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Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.
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Objectives: Pertussis, a highly contagious respiratory disease caused by Bordetella pertussis, is endemic in Brazil, but is underdiagnosed in adults due to atypical symptomatology and limited diagnosis time window. Brazil's Ministry of Health recommends decennial boosters in adults against diphtheria and tetanus, but not pertussis. After the COVID-19 pandemic, infectious diseases surged worldwide due to lack of natural exposure and reduced immunization coverage. Asthma and COPD populations are at increased risk of pertussis infection. This study assessed the cost-utility of decennial pertussis vaccination with Tdap vaccine versus no pertussis vaccination in Brazil's adult asthma and COPD populations in a high-incidence context. Method(s): A static cross-sectional population-based cost-utility model of decennial Tdap boosters in asthma patients >=50 years and COPD patients >=40 years was developed from the payer's perspective. Pertussis incidence from Sao Paulo's state surveillance system in the peak year 2014 was adjusted for underdiagnosis and relative risk of pertussis in asthma and COPD populations. Vaccine efficacy and coverage, and costs and outcomes discounted at 5%, were obtained from the literature and public databases. Deterministic and probabilistic sensitivity analyses, and scenario analyses were run, including alternative annual incidence. Result(s): In the asthma population, Tdap boosters would incur 7,065,788 Brazilian reais (BRL) direct costs and save 32.85 Life Years (LYs) and 262.13 Quality-Adjusted LYs (QALYs). In the COPD population, Tdap boosters would incur 41,102,844 BRL direct costs and save 157.47 LYs and 1,078.26 QALYs. Discounted incremental cost-utility ratios were 26,956 and 38,120 BRL/QALY in asthma and COPD populations, respectively. At a cost-effectiveness threshold of 1 Gross Domestic Product (GDP)/capita, 85.8% and 49.7% of simulations were cost-effective in asthma and COPD populations, respectively, while all simulations were cost-effective at a threshold of 3 GDP/capita. Conclusion(s): Implementing decennial Tdap boosters for adult asthma and COPD patients should be considered, given the favorable cost-utility profile in peak-incidence years.Copyright © 2023
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<Positive> In January 2023 (from 0:00 on January 1, 2023 to 24:00 on January 31), a total of 249 324 notifiable infectious diseases were reported nationwide (excluding Hong Kong, Macao Special Administrative Region and Taiwan, the same below). For example, 2 158 people died. Among them, no cases of morbidity or death were reported for Class A infectious diseases. Among Class B infectious diseases, there are no reports of morbidity and death in infectious atypical pneumonia, polio, human infection with highly pathogenic avian influenza, diphtheria, schistosomiasis, and human infection with H7N9 avian influenza. Except for the new coronavirus infection, the remaining 20 A total of 184,750 cases of Class B infectious diseases were reported, and 2,158 deaths were reported. The top 5 diseases with the highest number of reported cases were viral hepatitis (89 719 cases reported, 32 deaths reported), tuberculosis (53 730 cases reported, 327 deaths reported), syphilis (28 708 cases reported, 3 deaths were reported), gonorrhea (4 762 reported cases, 0 reported deaths) and brucellosis (reported cases, reported deaths), accounted for 97% of the total number of reported cases of Class B infectious diseases.
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Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and adverse effects of vaccines for the prevention of infections in adults with haematological malignancies.Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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This article discusses the worldwide routine vaccination coverage in 2021, as part of the Immunisation Agenda 2030, a global immunisation strategy to reduce morbidity and mortality from vaccine-preventable diseases. The report presents global, regional, and national estimates and trends in vaccination coverage through 2021, based on reviews of country-specific data, including administrative and survey-based coverage. Global estimates show that coverage with 3 doses of diphtheria, tetanus and pertussis-containing vaccine (DTPcv3) and the first dose of measles-containing vaccine (MCV1) decreased to their lowest levels since 2008. In 2021, 25.0 million infants were not vaccinated with DTPcv3, 2.1 million more than in 2020, and 5.9 million more than in 2019. The number of zero-dose children was 37% higher than in 2019, with 18.2 million infants not receiving any DTPcv dose by the age of 12 months. The report highlights that the full recovery from disruptions to immunisation programmes due to the COVID-19 pandemic will require context-specific strategies to find missed children, prioritise essential health services, and strengthen immunisation programmes to prevent outbreaks.
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Adult vaccination rates are low in the United States, despite clear benefits for reducing morbidity and mortality. Vaccine science is evolving rapidly, and family physicians must maintain familiarity with the most recent guidelines. The recommended adult immunization schedule is updated annually by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention. All eligible patients should receive SARS-CoV-2 vaccines according to the current guidelines. Adults without contraindications should also receive an annual influenza vaccine. Hepatitis A vaccine is recommended for adults with specific risk factors. All pregnant patients, adults younger than 60 years, and those 60 years and older who have risk factors should receive a hepatitis B vaccine. A 15- or 20-valent pneumococcal conjugate vaccine is recommended for all patients who are 65 years and older. Patients who receive 15-valent pneumococcal conjugate vaccine should receive a dose of 23-valent pneumococcal polysaccharide vaccine one year later. Adults 19 to 64 years of age should receive a pneumococcal vaccination if they have medical risk factors. A single dose of measles, mumps, and rubella vaccine is recommended for adults without presumptive immunity, and additional doses are recommended for patients with HIV and postdelivery for pregnant patients who are not immune to rubella. A tetanus and diphtheria toxoids booster is recommended every 10 years. For pregnant patients and those in close contact with young infants, a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine should be administered. The human papillomavirus vaccine is recommended for all people through 26 years of age. Herpes zoster vaccine is indicated for all adults 50 years and older.Copyright © 2022 American Academy of Family Physicians.
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Vaccination is effective in preventing the increase of disease, especially emerging infectious diseases (EIDs), and it is particularly important for people in close contact with infected sources and susceptible populations who are at increased risk of getting infectious diseases due to behavior, occupation or health. Despite targeted vaccination guidelines, inadequate vaccination of the key populations fails to receive widespread attention, resulting in a high-risk transition of disease from key populations to general populations. Strengthening the vaccination of the susceptible groups can effectively block the spread of pathogens to general populations, and reduce the consumption of medical resources in universal vaccination, which has significant economic value. In this review, we describe the prevalence of EIDs, analyze the experience and lessons of infectious disease vaccination in key populations through several cases, and further explore the causes for the decline in vaccination rates of key populations. According to the trends of EIDs, a plan to strengthen the vaccination of key populations is proposed to effectively prevent the transition of EIDs from key populations to general populations.
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Satisfying the needs of the national immunization program requires maintaining diphtheria-tetanus-pertussis (DTP)-hepatitis B (HB)-Haemophilus influenza B (Hib) production. Therefore, new hepatitis B sources are needed. This study aimed to evaluate the immunogenicity of the DTP-HB-Hib vaccine (Bio Farma) that used a different source of hepatitis B. A prospective randomized, double-blind, bridging study was conducted. Subjects were divided into two groups with different batch numbers. Healthy infants 6-11 weeks of age at enrollment were immunized with three doses of the DTP-HB-Hib vaccine after a birth dose of hepatitis B vaccine. Blood samples were obtained prior to vaccination and 28 days after the third dose. Adverse events were recorded until 28 days after each dose. Of the 220 subjects, 205 (93.2%) completed the study protocol. The proportion of infants with anti-diphtheria and anti-tetanus titers ≥ 0.01 IU/mL was 100%, with anti-HBsAg titers ≥ 10 mIU/mL was 100%, and with Polyribosylribitol Phosphate-Tetanus Conjugate (PRP-TT) titers > 0.15 µg/mL was 96.1%. The pertussis response rate was 84.9%. No serious adverse events related to the study vaccine occurred. The three-dose DTP-HB-Hib vaccine (Bio Farma) is immunogenic, well tolerated, and suitable to replace licensed-equivalent vaccines.
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Immunogenic carrier proteins such as the non-toxic diphtheria toxin variant, cross-reacting material 197 (CRM197), are widely used in subunit vaccine formulations to boost immunogenicity of chemically conjugated antigens. Conjugate vaccines are inherently expensive due to laborious manufacturing steps. Here, this work develops a particulate vaccine platform based on using engineered Escherichia coli to assemble CRM197-antigen fusion proteins into discrete submicron-sized particles. This approach enables precise loading of diverse antigens and epitopes enhancing their immunogenicity. A cost-effective, high-yield, and scalable biomanufacturing process is developed. Purified particulate CRM197-antigen vaccines are ambient-temperature stable. CRM197 particles incorporating pathogen-specific antigens or epitopes from SARS-CoV-2, Streptococcus pyogenes (group A), and Mycobacterium tuberculosis induced cell-mediated and humoral immune responses mediating protective immunity in respective animal models of infection. The CRM197 particle vaccine platform is versatile, enabling co-delivery of selected antigens/epitopes together with immunogenic CRM197 as discrete stable particles avoiding laborious manufacture of soluble CRM197 and antigen followed by chemical conjugation.
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COVID-19 , Animals , SARS-CoV-2 , Bacterial Proteins/chemistry , Vaccines, Synthetic , Vaccines, Conjugate , Antigens , EpitopesABSTRACT
Objective: In this paper, we examine the current crisis of regarding preparedness of healthcare industries in Pakistan, analyzing the causes, effects, and potential recommendations to this problem. Methods: Highlighting the efforts and issues surrounding this topic is necessary for developing and implementing research-based solutions that accurately reflect the current state of the healthcare industry. This short overview is prepared in accordance with accepted practices in published studies around the world. Our findings were based on a search of the literature databases PubMed, Google Scholar, Journals Online, and the Internet Library. Results: Searching for "Healthcare Preparedness in Pakistan" yielded the expected results. Particularly of interest to the researchers was the question of why, despite efforts to boost vaccination rates and emergency immunization response capacities in the event of epidemics, progress on SDG3 immunization indicators has been minimal. Immunization is critically important because vaccine-preventable diseases pose a significant risk to the general population. Pakistan's authorities and government should take deliberate action to increase immunization rates. Conclusion: Particularly disadvantaged countries and regions are hit the worst by climate change. Pakistan continues to be hit hard by diseases like acute watery diarrhea, dengue fever, malaria, and COVID-19 are on the rise as a result of the flooding, especially in shelters and areas where water and sanitation systems have been affected. After devastating floods in KP, Sindh, and Punjab, over 70 suspected cases of diphtheria were reported. Diphtheria epidemics illustrate the precarious position of flood victims. It would be catastrophic if the newly found diphtheria strain or the covid-19 variation reached the underserved flood victims. Immunization protects against life-threatening illnesses so its government responsibility to improve immunization rates in Pakistan.
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Vaccination, the transmission of "vaccine", a benign disease of cows, to immunize human beings against smallpox, was invented by Jenner at the end of the eighteenth century. Pasteur, convinced that the vaccine microbe was an attenuated form of the smallpox microbe, showed that, similarly, attenuated forms of other microbes immunized against animal diseases. When applying this principle to rabies, he realized that, in this case, the vaccine was in fact composed of dead microbes. One of his students immediately exploited this result to devise a vaccine against typhoid. The vaccines against diphtheria and tetanus, in 1921, opened a new route, that of immunization with molecules from the pathogenic microbes. Molecular biology then allowed the production of the immunogenic molecules by microorganisms such as yeast, or immunization by genetically modified viruses or messenger RNA inducing our own cells to produce these molecules.
La vaccination, transmission de la vaccine, maladie bénigne des vaches, pour immuniser les humains contre la variole, a été inventée par Jenner à la fin du XVIII e siècle. Pasteur, convaincu que le microbe de la vaccine est une forme atténuée de celui de la variole, montre que des formes atténuées d'autres microbes immunisent des animaux contre des maladies. Lors de l'application à la rage, il comprend que la préparation vaccinale qu'il utilise dans ce cas est en fait constituée de microbes tués. Conclusion aussitôt exploitée par l'un de ses élèves dans la conception d'un vaccin contre la typhoïde. Les vaccins contre la diphtérie et le tétanos, en 1921, ouvrent une troisième voie, celle de l'immunisation par des molécules provenant des microbes pathogènes. La biologie moléculaire va permettre la production de ces molécules immunogènes par des micro-organismes tels que des levures, ou bien l'immunisation par des virus génétiquement modifiés ou par de l'ARN messager, conduisant nos propres cellules à produire ces molécules.
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Smallpox , Female , Male , Humans , Animals , Cattle , RNA, MessengerABSTRACT
Here we document a rare, acute, infection caused by non-toxigenic Corynebacterium diphtheriae and the resulting unique and severe clinical sequelae. Our patient was a young man with no known pre-existing conditions that presented in cardiopulmonary arrest. We contrast this case with prior instances of non-toxigenic C. diphtheriae strain infection in the United States and summarize the literature that suggests systemic infection can result in cardiogenic toxicity. We speculate on a possible missed, pre-existing condition that could have increased this patient's susceptibility to poor clinical outcome.
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OBJECTIVE: To assess provider attitudes and practices regarding vaccination in pregnancy to discern strategies to increase vaccination rates in pregnancy, given that in the USA, various healthcare organizations recommend that pregnant individuals be vaccinated against influenza, pertussis, and SARS-CoV-2, but vaccination rates among gravidas remain suboptimal across these vaccines. METHODS: An Institutional Review Board-approved survey was disseminated to obstetric healthcare providers by email from June through October 2021. Questions assessed provider demographics, attitudes, and practices surrounding vaccination in pregnancy. A total of 192 providers consented, 179 initiated the survey, and 153 completed it entirely. Statistical software (SAS) was used to perform descriptive statistics. RESULTS: All providers strongly agreed/agreed that all pregnant individuals should receive vaccines in pregnancy. Following patient vaccination consent, 13% reported needing to refer patients to alternative sites for vaccine administration. Following patient vaccination decline, 13% did not determine reasons for refusal, 30% did not re-counsel at subsequent visits, and 92% did not ask another staff member to counsel the patient. CONCLUSION: Despite provider support for maternal immunization, uptake of vaccines in gravidas remains suboptimal, demonstrating a gap between provider recommendations and patient uptake. These data highlight opportunities for intervention regarding counseling and vaccine availability to increase vaccine uptake in pregnancy.
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A number of phytochemicals have been identified as promising drug molecules against a variety of diseases using an in-silico approach. The current research uses this approach to identify the phyto-derived drugs from Andrographis paniculata (Burm. f.) Wall. ex Nees (AP) for the treatment of diphtheria. In the present study, 18 bioactive molecules from Andrographis paniculata (obtained from the PubChem database) were docked against the diphtheria toxin using the AutoDock vina tool. Visualization of the top four molecules with the best dockscore, namely bisandrographolide (-10.4), andrographiside (-9.5), isoandrographolide (-9.4), and neoandrographolide (-9.1), helps gain a better understanding of the molecular interactions. Further screening using molecular dynamics simulation studies led to the identification of bisandrographolide and andrographiside as hit compounds. Investigation of pharmacokinetic properties, mainly ADMET, along with Lipinski's rule and binding affinity considerations, narrowed down the search for a potent drug to bisandrographolide, which was the only molecule to be negative for AMES toxicity. Thus, further modification of this compound followed by in vitro and in vivo studies can be used to examine itseffectiveness against diphtheria.
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Andrographis , Corynebacterium diphtheriae , Diphtheria , Diterpenes , Andrographis paniculata , Andrographis/chemistry , Diterpenes/pharmacology , Diterpenes/chemistry , Plant Extracts/pharmacology , Phytochemicals/pharmacologyABSTRACT
Background. Vaccine-preventable diseases pose a risk towards heart transplant recipients on lifelong immunosuppression. Immunization rates are low (30-80%) in solid organ transplants. The aim of this study was to examine the vaccination rates in our hospital's heart transplant recipients with a goal to expose deficiencies and formulate strategies to increase vaccination in this population. Methods. This study is a single-center retrospective chart review of patients aged 18 or older who received a heart transplant between January 1, 2012 and March 31, 2022 at our institutionin Temple, Texas.We documented vaccination status or seropositivity prior to or after transplant, as recommended by the American Society of Transplantation (AST) for influenza, hepatitis B, hepatitis A, measles, mumps, and rubella (MMR), 23-valent pneumococcal polysaccharide (PPSV23), 13-valent pneumococcal conjugate (PCV13), tetanus, diphtheria, and acellular pertussis (Tdap), varicella, zoster, and COVID-19 immunizations. We evaluated the association with an Infectious Disease (ID) consult. Odds ratios (OR) were calculated with 95% confidence intervals. Results. 72 patients received a heart transplant within the 10-year period. Demographics are noted in table 1. Table 2 presents the immunization status as follows: 48.7% for flu vaccine, 55.5% for Hepatitis B, 47.1% for Hepatitis A, 36.1% for MMR, 67.5% for PPSV23, 67.5% for PCV13, 54.1% for Tdap, 83.3% for Varicella and 13.8% for Zoster, and 53.5% for COVID-19. From 2016, an ID consult was required pre-transplant;45 patients (62.5%) had an ID consult before transplant. ID consult was associated with increased likelihood of receiving the MMR, PCV13, Tdap, and Zoster vaccines (table 3). Table 1 Patient demographics Table 2 Immunization status in heart transplant recipients Table 3 Immunization status associated with ID consult Conclusion. This study reveals the deficiency of vaccinations in our heart transplant patients, but an ID consult was associated with better immunization rates. To further increase compliance, we propose different interventions including close follow-up with ID, addressing vaccine costs, accessibility limitations, cultural hesitancy, and implementation of protocols.
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Purpose: Despite widely disseminated guidelines, pneumococcal and influenza vaccination coverage (VC) remains insufficient in patients with cancer receiving cancer treatment. We performed an interventional study to evaluate VC in patients with cancer treated at the medical oncology departments of three North-of-France hospitals and to assess the effect of medical staff training on VC in these patients. Methods: A standardized questionnaire assessed VC in adult patients with cancer receiving anticancer treatment at three day hospitals during December 2-7, 2019. Subsequently (January 2020), we organized educational training sessions for medical staff from each hospital to discuss the current vaccination guidelines. To assess the impact of training on pneumococcal and influenza VC, we re-administered the same questionnaire in March 2020. Because there are no specific guidelines on Diphtheria-Tetanus-Pertussis (DTP) vaccination and no improvement was expected, DTP VC acted as an internal control. Results: In total, 272 patients from all three hospitals were enrolled in the "before study"; 156 patients from only two hospitals were enrolled in the "after study" as medical training and data collection at the third were impossible because of administrative reasons and COVID-19 pandemic. The predictors were age for DTP VC; treatment center for pneumococcal VC; and age, sex, and tumor histology (adenocarcinoma vs. others) for influenza VC. Neither influenza VC (42.6% vs. 55.1%, p = 0.08), nor pneumococcal VC were significantly improved post-intervention (11.8% vs. 15.4%, p = 1). There seems to be a small effect in the most fragile for influenza VC. Conclusion: As expected, VC was very low in patients with cancer, consistent with the literature. There was no impact of the intervention for pneumococcal and influenza VC.
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According to the 2018 Hacettepe University Population and Health Survey report, of the married women between 25-49 age group;39% get married before the age of 20, 21% before the age of 18 and 4% before the age of 15 (1). According to the WHO report, in 2019, abortion was reported at a rate of 55% in unplanned pregnancies in adolescents, especially in countries with limited resources (2). According to CDC data, it has been reported that the Tdap vaccine administered in the 27-36 weeks of the pregnancy, reduces pertussis disease by 78% in the first two months of their infants, and it reduces the infant hospitalizations due to whooping cough by 90% (6-8). [...]the first dose is given at the first visit, the second dose is administered four weeks later, the third dose is given 6-12 months after the second dose, and the vaccination schedule is completed in three doses (3,8).
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› The prevention of infections is essential to athletes’ health and performance. Even mild infections can severely affect athletic performance and the eligibility to train and compete. One of the most effective means of avoiding severe infections are vaccinations. However, like the general population, athletes frequently do not receive the recommended vaccinations. › This shortcoming is largely based on fear of adverse vaccine reactions, concerns about the efficacy, misinterpretations, negligence, and poor communication. As sports medicine physicians are involved in the regular screening of adolescent, adult, and senior athletes, they are in a unique position to advise on an individual basis about the risks and benefits of an athlete-specific vaccination schedule. Thus, every preparticipation physical examination should be used to check the vaccination status and, if needed, optimize and update the athletes’ vaccination profile. › In this clinical review, recommendations for standard, travel, and specific-indication vaccinations in athletes will be given and their efficacy, timing, and administration in the sports context will be discussed. The review will be completed by recommended literature and useful apps for the sports medicine physician involved in the preparticipation physical examination of athletes. © 2022, Dynamic Media Sales Verlag. All rights reserved.