-
BMC Infectious Diseases Jun 2024Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with...
PURPOSE
Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox.
METHOD
We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load.
RESULTS
As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen.
CONCLUSION
In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.
Topics: Humans; Male; China; Retrospective Studies; Viral Load; Adult; Homosexuality, Male; HIV Infections; Middle Aged; Young Adult; Female
PubMed: 38926635
DOI: 10.1186/s12879-024-09537-0 -
NPJ Vaccines Jun 2024Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral...
Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and "prime-pull" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.
PubMed: 38926455
DOI: 10.1038/s41541-024-00912-1 -
MSphere Jun 2024James Romero-Masters works in the field of tumor virology, focusing on the role of the human papillomavirus oncogenes in pathogenesis. In this mSphere of Influence...
James Romero-Masters works in the field of tumor virology, focusing on the role of the human papillomavirus oncogenes in pathogenesis. In this mSphere of Influence article, they reflect on how the article "Mouse papillomavirus infection persists in mucosal tissues of an immunocompetent mouse strain and progresses to cancer" impacted them, informing their research strategies, and what it means for the mouse papillomavirus model.
PubMed: 38920397
DOI: 10.1128/msphere.00177-24 -
Acta Odontologica Latinoamericana : AOL Apr 2024Differentiating orofacial odontogenic pain/disorders from pain/disorders associated with maxillary sinusitis is important to avoid unnecessary dentalprocedures and to...
UNLABELLED
Differentiating orofacial odontogenic pain/disorders from pain/disorders associated with maxillary sinusitis is important to avoid unnecessary dentalprocedures and to properly refer patients to colleagues/dentists and vice versa.
AIM
To analyze the association between apical lesions and sinus changes and to evaluate the agreement between the diagnoses of an endodontist, a radiologist, an oral and maxillofacial surgeon, and an otolaryngologist.
MATERIALS AND METHOD
385 axial, coronal, and sagittal MSCT scans were selected using an image archiving andcommunication system (PACS). The examinations had been performed between 2018 and 2022.
RESULTS
Apical lesions were observed in 36.10% of sinusitis cases, 73.8% of unilateralsinusitis cases, 48.7% of sinus floor discontinuity cases, and 67.2% of cases in which endodontic treatment had been performed. Agreement between the diagnoses made by the endodontist and those made by the other investigators was high for most study variables (k > 0.60). The exceptions were mucosal thickening, for which agreement between the endodontist and the other investigators was intermediate (k=0.397), and the presence of periapicallesions (k=0.010), previous endodontic treatment (k=0.013), and mucosal thickness (k=0.024), for which agreement between endodontists and radiologists was low. Conclusions: There was an association between sinus changes and apical lesions.
Topics: Humans; Female; Male; Middle Aged; Multidetector Computed Tomography; Adult; Periapical Diseases; Maxillary Sinusitis; Aged; Young Adult; Adolescent; Diagnosis, Differential
PubMed: 38920129
DOI: 10.54589/aol.37/1/79 -
Iranian Journal of Immunology : IJI Jun 2024The development of a cytokine storm in Coronavirus Disease 2019 (COVID-19) infection can make the disease fatal. We hypothesize that this excessive cytokine production...
BACKGROUND
The development of a cytokine storm in Coronavirus Disease 2019 (COVID-19) infection can make the disease fatal. We hypothesize that this excessive cytokine production impairs mucosal healing. IL-17 and IL-22 are cytokines that play a key role in protecting and regenerating mucosal tissues.IL-17 and IL-22 support each other and the imbalance between them plays a role in the pathogenesis of many rheumatologic diseases.
OBJECTIVE
To investigate whether COVID-19 severity is related to IL17, IL-22, and the IL-17/IL-22 ratio.
METHODS
The study was planned prospectively and included 69 patients with active COVID-19 infection.Three groups were created: patients with upper respiratory tract infection, pneumonia, and cytokine storm. Blood samples were taken from the patients upon their first admission and serum levels of IL-17 and IL-22 were measured using the enzyme-linked immunosorbent assay (ELISA). We assessed the relationship between IL17, IL22, IL17/IL22 ratio, clinical and lung involvement by comparing them with the healthy group.
RESULTS
The levels of IL-17 were significantly higher in COVID-19 patients with upper respiratory tract infection compared to the control group (p=0.027). IL17/IL-22 ratio significantly increased in patients with cytokine storm compared to the healthy controls (p=0.027). Serum levels of IL-22 were negatively correlated with the CO-RADS score (r=-0.31, p=0.004), while IL-17/IL-22 ratio was positively correlated with the CO-RADS score (r= 0.29, p=0.008).
CONCLUSION
Levels of IL-17, IL-22 and IL-17/IL-22 may provide valuable insights into the progression of COVID-19.
PubMed: 38920022
DOI: 10.22034/iji.2024.100909.2721 -
DEN Open Apr 2025Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for... (Review)
Review
Gastric mucosal changes associated with long-term potassium-competitive acid blocker and proton pump inhibitor (PPI) therapy may raise concern. In contrast to that for PPIs, the evidence concerning the safety of long-term potassium-competitive acid blocker use is scant. Vonoprazan (VPZ) is a representative potassium-competitive acid blocker released in Japan in 2015. In order to shed some comparative light regarding the outcomes of gastric mucosal lesions associated with a long-term acid blockade, we have reviewed six representative gastric mucosal lesions: fundic gland polyps, gastric hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like gastric mucosal changes, gastric black spots, and stardust gastric mucosal changes. For these mucosal lesions, we have evaluated the association with the type of acid blockade, patient gender, infection status, the degree of gastric atrophy, and serum gastrin levels. There is no concrete evidence to support a significant relationship between VPZ/PPI use and the development of neuroendocrine tumors. Current data also shows that the risk of gastric mucosal changes is similar for long-term VPZ and PPI use. Serum hypergastrinemia is not correlated with the development of some gastric mucosal lesions. Therefore, serum gastrin level is unhelpful for risk estimation and for decision-making relating to the cessation of these drugs in routine clinical practice. Given the confounding potential neoplastic risk relating to infection, this should be eradicated before VPZ/PPI therapy is commenced. The evidence to date does not support the cessation of clinically appropriate VPZ/PPI therapy solely because of the presence of these associated gastric mucosal lesions.
PubMed: 38919514
DOI: 10.1002/deo2.400 -
Microbiology Spectrum Jun 2024Riboflavin (vitamin B) is the precursor of the flavin coenzymes, FAD and FMN, which play a central role in cellular redox metabolism. While humans must obtain riboflavin...
UNLABELLED
Riboflavin (vitamin B) is the precursor of the flavin coenzymes, FAD and FMN, which play a central role in cellular redox metabolism. While humans must obtain riboflavin from dietary sources, certain microbes, including (Mtb), can biosynthesize riboflavin . Riboflavin precursors have also been implicated in the activation of mucosal-associated invariant T (MAIT) cells which recognize metabolites derived from the riboflavin biosynthesis pathway complexed to the MHC-I-like molecule, MR1. To investigate the biosynthesis and function of riboflavin and its pathway intermediates in mycobacterial metabolism and physiology, we constructed conditional knockdowns (hypomorphs) in riboflavin biosynthesis and utilization genes in (Msm) and Mtb by inducible CRISPR interference. Using this comprehensive panel of hypomorphs, we analyzed the impact of gene silencing on viability, on the transcription of (other) riboflavin pathway genes, on the levels of the pathway proteins, and on riboflavin itself. Our results revealed that (i) despite lacking a canonical transporter, both Msm and Mtb assimilate exogenous riboflavin when supplied at high concentration; (ii) there is functional redundancy in lumazine synthase activity in Msm; (iii) silencing of or is profoundly bactericidal in Mtb; and (iv) in Msm, silencing results in concomitant knockdown of other pathway genes coupled with RibA2 and riboflavin depletion and is also bactericidal. In addition to their use in genetic validation of potential drug targets for tuberculosis, this collection of hypomorphs provides a useful resource for future studies investigating the role of pathway intermediates in MAIT cell recognition of mycobacteria.
IMPORTANCE
The pathway for biosynthesis and utilization of riboflavin, precursor of the essential coenzymes, FMN and FAD, is of particular interest in the flavin-rich pathogen, (Mtb), for two important reasons: (i) the pathway includes potential tuberculosis (TB) drug targets and (ii) intermediates from the riboflavin biosynthesis pathway provide ligands for mucosal-associated invariant T (MAIT) cells, which have been implicated in TB pathogenesis. However, the riboflavin pathway is poorly understood in mycobacteria, which lack canonical mechanisms to transport this vitamin and to regulate flavin coenzyme homeostasis. By conditionally disrupting each step of the pathway and assessing the impact on mycobacterial viability and on the levels of the pathway proteins as well as riboflavin, our work provides genetic validation of the riboflavin pathway as a target for TB drug discovery and offers a resource for further exploring the association between riboflavin biosynthesis, MAIT cell activation, and TB infection and disease.
PubMed: 38916330
DOI: 10.1128/spectrum.03207-23 -
BioRxiv : the Preprint Server For... Jun 2024Group B (GBS) asymptomatically colonizes the vagina but can opportunistically ascend to the uterus and be transmitted vertically during pregnancy, resulting in neonatal...
UNLABELLED
Group B (GBS) asymptomatically colonizes the vagina but can opportunistically ascend to the uterus and be transmitted vertically during pregnancy, resulting in neonatal pneumonia, bacteremia and meningitis. GBS is a leading etiologic agent of neonatal infection and understanding the mechanisms by which GBS persists within the polymicrobial female genital mucosa has potential to mitigate subsequent transmission and disease. Type VIIb secretion systems (T7SSb) are encoded by Firmicutes and often mediate interbacterial competition using LXG toxins that contain conserved N-termini important for secretion and variable C-terminal toxin domains that confer diverse biochemical activities. Our recent work characterized a role for the GBS T7SSb in vaginal colonization and ascending infection but the mechanisms by which the T7SSb promotes GBS persistence in this polymicrobial niche remain unknown. Herein, we investigate the GBS T7SS in interbacterial competition and GBS niche establishment in the female genital tract. We demonstrate GBS T7SS-dependent inhibition of mucosal pathobiont both using predator-prey assays and in the murine genital tract and found that a GBS LXG protein encoded within the T7SS locus (herein named group B streptococcal L XG T oxin A ) that contributes to these phenotypes. We identify BltA as a T7SS substrate that is toxic to and upon induction of expression along with associated chaperones. Finally, we show that BltA and its chaperones contribute to GBS vaginal colonization. Altogether, these data reveal a role for a novel T7b-secreted toxin in GBS mucosal persistence and competition.
IMPORTANCE
Competition between neighboring, non-kin bacteria is essential for microbial niche establishment in mucosal environments. Gram-positive bacteria encoding T7SSb have been shown to engage in competition through export of LXG-motif containing toxins, but these have not been characterized in group B (GBS), an opportunistic colonizer of the polymicrobial female genital tract. Here, we show a role for GBS T7SS in competition with mucosal pathobiont , both and . We further find that a GBS LXG protein contributing to this antagonism is exported by the T7SS and is intracellularly toxic to other bacteria; therefore, we have named this protein group B streptococcal L XG T oxin A (BltA). Finally, we show that BltA and its associated chaperones promote persistence within female genital tract tissues These data reveal previously unrecognized mechanisms by which GBS may compete with other mucosal opportunistic pathogens to persist within the female genital tract.
PubMed: 38915665
DOI: 10.1101/2024.06.10.598350 -
Microbiology Spectrum Jun 2024infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current...
infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current advances on phage-host studies. As a mucosal pathogen, we hypothesize that and its phages are linked to the bacteriophage adherence to mucus (BAM) model. This means that phage-host interactions could be influenced by mucin presence, impacting the success of phage infections on the host and consequently leading to the protection of the metazoan host. By using a group of four different phages, we tested three important phenotypes associated with the BAM model: phage binding to mucin, phage growth in mucin-exposed hosts, and the influence of mucin on CRISPR immunity of the bacterium. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. Improved phage growth was likely the result of phage exploitation of mucin-induced physiological changes in the host. We could not detect CRISPR activity in our system but identified two putative anti-CRISPR proteins coded by the phage. Overall, the differential responses seen for the phages tested show that the same bacterial species can be targeted by mucosal-associated phages or by phages not affected by mucus presence. In conclusion, the BAM model is relevant for phage-bacterium interactions in , opening new possibilities to improve phage therapy against this important pathogen by considering mucosal interaction dynamics.IMPORTANCESome bacteriophages are involved in a symbiotic relationship with animals, in which phages held in mucosal surfaces protect them from invading bacteria. is one of the many bacterial pathogens threatening humankind during the current antimicrobial resistance crisis. Here, we have tested whether and its phages are affected by mucosal conditions. We discovered by using a collection of four phages that, indeed, mucosal interaction dynamics can be seen in this model. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. These results link and its phages to the bacteriophage adherence to the mucus model and open opportunities to explore this to improve phage therapy, be it by exploiting the phenotypes detected or by actively selecting mucosal-adapted phages for treatment.
PubMed: 38912817
DOI: 10.1128/spectrum.03520-23 -
Mucosal Immunology Jun 2024Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious...
Regulatory T cells (Treg) are well-known to mediate peripheral tolerance at homeostasis, and there is growing appreciation for their role in modulating infectious disease immunity. Following acute and chronic infections, Tregs can restrict pathogen-specific T cell responses to limit immunopathology. However, it is unclear if Tregs mediate control of pathology and immunity in distal tissue sites during localized infections. We investigated a role for Tregs in immunity and disease in various tissue compartments in the context of "mild" vaginal Zika virus (ZIKV) infection. We found that Tregs are critical to generate robust virus-specific CD8 T cell responses in the initial infection site. Further, Tregs limit inflammatory cytokines and immunopathology during localized infection; a dysregulated immune response in Treg-depleted mice leads to increased T cell infiltrates and immunopathology in both the vagina and the central nervous system (CNS). Importantly, these CNS infiltrates are not present at the same magnitude during infection of Treg sufficient mice, in which there is not CNS immunopathology. Our data suggest that Tregs are necessary to generate a robust virus-specific response at the mucosal site of infection, while Treg-mediated restriction of bystander inflammation limits immunopathology both at the site of infection as well as distal tissue sites.
PubMed: 38908483
DOI: 10.1016/j.mucimm.2024.06.007