Sains Malaysiana 48(12)(2019): 2675–2682

http://dx.doi.org/10.17576/jsm-2019-4812-08

Helicobacter pylori Infection: Prevalence, Demographic Characteristics, Clarithromycin Resistance and Evaluation of the In-House Rapid Urease Test in Sungai Buloh Hospital, Malaysia

(Jangkitan Helicobacter pylori: Prevalens, Ciri Demografi, Kerintangan Klaritromisin dan Penilaian Ujian Pantas Urease Dalaman di Hospital Sungai Buloh, Malaysia)

NOR AKMAL MOKHTAR¹, NAJIHAN ABDUL SAMAT MUTTAQILLAH¹*, SALASAWATI HUSSIN¹, TUAN SUHAILA TUAN SOH², ZUBAIDAH ABDUL WAHAB² & MOHAMMAD SHUKRI JAHIT³

¹Department of Medical Microbiology & Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 56000 Cheras, Kuala Lumpur, Malaysia

²Department of Pathology, Sungai Buloh Hospital, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

³Department of Surgery, Sungai Buloh Hospital, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia

Diserahkan: 3 April 2019/Diterima: 23 September 2019

ABSTRACT

Helicobacter pylori infection remains an essential global research focus, and increasing clarithromycin resistance was reported to impact the efficacy of clarithromycin-based treatment regiments. The study objectives sought to understand the prevalence of H. pylori infection amongst patients from Sungai Buloh Hospital, Malaysia, its association with demographic factors, and the clarithromycin resistance rate. The in-house rapid urease test (IRUT) was also evaluated and compared to the Campylobacter-like organism (CLO) test using culture or histopathological testing as the gold standard for diagnosis. The gastric corpus biopsies of 352 patients were included, as well as their age group, gender and ethnicity. Clarithromycin susceptibility was measured using the E-test method. The overall prevalence of H. pylori infection was 15.1% (53/352). There was no significant association between the age groups, gender and ethnicity with regards to H. pylori infection. Four of the 13 viable isolates (30.8%) were clarithromycin-resistant. Although IRUT had a slightly lower specificity (94.9%) than that of the CLO test (95.9%), both tests had the same sensitivity values (81.1%). IRUT had a lower positive predictive value (74.1%) than the CLO test (78.2%) but showed a similar negative predictive value (96.5%) compared to the CLO test (96.6%). Both tests displayed a very good agreement (κ = 0.97). In conclusion, the overall prevalence of H. pylori infection in our study was generally low. The high proportion of clarithromycin-resistant isolates may not reflect the exact resistance rate due to the small number of positive cultures. Our IRUT is an acceptable alternative to the CLO test for the rapid diagnosis of H. pylori infections based on its comparable performance.

Keywords: Clarithromycin; Helicobacter pylori; rapid urease test

ABSTRAK

Jangkitan Helicobacter pylori kekal menjadi fokus penyelidikan global yang penting dan tahap kerintangan clarithromycin yang dilaporkan meningkat boleh memberi impak terhadap keberkesanan rejimen rawatan berasaskan clarithromycin. Objektif kajian ini adalah untuk mengkaji prevalens, asosiasi antara faktor demografi dan kadar kerintangan terhadap clarithromycin bagi jangkitan H. pylori dalam kalangan pesakit Hospital Sungai Buloh, Malaysia. Kami juga telah menilai dan membandingkan prestasi ujian pantas urease dalaman (IRUT) dengan ujian organisma seperti Campylobacter (CLO) menggunakan ujian kultur atau histopatologi sebagai piawai rujukan untuk diagnosis. Biopsi korpus gastrik daripada 352 pesakit telah dimasukkan dalam kajian ini dan data merangkumi kumpulan umur, jantina dan bangsa telah dianalisis. Kerentanan clarithromycin diukur menggunakan ujian E-test. Prevalens keseluruhan jangkitan H. pylori adalah 15.1% (53/352). Tiada asosiasi signifikan didapati antara jangkitan dan faktor demografi yang dikaji. Empat daripada 13 isolat berdaya hidup (30.8%) adalah rintang clarithromycin. Walaupun ujian IRUT mempunyai kekhususan yang sedikit lebih rendah (94.9%) daripada ujian CLO (95.9%), namun sensitiviti kedua-dua ujian adalah sama (81.1%). Nilai ramalan positif ujian IRUT adalah lebih rendah (74.1%) berbanding ujian CLO (78.2%) namun nilai ramalan negatif hampir sama (96.5%) dengan ujian CLO (96.6%). Kedua-dua ujian menunjukkan persetujuan yang sangat baik (κ = 0.97). Kesimpulannya, prevalens keseluruhan jangkitan H. pylori dalam kajian kami pada umumnya adalah rendah. Kadar bilangan isolat rintang clarithromycin yang tinggi mungkin tidak mencerminkan kadar rintangan sebenar memandangkan bilangan kultur positif yang sangat rendah. Prestasi ujian IRUT kami setanding dengan ujian CLO menjadikannya ujian alternatif yang boleh diterima sebagai ujian pantas bagi mengesan jangkitan H. pylori.

