Muhammad Miftahussurur

Diagnostic Methods of Helicobacter pylori Infection for Epidemiological Studies: Critical Importance of Indirect Test Validation.

Among the methods developed to detect H. pylori infection, determining the gold standard remains debatable, especially for epidemiological studies. Due to the decreasing sensitivity of direct diagnostic tests (histopathology and/or immunohistochemistry [IHC], rapid urease test [RUT], and culture), several indirect tests, including antibody-based tests (serology and urine test), urea breath test (UBT), and stool antigen test (SAT) have been developed to diagnose H. pylori infection. Among the indirect tests, UBT and SAT became the best methods to determine active infection. While antibody-based tests, especially serology, are widely available and relatively sensitive, their specificity is low. Guidelines indicated that no single test can be considered as the gold standard for the diagnosis of H. pylori infection and that one should consider the methods advantages and disadvantages. Based on four epidemiological studies, culture and RUT present a sensitivity of 74.2–90.8% and 83.3–86.9% and a specificity of 97.7–98.8% and 95.1–97.2%, respectively, when using IHC as a gold standard. The sensitivity of serology is quite high, but that of the urine test was lower compared with that of the other methods. Thus, indirect test validation is important although some commercial kits propose universal cut-off values.

Helicobacter pylori Infection in Thailand: A Nationwide Study of the CagA Phenotype

Background The risk to develop gastric cancer in Thailand is relatively low among Asian countries. In addition, the age-standardized incidence rate (ASR) of gastric cancer in Thailand varies with geographical distribution; the ASR in the North region is 3.5 times higher than that in the South region. We hypothesized that the prevalence of H. pylori infection and diversity of CagA phenotype contributes to the variety of gastric cancer risk in various regions of Thailand. Methods We conducted a nationwide survey within Thailand. We determined H. pylori infection prevalence by detecting H. pylori, using histochemical and immunohistochemical methods. The anti-CagA antibody and anti-East-Asian type CagA antibody (α-EAS Ab), which showed high accuracy in several East Asian countries, were used to determine CagA phenotype. Results Among 1,546 patients from four regions, including 17 provinces, the overall prevalence of H. pylori infection was 45.9% (710/1,546). Mirroring the prevalence of H. pylori infection, histological scores were the lowest in the South region. Of the 710 H. pylori-positive patients, 93.2% (662) were immunoreactive with the anti-CagA antibody. CagA-negative strain prevalence in the South region was significantly higher than that in other regions (17.9%; 5/28; p < 0.05). Overall, only 77 patients (11.6%) were immunoreactive with the α-EAS Ab. There were no differences in the α-EAS Ab immunoreactive rate across geographical regions. Conclusions This is the first study using immunohistochemistry to confirm H. pylori infections across different regions in Thailand. The prevalence of East-Asian type CagA H. pylori in Thailand was low. The low incidence of gastric cancer in Thailand may be attributed to the low prevalence of precancerous lesions. The low incidence of gastric cancer in the South region might be associated with the lower prevalence of H. pylori infection, precancerous lesions, and CagA-positive H. pylori strains, compared with that in the other regions.

Appropriate First-Line Regimens to Combat Helicobacter pylori Antibiotic Resistance: An Asian Perspective

Asia has the largest population of any continent and the highest incidence of gastric cancer in the world, making it very important in the context of Helicobacter pylori infection. According to current guidelines, standard triple therapy containing a proton pump inhibitor (PPI) and two antibiotics; amoxicillin (AMX) and clarithromycin (CAM) or metronidazole (MNZ), is still the preferred first-line regimen for treatment of H. pylori infection. However, the efficacy of legacy triple regimens has been seriously challenged, and they are gradually becoming ineffective. Moreover, some regions in Asia show patterns of emerging antimicrobial resistance. More effective regimens including the bismuth and non-bismuth quadruple, sequential, and dual-concomitant (hybrid) regimens are now replacing standard triple therapies as empirical first-line treatments on the basis of the understanding of the local prevalence of H. pylori antimicrobial resistance. Selection of PPI metabolized by the non-enzymatic pathway or minimal first pass metabolism and/or increasing dose of PPI are important to increase H. pylori eradication rates. Therefore, local antibiotic resistance surveillance updates, selection of appropriate first-line regimens with non-enzymatic PPI and/or increased doses of PPI, and detailed evaluation of patients’ prior antibiotic usage are all essential information to combat H. pylori antibiotic resistance in Asia.

