Helicobacter pylori Infection Is Associated with Higher CD4 T Cell Counts and Lower HIV-1 Viral Loads in ART-Na?ve HIV-Positive Patients in Ghana

Background

Worldwide, there is a high co-endemicity of HIV and H. pylori infection and there is growing evidence that H. pylori co-infection is associated with parameters of HIV disease progression. The objective of this study was to investigate the prevalence of H. pylori infection, and the association with clinical, immunological and virological parameters in a large cohort of HIV-infected individuals and uninfected controls in a West African country.

Methods

HIV-patients (n = 1,095) and HIV-negative individuals (n = 107) were recruited at a university hospital in Ghana. H. pylori status was determined using stool antigen testing. HIV-related, clinical and socio-demographic parameters were recorded and analyzed according to H. pylori status.

Results

The prevalence of H. pylori infection was significantly lower in HIV-positive compared to HIV-negative individuals (51.5 vs. 88%, p<0.0001). In HIV patients, H. pylori prevalence decreased in parallel with CD4+ T cell counts. In ART-naïve HIV-infected individuals, but not in those taking ART, H. pylori infection was associated with higher CD4 cell counts (312 vs. 189 cells/μL, p<0.0001) and lower HIV-1 viral loads (4.92 vs. 5.21 log10 copies/mL, p = 0.006). The findings could not be explained by socio-demographic confounders or reported use of antibiotics. Having no access to tap water and higher CD4+ T cell counts were identified as risk factors for H. pylori infection.

Conclusions

H. pylori prevalence was inversely correlated with the degree of immunosuppression. In ART-naïve individuals, H. pylori infection is associated with favorable immunological and virological parameters. The underlying mechanisms for this association are unclear and warrant investigation.     

Helicobacter pylori Eradication Prevents Metachronous Gastric Neoplasms after Endoscopic Resection of Gastric Dysplasia

Purpose

There is insufficient data about the role of eradication of H. pylori after endoscopic resection (ER) for gastric dysplasia. The aim was to investigate the benefit of H. pylori eradication after ER in patients with gastric dysplasia to prevent metachronous gastric neoplasms.

Materials and Methods

We retrospectively reviewed 1872 patients who underwent ER of gastric dysplasia. We excluded patients with a follow-up period of <2 years or who had not undergone tests for active H. pylori infection. A total of 282 patients were enrolled. The patients were categorized into those without active H. pylori infection (H. pylori-negative group, n = 124), those who successfully underwent H. pylori eradication (eradicated group, n = 122), and those who failed or did not undergo H. pylori eradication (persistent group, n = 36).

Results

Metachronous recurrence was diagnosed in 36 patients, including 19 in the H. pylori-negative group, 10 in the eradicated group, and 7 in the persistent group. The cumulative incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group in comparison with either of the H. pylori-persistent (non-eradicated or failed) groups (p = 0.039). Similarly, the incidence of metachronous recurrence was significantly lower in the H. pylori-eradicated group compared with the H. pylori-negative group (p = 0.041).

Conclusion

Successful H. pylori eradication may reduce the development of metachronous gastric neoplasms after ER in patients with gastric dysplasia.     

Effect of Eradication of Helicobacter pylori on Expression Levels of FHIT,IL-8 and P73 in Gastric Mucosa of First-Degree Relatives of Gastric Cancer Patients

Objectives

Helicobacter pylori (H. pylori) infection plays an important role in the carcinogenesis and development of gastric cancer. Eradication of H. pylori can effectively reduce the risk of gastric cancer, but the underlying mechanisms are not fully understood. This study aimed to investigate the effect of eradication of H. pylori on the expression levels of FHIT, IL-8 and P73 in the gastric mucosa of first-degree relatives of gastric cancer patients.

Methods

One hundred and thirty-two patients with functional dyspepsia having first-degree relatives with gastric cancer were prospectively recruited in this study. Nine patients presented with H. pylori infection and family histories of gastric cancer, 61 with H. pylori infection and without family histories of gastric cancer, 6 without H. pylori infection and with family histories of gastric cancer, and 56 without H. pylori infection and family histories of gastric cancer. The protein and mRNA expression levels of FHIT, IL-8 and P73 in gastric mucosa of the subjects were detected by immunohistochemical staining and polymerase chain reaction, respectively.

