• View in gallery

    Map of Peninsular Malaysia showing the northeastern region (State of Kelantan) and Kg Kuala Betis in Gua Musang district where the Orang Asli subjects were recruited.

  • View in gallery

    Graph showing Helicobacter pylori infection rate in Orang Asli (%) according to birth cohorts in years. Infection rates in Orang Asli showed a decreasing trend across three different periods with the lowest rates reported in birth cohorts after the 1970s when the state of sanitation and hygiene were better after resettlement to villages program implemented by government.

  • 1.

    Uyub AM, Raj SM, Visvanathan R, Nazim M, Aiyar S, Anuar AK, 1994. Helicobacter pylori infection in north-eastern peninsular Malaysia: evidence for an unusually low prevalence. Scand J Gastroenterol 29: 209213.

    • Search Google Scholar
    • Export Citation
  • 2.

    Raj SM, Yap K, Haq JA, Singh S, Hamid A, 2001. Further evidence for an exceptionally low prevalence of Helicobacter pylori infection among peptic ulcer patients in northeastern peninsular Malaysia. Trans R Soc Trop Med Hyg 95: 2427.

    • Search Google Scholar
    • Export Citation
  • 3.

    Goh KL, Parasakthi N, 2001. The racial cohort phenomenon: seroepidemiology of Helicobacter pylori infection in a multiracial south-east Asian country. Eur J Gastroenterol Hepatol 13: 177183.

    • Search Google Scholar
    • Export Citation
  • 4.

    Sasidharan S, Uyub AM, 2009. Prevalence of Helicobacter pylori infection among asymptomatic healthy blood donors in northern peninsular Malaysia. Trans R Soc Trop Med Hyg 103: 395398.

    • Search Google Scholar
    • Export Citation
  • 5.

    Sasidharan S, Uyub AM, Azlan AA, 2008. Further evidence of ethnic and gender differences for Helicobacter pylori infection among endoscoped patients. Trans R Soc Trop Med Hyg 102: 12261232.

    • Search Google Scholar
    • Export Citation
  • 6.

    Graham DY, Yamaoka Y, Malaty HM, 2007. Thoughts about populations with unexpected low prevalences of Helicobacter pylori infection. Trans R Soc Trop Med Hyg 101: 849851.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bonne C, Hartz H, Klerks JV, Posthuma JH, Radsma W, Tjokronegoro S, 1938. Morphology of the stomach and gastric secretion in Malays and Chinese and the different incidence of gastric ulcer and cancer in these races. Am J Cancer 33: 265279.

    • Search Google Scholar
    • Export Citation
  • 8.

    Tokudome S, Soeripto, Triningsih FX, Anantha I, Suzuki S, Kuruki K, 2005. Rare Helicobacter pylori infection as a factor for the very low stomach cancer incidence in Yogyakarta, Indonesia. Cancer Lett 219: 5761.

    • Search Google Scholar
    • Export Citation
  • 9.

    Iskandar C, 1976. Orang Asli: The Aboriginal Tribes of Peninsular Malaysia. Kuala Lumpur: Oxford University Press, 1011.

  • 10.

    Geoffrey B, Cynthia C, 2002. Tribal Communities in the Malay World: Historical, Cultural and Social Perspectives. Singapore: Institute of Southeast Asian Studies, 7205.

    • Search Google Scholar
    • Export Citation
  • 11.

    Laheij RJ, Straatman H, Jansen JB, Verbeek AL, 1988. Evaluation of commercially available Helicobacter pylori serology kits: a review. J Clin Microbiol 36: 28032809.

    • Search Google Scholar
    • Export Citation
  • 12.

    Raj SM, Lee YY, Choo KE, Noorizan AM, Zulkifli A, Radzi M, Ang SC, 2008. Further observations in an area with an exceptionally low prevalence of Helicobacter pylori infection. Trans R Soc Trop Med Hyg 102: 11631166.

    • Search Google Scholar
    • Export Citation
  • 13.

    Tay CY, Mitchell H, Dong Q, Goh KL, Dawes IW, Lan R, 2009. Population structure of Helicobacter pylori among ethnic groups in Malaysia: recent acquisition of the bacterium by the Malay population. BMC Microbiol 9: 126.

    • Search Google Scholar
    • Export Citation
  • 14.

