Understanding Mucosal Physiology and Rationale of Formulation Design for Improved Mucosal Immunity.

The oral and nasal cavities serve as critical gateways for infectious pathogens, with microorganisms primarily gaining entry through these routes. Our first line of defense against these invaders is the mucosal membrane, a protective barrier that shields the body's internal systems from infection while also contributing to vital functions like air and nutrient intake. One of the key features of this mucosal barrier is its ability to protect the physiological system from pathogens. Additionally, mucosal tolerance plays a crucial role in maintaining homeostasis by regulating the pH and water balance within the body. Recognizing the importance of the mucosal barrier, researchers have developed various mucosal formulations to enhance the immune response. Mucosal vaccines, for example, deliver antigens directly to mucosal tissues, triggering local immune stimulation and ultimately inducing systemic immunity. Studies have shown that lipid-based formulations such as liposomes and virosomes can effectively elicit both local and systemic immune responses. Furthermore, mucoadhesive polymeric particles, with their prolonged delivery to target sites, have demonstrated an enhanced immune response. This Review delves into the critical role of material selection and delivery approaches in optimizing mucosal immunity.

The impact of active cytomegalovirus infection on donor-derived cell-free DNA testing in heart transplant recipients.

BACKGROUND: Little is known about the relationship between cytomegalovirus (CMV) infections and donor-derived cell-free DNA (dd-cfDNA) in heart transplant recipients. METHODS: In our study, CMV and dd-cfDNA results were prospectively collected on single-organ heart transplant recipients. If the CMV study was positive, a CMV study with dd-cfDNA was repeated 1-3 months later. The primary aim was to compare dd-cfDNA between patients with positive and negative CMV results. RESULTS: Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV-positive and CMV-negative patients with the exception of a later median time post-transplant in the CMV-positive group (253 days vs. 120 days, p = .03). Dd-cfDNA levels were significantly higher in patients with CMV infections compared to those without (p < .001) with more patients in the CMV positive group showing dd-cfDNA results ≥.12% (75% vs. 8%, p < .001) and ≥.20% (58% vs. 8%, p = .002). Each 1 log10 copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log10 dd-cfDNA (p = .002). CONCLUSION: Our findings suggest that active CMV infections may raise dd-cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings.

Cardiac allograft vasculopathy in heart transplant recipients from hepatitis C viremic donors.

BACKGROUND: Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). METHODS: We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5 mm was considered significant for subclinical disease. RESULTS: Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20% versus 28.8% at 2 years, and 33.3% versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p = 0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p = 0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. CONCLUSION: Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.

On the potential role of naturally occurring carboxylic organic acids as anti-infective agents: opportunities and challenges.

Carboxylic organic acids are intermediates of central carbon metabolic pathways (e.g. acetic, propionic, citric, and lactic acid) long known to have potent antimicrobial potential, mainly at acidic pHs. The food industry has been leveraging those properties for years, using many of these acids as preservatives to inhibit the growth of pathogenic and/or spoilage fungal and bacterial species. A few of these molecules (the most prominent being acetic acid) have been used as antiseptics since Hippocratic medicine, mainly to treat infected wounds in patients with burns. With the growth of antibiotic therapy, the use of carboxylic acids (and other chemical antiseptics) in clinical settings lost relevance; however, with the continuous emergence of multi-antibiotic/antifungal resistant strains, the search for alternatives has intensified. This prospective article raises awareness of the potential of carboxylic acids to control infections in clinical settings, considering not only their previous exploitation in this context (which we overview) but also the positive experience of their safe use in food preservation. At a time of great concern with antimicrobial resistance and the slow arrival of new antimicrobial therapeutics to the market, further exploration of organic acids as anti-infective molecules may pave the way to more sustainable prophylactic and therapeutic approaches.

Using HCV-viremic organs for lung transplantation does not confer higher rejection rates compared to HCV-negative organs.

