Indonesia and Malaysia have low prevalence of H. pylori infection and low gastric cancer incidence

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Abstract​

Helicobacterpylori infects more than half the human population. However, the prevalence in Indonesia is low, as is the prevalence of gastric cancer. Hence, it could be instructive to compare these prevalence rates and their determining factors with those of countries that have high gastric cancer incidence. Ethnicity and genetic characteristics of H. pylori are important determinants of the H. pylori infection rate in Indonesia. The infection rate is higher in Bataknese, Papuans and Buginese than in Javanese, the predominant ethnic group. Ethnicity is also an important determinant of the genetic characteristics of H. pylori. Analysis of CagA in the EPIYA segment showed that the predominant genotypes in Papuans, Bataknese and Buginese are ABB-, ABD- and ABC-type CagA, respectively. Meanwhile, in the countries with high gastric cancer incidence, almost all strains had East Asian type CagA. An antibiotic susceptibility evaluation showed that the standard triple therapy can still be used with caution in several cities. There is a very high rate of resistance to second-line regimens such as levofloxacin and metronidazole. Recent studies have shown that furazolidone, rifabutin and sitafloxacin are potential alternative treatments for antibiotic-resistant H. pylori infection in Indonesia. Rather than focusing on early detection and eradication as in countries with high gastric cancer prevalence, countries with low gastric cancer prevalence should focus on screening the several groups that have a high risk of gastric cancer. (Gut Liver 2021;15:-665)

 

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INTRODUCTION​

Helicobacterpylori is the most successful human pathogen and is associated with dyspepsia. It is also a common and curable cause of peptic ulcers and gastric cancer.1-3 The infection prevalence was high is many areas such as in Africa and East Asia which reported as 79.1% and 56.1% respectively.4 Despite their high prevalence, the gastric cancer incidence was varied. East Asian region has high age-standardized rates (ASR) of 22.4 and its countries Korea, Mongolia, and Japan were known for the highest gastric cancer incidence in the world with the ASR of 39.6, 33.1, 27.5, respectively.5 However, the African region has very low ASR; 4.2 per 100,000 people. On contrary, there was also region that have both low prevalence of H. pylori infection and low incidence of gastric cancer; such as a populous archipelago country, Indonesia. The investigation on this low prevalence either infection and gastric cancer incidence is also necessary as a comparison to find the risk factor and H. pylori properties that may contributes to infection and gastric cancer pathogenesis.

Indonesia is the fourth most populous country in the world, with 267,842,296 people belonging to 300 ethnic groups in a total area of about 1,900,000 km2. Based on GLOBOCAN 2018, Indonesia was categorized as a low gastric cancer risk country with ASR of 1.22/100,000 (gco.iarc.fr).6 Our neighbor country, Malaysia was also reported to have low prevalence of H. pyloriinfection and low gastric cancer incidence (ASR of 5.2). Study in Malaysia reported that ethnicity play role in the H. pylori infection and gastric cancer and Malay ethnic is reported as low risk for gastric cancer compared to Chinese and Indian. Malay ethnic is also one of a large ethnic group in Indonesia. Indonesian’s Malayan descent have low gastric mucosal severity,7,8similar to that among Malayans in Malaysia and Singapore.9,10 Moreover, Indonesia consists of more ethnics that may provide more insight on the role of ethnicity and other factors.

 

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H. pylori can damage epithelial cells and induce an inflammatory response, resulting in severe histopathology, suggesting that H. pylori should be eradicated even in populations with a low prevalence of H. pylori.11 Detecting the presence of H. pylori is critically important, and validation of the tests for H. pylori is required, especially in areas with a low prevalence of H. pylori.12 In Indonesia, urine tests have been validated with sensitivity of 83.3% and specificity of 94.7%, and serological tests have been validated with sensitivity of 86.7% and specificity of 96.8%.13 Validation of the noninvasive urea breath test and stool antigen test is still required. Gastrointestinal endoscopy has limited availability and is predominantly utilized on Java Island, and it is not fully covered by health insurance.14 Invasive detection of H. pylori infection in Indonesia is still an unfavourable choice.

In this review, we provided the current status of H. pylori in low risk gastric cancer country about what factor differentiating to those with high incidence of gastric cancer, including prevalence and its risk factors, H. pylori associated diseases, virulence factors and the antibiotic resistance, with some proposed recommendations.

 

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PREVALENCE AND RISK FACTORS OF H. PYLORIINFECTION​

In general, the prevalence of H. pyloriinfection is more than 90% in peptic ulcer patients who are not using nonsteroidal anti-inflammatory drugs15 and 20% to 40% among patients with functional dyspepsia according to various diagnostic methods.16 In six studies of dyspeptic patients in Indonesia, the prevalence of H. pylori infection varied from 5.7% to 68%.17-19 The highest prevalence was found in Jakarta using the rapid urease test, culture and histology.20 The results of the urea breath test varied but usually found a low prevalence of H. pylori infection, from 0% to 11.2%.18,19,21 We found several reasons for these inconsistent results, including the accuracy of each H. pylori test, differences between location of the biopsy, differences between pathologists and variation in the evaluation criteria.22 Furthermore, most of these studies were conducted in the region where Javanese was the predominant ethnicity.

To clarify the reasons for these inconsistent results, our study in Surabaya, Java Island applied five different methods to detect H. pylori infection: culture, histology, immunohistochemistry, rapid urease test and urine antibody test and found that the prevalence of H. pylori infection was low (11.5%) based on at least one positive result among those five tests.22 We then expanded the study to include 849 patients from the five largest islands representing at least 13 ethnic groups. The prevalence was still considerably low with only 10.4% (Table 1).23,24 In contrast with neighboring countries such as Thailand and the Philippines, with prevalence rates of 76.1% and 60%, respectively,25,26 we found a low prevalence of 22.1%.27 Another survey in North Sulawesi province using urine tests in 251 adult patients of predominantly Minahasanese and Mongondownese ethnicity detected H. pylori in only 14.3% of subjects. A prevalence of H. pylori infection of only 3.8% was reported in a population of children in North Sulawesi, Indonesia.28

 

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The prevalence of H. pylori infection in Indonesia was generally low, in concordant with Malaysia and Singapore but in contrast with several other areas in Southeast Asia such as Vietnam or Thailand. Thus, epidemiology of H. pylori infection can be varied among regions.29 This low prevalence of H. pylori may be correlated with the low gastric cancer incidence in Indonesia. East Asian country such as Korea and Japan reported a high ASR of gastric cancer and also showed a high H. pylori infection prevalence; 54.0% and 51.4 % respectively (Table 2),4,5,8,23,27,30-37 even in some cases there were some probability to be infected with non-H. pylori organism.38These phenomena may support the role of H. pylori in the gastric cancer pathogenesis.

 

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A collaborative study among South Asian countries reported that host genetic susceptibility, genetic diversity of H. pylori and environmental factors were associated with H. pylori infection.39-41 Several habits may significantly increase H. pylori prevalence, such as eating food with fingers, rarely washing hands before eating, eating cucumbers more than once a week and drinking alcohol.42 Other risk factors, such as salary, source of water, type of latrine, history of medicine intake, religion, and smoking were associated with the prevalence of H. pylori infection in Indonesia.27 The most important factors related to the risk of H. pylori infection are differences in ethnicity and geographical areas in Indonesia. For example, we showed that, after adjustment for age and sex, the risk of H. pylori infection in people of Papuan, Batak, and Buginese ethnicity was 30.57-, 28.39- and 23.23-fold, respectively, higher than that in Javanese. Moreover, the prevalence of H. pyloriinfection among young people of these ethnic groups was higher than that among Javanese of the same age group.27

 

[syed putra]

Just eat properly well cooked meat. No fast chop chop wu hei half cooked meat.