Candida coinfection among patients with pulmonary tuberculosis in Asia and Africa; A systematic review and meta-analysis of cross-sectional studies.

Diagnosis of fungal co-infections in patients suffering from pulmonary tuberculosis has critical importance. Therefore, we aimed to determine the prevalence of candida coinfection in patients with pulmonary tuberculosis. The present systematic review of cross-sectional studies was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) Protocol. Studies published online in English from January 2001 to March 2019 were assessed. Literature search was done in Web of Science, MEDLINE/PubMed, and Scopus databases and search engines using keywords combinations of "pulmonary fungi", "pulmonary coinfection", OR "pulmonary mycosis", "pulmonary fungal infections/agents", OR "polymicrobial infection", OR "secondary infection", OR "mixed infections", "pulmonary candidiasis", "fungi coinfection", "fungal co-colonization", AND "pulmonary tuberculosis", OR "pulmonary TB", AND "Asia", AND "Africa". Data was analyzed using Comprehensive Meta-Analysis software (CMA). Heterogeneity between studies was evaluated by Cochran's Q and I2 tests. The pooled prevalence of candida coinfection among patients with pulmonary tuberculosis was 25.7% (95% CI: 23.7-27.9). C. albicans was the most prevalent Candida spp. with a pooled prevalence of 65.8% (95% CI: 54.3-75.7). Risk factors of candida coinfection were smoking, diabetes, advanced age, and low body mass index. The present review showed a high rate of candida coinfection among patients suffering from pulmonary tuberculosis. So, appropriate measures are necessary to early diagnose and treat these infections.

Investigation of CTLA-4 and CD86 gene polymorphisms in Iranian patients with brucellosis infection.

The protective immune response against Brucella involves T-cell-mediated immunity. T-lymphocyte receptors, CD28 and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), bind the same ligands, CD80 (B7-1) and CD86 (B7-2) on antigen-presenting cells and regulate T cell activation. CD28 delivers stimulatory signals whereas CTLA-4 provides inhibitory signals for T cell activation. Here, we investigated the association of four polymorphisms in CTLA4 (+49A/G [rs231775] and -318 C/T [rs5742909]) and its ligand CD86 (+1057 G/A [rs1129055] and +2379G/C [rs17281995]) with brucellosis infection. The study included 153 Iranian patients with active brucellosis and 128 healthy individuals as the control group. Genotyping of the CTLA4 and CD86 variants was performed using tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) and PCR-restriction fragment length polymorphism analysis, respectively. It was found that the CTLA4 -318 CT genotype and T allele were present more frequently in cases than in controls and are therefore associated with an increased risk for brucellosis (-318 TT genotype; OR = 2.544, P = 0.002). Likewise, the CD86 +1057 GA and AA genotypes and A allele were associated with an increased risk of brucellosis (+1057 AA genotype; OR = 3.81, P = 0.001). However, no statistically significant difference between brucellosis patients and controls in the allele and genotype distributions of CTLA4, +49A/G (P = 0.859) and CD86, +2379G/C (P = 0.476) was found. In conclusion, CTLA4 -318 CT genotype and T allele and the CD86 +057 GA and AA genotypes and A allele play roles as risk factors for developing brucellosis infection in Iran.

Relationship between γ-interferon gene polymorphisms and susceptibility to brucellosis infection.

Interferon-gamma (IFN-γ) is a pro-inflammatory cytokine that plays a pivotal role in the defense mechanism against Brucella infection. It was hypothesized that the IFN-γ in (+874 A/T in intron 1) TT and +5644 T/A, TT genotypes, which are reportedly associated with high IFN production, are associated with susceptibility to brucellosis in Iranian subjects. Genotyping of these IFN-γ variants by an allele-specific polymerase chain reaction method was performed in 281 subjects, comprising 153 patients with active brucellosis and 128 healthy controls. It was found that the +874 minor allele (A) and homozygote genotype (AA) were significantly more frequently present in brucellosis patients than in controls (OR = 2.588; 95% CI, 1.313-5.104; P = 0.006 for the AA genotype; OR = 1.575; 95% CI, 1.124-2.216; P = 0.010 for the A allele). However, the allelic and genotypic distribution of the IFN-γ polymorphism at position UTR5644 A>T did not differ significantly between patients and controls (P > 0.05). The distribution of haplotypes in this study suggests that the T/A haplotype (+874/UTR5644), which was present more frequently in controls than in patients, may protect subjects against Brucella infection. It is suggested that IFN-γ +874 AA genotype and A allele are risk factors for developing brucellosis infection in Iranian subjects.

Circulating levels of interleukin (IL)-12 and IL-13 in Helicobacter pylori-infected patients, and their associations with bacterial CagA and VacA virulence factors.

