Development, Strategies, and Challenges for Tularemia Vaccine.

Francisella tularensis is a facultative intracellular bacterial pathogen that affects both humans and animals. It was developed into a biological warfare weapon as a result. In this article, the current status of tularemia vaccine development is presented. A live-attenuated vaccine that was designed over 50 years ago using the less virulent F. tularensis subspecies holarctica is the only prophylactic currently available, but it has not been approved for use in humans or animals. Other promising live, killed, and subunit vaccine candidates have recently been developed and tested in animal models. This study will investigate some possible vaccines and the challenges they face during development.

Rickettsia conorii subsp. israelensis infection in a pediatric patient presenting skin rash and abdominal pain: a case report from Southeast Iran.

BACKGROUND: The healthcare system in Iran appears to overlook Mediterranean spotted fever (MSF) as an endemic disease, particularly in pediatric cases, indicating the need for greater attention and awareness. CASE PRESENTATION: A six-year-old patient with fever, abdominal pain, headache, skin rashes, diarrhea, vomiting, and black eschar (tache noire) from southeast Iran was identified as a rickettsiosis caused by Rickettsia conorii subsp. israelensis through clinical and laboratory assessments, including IFA and real-time PCR. The patient was successfully treated with doxycycline. CONCLUSIONS: Symptoms like rash, edema, eschar, and abdominal pain may indicate the possibility of MSF during the assessment of acute febrile illness, IFA and real-time PCR are the primary diagnostic methods for this disease.

Prevalence of Brucella melitensis and Brucella abortus aminoglycoside-resistant isolates: a systematic review and meta-analysis.

INTRODUCTION: Aminoglycosides are vital antibiotics for treating Brucella infections, because they interfere with bacterial protein production and are often combined with other antibiotics. They are cost-effective, have fewer side effects, and can penetrate biofilms. The prevalence of brucellosis has increased in recent years, increasing the need for effective treatments. In addition, the emergence of multidrug-resistant Brucella strains has highlighted the need for an updated and comprehensive understanding of aminoglycoside resistance. This systematic review aimed to provide a comprehensive overview of the global prevalence of aminoglycoside resistance in B. melitensis and B. abortus. METHODS: A systematic search of online databases was conducted and eligible studies met certain criteria and were published in English. Quality assessment was performed using the JBI Checklist. A random-effects model was fitted to the data, and meta-regression, subgroup, and outlier/influential analyses were performed. The analysis was performed using R and the metafor package. RESULTS: The results of this systematic review and meta-analysis suggested that the average prevalence rates of streptomycin, gentamicin, and amikacin resistance were 0.027 (95% confidence interval [CI], 0.015-0.049), 0.023 (95% CI, 0.017-0.032), and 0.008 (95% CI, 0.002-0.039), respectively. The prevalence of streptomycin resistance was higher in the unidentified Brucella group than in the B. abortus and B. melitensis groups (0.234, 0.046, and 0.017, respectively; p < 0.02). The prevalence of gentamicin resistance increased over time (r = 0.064; 95% CI, 0.018 to 0.111; p = 0.007). The prevalence of resistance did not correlate with the quality score for any antibiotic. Funnel plots showed a potential asymmetry for streptomycin and gentamicin. These results suggest a low prevalence of antibiotic resistance in the studied populations. CONCLUSION: The prevalence of aminoglycoside resistance in B. melitensis and B. abortus was low. However, gentamicin resistance has increased in recent years. This review provides a comprehensive and updated understanding of aminoglycoside resistance in B. melitensis and B. abortus.

Prevalence of Brucella melitensis and Brucella abortus Fluoroquinolones Resistant Isolates: A Systematic Review and Meta-Analysis.

Background: Brucellosis impact both animals and humans worldwide. However, using antibiotics for brucellosis remains controversial despite decades of research. Relapse can complicate treatment in this area. Since the mid-1980s, microbiologists, and physicians have studied fluoroquinolones' use for treating human brucellosis. The principal advantages of fluoroquinolones are their intracellular antimicrobial activity, low nephrotoxicity, good pharmacokinetics, and the lack of drug-level monitoring. Fluoroquinolones inhibit disease recurrence. In vitro and clinical data were used to study the prevalence of Brucella melitensis and Brucella abortus fluoroquinolone-resistant isolates. Methods: The PubMed, Scopus, Embase, and Web of Science databases were carefully searched until August 6, 2022, for relevant papers. The number of resistant isolates and sample size were used to estimate the proportion of resistant isolates, fitting a model with random effects, and DerSimonian-Laird estimated heterogeneity. Furthermore, meta-regression and subgroup analyses were used to assess the moderators to identify the sources of heterogeneity. Meta-analysis was performed using R software. Results: Forty-seven studies evaluated fluoroquinolone resistance in Brucella spp. Isolates. Fluoroquinolones have shown high in vitro efficacy against Brucella spp. The resistance rates to ofloxacin, sparfloxacin, fleroxacin, pefloxacin, and lomefloxacin were 2%, 1.6%, and 4.6%, respectively. Conclusion: Clinical in vitro tests demonstrated that fluoroquinolones can eradicate Brucella spp. Owing to first-line medication resistance, recurrence, and toxicity, it is essential to standardize the Brucella antimicrobial susceptibility test method for a more precise screening of resistance status. Fluoroquinolones are less resistant to fluoroquinolone-based treatments in modern clinical practice as alternatives to standard therapy for patients with brucellosis relapse after treatment with another regimen and in patients who have developed toxicity from older agents.

Prevalence of Brucella melitensis and Brucella abortus tetracyclines resistance: A systematic review and meta-analysis.

INTRODUCTION: Brucellosis is a zoonotic disease that can be transmitted from animals to humans. Brucellosis is caused by bacteria of the genus Brucella, which are typically transmitted through contact with infected animals, unpasteurized dairy products, or airborne pathogens. Tetracyclines (tetracycline and doxycycline) are antibiotics commonly used to treat brucellosis; however, antibiotic resistance has become a major concern. This study assessed the worldwide prevalence of tetracycline-resistant Brucella isolates. METHODS: A systematic search was conducted in Scopus, PubMed, Web of Science, and EMBASE using relevant keywords and Medical Subject Headings (MeSH) terms until August 13, 2022, to identify relevant studies for meta-analysis. A random effects model was used to estimate the proportion of resistance. Meta-regression analysis, subgroup analysis, and examination of outliers and influential studies were also performed. RESULTS: The prevalence rates of resistance to tetracycline and doxycycline were estimated to be 0.017 (95% confidence interval [CI], 0.009-0.035) and 0.017 (95%CI, 0.011-0.026), respectively, based on 51 studies conducted from 1983 to 2020. Both drugs showed increasing resistance over time (tetracycline: r = 0.077, P = 0.012; doxycycline: r = 0.059, P = 0.026). CONCLUSION: The prevalence of tetracycline and doxycycline resistance in Brucella was low (1.7%) but increased over time. This increase in tetracycline and doxycycline resistance highlights the need for further research to understand resistance mechanisms and develop more effective treatments.

Evaluation of Putative Toxin-antitoxins Systems in Clinical Brucella melitensis in Iran.

BACKGROUND: Toxin-antitoxin systems (TAs) are two-component elements, which are extensive in the bacterial genome and have a regulatory role in many cellular activities including, growth arrest, survival, biofilm formation, and bacterial persistence. OBJECTIVE: TAs have not well studied in Brucella spp. METHODS: We evaluated the presence of different toxin-antitoxin systems, including relE- rhhlike, Fic- Phd, Cog- Rhh, and cogT- cogAT in 40 clinical Brucella melitensis isolates using PCRbased sequencing assay. RESULTS: Our results showed the high presence of relE-rhh-like, Fic-Phd, Cog-rhh, and cogTcogAT s TAs genes in B. melitensis isolates that were 96.25%, 92.5%, 96.25%, and 95%, respectively. CONCLUSION: A high presence of TAs genes in clinical B. melitensis isolates revealed that the TA system could be an antibacterial target in B. melitensis but more investigation is necessitated to elucidate the exact roles of these genes.

Multiple-Locus Variable-Number Tandem-Repeat Analysis Genotyping of Brucella Isolates from Iran.

BACKGROUND: Brucellosis is considered a main health concern in humans and animals. Neither familiar molecular methods nor the classical biotyping techniques are acceptable for subtyping Brucella spp. Loci containing variable number tandem repeats (VNTRs) have recently demonstrated their practicality in typing isolates from human and animal origin despite the excessive genetic homogeneity in the genus Brucella. METHODS: The genotypic characteristics of sixty-six Brucella melitensis and thirty-four Brucella abortus isolates from veterinary samples and human brucellosis cases in Iran during 2014 - 2018. They were analyzed using multiple-locus variable-number tandem-repeat analysis (MLVA) which consisted of sixteen primer pairs and designed and classified as belonging to one of the three panels: panel 1 (MLVA-8: eight loci including Bruce06, Bruce08, Bruce11, Bruce12, Bruce42, Bruce43, Bruce45, and Bruce55), panel 2A (three loci including Bruce18, Bruce19, and Bruce21), and panel 2B (five loci including Bruce04, Bruce07, Bruce09, Bruce16, and Bruce30); MLVA-11 (panels 1 and 2A), and MLVA-16 (panels 1, 2A, and 2B) using BioNumerics software (Version 7.6). RESULTS: Using panel 1, 2A, and 2B (MLVA-16), 59 genotypes with a genetic similarity coefficient ranging from 91 to 100% were obtained from the 100 Brucella spp. isolates. For all isolates, only genotype 36 and genotype 26 were obtained using panels 1 and 2A, respectively. The B. abortus isolates showed variations at 9 different genotypes, while B. melitensis isolates have been dispersed in 50 different genotypes. Bruce16 and Bruce4 showed the highest discriminatory power. CONCLUSIONS: The MLVA-16 assay appeared to be a useful and important molecular genotyping tool that is capable of proving epidemiological linkages in outbreak and trace-back investigations and is helpful in improving the effectiveness of brucellosis control programs.