Evidence for Immunity against Tetanus, Diphtheria, and Pertussis through Natural Infection or Vaccination in Adult Solid Organ Transplant Recipients: A Systematic Review.

(1) Background: We aim to systematically review the current evidence on immunity against tetanus, diphtheria, and pertussis in adult solid organ transplantation (SOT) recipients, either through natural infection or vaccination. (2) Methods: This systematic review was conducted per PRISMA guidelines. We assessed the risk of bias using the Cochrane RoB 2 and ROBINS-I and summarized the findings narratively due to the heterogeneity of the studies. (3) Results: Of the 315 screened articles, 11 were included. Tetanus immunity varied between 55% and 86%, diphtheria immunity from 23% to 75%, and pertussis immunity was between 46% and 82%. Post-vaccination immunity showed variation across the studies, with some indicating reductions and others no change, with antibody responses influenced by transplanted organs, gender, age, and immunosuppressive regimens. The single randomized study exhibited a low risk of bias, while of the ten non-randomized studies, six showed moderate and four serious risks of bias, necessitating cautious interpretation of results. (4) Conclusions: SOT recipients exhibit considerable immunity against tetanus and diphtheria at transplantation, but this immunity decreases over time. Although vaccination can enhance this immunity, the response may be suboptimal, and the increased antibody levels may not persist, underscoring the need for tailored vaccination strategies in this vulnerable population.

Changes in vaccination uptake against pneumococcal disease, influenza, and coronavirus disease 2019 (COVID-19) before and after a Head and Neck cancer diagnosis.

BACKGROUND: Pneumonia is one of the main contributors to non-cancer mortality among patients with head and neck cancer (HNC). This study aimed to determine the vaccine uptake for pneumococcal polysaccharide and conjugate vaccines, quadrivalent influenza vaccines, and mRNA COVID-19 vaccines before and after an HNC diagnosis. Furthermore, the study investigated the timing of vaccination after a cancer diagnosis. MATERIALS & METHODS: This register based multicentre study included Danish patients ≥ 18y diagnosed with HNC between 2018 and 2021. The vaccine uptake was assessed by calculating cumulative incidence (CI), while the timing of vaccination after an HNC diagnosis was explored by calculating incidence rates of vaccination the first and second half year after a cancer diagnosis. RESULTS: The cumulative incidence of vaccine uptake for pneumococcal vaccines was estimated to be 8 % and 16 % one year before and after an HNC diagnosis, respectively. The CIs were 36 % and 38 % for quadrivalent influenza vaccines, respectively, whereas the CIs of vaccine uptake for mRNA COVID-19 vaccines were 60 % and 89 %. The IR of mRNA COVID-19 vaccinations the first half year after HNC diagnosis were 273 per 1000 person-months of follow-up (PMFU) and 111 per 1000 PMFU the second half year, respectively (IRR: 0.38, p < 0.001). Comparing the same periods, the IR of quadrivalent influenza vaccination was 28 per 1000 PMFU and 51 per 1000 PMFU (IRR: 1.95, 0 < 0.001). The IRs of pneumococcal vaccinations were 11 per 1000 PMFU and 14 per 1000 PMFU (IRR 1.28, p = 0.21). CONCLUSIONS: Although our study shows a significant increase in pneumococcal and COVID-19 vaccine uptake after HNC diagnosis, a gap remains in vaccine uptake before diagnosis, underscoring the need for increased awareness of vaccination options and recommendations. Our findings could serve as a reference for future recommendations.

Anemia in liver transplant recipients: prevalence, severity, risk factors, and survival.