OBJECTIVE: The aim of this study was to determine the association of the Helicobacter pylori virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) antibodies, with serum levels of interleukin (IL)-12 and IL-13 in H. pylori-infected duodenal ulcer (DU) patients and H. pylori-infected asymptomatic (AS) carriers in order to elucidate any correlation between them. METHODS: A total of 67 DU patients, 48 AS individuals, and 26 healthy H. pylori-negative subjects were enrolled in this study. Serum concentrations of IL-12 and IL-13 were determined by enzyme-linked immunosorbent assay (ELISA) method. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial virulence antigens p120 (CagA) and p95 (VacA). Serum concentrations of IL-12 and IL-13 were compared in 9 groups, including 4 AS phenotypes (CagA⁺VacA⁺, CagA⁺VacA⁻, CagA⁻VacA⁺, CagA⁻VacA⁻), 4 DU phenotypes (CagA⁺VacA⁺, CagA⁺VacA⁻, CagA⁻VacA⁺, CagA⁻VacA⁻), and 1 control group. RESULTS: The results revealed that DU patients positive for CagA, independent of the anti-VacA antibody status, showed drastically elevated levels of IL-12 (251 ± 43 pg/ml) when compared with the other groups (p = 0.0001). No significant difference was found between groups regarding levels of IL-13 (p > 0.05). CONCLUSIONS: Our findings indicate that in the DU group, the serum concentrations of IL-12 but not of IL-13 were influenced by bacterial CagA, independent of the VacA status, suggesting that high IL-12 levels may contribute to susceptibility to DU in CagA-positive individuals. These findings could possibly be considered to improve the predictive or prognostic values of inflammatory cytokines for DU, and also to design possible novel therapeutic approaches.

The association of interleukin-18 promoter polymorphisms and serum levels with duodenal ulcer, and their correlations with bacterial CagA and VacA virulence factors.

BACKGROUND: We analyzed the impact of interleukin (IL)-18 promoter polymorphisms on IL-18 serum levels in Helicobacter pylori-infected duodenal ulcer (DU) patients and healthy asymptomatic (AS) carriers. We also aimed to determine the association of the H. pylori virulence factors CagA and VacA antibodies with serum concentrations of IL-18 in order to elucidate any correlation between them. METHODS: Three groups of patients were enrolled: DU patients (67 individuals), AS carriers (48 individuals), and H. pylori-negative subjects (26 individuals). Serum concentrations of IL-18 were determined by ELISA. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial CagA and VacA. Genotyping of IL-18 promoter polymorphisms at positions - 137G/C and - 607C/A were performed by allele-specific primer PCR protocol. RESULTS: Our study revealed that serum IL-18 levels are positively influenced by CagA-positive H. pylori strains, so that maximum levels of IL-18 were detected in DU patients with the CagA(+) phenotype, regardless of the presence of the anti-VacA antibody. Regarding IL-18 promoter polymorphisms, the AA genotype and A allele at position - 607C/A were found to be significantly lower in DU patients than in AS carriers and H. pylori-negative subjects (p = 0.032 and 0.043, respectively). CONCLUSIONS: The IL-18 - 607C variant was associated with higher levels of serum IL-18 and an increased risk of DU. Moreover, our findings indicated that serum concentrations of IL-18 were influenced by CagA factor, irrespective of the VacA status, suggesting that high levels of IL-18 in CagA-positive subjects predisposes to susceptibility to DU.

Isolation and immunogenicity of extracted outer membrane vesicles from Pseudomonas aeruginosa under antibiotics treatment conditions.

BACKGROUND AND OBJECTIVES: Different types of antibiotics have been indicated to enhance the secretion of OMVs from Pseudomonas aeruginosa. We aimed to investigate the effect of meropenem and amikacin antibiotics on inducing the secretion of OMVs and immunologic features in P. aeruginosa. MATERIALS AND METHODS: The OMVs were prepared from P. aeruginosa under hypervesiculation condition (treatment with amikacin and meropenem), and extraction was carried out by the sequential ultracentrifugation. Physicochemical features of extracted OMVs were evaluated by electron microscopy and SDS-PAGE. To quantify antibody synthesis and function after immunization with OMV, we used ELISA, serum bactericidal activity, and opsonophagocytosis. Production of cytokines from splenocytes of immunized mice was measured with ELISA. RESULTS: Specific-antibody IgG production, particularly IgG1 subclass, increased in mice primed with hypervesiculation-derived OMVs compared to normal condition-derived OMVs. Serum bactericidal activity and opsonophagocytosis of secreted antibody was enhanced in mice primed with hypervesiculation-derived OMVs. Investigation of cytokine production showed the upregulation of IL-8, IL-12, IL-17, and TNF-α and downregulation of IL-10. CONCLUSION: Based on our findings, OMVs production can be increased by treating P. aeruginosa with amikacin and meropenem antibiotics. Moreover, hypervesiculation-derived OMV scan possibly activate the humoral and cellular immune response more than normal OMVs.

Correlation between biofilm formation and antibiotic resistance in Pseudomonas aeruginosa: a meta-analysis.

