Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 17, Issue 2, 2017

Background: The foodborne diseases are amongst the main causes of morbidity and mortality in the human communities. Giardia duodenalis, the causative agent of giardiasis, is one of the foodborne parasites, which has public health importance. The aim of the current study was to assess the prevalence of G. duodenalis among food handlers in Andimeshk County, southwest of Iran. Materials and Methods: This cross-sectional study was undertaken among 480 food handlers in 2015. The collected stool specimens were investigated using direct saline smear, Lugol's iodine- staining, and sucrose flotation methods. Results: The overall prevalence of G. duodenalis in the examined participants was 12 (2.5%). The higher prevalence 75% (9/12) was found among participants with medium and low levels of education and 25% (3/12) belonged to those with high level of education. Direct microscopic examinations revealed two (0.4%) positive cases infected with Hymenolepis nana, with one of them showing mixed infection with G. duodenalis. Conclusion: Based on the obtained results, infected food handlers could be a potential source of intestinal parasitic infections, and transmission can occur through contaminated food. Therefore, we suggest that food handlers training programs should be implemented to increase the awareness of food handlers and reduce the transmission of intestinal parasites.

Prosthetic joint infections (PJI) result in significant morbidity, mortality and cost to patients and the health system. Traditional treatment involves a twostaged revision and occasionally a single staged revision along with intravenous antibiotics (IV) and or oral antibiotics for several weeks to months. The use of a single staged revision along with an antibiotic which has a prolonged half life and is bactericidal would be ideal. We present 2 patients who were treated successfully with a single stage revision/antibiotic spacer and a new novel long acting lipoglycopeptide called oritavancin.

Background: Toxin antitoxin systems is the one of the important elements among pathogenic bacteria which have proven roles such as biofilm formation, cell programmed death and persister cells formation. Neisseria meningitidis causing serious diseases in humans must be highlighted. Objective: The current study aimed to identify the mazEF and relBE TA systems in N. meningitidis. Method: The potential TA loci were searched in RASTA database by bioinformatics analysis and then, experimental analysis was performed by PCR assay. PCR products were confirmed by sequencing. Results: Our findings demonstrated that mazEF and relBE TA systems were positive by PCR assay and results of sequencing confirmed the PCR results. Conclusion: Notably, our highlighted findings are the first report of mazEF and RelBE TA loci in N. meningitides. Finally, we strongly recommended that laboratory experiments should be performed to identify the roles of these TA loci in N. meningitides.

P. aeruginosa is one of the bacteria opportunistic that played main role in pathogenicity of patient in urinary tract infection (UTI) and respiratory tract infections. So, the aim of this study was to evaluate the prevalence of virulence genes including algD and pilA among Pseudomonas aeruginosa in urinary tract infection and tracheal isolates. After DNA extraction of clinical isolates, polymerase chain reaction was performed, and the results highlighted algD in all isolates, while pilA was dominant in tracheal isolates. We concluded that pathogenicity of urinary tract infection isolates is more than tracheal isolates, but future studies should confirm this.

Background: Enterococci infection rate, mortality and morbidity have been increased in recent decades accompanied by progressive emerging antimicrobial resistance. Vancomycin-resistant enterococci (VRE), important pathogen in hospitalized patients, has distinct antibiotic susceptibility to glycopeptides that varied genetically and can influence in choosing therapeutic agents. In this study, we aimed to determine the patterns of antimicrobial resistance according to the genotypic variations in VREs. Methods: Enterococci samples were isolated from different clinical specimens followed by antimicrobial susceptibility that was determined by the disk diffusion method during one year 2015-2016. Subsequently, VREs were selected and extraction of total DNA was performed using the QIAmp DNA mini kit. The eight oligonucleotide primer pairs were used to amplify the genes vanA, vanB, vanC1, vanC2, vanC2/3, esp, and hyl. Multiplex polymerase chain reaction (PCR) was performed to identify Van A, Van B, Van C, Van D and clonal complex 17 (CC17). Results: A total of 235 enterococci were isolated, including 121 and 114 Enterococcus faecalis and Enterococcus faecium, respectively. Most of VREs (42% of all enterococci) were E. faecium (91.1% vs. 8.9% E. faecalis). All VREs had Van A; and Van B, Van C and Van D genes were not found in any isolates. The frequency rate of CC17, genetic subset of E. faecium, was 68.3%. Conclusion: In conclusion, we can assume that the most frequent genotype of VRE in our country is VAN A and literally, the other genotypes

