Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 19, Issue 3, 2019

Background: Hepatitis B virus (HBV) infection remains a global health problem. As “cure” for chronic hepatitis B is of current priority, hepatitis B immunoglobulin (HBIG) has been utilized for several decades to provide post-exposure prophylaxis. In recent years, a number of monoclonal antibodies (mAbs) targeting HBV have been developed and demonstrated with high affinity, specificity, and neutralizing potency. Objective: HBV neutralizing antibodies may play a potentially significant role in the search for an HBV cure. In this review, we will summarize the recent progress in developing HBV-neutralizing antibodies, describing their characteristics and potential clinical applications. Results and Conclusion: HBV neutralizing antibodies could be a promising alternative in the prevention and treatment of HBV infection. More importantly, global collaboration and coordinated approaches are thus needed to facilitate the development of novel therapies for HBV infection.

Today’s microbial infections’ resistance to approved drugs, the emergence of new infectious diseases and lack of vaccines, create a huge threat to human health. Thus, there is an urgent need to create novel antimicrobial agents, but the high cost and prolonged timeline of novel drug discovery and development is the major barrier to make new drugs. Therefore, there is a need for specific cost effective approaches in order to identify new drugs for the treatment of various microbial infections. Drug repurposition is an alternative technique to find existing clinically approved drugs for other indications. This approach may enhance the portfolio of Pharmaceutical companies by reducing the time and money required for the development of new chemical entity. In literature, various studies have reported some encouraging results regarding the antimicrobial use of existing statin drugs. Further, some clinical studies have also shown the protective effect of statin drugs in reduction of the morbidity and mortality due to many infectious diseases but complete understanding is still lacking. Thus, there is a need for better understanding of the use of statin drugs, especially in the context of antimicrobial effects. In this review, we try to summarize the use of statin drugs in various infectious diseases and their proposed antimicrobial mechanism of action. Further, current challenges and future perspectives of repurposition of statin drugs as antimicrobial agents have also been discussed.

Background: In the United States, tick-borne illnesses account for a significant number of patients that have been seen and treated by health care facilities. This in turn, has resulted in a significant morbidity and mortality and economic costs to the country. Methods: The distribution of these illnesses is geographically variable and is related to the climate as well. Many of these illnesses can be diagnosed and treated successfully, if recognized and started on appropriate antimicrobial therapy early in the disease process. Patient with illnesses such as Lyme disease, Wet Nile illness can result in chronic debilitating diseases if not recognized early and treated. Conclusion: This paper covers illnesses such as Lyme disease, West Nile illness, Rocky Mountain Spotted fever, Ehrlichia, Tularemia, typhus, mosquito borne illnesses such as enteroviruses, arboviruses as well as arthropod and rodent borne virus infections as well. It covers the epidemiology, clinical features and diagnostic tools needed to make the diagnosis and treat these patients as well.

Background: Fasciolosis, an infectious disorder with a serious public health burden, is caused by two liver flukes belonging to the genus Fasciola. Iran is among the endemic areas for this disease. This study aimed to determine the seroprevalence of human fasciolosis in Iran. Methods: A systematic search was conducted in Embase, PubMed/MEDLINE, Web of Science (WoS), and Google Scholar, as well as Iranian databases including Scientific Information Database (SID), Magiran and Irandoc from January 2000 to June 2016. In order to determine fasciolosis prevalence, the DerSimonian-Laird random model was used. In order to assess the heterogeneity among studies, I2 and Q tests were used. To investigate the source of heterogeneity, meta-regressions based on the year of publication and sample size were performed. Sensitivity analysis was carried out to ensure the stability of obtained results. Results: Eleven relevant studies were included. According to the data analysis a prevalence rate of 2% [95% CI 1-5] was found. No statistically significant relationship between gender and disease prevalence could be detected. We found an OR of developing fasciolosis of 1.67 [95% CI: 0.42 - 6.60] in people who had consumed vegetables versus those who did not eat vegetables, even though this did not yield statistical significance. Conclusion: The findings of the current study can be valuable and help the health-care workers and policy-makers in programming and implementing ad hoc interventions in order to prevent the incidence of disease.