Extremely low Helicobacter pylori prevalence in North Sulawesi, Indonesia and identification of a Maori-tribe type strain: a cross sectional study

BackgroundSulawesi in Indonesia has a unique geographical profile with assumed separation from Sundaland. Studies of Helicobacter pylori in this region are rare due to the region’s rural location and lack of endoscopy equipment. Indirect methods are, therefore, the most appropriate for measuring H. pylori infection in these areas; with the disposable gastric brush test, we can obtain gastric juice as well as small gastric tissue samples for H. pylori culture. We investigated the prevalence of H. pylori infection and evaluated human migration patterns in the remote areas of North Sulawesi.MethodsWe recruited a total of 251 consecutive adult volunteers and 131 elementary school children. H. pylori infection was determined by urine antibody test. A gastric brush test was used to culture H. pylori. We used next-generation and polymerase chain reaction based sequencing to determine virulence factors and multi-locus sequence typing (MLST).ResultsThe overall H. pylori prevalence was only 14.3% for adults and 3.8% for children, and 13.6% and 16.7% in Minahasanese and Mongondownese participants, respectively. We isolated a single H. pylori strain, termed -Manado-1. Manado-1 was East Asian type cagA (ABD type), vacA s1c-m1b, iceA1 positive/iceA2 negative, jhp0562-positive/-(1,3) galT-negative, oipA ‘on’, and dupA-negative. Phylogenetic analyses showed the strain to be hspMaori type, a major type observed in native Taiwanese and Maori tribes.ConclusionsOur data support that very low H. pylori infection prevalence in Indonesia. Identification of hspMaori type H. pylori in North Sulawesi may support the hypothesis that North Sulawesi people migrated from north.

Effect of bacterial and host factors on Helicobacter pylori eradication therapy

Introduction: A clearer understanding of the factors affecting the cure rate of Helicobacter pylori infection might lead to the development of novel prevention strategies and therapeutic targets. Areas covered: This review covers two important issues that affect the eradication of H. pylori: bacterial and host factors. Several virulence factors have been shown to be predictors for gastroduodenal diseases. Successful treatment of H. pylori infection also depends on host genetic factors such as CYP2C19 and IL-1B. The latest evidence on host genetic factors is discussed. Expert opinion: The authors identify three main targets for achieving effective eradication therapy. The first therapeutic target is to identify counter measures for antibiotic-resistant H. pylori strains. Thus, antibiotic susceptibility should be checked in all patients, ideally, before the start of eradication treatment. The second therapeutic target is the inhibition of acid suppression. Maintaining a high intragastric pH for 24 h increases the effectiveness of some antibiotics and the eradication effects for H. pylori. The third therapeutic target is to identify high-risk groups; the CYP2C19 and IL-1B polymorphisms are candidates for significant risk factors. A personalized medical approach will likely increase the cure rate of H. pylori infection.

Risk Factors and Prevalence of Helicobacter pylori in Five Largest Islands of Indonesia: A Preliminary Study

The prevalence of Helicobacter pylori infection in Indonesia is still controversial and mainly investigated in the largest ethnic group, Javanese. We examined the prevalence of H. pylori infection using four different tests including culture, histology confirmed by immunohistochemistry and rapid urease test. We also analyzed risk factors associated with H. pylori infection in five largest islands in Indonesia. From January 2014–February 2015 we consecutively recruited a total of 267 patients with dyspeptic symptoms in Java, Papua, Sulawesi, Borneo and Sumatera Island. Overall, the prevalence of H. pylori infection was 22.1% (59/267). Papuan, Batak and Buginese ethnics had higher risk for H. pylori infection than Javanese, Dayak and Chinese ethnics (OR = 30.57, 6.31, 4.95; OR = 28.39, 5.81, 4.61 and OR = 23.23, 4.76, 3.77, respectively, P <0.05). The sensitivity and specificity for RUT and culture were 90.2%, 92.9% and 80.5%, 98.2%, respectively. The patients aged 50–59 years group had significantly higher H. pylori infection than 30–39 years group (OR 2.98, P = 0.05). Protestant had significantly higher H. pylori infection rate than that among Catholic (OR 4.42, P = 0.008). It was also significantly lower among peoples who used tap water as source of drinking water than from Wells/river (OR 9.67, P = 0.03). However only ethnics as become independent risk factors for H. pylori infection. Although we confirmed low prevalence of H. pylori in Javanese; predominant ethnic in Indonesia, several ethnic groups had higher risk of H. pylori infection. The age, religion and water source may implicate as a risk factor for H. pylori infection in Indonesia.

Helicobacter, Hygiene, Atopy, and Asthma

The hygiene hypothesis links environmental and microbial exposures in early life to the prevalence of atopy, allergy, and asthma. Helicobacter pylori infection is typically acquired in childhood and acquisition of the infection is associated with poor household hygiene. Some population surveys have shown an inverse association between H. pylori infection and atopy, allergy, and asthma leading to the suggestion that H. pylori infection may be protective against disease; others consider it simply a biomarker for poor household hygiene. We review the relevant surveys, cohort studies, meta-analyses, and studies testing the protective hypothesis. Overall, the results of surveys and cohort studies are inconsistent, whereas meta-analyses show a significant but weak inverse correlation. In contrast, studies directly testing the protection hypothesis in relation to asthma in populations with poor hygiene and low H. pylori prevalence failed to confirm a protective effect. H. pylori is a major cause of human disease including chronic gastritis, peptic ulcer, and gastric malignancies. H. pylori infections most likely serve as a biomarker for poor hygienic conditions in childhood. We conclude that while synergistic interactions between environmental factors in childhood are important determinants of the pathogenesis of atopy, allergy, and asthma; H. pylori is inversely related to good hygiene and thus its presence serves as a biomarker rather than for a specific prevention role for H. pylori or H. pylori antigens.

