Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 18, Issue 1, 2018

Zoonotic infections are increasingly becoming public health menaces and are usually transmitted to humans due to unsuitable environmental conditions. One of them is hepatic capillariasis, caused by the parasite Capillaria hepatica, primarily a disease of rodents, with hepatic manifestations in humans. Although its prevalence is very low, it can cause significant morbidity and mortality, with cases reported from all over the world. The main infective form for humans is the embryonated egg of the parasite, which hatches in the intestine and ultimately colonize the liver. The larvae mature and reproduce, and eventually form embryonated eggs, which cause chronic focal inflammation and septal hepatic fibrosis. Clinical presentation mainly consists of fever, abdominal pain, hepatomegaly and eosinophilia. Spurious infection with unembryonated eggs cause gastrointestinal symptoms. Diagnostic modalities include liver biopsy, ultrasonography, CT scan, immunological tests like ELISA and IIFT. The infection can be treated mainly with a combination of benzimidazoles like thiabendazole, mebendazole and albendazole; with corticosteroids. The study emphasizes the need for hepatic capillariasis to be considered as a differential diagnosis in cases of suspected hepatitis, leptospirosis, abdominal lymphadenopathy or other hepatic or parasitic infections prevalent in the region concerned; and meticulously assess the cases to facilitate early diagnosis and prompt treatment, thus reducing the distress faced by patients.

Components of the extracellular environment can be transported into cells by molecular mechanisms collectively termed endocytosis. Cells typically use a multitude of such internalization pathways. These endocytic transport pathways have a wide range of implications for physiological regulation as well as pathological processes. Many infectious diseases, for example, involve internalization of the pathogen into the cell as part of the infection process. Selective interference with the endocytic transport of a microbe, thus, represents a therapeutic strategy that may prevent infections or decrease the rate of their progression. Herein, we provide a brief review of strategies for discovery of novel anti-infection drugs and their pharmacological implications.

AIDS (acquired immune deficient syndrome) is a deadly human viral infectious disease caused by HIV (human immune-deficient virus) infection. Almost every AIDS patient losses his/her life before mid 1990s. AIDS was once the 1st disease killer in US (1993). After one decade hard work, antiviral drug cocktails-high active anti-retroviral therapy (HAART) have been invented for almost all HIV infection treatments. Due to the invention of HAART, 80-90% HIV/AIDS patients still effectively response to HAART for deadly AIDS episode controls and life saving. Yet, this type of HIV therapeutics is incurable. HIV/AIDS patients need to take HAART medications regularly and even life-long. To counteract this therapeutic drawback, more revolutionary efforts (different angles of therapeutic modes/attempts) are urgently needed. In this article, the major progresses and drawbacks of HIV/AIDS chemotherapy (HAART) to HIV/AIDS patients have been discussed. Future trends (updating pathogenesis study, next generations of drug developments, new drug target discovery, different scientific disciplinary and so on) are highlighted.

Background: Chest Radiograph accompanied by clinical and laboratory findings are required for diagnosis and follow-up of patients with suspected ventilatorassociated pneumonia (VAP). However, there are no reliable data whether follow-up chest-X-ray (CXR) is needed or not, moreover, when the physicians request CXR and how many times CXR is required. We aimed to determine association of the clinical improvement with resolution of pulmonary infiltrates as well as time of resolution. Materials and Methods: The patients with a diagnosis of VAP based on Clinical Pulmonary Infection Score (CPIS) were enrolled in this study. Clinical evaluation and follow-up were continued and CXR was performed sequentially in two-day intervals until clinical improvement or occurrence of other events including death. Fischer test was used to analyze the association of clinical improvement with radiographic resolution. Results: Out of the seventy -five patients, pneumonia was clinically improved in 48 cases. Mean duration of the clinical improvement was 5.3±4.5 days. Among these patients, pulmonary infiltrations in 44 patients were resolved completely (13.8±5.8 days). Twentyseven patients had no clinical improvement and all of them revealed no infiltration resolution according to the sequential imaging studies. Resolution of radiographic involvement significantly was associated with clinical improvement (p=0.000). Conclusion: Radiographic resolution occurs in most of patients who survived VAP and there is strong relationship between radiographic resolution and clinical improvement. Moreover, our data revealed that CXR clearance occurred earlier than anticipated previously. Thus, sequential follow-up CXR in VAP had no further clinical value.

