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1.  Widespread antibiotic resistance of diarrheagenic Escherichia coli and Shigella species 
Antibiotic resistance of enteric pathogens particularly Shigella species, is a critical world-wide problem and monitoring their resistant pattern is essential, because the choice of antibiotics is absolutely dependent on regional antibiotic susceptibility patterns. During summer 2013, an unusual increase in number of diarrheal diseases was noticed in Isfahan, a central province of Iran. Therefore, the antibiotic resistance of diarrheagenic Escherichia coli and Shigella species isolated were evaluated.
Materials and Methods:
According to the guideline on National Surveillance System for Foodborn Diseases, random samples from patients with acute diarrhea were examined in local laboratories of health centers and samples suspicious of Shigella spp. were further assessed in referral laboratory. Isolated pathogens were identified by standard biochemical and serologic tests and antibiotic susceptibility testing was carried out by disc diffusion method.
A total of 1086 specimens were obtained and 58 samples suspicious of Shigella were specifically evaluated. The most prevalent isolated pathogen was Shigella sonnei (26/58) followed by E. coli (25/58) and Shigella flexneri (3/58). A large number of isolated bacteria were resistant to co-trimoxazole (Shigella spp: 100%, E. coli: 80%), azithromycin (Shigella spp: 70.4%, E. coli: 44.0%), ceftriaxone (Shigella spp: 88.9%, E. coli: 56.0%) and cefixime (Shigella spp: 85.2%, E. coli: 68.0%). About88.3% of S. sonnei isolates, one S. flexneri isolate, and 56% of E. coli strains were resistant to at least three antibiotic classes (multidrug resistant).
Due to high levels of resistance to recommended and commonly used antibiotics for diarrhea, continuous monitoring of antibiotic resistance seems essential for determining best options of empirical therapy.
PMCID: PMC4078378  PMID: 25002896
Antibiotic resistance; diarrhea; Escherichia coli; Iran; Shigella
2.  HIV-Specific CD8+ T Lymphocytes in Blood of Long-Term HIV-Infected Hemophilia Patients 
BioResearch Open Access  2013;2(6):399-411.
Hemophilia patients infected with human immunodeficiency virus (HIV) 30 years ago show increased proportions of activated CD8+DR+ blood lymphocytes. We hypothesized that this might indicate a cellular immune response directed against HIV and might be the reason for long-term clinical stability of these patients. CD8+ peripheral blood lymphocytes (PBL) reactive with six HIV and two cytomegalovirus (CMV) pentamers were determined in heparinized whole blood. Additional lymphocyte subsets as well as plasma cytokines and HIV-1 load were studied. Long-term HIV-infected hemophilia patients with (n=15) or without (n=33) currently detectable HIV-1 load in the plasma showed higher proportions of CD8+ lymphocytes reactive with HIV (p<0.001) and CMV pentamers (p=0.010) than healthy individuals. The cellular anti-HIV response tended to be stronger and more polyclonal in patients during periods of viral replication than in patients with retroviral quiescence (p=0.077). Anti-HIV CD8+ lymphocyte responses were strongest in patients with high counts of activated CD8+DR+ T (r=0.353; p=0.014) and low CD19+ B lymphocyte counts (r=−0.472; p=0.001). Patients with or without HIV-1 viral load showed normal Th1 and Th2 plasma cytokine levels and high plasma interleukin-6 (versus healthy controls, p=0.001) and tumor necrosis factor-α (p=0.020). Hemophilia patients who have been living with HIV for more than 30 years showed a polyclonal CD8+ T-cell response against HIV and CMV. This cellular antiviral immune response was strongest during periods of HIV-1 replication and remained detectable during periods of HIV-1 quiescence. We hypothesize that the consistent cellular anti-HIV-1 response in combination with highly active antiretroviral therapy ensures stability and survival of these chronically HIV-1–infected hemophilia patients.
