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Int. Med J Vol. 6 No 2 December 2007
Incidence of Helicobacter pylori Infection using (13) C- Urea BreathTest and Gastric Biopsy Culture.
AJ Khairul*, A Anwar**, R Hamizah**, M Ramelah***
*Dept. of Medicine International Islamic University, Kuantan, Malaysia.
**,Dept. of Medicine UKM Medical Molecular Biology Institute (UMBI)
***, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Background
(13) C – urea breath test (UBT) is sensitive and specific for detection of Helicobacter pylori (H. pylori) infection. Gastric biopsy culture for H. pylori confirms the diagnosis. Here, we analyzed data of all patients who were investigated for H. pylori infection using both tests throughout the year 2005.
Materials and Methods
Retrospective data of 377 patients between the ages of 17 – 88 were identified through endoscopy records from January to December 2005. Upper endoscopy, UBT and gastric biopsy culture were performed on all patients simultaneously during each endoscopy session. Patients who had positive UBT and biopsy culture for H. pylori were treated with triple therapy of PPI, amoxicillin and clarithromycin for one week. A repeat of UBT was done at one-month post therapy.
Results and Analysis
Twenty-eight patients on the list had no available data on UBT and were omitted from the analysis. Ethnic group Chinese comprised of 45.4% (n=163), followed by Malay, 37.3% (n=134), Indian, 10.6% (n=38) and others, 3.9% (n=14). UBT was positive in 23.7% (n=85)(figure1). H. pylori culture was positive in 19.2% (n=69)(figure1). Sixteen patients with UBT positive had H. pylori culture negative, 18.8% (n=16/85)(figure2). Five patients with H. pylori culture positive had UBT negative, 7.2% (n=5/69)(figure3). Ethnic group Indian had the highest incidence of UBT positive, 47.4% (n=18/38), followed by Others (Sikhs and foreigners) 42.8% (n=6/14), the Chinese 27.6% (n=45/163) and the Malays 11.6% (n= 16/138). UBT positive was the highest in the age group of 50 and above, 64.7% (n=55/85), followed by the age group between 30 to 49, 21.2% (n=18/85) and the age group of 29 and below, 14.5% (n=12/85). Out of the 85 UBT positive patients 91.8% (n=78/85)(figure4) of them responded to the conventional one week of triple therapy (PPI, amoxicillin, clarithromycin) with negative UBT at one-month post therapy compared to only 8.2% (n=7/85)(figure4) who failed with positive UBT at one-month post therapy.
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Incidence of positive (13) C – urea breath test (UBT) was 23.7%. About 18.8% of patients had false positive and 7.2% had false negative for UBT. We found that positive UBT was the highest among the Indians ethnic group (47.4%) and the older age group of 50 and above (64.7%). Majority of UBT positive patients (91.8%) had good response to the one-week conventional triple therapy of PPI, amoxicillin and clarithromycin with negative UBT at one-month post therapy. In the category of ‘others’ (Sikhs and foreigners), who made the second highest among UBT positives, their numbers were too small and therefore warrants further study
Discussion
The prevalence rate of H. pylori infection is high in this country and it is associated with the development of peptic ulcer disease and gastric cancer. This study looked into the incidence rate of H. pylori infection, particularly among major ethnic groups, the Malays, the Chinese and the Indians using (13) C – urea breath test (UBT) and gastric biopsy culture in the University Hospital setting. We also looked into the outcome of treatment at one month post therapy by using similar test.
Many studies have proven that UBT is accurate in the diagnosis of H. pylori infection. Earlier, Perri F et al in his studies in 1998 suggested that UBT can be used as a predictor for intragastric H. pylori bacterial load and severity of gastritis[1]. Zagari RM et al in 2003 concluded that UBT correlated with H. pylori bacterial load and the activity of gastritis[2]. Numerous studies were also conducted worldwide to compare UBT with other methods of H. pylori detection such as culture, urease test and histology from gastric biopsy, serology and stool antigen assay ( HpSA ) and UBT was found to be comparatively accurate[3]. A multi centre study in Spain also concluded that UBT gave excellent accuracy both for the initial diagnosis of H. pylori infection and to confirm eradication after treatment[4]. Kato S et al compared UBT and stool antigen test with gastric biopsy among children in Japan who were infected with H. pylori and concluded the sensitivity, specificity, and accuracy for UBT were 95.0%, 98% and 96.4% respectively[5]. UBT has 2 types –the isotope ratio mass spectrometer (IRMS) and the infrared spectrometer (NDIRS). Both types have been found to be comparatively accurate[6].
