High Prevalence Rate of Microbial Contamination in Patient-Ready Gastrointestinal Endoscopes in Tehran, Iran: an Alarming Sign for the Occurrence of Severe Outbreaks.

An alarmingly increasing number of outbreaks caused by contaminated gastrointestinal (GI) endoscopes are being reported as a particularly concerning issue. This study is the first large-scale multicenter survey to evaluate the contamination of GI endoscopes in Tehran, Iran. This multicenter study was conducted among 15 tertiary referral and specialized gastrointestinal settings. Reprocessed GI endoscopes were sampled by the sequence of the flush-brush-flush method. Bacterial and viral contamination, as well as antimicrobial resistance, were explored by culture and molecular assays. A total of 133 reprocessed and ready-to-use GI endoscopes were investigated. In phase I and phase II, 47% and 32%, respectively, of the GI endoscopes were determined to be contaminated. GI flora was the most prevalent contaminant isolated from GI endoscopes, in which the most predominant bacteria were Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, in both phase I and II evaluations. The majority of the isolated bacteria in the current study were considered multidrug-resistant organisms (MDROs). More importantly, we recovered carbapenem-resistant nonfermentative Gram-negative bacilli (CRNFGNB), carbapenem-resistant Enterobacterales (CRE), extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales (ESBL-E), multidrug-resistant Clostridioides difficile, vancomycin-resistant Enterococcus (VRE), and drug-resistant Candida spp. Disconcertingly, our molecular assays revealed contamination of some reprocessed GI endoscopes with hepatitis B virus (HBV), hepatitis C virus (HCV), and even HIV. This multicenter study indicates a higher-than-expected contamination rate among reprocessed and ready-for-patient-use GI endoscopes, which suggests a higher-than-expected endoscopy-associated infection (EAI) risk, and potentially, morbidity and mortality rate, associated with endoscopy procedures in Tehran, Iran. IMPORTANCE In the light of severe outbreaks caused by multidrug-resistant microorganisms due to contaminated GI endoscopes, understanding to what extent GI endoscopes are inadequately reprocessed is crucial. Several studies assessed contamination of GI endoscopes with various outcomes across the world; however, the prevalence and risk factors of contaminated GI endoscopes and potential subsequent nosocomial spread are still unknown in Iran. The present study is the first large-scale multicenter survey to evaluate the microbial contamination of repossessed and ready-to-use GI endoscopes in Tehran, Iran. Our study showed a higher-than-expected contamination rate among reprocessed GI endoscopes, which suggests potential seeding of deadly but preventable outbreaks associated with endoscopy procedures in Iran. These results suggest that the current reprocessing and process control guidelines do not suffice in Iran. The current study is of particular importance and could provide insights into unrecognized and unidentified endoscopy-associated outbreaks in Iran.

Enhancement of therapeutic DNA vaccine potency by melatonin through inhibiting VEGF expression and induction of antitumor immunity mediated by CD8+ T cells.

To be effective, therapeutic cancer vaccines should stimulate both an effective cell-mediated and a robust cytotoxic CD8+ T-cell response against human papillomavirus (HPV)-infected cells to treat the pre-existing tumors and prevent potential future tumors. In this study, the therapeutic experiments were designed in order to evaluate antitumor effect against the syngeneic TC-1 tumor model. The anti-tumor efficacy of a HPV-16 E7 DNA vaccine adjuvanted with melatonin (MLT) was evaluated in a C57BL/6 mouse tumor model by measuring tumor growth post vaccination and the survival rate of tumor-bearing mice, analyzing the specific lymphocyte proliferation responses in control and vaccinated mice by MTT assay. The E7-specific cytotoxic T cells (CTL) were analyzed by lymphocyte proliferation and lactate dehydrogenates (LDH) release assays. IFN-γ, IL-4 and TNF-α secretion in splenocyte cultures as well as vascular endothelial growth factor (VEGF) and IL-10 in the tumor microenvironment were assayed by ELISA. Our results demonstrated that subcutaneous administration of C57BL/6 mice with a DNA vaccine adjuvanted with MLT dose-dependently and significantly induced strong HPV16 E7-specific CD8+ cytotoxicity and IFN-γ and TNF-α responses capable of reducing HPV-16 E7-expressing tumor volume. A significantly higher level of E7-specific T-cell proliferation was also found in the adjuvanted vaccine group. Furthermore, tumor growth was significantly inhibited when the DNA vaccine was combined with MLT and the survival time of TC-1 tumor bearing mice was also significantly prolonged. In vivo studies further demonstrated that MLT decreased the accumulation of IL-10 and VEGF in the tumor microenvironment of vaccinated mice. These data indicate that melatonin as an adjuvant augmented the cancer vaccine efficiency against HPV-associated tumors in a dose dependent manner.

The Early Results of a New Health Care Program Implementation in HBV Screening: an Iranian Experience.