    Mohamed R, Hanafiah A, Rose IM, Manaf MR, Abdullah SA, Sagap I, van Belkam A, Yaacob JA, 2009. Helicobacter pylori cagA gene variants in Malaysians of different ethnicity. Eur J Clin Microbiol Infect Dis 28: 865869.

    • Search Google Scholar
    • Export Citation
  • 15.

    Colin N, Center for Orang Asli Concerns, 1997. The Orang Asli of Peninsular Malaysia. Available at: http://www.magickriver.net/oa.htm. Accessed November 17, 2009.

    • Search Google Scholar
    • Export Citation
  • 16.

    Nurgalieva ZZ, Malaty HM, Graham DY, Almuchambetova R, Machmudova A, Kapsultanova D, Osato MS, Hollinger FB, Zhangabylov A, 2002. Helicobacter pylori infection in Kazakhstan: effect of water source and household hygiene. Am J Trop Med Hyg 67: 201206.

    • Search Google Scholar
    • Export Citation
  • 17.

    Ahmed KS, Khan AA, Ahmed I, Tiwari SK, Habeeb A, Ahi JD, Abid Z, Ahmed N, Habibullah CM, 2007. Impact of household hygiene and water source on the prevalence and transmission of Helicobacter pylori: a south Indian perspective. Singapore Med J 48: 543549.

    • Search Google Scholar
    • Export Citation
  • 18.

    Zhang L, Eslick GD, Xia XH, Wu C, Phung N, Talley NJ, 2009. Relationship between alcohol consumption and active Helicobacter pylori infection. Alcohol Alcohol 45: 16.

    • Search Google Scholar
    • Export Citation
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Helicobacter pylori Infection among Aborigines (the Orang Asli) in the Northeastern Region of Peninsular Malaysia

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  • Universiti Sains Malaysia, School of Medical Sciences, Kubang Kerian, Kelantan, Malaysia; Pantai Medical Centre, Kuala Lumpur, Malaysia; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; Michael E. DeBakey Veteran Affairs Medical Center and Baylor College of Medicine, Houston, Texas

Whether the exceptionally low prevalence of Helicobacter pylori (HP) infection reported among Malays is also present among aborigines (the Orang Asli) living in northeastern Peninsular Malaysia is unknown. We studied asymptomatic Orang Asli from settlements situated 210 km from the city of Kota Bharu. The HP infection status was confirmed by a validated serology test. Nineteen percent of 480 Orang Asli tested positive for HP infection. The prevalence was 40.6% in the birth cohort of the 1940s and declined steadily in later cohorts to under 10% among 12–30 year olds. This may be related to the phases of relocation from the jungles into resettlement camps and ultimately into designated villages near rivers. The low prevalence pattern after the 1970s was probably partly a result of improvement in sanitation and hygiene practice in these villages but other unidentified factors may also be operating.

Short Report

Epidemiologic data from Malaysia have repeatedly confirmed a low prevalence of Helicobacter pylori (HP) infection in the Malays compared with Indian and Chinese immigrants.16 The low prevalence of HP infection is consistent with evidence dating back to the early twentieth century that showed both peptic ulcer and gastric cancer were rare in the Malays but not in the Indian and Chinese migrant population.7,8 Helicobacter pylori infection among the aboriginal population of Malaysia has not been systematically studied. There are three major tribes of Orang Asli in Peninsular Malaysia, namely Negritos, Senoi, and Proto-Malays.9,10 The Temiar are a major tribal group of the Senoi and are mainly found in the jungles of northeastern Peninsular Malaysia bordering the states of Kelantan and Perak (Figure 1). Forced resettlement by the Malaysian government clustered most Orang Asli in less remote villages along with basic education and healthcare facilities. However, most remain illiterate and their understanding of personal hygiene and sanitation is rudimentary. They inhabit shared longhouses that are overcrowded with many families. One would suspect that these living conditions would foster the spread of HP infections. We report herewith data concerning the prevalence and predictors of HP infection among a subset of asymptomatic Orang Asli population in northeastern Peninsular Malaysia.

Figure 1.
Figure 1.

Map of Peninsular Malaysia showing the northeastern region (State of Kelantan) and Kg Kuala Betis in Gua Musang district where the Orang Asli subjects were recruited.