BACKGROUND: National data demonstrate that hepatitis C virus (HCV)-infected organ donors are increasingly being used in the US, including for lung transplantation. We aimed to assess whether there were any differences in the acute or chronic rejection rates at 1 year following lung transplantation from HCV-viremic versus uninfected donors. METHODS: We retrospectively reviewed all lung transplant recipients at our institution from April 1, 2017 to October 1, 2020 and then assessed various outcomes between those who received a transplant from HCV-viremic donors versus HCV-negative donors. Primary outcome was to determine if there was a higher incidence of acute and/or chronic allograft rejection when using HCV NAT+ lung donation. We carried out univariate and multivariate analyses. RESULTS: We transplanted 135 patients during the study period, including 18 from HCV-viremic donors. Standard induction therapy with basiliximab and maintenance triple drug immunosuppression was utilized per UC San Diego protocol. All 17 patients receiving HCV-viremic organs developed acute HCV infection and were treated in the postoperative period with 12 weeks of direct acting antivirals (DAA). HCV genotypes included 1, 2, and 3. DAA used included glecaprevir/pibrentasvir (12), sofosbuvir/velpatasvir (1), and ledipasvir/sofosbuvir (2) with drug choice determined by patient's medical insurance coverage. Sustained virological response at 12 weeks after end of DAA therapy (SVR12), indicative of a cure, was achieved in all (100%) recipients. No recipient had a serious adverse event related to HCV infection. The lung transplant recipient (LTR) HCV-viremic donors had lower rates of clinically significant rejection (5.9% vs. 11% LTR HCV-nonviremic donors), and no chronic lung allograft dysfunction at 1 year (vs. 5.9% LTR HCV-nonviremic donors). One-year survival was 100% in the LTR HCV-viremic donors compared to 95.8% in the LTR HCV-nonviremic donors. CONCLUSIONS: We demonstrate the feasibility and success of using HCV NAT + donors with excellent results and without a higher incidence of rejection. Longer term follow-up and a larger sample size are needed to allow this to be a more widely accepted practice for lung transplant programs and payors.

De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

Lung transplantation in HIV seropositive recipients: An analysis of the UNOS registry.

BACKGROUND: Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV-) recipients. METHODS: The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan-Meier analysis. RESULTS: The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV- recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. CONCLUSIONS: This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV- patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV- recipients.

Incidence and outcomes of fever of unknown origin after kidney transplant in the modern era.

BACKGROUND: While presumably less common with modern molecular diagnostic and imaging techniques, fever of unknown origin (FUO) remains a challenge in kidney transplant recipients (KTRs). Additionally, the impact of FUO on patient and graft survival is poorly described. METHODS: A cohort of adult KTRs between January 1, 1995 and December 31, 2018 was followed at the University of Wisconsin Hospital. Patients transplanted from January 1, 1995 to December 31, 2005 were included in the "early era"; patients transplanted from January 1, 2006 to December 31, 2018 were included in the "modern era". The primary objective was to describe the epidemiology and etiology of FUO diagnoses over time. Secondary outcomes included rejection, graft and patient survival. RESULTS: There were 5590 kidney transplants at our center during the study window. FUO was identified in 323 patients with an overall incidence rate of .8/100 person-years. Considering only the first 3 years after transplant, the incidence of FUO was significantly lower in the modern era than in the early era, with an Incidence Rate Ratio (IRR) per 100 person-years of .48; 95% CI: .35-.63; p < .001. A total of 102 (31.9%) of 323 patients had an etiology determined within 90 days after FUO diagnosis: 100 were infectious, and two were malignancies. In the modern era, FUO remained significantly associated with rejection (HR = 44.1; 95% CI: 16.6-102; p < .001) but not graft failure (HR = 1.21; 95% CI: .68-2.18; p = .52) total graft loss (HR = 1.17; 95% CI: .85-1.62; p = .34), or death (HR = 1.17; 95% CI: .79-1.76; p = .43. CONCLUSIONS: FUO is less common in KTRs during the modern era. Our study suggests infection remains the most common etiology. FUO remains associated with significant increases in risk of rejection, warranting further inquiry into the management of immunosuppressive medications in SOT recipients in the setting of FUO.

Investigation of circulating infectious agents in experimental Beagle dogs of a production colony and three research facilities in China from June 2021 to May 2022.

To understand the epizootiologic characteristics of pathogens and opportunistic infections in one Beagle dog production colony and three research facilities, viruses and mycoplasma were detected in 1777 samples collected from Beagle dogs in China by polymerase chain reaction/reverse transcription polymerase chain reaction, and bacteria were isolated and identified by 16S rRNA sequence analysis. In addition, genotyping of the major circulating viruses was carried out by amplification of gene fragments and homology analysis. Canine coronavirus (CCoV), Escherichia coli, canine parvovirus (CPV), Bordetella bronchiseptica, Clostridium perfringens, Mycoplasma cynos, Klebsiella pneumoniae, Streptococcus canis, canine astrovirus (CaAstV), canine kobuvirus (CaKV), Pseudomonas aeruginosa, Proteus mirabilis, Macrococcus canis, Pasteurella canis, canine bocavirus (CBoV) and canine adenovirus (CAdV) were detected in the samples. Single, double, triple and quadruple infections accounted for 6.6%, 1.4%, 1.2% and 0.96% of samples, respectively. CCoV strains in 81 samples included three genotypes, CCoV-I, CCoV-IIa and CCoV-IIb, by analysis of S gene. The rate of single infection of CCoV-I, CCoV-IIa or CCoV-IIb was 19%, 38% or 7.4% respectively. The double and triple infection rates of CCoV were 32.8% and 2.5% respectively. All CPV strains in 36 samples belonged to CPV-2c. There were three amino acid differences in the Fiber protein of CAdV-positive sample QD2022, compared with the reference strain Toronto A26/61 and the vaccine strain YCA-18. These results suggest that CCoV and CPV are primary infectious agents, and that these two viruses were often identified in mixed infections, or coinfections alongside mycoplasma or other bacteria. These results will provide the basis for improvements in prevention and control of naturally occurring infectious diseases in Beagle dog production colonies and research facilities.

