Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) ad hoc meeting, 28 June - 1 July 2024.

The World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) serves to independently review and evaluate vaccine-related research to maximize the potential impact of vaccination programs. From 28 June - 1 July 2024, IVIR-AC was convened for an ad hoc meeting to discuss new evidence on criteria for rubella vaccine introduction and the risk of congenital rubella syndrome. This report summarizes background information on rubella virus transmission and the burden of congenital rubella syndrome, meeting structure and presentations, proceedings, and recommendations.

Hypergammaglobulinemia D and Periodic Fever Syndrome (HIDS) in a 3-year-old Patient from Puerto Rico.

Mevalonate kinase deficiency is a rare autosomal recessive disease caused by mutations in the mevalonate kinase gene (MVK). Depending on the mutations, a patient with this deficiency can exhibit any one of a spectrum of rare autoinflammatory diseases, such as hypergammaglobulinemia D (hyper-IgD) with periodic fever syndrome and mevalonic aciduria. To date, approximately 300 cases with mutations in the MVK gene have been reported worldwide. Herein, we present a 3-year-old female from Puerto Rico with a history of fever, arthralgia, and skin lesions since her first month of age and who, upon genetic workup, was confirmed to have compound heterozygous mutations in the MVK gene. Given her medical history and the results of her genetic testing, she was diagnosed with hyper-IgD with periodic fever syndrome. She will be treated with canakinumab, an interleukin-1ß antagonist, after receiving the varicella and measles-mumps-rubella (MMR) vaccines.

Vaccinations at home: a new strategy to contain vaccine hesitancy? The experience of ASL Napoli 1 Centro, Italy.

Abstract: Vaccination coverage are generally geographically variable, even within large cities; furthermore, across target population are embedded difficult-to-reach clusters. To address this issue and improve coverage of mandatory vaccinations, a study group explored bringing vaccination at home as an interventional strategy. In a pilot experience, parents of unvaccinated and under vaccinated children of the 2020 birth cohort living in Naples, Italy were contacted by telephone to offer home administration of vaccinations. A specifically trained team arranged vaccinations visits at home. Coverage rates were evaluated at baseline and one month after the intervention strategy. A significant positive increase in hexavalent vaccine (+1.43%) and measles-mumps-rubella (+1.85%) coverage was registered despite the short duration of the pilot program. Home vaccination turned out to be a medical resource consuming but feasible and successful strategy to increase mandatory vaccinations coverage among the most difficult-to-reach and fragile segments of the pediatric population.

Measles resurgence in Armenia: unmasking health system vulnerabilities and crafting comprehensive eradication strategies - a review.

Measles is an acute febrile illness associated with rashes, fever and life-threatening complications. It is a vaccine-preventable disease with the Measles Mumps Rubella(MMR) vaccine but a recent global trend unveils a resurgence of measles in various parts of the world including Armenia. Measles was declared eliminated from Armenia in 2021 before reports of local outbreaks surfaced in 2023. The WHO identified discrepancies in the vaccination coverage during COVID-19. Measles also poses a great financial burden as a public health issue worldwide. Sociocultural factors impacting measles transmission are maternal education, healthcare access, migration, vaccine hesitancy, and socioeconomic status (Table 3). Efforts to control and eradicate measles from Armenia are run by a collaborative approach of national and international health bodies such as United Nations Children's Fund (UNICEF), WHO, Global Vaccine Alliance (GAVI), and the Ministry of Health. Thus, the resurgence of measles can be managed through widespread patient education, innovative approaches, strengthening the healthcare system and addressing vaccine hesitancy, sociocultural barriers, and humanitarian emergencies. This review investigates the complicated dynamics of measles inside Armenia's health system in depth. A thorough examination of measles incidence and immunization patterns highlights the shift from few cases and high vaccination rates to a comeback caused by imported viruses. The causes of its recurrence have been thoroughly investigated, including reduced immunization programs and vaccine hesitancy. The research delves further into the 'One Health' idea, assessing the possibility of interspecies transmission among nonhuman primates and examining the environmental factors that influence measles transmission. Among the challenges are weaknesses within Armenia's health system as well as the possibility of interruptions from the COVID-19 outbreak. In measles vaccination status, the combination of maternal education, postnatal care, and socioeconomic variables exposes the larger drivers at work. The study concludes with a comprehensive set of public health policy recommendations covering vaccination promotion, surveillance, healthcare provider education, public awareness, international collaboration, data analysis, law enforcement, emergency preparedness, research, and coordination. The research sheds light on the tangled web of measles dynamics, health system resilience, and contextual subtleties via this multifaceted approach, inviting readers to investigate the multiple strategies required for eliminating measles in Armenia.

Study to Assess the Clinical and Sociodemographic Profile of Measles in Children Admitted to a Tertiary Care Center: A Retrospective Study.

Background Measles remains a significant contributor to illness and death among young children, despite the presence of a safe and efficacious vaccine. One of the most highly transmissible viruses affecting humans is measles, which can be almost entirely prevented through vaccination. The recent surge in measles cases worldwide has been particularly notable in India. A total of 172 confirmed outbreaks of measles were recorded between October 2021 and September 2022, resulting in 12,589 cases. Measles, being highly contagious, is transmitted through the respiratory route. The disease affects 75 to 90% of susceptible household contacts, reaching peak infectivity three days before the rash emerges. The recent measles outbreak observed since January 2023 holds significance, as Bangalore district alone has reported around 500 cases. Therefore, the current study aims to evaluate the clinical and sociodemographic characteristics of measles in pediatric patients. Methods This was a retrospective study conducted over seven months. Data pertaining to demographics such as age, gender, parental occupation, parental educational background, and housing situation were gathered. Details regarding the child's immunization status, the onset of fever, and the onset of rash were also documented. Descriptive data was represented using mean, standard deviation, and percentage or proportion. Results Over the study period of seven months, 53 children were admitted due to measles. The majority of the individuals were female, accounting for 28 cases (52.8%). The typical clinical manifestations of measles such as cough, coryza, and conjunctivitis were documented in 45 (84.90%), 43 (81.13%), and 32 (60.37%) children, respectively. Specifically, two (3.77%), 14 (26.41%), 20 (37.73%), and 17 (32.07%) individuals were categorized as belonging to the upper middle, lower middle, upper lower, and lower socioeconomic strata. Six children in the nine- to 12-month age range had not received the measles-rubella (MR) vaccination. Thirteen (54.16%) out of 24 children aged one to five years had not received a single dose of the vaccine, while the children who had received at least one dose did not experience any complications. Among children aged less than nine months, nine to 12 months, and more than 12 months, three (100%), two (66.6%), and three (75%) respectively, experienced complications. All the patients recovered completely and were discharged from the hospital. Conclusion Measles is re-emerging as an infectious disease among children, as evidenced by the current outbreak. Study indicates that measles tends to impact infants and under five children more frequently. Through prompt and suitable medical intervention, all affected children experienced full recovery. It was observed that immunized children had fewer complications in comparison to their non-immunized counterparts. Acquiring a thorough understanding of the clinical profile of the illness is crucial for policymakers in developing essential guidelines for measles immunization coverage.

Seroprevalence and age-related susceptibility of TORCH infections in childbearing age women: A 5-year cross-sectional retrospective study and a literature review.

BACKGROUND: Serodiagnosis of TORCH infections should be performed in pre-pregnancy and reproductive-age women to prevent vertical transmission. Herein, we conducted a 5-year cross-sectional retrospective study in childbearing age women to provide prevalence data. Also, stratifying the cohort into three age groups, we identified those most susceptible to acute TORCH infections. METHODS: Between 2019 and 2023, serum samples from 2286 childbearing age women attending the "R. Dulbecco" University Hospital of Catanzaro were collected. Screening for TORCH pathogens, such as: Toxoplasma gondii (TOX), Cytomegalovirus (CMV), Rubella Virus (RUB), Parvovirus B19 (ParvoB19), Herpes Simplex Virus types 1 and 2 (HSV1, HSV2) and Treponema pallidum was carried out using serological tests. Chemiluminescent immunoassay was performed to detect TOX, CMV and ParvoB19 Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibodies, while Enzyme Linked Fluorescent Assay was performed to detect RUB IgM and IgG antibodies and CMV and TOX IgG Avidity. Enzyme Linked Immunosorbent Assay was performed to detect HSV1 IgG, HSV2 IgG, HSV1/2 IgM, T. pallidum total antibodies and RUB IgG Avidity. Binomial logistic regression models were developed to compare seroprevalence rates among different age groups. RESULTS: The highest immunological protection was observed for RUB infection (87 %), probably associated with vaccination practice, followed by HSV1 and CMV (82 % and 63 %). The 16-25 year age group results as the most susceptible to acute infections as demonstrated by odds of CMV IgM positivity (primary infection) which decreased with age. CONCLUSIONS: The TORCH serological screening program should be implemented in women before pregnancy to formulate strategies for serological screening of childbearing age women and guiding clinicians in making decisions.

Comparison of measles plaque reduction neutralization test (PRNT) and measles virus-specific IgG ELISA for assessment of immunogenicity of measles-mumps-rubella vaccination at 5-7 months of age and maternal measles antibodies.

Background: Assessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6-12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants < 9 months of age is lacking. Methods: A commercially available ELISA kit (Creative Diagnostics, DEIA359) for estimating measles seroprotection was evaluated in infants 5-7 months of age. In an immunogenicity substudy in the Danish MMR trial conducted between 2019-2021, infants (and mothers at baseline) were sampled before and one month after measles-mumps-rubella vaccination (MMR) or placebo as well as one month after routine MMR at 15 months. Measles IgG ELISA was compared to the gold standard but labor-intensive measles plaque reduction neutralization test (PRNT) by Pearson and Spearman correlations and by estimating sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Findings: Measles IgG levels compared to PRNT antibodies had a Pearson's correlation coefficient between 0.10-0.24. Seroprotection rates measured by ELISA in young infants were 10-14% lower than measured by PRNT. The sensitivity of the ELISA to detect serological protection compared to PRNT in the infant population differed markedly across sampling time points and was 14%, 40%, and 92% at baseline, post-intervention, and post-routine MMR, whereas the specificity was 99%, 93%, and 43%, respectively. The PPV and NPV were 68% and 87% in infants at baseline. Interpretation: The correlation between measles IgG and PRNT antibodies was low. Seroprotection was underestimated using ELISA. High-accuracy tests are needed to avoid misclassifications and practices that lead to primary or secondary vaccine failure or retention of vaccination in outbreak settings. Baseline PPV and NPV suggested some applicability of ELISA in predicting serological protection in this age group. However, PRNT may be the only accurate estimator of serological protection in young infants.

CSF-profile and hypocretin levels in children with narcolepsy type 1 and 2.

BACKGROUND: Narcolepsy is a rare neurological disease caused by dysfunction of hypocretin-producing neurons. Hypocretin concentrations in the cerebrospinal fluid (CSF) of less than 110 pg/ml are considered pathological in adults. OBJECTIVES: To compare hypocretin levels of children with narcolepsy type 1, type 2 and disease control groups, in addition to a detailed CSF analysis, clinical and polysomnographic parameters. METHODS: In a retrospective, cross-sectional study, children diagnosed with narcolepsy based on clinical and polysomnographic parameters, who received a CSF analysis and hypocretin measurement, in addition to controls, were included. CSF was analyzed for the presence of cells, total protein, lactate, intrathecal synthesis of antibodies against measles, rubella and/or varicella zoster, and oligoclonal bands. All children had a complete sleep study including a multiple sleep latency test (MSLT). RESULTS: 49 children with narcolepsy type 1, 15 children with type 2 and 37 children with other (suspected) neurological diseases were included. CSF routine analysis did not reveal any differences between the three groups. All children with narcolepsy type 1 had hypocretin levels of less than 110 pg/ml (range: 10-101 pg/ml). Hypocretin levels in type 2 patients ranged from 43 to 436 pg/ml (median 157 pg/ml). The median hypocretin level in the control cohort was 365 pg/ml (range: 153-583 pg/ml). In 4 children with narcolepsy type 2 the diagnosis was changed to narcolepsy level 1 because of a CSF hypocretin level of less than 110 pg/ml according to the recently proposed criteria, which consider the measurement of hypocretin in CSF. CONCLUSION: Children with narcolepsy type 1 showed significantly lower CSF hypocretin levels than children with narcolepsy type 2 and controls. As suggested by the recently published narcolepsy criteria, hypocretin levels of less than 110 pg/ml should be used as an additional criterion for the presence of narcolepsy type 1 in children.

Antenatal screening - The roles of medical and family history, routine tests, and examination findings.

Routine antenatal care includes history, examination, and several standard laboratory tests. Other than the original objectives, the generated data is seldom utilised for screening for adverse obstetric and perinatal outcomes. Although new approaches and sophisticated tests improve prediction of complications such as pre-eclampsia, these may not be available globally. Maternal age, race/ethnicity, anthropometry, and method of conception can influence the occurrence of pregnancy complications. The importance of medical and obstetric history is well documented but often ignored. Routine test results including blood picture, hepatitis B and rubella serology, and sexually transmitted diseases, have additional health implications. The awareness of, and the ability to utilise, available antenatal data and tests in obstetric management will enhance individualised obstetric risk assessment thus facilitating the targeting of high-risk gravidae for further management, including the use of specific and technology-driven tests where available, and close monitoring and treatment, in a cost-effective manner.

Associations of parental education with children's infectious diseases and their mediating factors: the Japan Environment and Children's Study (JECS).

BackgroundParents' educational background is presumed to influence the incidence of vaccine-preventable diseases in children through their decisions about vaccinations and other family lifestyle choices. Regarding voluntary vaccination, a household's economic situation may also be associated with non-vaccination. Therefore, this study investigated the association between parental education and vaccine-preventable diseases (varicella, mumps, influenza [flu], pertussis, measles, and rubella) in children, which currently remains elusive.MethodsWe used datasets from the Japan Environment and Children's Study, which included 104,062 fetal records; our study population comprised 80,930 children up to the age of three years. The associations between parental educational background and children's infectious diseases were examined using binomial logistic regression analysis. The mediating effects of household income, vaccination, and smoking were examined using a path analysis.ResultsFor varicella, mumps, and influenza covered by voluntary vaccination, a higher education level of the father was associated with a lower incidence of infection. The association between mothers' education and children's infection was limited. There were both income-mediated and non-income-mediated pathways between parental education and voluntary vaccination. For pertussis, measles, and rubella, which are covered by routine vaccines, there was no association between parental education and the child's infection.ConclusionAn association between parental education and childhood infections was observed. Additionally, providing financial support for vaccination and communicating the benefits of vaccination in a way that parents at all levels of education can understand will help reduce the incidence of infectious diseases among children.

Systematic review on molecular detection of congenital and neonatal infections caused by TORCH and SARS-CoV-2 in newborns' cerebrospinal fluid.

OBJECTIVE: To verify the use and identify advantages of molecular methods for congenital infections diagnosis in cerebrospinal fluid of neonates. DATA SOURCE: The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO), under CRD42021274210. The literature search was performed in databases: PubMed, Virtual Health Library/ Latin American and Caribbean Center on Health Sciences Information (VHL/BIREME), Scopus, Web of Science, Excerpta Medica database (EMBASE), Cochrane, ProQuest, and EBSCOhost. The search was carried out from August to October 2021 and updated in December 2022, respecting the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The selection sequence was: 1) Duplicate title removal; 2) Examination of titles and abstracts; 3) Full-text retrieval of potentially relevant reports; and 4) Evaluation of the full text according to eligibility criteria by two independent authors. Inclusion criteria considered randomized and non-randomized control trials, longitudinal, cross-sectional, and peer-reviewed studies in humans, published in English, Spanish, Italian, and Portuguese, with newborns up to 28 days old who had congenital neuroinfections by toxoplasmosis, rubella, cytomegalovirus, herpes simplex (TORCH), and others such as Treponema pallidum, Zika, parvovirus B-19, varicella zoster, Epstein-Barr, and SARS-CoV2, diagnosed by polymerase chain reaction (PCR). Two evaluators extracted the following information: author, year of publication, nationality, subjects, study type, methods, results, and conclusion. DATA SYNTHESIS: The most studied pathogen was herpes simplex. Several articles reported only nonspecific initial symptoms, motivating the collection of cerebrospinal fluid and performing PCR for etiological investigation. CONCLUSIONS: Molecular methods are effective to detect pathogen genomes in cerebrospinal fluid, which can impact clinical evolution and neurological prognosis.

Orientaciones para la búsqueda activa de casos de parálisis flácida aguda, sarampión y rubéola

La búsqueda activa es un instrumento de control de calidad de la vigilancia epidemiológica de rutina, pues permite detectar casos de enfermedades prevenibles por vacunación (EPV) que, por cualquier razón, pueden o no haber sido notificados al sistema. Tradicionalmente, la búsqueda activa se ha implementado de forma individual para documentar la ausencia o presencia de casos de parálisis flácida aguda (PFA), sarampión y rubéola, durante la vigilancia de rutina o ante la presencia de brotes. En este sentido, la búsqueda activa de casos de PFA, sarampión y rubéola es realizada en los establecimientos de salud (búsqueda activa institucional [BAI]), en las comunidades (búsqueda activa comunitaria [BAC]), y en los laboratorios (búsqueda activa por laboratorio [BAL]) a fin de identificar oportunidades para mejorar la sensibilidad del sistema de vigilancia epidemiológica de las EPV. Los casos detectados en la búsqueda activa deben notificarse, investigarse y clasificarse de acuerdo con las definiciones de casos recomendadas para la vigilancia de estas enfermedades. El propósito de esta publicación es brindar orientaciones técnicas e instrumentos de recolección de datos para realizar la búsqueda activa integral de PFA, sarampión y rubéola a nivel institucional (establecimientos de salud) y comunitario. La implementación conjunta de la búsqueda activa para estas tres enfermedades apunta a lograr una sinergia de los recursos humanos y financieros, según las consideraciones específicas de cada enfermedad. La publicación está dirigida a los profesionales de la salud de los niveles nacionales y subnacionales que son responsables de organizar e implementar la búsqueda activa en los establecimientos de salud y la comunidad, incluido el análisis de sus resultados y la elaboración del informe.

Immunization in the Americas: 2023 Summary

The countries of the Americas, with support from PAHO, have made remarkable progress in providing children with an umbrella of protection against basic vaccine-preventable diseases. Sustained high national immunization coverage levels, the eradication of polio, the interruption of endemic measles virus transmission, and efforts towards rubella and congenital rubella syndrome elimination are hemispheric benchmarks of this progress. Since 2020, the Region has also been facing the COVID-19 pandemic and major efforts have been taken to ensure administration of COVID-19 vaccines across all countries. Countries are now vaccinating age groups outside those usually targeted in the traditional childhood immunization program. Introducing seasonal influenza vaccine in adult populations at risk, vaccinating adolescents and adults, men, and women for rubella elimination, and defining the disease burden of cervical cancer are activities that support the critical need for national immunization programs to transition from child to family immunization. In support to countries, one of PAHO's roles is to disseminate information that can highlight progress and challenges faced in the Region. To that end, PAHO regularly publishes several technical documents related to immunization. The annually published "Immunization in the Americas" brochure summarizes immunization coverage in the Region of the Americas, in addition to illustrating the work done by the Region’s immunization programs for that year. Immunization in the Americas: 2023 Summary includes tables with the Region's demographic, morbidity, program management, financing, and socioeconomic data, as well as reported immunization coverage and surveillance indicators, among other items.

Orientaciones para la búsqueda activa de casos de parálisis flácida aguda, sarampión y rubéola / Guidelines for active case finding of acute flaccid paralysis, measles and rubella

La presente publicación describe las orientaciones técnicas e instrumentos de recolección de datos para realizar la búsqueda activa integral de parálisis flácida aguda, sarampión y rubéola a nivel institucional (establecimientos de salud) y comunitario. La implementación conjunta de la búsqueda activa para estas tres enfermedades pretende lograr una sinergia de los recursos humanos y financieros, tomando en cuenta las consideraciones específicas de cada enfermedad. Asimismo, presenta, en los anexos, los diagnósticos diferenciales e instrumentos de recolección de datos para otras enfermedades prevenibles por vacunación como difteria, tétanos, tétanos neonatal y tos ferina, en caso de que el país tenga interés en incluir alguna de estas enfermedades durante la implementación de la búsqueda activa

Technology versus nostalgia; A randomized controlled trial of the effect of virtual reality and kaleidescop on pediatric pain, fear and anxiety management during immunization.

BACKGROUND: Routine vaccination procedures, while crucial for public health, can induce pain, fear, and anxiety in children. Distraction techniques such as virtual reality and kaleidoscope have been proposed to alleviate these negative experiences during vaccinations. OBJECTIVE: This study aimed to compare the effectiveness of virtual reality and kaleidoscope as distraction methods in reducing pain, fear, and anxiety during routine vaccination in children aged 48 months. DESIGN: This randomized controlled trial allocated children aged 48 months receiving the measles-mumps-rubella vaccine into three groups: virtual reality (n = 42), kaleidoscope (n = 42), and control (n = 42). SETTING(S): The study was conducted in a pediatric clinic. PARTICIPANTS: The study included a total of 126 children aged 48 months. METHODS: Pain and fear levels were assessed by both researchers and children before and after the vaccination procedure, while anxiety was evaluated by children after vaccination. Pain was measured using the Wong Baker Faces Pain Rating Scale, fear with the Children's Fear Scale, and anxiety with the Child Anxiety Scale-State Version. RESULTS: Post-vaccination pain, fear, and anxiety scores were significantly lower in the kaleidoscope group compared to both the virtual reality and control groups (p < .05). CONCLUSIONS: Using kaleidoscope during vaccination in 48-month-old children effectively reduced pain, fear, and anxiety. Integrating kaleidoscope as a distraction method during routine vaccination procedures may enhance the vaccination experience and potentially improve adherence to vaccination schedules. REGISTRATION: Clinical trials number is NCT0611XXXX.

Epidemic in the time of the COVID-19 pandemic: News media framing of the MMR vaccination controversy in Serbia.

Rising vaccine hesitancy is often related to negative vaccination media coverage. It is generally accepted that the media played a great role in spreading the MMR (measles, mumps, and rubella) childhood vaccination scare first in the UK and then worldwide. During the COVID-19 pandemic, the MMR vaccination rate dropped further in some countries. This paper examines the Serbian news media framing of the MMR vaccination controversy in the period 2019-2023 (periods of declining MMR vaccination rate, rising COVID-19 vaccine hesitancy and the 2023 measles outbreaks). Furthermore, the paper questions whether the COVID-19 pandemic influenced the MMR vaccine narrative in the newspapers. For this reason, quality content analysis of the press in combination with framing approaches (diagnostic-prognostic-motivational framing tasks and responsibility framing) were used. In total, 122 articles dealing with the MMR vaccine and measles epidemics were analysed. According to the press, the most significant cause of the declining MMR rate is anti-vaccination campaigns and conspiracy theories by the "anti-vax lobby" (diagnostic frames). The pandemic was the other significant cause for the intake drop. Achieving herd immunity through vaccine uptake is offered as the best solution (prognostic frames). Finally, MMR vaccination campaigns and penalties for non-compliant parents and vaccine refusers are proposed as calls to action (motivational frames). During this period, the press did not publish any "sensational anti-vax stories". Considering the low MMR vaccine numbers in Serbia in this period, positive media messages did not have a significant influence on improving the vaccination rate. Thus, I suggest that Serbian parents distrust vaccination information presented by the dominant news, including the advice of health experts.

Wells syndrome following vaccination: A pediatric case with positive patch test to gelatin.

We report a 12-month-old boy with a skin eruption that developed 15 days after receiving the measles, mumps, rubella (MMR), pneumococcal, and meningococcal vaccines, consistent with the diagnosis of Wells syndrome. Patch testing showed a positive reaction to gelatin, which is used as a stabilizer for both live and inactivated vaccines. Gelatin was only present in the MMR vaccine.

Cytokine Storm Syndrome Associated with Hemorrhagic Fever and Other Viruses.

A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16. CSS associated with COVID-19 is also discussed separately (Chapter 22). This chapter will focus on other viruses including the hemorrhagic fever viruses, influenza, parainfluenza, adenovirus, parvovirus, hepatitis viruses, measles, mumps, rubella, enterovirus, parechovirus, rotavirus, human metapneumovirus and human T-lymphotropic virus. The published literature consists of many single case reports and moderate-sized case series reporting CSS, in most circumstances meeting the 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). There is no published clinical trial evidence specifically for management of HLH associated with these viruses. In some situations, patients received supportive therapy and blood product transfusions only but in most cases, they were treated with one or more of intravenous corticosteroids, intravenous immunoglobulin and/or etoposide. These were successful in many patients although in significant numbers progression of infection to CSS was associated with mortality.

Health and Economic Benefits of Routine Childhood Immunizations in the Era of the Vaccines for Children Program - United States, 1994-2023.

Since 1994, the U.S. Vaccines for Children (VFC) program has covered the cost of vaccines for children whose families might not otherwise be able to afford vaccines. This report assessed and quantified the health benefits and economic impact of routine U.S. childhood immunizations among both VFC-eligible and non-VFC-eligible children born during 1994-2023. Diphtheria and tetanus toxoids and acellular pertussis vaccine; Haemophilus influenzae type b conjugate vaccine; oral and inactivated poliovirus vaccines; measles, mumps, and rubella vaccine; hepatitis B vaccine; varicella vaccine; pneumococcal conjugate vaccine; hepatitis A vaccine; and rotavirus vaccine were included. Averted illnesses and deaths and associated costs over the lifetimes of 30 annual cohorts of children born during 1994-2023 were estimated using established economic models. Net savings were calculated from the payer and societal perspectives. Among approximately 117 million children born during 1994-2023, routine childhood vaccinations will have prevented approximately 508 million lifetime cases of illness, 32 million hospitalizations, and 1,129,000 deaths, at a net savings of $540 billion in direct costs and $2.7 trillion in societal costs. From both payer and societal perspectives, routine childhood vaccinations among children born during 1994-2023 resulted in substantial cost savings. Childhood immunizations continue to provide substantial health and economic benefits, while promoting health equity.