Citation: The American Society of Tropical Medicine and Hygiene 83, 5; 10.4269/ajtmh.2010.10-0226

We studied Orang Asli living near Kg Kuala Betis in the southern district of Gua Musang in the state of Kelantan in northeastern Peninsular Malaysia. The town of Gua Musang is 180 km south of the capital city Kota Bahru (Figure 1). Kg Kuala Betis is the base for the office of Orang Asli Welfare Department or Jabatan Hal Ehwal Orang Asli (JHEOA). The study location consisted of three Orang Asli settlements/villages or “Pos” situated 10–30 km from Kg Kuala Betis in an area accessible only by four-wheel drive vehicles. The total population of Orang Asli in these blocks was 6,000. Screening took place in 2001 after official clearance from the JHEOA and data collection was completed in 2002. All subjects were > 12 years of age and randomly selected from households in the villages to reach a sample size of 480 subjects. This sample size was calculated using PS software to achieve a power of 80% and precision of 0.05. Because of problems with literacy, verbal informed consent was obtained after explanation of study procedures. Children were recruited only after parental consent was given. The study was reviewed and approved by the Human Ethics Committee of Universiti Sains Malaysia (USM) and supported by a USM short term grant.

A detailed investigator-directed questionnaire was administered to each subject with the help of an Orang Asli interpreter. The questionnaire included age, sex, place of birth, marital status, occupation, religion, educational level, total household occupants, smoking status, alcohol consumption, herbal plants and roots usage, source of water supply, eating exotic food from the jungle (including porcupines and tapirs), consumption of “budu” (a local anchovy sauce eaten only by the people in Kelantan), boiling of drinking water, previous history of gastrointestinal symptoms (dyspepsia, haematemesis, malaena and water brash), family history of gastric disease and past medical history (hypertension, diabetes mellitus, and coronary heart disease). Helicobacter pylori status was determined using a commercially available enzyme-linked immunosorbent assay (ELISA) serology test for immunoglobulin G (IgG) antibody (Uni-Gold H. pylori test; Trinity Biotech, UK).11 Blood samples (2.5 mL) were drawn from each subject and either analyzed on site or stored between 2 and 8°C until analysis. A titer of 1:300 or higher for IgG antibody was regarded as indicating HP infection. This cutoff value had been validated earlier in a group of 40 subjects in Universiti Sains Malaysia who had undergone upper endoscopy. Statistical analysis was performed using the computer package SPSS for Windows (version 11.0, SPSS, Inc, Chicago, IL). Simple logistic regression analysis was used to assess the association between possible variables with HP infection. Multiple logistic regression analysis (forward LR method) was performed when differences in key variables of infection were identified from simple logistic regression analysis.

We recruited 480 subjects from the three Orang Asli settlements with a mean age of 31 ± 13 years (range 13–87 years). There were almost equal number of males (47.1%) and females. The majority of subjects were born (88.5%) and raised (98.5%) in Kelantan. However, place of birth had no influence on infection rates as shown in Table 1. Many were jungle product collectors (33.5%) and 40.2% received no education or only primary education (58.3%). The subjects lived in large families with 92.3% having more than eight members per family. Government supplied piped water was accessible to only 37.1% of subjects. Most were smokers (61%) but only 7.5% drank alcohol. Out of 480 subjects, 19% tested positive for HP infection using the serology test. Prevalence by birth cohorts is shown in Figure 2. A higher prevalence was observed among birth cohorts in the period between 1940s through 1960s (13/32 subjects or 40.6% in 1940s, 26/75 subjects or 34.7% in 1950s, and 26/116 subjects or 22.4% in 1960s) but fell to below 10% after the 1970s (9/138 subjects or 6.5% in 1970s and 8/102 subjects or 7.8% in 1980s). Importantly, most of those 60 or older in the period between 1910s and 1930s had an HP prevalence of 9/17 or 52.9%. Because they lived through the relocation periods and were exposed to the younger cohorts, it is not possible to know the prerelocation prevalences. Because of differences in key variables from simple logistic regression analysis, we performed multiple logistic regression analysis (forward LR method) with positivity for HP infection as the dependent variable and age, sex, occupation, educational level, number of family members in each household, smoking status, alcohol consumption, herbal plants and roots use, source of water supply, diet of exotic foods and family history of gastric disease as the independent variables (Table 2). Older age (odds ratio [OR] 1.04; 95% confidence interval [CI] = 1.02–1.07), a history of herbal plants and root use (OR 2.11; 95% CI = 1.08–4.16), and a large family size (OR 1.21; 95% CI = 1.01–1.47) were strong predictors of infection (Table 1). Any formal education and use of government piped water source were protective factors against HP infection.

