Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 19, Issue 2, 2019

Human hydatid cyst or cystic echinococcosis is a life-threatening zoonotic disease that occurs in most countries worldwide and is recognized as a major public health problem. Following ingestion of Echinococcus granulosus eggs, hydatid cysts which are the larval stage of the worm are formed mostly in liver and lungs, and occasionally in other organs of human. The usual treatment for hydatid cyst is open surgery. One of the problems following surgery is the recurrence. In the last decades, albendazole has been used for the treatment of hydatid cyst. This drug can be used alone or jointly with surgical procedures. However, its efficacy has not been well documented. Thus, in this work, the treatment of hydatid cyst with albendazole in different investigations including case studies, clinical trials in human and experimental works in animals has been reviewed. According to the findings of this review, it can be concluded that treatment of hydatid cyst with albendazole may be associated with the prevention of recurrence and reduction of the size and death of the hydatid cysts.

Background: Infections caused by Nocardia are rare, but misguided to clinicians, especially if there is a delay in the diagnosis and/or low response to chemotherapy. The incidence of nocardiosis is increasing constantly worldwide, and the situation is getting worse if we consider immunocompromised individuals, such as human immune virus (HIV) positive patients since they are at higher risk. Surgical amputation, although not common, but should be considered as a result in some cases that cause partial disability. Aims: To throw light on the situation of nocardiosis in Sudan, the possible reasons for the increased prevalence are investigated and discussed the possible strategies for prevention and control. Data Review: PubMed investigations were adopted using terms that included nocardiosis in Sudan as well as in other parts of the world. Part of the review has been retrieved from the main library of the postgraduate college, University of Khartoum and University of Newcastle upon Tyne. Findings: In Sudan, nocardiosis revealed wide geographical distribution; different cases were reported from western, middle as well as the northern parts of the country. Moreover, several clinical presentations were seen. While pulmonary, coetaneous and subcutaneous infections represent the primary types caused by Nocardia, disseminated infection in two or more organs had also been reported. As in all other infectious diseases, opportunistic nocardiosis is more prevalent among HIV patients. Zoonotic transmission of the disease was also proved; several cases of bovine and caprine mastitis were due to one or another species of Nocardia. The effect of ecology on the prevalence and pathogenicity of Nocardia is proved by the isolation of Nocardia and other actinomycetes from Sudanese soil, which represents the most probable source of infection. Regarding treatment, effective results are usually obtained by the use of sulfonamides and thirdgeneration cephalosporins. However, surgical interference is also used when necessary, such as in cases of drainage of abscesses. Conclusion: Since the description of Nocardia by Edmond Nocard in 1888, it started to be well known worldwide. In Sudan, however, the awareness regarding this bacterium is still below the level and is only due to the end of the fifties of the twentieth century, which is relatively late. Hence, attention towards this neglected pathogen may lead to early recognition and prompt treatment, resulting in complete cure.

Introduction: Cystic echinococcosis is a neglected zoonotic disease with worldwide distribution, which occurs mainly in pastoral regions. Echinococcus granulosus sensu stricto, is the main agent of human infection. Although Iran is an endemic area for CE in the Middle East, lack of data regarding the disease among rural inhabitants of Khuzestan province in recent years, persuaded us to perform the current study. Methodology: This cross–sectional study was conducted in 2016 using simple random sampling method in 15 villages of Shushtar County, southwestern Iran. Three hundred and fourteen rural inhabitants were examined using AgB- ELISA test for CE. Result: From 314 patients included in the study, females and males were 244 (77.7%) and 70 (22.3%), respectively. Of these, 227 (72.3%) were in close contact with dogs, out of which 173 (70.9%) of them were females and 54 (29.1%) were males. ELISA detected three (1%) seropositive cases among investigated population. All three positive cases were females and in close contact with dogs. Furthermore, the positive cases were in the age range of 21-50. None of the 70 examined males were positive. Conclusion: This study is the first report of CE in rural areas of Shushtar, Southwest Iran, which indicated seroprevalence of CE among rural areas with a high prevalence rate of infection among females. It seems that the rural population of the region are at the risk of exposure to E. granulosus eggs. Therefore, more studies are required to evaluate the human CE in all parts of the province using serological and ultrasound methods.

