Current situation of Helicobacter pylori infection in Indonesia

Ari F. Syam

The epidemiology of Helicobacter pylori (H. pylori) has been changing over the past decades. Indonesia was reported have a low prevalence of H. pylori infection compared to other countries in Asia. Some studies in Indonesia have evaluated that poor sanitation, age, religion, ethnicity are the risk factors for H. pylori infection. Compared to other diagnostic tests, the urine test will be reliable for the detection of H. pylori in Indonesia because it is non-invasive and low cost with high accuracy. Although we have already performed studies on the prevalence of H. pylori infection in several ethnics, we still have some questions that remain unclear regarding H. pylori infection in Indonesia. Therefore, we have a need to build a H. pylori center that provide facilities for culturing, evaluating antibiotic resistance, and obtaining the genotype information that may explain the differences in H. pylori infection among ethnic groups in Indonesia.

Keywords

current situation, Helicobacter pylori infection, prevalence, risk factor

As a developing country in Southeast Asia, Indonesia is an archipelago with a multi-ethnic society (more than 1,000 ethnic and sub-ethnic groups). The age-standardized incidence of gastric cancer in Indonesia has been reported to be 2.8/100,000, which is low compared with the one recorded among other Asian countries.1 Indonesia, with its different ethnicities, cultures, life-styles and religions, presents an appropriate model to examine the effects of migration and co-evolution on the bacteria-host interactions involved in the Helicobacter pylori (H. pylori) infection.

Until March 2013, only 313 hospitals provided gastrointestinal endoscopy services in Indonesia. Although these hospitals were distributed in 33 provinces in the country, 72% (98/136) of them were located on Java island.2 This uneven distribution makes it difficult for our physicians to establish a diagnosis of H. pylori.

The epidemiology of H. pylori has been changing over the past decades, with a decrease in the prevalence of infection in most countries. The changing epidemiology of the bacterium has been associated with a decline in peptic ulcer disease and gastric cancer. A Malaysian study reported by Leow et al3 found that in the period of 1989–1990, the overall prevalence of H. pylori was 51.7%. This prevalence decreased to 30.3% in the second period, 1999–2000, and to 11.1% in the third period, 2009–2010 (p<0.001).3

Syam et al reported a prevalence of H. pylori infection of 22.1% (59/267).4 In contrast to other countries in Asia, we have a low prevalence of H. pylori infection. We attempted to identify the risk factors for H. pylori infection, but found inconsistencies in terms of locations. Hence, questions remain about H. pylori infection in Indonesia are, first, what are the risk factors for the H. pylori infection in Indonesia? And second, why does the incidence of the H. pylori infection remain low in Indonesia?

In addition to these problems, we aim to identify the best test for H. pylori screening in Indonesia.

What are the risk factors for the H. pylori infection in Indonesia?

Some studies have evaluated the risk factors for H. pylori in Indonesia. The latest study reported by Darnindro et al5 found that the incidence of H. pylori infection in patients with poor sanitation was higher compared with patients who had a good sanitation status. The lower the sanitation status, the higher the risk of H. pylori infection (OR=2.5; 95% CI=1.01–6.19; p=0.044). Furthermore, the use of public toilets can increase the spread of infection because of individual’s lack of hygienic behaviour. Also, the use of wells, especially shallow wells, as a water source increases the risk of transmission of H. pylori.5 Darnindro et al5 reported that the incidence of H. pylori infection in areas with a low clean water index was higher than in areas with a high clean water index. The lower the index, the greater the risk of H. pylori infection (OR=1.524; 95% CI=0.57–4.04; p=0.396). Darnindro et al5 also showed that 13.5% of their sample had a high crowding index, although the association between H. pylori infection and crowding did not achieve statistical significance (OR=1.2; 95% CI=0.37–4.49).5

Our study, conducted from January 2014 to February 2015, involved a total of 267 patients with dyspeptic symptoms on Java, Papua, Sulawesi, Borneo, and Sumatra islands. The patients aged 50–59 had a significantly higher H. pylori infection rate than did the 30–39-yearold group (OR=2.98; p=0.05). The Protestants had a significantly higher H. pylori infection rate than did the Catholics (OR=4.42; p=0.008). The infection rate was also significantly lower among people who used tap water as their source of drinking water compared with those who drank from wells or rivers (OR=9.67; p=0.03).4