Information about anemia in liver transplant (LTx) recipients is scarce. We investigated the prevalence and severity of anemia before and within the first-year post-LTx, risk factors for having anemia before LTx, and 1-year survival according to anemia status before LTx. This retrospective cohort study received data from The Knowledge Center for Transplantation database at Rigshospitalet, Copenhagen, Denmark. Uni- and multivariate logistic regression were used to investigate factors associated with anemia and a Kaplan-Meier plot to illustrate the probability of survival. We included 346 first-time adult LTx recipients. The median age was 50 years (IQR: 42-57), and 203 (59%) were male. The prevalence of anemia before and 1-year post-LTx were 69 and 45%, respectively. Male sex (aOR 4.0 [95% CI: 2.2-7.2]; p < 0.001) and each unit increase in MELD score (aOR 1.2 [95% CI: 1.1-1.2]; p < 0.001) were positively associated with anemia before LTx. Compared to autoimmune liver diseases, LTx recipients with fulminant hepatic failure (aOR 0.03 [0.00-0.17]; p = 0.001) had lower odds for anemia. The 1-year survival in LTx recipients who had and did not have anemia before transplantation were 93 and 91% (p = 0.47). Anemia was frequent among LTx recipients, and anemia before LTx did not affect 1-year survival.

Implementation of a vaccination clinic for adult solid organ transplant candidates: A single-center experience.

Vaccination is an evidence-based strategy to prevent or reduce the severity of infectious diseases (ID). Here, we aimed to describe the experience of implementing a vaccination clinic specifically targeting liver, heart, lung, and combined dual organ transplantation at a single transplantation center in Denmark. In this cohort of 242 solid organ transplant (SOT) candidates, we investigated seroprotection and the proportion of recommended vaccinations documented before transplantation. Furthermore, we registered completed vaccinations after ID consultations. The median age in our cohort was 53 years (IQR, 42-60), 60% were males (n = 135), and liver transplants (n = 138; 57%) were the most frequently planned organ transplants. Before the consultation to the vaccination clinic, influenza and pneumococcal vaccines had the highest proportion of documented vaccination (58% and 37%, respectively). Serological protection was more frequently observed for measles, mumps, or rubella (MMR, approximately 90% for each), while only 30% (n = 72) of SOT candidates showed seroprotection against pneumococcal disease. All SOT candidates required at least one of the recommended vaccines, and over 90% required three or more. At least 10% of patients in our cohort needed a live attenuated vaccine for either MMR or yellow fever. The most frequently administered vaccine was the tetanus-diphtheria-acelullar pertussis (Tdap) booster (n = 217; 90%), influenza vaccination was either administered (n = 16; 7%) or recommended (n = 226; 93%), PCV13 was administered (n = 155; 64%) or recommended (n = 27; 11%), and PPSV23 was either administered (n = 18; 7.4%) or recommended (n = 140; 58%). All SOT candidates adhered completely to their vaccination schedules. Based on our findings, we recommend prioritizing vaccination before transplantation by providing ID consultations for SOT candidates.

Prediction of herpes virus infections after solid organ transplantation: a prospective study of immune function.

Introduction: Herpes virus infections are a major concern after solid organ transplantation and linked to the immune function of the recipient. We aimed to determine the incidence of positive herpes virus (cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1/2 (HSV-1/2), and varicella zoster virus (VZV)) PCR tests during the first year post-transplantation and assess whether a model including immune function pre-transplantation and three months post-transplantation could predict a subsequent positive herpes virus PCR. Methods: All participants were preemptively screened for CMV, and EBV IgG-negative participants were screened for EBV during the first year post-transplantation. Herpes virus PCR tests for all included herpes viruses (CMV, EBV, HSV-1/2, and VZV) were retrieved from the Danish Microbiology database containing nationwide PCR results from both hospitals and outpatient clinics. Immune function was assessed by whole blood stimulation with A) LPS, B) R848, C) Poly I:C, and D) a blank control. Cytokine concentrations (TNF-α, IL-1ß, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α, and IFN-γ) were measured using Luminex. Results: We included 123 liver (54%), kidney (26%), and lung (20%) transplant recipients. The cumulative incidence of positive herpes virus PCR tests was 36.6% (95% CI: 28.1-45.1) during the first year post-transplantation. The final prediction model included recipient age, type of transplantation, CMV serostatus, and change in Poly I:C-induced IL-12p40 from pre-transplantation to three months post-transplantation. The prediction model had an AUC of 77% (95% CI: 61-92). Risk scores were extracted from the prediction model, and the participants were divided into three risk groups. Participants with a risk score <5 (28% of the cohort), 5-10 (45% of the cohort), and >10 (27% of the cohort) had a cumulative incidence of having a positive herpes virus PCR test at 5.8%, 25%, and 73%, respectively (p < 0.001). Conclusion: In conclusion, the incidence of positive herpes virus PCR tests was high, and a risk model including immune function allowed the prediction of positive herpes virus PCR and may be used to identify recipients at higher risk.