Objectives: Nowadays, due to the biofilm formation among coagulase-negative staphylococci (CoNS), acquisition of antibiotic resistance and virulence genes could be noted. These organisms resemble other staphylococcus that harbor mecA gene, which encode methicillin resistance but the diversity in CoNS is higher than other species. Based on increasing antibiotic resistance in Staphylococcus haemolyticus, analyzing of phenotypic and genotypic biofilm formation, antibiotic resistance and genes involved in this process, SCCmec and ACME typing were the aims of the current study. Methods: 256 clinical CoNS isolates were collected that 49 isolates were identified as S. haemolyticus. For evaluation the antibiotic resistance patterns, disk agar diffusion method was applied, and also biofilm assay carried out among methicillin resistant S. haemolyticus and SCCmec and ACME typing. Results: The results of antibiotic susceptibility indicated that the highest resistance was found for cotrimoxazole and erythromycin (86.6%) and the frequency of blaA (96.5%) and msrA (79.3%) genes was much higher than others. Among MRSH isolates 58.6 % showed a weak biofilm phenotype and 41.4% demonstrated a moderate biofilm density. Also, among the biofilm correlated genes, IS 256 (79.31%) was the most frequent. The SCCmec typing of MRSH isolates indicated that the type V was dominant. Conclusion: Our findings indicated that the correlation between high rates of existence Is 256 gene and high prevalence of weak biofilm phenotype was among MRSH isolates. The current study revealed that multiple antibiotic resistance existed in S. haemolyticus isolates that is a warning for public health.

Introduction: The evolution of antibiotics in the last century has revolutionized the field of medicine and led this field to higher level of success in treating mild to severe infections, but the inappropriate use of these life saving drugs has been accompanied with the appearance of resistant strains to these agents. Aims & Objectives: The aim of the study was to determine the prevalence rate of high and low-level mupirocin resistance in methicillin resistant staphylococcus,and to find out resistance to other antibiotics. Materials & Methods: This study was conducted on 100 Staphylococcus isolates recovered from pus samples. Conventional disc diffusion tests were used for the detection of high and low level mupirocin resistance (mupirocin 5μg and 200μg discs) and for various other antimicrobials for example cephalexin, erythromycin, doxycycline, oxacillin, linezolid etc. Results: Outof 100 Staphylococcus isolates processed during the study period in the department of microbiology, 74 were Staphylococcus aureus (S.aureus) and 26 were Coagulase negative Staphylococcus (CoNS). Among S.aureus 43.4% were Methicillin resistant Staphylococcus aureus (MRSA) and 56.6% were Methicillin sensitive Staphylococcus aureus (MSSA), whereas among CoNS 42% were methicillin resistant and 58% were methicillin sensitive. We observed 6.75% of high level mupirocin resistance among Staphylococcus aureus and 19.23% among Coagulase negative staphylococcus. Conclusion: It was concluded that an inappropriate excessive use of mupirocin leads to a rapid increase in high-level resistance to mupirocin and other antibiotics in CoNS, affecting the treatment lines and success rate of infection control in hospital settings.

Background: Doxorubicin is a well-established chemotherapeutic agent for the treatment of childhood acute lymphoblastic leukemia (ALL), but its efficacy is often limited by its related cardiotoxicity. Protection against doxorubicin-induced cardiotoxicity can be of great value, especially for children. Silymarin has a potent antioxidant property that can be helpful in preventing cardio-toxicity. Objective: ‘To assess the possible protective role of silymarin against early doxorubicin-induced cardiotoxicity in children with ALL’. Subjects and Methods: This study was conducted on 80 children with ALL, including 40 patients under doxorubicin therapy and silymarin 420 mg/day for one week after each doxorubicin dose starting from the day of doxorubicin infusion (Group I) and 40 patients under doxorubicin therapy and placebo (Group II). ‘Conventional echo-Doppler measures of left ventricular systolic and diastolic functions and pulsed wave tissue Doppler of lateral mitral annulus were done for all patients’. Results: After doxorubicin therapy, there was a significant higher reduction of systolic function [ejection fraction (EF), fraction shortening (FS) and s wave] in Group II compared with Group I and non-significant reduction of diastolic function [E/A ratio or e/a ratio] in both Groups. Although serum troponin increases in both groups after doxorubicin therapy, the increase of troponin is significantly lower in group I compared with group II. Conclusion: Silymarin decreased early Doxorubicin-induced left ventricular systolic function disturbances and can be recommended as an adjuvant drug in patients with ALL under doxorubicin therapy. Recommendation: ‘Multicenter studies on a large number of patients with longer follow up’ periods to prove the protective role of silymarin in early and late Doxorubicin-induced cardiotoxicity.