Results

Compared with the patients without H. pylori infection and family histories of gastric cancer, both the protein and mRNA levels of FIHT significantly decreased in patients with H. pylori infection and/or family histories of gastric cancer, and both the protein and mRNA levels of IL-8 significantly increased. After eradication of H. pylori, both the protein and mRNA levels of FHIT were significantly higher, and both the protein and mRNA levels of IL-8 were significantly lower. However, H. pylori infection and family histories of gastric cancer had no major effect on P73 expression.

Conclusions

Down-regulation of FHIT and up-regulation of IL-8 may be involved in the pathogenesis of H. pylori infection in the first-degree relatives of gastric cancer patients.     

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.     

Helicobacter pylori Eradication on the Prevention of Metachronous Lesions after Endoscopic Resection of Gastric Neoplasm: A Meta-Analysis

Background

There is controversy about the effect of Helicobacter pylori (H. pylori) eradication on the prevention of metachronous gastric cancer after endoscopic resection (ER).

Aims

The aim of this study was to systematically evaluate the effect of H. pylori eradication on the prevention of metachronous gastric lesions after ER of gastric neoplasms.

Methods

We performed a systematic search of PubMed, EMBASE, the Cochrane Library, and MEDLINE that encompassed studies through April 2014. Our meta-analysis consisted of 10 studies, which included 5881 patients who underwent ER of gastric neoplasms.

Results

When we compared the incidence of metachronous lesions between H. pylori-eradicated and non-eradicated groups, H. pylori eradication significantly lowered the risk of metachronous lesions after ER of gastric neoplasms (five studies, OR = 0.392, 95% CI 0.259 – 0.593, P < 0.001). When we compared H. pylori-eradicated and persistent groups, again, H. pylori eradication significantly lowered the incidence of metachronous lesions after ER of gastric neoplasms (six studies, OR = 0.468, 95% CI 0.326 – 0.673, P < 0.001). There was no obvious heterogeneity across the analyzed studies.

Conclusions

This meta-analysis suggests a preventive role for H. pylori eradication for metachronous gastric lesions after ER of gastric neoplasms. Thus, H. pylori eradication should be considered if H. pylori infection is confirmed during ER.     

Fluorescence In Vivo Hybridization (FIVH) for Detection of Helicobacter pylori Infection in a C57BL/6 Mouse Model

Introduction

In this study, we applied fluorescence in vivo hybridization (FIVH) using locked nucleic acid (LNA) probes targeting the bacterial rRNA gene for in vivo detection of H. pylori infecting the C57BL/6 mouse model. A previously designed Cy3_HP_LNA/2OMe_PS probe, complementary to a sequence of the H. pylori 16S rRNA gene, was used. First, the potential cytotoxicity and genotoxicity of the probe was assessed by commercial assays. Further, the performance of the probe for detecting H. pylori at different pH conditions was tested in vitro, using fluorescence in situ hybridization (FISH). Finally, the efficiency of FIVH to detect H. pylori SS1 strain in C57BL/6 infected mice was evaluated ex vivo in mucus samples, in cryosections and paraffin-embedded sections by epifluorescence and confocal microscopy.

Results

H. pylori SS1 strain infecting C57BL/6 mice was successfully detected by the Cy3_HP_LNA/2OMe_PS probe in the mucus, attached to gastric epithelial cells and colonizing the gastric pits. The specificity of the probe for H. pylori was confirmed by microscopy.

Conclusions

In the future this methodology can be used in combination with a confocal laser endomicroscope for in vivo diagnosis of H. pylori infection using fluorescent LNA probes, which would be helpful to obtain an immediate diagnosis. Our results proved for the first time that FIVH method is applicable inside the body of a higher-order animal.     

Environmental Factors Related to Multiple Sclerosis in Indian Population

Background

Multiple sclerosis (MS) is less prevalent among Indians when compared to white populations. Genetic susceptibility remaining the same it is possible that environmental associations may have a role in determining disease prevalence.

Aims

To determine whether childhood infections, vaccination status, past infection with Helicobacter pylori (H.pylori), diet, socioeconomic and educational status were associated with MS.

Material and Methods

139 patients and 278 matched control subjects were selected. A validated environmental exposure questionnaire was administered. Estimation of serum H.pylori IgG antibody was done by ELISA. Patients and controls were genotyped for HLA-DRB1*15:01.