PMCID: PMC3869412  PMID: 24380050
CMV; HIV-specific CD8+ T lymphocytes in blood; long-term HIV-infected hemophilia patients; stable disease
3.  Hepatitis A Virus Seropositivity in Nurses and Paramedical Personnel at a University Hospital in North Iran 
The status of hepatitis A virus (HAV) among health care workers has not been studied yet in Iran.
This study aimed to evaluate the HAV seropositivity among the healthcare personnel in Ayatollah Rohani Hospital, Babol, Iran, according to age, number of working years, and other demographic data.
Patients and Methods
This cross sectional study was performed on all nurses, nurses' aid, and paramedical technicians at Ayatollah Rohani Hospital, Babol, from March 2011 to March 2012. Blood was obtained from all cases (466) and the sera were separated. All serum samples were tested for anti-HAV antibodies (IgG) by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by logistic regression analysis using SPSS software, version 18.
330 out of 466 (71%) persons were positive for anti-HAV antibodies (IgG) with no significant difference between females (71.5%) and males (70%) (P = 0.89, 95% CI. 0.533-2.083). The lowest sero-prevalence rate was observed in the 20-29 year age group (57.8%). Seropositivity for HAV significantly increased with age (P < 0.000, 95% CI. 1.626-3.262), 77.4% for 30-39 years and 85.3% for more than 40 years. The seropositivity rate also increased significantly in accordance with the number of working years (P = 0.012, 95%CI. 1.098-2.170). 110 out of 353 (31.2%) cases were seronegative among those with less than 5 years of working time. An obvious decrease of seronegative rate of HAV was seen in those with 5-10 years (27%) and more than 10 years (14.3%) of working time.
These findings indicate relatively high prevalence rate of HA infection among nurses and paramedical personnel at this hospital. Nevertheless, 30% of the health workers have been seronegative and are still at risk of HA infection development. Considering that the disease has more severe course as age increases, improvement of standard hygiene and prevention strategies are recommended. Furthermore, vaccination may play a significant role in the occupational health policy to protect the susceptible health care workers population in the future.
PMCID: PMC3838651  PMID: 24349729
Hepatitis A virus, Nurses; Allied Health Personnel; HIV Seroprevalence
4.  Primary percutaneous coronary intervention in the Isfahan province, Iran; A situation analysis and needs assessment 
ARYA Atherosclerosis  2013;9(1):38-44.
Primary percutaneous coronary intervention (PPCI) is considered as a choice of treatment in ST-elevation myocardial infarction (STEMI). PPCI has been performed in the Isfahan Province for several years. This study was performed to describe the situation, and determine in-hospital and early (30 days) clinical outcomes of the patients in order to provide sufficient evidence to evaluate and modify this treatment modality if necessary.
All patients, who underwent PPCI for STEMI from July to December 2011 at Chamran and Saadi Hospitals (PPCI centers in the Isfahan Province), were included in this case series study. Premedication, angioplasty procedure, and post-procedural treatment were performed using standard protocols or techniques. All discharged patients were followed for 30 days by phone. Endpoints consisted of clinical success rate, and in-hospital and 30 day major adverse cardiac events (MACEs) (death, reinfarction, stroke, and target vessel revascularization).
93 patients (83 (89.2%) at Chamran Hospital and 10 (10.8%) patients at Saadi Hospital) had PPCI. Mean Age of the patients was 59.60 ± 11.10 and M/F ratio was 3.89. From the 181 involved vessels (involved vessels/patient ratio = 1.97 ± 0.70), the treatment of 105 lesions (lesions/patient ratio = 1.13 ± 0.368) was attempted. The clinical success rate was 72%. Pain-to-door and door-to-balloon times were, respectively, 255.1 ± 221.4 and 148.9 ± 168.5 min. The reason for failure was impaired flow (n = 17 (18.3%)), failure to cross with a guidewire (n = 2 (2.2%)), suboptimal angiographic results (n = 2 (2.2%)), and death in one patient. The in-hospital and 30 days MACE rates were, respectively, 8.6% and 3.2%.