Background & Aims: Sofosbuvir is a powerful drug for the treatment of hepatitis C virus (HCV) infection. In comparison to preceding remedies, sofosbuvirbased regimens provide a higher cure rate, fewer side effects, and much lower duration of treatment. The aim of the work was to assess the efficacy and safety of sofosbuvir plus ribavirin with or without peginterferon-alfa in the treatment of a cohort of Egyptian patients with hepatitis C virus infection. Methods: Two hundred treatment naive patients who were HCV-antibody positive and HCV RNA by PCR positive aged more than 18 years were enrolled in the study and patients were classified into two groups: Group I which included 100 patients who received dual therapy with sofosbuvir plus oral weight based ribavirin for 24 weeks and Group II which included 100 patients on triple therapy with sofosbuvir plus oral weight based ribavirin (as with the dual therapy) and a 180 mcg Peg-INF alpha 2a subcutaneous injection weekly for 12 weeks. The primary end point was a sustained virological response at 12 weeks after end of the treatment determined by quantitative PCR for HCV. Results: Both patients groups had high sustained virological response that was higher in patients receiving triple than dual therapy (94% vs 83%). The adverse events that occurred in the two groups of patients were more evident in a group of patients receiving triple therapy. The side effects were mainly flu like symptoms. Conclusions: The triple regimen of Pegylated interferon, sofosbuvir plus ribavirin is safe and effective in the treatment of Egyptian patients with hepatitis C virus as well as sofosbuvir and ribavirin alone wit

Background: Saliva is a complex oral biologic fluid secreted by major and minor salivary glands. Saliva has immunological, enzymatic and antioxidant defense mechanisms. Infection with human immunodeficiency virus (HIV) is a life-threatening disease. Objective: The aim of this study was to evaluate salivary vitamin C and catalase levels in HIV-positive patients in comparison to a healthy control group. Method: Forty-nine HIV-infected individuals and 49 healthy subjects were selected. Five mL of unstimulated saliva was collected in 5 minutes using a sterilized Falcon tube with Navazesh method. Catalase and vitamin C levels were assessed by spectrophotometric assay. Data were analyzed with STATA 12. Results: Salivary catalase levels were 7.99±2.40 and 8.37±1.81 in the case and control groups, respectively. Catalase level was lower in the case group but the difference was not statistically significant (P=0.380). Salivary vitamin C levels in the case and control groups were 3.76±1.92 and 4.87±2.20, respectively (P=0.009). Conclusion: HIV can alter salivary antioxidant capacity as well as vitamin C and catalase levels. Saliva may reflect serum antioxidative changes in these patients. Therefore, further research is necessary on salivary and serum oxidants and the antioxidant changes.

Background: H1N1 (hemagglutinin-H-neuroaminidase-N) influenza infection is associated with high morbidity and mortality because of associated complications and related factors. Predictors of mortality in H1N1 patients are studied with very few without seasonal/pandemic declaration. This study was carried out to describe the clinical features, complications and different risk factors that affect the outcome in the patients with confirmed H1N1influenza infection. Methods: A retrospective study was done in Kasturba Medical College Hospital, Manipal, India by analyzing the medical records of 141 patients admitted from January, 2011 to June, 2015. Results: Of the 141 patients in the study, 51.1% of the patients were female with a mean age of 32±16.2 years. Fever with headache was observed in 92.9% patients while cough in 78.7% patients and breathlessness in 54.6% patients. On the basis of disease severity, 53.2% of the patients were put on mechanical ventilation. For all the patients, treatment for influenza management began with oseltemivir. Diuretics, antianxiety and corticosteroids were given as supportive and symptomatic care which contributed to high mortality in hospitalized patients. Mean hospitalization period was 8.5 days. During the hospitalization, patients developed different complications i.e. 31.20% patients developed respiratory tract infections, while 17.7% patients developed ARDS and 14.4% patients developed sepsis. The mortality rate of this study population was found to be 29.1 %. Conclusion: It was observed that low oxygen saturation during admission, high blood urea level, use of diuretics, corticosteroids, anti-anxiety drugs and complications like ARDS, sepsis influence the mortality rate of patients with H1N1 infection.