Background: Rapid and accurate diagnosis of patients with suspected bacterial meningitis (BM) is crucial to prevent potential subsequent mortality and morbidity. The aim of this study was to explore the diagnostic value of the rapid leukocyte esterase (LE) strip test in identifying pleocytosis in cerebrospinal fluid (CSF) samples of patients with suspected BM. Methods: A total of 126 patients with suspected meningitis were enrolled in this prospective study. Microscopic examination (cell count and differential) and leukocyte esterase (LE) rapid strip test were performed on cerebrospinal fluid (CSF) samples. Sensitivity, specificity, positive predictive value and negative predictive value of the LE test were determined. Results: Fifty-two patients (41%) had pleocytosis in the CSF, while 48 (38%) patients had a positive rapid LE strip test result. The diagnostic accuracy of this test for pleocytosis was translated to a sensitivity of 84.6% (95%CI 71.9, 93.1) and a specificity of 94.5% (95%CI 86.7, 98.5), with an area under the receiver operating curve of 0.88. Conclusion: The LE strip test, through rapid and accurate determination of CSF pleocytosis, could be considered as an additional test in the diagnosis of bacterial meningitis. It can be tested at bedside and is feasible to do in resource-limited settings.

Objective: Antioxidants protect the body against cellular damage. Saliva has immunological, enzymatic and antioxidant defense systems. Uric acid is the main and predominant salivary antioxidant. The aim of this study was to evaluate salivary uric acid levels and pH in HIV-infected patients in the west of Iran. Methods: HIV-infected patients were selected from behavioral advisory centers of Hamadan and Kermanshah Provinces, west of Iran. Saliva was collected between 8 and10 in the morning. Five mL of whole unstimulated saliva was collected in 5 minutes by spitting into sterilized Falcon tubes based on Navazesh method; pH was measured with a pH meter and uric acid was assessed with spectrophotometric method. Data were analyzed with STATA 12. Results: Salivary pH in the HIV-positive group was lower (6.99±0.46) than the healthy controls (7.14±1.03) but the difference was not statistically significant (P=380). Uric acid concentrations in HIV-infected patients (2.94±2.14) were significantly lower in comparison to the healthy controls (5.21±2.30). The results showed a statistically significant decrease in the case group (P=0.001). Mean age and DMFT index of the case group were higher than the control group. Conclusion: Uric acid, the main antioxidant of saliva, was significantly lower in HIVinfected individuals; pH also was lower in these patients. HIV can alter salivary antioxidant status, which can influence patients' oral health status. Diet with antioxidant properties might be helpful in these patients. More research is necessary to discover true antioxidant and salivary changes and their relation with HIV consequences in future.

Background: Today considerable number of drugs are produced from plants. Several plants with antibacterial and healing applications are used in medicine such as Roman chamomile (Chamaemelum nobile L.). Wound infection is one of the most prevalent infections among infectious diseases around the world. Due to appearance of drug resistance, researchers are now paying attention to medicinal plants. Therefore, this study was designed to investigate the antimicrobial and wound healing properties of C. nobile against Pseudomonas aeruginosa using in vivo conditions. Methods: Ethanolic extract of C. nobile was provided using standard method. The 5% C. nobile ointment was prepared by dissolving lyophilized extract in eucerin. Forty five male rats were obtained from Ilam university. After anesthetization and wound creation, wounds were infected by P. aeruginosa. The rats were divided into three groups, group I was treated with C. nobile ointment, group II was treated with tetracycline ointment and the third group was treated with base gel as control group. Results: Antibacterial and wound healing activities of C. nobile ointment were more than tetracycline ointment significantly. Our results indicated that extract of C. nobile had effective antibacterial activity and accelerated the progression of wound healing. Conclusion: Our study indicated that antibacterial and wound healing activities of C. nobile ointment were notable. C. nobile therapy in combination with antibiotics can also be useful because medicinal plants contents operate in synergy with antibiotics. These results revealed the value of plant extracts to control antibiotic resistant bacteria in wound infections.