Figure 2.
Figure 2.

Graph showing Helicobacter pylori infection rate in Orang Asli (%) according to birth cohorts in years. Infection rates in Orang Asli showed a decreasing trend across three different periods with the lowest rates reported in birth cohorts after the 1970s when the state of sanitation and hygiene were better after resettlement to villages program implemented by government.

Citation: The American Society of Tropical Medicine and Hygiene 83, 5; 10.4269/ajtmh.2010.10-0226

Table 1

Risk factors for HP infection among Orang Asli tribes in northeastern peninsular Malaysia

A: Simple logistic regression analysis
FactorOR95% CI for ORP value
Age (years)1.0651.045–1.0850.001
Birth place (Kelantan vs. others)0.8180.412–1.6230.566
Gender (male vs. female)1.6481.039–2.6120.034
Occupation: farmer2.4781.311–4.6830.005
Occupation: jungle1.6411.029–2.6190.038
Occupation: student0.3190.124–0.8180.017
Any education0.2090.127–0.3440.001
Total household occupants1.1981.004–1.4300.045
Smoking4.4052.409–8.0550.001
Alcohol consumption3.0331.486–6.1920.002
Herbal plants and roots use5.5743.179–9.7710.001
Eating budu0.6270.238–1.6540.346
Eating exotic foods3.1561.405–7.0870.005
Family history of gastric disease2.1261.306–3.4620.002
Government piped water source0.5110.305–0.8540.010
B: Multiple logistic regression analysis
FactorOR95% CI for ORP value
Age (years)1.0431.018–1.0680.001
Any education0.4810.256–0.9010.022
Family size1.2151.007–1.4650.042
Herbal plants and roots use2.1151.077–4.1560.030
Government piped water source0.5440.301–0.9840.044

OR = odds ratio; CI = confidence interval; P value is significant if P < 0.05.

Table 2

Characteristics of HP infected and non-infected groups among Orang Asli tribes in northeastern peninsular Malaysia*

FactorHP + ve (N = 91)HP − ve (N = 389)
Age (years) (mean ± SD)39.9 ± 1428.9 ± 12
Birth place (% in Kelantan)86.888.9
Gender (% of male)57.144.7
Occupation: farmer (%)18.78.5
Jungle product collector (%)42.931.4
Student (%)5.515.4
Housewife (%)27.537.5
Not working (%)3.34.6
Other (%)2.22.6
Education: none (%)70.333.2
Primary (%)28.665.3
Secondary (%)01.5
College or university (%)1.10
Total household occupants (mean ± SD)9.1 ± 18.8 ± 1
Smoking (%)84.655.5
Alcohol consumption (%)15.45.7
Herbal plants and roots use (%)34.18.5
Eating budu (%)5.58.5
Eating exotic foods (%)92.279.2
Family history of gastric disease (%)69.251.4
Past history of dyspepsia (%)45.118.8
Government piped water source (%)25.339.8

N = number of Orang Asli subjects; SD = standard deviation; + ve = positive; − ve = negative.

The prevalence of HP infection among Malays in the northeastern region is exceptionally low13,12 and of interest. A recent study found the majority of HP strains obtained from the Malays were the same origin as those of immigrant Indians suggesting that infection among Malays was acquired after mixing with immigrant populations.13,14 Helicobacter pylori prevalence in the Orang Asli was high in the birth cohort of the 1940s and declined rapidly in subsequent birth cohorts to less than 10% in those born in the 1970s and 1980s (Figure 2). We speculate the pattern reflected acquisition of the infection during periods of aboriginal contact with outsiders. The period from 1948–1960 saw the forced relocation of the Orang Asli from the interior jungles into less remote resettlement camps as a consequence of the conflict between the British colonial government and communist insurgents.15 They were later relocated to designated villages that initially had poor sanitation and hygiene with water being obtained mainly from rivers with adjacent primitive toilets. Improved provision of clean water and better toilet facilities in the villages from the 1970s onward may partly explain the decline in HP prevalence.16,17 However, the extraordinarily low HP infection rates among 12–30 year olds in a community that remains among the most socioeconomically disadvantaged in the country suggests that there are as yet unknown factors that limit the transmissibility of the bacteria in the area.