Kata kunci: Clarithromycin; Helicobacter pylori; ujian pantas urease

RUJUKAN

Ahmad, N., Zakaria, W.R. & Mohamed, R. 2011. Analysis of antibiotic susceptibility patterns of Helicobacter pylori isolates from Malaysia. Helicobacter 16(1): 47-51.

Alfizah, H., Norazah, A., Hamizah, R. & Ramelah, M. 2014. Resistotype of Helicobacter pylori isolates: The impact on eradication outcome. J. Med. Microbiol. 63(Pt 5): 703-709.

Alfizah, H., Rizal, A.M., Isa, M.R., Aminuddin, A., Jasmi, A.Y. & Ramelah, M. 2010. Four year analysis of Helicobacter pylori infection among patients with dyspepsia at Universiti Kebangsaan Malaysia Medical Centre. Medicine & Health 5(1): 13-21.

Altman, D.G. 1991. Practical Statistics for Medical Research. London: Chapman and Hall.

Chieng, J.Y., Pan, Y. & Loong, Y.Y. 2015. Prevalence of Helicobacter pylori infection among patients attending gastroenterology endoscopy unit at Serdang Hospital. Malaysian Journal of Medicine and Health Sciences 11(1): 11-17.

CLSI. 2010. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria; Approved Guideline - 2nd ed. CLSI document M45-A2. Wayne: Clinical and Laboratory Standards Institute.

Ernst, P.B. & Gold, B.D. 2000. The disease spectrum of Helicobacter pylori: The immunopathogenesis of gastroduodenal ulcer and gastric cancer. Annu. Rev. Microbiol. 54: 615-640.

Ghotaslou, R., Leylabadlo, H.E. & Asl, Y.M. 2015. Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature review. World. J. Methodol. 5(3): 164-174.

Goh, K.L. 2018. Lessons learnt from the epidemiology of Helicobacter pylori infection in Malaysia: JGHF Marshall and Warren Lecture 2017. J. Gastroenterol. Hepatol. 33(2018): 1177-1184.

Goh, K.L. 2009. Epidemiology of Helicobacter pylori infection in Malaysia - Observations in a multiracial Asian population. Malays. J. Med. Sci. 64(3): 187-192.

Goh, K.L. & Navaratnam, P. 2011. High Helicobacter pylori resistance to metronidazole but zero or low resistance to clarithromycin, levofloxacin, and other antibiotics in Malaysia. Helicobacter 16(3): 241-245.

Goh, K.L. & Parasakthi, N. 2001. The racial cohort phenomenon: Seroepidemiology of Helicobacter pylori infection in a multiracial South-East Asian country. Eur. J. Gastroenterol. Hepatol. 13(2): 177-183.

Graham, D.Y. 1991. Helicobacter pylori and the endoscopist: Whether to diagnose. Gastrointest. Endosc. 37(5): 577-579.

Graham, D.Y. & Fischbach, L. 2010. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut 59(8): 1143-1153.

Hooi, J.K.Y., Lai, W.Y., Ng, W.K. Suen, M.M.Y., Underwood, F.E., Tanyingoh, D., Malfertheiner, P., Graham, D.Y., Wong, V.W.S., Wu, J.C.Y., Chan, F.K.L., Sung, J.J.Y., Kaplan, G.G. & Ng, S.C. 2017. Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gasteroenterology 153(2): 420-429.

Ibrahim, A., Morais, S., Ferro, A., Lunet, N. & Peleteiro, B. 2017. Sex-differences in the prevalence of Helicobacter pylori infection in pediatric and adult populations: Systematic review and meta-analysis of 244 studies. Dig. Liver. Dis. 49(7): 742-749.

Kaur, G. & Naing, N.N. 2003. Prevalence and ethnic distribution of Helicobacter pylori infection among endoscoped patients in North Eastern Peninsular Malaysia. Malays. J. Med. Sci. 10(2): 66-70.

Kuipers, E.J., Uyterlinde, A.M., Peña, A.S., Hazenberg, H.J.A., Bloemena, E., Lindeman, J., Klinkenberg-Knol, E. & Meuwissen, S.G.M. 1995. Increase of Helicobacter pylori-associated corpus gastritis during acid suppressive therapy: Implications for long-term safety. Am. J. Gastroenterol. 90(9): 1401-1406.

Lee, H.C., Huang, T.C. & Lin, C.L. 2013. Performance of routine Helicobacter pylori invasive tests in patients with dyspepsia. Gastroenterol. Res. Pract. 2013: 1-5.