Background: Mycobacterium tuberculosis remains as a vital threat to global health and its diagnosis is still complicated. Since there is no gold standard for the diagnosis of latent tuberculosis infection (LTBI), its diagnosis routinely relies on measurement of host immune responses to M. tuberculosis antigens using the Tuberculin Skin Test (TST) and Interferon-Y Release Assays (IGRAs). Objective: The aim of this study was to evaluate LTBI among hospitalized children and their parents/ guardians as general populations. Methods: A cross-sectional study comparing TST and IGRA for the diagnosis of suspected LTBI was performed in children and their guardians (as general population) in Children Medical Center, an Iranian referral hospital. Results: In this study, 81 patients hospitalized in CMC and 102 patient's guardians were included. A total of 57 patients (70.4%) had performed a TST and were interpreted during the study. Among them, 32 (56%) had a positive test result when a cut-off of 10 mm induration. There were fewer positive IGRA test results than positive TST results (33% versus 56%) in children. Among guardians, TST and IGRA were positive in 41% and 40% respectively. The agreement between the IGRA test and the TST among them was 0.7, while this was as slightly lower in children (0.63). Conclusion: The results of our study indicate that the IGRA test has a higher specificity than TST, especially in children, while the frequency of positive results with both tests in adults was similar. Considering the false positive results reported with the TST, replacement of the IGRA test with TST in children is recommended.

Background: PA-824 analogues have been proposed on a promising approach for treating MDR/XDR tuberculosis. In order to understand the structural requirement of reported extended side chain analogues were studied to get insight into their structural requirements responsible for high affinity as a ligand-based pharmacophore, 3D-QSAR model have been developed. Docking and molecular dynamics studies revealed the better binding interaction of inhibitor binding pocket of deazaflavin dependent nitroreductase (Ddn) with cofactor F420 crystal. Methods: For pharmacophore generation and atom-based 3D-QSAR analysis, a dataset of 84 compounds were selected which were carried out using PHASE. The docking studies were performed using Glide module consists of five steps protein preparation, ligand preparation, receptor grid generation, actual docking procedure and finally viewing the docking results using the poseviewer. QikProp provides ranges for comparing a particular molecule’s properties with those of 95% of known drugs. Molecular dynamics (MD) simulations for docking complex of deazaflavin dependent nitroreductase (Ddn) with molecule 63 were performed using Desmond. Prime Molecular Mechanics/Generalized-Born/Surface Area (MM-GBSA) was used for the calculation of binding free energy for the docked complexes. Results: The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of R2 = 0.8988 for training set compounds, higher variance ratio F= 127.3 and the model generated showed excellent predictive power, with a correlation coefficient of structure to analyses Q2= 0.8543 for a randomly chosen test set of 17 compounds. The binding position of most active molecule 63 is shown in figure 4. Several favorable interactions between ligand and enzyme clearly observed; H-bond showed between O atom presence as spacer in C-6- 2-Nitro-6-{[4-(trifluoromethoxy) benzyl] oxy}-6,7-dihydro-5H-imidazo[2,1-b] [1,3] oxazine and Asn 62. Weak hydrogen bonding observed between N1 atom in imidazole ring and Asn91. The binding of imidazole nucleus occurs at site, which has extensive hydrophobic interaction with Arg60 residues. All these pharmacokinetic parameters within the acceptable range defined for human use, thereby indicating their potential as drug- like molecule. Stability of deazaflavin dependent nitroreductase (Ddn) with molecule 63 complex was evaluated through 100 ns molecular dynamic simulations. Main contributions to the tight binding of molecule 63 to Ddn are the exceptionally electrostatics (dG_bind_Coulomb) and enhance hydrogen bond interactions (dG_bind_Hbond). Conclusion: Docking, MM-GBSA, MD stimulation, pharmacophore model and 3D-QSAR studies as well as QikProp pharmacokinetic analysis presented in this paper is hoped to be a primer towards the development of various novel PA-824 with different chemical scaffolds and further its biological activity predictions to invent novel, potent, selective and safe PA-824 analogues for the treatment of MDR/XDR tuberculosis. Moreover, further use of contemporary experimental and computational techniques to data presented here may widen its scope and applicability.