Background: Cystic echinococcosis/ hydatidosis is one of the most important parasitic zoonoses worldwide. Usually, surgery is used for the treatment of active cysts. Due to the risk of cyst rupture during surgery, a protoscolicidal agent is usually injected into the cyst before surgery to prevent secondary cyst formation in case of cyst rupture. Due to the side effects of chemical protoscolicidal agents attempts have been focused on herbal medicine. In this regard, Allium sativum has already been used; however, the protoscolicidal effect of Allium hirtifolium from Allium family has not been investigated, so far. Objective: The present study was conducted in order to assess the protoscolicidal effect of methanolic extract of Allium hirtifolium in different concentrations, temperature and exposure times. Cetrimide as a positive control and DMSO as a negative control were also used in this study. Methods: The viability of protoscoleces was determined by 0.1% eosin staining method. Results: The protoscolicidal effect of Allium hirtifolium on protoscoleces was as follows: The mean percent and standard deviation (SD) of protoscolicidal activity of 50 mg/ml concentration of Allium hirtifolium extract in room temperature at 10, 20, 30, 40 and 50 minutes of exposure was 5.88±2.39, 8.59±4.54, 11.82±5.81, 12.31±6.16and 16.96±8.42 respectively; while at 37°C it was 9.10±5.01, 11.52±7.36, 18.64±4.36, 27.07±6.57 and 38.15±12.80, respectively. Conclusion: In conclusion, although Allium hirtifolium from Allium family is similar to Allium sativum; the protoscolicidal effect of its methanolic extract is not similar and less than A. sativum extract.

Introduction: Aeromonas have recently emerged as opportunistic pathogens and only a few studies are available regarding the isolation of these bacteria from burn wound infections. This study aimed at isolating Aeromonas as an infrequent cause of infection in this group of immunocompromised patients. Methods: A total of 300 samples were collected from the wounds of burn patients hospitalized in Gotbodin Shirazi Burn Center in 2013. The samples were cultured on Aeromonas specific media and then confirmed using standard biochemical tests and 16S rRNA gene amplification and sequencing. The antibiotic susceptibility of the isolates was determined using the disk diffusion and broth microdilution methods. Results: Biochemical tests demonstrated five presumptive samples of Aeromonas, while, molecular testing confirmed only three. All isolates were resistant to ampicillin-sulbactam, erythromycin, oxacillin, and vancomycin. However, they were susceptible to gentamicin, meropenem, nitrofurantoin, chloramphenicol, cephalexin, and cefotaxime. Two Aeromonas veronii isolates were resistant to sulfamethoxazole-trimethoprim and sensitive to nalidixic acid, while Aeromonas bestiarum was sensitive to the former and resistant to the latter antibiotics. Lastly, only one of the A. veronii isolates was found to be resistant to tetracycline. Conclusion: This study is the first to report on the isolation of Aeromonas spp. from burn patients in Iran. Moreover, this is the first report of isolating A. bestiarum from burn wounds. The results of this study confirm earlier findings that the use of molecular methods is essential to accurately identify these bacteria.

Objective: Helicobacter pylori is a Gram-negative bacterium which has a serious effect on up to half of the world’s population and has been related to different gastric diseases. The goal of this study was to assess the frequency of babA, cagE and cagA genotypes among H. pylori strains isolated from gastric biopsies of endoscopic patients in the north of Iran. Methods: The present study was performed on 90 strains of H. pylori isolated from patients with gastric diseases (Gastric ulcer (GU), Duodenal ulcer (DU), Gastritis (G), Non-ulcer dyspepsia (NUD) and Gastric adenocarcinoma (GC)). DNA was extracted from all isolated strains and PCR method was performed to detect the prevalence of babA2, cagE and cagA genes using specific primers. Results: Among 90 samples of H. pylori, babA2, cagE, and cagA genes were detected in 42.2%, 30% and 82.2% of strains respectively. The statistical analysis showed that the prevalence of cagA gene in GU, G, DU, and NUD was significantly higher than other genes. Moreover, cagA, and babA2 genes were significantly more prevalent in GC patients compared to cagE gene. Our isolates exhibited 8 distinct arrangements of virulence patterns. The occurrence of cagA (35.6%) was the most prevalent pattern followed by cagA/babA2 (20%) and cagA/babA2/cagE (14.4%). Conclusion: In summary, as first report from Guilan province in the north of Iran, we showed significant association between the presence of babA2, cagE, and cagA genes in different types of gastric disorders.