Prevalence of emphysema in people living with human immunodeficiency virus in the current combined antiretroviral therapy era: A systematic review.

Before introducing combination antiretroviral therapy (cART), a higher prevalence of emphysema in people living with HIV (PLWH) than in the background population was reported. This systematic literature review aimed to investigate the prevalence of emphysema in PLWH and to compare the prevalence between PLWH and controls in the current cART era. A systematic literature search was conducted in PubMed, EMBASE, Scopus, and Web of Science (WOS), searching for "human immunodeficiency virus (HIV)" and "emphysema" from January 1, 2000 to March 10, 2021. Eligible studies were published after the introduction of cART, included PLWH, and reported the prevalence of emphysema. A total of 17 studies were included, and nine studies also included controls. The weighted average prevalence of emphysema in PLWH was 23% (95% CI: 16-30). In studies including both PLWH and controls the weighted average prevalence were 22% (95% CI: 10-33) and 9.7% (95% CI: 2.3-17), respectively (p = 0.052). The prevalence of emphysema in never-smoking PLWH and controls was just reported in one study and was 18 and 4%, respectively (p < 0.01). Thirteen of the studies had a moderate risk of bias, mainly due to selection of patients. A tendency to higher prevalence of emphysema was found in PLWH in comparison to controls in the current cART era. However, in the included studies, the definition of emphysema varied largely. Thus, to have a clear overview of the prevalence, further studies with well-designed cohorts of PLWH and controls are warranted.

Incidence, Risk Factors, and Consequences of Human Alphaherpesvirus Infections in Patients With Psoriasis Who Initiate Methotrexate or Biologic Agents.

BACKGROUND: Immunosuppressive agents may increase the risk of infections with human alphaherpesviruses. METHODS: We included all adult patients with moderate to severe psoriasis who initiated methotrexate (MTX) or biologic agents in a retrospective cohort study. An episode of alphaherpesviruses infection was defined as filling a prescription for systemic acyclovir, valacyclovir, or famciclovir. Using nationwide registries, we determined the incidence, risk factors, 180-day hospital contacts, and 30-day mortality following infection. RESULTS: We included 7294 patients; 4978 (68%) received MTX, and 2316 (32%) biologic agents. The incidence rates (95% confidence intervals) of alphaherpesviruses were 23 (20-27), 26 (19-35), 17 (11-27), and 6.7 (1.3-21) per 1000 person-years of follow-up in patients on MTX, tumor necrosis factor alpha (TNF-α) inhibitors, interleukin 12/23 (IL-12/23) inhibitors, and interleukin 17 (IL-17) inhibitors, respectively. Males had an unadjusted hazard ratio (HR) of 0.47 (P < .001) for alphaherpesvirus infection. Patients on IL-17 inhibitors had an adjusted HR of 0.24 (P = .048) compared to TNF-α inhibitors. Within 180 days after infection, 13%, 7.5%, and <0.5% of patients on MTX, TNF-α inhibitors, and IL-12/23 or IL-17 inhibitors, respectively, had hospital contacts, and the 30-day mortality for all groups was <0.5%. CONCLUSIONS: The incidence and risk of alphaherpesvirus infections were comparable between patients on MTX and TNF-α inhibitors, whereas use of IL-17 inhibitors was associated with a lower risk.

Caspofungin-Induced Cardiotoxicity in Patients Treating for Candidemia.

