Staphylococcal enterotoxins as good candidates for cancer immunotherapy: a systematic review.

BACKGROUND: Cancer is considered as one of the leading causes of death today. The wrong lifestyles have led to an increase in the incidence rate of this deadly disease. There are many complications associated with common treatments of this disease. Immunotherapy is one of the new approaches taken recently. The purpose of this systematic review was to evaluate the studies on Staphylococcus aureus enterotoxins as a treatment of cancer worldwide. STUDY DESIGN: We conducted a systematic review of articles published in PubMed, Cochrane, Scopus and Google scholar databases from 1995 to 2016 to evaluate the effects of Staphylococci enterotoxins on cancer. METHODS: Eligible studies were evaluated qualitatively based on a checklist prepared by two independent reviewers, and they were subsequently matched. RESULTS: Our review identified 97 records through searching PubMed and Cochrane database and 1306 records through searching Google scholar and Scopus. Forty six studies were excluded from PubMed and Cochrane database and 1281 studies were excluded from Google scholar and Scopus after screening abstracts and titles. Therefore, our systematic review was based on 51 publications on PubMed and Cochrane, and 25 publications on Google scholar and Scopus, which met our criteria. Staphylococcal enterotoxin A was the most commonly used toxin in these studies. The side effects of using this toxin in immunotherapy have been reported to be low and all studies have identified this toxin as a suitable option for immunotherapy. CONCLUSIONS: The data obtained from these studies showed that due to the low rates of complications, Staphylococcal enterotoxins have the potential to induce immune system against various cancers as super-antigens. Therefore, they can be considered as a suitable candidate for immunotherapy of cancer.

The reliability of rifampicin resistance as a proxy for multidrug-resistant tuberculosis: a systematic review of studies from Iran.

In Iran, patients showing rifampicin (RIF) resistance detected by the Xpert® MTB/RIF assay are considered as candidates for multidrug-resistant tuberculosis (MDR-TB) treatment. Despite the fact that RIF resistance has been used as a proxy for MDR-TB, little is known about the proportion of isoniazid (INH) resistance patterns in RIF-resistant TB. We systematically searched MEDLINE, Embase, and other databases up to March 2017 for studies addressing the proportion of INH resistance patterns in RIF-resistant TB in Iran. The data were pooled using a random effects model. Heterogeneity was assessed using Cochran's Q and I2 statistics. A total of 11 articles met the eligibility criteria. Data analysis demonstrated that 33.3% of RIF-resistant isolates from new TB cases and 14.8% of RIF-resistant isolates from previously treated cases did not display resistance to INH. The relatively high proportion of INH susceptibility among isolates with RIF resistance indicated that RIF resistance may no longer predict MDR-TB in Iran. Therefore, the detection of RIF resistance by the Xpert MTB/RIF assay will require complementary detection of INH resistance by other drug susceptibility testing (DST) methods in order to establish the diagnosis of MDR-TB.

Rifampicin resistance in Mycobacterium tuberculosis in Iran: a two-centre study.

Multidrug-resistant tuberculosis remains a challenge. In this study, we investigated the incidence of rifampicin (RIF) resistance in Mycobacterium tuberculosis in a large number of pulmonary specimens. A two-center study in Tehran, the capital of Iran, was performed with 6624 pulmonary samples of patients with tuberculosis (TB) who were subjected to detection of RIF-resistant TB by GeneXpert MTB/RIF assay between May 2014 and July 2018. Conventional drug susceptibility testing was performed to confirm the results. Xpert MTB/RIF identified a total of 96 positives for M. tuberculosis, of which 5 (5.3%) samples were found to be RIF-resistant TB. All RIF-resistant and sensitive isolates detected by GeneXpert were phenotypically confirmed by drug susceptibility testing. These results indicated that the Xpert MTB/RIF test can be used as a rapid diagnostic method and can potentially decrease the morbidity associated with diagnostic delay and mistreatment.

Synergistic effects between Staphylococcal enterotoxin type B and Monophosphoryl lipid A against mouse fibrosarcoma.

