Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 16, Issue 2, 2016

Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

Purpose: Escherichia coli are the most frequent cause of gram negative bloodstream infection. This study was done to evaluate the association of risk factors, antimicrobial susceptibility pattern and detection of TEM, SHV and CTX M genes in the extended spectrum beta lactamase (ESBL) producing E.coli. Materials and Methods: 11,133 blood samples were processed in BacT/Alert bottles. Bacteria grown were identified and antibiotic susceptibility patterns were studied using VITEK2 system. ESBL production was tested using phenotypic method, VITEK system and by PCR. Statistical package SPSS Version 11.5 was used to do the analysis. Results: Blood culture positive isolates were 1530 (13.7%), among which 108 were identified as Escherichia coli. The most common risk factor associated with E.coli bacteremia was diabetes and common source was UTI. E.coli were resistant to Ampicillin (86%), Piperacillin (82.4%), Ceftazidime (80.6%), Ceftriaxone (80.6%), Cefipime (77%), Aztreonam (80.6%) and Fluoroquinolones (80%). Isolates were sensitive to Carbapenems and combination drugs. ESBL was produced by 76%. CTX M bla (betalactamase) gene was common in all the ESBL isolates. Conclusion: ESBL producing E.coli isolates were observed to be multi drug resistant. Owing to the high prevalence of ESBL.Carbapenems are clearly the drug of choice for empirical treatment in these cases.Ertapenem may be used to prevent development of carbepenem resistant pseudomonas or acinetobacter isolates in the hospital settings. To limit the earlier development of resistance to carbepenems, it is better to de-escalate to combination drugs like piperacillin tazobactum with aminoglycosides after the susceptibility report.

Objective: Evaluation of anti-tubercular therapy on endometrium in Female Genital Tuberculosis. Method: Total of 50 women having FGTB on endometrial aspirate (positive AFB, epithelioid granuloma, positive PCR, laparoscopy or hysteroscopy findings) were enrolled. Ultrasound was performed for endometrial thickness, mean resistive index and pulsatility index before and after anti-tubercular therapy (ATT). Diagnostic hysteroscopy was performed for intra-uterine adhesions and to visualise cavity before and after ATT. Results: Menstrual cycle improved after anti-tubercular therapy (ATT). Endometrial aspirate findings improved with disappearance of AFB, epithelioid granuloma and decrease in PCR (94%vs 33%). After ATT, ultrasound examination of endometrial thickness improved from 7.01±1.48 mm to 7.51±1.48 mm while mean resistive index and pulsatility index decreased from 0.729±0.304 to 0.692±0.399 and 1.180 to 1.138. With ATT, improvement was seen in hysteroscopic findings with normal looking cavity increasing from 18(36%) to 34(72.1%) and pale looking cavity decreasing from 20(42.5%) to 8(16.8%). Before ATT, prevalence of intrauterine adhesions was 62% which decreased to 28.7% after ATT. Improvement was significant only in grade I adhesions from 34% to 2.1%, (p<0.001). There was no improvement in higher grade of intrauterine adhesions with ATT with grade II (6% vs 4.2%) and grade 2a (4% vs 2.1%), grade III being (2% vs 2.1%), grade II a (4% vs 4.2%), grade Va (4% vs 4.2%) and grade Vb (8% vs 10.6%) before and after ATT respectively. Conclusion: Early ATT improved menstrual cycle, endometrial thickness and reduced incidence of grade I adhesions. Advanced stages did not show any improvement.

Background: Quickness of diagnosis and getting results in prisons is lower than other settings. The present study aimed to assess the quickness of HIV and Tuberculosis diagnostic process in the Great Tehran Prison. Materials and Methods: The present study evaluated the quickness of HIV diagnostic testing (ELISA, Western Blot and CD4 count) in the Great Tehran Prison over the period of October 2013 to May 2014. Also, all suspected tuberculosis (TB) patients in the prison were examined for the occurrence of active TB through collecting 35 chest X-rays and 215 sputum specimens for acid-fast bacillus (AFB) testing at the health center laboratory. Results: The average interval between when test requests were made by a physician and when HIV ELIZA/ Western Blot was obtained was relatively long time. On average, the interval between a physician's requests for CD4 count to assess the results was eight days. The average time interval between test requests by a physician to deliver sputum samples to the laboratory was four days. However, the average time interval between a physician's requests for sputum samples to assess the results was 16 days. Conclusion: Due to the significance of positive and negative results for making decision on diagnosis, initiation and follow up of treatment procedure, the time intervals should become shorter.

Objective: The aim of this study was to report the epidemiological, clinical and laboratory profiles of HIV-infected patients who admitted to HIV/AIDS laboratory of Imam Khomeini Hospital in Tehran, Iran. Methods: HIV positive patients referred to the HIV/AIDS reference laboratory between December 2012 to March 2013 were included in the study. Their demographic characteristics, behavioral and personal history were assessed. Ninety nine patients’ files from the medical records at the Voluntary Counseling and Testing Center (VCT) were selected and evaluated. Data was analyzed using SPSS for Windows Version 16. We used Pearson’s chi-squared, one-way ANOVA and post hoc tests to examine differences in proportions. Results: Of 99 participants in the present study, 68.7% were males, the mean age of the patients was 36±1.2 years and about 60% were married and almost half of them were self-employed. The most common transmission route was injection drug use. There was a statistically significant difference in CD4 count among different age groups (P = 0.028). Also, there was significant association between CD4 count and narcotic types (F=3.71, P = 0.012). Patients who used opium, had significantly higher CD4 than who used two or more narcotics (P = 0.005). Conclusion: Our findings are helpful in understanding the demographic, clinical and laboratory profile of people living with HIV/AIDS. Consideration of useful interventions for high- risk groups and paying more attention to socio demographic background are needed for health care providers.

Malaria is a parasitic disease, widespread along the tropical regions of the world. The disease has killed 4, 38,000 individuals in the year 2015 (WHO). The malaria parasite, Plasmodium falciparum, has evolved resistance to front-line antimalarials over the decade, necessitating the identification of new drug targets. Protein kinases are excellent drug targets since they participate in critical cell-signaling cascades. We have identified a putative RIO-like protein kinase, PFD0975w, from the Plasmodium kinome. It is believed to play a key role in ribosome biogenesis. We have cloned and over-expressed the protein in E. coli and purified it to homogeneity. The recombinant protein is of molecular weight 36.3±1.2 kDa. Purified recombinant PFD0975w is active in vitro and binds ATP. PFD0975w exhibits a unique localization pattern in each RBC stage. PFD0975w localizes within the parasite cytosol during ring stage and spread throughout the infected RBCs during trophozoite and schizont stages with the strongest expression signal during the trophozoite phase indicating the importance of the enzyme in parasite growth and survival. Interestingly, the localization pattern of the protein also responds to stress conditions such as starvation and antimalarial drug pressure. It exhibits punctuate pattern in the treated parasite during trophozoite and schizont stages compared to untreated parasites, indicating some role of the putative kinase in cellular stress handling. Our results indicate PFD0975w is a potential drug target in the malaria parasite and active recombinant PFD0975w can be exploited to identify, validate or design novel inhibitors.

Urinary tract infections are one of the leading cause of morbidity in admitted patients. Most commonly caused by Escherichia coli, but there are some variants which are commonly reported in urinary tract infection. This study was about to speciate such isolate like E.fergusonnii and find out its antibiogram.