BACKGROUND According to the reports of World Health Organization (WHO) and Centers for Disease Control and Prevention, the prevalence of chronic hepatitis B infection in Iran has decreased from 2-7% in 2001 to 1.3-0.8% in children aged 2-14 years. In 2010 the Institute of Medicine recommended more comprehensive screening by primary care physicians (PCPs) for evaluation, vaccination, and management of infected patients for further decrease in the prevalence of chronic HBV infection. Thus, with contribution of the Health Department, we developed a practical flowchart for PCPs to start active screening of hepatitis B virus (HBV) in all visited patients and refer the positive cases for further evaluation and management to Taleghani Hospital. METHODS With collaboration of Health Department of Shahid Beheshti University of Medical Sciences), physicians of health centers were asked to screen all their patients for HBsAg. Positive cases were referred to Taleghani Hospital. They were first registered and educated about their disease, life style, and prevention methods. Their first degree families were screened for HBV infection too and were referred for vaccination if needed. According to the results of lab tests, appropriate management was done by a hepatologist. RESULTS Since implementation of this program, we have encountered a significant rise in patient detection (even in high risk groups). Many of them were not aware of their disease and most of those who were aware of their disease were not managed appropriately. Family screening and vaccination were inadequate and need more emphasis. CONCLUSION Although health system is active about screening of HBV infection in high risk populations, it is not perfect. It seems that health system needs to upgrade the screening and management programs of HBV infection.

Subtype analysis of Cryptosporidium parvum and Cryptosporidium hominis isolates from humans and cattle in Iran.

Cryptosporidium is an intestinal parasite associated with severe acute diarrhea in humans and animals. To investigate subtypes of Cryptosporidium spp. isolated from humans and cattle in Iran, 47 Cryptosporidium parvum (22 from children and 25 from cattle) and three Cryptosporidium hominis from children were characterized by sequence analysis of the 60 kDa glycoprotein (gp60) gene. Nine subtypes (two of C. hominis and seven of C. parvum) in four subtype families were identified. Cattle were mainly infected with C. parvum IIa subtypes and humans mostly with the C. parvum IIa and IId subtypes. Consequently, cattle could be a source of human infection with C. parvum IIa in Iran. However, the occurrence of subtype IId families in Iranian children, suggests that other infection sources might also be involved in C. parvum transmission. To our knowledge, this is the first published record and description of Cryptosporidium subtypes in Iran.

Evaluation of Zinc Plasma Level in Iranian Cirrhotic Patients due to Hepatitis B and Hepatitis C.

BACKGROUND AND AIMS: Zinc (Zn) has various significant roles in physiological functions of the liver. Furthermore, it has been reported that the administration of zinc has an important role in pharmacotherapy of viral hepatitis. Cirrhotic patients with decrease in plasma zinc level have been covered in previous studies. It is seemingly necessary to assess the zinc level, in Iranian cirrhotic patients, as a distinct population, Because of the large phytate amounts in Iranians diet. Regarding to etiology, disease progress, and treatment, there are some differences in the 2 most common causes of cirrhosis in the Iranian population (hepatitis B and hepatitis C) and it is possible that the zinc level may be different between the two. This study was done to shadow some lights on the subject. METHODS: Between April 2008 and November 2008, plasma zinc level was determined, by atomic absorption method, in 60 cirrhotic inpatients treated due to hepatitis B or hepatitis C in Talighani hospital (a referral center for gastrontestinal and liver diseases in Tehran, Iran). RESULTS: Mean ± standard deviation (SD) plasma zinc levels determined 0.34±0.22 mg/L and 0.37±0.22 mg/L in hepatitis B and hepatitis C patients respectively. Analysis of t-test showed there is no significant difference between 2 groups regarding to plasma zinc level (P = 0.745). CONCLUSIONS: It is concluded that zinc level of studied cirrhotic patients is less than half of the normal range. Moreover, there is no difference in plasma zinc level between cirrhotic patients due to hepatitis B or hepatitis C. Regarding to this result, supplementation with complementary zinc, may be recommended in both groups in order to optimize the nutritional support and probably better the treatment response.

Effects of amino acid substitution polymorphisms of two DNA methyltransferases on susceptibility to sporadic colorectal cancer.

BACKGROUND AND AIM: The present study was designed to consider whether amino acid substitution polymorphisms in O6-methylguanine-DNA methyltransferase (MGMT) and DNA methyl transferase 1 (DNMT1) genes may be associated with the genetic susceptibility to sporadic colorectal cancer. PATIENTS AND METHODS: We assessed eight non-synonymous polymorphisms of these two genes by PCR/pyrosequencing. Our population consisted of 208 individuals with sporadic colorectal cancer and 213 controls. Allele frequencies and genotypes were compared between the two groups. RESULTS: The calculated odds ratios indicated no association between DNMT1 and colorectal cancer. However, there was a significant association between two polymorphisms in MGMT with sporadic colorectal cancer: Arg128Gln (OR, 5.53; 95% CI) and Gly160Arg (OR, 3.04; 95% CI). CONCLUSIONS: These findings could be indicative of factors contributing to high occurrence of Iranian colorectal cancer patients.