Background: Tuberculosis [TB] is one of the most important infectious diseases among prisoners. TB Screening plays an important role in prevention among prisoners and their visitors, also better caring of the patients. Active case finding is one of screening methods that is relatively an easy one to find TB suspected prisoners. Therefore, we aimed to assess the prevalence of TB in male prisoners in Tehran, Iran. Methods: This study was conducted among male prisoners in Great Tehran Prison to screen and diagnose TB patients from October 2013 to May 2014. We used active case finding [ACF] as a screening method to find TB suspected prisoners in which healthcare staff explained TB symptoms for prisoners and individuals with those symptoms referred to the clinic for further work up (sputum sample tests). Results: In total of 6900 prisoners, 448 (6.5%) prisoners were TB suspected by ACF and only nine patients were diagnosed with tuberculosis, indicating the prevalence of 0.13%. Conclusion: The relatively low TB prevalence within prisoners besides considering likely common symptoms in ACF may result in many false positive cases during screening (6.5% vs. 0.13%). But, ACF is more fast, easy and affordable method to find TB suspected prisoners. Also, during this active method, prisoners are trained about TB symptoms so, it has a more prolonged effect towards screening goals.

Background: Successful management of periodontitis requires treatment strategy that integrates therapies addressing both pathogen and host aspects of disease etiology. To evaluate sub gingivally applied curcumin gel in treatment of chronic periodontitis based on clinical and biochemical parameters. Materials & Methods: A randomized, double blind, parallel-group trial was carried out on 30 patients suffering from chronic generalized periodontitis with probing pocket depth≥5mm on at least 4 sites who were then randomly allocated to two groups. Control group was treated with Scaling and Root Planing (SRP) alone while experimental group was treated with SRP followed by subgingival application of curcumin gel. Saliva collection was done and the clinical parameters were recorded at baseline and follow up periods. Saliva analysis for IL-1β was done by ELISA. The statistical differences for the intra-group and intergroup measurements were analyzed by using Mann Whitney test. Spearman’s rank correlation coefficient was used to examine the relationship between Interleukin - 1β and clinical parameters. Results: Study elucidated mild adjunctive benefit of curcumin gel in reduction of gingival inflammation for a limited period of time. Though improvement in other clinical parameters was also greater in subjects treated with curcumin gel, results were not statistically different from those treated with SRP alone. None of the subjects who received curcumin gel experienced any adverse effect. Conclusion: Within limitations, it can be concluded that single application of curcumin (turmeric) gel has limited added benefit over scaling and root planing in treatment of chronic periodontitis.

Background & Aims: Hepatitis C virus infection is a major public health problem in Egypt with a risk for morbidity and mortality due to chronic liver disease complications. Worldwide, Egypt has the highest prevalence of HCV infection with the overall prevalence of about 14.7%. The aim of this study was to evaluate the antiviral efficacy, safety, and tolerability of sofosbuvir (SOF) plus Pegylated Interferon (Peg- IFNa) and Ribavirin (RBV) in Egyptian patients with chronic hepatitis C virus (HCV) infection. Methods: This study was carried out in 1200 patients with chronic hepatitis C virus infection who were eligible for interferon therapy. They were treated with the triple therapy of sofosbuvir 400 mg once daily, Peg-INF subcutaneous injection weekly for 12 weeks in combination with oral weight-based ribavirin. The primary outcome measures were the number of patients with successful eradication of the virus evidenced by the sustained virologic response (SVR) at 12 Weeks. After discontinuation of Therapy (SVR12), the secondary outcome measures were the incidence of adverse effects associated with the tested HCV therapy. Result: The mean age of the patients was 49.32 ± 6.97 years. 45.9% of them were males and 54.1% were females.70 patients (5.8%) had a history of previous HCV treatment. ''1077 (89.8%)'' of patients achieved successful eradication of virus while ''106 (8.8%)'' were resistant to treatment and ''17 (1.4%)'' stopped treatment. Good predictors of response to the triple therapy were female gender, treatment naive and non-cirrhotic patients. Conclusion: The triple regimen of Pegylated interferon, sofosbuvir plus ribavirin is safe and effective in the treatment of Egyptian patients with hepatitis C virus and is associated with real-life SVR12 rates of 89.8%.