Attempts to explore why Orang Asli have a “natural” low prevalence of HP have not identified any specific responsible factor. Of interest, eating exotic rare jungle animals (porcupines and tapirs) appeared to increase the risk of HP infection but it is considered unlikely that the wild animals harbor the infection. It is possible however that shared use of blow pipes made from bamboo to hunt jungle animals or shared food utensils favor HP infection. Herbal plants and roots use appeared to increase the risk of HP infection as did ingestion of alcohol. Both can damage the gastric mucosa but could just as likely be markers for other practices.18 More likely, both practices were associated with shared utensils or other traditional methods of preparation which favor HP infection.

The study limitations include convenience sampling because of the logistic difficulties of communication, transportation, and access to the Orang Asli. However, we made all possible efforts to gather a sample from as many households as possible from the three settlements. In addition, even with the help of an interpreter, complete data acquisition from the questionnaire was not always possible. Even though the serology kit for HP IgG was validated with good sensitivity and specificity, a combination of tests might have improved detection rates. The determination of strain would be extremely helpful but obtaining the tissues for testing was limited by logistic and ethical issues.

Acknowledgments:

We are grateful to the Kelantan State Orang Asli Welfare Department, the village elders (“Tok Batin”), the medical assistants, and all the study subjects for their cooperation and assistance during the study. We also thank Venkatesh R. Nair and Gurjeet Kaur (Pathology Department, Universiti Sains Malaysia) for their help with histopathological diagnosis of Helicobacter pylori infection during validation of the serology tests.

  • 1.

    Uyub AM, Raj SM, Visvanathan R, Nazim M, Aiyar S, Anuar AK, 1994. Helicobacter pylori infection in north-eastern peninsular Malaysia: evidence for an unusually low prevalence. Scand J Gastroenterol 29: 209213.

    • Search Google Scholar
    • Export Citation
  • 2.

    Raj SM, Yap K, Haq JA, Singh S, Hamid A, 2001. Further evidence for an exceptionally low prevalence of Helicobacter pylori infection among peptic ulcer patients in northeastern peninsular Malaysia. Trans R Soc Trop Med Hyg 95: 2427.

    • Search Google Scholar
    • Export Citation
  • 3.

    Goh KL, Parasakthi N, 2001. The racial cohort phenomenon: seroepidemiology of Helicobacter pylori infection in a multiracial south-east Asian country. Eur J Gastroenterol Hepatol 13: 177183.

    • Search Google Scholar
    • Export Citation
  • 4.

    Sasidharan S, Uyub AM, 2009. Prevalence of Helicobacter pylori infection among asymptomatic healthy blood donors in northern peninsular Malaysia. Trans R Soc Trop Med Hyg 103: 395398.

    • Search Google Scholar
    • Export Citation
  • 5.

    Sasidharan S, Uyub AM, Azlan AA, 2008. Further evidence of ethnic and gender differences for Helicobacter pylori infection among endoscoped patients. Trans R Soc Trop Med Hyg 102: 12261232.

    • Search Google Scholar
    • Export Citation
  • 6.

    Graham DY, Yamaoka Y, Malaty HM, 2007. Thoughts about populations with unexpected low prevalences of Helicobacter pylori infection. Trans R Soc Trop Med Hyg 101: 849851.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bonne C, Hartz H, Klerks JV, Posthuma JH, Radsma W, Tjokronegoro S, 1938. Morphology of the stomach and gastric secretion in Malays and Chinese and the different incidence of gastric ulcer and cancer in these races. Am J Cancer 33: 265279.

    • Search Google Scholar
    • Export Citation
  • 8.

    Tokudome S, Soeripto, Triningsih FX, Anantha I, Suzuki S, Kuruki K, 2005. Rare Helicobacter pylori infection as a factor for the very low stomach cancer incidence in Yogyakarta, Indonesia. Cancer Lett 219: 5761.

    • Search Google Scholar
    • Export Citation
  • 9.

    Iskandar C, 1976. Orang Asli: The Aboriginal Tribes of Peninsular Malaysia. Kuala Lumpur: Oxford University Press, 1011.

  • 10.