MacFaddin, J.F. 1980. Biochemical Tests for Identification of Medical Bacteria. 2nd ed. Baltimore: Williams & Wilkins Co.

McMahon, B.J., Hennessy, T.W., Bensler, J.M., Bruden, D.L., Parkinson, A.J., Morris, J.M., Reasonover, A.L., Hurlburt, D.A., Bruce, M.G., Sacco, F. & Butler, J.C. 2003. The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections. Ann. Intern. Med. 139(6): 463-469.

Mégraud, F. 2004. H. pylori antibiotic resistance: Prevalence, importance, and advances in testing. Gut 53(9): 1374-1384.

Ng, F.H., Wong, S.Y. & Ng, W.F. 1997. Storage temperature of the unbuffered rapid urease test. Am. J. Gastroenterol. 92(12): 2230-2231.

Occhialini, A., Urdaci, M., Doucet-Populaire, F., Bébéar, C.M., Lamouliatte, H. & Mégraud, F. 1997. Macrolide resistance in Helicobacter pylori: Rapid detection of point mutations and assays of macrolide binding to ribosomes. Antimicrob. Agents. Chemother. 41(12): 2724-2728.

Peretz, A., Paritsky, M., Pastukh, N., Koifman, A., Brodsky, D., Glyatman, T. & On, A. 2015. Improvement and optimization of the classical gastric biopsy culture technique for Helicobacter pylori diagnosis using trypsin. J. Med. Microbiol. 64(6): 642-645.

Pue, G.H. & Sulaiman, N. 2013. “Choose One!”: Challenges of inter-ethnic marriages in Malaysia. Asian Soc. Sci. 9(17): 269-278.

Raymond, J., Bergeret, M. & Kalach, N. 2008. Helicobacter pylori infection in children. Presse. Med. 37: 513-518.

Roma-Giannikou, E., Roubani, A., Sgouras, D.N., Panayiotou, J., van-Vliet, C., Polyzos, A., Roka, K. & Daikos, G. 2010. Endoscopic tests for the diagnosis of Helicobacter pylori infection in children: Validation of rapid urease test. Helicobacter 15(3): 227-232.

Saniee, P., Shahreza, S. & Siavoshi, F. 2015. Negative effect of proton pump inhibitors (PPIs) on Helicobacter pylori growth, morphology and urease test and recovery after PPI removal - An in vitro study. Helicobacter 21(2): 143-152.

Sasidharan, S., Lachumy, S.J., Ravichandran, M. Yoga Latha, L. & Surya Gegu, S.R. 2011. Epidemiology of Helicobacter pylori among multiracial community in Northern Peninsular, Malaysia: Effect of age across race and gender. Asian. Pac. J. Trop. Med. 4(1): 72-75.

Savoldi, A., Carrara, E., Graham, D.Y., Conti, M. & Tacconelli, E. 2018. Prevalence of antibiotic resistance in Helicobacter pylori: A systematic review and meta-analysis in World Health Organization regions. Gastroenterology 155(5): 1372-1382.

Scott, D.R., Marcus, E.A., Weeks, D.L. & Sachs, G. 2002. Mechanisms of acid resistance due to the urease system of Helicobacter pylori. Gastroenterology 123(1): 187-195.

Siddique, I., Al-Mekhaizeem, K., Alateeqi, N., Memon, A. & Hasan, F. 2008. Diagnosis of Helicobacter pylori: Improving the sensitivity of CLO test by increasing the number of gastric antral biopsies. J. Clin. Gastroenterol. 42(4): 356-360.

Suerbaum, S. & Michetti, P. 2002. Helicobacter pylori infection. N. Engl. J. Med. 347: 1175-1186.

Teh, X., Khosravi, Y., Lee, W.C. Leow, A.H.R., Loke, M.F., Vadivelu, J. & Goh, K.L. 2014. Functional and molecular surveillance of Helicobacter pylori antibiotic resistance in Kuala Lumpur. PLoS ONE 9(7): e101481.

van der Hulst, R.W., Verheul, S.B., Weel, J.F., Gerrits, Y., ten Kate, F.J.W., Dankert, J. & Tytgat, G.N.J. 1996. Effect of specimen collection techniques, transport media, and incubation of cultures on the detection rate of Helicobacter pylori. Eur. J. Clin. Microbiol. Infect. Dis. 15(3): 211-215.

Xia, H.X., Keane, C.T. & O’Morain, C.A. 1994. Pre-formed urease activity of Helicobacter pylori as determined by a viable cell count technique - Clinical implications. J. Med. Microbiol. 40(6): 435-439.

*Pengarang untuk surat-menyurat; email: muttaqillah@ppukm.ukm.edu.my