Objective: The present study assessed the prevalence of adverse drug reactions (ADRs) among HIV positive patients taking antiretroviral therapy referred to Imam Khomeini Hospital in Tehran, Iran. Methods: This is a cross sectional study regarding side effects of Highly Active Antiretroviral Therapy (HAART) in HIV positive patients referred to Voluntary Counseling and Testing (VCT) center in Imam Khomeini Hospital of Tehran, Iran during a period of the year 2009 to 2010. Two hundred patients under antiretroviral treatment evaluated for the side effects of drug based on available records, face to face interviews and written lab data. Results: Data was collected from a sample of 200 HIV positive patients (72% male). Injection drug use was the most common route of HIV transmission. Co-Infections with Hepatitis C virus (HCV) found in the majority of patients (60.5%). Tuberculosis was the most prevalent opportunistic infection. One hundred eighty eight (94%) patients experienced at least one adverse drug reaction. The most frequent clinical and paraclinical findings were skin rash (28%) and abnormal liver function tests (36%). Conclusion: Given the high prevalence of adverse drug reactions among HIV positive patients taking antiretroviral therapy (ART) in this study, clinicians should be aware of ADRs at the initiation of ART as complications can affect patients' adherence to the therapy.

Leishmania is an intracellular protozoan parasite which causes Leishmaniasis, a global health problem affecting millions of people throughout 89 different countries in the world. The current treatment which includes use of amphotericin B, antimonials, and others has major drawbacks due to toxicity, resistance, and extraordinary high cost. So there is an urgent need of development of new drug targets to fight against leishmaniasis. In this regard we have selected Leishmania donovani Ca2+ ion channel (Ld-CC) as potential drug target. Ld-CC regulates concentration of Ca2+ ions which is involved in several functions like flagellar motion, mitochondrial oxidative metabolism and entry inside the macrophages. Since Ld-CC has not been characterised yet, we performed homology modelling of Leishmania donovani Ca2+ ion channel (Ld-CC) and docking studies of ligand library against this channel. 542 compound library of National Cancer Institute (NCI) diversity 3 dataset selected for screening studies. The ligands ZINC17287336 and ZINC29590262 were selected as best energy conformers because they show highest binding affinity towards its target (Ld-CC). They interact with the active site residues in the pocket of Ld-CC which suggests that the docked conformations are good and acceptable. Moreover, these two selected compounds also have relatively high binding affinity than nifedipine and verapamil, known human calcium channel blockers which had been reported to have mild anti-leishmanial activity. Among these two top screened inhibitors the ligand ZINC29590262 shows poor binding affinity towards the Human voltagedependent L-type calcium channel subunit alpha-1C in comparison to the Ld-CC. Therefore, we proposed this ligand as the best inhibitor which shows 40% more binding affinity with Ld-CC than the human-VDCC. These results suggest that our screened ligand ZINC29590262 could act as novel drug and may show much better antileishmanial activity.

Toxins are one among the numerous virulence factors produced by the bacteria. These are powerful poisonous substances enabling the bacteria to encounter the defense mechanism of human body. The pathogenic system of Staphylococcus aureus is evolved with various exotoxins that cause detrimental effects on human immune system. Four toxins namely enterotoxin A, exfoliative toxin A, TSST-1 and γ-hemolysin were downloaded from Uniprot database and were analyzed to understand the nature of the toxins and for drug target validation. The results inferred that the toxins were found to interact with many protein partners and no homologous sequences for human proteome were found, and based on similarity search in Drugbank, the targets were identified as novel drug targets.

The Crimean-Congo hemorrhagic fever is a zoonotic disease transmitted by ticks and is characterized by fever and bleeding. It was seen for the first time in the south of present day Ukraine and thus named, Crimean fever. 1 In 1956, the virus was isolated in a patient with similar symptoms residing in Congo, Kenya and the virus was named Congo virus. The viruses causing these two diseases were the same and hence was termed Crimean-Congo hemorrhagic fever virus (CCHFV). Humans are the only known host that develops disease.