Biofilm formation is one of the important resistance mechanisms in Pseudomonas aeruginosa. This study aimed to consider the correlation between biofilm formation and antibiotic resistance in Pseudomonas aeruginosa through a systematic review and meta-analysis. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) strategies. Scientific databases were searched by MeSH terms and keywords such as "Pseudomonas aeruginosa", "biofilm formation", "antibiotic resistance", "prevalence" AND "Iran", to obtain articles published from 1st January 2016 to 30th November 2019. Studies recording biofilm formation and antibiotic resistance in P. aeruginosa recovered from clinical samples of Iranian patients were included. Data analysis was performed using CMA software. The combined biofilm formation rate was reported as 87.6 % (95% CI: 80-92.5). The heterogeneity index among the selected articles was Q2=96.5, I2=85.5, and t=0.26 (p=0.16). The pooled occurrences of strong, moderate and weak biofilms were 47.7% (95% CI: 28.7-67.3), 30.2% (95% CI: 19.4-43.8), and 27.4% (95% CI: 8.8-59.8), respectively. The pooled prevalence of MDR P. aeruginosa strains was as follows: 62.5% (95% CI: 40-77.2). The highest combined rates of antibiotic resistance were against ceftriaxone and tobramycin with the rates of 79.2.9% (95% CI: 54.2-96.2) and 64.4% (95% CI: 36.3-92), respectively. Also, the lowermost antibiotic resistance rates were against colistin and polymyxin B, with the prevalence of 2.1% (95% CI: 0.2-18.1), and 3% (95% CI: 0.5-17.3), respectively. More than half of the studies included in the present review showed a significant correlation between biofilm formation and antibiotic resistance pattern.

Meta-Analysis of Biofilm Formation, Antibiotic Resistance Pattern, and Biofilm-Related Genes in Pseudomonas aeruginosa Isolated from Clinical Samples.

Resistant microorganisms such as Pseudomonas aeruginosa grow by developing biofilms in hospitals. We aimed to investigate the biofilm formation and the frequencies of biofilm-related genes and their associations with antibiotic resistance pattern in P. aeruginosa isolated from Iranians' clinical samples. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a systematic literature search in scientific databases using medical subject heading terms, including "Pseudomonas aeruginosa," "biofilm formation," "biofilm-related genes," "antibiotic resistance," and "prevalence," to obtain related articles published from 1st January, 2000, to 30th March, 2019. The studies reporting the prevalence of biofilm formation, the frequencies of biofilm-related genes, and the antibiotic resistance pattern in P. aeruginosa retrieved from Iranian patients were included. Meta-analysis was performed using the Comprehensive Meta-Analysis software. The pooled rate of biofilm formation was calculated as 86.5% (95% confidence interval [CI]: 79-91.6). The combined frequencies of strong, moderate, and weak biofilms were 51% (95% CI: 37.4-64.4), 29.2% (95% CI: 20.9-39.1), and 25.4% (95% CI: 11.5-47.2), respectively. The pooled prevalence of laslR, algD, algU, ppyR, and pelF genes were 93.6% (95% CI: 88.1-96.6), 91.4% (95% CI: 80.8-96.4), 89.3% (95% CI: 85.2-92.3), 98.7% (95% CI: 96.5-99.6), and 93% (95% CI: 82.7-97.3), respectively. The highest combined antibiotic resistance rates of P. aeruginosa isolates were against piperacillin/tazobactam (90%). This study showed that biofilm formation was higher in multidrug-resistant (MDR) P. aeruginosa than non-MDRs. A significant correlation was observed between biofilm formation and antibiotic resistance in 50% of studies included in this review.

Correlation Between Biofilm Formation and Antibiotic Resistance in MRSA and MSSA Isolated from Clinical Samples in Iran: A Systematic Review and Meta-Analysis.

Objectives: This study aimed at reviewing the correlation between biofilm formation and antibiotic resistance in methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) isolates. Materials and Methods: This review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols. The literature search was conducted in PubMed, Web of Science (ISI), and Scopus databases. Combinations of Mesh terms such as "biofilms" OR "biofilm formation," AND "Drug Resistance" OR "Antimicrobial Drug Resistance" OR "Antibiotic Resistance" AND "Staphylococcus aureus" OR "Methicillin-resistant Staphylococcus aureus" or "MRSA" AND "Methicillin-sensitive Staphylococcus aureus" OR "MSSA" AND "biofilm-related genes" AND "Prevalence" AND "Iran" were searched. Two reviewers independently searched the databases. Analyses were performed in Comprehensive Meta-Analysis software. The random-effects model was used to obtain the combined prevalence with a 95% confidence interval (CI). Results: The combined prevalence of MRSA retrieved from Iranian clinical samples was 48.3% (95% CI: 40.8-55.9). The pooled rate of biofilm formation in MRSA strains was reported as 80.9% (95% CI: 67.8-89.4). Overall, 52.9%, 45.3%, and 22.5% of MRSA isolates were strong, moderate, and weak biofilm producers, respectively. The highest frequency of biofilm-related genes was observed for icaD gene (67.7%) followed by clfA gene with a frequency of 64.7%. Among seven studies that addressed the relationship between biofilm formation and antibiotic resistance, six reported positive associations. Conclusions: Regarding the MRSA strains, they had a significantly higher ability of biofilm formation than MSSA strains; therefore, preventive measures against infections caused by them are required.