Background and Aims: Hepatitis viruses are not transmitted via gastrointestinal endoscopy except if there are any mistakes in sterilization and disinfection of the endoscope that disrupt the infection control measures. So we aimed to measure the risk of transmitting HCV by GI endoscopy at department of Tropical Medicine and infectious Diseases, in a major University hospital in Egypt. Methods: Our study was conducted on four hundred patients with exclusion of those with HCV, HBV, and/or HIV positive antibodies. An ethical committee approval and a given consent were taken prior to enrollment on the study. Our patients are grouped into the following; 100 patients undergoing upper GI endoscopy without biopsy as group I; 100 patients undergoing upper GI endoscopy with biopsy as group II; 100 patients undergoing lower GI endoscopy without biopsy as group III and 100 patients undergoing lower GI endoscopy with biopsy as group IV. HCV antibodies were done 3 months after endoscopy with exclusion of other risks of HCV infection by a detailed questionnaire. Results: Only one case was reported positive after 3 months of procedure; it was after colonoscopy with biopsy using reusable forceps. Conclusions: Strict infection control measures of the GI endoscopes despite being effective in preventing HCV transmission, the reuse of disinfected biopsy forceps may be associated with a risk of transmission. So, we recommend using disposable forceps for every patient to omit the risk of HCV transmission during endoscopy.

Background: Intestinal parasitic infections are the one of the most common health problems in developing countries. Objective: A number of patients die annually due to complications caused by these parasites.Therefore, the aim of this study was to investigate the rate and type of parasitic infections, determine the factors affecting them in Ilam city and also provide strategies to prevent them.In this descriptive cross-sectional study conducted in one of the Ilam labs in 2016, 417 stool specimens were randomly collected. All specimens were examined using direct and ethanol formaldehyde.Suspect specimens were examined using Trichrom staining. Demographic information was also recorded in a questionnaire, and finally the results were analyzed using statistical software SPSS 20.The data were then compared with Chi-square test. Results: Out of the 417 patients examined, 59 (14.1%) were infected with intestinal parasites. The type of parasitic infection in 9.4% was Blastocystis hominis, 3.6% Entamoeba coli, 0.5% Entamoeba histolytica, 0.5% Giardia and 0.2% Trichomonas hominis. Conclusion: Despite the improvement of public health, parasitic infections are still considered as one of the health problems in the city of Ilam. Therefore, proper planning, public health education, raising the level of health in the area and the provision of safe drinking water are some of the ways to reduce parasitic infections in the region.

Objective: Appropriate mobile-based self-management strategies can be as new approaches to decelerate the HIV infection progression and improve the quality of life. This study aims at (i) identifying in the literature mobile-based self-management strategies for HIV care and (ii) prioritizing those from the point of view of infectious diseases specialists. This study provides some clues to design useful mobile-based self-management tools for HIV patients, from the point of view of practitioners. Methods: This mixed methods study was done in two main phases. In the first phase, a review was conducted in: PubMed, Web of Science, Science Direct, Scopus, and Ovid. In this manner, related studies published between 2010 and 2017 and in the English language were reviewed. In the second phase, identified mobile-based self-management strategies were scored and prioritized by 23 participants. Frequency distribution and mean reports were calculated using SPSS statistical software. Results: By detailed reviewing of 24 related articles, the HIV mobile-based self-management strategies were identified in 47 categories and subcategories. According to the findings, "enhance the quality of life" was the main self-management strategy addressed by reviewed studies. However, "antiretroviral therapy and medication adherence" was reported at a higher rate to be a more helpful strategy than "enhance the quality of life". Conclusion: In this study, helpful HIV mobile-based self-management strategies were identified that can be used to guide self-management interventions which have the potential to improve the healthcare services for people living with HIV.