PURPOSE: Staphylococcal enterotoxin B (SEB) is a potent inducer of cytotoxic T-cell activity, cytokine production and necrosis induction in vivo. Monophosphoryl lipid A (MPL) is an adjuvant derived from the lipopolysaccharide of E. coli, Salmonella Minnesota Re595 and other gram negative bacteria. We investigated the possibility of the therapeutic application of SEB+ MPL in mice with fibrosarcoma. METHODS: The antitumor effect of SEB+MPL, SEB and MPL in mice with inoculated fibrosarcoma tumor (WEHI-164) was examined by intravenous (i.v.) and intratumoral (i.t.) injection and the sizes of the inoculated tumors, IFN-gamma production, and CD4(+)/CD8(+) T cell infiltration were determined. The inoculated tumors were also examined histologically. RESULTS: In the i.v.-injected group of mice with SEB+ MPL, reduction of tumor size showed a significant difference compared with mice in the i.t., the i.v. (MPL)-injected groups and the negative control group (p < 0.02). Moreover, the mice in the i.v. (SEB+ MPL)-injected group showed significantly higher levels of IFN-gamma (p < 0.009) and CD4(+)/CD8(+) T cell infiltration when compared with the other groups (p < 0.02). A significantly higher frequency of necrosis in tumor tissues was also observed in mice in the i.v. (SEB+ MPL)-injected group in comparison with other groups (p < 0.009). CONCLUSION: Our findings suggest that tumor cell death is caused by increased cytotoxic T-cell activity, cytokine levels, in response to IV injection of SEB+MPL. They also suggest that tumor cell death by synergistic effect of one of the strongest bacterial superantigens (SEB) with monophosphoryl lipid A and SEB+MPL may be a good option for use as a novel therapy in patients with fibrosarcoma.

High rates of nontuberculous mycobacteria isolation from patients with presumptive tuberculosis in Iran.

Nontuberculous mycobacteria (NTM) can cause disease which can be indistinguishable from tuberculosis (TB), posing a diagnostic and therapeutic challenge, particularly in low- and middle-income settings. We aimed to investigate the mycobacterial agents associated with presumptive clinical pulmonary TB in Iran. A total of 410 mycobacterial isolates, obtained between March 2014 and January 2016, from 7600 clinical samples taken from consecutive cases of presumptive diagnosis of TB were identified. Phenotypic and molecular tests were used to identify the isolated organisms to the species level. Single-locus and multilocus sequence analysis based on 16S rRNA, rpoB, hsp65 and ITS locus were used to confirm the results. Of 410 consecutive strains isolated from suspected TB subjects, 62 isolates (15.1%) were identified as NTM. Patients with positive NTM cultures met American Thoracic Society diagnostic criteria for NTM disease. Mycobacterium simiae was the most frequently encountered (38.7%), followed by Mycobacterium fortuitum (19.3%), M. kansasii (17.7%) and M. avium complex (8.0%). Isolation of NTM, including M. simiae, from suspected TB cases is a serious public health problem and merits further attention by health authorities, physicians and microbiologists.

A multiplex PCR method for detection of Aspergillus spp. and Mycobacterium tuberculosis in BAL specimens.

OBJECTIVE: The aim of this study was the detection of Aspergillus species and Mycobacterium tuberculosis together in bronchoalveolar lavage (BAL) using of multiplex PCR. MATERIAL AND METHODS: In this study, from September 2012 until June 2013, 100 bronchoalveolar lavage (BAL) specimens were collected from patients suspected of tuberculosis (TB). After the direct and culture test, multiplex PCR were utilized in order to diagnose Aspergillus species and M. tuberculosis. Phenol-chloroform manual method was used in order to extract DNA from these microorganisms. Aspergillus specific primers, M. tuberculosis designed primers and beta actin primers were used for multiplex PCR. RESULTS: In this study, by multiplex PCR method, Aspergillus species were identified in 12 samples (12%), positive samples in direct and culture test were respectively 11% and 10%. Sensitivity and specificity of this method in comparison to direct test were respectively 100% and 98.8%, also sensitivity and specificity of this method in comparison to culture test were respectively 100% and 97.7%. In this assay, M. tuberculosis was identified in 8 samples (8%). Mycobacterium-positive samples in molecular method, direct and culture test were respectively 6%, 5% and 7%. Sensitivity and specificity of PCR method in comparison to direct test were 80% and 97.8% also sensitivity and specificity of this method in comparison to culture test was 71.4% and 98.9%. CONCLUSION: In the present study, multiplex PCR method had higher sensitivity than direct and culture test in order to identify and detect Aspergillus, also this method had lower sensitivity for identification of M. tuberculosis, suggesting that the method of DNA extraction was not suitable.

Rapid screening of rpoB and katG mutations in Mycobacterium tuberculosis isolates by high-resolution melting curve analysis.