The major ethnicities in the study of Darnindro et al5 were Javanese (45.9%), Bugis (18%), and Sundanese (15.3%). The incidence of H. pylori infection among Javanese in their study was 17.9%, whereas it was 30% among Bugis, and 29.4% among Sundanese.5 Our epidemiology study in five major islands in Indonesia yielded a similar trend.4 There were significant differences in the prevalence of H. pylori infection in terms of ethnic groups (p<0.001). The highest prevalence of H. pylori infection was found among Papuan patients: 9/21 (42.9%) tested positive for H. pylori. This compared with 28/70 (40.0%) of Batak patients, 11/30 (36.7%) of Buginese patients and just 7/54 (13.0%) of Chinese patients. There was no significant difference in the H. pylori infection rate between Surabayan Chinese (15.4%, 4/26) and Pontianak Chinese (12.5%, 3/24; P=0.93). Three Dayak patients (7.5%) were positive for H. pylori infection. The comparison of these two studies allowed us to conclude that ethnicity is one of the risk factors for H. pylori infection.4

Why does the incidence of H. pylori infection remain low in Indonesia?

The causes of the low H. pylori infection rate in Indonesia remain unknown. We would expect H. pylori infection to be as high in this country as in other developing countries, because the sanitation infrastructure remains to be constructed. Most of Indonesians still do not have direct access to clean water. Table 1 presents a summary of previous studies that examined the prevalence of H. pylori infection and gastric cancer in Indonesia. Although a number of researchers have investigated this, the results are controversial and contradictory (0–68%).6,7 This could be attributable to the different study populations and different tests used for H. pylori diagnosis.8 Moreover, most of these studies investigated only the largest ethnic group, the Javanese.6,7,9,10 In a previous study, Miftahussurur et al confirmed that the prevalence of H. pylori infection in Surabaya (Java island) was low, only 11.5%, diagnosed using five different methods.8

It is still to be expected that our geneticpolymorphism evaluation of the possibility that some ethnic groups, such as the Javanese and most of the ethnic groups in Sumatra (Acehnese, Minang, and Palembang), might have immunity against H. pylori infection. It is also possible that some diets may be useful in preventing H. pylori infection. In addition to the remaining question of why the prevalence of H. pylori is low in Indonesia, another enigma emerges: why do some ethnic groups, such as the Papuans, Bugis (South Celebes) and Batak (North Sumatra), have a high prevalence of H. pylori infection compared with other ethnicities?

What is the best tool for establishing the diagnosis of H. pylori infection in Indonesia?

We performed several studies to identify the best H. pylori diagnostic test for the Indonesian population, such as Pronto Dry, H. pylori stool antigen (HpSA), or a urine test.

In 2003–2004, we evaluated the rapid urease test (Pronto Dry) in patients with dyspepsia in several endoscopic centers in Indnesia. The study was conducted in patients with dyspepsia who underwent endoscopic examination in the endoscopic centers of several cities in Indonesia, as follows: Cipto Mangunkusumo Hospital Jakarta, Hasan Sadikin Hospital Bandung, Sardjito Hospital Yogyakarta, Soetomo Hospital Surabaya, Adam Malik Hospital Medan and Sanglah Hospital Denpasar. The study took place from January 2003 to April 2004. Out of 525 cases, 56 cases were considered H. pylori positive based on the criteria used, 39 tested positive using Pronto Dry, and 17 tested negative using Pronto Dry. The overall sensitivity and specificity of Pronto Dry were 69.7% and 95.7%, respectively. Its positive predictive value was 66.1%, its negative predictive value was 96.4% and its overall accuracy rate was 92.9%. When we calculated the sensitivity and specificity at each endoscopic center, the results varied.11

Our study evaluating the HpSA test found that the area under the receiver operating characteristic (ROC) curve was 0.722 (95% CI=0.518–0.927). Using a cut-off value of 0.274 instead of 0.16 (as recommended by the manufacturer), the sensitivity and specificity were 66.7% and 78.9%, respectively.9

To confirm the accuracy of the urine test (RAPIRUN), we compared the results of the test with histology confirmed by immunohistochenmistry (IHC) and culture. From this study, we could confirm the high accuracy of RAPIRUN, which is a rapid immunochromatographic method for the determination of anti-H. pylori IgG in urine. We found identical results between histology confirmed by IHC and culture (12/88, 13.6%). Only two samples tested positive using the urine test, but were found to be negative using the two gold-standard tests. Conversely, four samples tested negative using the urine test but were found to be positive using histology confirmed by IHC and culture. The overall sensitivity and specificity of RAPIRUN were 83.3% and 94.7%, respectively. Its positive predictive value was 71.4%, its negative predictive value was 97.3% and its overall accuracy rate was 93.2%. This urine test will be reliable for the detection of H. pylori in Indonesia.12 This result was also in agreement with a previous report from North Sulawesi which found that the results of urine tests using a similar kit were identical to those obtained using the anti-H. pylori antibody serum test.13 As a non-invasive test, the urine test is user friendly and combines low cost with high accuracy; therefore, it is the best option for measuring H. pylori status in remote areas that lack of an endoscopy system, such as much of Indonesia. This urine test can also be very useful for mass screening.