Tick infestation in spur-thighed tortoise population: a pilot study for unraveling epidemiological patterns and demographic consequences.

Ectoparasites, such as ticks, modulate host population dynamics by impacting demographic traits. They transmit infectious agents among their hosts, posing a critical threat to animal and public health. This study aimed to characterize and analyze the Hyalomma aegyptium infestation on one of its main hosts, the spur-thighed tortoise, its effects on demographic traits, and to determine the diversity of infectious agents present in both ticks and tortoises in the Maamora forest (northwestern Morocco). Our results show that 100% of the tortoises were parasitized by adult ticks in spring, an infestation intensity of 4 ticks/tortoise (5.1 and 3.6 ticks/tortoise in males and females, respectively; 4.2 and 3.3 ticks/tortoise in gravid and non-gravid females, respectively) and an abundance ranging from 1 to 12. Although without significant differences, male tortoises had higher tick abundances than females. The interaction of tortoise sex and body condition was significantly related to tick abundance, male body condition decreased with higher tick abundance in contrast to females. Nevertheless, the interaction of body condition and reproductive stage of females was not significantly related to tick abundance. Gravid females were significantly associated with tick abundance, showing a slightly higher infestation than non-gravid females. Molecular analysis of pooled tick samples revealed the presence of Ehrlichia ewingii, Candidatus Midichloria mitochondrii, and Rickettsia africae, with a minimum infection rate of 0.61 to 1.84%. However, blood sample analysis of the tortoises was infectious agent-free, pinpointing a lack of significant health problems. Given the possible effect on the transmission of zoonotic diseases by spur-thighed tortoises associated with their frequent collection as pets, it should be surveyed to control possible human health problems. In conservation terms, as a long-lived species, the role of tick infestation in demographic traits might be included in the management and conservation programs of spur-thighed tortoises.

Bovine infectious abortion: a systematic review and meta-analysis.

The aim of the present systematic review and meta-analysis was to identify the main infectious agents related to bovine abortion worldwide in the period between 2000 and 2022. First, we investigated the global prevalence of infectious agents related to bovine abortion. For this analysis, only 27 articles detected of a wide panel of agents were included. The random effects model revealed that the estimated prevalence of the abortifacient agents in bovine abortion was 45.7%. The heterogeneity among studies was high, but Egger's test showed that there was no publication bias, even though the total number of samples analyzed in these articles was variable. There was no significant effect of the year of the study publication on the estimated prevalence, although an increasing trend was observed over time, possibly due to the implementation of new diagnostic techniques. Then, we analyzed the prevalence of the main transmissible agents in bovine abortion. For this analysis, 76 studies that analyzed 19,070 cases were included. Some infectious agent was detected in 7,319 specimens, and a final diagnosis was reached in 3,977 of these, when both the infectious agent and compatible histopathological changes were detected. We found that Neospora caninum was the most detected agent (22.2%), followed by opportunistic bacteria (21.4%), Chlamydiaceae family (10.9%) and Coxiella burnetii (9.5%). Regarding viral agents, bovine herpes virus type 1 and bovine viral diarrhea displayed similar prevalence rates (approximately 5%). After considering the description of specific histopathological changes, our analyzes showed that N. caninum was a confirmed cause of abortion in 16.7% of the analyzed cases, followed by opportunistic bacteria (12.6%) and Chlamydia spp. (6.8%); however, C. burnetii was only confirmed as a cause of abortion in 1.1% of the cases. For all agents, the heterogeneity among studies was high, and the subgroup analyzes discarded the diagnostic method as the cause of such heterogeneity. This study provides knowledge about the global prevalence of the different infectious agents related to bovine abortion, the most coming of which is N. caninum. In addition, this review reveals the existing deficiencies in the diagnosis of bovine abortion that must be addressed in the future.

Remotely sensed localised primary production anomalies predict the burden and community structure of infection in long-term rodent datasets.

The increasing frequency and cost of zoonotic disease emergence due to global change have led to calls for the primary surveillance of wildlife. This should be facilitated by the ready availability of remotely sensed environmental data, given the importance of the environment in determining infectious disease dynamics. However, there has been little evaluation of the temporal predictiveness of remotely sensed environmental data for infection reservoirs in vertebrate hosts due to a deficit of corresponding high-quality long-term infection datasets. Here we employ two unique decade-spanning datasets for assemblages of infectious agents, including zoonotic agents, in rodents in stable habitats. Such stable habitats are important, as they provide the baseline sets of pathogens for the interactions within degrading habitats that have been identified as hotspots for zoonotic emergence. We focus on the enhanced vegetation index (EVI), a measure of vegetation greening that equates to primary productivity, reasoning that this would modulate infectious agent populations via trophic cascades determining host population density or immunocompetence. We found that EVI, in analyses with data standardised by site, inversely predicted more than one-third of the variation in an index of infectious agent total abundance. Moreover, in bipartite host occupancy networks, weighted network statistics (connectance and modularity) were linked to total abundance and were also predicted by EVI. Infectious agent abundance and, perhaps, community structure are likely to influence infection risk and, in turn, the probability of transboundary emergence. Thus, the present results, which were consistent in disparate forest and desert systems, provide proof-of-principle that within-site fluctuations in satellite-derived greenness indices can furnish useful forecasting that could focus primary surveillance. In relation to the well-documented global greening trend of recent decades, the present results predict declining infection burden in wild vertebrates in stable habitats; but if greening trends were to be reversed, this might magnify the already upwards trend in zoonotic emergence.

Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

Impact of pathogenic bacterial communities present in wastewater on aquatic organisms: Application of nanomaterials for the removal of these pathogens.

Contaminated wastewater (WW) can cause severe hazards to numerous delicate ecosystems and associated life forms. In addition, human health is negatively impacted by the presence of microorganisms in water. Multiple pathogenic microorganisms in contaminated water, including bacteria, fungi, yeast, and viruses, are vectors for several contagious diseases. To avoid the negative impact of these pathogens, WW must be free from pathogens before being released into stream water or used for other reasons. In this review article, we have focused on pathogenic bacteria in WW and summarized the impact of the different types of pathogenic bacteria on marine organisms. Moreover, we presented a variety of physical and chemical techniques that have been developed to provide a pathogen-free aquatic environment. Among the techniques, membrane-based techniques for trapping hazardous biological contaminants are gaining popularity around the world. Besides, novel and recent advancements in nanotechnological science and engineering suggest that many waterborne pathogens could be inactivated using nano catalysts, bioactive nanoparticles, nanostructured catalytic membranes, nanosized photocatalytic structures, and electrospun nanofibers and processes have been thoroughly examined.

Molecular Survey of Rodent-Borne Infectious Agents in the Ferlo Region, Senegal.

Zoonotic pathogens are responsible for most infectious diseases in humans, with rodents being important reservoir hosts for many of these microorganisms. Rodents, thus, pose a significant threat to public health. Previous studies in Senegal have shown that rodents harbour a diversity of microorganisms, including human pathogens. Our study aimed to monitor the prevalence of infectious agents in outdoor rodents, which can be the cause of epidemics. We screened 125 rodents (both native and expanding) from the Ferlo region, around Widou Thiengoly, for different microorganisms. Analysis, performed on rodent spleens, detected bacteria from the Anaplasmataceae family (20%), Borrelia spp. (10%), Bartonella spp. (24%) and Piroplasmida (2.4%). Prevalences were similar between native and the expanding (Gerbillus nigeriae) species, which has recently colonised the region. We identified Borrelia crocidurae, the agent responsible for tick-borne relapsing fever, which is endemic in Senegal. We also identified two other not-yet-described bacteria of the genera Bartonella and Ehrlichia that were previously reported in Senegalese rodents. Additionally, we found a potential new species, provisionally referred to here as Candidatus Anaplasma ferloense. This study highlights the diversity of infectious agents circulating in rodent populations and the importance of describing potential new species and evaluating their pathogenicity and zoonotic potential.

Diagnostic and management roles of FDG PET/CT imaging in post-transplant lympho-proliferation in pediatric heart transplantation.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of pediatric heart transplant (PHTx). 18F-FDG PET/CT has been used to differentiate early lympho-proliferation from more advanced PTLD. We report our experience with PET/CT in the management of PTLD following PHTx. METHODS: This was a retrospective study of 100 consecutive PHTx recipients at our institution between 2004 and 2018. Patients who underwent PET/CT or conventional CT scans to evaluate for PTLD or high Epstein-Barr viral load were included. RESULTS: Males, eight females. Median age at transplant was 3.5 months (IQR = 1.5-27.5). Median age at PTLD diagnosis was 13.3 years (IQR = 9.2-16.1). Median time between transplant and PTLD diagnosis was 9.5 (IQR = 4.5-15) years. Induction agents were used in 12 patients (50%): Thymoglobulin (N = 9), anti-IL2 (N = 2), and Rituximab (N = 1). Eighteen patients (75%) had PET/CT, of whom 14 had 18FDG-avid PTLD. Six had conventional CT. Nineteen patients (79.2%) had diagnostic biopsy confirmation of PTLD, and 5 (20.8%) had excisional biopsies. Two patients had Hodgkin's lymphoma; nine had monomorphic PTLD; eight had polymorphic PTLD; five were classified as other. Nine patients had monomorphic PTLD, including seven with diffuse large cell lymphoma (DLBC) and one with T cell lymphoma. The majority (16/24) had multi-site involvement at PTLD diagnosis, and PET/CT showed that 31.3% (5/16) had easily accessible subcutaneous nodes. Seventeen patients (overall survival 71%) underwent successful treatment without recurrence of PTLD. Of seven deaths (7/24, 29%), five had DLBC lymphoma, one had polymorphic PTLD and one had T-cell lymphoma. CONCLUSION: PET-CT allowed simultaneous anatomical and functional assessment of PTLD lesions, while guiding biopsy. In patients with multiple lesions, PET/CT revealed the most prominent and active lesions, improving diagnostic accuracy.

High prevalence of blaCTX-M-15 type extended-spectrum beta-lactamases in Gambian hooded vultures (Necrosyrtes monachus): A threatened species with substantial human interaction.

One hundred fecal samples from hooded vultures in the Gambia (Banjul area) were investigated for the presence of bacteria with extended-spectrum cephalosporin- (ESBL/AmpC), carbapenemases, and colistin resistance. No Enterobacteriales carrying carbapenemases or resistance against colistin were detected. Fifty-four ESBL-producing Escherichia coli and five ESBL-producing Klebsiella pneumoniae isolates were identified in 52 of the samples, of which 52 E. coli and 4 K. pneumoniae yielded passed sequencing results. Fifty of the E. coli had ESBL phenotype and genotype harboring blaCTX-M genes, of which 88.5% (n = 46) were the blaCTX-M-15 gene, commonly found on the African continent. Furthermore, the genetic context around blaCTX-M-15 was similar between isolates, being colocalized with ISKpn19. In contrast, cgMLST analysis of the E. coli harboring ESBL genes revealed a genetic distribution over a large fraction of the currently known existing E. coli populations in the Gambia. Hooded vultures in the Gambia thus have a high ESBL E. coli-prevalence (>50%) with low diversity regarding key resistance genes. Furthermore, given the urban presence and frequent interactions between hooded vultures and humans, data from this study implies hooded vultures as potential vectors contributing to the further dissemination of antibiotic-resistance genes.

Impact of Omicron BA.1 infection on BA.4/5 immunity in transplant recipients.

Mutations in the spike protein of SARS-CoV-2 have allowed Omicron subvariants to escape neutralizing antibodies. The degree to which this occurs in transplant recipients is poorly understood. We measured BA.4/5 cross-neutralizing responses in 75 mostly vaccinated transplant recipients who recovered from BA.1 infection. Sera were collected at 1 and 6 months post-BA.1 infection, and a lentivirus pseudovirus neutralization assay was performed using spike constructs corresponding to BA.1 and BA.4/5. Uninfected immunized transplant recipients and health care worker controls were used for comparison. Following BA.1 infection, the proportion of transplant recipients with neutralizing antibody responses was 88.0% (66/75) against BA.1 and 69.3% (52/75) against BA.4/5 (P = .005). The neutralization level against BA.4/5 was approximately 17-fold lower than that against BA.1 (IQR 10.6- to 45.1-fold lower, P < .0001). BA.4/5 responses declined over time and by ≥0.5 log10 (approximately 3-fold) in almost half of the patients by 6 months. BA.4/5-neutralizing antibody titers in transplant recipients with breakthrough BA.1 infection were similar to those in immunized health care workers but significantly lower than those in uninfected triple-vaccinated transplant recipients. These results provide evidence that transplant recipients are at ongoing risk for BA.4/5 infection despite vaccination and prior Omicron strain infection, and additional mitigation strategies may be required to prevent severe disease in this cohort.

BK DNAemia and native kidney polyomavirus nephropathy following lung transplantation.

BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients.