. pylori have been broadly divided into invasive and non-invasive methods. Endoscopic imaging, histology, rapid urease test (RUT), and culture are invasive methods, whereas urea breath test (UBT), serology and stool antigen test (SAT) are non-invasive methods.^[26] Molecular approaches such as the use of conventional and quantitative polymerase chain reaction (PCR) targeting H. pylori DNA in stool or biopsy samples are also diagnostic methods for H. pylori with high sensitivity and specificity.^[27] The aforementioned diagnostic methods have found their use in the diagnosis of H. pylori in different health facilities and settings in Nigeria as shown in [Table 1].

Table 1: Invasive and noninvasive diagnostic methods reported by various studies in Nigeria

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Although endoscopy comes with its discomfort and other drawbacks such as cost, availability of facilities, and expertise, it remains a pivotal method in the diagnosis of H. pylori.^[48] The procedure enables biopsies to be collected majorly from the antrum and corpus of the stomach which are needed for Rapid Urease Test (RUT) and culture of H. pylori. Furthermore, endoscopy provides specific gastric mucosal features that could infer or be associated with H. pylori infection.^[49]

One of the gold standards for H. pylori diagnosis is histology. Histological assessment is based on the updated Sydney System, which provides information on H. pylori (direct visualization), degree of active and chronic inflammation. Histology is essential in the diagnosis of H. pylori. It has the advantage of providing the extent of inflammation and associated conditions such as intestinal metaplasia, atrophic gastritis, and gastric cancer.^[50] RUT that explores the copious urease-producing ability of H. pylori has been found useful in the primary diagnosis of H. pylori but not recommended for use in the assessment of eradication after treatment.^[25] Culture has been considered as a gold standard in H. pylori diagnosis. However, culture of H. pylori is expensive because it requires trained hands, special culture media with supplements, and other materials to facilitate growth.^[5],[49] Culture of H. pylori has the advantages of enabling susceptibility testing and evaluation of the virulence or other genetic features of H. pylori isolates.^[45],[46]

Although considered inferior to monoclonal Stool Antigen Test (SAT) and UBT, serology in the diagnosis of H. pylori is useful for epidemiologic studies on H. pylori infection. It does not differentiate between active and past infections and so cannot be used for further studies such as antimicrobial susceptibility testing.^[26],[48] Several, studies in Nigeria have reported the use of serology in the detection of H. pylori infection in both children and adults [Table 1].

UBT has proven to be a highly accurate noninvasive method for the diagnosis of H. pylori infection and adequate for assessing eradication of the pathogen after treatment.^[27] Onyekwere et al.^[41] reported the use of repeated UBT in assessing the efficacy of rabeprazole, clarithromycin, and amoxicillin H. pylori eradication therapy in patients in Lagos Nigeria. In another study in South-South and South-Western Nigeria, Smith et al.^[51] used UBT in determining the prevalence of H. pylori infection among dyspeptic patients with and without type 2 diabetes mellitus. Similarly, in a related study, Jemilohun et al.^[40] also reported the use of UBT in determining the prevalence of H. pylori among people in South-West Nigeria. A widely used inexpensive non-invasive method of diagnosing active H. pylori infection, is the SAT. As in the case of UBT, SAT is also used in evaluating effective eradication of H. pylori before and after therapy.^[52] Use of PCR in amplifying H. pylori DNA in samples for the purpose of diagnosis of H. pylori infection has been reported both in the invasive and non-invasive approaches.^[25] In terms of accuracy, sensitivity and specificity molecular methods are highly reliable but could be expensive.

Treatment

Once H. pylori is detected in a person with PUD, for instance, the usual treatment of the patient involves eradicating the organism and allowing the ulcer to heal, this is to avoid gastric cancer and life-time risk of PUD.^[53] Patients who have H. pylori infection and also have an ulcer are most likely to benefit from being treated. The treatment of patients who only have heartburn or acid reflux and H. pylori is controversial, but risk assessment and benefit of the patient in any case should be undertaken by the clinician.^[54] The choice of antibiotics for treatment is based on drug availability, local recommendation, and H. pylori resistance pattern. Previous exposure to antibiotic must be taken into consideration before treatment of the patient.

The challenges encountered in the process of H. pylori treatment and eradication include imbalance in the gut microbial community, increase in the resistance rate of H. pylori to antibiotics due to indiscriminate use, variation in treatment protocol from one location to another.^[55] Several lines of treatments have been proposed for the treatment of H. pylori infection as shown in [Table 2].

