Protocols to Manufacture an Oncolytic Measles Virus-Sensitive Immunocompetent Mouse Model of Medulloblastoma.

Oncolytic virotherapy translational research in the current era is heavily focused on the interaction of the immune system and tumor microenvironment with oncolytic viruses. Preclinical xenograft studies using human cells in immunodeficient mouse models does not serve this purpose. As a consequence, developing syngeneic immunocompetent murine cancer models sensitive to infection and growth of specific oncolytic viruses is required. The group 3 subtype of medulloblastoma, among the four molecular subgroups-WNT, SHH, Group 3, and Group 4, has the worst prognosis and the poorest outcome. Sadly, current treatments cause long-term toxicity and morbidity to survivors adversely affecting their quality of life. Alternate effective therapy with less side effects is urgently needed. We have shown that oncolytic measles virus (MV) is effective against localized as well as CSF-disseminated medulloblastoma in immunodeficient mouse models. To study the interaction of immune system with oncolytic measles virotherapy, we have developed a murine group 3 medulloblastoma cell line (CSCG) that is infectible by MV, is killed by MV, allows replication of MV, and is tumorigenic in the brain of syngeneic transgenic immune-competent mice. Intratumoral injection of MV results in significant prolongation of survival in mice bearing CSCG tumors in the brain. This model provides the first suitable platform to examine therapeutic regimens of MV therapy for MB tumors in the presence of intact immune system. Here, we describe our lab protocols to develop this cell line and the mouse model.

Emerging and Re-emerging Infections in Children: COVID/ MIS-C, Zika, Ebola, Measles, Varicella, Pertussis ... Immunizations.

The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal.

Congenital Measles in a Premature 25-week Gestation Infant.

We describe a premature infant with congenital measles. Laboratory testing confirmed measles in the mother (polymerase chain reaction- and IgM-positive) and congenital measles in the infant (polymerase chain reaction-positive, culture-positive and IgM-positive). The infant never developed a rash, pneumonia, or neurologic complications. This case supports using compatible laboratory findings to diagnose congenital measles in infants without clinical manifestations of measles.

Measles epidemic in pediatric population in Greece during 2017-2018: Epidemiological, clinical characteristics and outcomes.

BACKGROUND AND AIM: A measles outbreak occurred in Greece during 2017-2018 affecting mainly pediatric population. The aim of the study was to describe the epidemiological and clinical characteristics of the cases diagnosed in the major pediatric tertiary hospital of Athens, where 26.5% of national pediatric measles cases were diagnosed and treated. METHODS: This is a retrospective study of children 0-16 years old, who presented at the emergency department and/or were hospitalized with clinical presentation compatible with measles and diagnosis was confirmed with molecular detection of the measles RNA in pharyngeal swabs. Epidemiological, clinical and laboratory characteristics were retrieved from medical records and analyzed. RESULTS: A total of 578 children with measles were identified during the study period. 322 (55.7%) were male with median age 36 months (range:1-193), while the largest number of documented cases (251; 43.4%) were children aged 1-5 years. Most children (429/578; 74.2%) belonged to the Roma minority and only 64 (11.1%) had Greek origin. 497 (91.5%) children were unvaccinated and 37 (6.8%) were partially vaccinated with measles vaccine. Hospitalization was required for 342 (59.2%) children, whereas one or more complications were reported in 230 (67.2%) of them. Most frequent complications were elevated transaminases (139; 40.6%), acute otitis media (72; 21%), dehydration (67; 19.6%) and pneumonia (58; 16.9%). 11 children (3.2%) required intensive care admission for altered mental status/status epilepticus (3), sepsis (2) and ARDS (6). 119/342 (34.8%) children were treated with antibiotics because of possible or confirmed bacterial coinfection. One death was reported, concerning an 11-month-old unvaccinated infant, with underlying dystrophy, who died of sepsis. CONCLUSION: Measles is not an innocent viral infection, as it is still characterized by high morbidity and complications rates. Unvaccinated or partially vaccinated populations could trigger new outbreaks, resulting in significant cost in public health. To avoid future measles outbreaks, high vaccination coverage should be achieved, as well as closing immunity gaps in the population and ensuring high-quality measles surveillance.

De curandis hominum morbis: An 18th century medical prescription for measles and smallpox in the Nuevo Reino de Granada / De curandis hominum morbis: una receta médica del siglo XVIII para el sarampión y las viruelas en el Nuevo Reino de Granada

A collection of more than one hundred medical recipes from the late 18th century was donated by Presbyter Cipriano Rodríguez Santa María, institutional eponym of the collection at the Historical Archive "Octavio Arizmendi Posada" of the library of the Universidad de La Sabana in Colombia. These texts represent an important historical and medical legacy and they constitute an important basis for understanding the colonial and traditional therapeutics related to various diseases. In this article, we describe one of these recipes for the treatment of smallpox and measles as a contribution to the history of medicine in Colombia.

En el Archivo Histórico de la Biblioteca "Octavio Arizmendi Posada" de la Universidad de La Sabana, se encuentra una colección de más de un centenar de recetas médicas de finales del siglo XVIII donadas por el presbítero Cipriano Rodríguez Santa María, epónimo institucional del archivo. Estos textos son un legado histórico médico y un fundamento para comprender la terapéutica colonial y tradicional de diversas enfermedades. En este artículo, se describen algunas recetas para el tratamiento de la viruela y el sarampión, como aporte a la historia de la medicina en Colombia.

Paediatric respiratory isolation: A challenge for a secondary care hospital! A service innovation project.

OBJECTIVE: The aim of this project was to broaden the secondary care hospital's scope of services and provide safe, effective and quality care for the patient presenting with measles. METHODS: Six Sigma DMAIC [define measure, analyze, improve, and control (DMAIC)] methodology was used in this quality improvement project. The quality project was started in October 2015 using a Gantt chart quality tool. RESULTS: The paediatric team with the support of administration of the hospital has established isolation rooms and devised a policy for the care and management of patient with airborne infection to avoid cross transmission. During six months period after establishment of isolation room there were sixty two suspected or confirmed measles cases who were admitted in our hospital, out of them only 4(6.4%) of patients were referred because of their sick condition and need of ventilator support. Further, the percentage of patient's satisfaction level also improved from 60 to 80%. CONCLUSIONS: After this clinical service innovation, there was significant reduction in referrals of measles patients to another hospital and consequently there was an increase in the patient's satisfaction.

Computational modelling and optimal control of measles epidemic in human population.

Measles is an awfully contagious acute viral infection. It can be fatal, causing cough, red eyes, followed by a fever and skin rash with signs of respiratory infection. In this paper, we propose and analyze a model describing the transmission dynamics of a measles epidemic in the human population using the stability theory of differential equations. The model proposed undergoes a backward bifurcation for some parameter values. Sensitivity analysis is carried out on the model parameters in order to determine their impact on the disease dynamics. We extend the model to an optimal control problem by including time-dependent control variables: prevention, treatment of infected people and vaccination of the susceptible humans. In an attempt to minimize the infected people and the cost applied we design the cost functional. Next, we show that optimal control exists for the system, and the Pontryagin maximum principle is employed to characterize the continuous controls. Numerical simulation is performed to justify the analytical results and discussed quantitatively.

Transverse myelitis following measles vaccination in a rhesus macaque (Macaca mulatta).

A 16-year-old rhesus macaque presented with progressive, ascending quadriparesis following measles vaccination. He was diagnosed with transverse myelitis following MRI, gross necropsy, and histopathology. This is the first report of transverse myelitis in a rhesus macaque following measles vaccination.

[Measles: from a simple rash - to a fatal outcome ?] / Rougeole: du « simple rash ¼ à l'issue fatale.

Measles is a disease that was considered as relegated to medical history, since an extremely efficient vaccine had been developed. However, in Switzerland and elsewhere there has been an increasing number of epidemics in the past years, and the highest number of new cases this year. Based on two clinical cases showing very different outcomes, we discuss the disease, its clinic, complications, management, and the challenges remaining in obtaining a sufficient vaccination coverage worldwide as well as in our country.

La rougeole est une maladie que l'on pensait pouvoir reléguer aux annales de la médecine, suite au développement d'un vaccin efficace. On assiste pourtant à une recrudescence d'épidémies en Suisse comme ailleurs, avec un nombre record de cas cette année. Sur la base de deux cas montrant des décours très différents, nous discutons la maladie, sa clinique, ses complications, sa prise en charge et les défis que pose encore la réalisation d'une couverture vaccinale efficace au niveau régional comme global.

Impact of the 2017 measles outbreak on the emergency care system of a large tertiary-care teaching hospital in Italy: a retrospective analysis.

BACKGROUND: A large outbreak of measles has spread across Italy over the year 2017. Its impact on emergency department (ED) of a tertiary-care teaching hospital and the related critical issues in public health were evaluated. METHODS: Medical records of adults discharged from January to December 2017 with diagnosis of 'measles' or 'measles suspicion' were collected and analyzed. RESULTS: From a total of 58 579 admissions, 218 medical records matched enrollment criteria. Measles infection was confirmed in 55.3% of patients, excluded in 26.2%, and judged as possible or probable in 18.3% of cases. Considered that the vaccination status was unknown in 89.2% of patients, the mean time spent in temporary isolation rooms (TIRs) waiting serological results was 1.7 ± 0.8 days. Measles-free patients spent a mean of 1.9 ± 0.9 days in TIRs, meaning a cumulative unnecessary time of isolation of 106.4 days. Despite most of patients were pauci-simptomatic and with a low burden of comorbidities, only 28.6% of them reported a previous out-of-hospital medical contact. Moreover an assessment of moderately critical conditions was assigned to 89.6% of cases, representing an over-valuation of the severity of the cases. Antibiotic therapy had been prescribed in 69.0% of cases and 57.7% of patients were hospitalized. We found no differences in terms of median time spent in TIRs, rate of hospitalization and antibiotic prescription between measles cases and measles-free patients. CONCLUSION: A preventable high-infective disease outbreak can lead to a misapply of ED facilities in terms of unjustified admissions, time spent in TIRs, antibiotic prescription and in hospitalization rate.