Background: With recent progress in the treatment of people living with HIV (PLWH) and their increased rate of survival, health-related quality of life (HRQoL) has become an important issue. Objective: In the present study, we aimed to investigate the association of current CD4 cell count, baseline CD4 cell count, nadir CD4 cell count, and plasma viral load with health-related quality of life in PLWH. Methods: Participants were 67 PLWH who were under the treatment of antiretroviral therapy (ART) in Imam Khomeini Hospital of Tehran, Iran in 2016. Participants were divided into the two groups with high and low levels of current CD4 cell count, baseline CD4 cell count, nadir CD4 cell count and plasma viral load. We used independent sample t-test for data analysis using SPSS 22 software. Results: Our results demonstrated that for current CD4 cell count, the group differences were significant for total scores of HRQoL (P=0.028), also in the components of physical functioning (P=0.032), role limitation due to physical health problems (P=0.006), and role limitation due to emotional problems (P=0.009). Our data analysis showed that for baseline CD4 cell count (P=0.62), nadir CD4 cell count (P=0.29), and viral load group (P=0.78), the differences were not significant for HRQoL. Conclusion: Knowing the association between current CD4 count and health-related quality of life, adherence to ART might be a motivator for PLWH to enhance their health-related quality of life.

Background: The introduction of Antiretroviral Therapy (ART) has resulted in the emergence of some metabolic complications including hyperglycemia and diabetes mellitus among HIV positive patients. The aim of this study was to investigate the prevalence of hyperglycemia, diabetes mellitus and their associated risk factors in HIV positive patients. Methods: This cross-sectional study was conducted on HIV positive patients who visited Voluntary Counseling and Testing (VCT) center of Imam Khomeini Hospital, Tehran, Iran (2004-2013). Medical records of patients were reviewed retrospectively. A logistic regression model was applied for analysis of the association between glycemic status and relevant risk factors. Results: Out of 480 patients who were included in this study, 267 (55.6%) had hyperglycemia, including 28 (5.8%) with diabetes mellitus and 239 (49.8%) with pre-diabetes. The higher frequency of hyperglycemia, was found to be significantly associated with older age (OR for patients #131;40 years old, 2.260; 95% CI, 1.491, 3.247), male gender (OR, 1.555; 95% CI, 1.047, 2.311), higher Body Mass Index (OR for patients with BMI#131;25 Kg/m², 1.706; 95% CI, 1.149, 2.531) and prolonged duration of HIV infection (OR for patients with duration of HIV infection ≥60 months, 2.027; 95% CI, 1.372, 2.992). Conclusion: Hyperglycemia, especially pre-diabetes, is highly frequent among Iranian people living with HIV. Male gender, older age, prolonged duration of HIV infection, and higher BMI were associated with a higher prevalence of hyperglycemia. Hence, it is important to screen all HIV infected patients at the time of diagnosis and then periodically for hyperglycemia.

Background: Many synthetic procedures were reported till date to prepare pyrazoline derivatives. Some have published pyrazolines from different chalcone derivatives in the literature. Objective: A series of new pyrazolines containing novel 2,5-dichloro-3-acetylthiophene chalcone moiety (PZT1-PZT20) have been synthesized, characterized by 1HNMR and 13CNMR and evaluated for them in vitro antitubercular activity against M. tuberculosis H37Rv strain and in vitro anticancer activity against DU-145 prostate cancer cell lines and all compounds were also screened for molecular docking studies against specific targeted protein domains. Methods: All compounds were screened for potential activity against Mycobacterium tuberculosis H37Rv (MTB) strain and anticancer activity against DU-149 prostate cancer cell lines using MTT cytotoxicity assay. Results: Among the series, compound PZT5 with 2”, 4”-dichlorophenyl group at 5-position on the pyrazoline ring exhibited the most potent antitubercular activity (MIC=1.60 μg/mL) and compounds PZT2, PZT9, PZT11, PZT15, and PZT20 showed similar antitubercular activity against standard pyrazinamide (MIC=3.12 μg/mL) by broth dilution assay. PZT15 and PZT17 with 4”- pyridinyl and 2”-pyrrolyl groups on pyrazoline ring were found to exhibit better anticancer activity against DU-149 prostate cancer cell lines with IC50 values of 2.0±0.2 μg/mL and 6.0±0.3 μg/mL respectively by MTT assay. The preliminary structure-activity relationship has been summarized. The molecular docking studies with crystalline structures of enoyl acyl carrier protein reductase InhA interaction with target protein (2NSD; PDB and 3FNG; PDB) of Mycobacterium tuberculosis H37Rv (MTB) strain have also exhibited good ligand interaction and binding affinity. Ligand interaction and binding affinity were estimated using crystal structures of both types of enoyl acyl carrier protein reductase InhA (3FNG.pdb) and found to be much higher (-16.70 to - 19.20 kcal/mol) compared with pyrazinamide (-10.70 kcal/mol) as a standard target molecule. Whereas the binding affinities of six active compounds with crystal structure of other type of enoyl acyl carrier protein reductase InhA (2NSD.pdb) were much similar and higher (-9.30 to - 11.20 kcal/mole) than pyrazinamide (-11.10 kcal/mole). Conclusion: These new pyrazolines would be promising potent inhibitors of drug sensitive and drug resistant Mycobacterium tuberculosis strain and potential anticancer agents against prostate cancer and other prototypes of cancers.