Table 2: Different regimens used for Helicobacter pylori eradication

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The standard first-line treatment (triple therapy) must be taken for 10 to 14 days, this triple therapy consists of the proton pump inhibitors with two antibiotics (a combination of clarithromycin and amoxicillin or clarithromycin and metronidazole or clarithromycin and tetracycline.^[58]

A second-line therapy includes the combination of two antibiotics (tetracycline and metronidazole), with PPI and bismuth.^[34] In a population with clarithromycin resistance (clarithromycin resistance >15–20% and quinolone resistance <10%) a quinolone containing triple therapy can be considered because of the eradication rates reported being between 72% and 96%.^[59],[60] There is insufficient data on resistance rate of fluoroquinolones in Nigeria and it is likely that levofloxacin resistance is on the rise.

If there is resistance to quinolones, a quadruple drug combination is available as third-line treatment option for H. pylori which includes a proton pump inhibitor with bismuth and two antibiotics, sometimes three antibiotics.^[58] In some other cases, proton-pump inhibitors, such as omeprazole (Prilosec), lansoprazole (Prevacid), or esomeprazole (Nexium), bismuth subsalicylate (Pepto-Bismol) are used. Low resistances have been reported with rifabutin therapy but it is not a commonly used drug combination. Once H. pylori are eradicated, the chance of being infected again is very low.^[61]

The choice for H. pylori eradication investigation is UBT and SAT (where UBT is not available and with high cost) because serology will detect both past and current infection, so it is not suitable for eradication confirmation.^[62] Most times this is not done because of the cost, but it is recommended in H. pylori-associated MALT lymphoma, ulcer, early gastric cancer resection, and recurrent dyspepsia. This should be carried out after 1–2 months after treatment completion.^[58]Helicobacter pylori gastritis is considered an infectious disease irrespective of complication and symptoms and H. pylori eradication cures gastritis as stipulated in the Maastricht V consensus guideline. Furthermore, the test and treat strategy seems to be the best bet since H. pylori is a known carcinogen.^[63] Hence, the test and treat approach is recommended for uninvestigated dyspepsia particularly in areas where there is high H. pylori prevalence and most especially in young individuals. However, when symptoms such as dysphagia, iron deficiency anemia, weight loss and overt gastrointestinal bleeding are present the test and treat strategy is not advised.^[58]

Eradication therapy has found use in delineating H. pylori-associated dyspepsia from functional dyspepsia. In the Kyoto global consensus report, it was stated that a sustained relief of symptoms for 6–12 months after eradication therapy is considered H. pylori-associated dyspepsia. On the contrary, recurrence of symptoms after eradication therapy is judged as functional dyspepsia.^[63]

FACTORS RESPONSIBLE FOR TREATMENT FAILURE IN HELICOBACTER PYLORI INFECTION

Outcome of treatment is affected by different factors such as poor patient compliance to treatment, possibly leading to emergence of resistance during treatment, duration of therapy (too short), H. pylori virulence factors, ineffective antisecretory therapy, improper drug doses, host genetic factors and antibiotics resistance pattern of the H. pylori strains.^[64]

In a study by Olokoba et al.,^[34] an increased rate of resistance to antibiotics used in the treatment for H. pylori in the southwest Nigeria was reported. The causes of resistance are diverse ranging from efflux pump inhibition, mutation, and low cell wall permeability which might have resulted in eradication failure. Different resistance strategies to antibiotics in H. pylori in Nigeria have been reported which include drug inactivation through the production of ß-lactamase, alteration of the binding sites of the target, for example, alteration of the penicillin-binding protein which is the target site of penicillin and reduced drug accumulation which is attributed to the possession of active efflux pumps which excrete toxic chemical compounds and drugs out of the cell.^{[5],[6],[45],[65]}

Onyekwere et al.,^[41] reported their study on the efficacy of first-line triple therapy using rabeprazole 20 mg, clarithromycin 500 mg and amoxicillin 1g for the treatment and eradication of H. pylori on subjects attending the endoscopic units of Lagos State University Teaching Hospital, Ikeja. A 95% improvement and 87% eradication rate were observed with no statistical significance between the ten days or seven days treatment duration.

Solomon et al.^[66] reported in Southwest Nigeria (Ekiti state) the outcome of different triple therapy combination which includes rabeprazole, amoxyl, clarithromycin group (RAC), rabeprazole, amoxyl, metronidazole (RAM), omeprazole, tinidazole, clarithromycin (OTC), rabeprazole, amoxyl, levofloxacin (RAL), rabeprazole and clarithromycin, metronidazole (RCM). It was observed that RCM had the highest eradication rate of 77.8%, RAL 53.3%, OTC 44.4%, RAM 44.4%, and RAC 30%.