Echinocandins selectively inhibit fungal cell wall synthesis and, therefore, have few side effects. However, there are reports of hemodynamic and cardiac complications. We conducted this study to investigate the effects of caspofungin both on the noninvasive echocardiographic indices of myocardial function and myocardial injury based on serum high-sensitivity cardiac troponin I (hs-cTnI) levels. This study was conducted on patients treated for candidemia. The hs-cTnI level and echocardiographic parameters were measured before and 1 h after the infusion of the induction dose of caspofungin. Data were compared between central and peripheral venous drug administration routes. Fifteen patients were enrolled in the study. There were no significant differences in the echocardiographic parameters between the baseline and post-treatment period. The mean hs-cTnI level exhibited a significant rise following drug administration (0.24 ± 0.2 ng/mL vs 0.32 ± 0.3 ng/mL; p = 0.006). There was also a significant difference concerning the hs-cTnI level between central and peripheral venous drug administration routes (p = 0.034). Due to differences in the hs-cTnI level, it appears that the administration of caspofungin may be associated with myocardial injury. Our findings also showed a higher possibility of cardiotoxicity via the central venous administration route.

Post-Transplantation Anemia and Risk of Death Following Lung Transplantation.

BACKGROUND: Post-transplantation anemia (PTA) is frequent among solid organ transplant recipients and has been associated with increased morbidity and mortality. However, the prevalence and impact of PTA in lung transplant recipients is still not elucidated. METHODS: We performed a retrospective cohort study of adult Danish lung transplant recipients between January 2010 and December 2019. The prevalence and severity of PTA were determined during the first three years post-transplantation. Associations between PTA and selected risk factors were established using uni- and multivariate logistic regression models. RESULTS: A total of 278 patients were included. At one and three years post-lung transplantation the prevalence of PTA was 75% and 52%, respectively. Male sex was associated with increased odds of PTA at all time points (aOR ranging from 2.3, 95% CI 1.1-4.6, P = 0.02 to 5.9, 95% CI 2.6-14, P < .001). Cystic fibrosis was also associated with anemia at one-year post-transplantation (aOR 4.3, 95% CI 1.2-17, P = 0.03). We found no strong associations between PTA and renal function or viral infections. Excess mortality in recipients with moderate or severe anemia compared to patients with mild or no anemia was borderline statistically significant at one-year post-lung transplantation (aHR 2.0, 95% CI 0.9-4.4, P = 0.07). DISCUSSION: Post-transplantation anemia is very common in Danish lung transplant recipients. Male sex and cystic fibrosis are independent risk factors for development of anemia. Further investigation on PTA, the underlying mechanisms, and its clinical impact is needed.

Incidence and severity of SARS-CoV-2 infections in liver and kidney transplant recipients in the post-vaccination era: Real-life data from Denmark.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has been associated with a high risk of adverse outcomes in solid organ transplant (SOT) recipients in the pre-vaccination era. In this retrospective cohort study, we examined the incidence and severity of COVID-19 in kidney and liver transplant recipients in Denmark in the post-vaccination era, from December 27, 2020, to December 27, 2021. We included 1428 SOT recipients with 143 cases of first-positive SARS-CoV-2 PCR test. The cumulative incidence of first-positive SARS-CoV-2 PCR test 1 year after initiation of vaccination was 10.4% (95% CI: 8.8-12.0), and the incidence was higher in kidney than in liver transplant recipients (11.6% [95% CI: 9.4-13.8] vs. 7.4% [95% CI: 5.1-9.8], p = .009). After the first-positive SARS-CoV-2 PCR test, the hospitalization rate was 31.5% (95% CI: 23.9-39.1), and 30-day all-cause mortality was 3.7% (95% CI: 0.5-6.8). Hospitalization was lower in vaccinated than in unvaccinated SOT recipients (26.4% [95% CI: 18.1-34.6] vs. 48.5% [95% CI: 31.4-65.5], p = .011), as was mortality (1.8% [95% CI: 0.0-4.3] vs. 9.1% [95% CI: 0.0-18.9], p = .047). In conclusion, SOT recipients remain at high risk of adverse outcomes after SARS-CoV-2 infections, with a lower risk observed in vaccinated than in unvaccinated SOT recipients.

Characteristics and Outcomes of Patients with Delftia acidovorans Infections: a Retrospective Cohort Study.

Delftia acidovorans (D. acidovorans) is a Gram-negative bacteria and an uncommon cause of human infections. This retrospective cohort study investigated clinical and microbiological characteristics and outcomes of patients with D. acidovorans infections. We included patients with culture-confirmed D. acidovorans infections attending Rigshospitalet, during 2002-2020. Fifty-nine patients with a median interquartile ranges (IQR) age of 47 (15-67) years were included. Thirty-five (59%) were males, and 57 (97%) had at least one comorbidity, including 25 (42%) with solid or hematologic malignancies. Eight (14%) were admitted to ICU, and 15 (25%) died within 365 days after infection. Persistent infection was found in 4 (6.8%) patients, and 41 (70%) had polymicrobial cultures, mainly with Pseudomonas spp. and Stenotrophomonas maltophilia. More than 85% of the D. acidovorans isolates were susceptible to meropenem or ceftazidime. Although, 88% and 62% of the isolates were resistant to gentamicin and colistin, respectively. D. acidovorans infections mainly affect patients with preexisting comorbidities, including malignancies. In the first year, all-cause mortality is considerable, polymicrobial cultures are common, and meropenem or cephalosporins with antipseudomonal activity could be the antibiotics of choice. IMPORTANCE Delftia acidovorans (D. acidovorans) is a Gram-negative bacteria that can cause infection in immunocompetent and immunocompromised individuals. The current knowledge comes mainly from case reports and case series. In this retrospective cohort study, we found that D. acidovorans infections mainly affect male patients with preexisting comorbidities, including malignancies. Persistent infections were not common, and most of the patients had polymicrobial cultures, mainly with Pseudomonas spp. and Stenotrophomonas maltophilia. More than 85% of the D. acidovorans isolates were susceptible to meropenem or ceftazidime. In contrast, 88% and 62% of the isolates were resistant to gentamicin and colistin, respectively.

The Epidemiological, Clinical, Mycological, and Pathological Features of Rhino-cerebral Mucormycosis: A Systematic Review.

Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until December 31st 2018. Data sources included PubMed, Scopus, EMBASE, Web of Science, Science Direct, and Proquest without limiting the time of publication. We included 287 articles corresponding to 345 cases of CM. Out of the 345 cases, 206 (60%) were male with a median age of 44 years; 130 (38%) were reported from North America; 87 (25%) from Asia; and 84 (24%) from Europe. The median time from onset of symptoms to presentation was 3-7 days (65/345, 65%). The highest mortality was observed among patients with diabetes mellitus (P=0.003). Debridement of infected brain tissue was associated with improved survival in CM cases (OR 1.5; 95% CI 01.3-1.8; P<0.0001). The use of liposomal amphotericin B (L-AMB) was significantly associated with patients' recovery (OR 2.09; 95% CI 1.2-3.4; P=0.003). The combination of L-AMB and posaconazole (12.5%) was more effective than the monotherapy treatment of CM cases (P=0.009). Clinicians should consider DM as an important risk factor for CM. Moreover, surgical debridement and antifungal combination therapy could be an effective approach in the management of CM patients.

Efficacy, immunogenicity, and evidence for best-timing of pneumococcal vaccination in splenectomized adults: a systematic review.

INTRODUCTION: Streptococcus pneumoniae is the most frequent cause of overwhelming post-splenectomy infections. Pneumococcal vaccination is generally recommended for splenectomized individuals. However, most of our knowledge comes from a few observational studies or small randomized clinical trials. We conducted this systematic review to assess the evidence of efficacy, antibody response, and the best timing for pneumococcal vaccination in splenectomized individuals. AREAS COVERED: The systematic review was conducted according to the PRISMA guidelines. We screened 489 articles, included 21 articles, and assessed the risk of bias using Cochrane RoB 2 and ROBINS-I. We summarized the findings narratively due to the heterogeneity of the studies. EXPERT OPINION: Splenectomized individuals seem to have adequate antibody responses to pneumococcal vaccines. No differences in antibody responses were observed compared to healthy controls, except in one study. The studies were heterogeneous, and the majority had moderate to high degree of bias. There is a lack of clinical evidence for efficacy and best timing of pneumococcal vaccination in splenectomized individuals. Randomized clinical trials addressing these issues are needed.