Introduction: The aim of the current study was to investigate the prevalence of virulence genes in uropathogenic Escherichia coli (UPEC) isolates in Ilam. Materials and Methods: For this purpose, a total of 80 UPEC isolates were collected for patients with UTIs during a 6 months period. The multiplex polymerase chain reaction (multiplex PCR) was used to detect the papEF, fimH, iucD, hlyA, fyuA, and ompT genes. Results: The prevalence of fimH, papEF, iucD, fyuA, hlyA, hlyA, and ompT genes were 87.5%, 47.5%, 60%, 67.5%, 27.5%, 47.5% and 71.2%, respectively. Among all of the isolates, 27 profiles were obtained. Conclusion: Our findings demonstrated that the most prevalence was found for fimH, and different distribution of virulence genes suggested different ability of pathogenicity.

Background: Cell phones have become one of the necessary means of life and they are commonly used almost everywhere by every population. Colonized microorganisms on cell phones can be easily cross-transmitted. Given the widespread prevalence of nosocomial infections, this study aimed to determine the frequency of bacterial contamination and antibiotic resistance in cell phones of healthcare workers (HCWs) in a tertiary care hospital, from southwest of Iran. In this cross-sectional study conducted between April and June 2016, sampling were performed from cell phones of 25 nurses and 75 medical students. Methods: Samples were collected from each cell phone by a moistened cotton swap dipped in normal saline prior and after decontamination with available alcohol-based handrubs. Identification of bacterial isolates was performed by conventional microbiologic methods. Antibiotic susceptibility pattern of the isolates was determined using the disk diffusion method. The contamination rates of cell phones prior and after disinfection were 88% and 52%, respectively. Ninety-nine (71.2%) out of 139 isolated distinct bacterial colonies prior to cleaning were potentially nosocomial pathogens. Of them, staphylococci (88.9%) were the most prevalent bacteria, in which 40.9% were methicillin-resistant isolates. The majority of Gram-positive and - negative isolates were susceptible to the tested antimicrobials. Totally, contamination rate of cell phones was significantly reduced after decontamination. Regular disinfection of the hands and cell phones was significantly associated with reduction of colonization of the methicillin-resistant isolates. Result & Conclusion: These findings emphasize the restricted use of cell phones and encourage the higher compliance with hygienic practices in hospitals to reduce the risk of nosocomial infections.

Background: Hepatitis E virus (HEV) is one the leading causes of maternal and fetal mortality. Nevertheless, in some geographical locations, especially Egypt, despite having high frequency of HEV seropositivity, HEV infection follows an asymptomatic or mild course during pregnancy. These anomalous observations have distracted attention from the importance of HEV infection in pregnant women. Methods: While tragic cases of HEV-infected pregnant women cannot be neglected any longer. Conclusion: These circumstances create a strong demand for the increasing awareness of HEV infection through training programs, appropriate management of HEV infection among pregnant women, routine screening of pregnant women for timely diagnosis of HEV infection, proper treatment of HEVinfected patients, optimal preventive measures, and development of a prophylactic vaccine against HEV infection.