What should be done?

We have the means to establish a center dedicated to the study of H. pylori infection in Indonesia. We expect to collect samples from the five largest islands in Indonesia. We have a system to manage the samples, including their storage at -20 or -80°C. We have experience in culturing other bacteria and using them in molecular biology studies. We have already performed studies and obtained updates on the prevalence of H. pylori infection in several ethnic groups; we now need to build a H. pylori center to address the remaining unanswered questions, based on the following steps (1) providing a facility for culturing H. pylori and evaluating antibiotic resistance to H. pylori and (2) providing a facility to perform molecular biology studies and to obtain genotypic information that may partly explain the differences in H. pylori infection rates among ethnic groups in Indonesia.

1. Indonesia: Estimated age-standardized incidence and mortality rates: both sexes. [Internet] 2012 [cited 2016 Jan 20]. Available from: www. http://globocan.iarc.fr/ Pages/fact_sheets_population.aspx
2. Makmun D. Present status of endoscopy, therapeutic endoscopy and the endoscopy training system in Indonesia. Dig Endosc. 2014;26(Suppl2):2–9.
3. Leow AH, Lim YY, Liew WC, Goh KL. Time trends in upper gastrointestinal diseases and Helicobacter pylori infection in a multiracial Asian population--a 20-year experience over three time periods. Aliment Pharmacol Ther. 2016;43(7):831–7.
4. Syam AF, Miftahussurur M, Makmun D, Nusi IA, Zain LH, Zulkhairi, et al. Risk factors and prevalence of Helicobacter pylori in five largest islands of Indonesia: a preliminary study. PLoS ONE;10(11):e0140186.
5. Darnindro N, Syam AF, Fauzi A, Rumende CM. Seroprevalence and socio-demographic factors of Helicobacter pylori infection in patients with dyspepsia in Kalibaru primary health care north Jakarta. Acta Med Indones. 2015;47(4):297–303.
6. Tokudome S, Samsuria Soeripto WD, Triningsih FX, Suzuki S, Hosono A, Triono T, et al. Helicobacter pylori infection appears essential for stomach carcinogenesis: observations in Semarang, Indonesia. Cancer Sci. 2005;96(12):873–5.
7. Abdullah M, Ohtsuka H, Rani AA, Sato T, Syam AF, Fujino MA. Helicobacter pylori infection and gastropathy: a comparison between Indonesian and Japanese patients. World J Gastroenterol. 2009;15(39):4928–31.
8. Miftahussurur M, Shiota S, Suzuki R, Matsuda M, Uchida T, Kido Y, et al. Identification of Helicobacter pylori infection in symptomatic patients in Surabaya, Indonesia, using five diagnostic tests. Epidemiol Infect. 2015;143(5):986–96.
9. Syam AF, Rani AA, Abdullah M, Manan C, Makmun D, Simadibrata D, et al. Accuracy of Helicobacter pylori stool antigen for the detection of Helicobacter pylori infection in dyspeptic patients. World J Gastroenterol. 2005;11(3):386–8.
10. Saragih JB, Akbar N, Syam AF, Sirait S, Himawan S, Soetjahyo E. Incidence of Helicobacter pylori infection and gastric cancer: an 8-year hospital based study. Acta Med Indones. 2007;39(2):79–81.
11. Syam AF, Abdullah M, Rani AA, Nurdjanah S, Adi P, Djumhana A, et al. Evaluation of the use of rapid urease test: Pronto Dry to detect H. pylori in patients with dyspepsia in several cities in Indonesia. World J Gastroenterol. 2006;12(38):6216–8.
12. Syam AF, Miftahussurur M, Uwan WB, Simanjuntak D, Uchida T, Yamaoka Y. Validation of urine test for detection of Helicobacter pylori infection in Indonesian population. BioMed Res Int. 2015;2015(152823):1–6.
13. Miſtahussurur M, Tuda J, Suzuki R, Kido Y, Kawamoto F, Matsuda M, et al. Extremely low Helicobacter pylori prevalence in North Sulawesi, Indonesia, and identification of a Maori-tribe-type strain: a crosssectional study. Gut Pathog. 2014;6(42):1–8.

Copyright @ 2016 Authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are properly cited.