Introduction: Pseudomonas aerouginosa is an important opportunistic pathogen which causes clinical infections among ill patients. Metallo- Beta- lactamases (MBLs) are important mechanisms of carbapenem (drug of choice) resistance among Pseudomonas aerouginosa isolates. The aim of this study was to determine B- lactamases genes (bla-genes) in P. aerouginosa isolates and to detect percentage of MBLs among P. aerouginosa isolates in different wards. Material and Methods: Clinical isolates of P. aerouginosa in patients hospitalized at Children's Medical Center were collected in two years using a sterile swab. For differentiation and identification of strains the BHI media, Sytrymaid agar and Oxidase test were used and Kirby Baure method antibiotic susceptibility and PCR assay were performed for detection of bla-genes. Results: Based on the study results from a total of 269 isolates of P. aerouginosa, 39 isolates were found to be imipenem resistant. From these isolates, 19 strains of P. aerouginosa isolates were determined to be MBL producers by phenotypic method. All of the Imipenem resistant P. aerouginosa isolates were examined by PCR for the presence of the bla-genes. All MBL- producing isolates carried bla-IMP Genes. And the results of the antibiogram showed the greatest resistance to the Nitrofurantoin, Nalidixic acid and Cotrimoxazole and Cefixime (100%) and resistance to other antibiotics was also significant. Conclusion: Considering the prevalence and clinical importance of MBL producing isolates, rapid identification of them and use of the appropriate infection control measures are necessary to prevent further spread of them by these organisms and to help treatment of Infections.

Background: Helicobacter pylori are gram-negative spiral shaped bacteria, with sheathed flagella. H. pylori infection is one of the most common chronic infections in humans. Infection is usually acquired during childhood, and becomes a lifelong infection in most people unless treated. The aim of this study was to evaluate serum levels of oxidative stress indices in children with H. pylori infection. Material and Methods: The present study was carried out on 60 children infected with H. pylori including 28 males, 32 females with their age ranging from 7-10 years and mean age value of 8.5 ± 1.65 ( Group I). This study included also 60 children as a control group including 26 males, 34 females with their age ranging from 7-11 and mean age value of 8.99 ± 1.63 (Group II). For all children in groups I the following were done: Diagnosis of H. pylori infection through H. pylori stool antigen testing using enzyme immunoassay kit and gastric antrum mucosal biopsies which were tested for urease activity using Campylobacter like organism test (CLO test). Measurements of serum oxidative stress markers including Superoxide dismutase (SOD), Malondialdhyde, Glutathione, Catalase and Nitric oxide were done in patients and controls. Results: Serum nitric oxide and reduced glutathione were significantly lower in patients compared to controls while serum MDA, Serum catalase and Serum SOD were significantly higher in patients compared to controls (nitric oxide was 91.111 ±6.366 in patients versus 107.211±2.121 in controls with p value of 0.001, reduced glutathione in patients was 2.457± 0.081 versus 2.889±0.491 in controls with p value of 0.001, serum MDA in patients was 140.22±5.18 versus 116.22±2.98 in controls with p value of 0.001, catalase was 401.645± 4.344 versus 278.221±71.712 in controls with p value of 0.001 and SOD in patients was 16.936±9.145 versus 5.578±0.231 in controls with p value of 0.001). Conclusion: H. pylori infection is associated with oxidative stress with significantly lower serum nitric oxide and reduced glutathione and significantly higher serum MDA, catalase and SOD in patients compared to controls. Recommendations: Antioxidants may be beneficial adjuvant treatment in H. pylori infection as H. pylori infection is associated with oxidative stress.

Background: ‘Helicobacter pylori’ “H. pylori” is one of the most common infections that colonizes human gastric mucosa and generates reactive oxygen and nitrogen species. The aim of this study was to evaluate the oxidative stress markers in the gastric mucosa of “H. pylori”– infected children. Patients and Methods: The present study was carried out on 60 children infected with “H. pylori” including 28 males, 32 females with their age ranging from 7-10 years and mean age value of 8.5 ± 1.65 years (Group I). This study included also 60 healthy children as a control group including 26 males and 34 females with their age ranging from 7-11 years and mean age value of 8.99 ± 1.63 years (Group II). All children were subjected to full history taking, thorough clinical examination, diagnosis of “H. pylori” infection through “H. pylori” stool antigen testing using enzyme immunoassay kit (Group I and II) and gastric antrum mucosal biopsies which were tested for urease activity using Campylobacter like organism test (CLO test) (Group I only) and measurement of gastric mucosal oxidative stress markers including Malondialdehyde (MDA), Superoxide dismutase (SOD), reduced glutathione (GSH), Catalase and nitric oxide (NO) [The sum of Nitrite (NO2-) and Nitrate (NO3-)]. Results: The main clinical presentations in studied patients and controls were recurrent abdominal pain, recurrent vomiting, dyspepsia and hematemesis with no significant difference between patients and controls as regard abdominal pain, vomiting or dyspepsia but hematemesis was found only in patients. There were significant differences between patients and controls as regard site and duration of abdominal pain with epigastrium being the most common site of pain in patients versus diffuse abdominal pain in control group with significantly longer duration of abdominal pain in patients compared with controls. “H. pylori” infected children has significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, catalase and SOD compared to controls (nitric oxide was 85.68 ± 23.16 nmol/gm in patients versus 106.423±2.111 nmol/gm in controls, reduced glutathione in patients was 1.83 ± 0.16 nmol/gm versus 2.44 ± 0.07 nmol/gm in controls, MDA in patients was 189.15 ± 6.14 nmol/gm versus 166.21 ± 3.13 nmol/gm in controls, catalase was 57.38 ± 19.85 unit/gm in patients versus 36.51 ± 2.34 unit/gm in controls and SOD in patients was 375.52 ± 26.51 unit/gm versus 318.51 ± 32.06 unit/gm in controls. Conclusion: “H. pylori” infection is associated with gastric mucosal oxidative stress with significantly lower gastric mucosal nitric oxide and reduced glutathione and significantly higher gastric mucosal MDA, Catalase and SOD in patients compared to controls. Recommendations: Antioxidants may be an important adjuvant therapy for “H. pylori” infection as this infection is associated with gastric mucosal oxidative stress.

Background: Extended spectrum beta lactamases (ESBL) are responsible for increased resistance to third generation cephalosporins. Proteus species is an important cause of both community acquired and nosocomial infections. The Proteus species is usually susceptible to beta lactam drugs but there is progressive increase in beta lactam resistance and recently, ESBLs are also fast spreading to this species. Objective: This study was conducted to study ESBL production and occurrence of TEM, SHV and CTX-M beta lactamases in clinical isolates of Proteus species in a tertiary care center. Method: This prospective hospital based study was carried out in Microbiology, Kasturba Medical College, Mangalore over 9 months. All non-duplicate consecutive Proteus isolates were identified and antibiotic susceptibility testing was done. ESBL detection was done by double disk synergy method and TEM, SHV, CTX-M genes were detected by PCR. Results: 84 Proteus isolates from urine (29), blood (1), respiratory secretions (2), tissue (20) and exudates (47) were included in the study. 20.2% (17) were ESBL positive by disk synergy method. CTX-M was present in 6, TEM in 2 and both in 9 isolates. SHV was not present in any isolate. Conclusion: Our findings showed that 20% of clinical isolates of Proteus species were ESBL producers. 52% of ESBL positive isolates carried both TEM and CTX-M genes followed by CTX-M alone (35%) and only 11% had TEM alone. This stresses on the fact that ESBL detection should be done routinely in Proteus isolates and the genotype surveyed periodically for better management.

Aim: To evaluate the feasibility of the revised “Clinical Guideline for HIV and TB” in the Great Tehran Prison during October 2013 to June 2014. Methods: The guideline includes all aspects of HIV/TB diagnosis based on active case finding (ACF), treatment and care services. Before the implementation, a focus group discussion was conducted, and attended by experts on prison health. The objective was to identify defects and limitations of the guideline. After the discussion, the guideline was revised. The Great Tehran Prison contains three separate units; all prisoners are taken first to “reception and identification unit (quarantine)” and then send to two housing units according to their legal status. An HIV ACF strategy was employed in the quarantine, and two units through a voluntary provider-initiated HIV testing. Three staff of the triangular clinic trained the prisoners about common routes of HIV transmission and the symptoms of TB in the units. In the quarantine, all prisoners were examined for all HIV-risk factors, HIV testing and symptoms of TB. In unit one, healthcare staff continued the ACF process, while in unit two, the peers of prisoners were assigned as the healthcare communicators to proceed with the strategy. At this caring process, when the test result was positive, then the process of care, treatment and follow ups was initiated. Moreover, the use of directly observed therapy (DOT) for antiretroviral therapy (ART) and TB was applied to the sick prisoners. There was also a follow-up caring for released prisoner to refer them to care and treatment services outside the prison. Results: The guideline was implemented in the prison successfully. Conclusion: Regarding feasibility of the guideline, the investigators of this study suggest that the guideline should be implemented in other prisons across the country.

Multi drug resistant (MDR) Pseudomonas aeruginosa and Extended- Spectrum-lactamase (ESBL) Enterobacteriaceae are becoming an increasing difficult clinical problem. Immediate resistance to some of the new antimicrobials such as ceftolozane/tazobactam is unusual and is due to a variety of mechanisms such as hyper-production of inactivating enzymes and gene mutation. In addition, previous antimicrobial administration is a well-recognized risk factor to develop resistance. We present a patient with a liver abscess where the organism was resistant to ceftolozane/tazobactam resulting in a poor clinical outcome.