Primary immunodeficiency associated with a SAMD9L mutation

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.

It's Worth a Shot

The presentation contained information about the virus, how it spreads, the vaccine, who should and should not take it, when it is recommended to be taken, how it invokes an immune response on a cellular level, and what role protein synthesis plays in the vaccine. Students and their partners were given one of seven viruses to research: measles, mumps, rubella, influenza, hepatitis B, rabies, or COVID-19. Students researched the disease and its vaccine type using credible sources, such as the Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), Johns Hopkins University, etc. Students answered the following questions: * How does the virus spread? * What are the symptoms of the virus? * How common is the virus? (statistical number) * What does the virus look like? (include picture with antigens shown) * When is the vaccine recommended by the CDC? * How often does the booster for the vaccine need to be taken? * Who should not receive the vaccine? * How does the vaccine work on a cellular level? (Be specific about the type of vaccine and how it invokes an immune response) * What role does protein synthesis play in the vaccine? * What is the vaccine efficacy or effectiveness? * Does the vaccine do any of the following: * Change the host cell's DNA? * Give the person the disease?

Systemic Viral Infections and the Eye

Ocular manifestations of systemic viral infections are common. Because viral infection syndromes may be nonspecific, diagnosis of a particular viral infection often requires understanding of the risk factors and transmission modes of viral pathogens. Careful review of both history of the disease and the ocular exam findings can be helpful in narrowing down the differential diagnosis for the systemic condition and vice versa. A history of exposures, including animal exposures, sexual exposures, and travel, as well as the vaccination history and general medical history helps guide the workup and treatment of viral infections. Diagnostic testing for viral infections may include blood testing for serologic studies and viral detection, samples from involved extraocular organs, as well as ocular samples that can confirm a diagnosis and facilitate initiation of optimal therapy while minimizing side effects from exposure to unnecessary antiviral agents. Importantly, patients with HIV or other immunocompromising conditions may simultaneously have more than one active infection and also may manifest with syndromes that are atypical and have serologic testing that is less accurate. Careful and aggressive diagnostic evaluation of ocular symptoms is especially important in these patients, as are efforts to improve immune function while monitoring for the possible impact of immune reconstitution on the clinical course. © Springer Nature Switzerland AG 2022.

Covid-19 Infection Presenting as Acute Pancreatitis

Purpose of study Introduction COVID-19 emerged at the end of 2019 as an epidemic of respiratory disease in Wuhan, China that later spread globally and was declared as pandemic. The common clinical manifestations of COVID-19 infection include fever, cough, myalgias, headache, sore throat, anosmia, nasal congestion, fatigue and chest pain. The most serious complications include bilateral multifocal pneumonia and acute respiratory distress syndrome. Acute pancreatitis is rarely reported in association with COVID-19 infection. We report a case of acute pancreatitis secondary to COVID-19 infection. Case Report: A 69-year-old man with past medical history of hyperlipidemia and seizure disorder presented with two days of epigastric pain radiating to back. The patient reported fever, malaise and dry cough for the last 3 days. Home medication included atorvastatin and carbamazepine for 10 and 15 years respectively. The patient denied smoking and alcohol use. COVID- 19 PCR was positive. Labs showed WBC of 3800/muL, hgb 11.8 g/dL, calcium 8.4 mg/dL , lipase 426 U/L, D-Dimer 179 ng/ml DDU, High sensitivity C-reactive protein 27.5 mg/L (normal <5 mg/L) ALT 26 U/L, AST 31 U/L, alkaline phosphatase 103 U/L and total bilirubin 0.3 mg/dL. Ultrasound of the right upper quadrant and CT abdomen showed normal pancreas, common bile duct and gallbladder with no evidence of gallstones. Triglyceride level was 70 mg/dL (<149 mg/dL) on the lipid panel. The patient was diagnosed with acute pancreatitis and received treatment with IV fluids and pain medication. The symptoms improved gradually and the patient was discharged home with resumption of home medications. Methods used Case Report Summary of results The common differentials for acute pancreatitis include alcohol use, gallstones, hypertriglyceridemia, viral infections like mumps and measles, hypercalcemia and medication-related, etc. Normal AST, ALT, alkaline phosphatase and total bilirubin along with absence of gallstones and normal common bile duct ruled out alcoholic and biliary pancreatitis. Normal calcium level and triglyceride level rule out hypercalcemia and hypertriglyceridemia as the cause of pancreatitis. Carbamazepine has rarely been reported to cause acute pancreatitis typically soon after the initiating the therapy or with increase in the dose. The use of carbamazepine for more than 15 years without any recent dose change makes this unlikely as the cause of pancreatitis. The onset of acute pancreatitis during the timeline of COVID-19 constitutional symptoms and absence of other risk factors suggests that COVID-19 infection is responsible for acute pancreatitis in our patient. Conclusions We report a case of acute pancreatitis secondary to COVID-19 infection. Further studies are warranted to better understand the etiology and the pathophysiology of acute pancreatitis secondary to COVID-19 infection.

Viral Vaccines

Since antiquity, humans have strived to find ways to prevent the suffering and mortality caused by infectious pathogens. No interventions in medical history have had a bigger impact on human health than the development of preventative vaccines against infectious diseases. Viruses represent important pathogens responsible for epidemics and, in the case of influenza and SARS-CoV-2, global pandemics responsible for substantial - and sometimes staggering - morbidity and mortality. This article reviews the viral vaccines used today in clinical practice, summarizes the differences in vaccine design and manufacturing, and identifies priorities for future research and development of new viral vaccines. © 2022 Elsevier Inc. All rights reserved.

A lesson from MMR: is choice of vaccine the missing link in promoting vaccine confidence through informed consent?

A recent study suggests that vaccine hesitancy amongst key demographics – including females, younger individuals, and certain ethnic groups – could undermine the pursuit of herd immunity against COVID-19 in the United Kingdom. At the same time, the UK Joint Committee on Vaccination and Immunization (JVCI) indicated that it will not facilitate the choice between available COVID-19 vaccines. This paper reflects upon lessons from the introduction of the UK's combined Measles, Mumps and Rubella (MMR) vaccine strategy of the 1980s when Member of Parliament Miss Julie Kirkbride argued that had parents been allowed to choose between vaccine variants, then the crisis of low herd immunity – and subsequent outbreaks – could have been avoided. This paper explores this argument, as applied to the COVID-19 vaccination strategy, by considering how three key elements of informed consent – disclosure of risk, benefit, and reasonable alternatives – may be employed to tackle vaccine hesitancy and build vaccine confidence.

Vaccines for the prevention of infections in adults with haematological malignancies

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.

Adult Vaccination

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.

THE PRACTICAL GUIDANCE ON IMMUNIZATION OF WAR REFUGEES FROM UKRAINE.

Implementation of national vaccination programme as well as providing catch-up immunization schedule for war refugees from Ukraine is a challenge for Polish primary care physi-cians. Measles, mumps, rubella, polio and COVID-19 catch-up vaccinations are considered a priority. The Ukrainian Immunization Programme is similar to the Polish one, but it does not include vaccination against pneumococcal disease and rotavirus. Moreover there are differences between Ukrainian and Polish vaccination schedules against pertussis, polio and Haemophilus influenzae. In this article we present principles and practical guidelines for preparing catch-up immunization schedules for refugees from Ukraine, as well as a list of vaccine preparations available in Ukraine and their Polish equivalents. For preparations available only in Ukraine, a vaccine with the most similar composition was proposed.Copyright © 2022, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

Mild Encephalitis/Encephalopathy with a Reversible Lesion in The Splenium.

Mild encephalitis/encephalopathy with a reversible lesion in the splenium (MERS) is a clinico-radiological syndrome with mild central nervous system symptoms and a reversible lesion in the splenium of the corpus callosum. It is mainly associated with a number of viral and bacterial infections, including Coronavirus disease 2019 (COVID-19). In this paper, we report four MERS patients. One had a mumps infection, the second had aseptic meningitis, the third had Marchiafava-Bignami disease, and the fourth had atypical pneumonia associated with COVID-19 infection.

Mumps in Poland in 2020.

INTRODUCTION: Mumps is an acute, generalized viral disease whose source of infection is the infected person. In 2003, vaccination against mumps became compulsory in Poland, performed according to a twodose scheme. The combined MMR vaccine (against measles, mumps and rubella) was introduced as part of the Protective Vaccination Program (PVP), which influenced the number of cases in Poland. AIM: The aim of the study was to evaluate the epidemiological indicators of mumps in Poland in 2020 compared to previous years. METHODS: The analysis of the epidemiological situation of mumps in Poland in 2020 was based on the interpretation of data from the bulletin "Infectious diseases and poisonings in Poland in 2020" and "Vaccinations in Poland in 2020". RESULTS: In 2020, 582 cases of mumps were registered in Poland. The total incidence was 1.5 per 100,000 inhabitants and was lower compared to 2019. The highest incidence was 2.0 per 100,000 inhabitants were registered in the Swietokrzyskie Voivodeship and the lowest - 0.7 in the Dolnoslaskie Voivodeship. The highest incidence (24.6/100,000) was recorded in children aged 5-9 years. The incidence of men (1.8/100,000) was higher than that of women (1.2/100,000). In 2020, 6 patients were hospitalized in Poland due to mumps, which was less than in 2019 (22 patients). The level of vaccination against mumps in children aged 3 was lower by 0.7 percentage points compared to 2019 and amounted to 91.9% across Poland. CONCLUSIONS: In 2020, there was a decrease in the number of mumps cases compared to the previous year. The lower incidence may have been the result of a reduction in mumps virus transmission due to a change in population health behavior during the COVID-19 pandemic. Due to the epidemiological threat, the functioning of nurseries, kindergartens and schools was also temporarily suspended, which resulted in a reduction in the incidence of mumps in younger age groups, which are the main group of patients.

[Quality analysis of a combined domestic vaccine for the prevention of measles, rubella and mumps].

INTRODUCTION: The need to maintain a high level of vaccination coverage against measles, rubella and mumps in conditions of an increased risk of outbreaks of infections due to violations of vaccination tactics associated with the pandemic of coronavirus infection and due to the unfavorable epidemic situation in neighboring countries determines the advisability of using a combined vaccine for the simultaneous prevention of these three socially significant infections. THE AIM OF THE STUDY: to analyze the quality of commercial series of a new domestic combined cultured live vaccine against measles, rubella and mumps (MRM) throughout the entire time of its manufacturing according to all specification indicators in regulatory documentation (RD). MATERIALS AND METHODS: The object of the study was the combined cultured live vaccine against measles, rubella and mumps. The analysis of the quality of the drug was carried out according to 86 consolidated production protocols of manufactured series, as well as according to the results of control of these series in the Testing Center for Quality Expertise of the Federal State Budgetary Institution NCESMP of the Ministry of Health of the Russian Federation. RESULTS: It is shown that the quality of the combined drug for the prevention of measles, rubella and mumps corresponds to the RD in all studied indicators. The drug does not contain an antibiotic. Bovine serum albumin, which is a technological impurity, is detected in quantities more than 5 times lower than the established norm. A comparison of the specific activity of the viral components of new combined domestic vaccine and the components of the bivalent vaccine against measles and mumps produced by the company in 20192021 showed that the spread of the activity values of the viral components in the new drug and in the series of mumps-measles vaccine was minimal, which allowed us to make a conclusion about the stability of the production technology. CONCLUSION: The quality of the new domestic combined vaccine for the prevention of measles, rubella and mumps meets WHO requirements. The results of the conducted studies indicate the stability of production and the standard quality of the drug. The use of a combined vaccine against three significant infections will ensure the necessary level of vaccination coverage in the population. Information about the results of studies can help reduce the number of vaccination refusal.

CEC01-03 Safety of vaccines: a current perspective

Vaccines are powerful tools for preventing infection or disease from the infectious pathogens they target, but they may induce additional effects unrelated to the intended targets. Similar to other pharmaceutical products, vaccines may cause side effects, but tolerance to these is extremely low due to the use of vaccines in healthy people, particularly children. Redness, swelling or soreness at the site of injection are common for many vaccines under the term of reactogenicity. High fever can be present at a rate of 1/100 to /100 000 as can fever-induced convulsions from vaccines such as measles, mumps or rubella. Rotavirus vaccines are suspected to be associated with intussusception in about 1/100 000 first doses. Allergic reactions are in the same range. The massive H1N1 vaccination in the world has also been potentially associated with an increase in narcolepsia in patients with a risk allele. More recently, the SARS-CoV-2 vaccine ChAdOx1 nCov-19 have been found to cause a thromboembolic complication termed vaccine-induced immune thrombotic thrombocytopenia in very few people. Consequently, vaccines must undergo vigorous assessment before and after licensure to minimize safety concerns. Potential safety concerns should be identified as early as possible during the development for vaccines. In this CEC, along with courses, the attendees will have to work in small groups on real case studies associating non-clinical development and regulatory strategies. Copyright © 2022 Elsevier B.V.

Mitigating Vaccine Hesitancy and Building Trust to Prevent Future Measles Outbreaks in England.

Measles, a highly infectious respiratory viral infection associated with severe morbidity and mortality, is preventable when coverage with the highly effective measles, mumps and rubella vaccine (MMR) is ≥95%. Vaccine hesitancy is responsible for measles outbreaks in countries where measles had previously been eliminated, including in England, and is one of the ten threats to global public health identified by the World Health Organization (WHO). Official administrative 2012-2021 data on measles incidence and MMR coverage in England were reviewed alongside a scoping literature review on factors associated with MMR uptake in England. Whilst measles incidence has reduced significantly since 2012, sporadic measles outbreaks in England have occurred with geographic disparities and variations in MMR coverage. Over the last decade, MMR uptake has fallen across all regions with no area currently reaching the WHO target of 95% coverage of both doses of MMR necessary for herd immunity. Factors associated with MMR coverage overlap with the 3C (convenience, complacency and confidence) model of vaccine hesitancy. The COVID-19 pandemic has reinforced pre-existing vaccine hesitancy. Increasing MMR uptake by reducing vaccine hesitancy requires allocated funding for area-based and targeted domiciliary and community-specific immunisation services and interventions, public health catch-up campaigns and web-based decision aid tools.

Improved Immunogenicity of the Inactivated F Genotype Mumps Vaccine against Diverse Circulating Mumps Viruses in Mice.

Mumps is an acute infectious disease caused by the mumps virus (MuV). Despite high global vaccination coverage, mumps outbreaks continue to occur, even in vaccinated populations. Therefore, we aimed to identify candidate vaccines that can induce an immunogenic response against diverse MuV genotypes with greater efficacy than the currently available options. Vaccine candidates were sourced using formalin-inactivated viral strains. The inactivated vaccines were administered to BALB/c mice (through a primer and booster dose administered after a three-week interval). We tested the neutralizing antibodies of the candidate vaccines against various MuV genotypes to determine their overall efficacy. The formalin-inactivated F genotype vaccine was found to have higher cross-neutralizing titers against genotypes F, H, and G as well as significant Th1 cytokines responses, IFN-γ, TNF-α, and IL-2 than the Jeryl Lynn (JL) vaccine. Our findings suggest that the inactivated F genotype mumps vaccine has higher immunogenicity than the JL vaccine against diverse circulating MuVs.

Measles and travel: an update for general practice nurses

Measles remains a risk for international travellers. The ongoing COVID-19 pandemic has interrupted many routine childhood vaccine schedules worldwide, resulting in an upsurge in measles cases. A travel consultation is an opportunity to offer measles, mumps and rubella (MMR) vaccine for both personal protection of individual travellers and as a public health intervention.

Child vaccination coverage of selected infectious disease in the Czech Republic

Introduction: Vaccination control is performed by all European Union countries, but uniform standards for the collection of valid data are still lacking. The analysis of vaccination data is used to evaluate vaccination programs and their effectiveness in preventing the occurrence of infectious diseases at the national level. Vaccination information also helps to plan the required amount of vaccines in advance so that outages do not occur and deliveries are smooth. Various methods are used for the purpose of determining vaccination coverage, namely administrative methods, surveys, including seroprevalence or direct use of data from immunization programs. Methods based on the use of data from vaccination registers are another way of obtaining information about vaccinations. Thanks to the change in the payment of compulsory vaccination and the introduction of paid vaccination from health insurance, we have now had the opportunity in the Czech Republic to monitor and analyze data from health insurance companies on the vaccination of the population in selected preventable diseases. The data are managed by the Institute of Health Information and Statistics of the Czech Republic within the National Health Information System and national health registers. Data from health insurance companies on the number of reported vaccination doses, including used vaccines, are available in the National Register of Paid Health Services. The register contains data from health insurance companies in the inpatient and outpatient areas, including complete data on reported diagnoses, procedures and treatment. The national information system of the public administration enables the determination of the number of administered doses of the vaccine on the basis of the used registers, also in relation to the number of inhabitants of the given year of birth and their permanent residence. Vaccination in children: Full-term infants born from 1 January 2018 are vaccinated with a combined vaccine against diphtheria, tetanus, pertussis, viral hepatitis B, poliomyelitis and invasive infections caused by Haemophilus influenzae type b (hexavaccine) in scheme 2 + 1, unlike the original 3 + 1 dose, which remains valid for premature babies born before the 37th gestational week of pregnancy. The National Register of Paid Health Services data were used to monitor vaccination coverage. Vaccination in the case of hexavaccine in infants born in 2018 reached 94.8%, in children born in 2019 then 95.2% with the monitored parameter of administration of at least one dose of vaccine up to one year of age. A similar change of the scheme to 2 + 1 occurred in the case of optional vaccination against pneumococcal infections in infants, where we observe an increase in vaccination coverage from 66.9% in chlidren born in 2017 to 73% in children born in 2019 when monitoring the administration of at least one dose up to one year of age. In the case of the combined measles, mumps and rubella (MMR) vaccine, above 90% (90.3%) of two-year-olds born in 2018 receive a first dose vaccination. The revaccination against tetanus, diphtheria and pertussis (Tdap) in five-year-olds in 2019 reached 90%, in the previous year 2018 it was 91.2%. In the case of revaccination of children aged 10-11 years with the combined vaccine together with revaccination against poliomyelitis (Tdap-IPV), based on the data for 2020, the vaccination coverage reached 91.7%, while in the previous year of children it was 94.5%. In the case of vaccination against human papillomavirus (HPV) diseases, there is a slight increase in the number of vaccinated girls and boys, with a current vaccination prediction of 63.6% for girls in 2020 and 42.6% for boys. In addition, in 2020, thanks to the amendment to Act No. 48/1997 Coll. on public health insurance, we managed to launch optional paid vaccinations for infants and toddlers against meningococcal infections and thus extend the national immunization program to include additional vaccinations. Despite this spread, there has been no decrease in vaccination coverage in infa ts and toddlers with other vaccines. Conclusion(s): Despite the ongoing epidemic of covid-19, preventive child care was maintained in the Czech Republic in 2020 and there was no decrease in vaccination coverage for compulsory and optional (paid) vaccinations for infants and toddlers. On the contrary, we managed to implement additional optional vaccinations paid for from public health insurance funds, also thanks to the acceleration of the legislative process within the declared state of emergency. The epidemic shows the importance of adherence to preventive measures and the need for early prevention of the disease using vaccination programs. Unfortunately, the burden of the epidemics has been delayed by the possibility of repeated publication of updated data on vaccination coverage of children from the national registers of paid health care and are thus published at a delay. The lack of data obtained in this way still remains, the method is limited only for paid vaccinations from public health insurance funds, ie without records of vaccinations paid for by the parents of children. In the future, we will not do without registers of vaccinations based on information obtained from medical records of vaccinated individuals in the form of electronic vaccination records. Copyright © 2021, EEZY Publishing, s.r.o.. All rights reserved.

A SHOT IN THE ARM FOR CHILD HEALTH: THE JOURNAL OF THE HEALTH VISITORS' ASSOCIATION

Childhood vaccination rates are generally high in the UK, but there is considerable room for improvement. Two major issues are currently a cause for concern. The first is a small but gradual decline in uptake each year since 2012/13, and the other, persistent inequalities in uptake, with large variation between geographic areas and population groups. Here, Bedford reviews the current vaccine uptake and the possible causes of the decline.