Among major ethnic groups in Malaysia, the prevalence rates among the Malays were the lowest from 11.9 to 29.2%, while the Chinese ranged from 26.7 to 57.5%, and the Indians in two studies were the highest with 49.4 and 52.3%[7]. Higher rates were also found in the older age group[7]. This findings were comparable with our data where the Indians were the highest with 47.4%, followed by the Chinese 27.6% and the Malays 11.6%. In East Malaysia, the highest rate was found among the indigenous group in Kota Kinabalu[7]. This pattern of infection in a multiracial population in Malaysia is called the 'racial cohort' phenomenon[7]. Further study on the mode of transmission of H. pylori infection could provide explanation for this phenomenon.
A prospective controlled study conducted by University of Malaya found the gastric cancer incidence rate correlated with H. pylori seropositivity for both the Chinese and Malays but not the Indians, despite being in the highest prevalence[8].
Among the Chinese, H. pylori infection posed a 2.5 fold risk of developing gastric cancer[9]. Therefore, being Chinese is an independent risk factor. Other risk factors include low level of education, cigarette smoking, fish sauce, mouldy food, irregular dinners, family history of malignancy and high intake of salted fish and vegetables[9,10]. High intake of fresh fruits and vegetables was found to be protective[9]. The low prevalence rate of gastric cancer among the Indians has been a subject of discussion. A randomized community health survey in Singapore gave similar result thus, the assumption that host factor and environmental factor could be the other reason.[8]. This paradox was called the “Indian enigma”[9].
Studies looking into the characteristic of H. pylori organism might give some clues to this question. H. pylori is associated with certain genotypes and virulence factors such as cytotoxin associated genes A ( cagA ), E ( cagE) and vacuolating cytotoxin ( vacA) genotypes. Ramelah M et al found that although there was no association between any of the cagA subtypes with peptic ulcer disease, a significant association between cagA subtypes with a specific ethnic group was observed[11]. Specific-cagA subtype A strains were predominantly isolated from the Chinese compared to the Malays and Indians. CagA subtype B strains were predominantly isolated from the Malays and Indians compared to the Chinese[11]. The cagA type A strains of H. pylori found among the Chinese patients who have a higher risk of peptic ulcer disease could be used as an important clinical biomarker for a more severe infection [11].
In terms of the management of H. pylori infection, The Working Party Report on the Management of Helicobacter pylori in 1998 serves as the clinical practice guideline for Malaysian doctors. UBT and rapid urease test by endoscopy are the recommended mode of diagnosis. For negative test but with high index of suspicion for H. pylori infection, a histology from gastric biopsy should be performed [12]. According to The European Helicobacter Study Group (EHSG) consensus, indication for treatment of H. pylori includes gastro-duodenal pathologies such as peptic ulcer disease and low-grade gastric mucosa-associated lymphoid tissue lymphoma (MALT lymphoma), atrophic gastritis, first-degree relatives of gastric cancer patients, unexplained iron deficiency anaemia and chronic idiopathic thrombocytopenic purpura[13]. However, it is also advisable for patients on long term NSAIDs ( non steroidal anti-inflammatory drug) with history of peptic ulcer or dyspepsia and those with resected early gastric cancer to be tested and treated [12].
The Working Party Report recommends, as first line treatment a 7-day combination triple therapy of a proton pump inhibitor, clarithromycin and metronidazole or amoxicillin. However, metronidazole resistance has been reported in a high percentage of strains(77%) isolated from patients locally and none has been found to be resistance to clarithromycin [14]. Therefore, clarithromycin is a better option for treatment and culture should be used to monitor resistance. Adding Bismuth to the combination triple therapy is also a first choice treatment option if available [13].
In conclusion, H. pylori infection remains as an important subject to be studied particularly the mode of transmission and virulence factor. The combination triple therapy is the most effective treatment so far, however antibiotic resistance is the area that should be carefully monitored.
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