Preventable Infections in Children with Leukodystrophy.
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ABSTRACT:
SUBMITTER: Anderson HM
PROVIDER: S-EPMC4063358 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pretravel advice should be tailored to the individual following a thorough review of his or her itinerary, planned activities, and host characteristics. In addition to vaccinations and malaria chemoprophylaxis, a pretravel consultation should include advice on regionally endemic or emerging non–vaccine-preventable infections that can cause severe illness or chronic morbidity. These include mosquito-borne infections such as dengue, chikungunya, and Zika, and regionally endemic severe respiratory infections such as Middle East respiratory syndrome (MERS) and some strains of avian influenza. Zika virus is notable given its capacity for sexual transmission and association with congenital birth defects. Preventive advice for other potentially relevant infections associated with specific exposures or activities (e.g., schistosomiasis and leptospirosis from freshwater exposure) should be provided where relevant. Understanding the epidemiology and prevention of these infections is crucial to providing a comprehensive pretravel consultation.
| S-EPMC7152013 | biostudies-literature
Project description:ImportancePediatric transplant recipients are at risk for vaccine-preventable infections owing to immunosuppression, suboptimal response to vaccines before and after transplant, and potential underimmunization if transplant occurred early in life. However, the incidence and burden of illness from vaccine-preventable infections in this population is unknown.ObjectivesTo evaluate in pediatric solid organ transplant recipients the number of hospitalizations for vaccine-preventable infections in the first 5 years after transplant and to determine the associated morbidity, mortality, and costs.Design, setting, and participantsA retrospective cohort study from January 1, 2004, to December 31, 2011, with 5 years of follow-up per participant (unless they died during the study period). The participants of this multicenter study through the Pediatric Health Information System were solid organ transplant recipients who were younger than 18 years at the time of transplant. Analysis began in July 2017.ExposuresTransplant.Main outcomes and measuresHospitalizations for a vaccine-preventable infection during the first 5 years after transplant were ascertained using International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, clinical modification diagnosis codes. Data were collected on clinical care, outcomes, and costs during these hospitalizations.ResultsOf 6980 transplant recipients identified, there were 3819 boys (54.7%), and the mean (SD) age at transplant was 8 (6.2) years. Overall, 1092 patients (15.6%) had a total of 1471 cases of vaccine-preventable infections. There were 187 of 1471 cases (12.7%) that occurred during transplant hospitalization. The case fatality rate was 1.7% for all infections. Excluding infections that occurred during transplant hospitalization (when all patients go to the intensive care unit), 213 of 1257 patients (17.0%) were hospitalized with a vaccine-preventable infection requiring intensive care. In multivariable analysis, age younger than 2 years at time of transplant and receipt of a lung, heart, intestine, or multivisceral organ were positively associated with increased risk of a hospitalization from a vaccine-preventable infection.Transplant hospitalizations complicated by vaccine-preventable infections were $120 498 more expensive (median cost) than transplant hospitalizations not complicated by vaccine-preventable infections.Conclusions and relevanceHospitalization for vaccine-preventable infections occurred in more than 15% of solid organ transplant recipients in the first 5 years after transplant at a rate of up to 87 times higher than in the general population. There was significant morbidity, mortality, and costs from these infections, demonstrating the importance of immunizing all transplant candidates and recipients. Further research on improving immunization delivery, preventing nosocomial infections, and monitoring response to vaccines in the transplant population is needed.
| S-EPMC6439884 | biostudies-literature
Project description:ImportanceVaccine responses are decreased in solid organ transplant (SOT) recipients, and given the complexity of implementation, vaccination programs may be suboptimal. The actual burden of vaccine-preventable infections (VPIs) among SOT recipients remains unclear.ObjectivesTo assess the incidence rate of VPIs among SOT recipients and to evaluate whether SOT recipients are at increased risk for specific VPIs compared with the general population.Design, setting, and participantsThis nationwide cohort study used data from the Swiss Transplant Cohort Study on VPIs in individuals who underwent SOT from May 2008 to June 2019 (follow-up until December 2019) and data from the Swiss Federal Office of Public Health on notifiable VPIs in the general population in the same period. Data were analyzed from January 2021 to June 2022.ExposuresSolid organ transplant.Main outcomes and measuresThe main outcomes were the incidence rate of the following VPIs in SOT recipients: hepatitis A and B, diphtheria, Haemophilus influenzae infection, influenza, measles, mumps, pertussis, pneumococcal disease, poliomyelitis, meningococcal disease, rubella, tetanus, tick-borne encephalitis, and varicella zoster virus infection. Age-adjusted standardized incidence ratios were used to assess whether VPIs occurred more frequently in SOT recipients compared with the general population. For SOT recipients, factors associated with occurrence of VPIs were explored and the associated morbidity and mortality assessed.ResultsOf 4967 SOT recipients enrolled (median age, 54 years [IQR, 42-62 years]; 3191 [64.2%] male), 593 (11.9%) experienced at least 1 VPI. The overall VPI incidence rate was higher in the population that underwent SOT (30.57 per 1000 person-years [PY]; 95% CI, 28.24-33.10 per 1000 PY) compared with the general population (0.71 per 1000 PY). The standardized age-adjusted incidence ratio for notifiable VPIs in SOT recipients was higher compared with the general population (27.84; 95% CI, 25.00-31.00). In SOT recipients, influenza and varicella zoster virus infection accounted for most VPI episodes (16.55 per 1000 PY [95% CI, 14.85-18.46 per 1000 PY] and 12.83 per 1000 PY [95% CI, 11.40-14.44 per 1000 PY], respectively). A total of 198 of 575 VPI episodes in the population that underwent SOT (34.4%) led to hospital admission, and the occurrence of a VPI was associated with an increased risk for death and/or graft loss (hazard ratio, 2.44; 95% CI, 1.50-3.99; P = .002). In multivariable analysis, age 65 years or older at the time of transplant (incidence rate ratio [IRR], 1.29; 95% CI, 1.02-1.62) and receipt of a lung (IRR, 1.77; 95% CI, 1.38-2.26) or a heart (IRR, 1.40; 95% CI, 1.05-1.88) transplant were associated with an increased risk of VPI occurrence.Conclusions and relevanceIn this study, 11.9% of SOT recipients experienced VPIs, and the incidence rate was higher than in the general population. There was significant morbidity and mortality associated with these infections in the population that underwent SOT, which highlights the need for optimizing immunization strategies.
| S-EPMC10148200 | biostudies-literature
Project description:BackgroundAn estimated 4% of hospital admissions acquired healthcare-associated infections (HAIs) and accounted for $9.8 (USD) billion in direct cost during 2011. In 2010, nearly 140 000 of the 3.5 million potentially preventable hospitalizations (PPHs) may have acquired an HAI. There is a knowledge gap regarding the co-occurrence of these events.AimsTo estimate the period occurrences and likelihood of acquiring an HAI for the PPH population.MethodsRetrospective, cross-sectional study using logistic regression analysis of 2011 Texas Inpatient Discharge Public Use Data File including 2.6 million admissions from 576 acute care hospitals. Agency for Healthcare Research and Quality Prevention Quality Indicator software identified PPH, and existing administrative data identification methodologies were refined for Clostridium difficile infection, central line-associated bloodstream infection, catheter-associated urinary tract infection, and ventilator-associated pneumonia. Odds of acquiring HAIs when admitted with PPH were adjusted for demographic, health status, hospital, and community characteristics.FindingsWe identified 272 923 PPH, 14 219 HAI, and 986 admissions with PPH and HAI. Odds of acquiring an HAI for diabetic patients admitted for lower extremity amputation demonstrated significantly increased odds ratio of 2.9 (95% confidence interval: 2.16-3.91) for Clostridium difficile infection. Other PPH patients had lower odds of acquiring HAI compared to non-PPH patients, and results were frequently significant.ConclusionsClinical implications include increased risk of HAI among diabetic patients admitted for lower extremity amputation. Methodological implications include identification of rare events for inpatient subpopulations and the need for improved codification of HAIs to improve cost and policy analyses regarding allocation of resources toward clinical improvements.
| S-EPMC5582652 | biostudies-literature
Project description:To determine maternal and neonatal specific antibody levels to selected vaccine-preventable infections (pertussis, Haemophilus influenzae type b (Hib), tetanus and pneumococcus).Prospective cohort study.A UK secondary care maternity unit (March 2011-January 2012).Mothers and infants within 72 h of delivery were eligible. Unwell individuals, mothers less than 18 years of age, and infants born at less than 36 weeks gestation, or weighing less than 2500 g, were excluded. HIV-infected mothers were included. 112 mother-infant pairs were recruited. Samples from 111 mothers and 109 infants (108 pairs) were available for analysis.Specific antibody levels were determined using standard commercial ELISAs. Specific antibody to pertussis antigens (PT and FHA) of >50 IU/ml, defined as 'positive' by the test manufacturer, were interpreted as protective. Antitetanus antibody titres >0.1 IU/ml and anti-Hib antibody titres >1 mg/l were regarded as protective.Only 17% (19/111) of women exhibited a protective antibody response against pertussis. 50% (56/111) of women had levels of antibody protective against Hib and 79% (88/111) against tetanus. There was a strong positive correlation between maternal-specific and infant-specific antibodies' responses against pertussis (rs=0.71, p<0.001), Hib (rs=0.80, p<0.001), tetanus (rs=0.90, p<0.001) and pneumococcal capsular polysaccharide (rs=0.85, p<0.001). Only 30% (33/109) and 42% (46/109) of infants showed a protective antibody response to pertussis and Hib, respectively. Placental transfer (infant:mother ratio) of specific IgG to pertussis, Hib, pneumococcus and tetanus was significantly reduced from HIV-infected mothers to their HIV-exposed, uninfected infants (n=12 pairs) compared with HIV-uninfected mothers with HIV-unexposed infants (n=96 pairs) by 58% (<0.001), 61% (<0.001), 28% (p=0.034) and 32% (p=0.035), respectively.Low baseline antibody levels against pertussis in this cohort suggest the recently implemented UK maternal pertussis immunisation programme has potential to be effective.
| S-EPMC3641500 | biostudies-other
Project description:IntroductionAssessing vaccine serologic status presents opportunities to provide live vaccinations to kidney transplant candidates (KTC). This is especially important given the increased risk of infection while taking lifelong immunosuppression following transplant and the inability to routinely provide live vaccines to patients on immunosuppressive medications. In March 2019, the American Society of Transplantation Infectious Disease Community of Practice (AST-IDCOP) released updated guidelines for vaccination of KTC, which emphasize pretransplant viral serology screening and live vaccine administration prior to transplant.Primary endpointThe primary endpoint of this study was to determine adherence to AST-IDCOP guidelines for live measles, mumps, and rubella (MMR) and VZV vaccination prior to transplant in KTC non-immune by serology.MethodsThis retrospective, descriptive study examined serologic status and rates of live vaccination in 672 patients listed for kidney transplant at our center between July 2014 and July 2019. Secondary endpoints included subgroup analysis of adherence to full AST-IDCOP vaccination recommendations and validation of CDC presumed immunity definitions for measles and VZV.ResultsSeventeen patients (2.7%) were nonimmune by serology for VZV, while 182 (27.1%) were nonimmune by serology to MMR. In a subgroup analysis of the seronegative KTC, none received VZV vaccination, and 6% received MMR vaccination prior to transplant or last follow-up.ConclusionsOverall, a large portion of KTC had immunity gaps that were not resolved before transplantation. These findings are limited due to the retrospective, single-center nature of this study and should be confirmed with larger, prospective assessments of serologic status and vaccine administration.
| S-EPMC9874435 | biostudies-literature
Project description:BACKGROUNDLittle is known about pathogen-specific humoral immunity after chimeric antigen receptor-modified T (CAR-T) cell therapy for B cell malignancies.METHODSWe conducted a prospective cross-sectional study of CD19-targeted or B cell maturation antigen-targeted (BCMA-targeted) CAR-T cell therapy recipients at least 6 months posttreatment and in remission. We measured pathogen-specific IgG against 12 vaccine-preventable infections and the number of viral and bacterial epitopes to which IgG was detected ("epitope hits") using a serological profiling assay. The primary outcome was the proportion of participants with IgG levels above a threshold correlated with seroprotection for vaccine-preventable infections.RESULTSWe enrolled 65 children and adults a median of 20 months after CD19- (n = 54) or BCMA- (n = 11) CAR-T cell therapy. Among 30 adults without IgG replacement therapy (IGRT) in the prior 16 weeks, 27 (90%) had hypogammaglobulinemia. These individuals had seroprotection to a median of 67% (IQR, 59%-73%) of tested infections. Proportions of participants with seroprotection per pathogen were comparable to population-based studies, but most individuals lacked seroprotection to specific pathogens. Compared with CD19-CAR-T cell recipients, BCMA-CAR-T cell recipients were half as likely to have seroprotection (prevalence ratio, 0.47; 95% CI, 0.18-1.25) and had fewer pathogen-specific epitope hits (mean difference, -90 epitope hits; 95% CI, -157 to -22).CONCLUSIONSeroprotection for vaccine-preventable infections in adult CD19-CAR-T cell recipients was comparable to the general population. BCMA-CAR-T cell recipients had fewer pathogen-specific antibodies. Deficits in both groups support the need for vaccine and immunoglobulin replacement therapy studies.FUNDINGSwiss National Science Foundation (Early Postdoc Mobility grant P2BSP3_188162), NIH/National Cancer Institute (NIH/NCI) (U01CA247548 and P01CA018029), NIH/NCI Cancer Center Support Grants (P30CA0087-48 and P30CA015704-44), American Society for Transplantation and Cellular Therapy, and Juno Therapeutics/BMS.
| S-EPMC8262349 | biostudies-literature
Project description:ObjectiveVaccination against preventable infections is widely recommended for patients with systemic rheumatic disease. The coronavirus disease 2019 (COVID-19) pandemic has highlighted variability in attitudes toward vaccination, particularly with the use of novel vaccine platforms. We studied attitudes toward vaccination against COVID-19 and other preventable infections among patients with systemic rheumatic disease and compared these against the general population.MethodsWe surveyed patients treated at Brigham and Women's Hospital for systemic rheumatic disease using a secure web-based survey or paper survey in English or Spanish, from December 2020 to April 2021. We included survey questions used in the nationwide Harris Poll (October 2020 and February 2021), allowing the comparison of responses with those from the general population. Response frequencies were estimated and compared using descriptive statistics.ResultsOf 243 participants (25% response rate), the mean age was 56 years, 82% were women, and 33% were nonwhite. Rheumatoid arthritis (50%) and systemic lupus erythematosus (28%) were the most common diagnoses. Thirty percent had been hospitalized previously for any infection. Seventy-six percent worried a lot or somewhat about contracting COVID-19. Attitudes toward vaccination were very favorable, with 92% having received a flu shot in the past year and 84% desiring a COVID-19 vaccine as soon as possible compared with 30% to 40% of Harris Poll respondents (P < 0.001). Physician recommendation to receive a vaccine and desire to avoid infection were the most common reasons for desiring vaccinations.ConclusionVaccine acceptability, including toward COVID-19 vaccines, was high among this population of patients with systemic rheumatic disease seen at an academic medical center cohort. Physician recommendation is a key factor for vaccine uptake.
| S-EPMC8652709 | biostudies-literature
Project description:Objective To analyze the efficiency of unrelated umbilical cord blood transplantation (UCBT) in the treatment of hereditary leukodystrophy following busulfan- and cyclophosphamide-based myeloablative chemotherapy. Methods A retrospective study was performed in patients with hereditary leukodystrophy who underwent UCBT after myeloablative chemotherapy between April 2015 and March 2020. Results The study cohort included 12 pediatric patients (ten males), nine with cerebral adrenoleukodystrophy (ALD) and three with juvenile globoid cell leukodystrophy (GLD). All received HLA-matched or partially mismatched unrelated UCBT. There were no cases of graft rejection. Median neutrophil engraftment time was 20 days [12–33 days] and median platelet engraftment time was 29 days [14–65 days]. Median follow-up was 36 months [1–86 months], and the overall survival rate for patients with cerebral ALD and juvenile GLD after UCBT was 77.8% (7/9) and 100% (3/3), respectively. In patients with ALD, although lipid profiles (serum very-long-chain fatty acid) were improved post-UCBT, six patients demonstrated worse neurologic function score and performance status post-UCBT, and six patients had higher Loes scores at last follow-up compared with baseline. In patients with juvenile GLD, all patients showed stable neurologic function score and performance status despite the Loes score of one patient increased slightly after transplantation. Conclusion In patients with cerebral ALD, patients with no or mild neurological symptoms can benefit from UCBT, while UCBT cannot reverse advanced disease. In patients with juvenile GLD, UCBT is safe and contributes to stabilize neurological function.
| S-EPMC9561100 | biostudies-literature
Project description:Hypomyelinating leukodystrophies are a heterogeneous group of inherited white matter disorders characterized by a predominant absence of myelin deposits in the central nervous system.Case presentationThe patient was a one-year-old girl child. She at the age of 6 months was hospitalized due to loose, muscle weakness, and an upward gaze for 7-8 min with complaints of fever and convulsions.Clinical discussionUsing the test of whole exome sequencing, a nonsense homozygous mutation was found in the PYCR2 gene, which a mutation in the PYCR2 gene causes hypomyelinating leukodystrophy type 10 disease.ConclusionAdvances in the field of genetics, increased awareness, and the increasing availability of genetic testing in small cities in developing countries are helping to better assess complex neurological disorders and establish a complete diagnosis.
| S-EPMC10205227 | biostudies-literature