In a multicenter study in Nigeria involving the southwest and the north, H. pylori isolates were subjected to four antibiotics used in the treatment of dyspeptic patients for which the susceptibility pattern showed resistance rate to metronidazole 99.1%, amoxicillin 33.3%, clarithromycin 14.4% and tetracycline 4.5%.^[46]

In another study by Bello et al.,^[29] carried out at Aminu Kano Teaching Hospital (AKTH) in Northern Nigeria on the susceptibility pattern of 109 H. pylori isolated from 302 dyspeptic subjects. The 109 isolates were subjected to about eight different antibiotics (tetracycline, amoxicillin, levofloxacin, clarithromycin, metronidazole, ciprofloxacin, tinidazole, and cefuroxime) using the disc diffusion method. Levofloxacin and clarithromycin were highly susceptible with 0% resistance, but tetracycline, cefuroxime, metronidazole, ciprofloxacin, tinidazole, and amoxicillin were highly resistant at the rate of 100%, 100%, 100%, 100%, 100%, and 90.8%, respectively. The inconsistency in the resistance pattern was reported to be due to the administration of over-the-counter drugs without prescription, local antibiotic prescription practice and antimicrobial susceptibility testing method used.^[46] Although, the recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) stipulate E-test and minimum inhibitory concentration (MIC) breakpoints, Tangx et al.^[67] showed the cost-effectiveness and comparability of the disk diffusion test for H. pylori.

The cheapness and availability of ampicillin and amoxicillin in oral forms may explain the high rate of abuse of these antibiotics.^[68] At the moment, the recommendation has been made to replace amoxicillin with levofloxacin in the triple therapy used for H. pylori eradication in Nigeria.^[29] A study in Nigeria also reported a higher risk of H. pylori in subjects with indiscriminate use of antibiotics.^[24]

Palamides et al.,^[5] recommended a change in treatment protocol after carrying out susceptibility testing on H. pylori isolates from 23 subjects from Nigeria, the resistance rate for metronidazole was 100%, tetracycline was 13%, clarithromycin was 28% and about one-third of the isolates are resistant to amoxicillin.

Sugano et al.^[63] recommended that in the choice of eradication therapy, regimen with ≥ 90% eradication rate should be chosen in that region or population for treatment. From the data available from Nigeria,^[41],[66] the eradication rate was below 90% [Table 3], which means that intense research is still needed in studying new therapeutic combinations in addition to bismuth salts and proton-pump which will be more effective in the eradication of H. pylori. Such antibiotics may include rifampicin, levofloxacin, doxycycline, rifaximin, and furazolidone-based therapies. Other drugs recommended are lactoferrin-based drugs which need further research.^[34] There is an indication to review the current H. pylori antibiotic combination therapy in Nigeria. Since there is limited data, the need for randomized control trials on the different drug regimens that could give at least a 90% eradication rate is important.

Table 3: Combination of antibiotics used in the treatment of Helicobacter pylori infection in Nigeria and their eradication rates

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THE ROLE OF HERBS AND PROBIOTICS IN THE TREATMENT OF HELICOBACTER PYLORI IN NIGERIA

The use of herbs for the treatment of H. pylori remains controversial because of the non-availability of data, appropriate dosage non-standardised length of therapy and formulations. However, Smith et al.,^[69] 2003 investigated the antibacterial activity of C. papaya and M. lucida, 80% of the H. pylori were susceptible to the ethanolic extracted herbs with inhibition zones ranging from 5 to 20 mm. Their results suggested these two herbs could be used in the future for the treatment of ulcer and gastritis in Nigeria.

Although the use of probiotics in combination with other treatment regimens in the treatment and eradication of H. pylori infection is gaining ground, there seem to be no data available in Nigeria. A recent randomized control trial, reported the combined mixture of probiotics with Saccharomyces boulardii (SB) to modestly increase eradication efficacy while reducing side effects in Greece.^[70] Similarly in another study, the use of only SB in combination with quadruple therapy for H. pylori eradication was found to have only reduced side effects and not enhance eradication.^[71]

Conclusion

Helicobacter pylori infection is prevalent in Nigeria with increasing rates of resistance to antibiotics. Surveillance in the area of epidemiological studies, treatment, and eradication evaluation should be emphasized. More sensitive and specific diagnostic procedures such as UBT and culture should be advocated to facilitate prompt diagnosis and effective treatment of H. pylori infection in Nigeria. Community-based studies are advocated to capture the actual prevalence of H. pylori in adults in Nigeria to eliminate the bias stemming from available data predicated on hospital-based studies.

Financial support and sponsorship

Not applicable.

Conflicts of interest

There are no conflicts of interest.

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