Low success rate in our series could be due to prolonged pain-to-door and door-to-balloon times and lack of an established, definite protocol to regularly perform PPCI in a timely fashion. We should resolve these problems and improve our techniques in order to prevent and treat slow/no-reflow phenomenon.
PMCID: PMC3653265  PMID: 23696758
Acute Coronary Syndrome; Myocardial Infarction; Percutaneous Transluminal Coronary Angioplasty; Cardiogenic Shock; No-Reflow Phenomenon
5.  In-vitro inhibition of IFNγ+ iTreg mediated by monoclonal antibodies against cell surface determinants essential for iTreg function 
BMC Immunology  2012;13:47.
IFNγ-producing CD4+CD25+Foxp3+ PBL represent a subtype of iTreg that are associated with good long-term graft outcome in renal transplant recipients and suppress alloresponses in-vitro. To study the mechanism of immunosuppression, we attempted to block cell surface receptors and thereby inhibited the function of this iTreg subset in-vitro using monoclonal antibodies and recombinant proteins.
PBL of healthy control individuals were stimulated polyclonally in-vitro in the presence of monoclonal antibodies or recombinant proteins against/of CD178, CD152, CD279, CD28, CD95, and HLA-DR. Induction of IFNγ+ iTreg and proliferation of effector cells was determined using four-color fluorescence flow cytometry. Blockade of iTreg function was analyzed using polyclonally stimulated co-cultures with separated CD4+CD25+CD127-IFNγ+ PBL.
High monoclonal antibody concentrations inhibited the induction of CD4+CD25+Foxp3+IFNγ+ PBL (anti-CD152, anti-CD279, anti-CD95: p < 0.05) and CD4+CD25+CD127-IFNγ+ PBL (anti-CD178, anti-CD152, anti-CD279, anti-CD95: p < 0.05). Effector cell proliferation increased with increasing antibody concentrations in culture medium (anti-CD178 and anti-CD279: p < 0.05). Conversely, high concentrations of recombinant proteins induced formation of CD4+CD25+Foxp3+IFNγ+ PBL (rCD152 and rCD95: p < 0.05) and decreased cell proliferation dose-dependently (rCD178 and rCD95: p < 0.05). Our data suggest an inverse association of iTreg induction with effector cell proliferation in cell culture which is dependent on the concentration of monoclonal antibodies against iTreg surface determinants. 3-day co-cultures of polyclonally stimulated PBL with separated CD4+CD25+CD127-IFNγ+ PBL showed lower cell proliferation than co-cultures with CD4+CD25+CD127-IFNγ- PBL (p < 0.05). Cell proliferation increased strongly in CD4+CD25+CD127-IFNγ- PBL-containing co-cultures in the presence of monoclonal antibody (anti-CD28, anti-CD152, anti-CD279: p < 0.05) but remained low in co-cultures with CD4+CD25+CD127-IFNγ+ PBL (with the exception anti-CD28 monoclonal antibody: p < 0.05). Monoclonal antibodies prevent iTreg induction in co-cultures with CD4+CD25+CD127-IFNγ- PBL but do not efficiently block suppressive iTreg function in co-cultures with CD4+CD25+CD127-IFNγ+ PBL.
CD178, CD152, CD279, CD28, CD95, and HLA-DR determinants are important for induction and suppressive function of IFNγ+ iTreg.
PMCID: PMC3482559  PMID: 22905732
IFNγ+ iTreg; IFNγ+Foxp3+; IFNγ+CD127-; CD178; CD152; CD279; CD28; CD95; HLA-DR; Inhibition; Cell proliferation
6.  Cytokine expression during early and late phase of acute Puumala hantavirus infection 
BMC Immunology  2011;12:65.
Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection.
We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa .
High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection.
PMCID: PMC3259039  PMID: 22085404

Results 1-6 (6)