Surveillance of Helicobacter pylori Antibiotic Susceptibility in Indonesia: Different Resistance Types among Regions and with Novel Genetic Mutations.

Information regarding Helicobacter pylori antibiotic resistance in Indonesia was previously inadequate. We assessed antibiotic susceptibility for H. pylori in Indonesia, and determined the association between virulence genes or genetic mutations and antibiotic resistance. We recruited 849 dyspeptic patients who underwent endoscopy in 11 cities in Indonesia. E-test was used to determine the minimum inhibitory concentration of five antibiotics. PCR-based sequencing assessed mutations in 23S rRNA, rdxA, gyrA, gyrB, and virulence genes. Next generation sequencing was used to obtain full-length sequences of 23S rRNA, infB, and rpl22. We cultured 77 strains and identified 9.1% with clarithromycin resistance. Low prevalence was also found for amoxicillin and tetracycline resistance (5.2% and 2.6%, respectively). In contrast, high resistance rates to metronidazole (46.7%) and levofloxacin (31.2%) were demonstrated. Strains isolated from Sumatera Island had significantly higher metronidazole resistance than those from other locations. Metronidazole resistant strains had highly distributed rdxA amino acid substitutions and the 23S rRNA A2143G mutation was associated with clarithromycin resistance (42.9%). However, one strain with the highest MIC value had a novel mutation in rpl22 without an A2143G mutation. Mutation at Asn-87 and/or Asp-91 of gyrA was associated with levofloxacin-resistance and was related to gyrB mutations. In conclusions, although this is a pilot study for a larger survey, our current data show that Indonesian strains had the high prevalence of metronidazole and levofloxacin resistance with low prevalence of clarithromycin, amoxicillin, and tetracycline resistance. Nevertheless, clarithromycin- or metronidazole-based triple therapy should be administered with caution in some regions of Indonesia.

Helicobacter pylori antibiotic susceptibility patterns in Bangladesh: Emerging levofloxacin resistance

INTRODUCTION The most recent study to report Helicobacter pylori antibiotic resistance rates in Bangladesh was published 15 years ago and did not include levofloxacin. We therefore aimed to determine the current antibiotic susceptibility of H. pylori to amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin in Bangladesh. METHODOLOGY This study included 133 consecutive patients who underwent endoscopy examination at Dhaka Medical College in November 2014. The serial two-fold agar dilution method was used to determine the minimum inhibitory concentrations of the five antibiotics. RESULTS Among 56 cultured strains, H. pylori showed high rates of resistance to clarithromycin and metronidazole (39.3% and 94.6%, respectively). Moreover, levofloxacin showed an emerging antimicrobial resistance pattern (66.1%), which was higher in patients with gastritis than that in those with peptic ulcers (p = 0.02). The resistance rate of levofloxacin was significantly higher in patients living in Dhaka city compared to those living in the village (p = 0.049). However, amoxicillin and tetracycline resistance rates were very low. Resistance to both metronidazole and levofloxacin was most commonly observed. CONCLUSIONS The rates of resistance to clarithromycin, metronidazole, and levofloxacin were high in Bangladesh, which suggests that triple therapy based on these drugs may not be useful as first-line therapies in Bangladesh. Alternative strategies such as furazolidone-based triple therapy, bismuth-based quadruple therapies, or sequential therapy may be more effective for patients in in Bangladesh.

CONCOMITANT SEXUALLY TRANSMITTED DISEASES IN PATIENTS WITH DIAGNOSED HIV/AIDS: A RETROSPECTIVE STUDY

Background: Human immunodeficiency virus (HIV) is a virus that causes Acquired Immunodeficiency Syndrome (AIDS) which weaken the human immune system and thus increasing the incidence of sexually transmitted infections (STIs) and vice versa. Materials and Methods: A retrospective study of STIs in HIV/AIDS patients in Unit Perawatan Intermediate Penyakit Infeksi (UPIPI) Dr. Soetomo General Hospital Surabaya was conducted from January 1st, 2013 to December 31st, 2014. We examined the number and type of STIs, age distribution, gender, occupation, number of CD4+, and antiretroviral treatment of patients with HIV/AIDS. The data were presented in a descriptive analysis. Results: The percentage of STIs patients was 4.2% (148 of 3.350) of all patients with HIV/AIDS in the UPIPI Outpatient Clinic of Dr. Soetomo General Hospital. Most patients were 25-44 years old (70.9%) including 54.7% were males, 8.0% were housewives, and 1.4% were students. The five highest prevalence of STIs were condylomata acuminate (43.9%), non-specific genital ulcers (11.5%), syphilis (10.7%), genital herpes (10.1%), and scabies (8.1%). The sexual predilections consisted of heterosexual (70.9%), homosexual (12.2%), bisexual (2.0%), and no data (14.9%). Patients with the number of CD4+ <200 mm3 was 52.0% and 79.1% of the patients received ARV therapy. Conclusion: STIs and HIV/AIDS were closely related. HIV/AIDS could increase the incidence of STIs and STIs could elevate HIV/AIDS.