BACKGROUND: Early detection of multidrug-resistant tuberculosis (MDR-TB) is essential to prevent its transmission in the community and initiate effective anti-TB treatment regimen. MATERIALS AND METHODS: High-resolution melting curve (HRM) analysis was evaluated for rapid detection of resistance conferring mutations in rpoB and katG genes. We screened 95 Mycobacterium tuberculosis clinical isolates including 20 rifampin resistant (RIF-R), 21 isoniazid resistant (INH-R) and 54 fully susceptible (S) isolates determined by proportion method of drug susceptibility testing. Nineteen M. tuberculosis isolates with known drug susceptibility genotypes were used as references for the assay validation. The nucleotide sequences of the target regions rpoB and katG genes were determined to investigate the frequency and type of mutations and to confirm HRM results. RESULTS: HRM analysis of a 129-bp fragment of rpoB allowed correct identification of 19 of the 20 phenotypically RIF-R and all RIF-S isolates. All INH-S isolates generated wild-type HRM curves and 18 out of 21 INH-R isolates harboured any mutation in 109-bp fragment of katG exhibited mutant type HRM curves. However, 1 RIF-R and 3 INH-R isolates were falsely identified as susceptible which were confirmed for having no mutation in their target regions by sequencing. The main mutations involved in RIF and INH resistance were found at codons rpoB531 (60% of RIF-R isolates) and katG315 (85.7% of INH-R isolates), respectively. CONCLUSION: HRM was found to be a reliable, rapid and low cost method to characterise drug susceptibility of clinical TB isolates in resource-limited settings.

Design of a multiplex PCR method for detection of toxigenic-pathogenic in Vibrio cholerae.

OBJECTIVE: To study virulence and regulatory genes (hlyA, ctxB, tcpI) in clinical strains of Vibrio cholerae (V. cholerae), simultaneously. METHODS: Three important genes, tcpI, hlyA and ctxB were used for detection of toxigenic and pathogenic V. cholera by chain reaction assay method. RESULTS: According to the results of the PCR, the incidence of hlyA, tcpI, and ctxB genes in clinical isolates was obtained as 94.7% (72 sample), 90.8% (69 sample), and 92.1% (70 sample), respectively. Five strains possessed all genes except ctxB, six strains possessed all genes except tcpI, four strains possessed all genes except hlyA, one strain possessed only hlyA and 60 strains contained a combination of three genes, Including hlyA, ctxB and tcpI. CONCLUSIONS: Result show that this method could be reliable to detect toxigenic-pathogenic strains of V. cholerae in Iran.

Antibiotic-coated pins for prevention of pin-tract infection: a rabbit study.

PURPOSE. To evaluate the efficacy of antibiotic-coated pins for prevention of pin tract infection in a rabbit model. METHODS. 10 rabbits were divided into 2 groups. A unilateral external fixator was applied to the tibia with 4 self-taping 1.8-mm pins. In the test group, pins were coated with hydroxyapatite and antibiotic. In the control group, pins were not coated. All pins were then placed in Staphylococcus aureus- containing media. At postoperative day 5, all 40 pin sites were subcutaneously inoculated with S aureus. The sites were clinically examined for signs of pin tract infection. Nine days later, a piece of soft tissue around the pin site was harvested for microbiologic examination. RESULTS. In the test group, all except one pin sites appeared clean and without clinical infection, and the culture media remained clear. In the control group, all pin sites showed evidence of clinical infection and yielded positive cultures, and the culture media became dark indicating growth of S aureus. CONCLUSION. Antibiotic-coated pins were effective in preventing pin tract infection.

Development of a new DNA extraction protocol for PFGE typing of Mycobacterium tuberculosis complex.

A modified pulsed-field gel electrophoresis (PFGE) protocol was developed and applied to clinical isolates of Mycobacterium tuberculosis complex to reduce the cost of using lyticase. This protocol reduces the expense of PFGE typing of Mycobacterium tuberculosis complex as it removes the use of lyticase during the spheroplast formation from these bacteria.

A survey of traditional Iranian food products for contamination with toxigenic Clostridium botulinum.

This study aimed to determine the rate of Clostridium botulinum contamination in some traditional Iranian food products (cheese, kashk and salted fish) and evaluate the efficacy of the mouse bioassay method in detection of C. botulinum toxins in these foods. A total of 131 samples (57 cheese, 11 kashk and 63 salted fish) were collected and examined to determine the rate of contamination by C. botulinum. Standard monovalent anti-toxins were used to determine the types of toxin. C. botulinum bacteria were detected in 4.58% of the examined samples (1.52% of cheese and 3.06% of salted fish samples). While no contamination was detected in the kashk samples, C. botulinum types A and E were found to be dominant in cheese and salted fish samples, respectively. These results indicate-some traditional Iranian foods may be contaminated with different types of C. botulinum, and the consumption of these products, either raw or cooked, may contribute to food-borne intoxications.