Results

In our cohort a significant association was seen with measles (p <0.007), vegetarian diet (p < 0.001, higher educational status (p <0.0001) and urban living (p <0.0001). An inverse relationship was seen with H.Pylori infection and MS (p <0.001). Measles infection (OR 6.479, CI 1.21- 34.668, p< 0.029) and high educational status (OR 3.088, CI 1.212- 7.872, p< 0.018) were significant risk factors associated with MS. H.pylori infection was inversely related to MS (OR 0. 319, CI 0.144- 0.706, p <0.005).

Conclusions

Environmental influences may be important in determining MS prevalence.     

Association between TNFA Gene Polymorphisms and Helicobacter pylori Infection: A Meta-Analysis

Background

Several host genetic factors are thought to affect susceptibility to Helicobacter pylori infection-related diseases, including tumor necrosis factor (TNF)-α. Previous studies have evaluated the association between TNFA gene polymorphisms and H. pylori infection, but the results were inconclusive. We conducted this meta-analysis to clarify the association between TNFA polymorphisms and H. pylori infection.

Methods

Published literature within PubMed, Embase, and the Cochrane Library were used in our meta-analysis. Data were analyzed with the Stata13.1 software package using pooled odds ratios (ORs) with 95% confidence intervals (CI).

Results

A total of 24 studies were included in our study. The TNFA -308G>A polymorphism was associated with decreasing H. pylori infection (AA vs. AG+GG, OR = 0.64, 95% CI = 0.43–0.97; AA vs. GG, OR = 0.64, 95% CI = 0.43–0.97). A significantly decreased risk was also found for -1031T>C polymorphism (CC vs. CT+TT, OR = 0.61, 95% CI = 0.44–0.84). -863C>A polymorphism was associated with increasing risk of H. pylori infection (AA+AC vs. CC, OR = 1.47, 95% CI = 1.16–1.86; A allele vs. C allele, OR = 1.40, 95% CI = 1.14–1.72). There was no significant association between -857C>T polymorphism and H. pylori infection. When stratified analysis was conducted on H. pylori infection detection methods, -857C>T and -863C>A polymorphisms were associated with H. pylori infection for the non-ELISA subgroup. When stratified for ethnicity or study design, -863C>A significantly increased the risk and -1031T>C decreased the risk for the Asian subgroup and hospital-based subgroup.

Conclusion

Results of our meta-analysis demonstrate that TNFA -308G>A and -1031 T>C polymorphisms may be protective factors against H. pylori infection, and -863C>A may be a risk factor, especially in Asian populations. Further studies with larger sample sizes are required to validate these results.     

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival

Background

We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region.

Methods

Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

Results

A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

Conclusion

In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.     

Antisecretory,Gastroprotective, Antioxidant and Anti-Helicobcter Pylori Activity of Zerumbone from Zingiber Zerumbet (L.) Smith

Background

Zingiber zerumbet Smith is a perennial herb, broadly distributed in many tropical areas. In Malaysia, it’s locally known among the Malay people as “lempoyang” and its rhizomes, particularly, is widely used in traditional medicine for the treatment of peptic ulcer disease beyond other gastric disorders.

Aim of the study

The aim of the current study is to evaluate the gastroprotective effect of zerumbone, the main bioactive compound of Zingiber zerumbet rhizome, against ethanol-induced gastric ulcer model in rats.

Materials and Methods

Rats were pre-treated with zerumbone and subsequently exposed to acute gastric ulcer induced by absolute ethanol administration. Following treatment, gastric juice acidity, ulcer index, mucus content, histological analysis (HE and PAS), immunohistochemical localization for HSP-70, prostaglandin E2 synthesis (PGE₂), non-protein sulfhydryl gastric content (NP-SH), reduced glutathione level (GSH), and malondialdehyde level (MDA) were evaluated in ethanol-induced ulcer in vivo. Ferric reducing antioxidant power assay (FRAP) and anti-H. pylori activity were investigated in vitro.