Background: Tuberculosis (TB) among Diabetes Mellitus (DM) population is more expected to fail treatment of TB due to smear-negative TB. Objective: We sought to compare and evaluate different methods to study the frequency of TB infections among DM patients. Methods: Blood, sputum and urine samples were collected from 500 newly identified diabetic patients from different diabetic clinics in Warangal districts. Smear microscopy, Culture and Line Probe Assay by Polymerase Chain Reaction (LPA PCR) were used for identification of tuberculosis. Results: Based on the chest X-Ray of 200 diabetic patients, suspected with pulmonary infections, 113 were males, 85 were females and 2 were children. All 200 patients were tested for tuberculosis infections, 55 were confirmed based on chest X-ray lesions. Off 55 patients, 30 were positive and 25 were negative for AFB microscopy, but were shown positive for chest X-ray. 22 were reported to be culture positive on solid media and identified as Mycobacterium tuberculosis based on morphology and biochemical methods. 36 samples were identified to be positive for LED, FM microscopy and LPA. Off 36 positive samples, 2 were MDR-TB and 34 were MTB based on LPA PCR method. Off 25 smear negative samples, 2 were identified as culture positive and confirmed to be MTB by morphological, biochemical tests. Conclusion: Smear Negative Microscopy plays a vital role in the spread of tuberculosis infection among diabetic patients. Along with the smear microscopy, there is a need to rely on other methods for rapid identification and diagnosis of tuberculosis among the diabetic patients to control the spread of infection in the community and household contacts.

Background: A polyherbal formulation (Herboheal) traditionally indicated for woundcare was investigated for its anti-virulence potential against the notorious pathogen Staphylococcus aureus. Objective: This study aimed at evaluating anti-virulence potential of Herboheal formulation against S. aureus in vitro as well as in vivo, followed by studying its effect on target bacterium’s gene expression at the whole transcriptome level. Methods: In vitro efficacy of the test formulation was evaluated using broth dilution assay, whereas in vivo efficacy was assayed employing the nematode Caenorhabditis elegans as the model host. Molecular targets of the test formulation in S. aureus were elucidated through whole transcriptome analysis. Results: This formulation could exert inhibitory effect on bacterial growth and quorum sensingregulated pigment (staphyloxanthin) production at ≥ 0.025% v/v. It not only could inhibit S. aureus biofilm formation, but also eradicated pre-formed biofilm effectively. This formulation could modulate antibiotic susceptibility of S. aureus, enhanced its susceptibility to human serum heavily, while compromising its haemolytic potential. Herboheal-treated bacteria expressed notably lesser virulence towards the nematode worm Caenorhabditis elegans. Even repeated exposure of S. aureus to this polyherbal formulation did not give rise to resistant phenotype. Whole transcriptome analysis revealed genes associated with hemolysis, virulence, enzyme activity, transport, basic cellular processes, quorum sensing, and transcriptional regulators as the major targets of Herboheal in S. aureus. Conclusion: This study validates the traditional use of Herboheal formulation in wound-care by demonstrating its efficacy against one of the pathogenic bacteria most commonly involved in wound infections.

Introduction: Skin lesions represent lesions that result in loss of tissues and their joints and often this cutaneous process is a primary or secondary consequence of structural changes in the same skin surface. Type 2 diabetic subjects developing chronic skin lesions in the lower limbs in the western world are steadily increasing. We conducted a study on the etiologic incidence of chronic skin lesions in type II diabetic subjects in the lower limbs compared to subjects with chronic skin lesions (controls). Materials and Methods: Thirty subjects (group "A") with Chronic Skin Lesions (CSL controls) (19 F-11M, mean age 67.5±7.2) in the lower limbs were admitted to our study according to a randomization scheme and compared a thirty (group “B”) type II diabetic patients (18F-12M, mean age 73.5±4.9) with chronic skin lesions (CSL). These two groups "A" and "B" have been studied and compared on the basis of infectious etiology responsible for the infectious skin process. Result: In the subjects of the "A" group we found a positive bacteriological colony test of 9 examinations corresponding to the total 30.0%. In the group called "B" we obtained a colony test positive of 12 subjects over 30 corresponding to 40.0% of the examinations. For the number of bacterial species identified in the "A" group we obtained 7 monomicrobial and 2 poly microbial bacteriological tests, while in the "B" group we observed 3 mono microbial and 9 poly microbial tests. All bacteriological isolates showed "in vitro" sensitivity to satisfactory aminoglycosides with MICs range of 0.78- 1.56mg/L. Conclusions: Data from this study show a different etiology among diabetic subjects than nondiabetic subjects. In fact, in the "B" group, more poly microbial bacteriological findings are found in positive culture studies with subjects in group "A". This phenomenon confirms an alteration of the skin microbiome of diabetic subjects with modification of the "opportunistic role" of some species of the skin bacterial flora.