Achromobacter spp. in a Cohort of Non-Selected Pre- and Post-Lung Transplant Recipients.

Achromobacter is an opportunistic pathogen that mainly causes chronic lung infections in cystic fibrosis (CF) patients and is associated with increased mortality. Little is known about Achromobacter spp. in the lung transplant recipient (LTXr) population. We aimed at describing rates of Achromobacter spp. infection in LTXr prior to, in relation to, and after transplantation, as well as all-cause mortality proportion in infected and uninfected LTXr. We included 288 adult LTXr who underwent lung transplantation (LTX) between 1 January 2010 and 31 December 2019 in Denmark. Bronchoalveolar lavage was performed at regular intervals starting two weeks after transplantation. Positive cultures of Achromobacter spp. were identified in nationwide microbiology registries, and infections were categorized as persistent or transient, according to the proportion of positive cultures. A total of 11 of the 288 LTXr had transient (n = 7) or persistent (n = 4) Achromobacter spp. infection after LTX; CF was the underlying disease in 9 out of 11 LTXr. Three out of the four patients, with persistent infection after LTX, also had persistent infection before LTX. The cumulative incidence of the first episode of infection one year after LTX was 3.8% (95% CI: 1.6-6.0). The incidence rates of transient and persistent infection in the first year after LTX were 27 (12-53) and 15 (5-37) per 1000 person-years of follow-up, respectively. The all-cause mortality proportion one year after LTX was 27% in the Achromobacter spp. infected patients and 12% in the uninfected patients (p = 0.114). Achromobacter spp. mainly affected LTXr with CF as the underlying disease and was rare in non-CF LTXr. Larger studies are needed to assess long-term outcomes of Achromobacter spp. in LTXr.

Bacterial and fungal bloodstream infections in solid organ transplant recipients: results from a Danish cohort with nationwide follow-up.

OBJECTIVES: Bloodstream infections (BSI) are prevalent after solid organ transplantation (SOT). In this study, we aimed to investigate the incidence and risk factors for BSI in the first 5 years post-transplantation. METHODS: The study included 1322 SOT (kidney, liver, lung and heart) recipients transplanted from 2010 to 2017 with a total of 5616 years of follow-up. Clinical characteristics and microbiology were obtained from the Centre of Excellence for Personalized Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) data repository with nationwide follow-up. Incidence was investigated in the different SOT groups. Risk factors associated with BSI were assed in the combined group in time-updated multivariable Cox regressions. RESULTS: The cumulative incidence of first BSI in the first 5 years post-transplantation differed in the SOT groups with a lower incidence in heart transplant recipients than in the other SOT groups (heart: 4.4%, CI 0.0-9.7%, vs. kidney: 24.6%, CI 20.9-28.2%, liver: 24.7%, CI 19.4-29.9%, and lung: 19.6%, CI 14.5-24.8%, p <0.001). Age above 55 years (HR 1.71, CI 1.2-2.4, p=0.002) and higher Charlson comorbidity index score (HR per unit increase: 1.25, CI 1.1-1.4, p<0.001) at transplantation, current cytomegalovirus (CMV) infection (HR 4.5, CI 2.6-7.9, p<0.001) and current leucopenia (HR 13.3, CI 3.7-47.9, p<0.001) were all associated with an increased risk of BSI. CONCLUSION: In SOT recipients, the incidence of BSI differed with the type of transplanted organ. Risk of BSI was higher in older recipients and in recipients with comorbidity, current CMV infection or leucopenia. Thus, increased attention towards BSI in recipients with these characteristics is warranted.