Results

The results showed that the intragastric administration of zerumbone protected the gastric mucosa from the aggressive effect of ethanol-induced gastric ulcer, coincided with reduced submucosal edema and leukocyte infiltration. This observed gastroprotective effect of zerumbone was accompanied with a significant (p <0.05) effect of the compound to restore the lowered NP-SH and GSH levels, and to reduce the elevated MDA level into the gastric homogenate. Moreover, the compound induced HSP-70 up-regulation into the gastric tissue. Furthermore, zerumbone significantly (p <0.05) enhanced mucus production, showed intense PAS stain and maintained PG content near to the normal level. The compound exhibited antisecretory activity and an interesting minimum inhibitory concentration (MIC) against H. pylori strain.

Conclusion

The results of the present study revealed that zerumbone promotes ulcer protection, which might be attributed to the maintenance of mucus integrity, antioxidant activity, and HSP-70 induction. Zerumbone also exhibited antibacterial action against H. pylori.     

Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults

Background

Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome.

Methods

As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18–30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline.

Results

We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000–170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders.

Conclusions

Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen and be cautious in the clinical management of H. pylori infection, particularly in immunocompromised patients.     

Epstein Barr Virus and Helicobacter pylori Co-Infection Are Positively Associated with Severe Gastritis in Pediatric Patients

Background

H. pylori infection is acquired during childhood and causes a chronic inflammatory response in the gastric mucosa, which is considered the main risk factor to acquire gastric cancer (GC) later in life. More recently, infection by Epstein-Barr virus (EBV) have also been associated with GC. The role of EBV in early inflammatory responses and its relationship with H. pylori infection remains poorly studied. Here, we assessed whether EBV infection in children correlated with the stage of gastritis and whether co-infection with H. pylori affected the severity of inflammation.

Methodology/Principal Findings

333 pediatric patients with chronic abdominal pain were studied. From them, gastric biopsies were taken and inflammation graded according to the Sydney system; peripheral blood was drawn and antibodies against EBV (IgG and IgM anti-VCA) and H. pylori (IgG anti-whole bacteria and anti-CagA) were measured in sera. We found that children infected only by EBV presented mild mononuclear (MN) and none polymorphonuclear (PMN) cell infiltration, while those infected by H. pylori presented moderate MN and mild PMN. In contrast, patients co-infected with both pathogens were significantly associated with severe gastritis. Importantly, co-infection of H. pylori CagA+/EBV+ had a stronger association with severe MN (PR 3.0) and PMN (PR 7.2) cells than cases with single H. pylori CagA+ infection.

Conclusions/Significance

Co-infection with EBV and H. pylori in pediatric patients is associated with severe gastritis. Even single infections with H. pylori CagA+ strains are associated with mild to moderate infiltration arguing for a cooperative effect of H. pylori and EBV in the gastric mucosa and revealing a critical role for EBV previously un-appreciated. This study points out the need to study both pathogens to understand the mechanism behind severe damage of the gastric mucosa, which could identified children with increased risk to present more serious lesions later in life.     

Polymorphisms of the DNA Methyltransferase 1 Associated with Reduced Risks of Helicobacter pylori Infection and Increased Risks of Gastric Atrophy

Introduction

DNA methyltransferase-1(DNMT1) is an important enzyme in determining genomic methylation patterns in mammalian cells. We investigated the associations between SNPs in the DNMT1 gene and risks of developing H. pylori seropositivity, gastric atrophy and gastric cancer in the Chinese population.

Methods

The study consisted of 447 patients with gastric cancer; 111 patients with gastric atrophy; and 961 healthy controls. Five SNPs, rs10420321, rs16999593, rs8101866, rs8111085 and rs2288349 of the DNMT1 gene were genotyped. Anti-H.pylori IgG was detected by ELISA. Gastric atrophy was screened by the level of serum pepsinogen Ιand II and then confirmed by endoscopy and histopatholgical examinations.

Results

The age- and sex-adjusted OR of H. pylori seropositivity was 0.67 (95%CI: 0.51–0.87) for rs8111085 TC/CC genotypes, significantly lower than the TT genotype in healthy controls. The adjusted OR of H.pylori seropositivity was 0.68 (95%CI: 0.52–0.89) for rs10420321 AG/GG genotypes. In addition, patients carrying rs2228349 AA genotype have a significantly increased risk for H.pylori seropositivity (OR = 1.67; 95%CI: 1.02–2.75). Further haplotype analyses also showed that the ATTTG and ATCTA are significantly associated with increased risks in H.pylori infection compared to the GTCCG haplotype (OR = 1.38, 95%CI: 1.08–1.77; OR = 1.40, 95% CI: 1.09–1.80). The adjusted ORs of gastric atrophy were 1.66 (95%CI: 1.06–2.61) for rs10420321 GG genotype, and 1.67 (95%CI 1.06–2.63, P = 0.03) for rs8111085 CC genotype, but no association was found between SNPs in the DNMT1 gene and risk of developing gastric cancer.

Conclusions

Individuals with rs10420321 GG and rs8111085 CC genotype of the DNMT1 gene were associated with reduced risks for H.pylori infection. On the other hand, higher risks of gastric atrophy were found in the carriers with these two genotypes compared to other genotypes. Our results suggested that SNPs of DNMT1 could be used as genotypic markers for predicting genetic susceptibilities to H.pylori infection and risks in gastric atrophy.     

The Rate of Helicobacter pylori Seropositivity in a Group of Korean Patients with HLA-B27-Associated Acute Anterior Uveitis

Purpose

To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU) in Korean patients.

Methods

Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included 72 non-uveitis patients and 35 age- and sex-matched healthy controls in the study.

Results

Of the 106 patients with AAU, 41 (38.7%) were HLA-B27-positive, and 45 (42.5%) were seropositive for H. pylori. Patients with HLA-B27-positive AAU had a significantly lower prevalence of H. pylori seropositivity compared to those with HLA-B27-negative AAU and healthy controls (24.4% vs. 53.8%, p = 0.003; 24.4% vs. 57.1%, p = 0.004, respectively). In the non-uveitis group, however, HLA-B27-positive patients exhibited similar H. pylori seropositivity prevalence to HLA-B27-negative patients and healthy controls (45.5% vs. 55.7%, p = 0.529; 45.5% vs. 57.1%, p = 0.497, respectively). In multivariate analysis, a low prevalence of H. pylori seropositivity was significantly associated with HLA-B27-positive AAU (odds ratio = 0.340, 95% confidence interval 0.135–0.855, p = 0.022).

Conclusions

Our results suggest an inverse association between H. pylori seropositivity and HLA-B27-positive AAU. Further investigation of this association is needed, given the low prevalence of H. pylori seropositivity observed in patients with HLA-B27-positive AAU.     

Changes in Metabolic Hormones in Malaysian Young Adults following Helicobacter pylori Eradication

Background

More than half of the world’s adults carry Helicobacter pylori. The eradication of H. pylori may affect the regulation of human metabolic hormones. The aim of this study was to evaluate the effect of H. pylori eradication on meal-associated changes in appetite-controlled insulinotropic and digestive hormones, and to assess post-eradication changes in body mass index as part of a currently on-going multicentre ESSAY (Eradication Study in Stable Adults/Youths) study.

Methods

We enrolled 29 H. pylori-positive young adult (18–30 year-old) volunteer subjects to evaluate the effect of H. pylori eradication on meal-associated changes on eight gastrointestinal hormones, using a multiplex bead assay. Changes in body mass index and anthropometric measurements were recorded, pre- and post-eradication therapy.

Results

Pre-prandial active amylin, total peptide YY (PYY) and pancreatic polypeptide (PP) levels were significantly elevated 12 months post-eradication compared with baseline (n = 18; Wilcoxon''s signed rank test, p<0.05). Four of the post-prandial gut metabolic hormones levels (GLP-1, total PYY, active amylin, PP) were significantly higher 12 months post-eradication compared to baseline (n = 18; p<0.05). Following H. pylori eradication, the BMI and anthropometric values did not significantly change.

Conclusions

Our study indicates that H. pylori eradication was associated with long-term disturbance in three hormones (active amylin, PP and total PYY) both pre- and post-prandially and one hormone (GLP-1) post-prandially. Longer post-eradication monitoring is needed to investigate the long-term impact of the observed hormonal changes on metabolic homeostasis.     

Different HCV Genotype Distributions of HIV-Infected Individuals in Henan and Guangxi,China

Background

Due to shared transmission routes, hepatitis C virus (HCV) infection is highly prevalent among people infected with human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is associated with hepatotoxicity, leading to the negative effects on patients with HIV/HCV co-infection. In order to provide valuable information for HCV management in this particular population, we investigated the HCV genotypes in HIV-infected individuals from Henan and Guangxi, the two provinces with the most HIV-infected cases in China.

Methods

Individuals, who acquired HIV infection through various risk routes, were recruited from Henan and Guangxi. Test of antibodies against HCV (anti-HCV) was conducted, and detection of HCV RNA was performed by PCR amplification. HCV subtypes were determined by direct sequencing of amplicons, followed by phylogenetic analysis.

Results

We recruited a total of 1,112 HIV-infected people in this present study. Anti-HCV was detected from 218 (50.1%) patients from Henan and 81 (12.0%) patients from Guangxi, respectively. The highest prevalence of HIV/HCV co-infection was observed from FBDs (former blood donors) (87.2%) in Henan and IDUs (intravenous drug users) (81.8%) in Guangxi, respectively. The seroprevalence rate of HCV among people with sexual contact was significantly higher in Henan than in Guangxi (18.7% vs. 3.5%, P<0.05). The positive rate of HCV RNA in Henan and Guangxi was 30.6% (133/435) and 11.2% (76/677), respectively. Moreover, we found that 20 anti-HCV negative samples were HCV positive by PCR amplification. HCV subtype 1b (52.7%) was predominant in Henan, followed by subtype 2a (41.9%). The most frequently detected subtypes in Guangxi were 6a (35.6%) and 3b (32.9%).

Conclusion

The HCV genotype distributions were different in HIV-infected people from Henan and Guangxi. HIV/HCV co-infection was not only linked to the transmission routes, but also associated with the geographic position.     

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha,South Africa: Impact on Mortality and Treatment Success

Setting

Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.

Objective

To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.

Design

A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.

Results

Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm³. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2–8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2–8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1–18.1), CD4 count ≤100 (aHR 2.1, CI 1.0–4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1–5.4).

Conclusions

Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.     

H. pylori CagL-Y58/E59 Prime Higher Integrin α5β1 in Adverse pH Condition to Enhance Hypochlorhydria Vicious Cycle for Gastric Carcinogenesis

Background/Aims

H. pylori CagL amino acid polymorphisms such as Y58/E59 can increase integrin α5β1 expression and gastric cancer risk. Hypochlorhydria during chronic H. pylori infection promotes gastric carcinogenesis. The study test whether CagL-Y58/E59 isolates may regulate integrin α5β1 to translocate CagA via the type IV secretory system even under adverse pH conditions, and whether the integrin α5β1 expression primed by H. pylori is a pH-dependent process involving hypochlorhydria in a vicious cycle to promote gastric carcinogenesis.

Methods

The expressions of integrin α5 and β1, CagA phosphorylation, IL-8, FAK, EGFR, and AKT activation of AGS cells exposed to CagL-Y58/E59 H. pylori, isogenic mutants, and different H. pylori CagL amino acid replacement mutants under different pH values were determined. Differences in the pepsinogen I/II ratio (indirectly indicating gastric acidity) and gastric integrin α5β1 expression were compared among the 172 H. pylori-infected patients with different cancer risks.

Results

Even under adversely low pH condition, H. pylori CagL-Y58/E59 still keep active integrin β1 with stronger binding affinity, CagA translocation, IL-8, FAK, EGFR, and AKT activation than the other mutants (p<0.05). The in vitro assay revealed higher priming of integrin α5β1 by H. pylori under elevated pH as hypochlorhydria (p<0.05). In the H. pylori-infected patients, the gastric integrin α5β1 expressions were higher in those with pepsinogen I/II ratio <6 than in those without (p<0.05).

Conclusions

H. pylori CagL-Y58/E59 prime higher integrin under adverse pH and may involve to enhance hypochlorhydria vicious cycle for gastric carcinogenesis, and thus require an early eradication.     

Mycobacterium tuberculosis Complex and HIV Co-Infection among Extrapulmonary Tuberculosis Suspected Cases at the University of Gondar Hospital,Northwestern Ethiopia

Background

Extrapulmonary Tuberculosis (EPTB) and Human Immunodeficiency Virus (HIV) infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients.

Method

An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of < 0.05 was taken as statistically significant.

Results

A total of 141 extrapulmonary suspected patients were enrolled in this study. The overall prevalence of culture confirmed extrapulmonary tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37). Tuberculosis lymphadenitis was the predominant (78.4%) type of EPTB infection followed by tuberculosis cold abscess (10.7%). Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013).

Conclusion

The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed.