Pathogens and Global Health最新文献

Bordetella pertussis is the causative agent of a respiratory infection called pertussis (whooping cough) that can be fatal in newborns and infants. The pathogen produces a variety of antigenic compounds which alone or simultaneously can damage various host cells. Despite the availability of pertussis vaccines and high vaccination coverage around the world, a resurgence of the disease has been observed in many countries. Reasons for the increase in pertussis cases may include increased awareness, improved diagnostic techniques, low vaccine efficacy, especially acellular vaccines, and waning immunity. Many efforts have been made to develop more effective strategies to fight against B. pertussis and one of the strategies is the use of outer membrane vesicles (OMVs) in vaccine formulations. OMVs are attracting great interest as vaccine platforms since they can carry immunogenic structures such as toxins and LPS. Many studies have been carried out with OMVs from different B. pertussis strains and they revealed promising results in the animal challenge and human preclinical model. However, the composition of OMVs differs in terms of isolation and purification methods, strains, culture, and stress conditions. Although the vesicles from B. pertussis represent an attractive pertussis vaccine candidate, further studies are needed to advance clinical research for next-generation pertussis vaccines. This review summarizes general information about pertussis, the history of vaccines against the disease, and the immune response to these vaccines, with a focus on OMVs. We discuss progress in developing an OMV-based pertussis vaccine platform and highlight successful applications as well as potential challenges and gaps.

Aberrant activation of the immune system has been attributed with etiology and pathogenesis of coronavirus disease 2019 (COVID-19). Here, the transcript levels of toll-like receptors (TLRs) were measured in the nasopharyngeal epithelial cells obtained from COVID-19 patients to assess the involvement of these molecules in the clinical outcome of COVID-19 patients. Nasopharyngeal swab samples were used to obtain epithelial cells from 120 COVID-19 patients and 100 healthy controls. COVID-19 cases were classified into those having clinical symptoms/needing for hospitalization, having clinical symptoms/not needing for hospitalization, and those without clinical symptoms‌. The mRNA expression levels of TLRs were measured in the nasopharyngeal epithelial cells. Overall, mRNA expression of TLR1, TLR2, TLR4, and TLR6 was significantly higher in COVID-19 cases compared to controls. The mRNA expression of TLRs were all higher significantly in the samples from COVID-19 patients having clinical symptoms and needing hospitalization as well as in those with clinical symptoms/not needing for hospitalization in comparison to controls. TLR expression was significantly higher in those with clinical symptoms/needing for hospitalization and those with clinical symptoms/not needing for hospitalization compared to COVID-19 cases without clinical symptoms. In cases with clinical symptoms/needing for hospitalization and those with clinical symptoms/not needing for hospitalization, there was a correlation between TLR expression and clinicopathological findings. In conclusion, aberrant expression of TLRs in the nasopharyngeal epithelial cells from COVID-19 cases may predict the severity of the diseases and necessity for supportive cares in the hospital.

Mixed parasitic infections could affect the host immunological responses and re-design the pathogenesis of each other. The impact of Toxoplasma gondii (T. gondii) and Trichinella spiralis (T. spiralis) co-infection on the immune response remains unclear. The objective of the present study was to investigate the possible effect of chronic trichinellosis on the immune response of rats infected with T. gondii virulent RH strain. Animals were divided into four groups: group I: non-infected negative control; group II: infected with T. spiralis; group III: infected with T. gondii and group IV: infected with T. spiralis then infected with T. gondii 35 days post T. spiralis infection (co-infected group). The interaction between T. spiralis and T. gondii was evaluated by histopathological examination of liver and brain tissues, immunohistochemical expression of inducible nitric oxide synthase (iNOS), and β-catenin in the brain tissues, and CD4⁺ and CD8⁺ T cells percentages, and tumor necrosis factor (TNF)-alpha expression in the spleen tissues. Along with, splenic interleukin (IL)-4 and IL-10 mRNA expression levels were measured 15 days post-Toxoplasma infection. Our study revealed that prior infection with T. spiralis leads to attenuation of Th1 response against T. gondii, including iNOS, TNF-α, and CD8⁺ T-cell response with improvement of the histopathological changes in the tissues. In conclusion, in the co-infected rats, a balanced immune response has been developed with the end result, improvement of the histopathological changes in the liver and brain.

The suppressor of the cytokine signaling-1 (SOCS1) gene is a short sequence located on chromosome 16 that functions to induce an appropriate immune response and is an essential physiological regulator of interferon (IFN) signaling. In addition to comparing the global DNA and SOCS1 gene promoter methylation status between our patients with coronavirus disease 2019 (COVID-19) and healthy controls, this study demonstrates the effect of the SOCS1 rs33989964 polymorphism on patients with COVID-19. The study group included 139 patients diagnosed with COVID-19 in our hospital's clinics between June and December 2020, and the control group included 78 healthy individuals. After comparing the initial gene polymorphisms of the patients with the healthy control group, three separate clinical subgroups were formed. The gene polymorphism distribution and the methylation status of SOCS1 were examined in these clinical subgroups. Hypomethylation of the SOCS1 gene was observed in the COVID-19 patient group compared to the healthy control group (p = 0.001). Between the patients divided into two separate clinical subgroups, those with severe and mild infections, the Del/Del genotype of the SOCS1 gene was more common in patients with severe infection than in patients with mild infection (p = 0.018). Patients with the CA/CA and CA/Del genotypes were 0.201 times more likely to have a severe infection (95% CI: 0.057-0.716, p = 0.007). Having a non-Del/Del genotype was a protective factor against severe infection. The effect of the SOCS1 rs33989964 polymorphism and methylation status of the SOCS1 gene throughout the COVID-19 pandemic could be significant contributions to the literature.

Cutaneous leishmaniasis (CL), caused by an obligate intracellular protozoan parasite from the genus Leishmania, imposing a significant burden on underdeveloped countries especially those located in the Middle East. Four electronic databases were searched to evaluate the prevalence of CL in the Middle East. The random effects model (95% confidence intervals (CI)) were applied to determine the overall and subgroup pooled prevalence. Heterogeneity was assessed by Cochran's Q test and I2 statistics. Among 2424 peer-reviewed papers, 37 datasets from 34 studies were included in the current meta-analysis. 285560 individuals were assessed across 9 Middle Eastern countries. The pooled prevalence of CL was estimated at 12% (95% CI 9-15 %; 10718/285560). The highest prevalence rate was observed in Syria (39%, 37-42%), and the lowest one was found in Iraq and Lebanon (0%, 0-1%). The prevalence of CL in studies that applied LST assays had the highest rate (48%, 17-80%). The infection rate in males was similar to females (7%, 4-10%). The prevalence of infection in individuals living in urban areas was higher than in rural areas (14%, 10-19%). The prevalence of CL in the age group 0-15 years was higher than in individuals 16-40 and >40 years (9%, 6-13%). Most of the lesions were found on the face, and single lesions were more prevalent than two and three ones. In conclusion, the occurrence of CL was considerable in Middle Eastern countries. Therefore, more efforts should be made to precisely report the CL in this region for developing appropriate preventive and controlling strategies.  .

The availability of the genomic sequence of the malaria mosquito Anopheles gambiae has in recent years sparked the development of transgenic technologies with the potential to be used as novel vector control tools. These technologies rely on genome editing that confer traits able to affect vectorial capacity. This can be achieved by either reducing the mosquito population or by making mosquitoes refractory to the parasite infection. For any genetically modified organism that is regarded for release, molecular characterization of the transgene and flanking sites are essential for their safety assessment and post-release monitoring. Despite great advancements, Whole-Genome Sequencing data are still subject to limitations due to the presence of repetitive and unannotated DNA sequences. Faced with this challenge, we describe a number of techniques that were used to identify the genomic location of a transgene in the male bias mosquito strain Ag(PMB)1 considered for potential field application. While the initial inverse PCR identified the most likely insertion site on Chromosome 3 R 36D, reassessment of the data showed a high repetitiveness in those sequences and multiple genomic locations as potential insertion sites of the transgene. Here we used a combination of DNA sequencing analysis and in-situ hybridization to clearly identify the integration of the transgene in a poorly annotated centromeric region of Chromosome 2 R 19D. This study emphasizes the need for accuracy in sequencing data for the genome of organisms of medical importance such as Anopheles mosquitoes and other tools available that can support genomic locations of transgenes.

The effect of MMV665941 on the growth of Babesia microti (B. microti) in mice, was investigated in this study using a fluorescence-based SYBR Green I test. Using atom Pair signatures, we investigated the structural similarity between MMV665941 and the commonly used antibabesial medicines diminazene aceturate (DA), imidocarb dipropionate (ID), or atovaquone (AV). In vitro cultures of Babesia bovis (B. bovis) and, Theileria equi (T. equi) were utilized to determine the MMV665941 and AV interaction using combination ratios ranged from 0.75 IC₅₀ MMV665941:0.75 IC₅₀ AV to 0.50 IC₅₀ MMV665941:0.50 IC₅₀ AV. The used combinations were prepared depending on the IC₅₀ of each drug against the in vitro growth of the tested parasite. Every 96 h, the hemolytic anemia in the treated mice was monitored using a Celltac MEK-6450 computerized hematology analyzer. A single dose of 5 mg/kg MMV665941 exhibited inhibition in the B. microti growth from day 4 post-inoculation (p.i.) till day 12 p.i. MMV665941 caused 62.10%, 49.88%, and 74.23% inhibitions in parasite growth at days 4, 6 and 8 p.i., respectively. Of note, 5 mg/kg MMV665941 resulted in quick recovery of hemolytic anemia caused by babesiosis. The atom pair fingerprint (APfp) analysis revealed that MMV665941 and atovaquone (AV) showed maximum structural similarity. Of note, high concentrations (0.75 IC₅₀) of MMV665941 and AV caused synergistic inhibition on B. bovis growth. These findings suggest that MMV665941 might be a promising drug for babesiosis treatment, particularly when combined with the commonly used antibabesial drug, AV.

Following transfer into the primary arbovirus vector Aedes aegypti, several strains of the intracellular bacterium Wolbachia have been shown to inhibit the transmission of dengue, Zika, and chikungunya viruses, important human pathogens that cause significant morbidity and mortality worldwide. In addition to pathogen inhibition, many Wolbachia strains manipulate host reproduction, resulting in an invasive capacity of the bacterium in insect populations. This has led to the deployment of Wolbachia as a dengue control tool, and trials have reported significant reductions in transmission in release areas. Here, we discuss the possible mechanisms of Wolbachia-virus inhibition and the implications for long-term success of dengue control. We also consider the evidence presented in several reports that Wolbachia may cause an enhancement of replication of certain viruses under particular conditions, and conclude that these should not cause any concerns with respect to the application of Wolbachia to arbovirus control.

The production of β-lactamases is a prevalent mechanism that poses serious pressure on the control of bacterial resistance. Furthermore, the unavoidable and alarming increase in the transmission of bacteria producing extended-spectrum β-lactamases complicates treatment alternatives with existing drugs and/or approaches. Class D β-lactamases, designated as OXA enzymes, are characterized by their activity specifically towards oxacillins. They are widely distributed among the ESKAPE bugs that are associated with antibiotic resistance and life-threatening hospital infections. The inadequacy of current β-lactamase inhibitors for conventional treatments of 'OXA' mediated infections confirms the necessity of new approaches. Here, the focus is on the mechanistic details of OXA-10, OXA-23, and OXA-48, commonly found in highly virulent and antibiotic-resistant pathogens Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter spp. to describe their similarities and differences. Furthermore, this review contains a specific emphasis on structural and computational perspectives, which will be valuable to guide efforts in the design/discovery of a common single-molecule drug against ESKAPE pathogens.

With the current expansion of vector-based research and an increasing number of facilities rearing arthropod vectors and infecting them with pathogens, common measures for containment of arthropods as well as manipulation of pathogens are becoming essential for the design and running of such research facilities to ensure safe work and reproducibility, without compromising experimental feasibility. These guidelines and comments were written by experts of the Infravec2 consortium, a Horizon 2020-funded consortium integrating the most sophisticated European infrastructures for research on arthropod vectors of human and animal diseases. They reflect current good practice across European laboratories with experience of safely handling different mosquito species and the pathogens they transmit. As such, they provide experience-based advice to assess and manage the risks to work safely with mosquitoes and the pathogens they transmit. This document can also form the basis for research with other arthropods, for example, midges, ticks or sandflies, with some modification to reflect specific requirements.