    Geoffrey B, Cynthia C, 2002. Tribal Communities in the Malay World: Historical, Cultural and Social Perspectives. Singapore: Institute of Southeast Asian Studies, 7205.

    • Search Google Scholar
    • Export Citation
  • 11.

    Laheij RJ, Straatman H, Jansen JB, Verbeek AL, 1988. Evaluation of commercially available Helicobacter pylori serology kits: a review. J Clin Microbiol 36: 28032809.

    • Search Google Scholar
    • Export Citation
  • 12.

    Raj SM, Lee YY, Choo KE, Noorizan AM, Zulkifli A, Radzi M, Ang SC, 2008. Further observations in an area with an exceptionally low prevalence of Helicobacter pylori infection. Trans R Soc Trop Med Hyg 102: 11631166.

    • Search Google Scholar
    • Export Citation
  • 13.

    Tay CY, Mitchell H, Dong Q, Goh KL, Dawes IW, Lan R, 2009. Population structure of Helicobacter pylori among ethnic groups in Malaysia: recent acquisition of the bacterium by the Malay population. BMC Microbiol 9: 126.

    • Search Google Scholar
    • Export Citation
  • 14.

    Mohamed R, Hanafiah A, Rose IM, Manaf MR, Abdullah SA, Sagap I, van Belkam A, Yaacob JA, 2009. Helicobacter pylori cagA gene variants in Malaysians of different ethnicity. Eur J Clin Microbiol Infect Dis 28: 865869.

    • Search Google Scholar
    • Export Citation
  • 15.

    Colin N, Center for Orang Asli Concerns, 1997. The Orang Asli of Peninsular Malaysia. Available at: http://www.magickriver.net/oa.htm. Accessed November 17, 2009.

    • Search Google Scholar
    • Export Citation
  • 16.

    Nurgalieva ZZ, Malaty HM, Graham DY, Almuchambetova R, Machmudova A, Kapsultanova D, Osato MS, Hollinger FB, Zhangabylov A, 2002. Helicobacter pylori infection in Kazakhstan: effect of water source and household hygiene. Am J Trop Med Hyg 67: 201206.

    • Search Google Scholar
    • Export Citation
  • 17.

    Ahmed KS, Khan AA, Ahmed I, Tiwari SK, Habeeb A, Ahi JD, Abid Z, Ahmed N, Habibullah CM, 2007. Impact of household hygiene and water source on the prevalence and transmission of Helicobacter pylori: a south Indian perspective. Singapore Med J 48: 543549.

    • Search Google Scholar
    • Export Citation
  • 18.

    Zhang L, Eslick GD, Xia XH, Wu C, Phung N, Talley NJ, 2009. Relationship between alcohol consumption and active Helicobacter pylori infection. Alcohol Alcohol 45: 16.

    • Search Google Scholar
    • Export Citation

Author Notes

*Address correspondence to Yeong Yeh Lee, Department of Medicine, Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia. E-mail: yylee@kck.usm.my

Financial support: The study was supported by the Universiti Sains Malaysia (USM) short term grant (reference: 304/PPSP/6131251).

Disclosure: David Y. Graham is a consultant for Novartis in relation to vaccine development for treatment or prevention of H. pylori infection. He is also a paid consultant for Otsuka Pharmaceuticals and until July 2007 was a member of the Board of Directors of Meretek Diagnostics, the manufacturer of the 13C-urea breath test. He also receives royalties on the Baylor College of Medicine patent covering materials related to 13C-urea breath test. All other authors report no relevant conflicts.

Authors' addresses: Amry Abdul Rahim and Yeong Yeh Lee, Department of Medicine, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia, E-mails: dramryusm@hotmail.com and yylee@kck.usm.my. Noorizan Abdul Majid and Keng Ee Choo, Department of Paediatrics, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia, E-mails: noorizan@kb.usm.my and kechoo@kb.usm.my. Sundramoorthy Mahendra Raj, Pantai Hospital, Kuala Lumpur, Malaysia, E-mail: mahendraraj58@gmail.com. Mohammad H. Derakhshan, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom, E-mail: m.derakhshan@clinmed.gla.ac.uk. David Y. Graham, Michael E. DeBakey Veteran Affairs Medical Center and Baylor College of Medicine, Houston, TX, E-mail: dgraham@bcm.tmc.edu.

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