Knowledge and home treatment of measles infection by caregivers of children under five in a low-income urban community, Nigeria.

BACKGROUND:  Despite the availability of a safe and effective vaccine for over 50 years, measles remains a leading cause of death among young children in developing countries. AIM:  This study assessed the knowledge and home treatment of measles by caregivers of children under 5 years. SETTING:  Abebi community, Ibadan, Oyo State, Nigeria. METHODS:  A descriptive cross-sectional study of 509 caregivers of children aged 6 months to 5 years in a semi-urban community in Ibadan was conducted using a multi-stage sampling method. An interviewer administered structured questionnaire was used to collect information on socio-demographic characteristics, knowledge of aetiology, main symptoms and signs, and home treatment of measles. Chi-square test and logistic regression were used to explore associations at 5% level of significance. RESULTS:  Most of the caregivers were females (96.3%), married (86.1%) and were the biological parents of the children (90.9%). More than half had good knowledge of the cause (59.7%) and main symptoms and signs (52.8%) of measles. However, the composite knowledge was good in 57.6% of caregivers. Over half (54.4%) of the caregivers reported that their children ever had measles. Majority (91.3%) of caregivers whose children had measles gave home treatment, while 24 (8.7%) sought treatment from health facilities alone. There was a significant association between caregivers' educational status, age, tribe and marital status and their knowledge of measles; however, tribe was the only significant predictor of knowledge after regression analysis. Caregivers from other tribes were 3.3 times more likely to have good knowledge of measles than Yoruba caregivers. Caregivers who were 35 years and older compared to those younger than 35 years (OR: 0.625; 95% CI: 0.425-0.921) and those who were not currently married compared to those married (OR: 0.455; 95% CI: 0.273-0.758) had lower odds of having good knowledge of measles, respectively. CONCLUSION:  Home treatment by caregivers of children with measles is high. Health education on the cause, prevention and treatment of measles should be provided for caregivers.

[Dramatic achievements in infectious disease prevention and treatment in China during the past 70 years].

At the beginning of the founding of People's Republic of China, infectious diseases, such as smallpox, plague, cholera, dysentery, typhoid, measles, diphtheria, pertussis, meningitis, mumps, schistosomiasis, Kala Azar, hemorrhagic fever, leptospirosis, encephalitis B, typhus, malaria, Kala Azar, leprosy, scarlet fever and pinkeye, remained as epidemic in the country and endangered people's health. During the past 70 years, the Chinese government spent huge efforts in infectious disease prevention and treatment by promulgating and implementing series of relative policies, laws and strategies, and also encouraged all Chinese people to participate in. The achievements of these efforts in controlling infectious disease epidemic were extremely successful. Today, the outbreaks and epidemic of infectious diseases in China were rarely happened with the rapid decreases in incidence and mortality rates of all notifiable infectious diseases. Smallpox was eradicated, and polio, filariasis, leprosy and neonatal tetanus were nearly eradicated. In addition, the incidence rates of vaccine-preventable diseases, i.e. measles, diphtheria, pertussis, meningitis, encephalitis B, hepatitis A, mumps, rubella, tuberculosis, were dramatically decreased and remained at relatively low levels for years. The incidence and prevalence rates of hepatitis B infection in Children decreased significantly and reached the phase objectives. Moreover, incidence rates of natural iatrogenic infectious diseases, i.e. diarrhea, typhoid and other intestinal infectious diseases, leptospirosis and schistosomiasis, and vectorborne diseases, i.e. typhus, malaria, Kala Azar, reached the lowest and some even closed to be eliminated in China. In general, infectious diseases dropped to the tenth from the top one leading cause of all deaths, which means that the achievement of Chinese infectious disease prevention and treatment strategies contributed tremendously in improving Chinese people's health status and life expectancy.

Knowledge and home treatment of measles infection by caregivers of children under five in a low-income urban community, Nigeria

Background: Despite the availability of a safe and effective vaccine for over 50 years, measles remains a leading cause of death among young children in developing countries.Aim: This study assessed the knowledge and home treatment of measles by caregivers of children under 5 years.Setting: Abebi community, Ibadan, Oyo State, Nigeria.Methods: A descriptive cross-sectional study of 509 caregivers of children aged 6 months to 5 years in a semi-urban community in Ibadan was conducted using a multi-stage sampling method. An interviewer administered structured questionnaire was used to collect information on socio-demographic characteristics, knowledge of aetiology, main symptoms and signs, and home treatment of measles. Chi-square test and logistic regression were used to explore associations at 5% level of significance.Results: Most of the caregivers were females (96.3%), married (86.1%) and were the biological parents of the children (90.9%). More than half had good knowledge of the cause (59.7%) and main symptoms and signs (52.8%) of measles. However, the composite knowledge was good in 57.6% of caregivers. Over half (54.4%) of the caregivers reported that their children ever had measles. Majority (91.3%) of caregivers whose children had measles gave home treatment, while 24 (8.7%) sought treatment from health facilities alone. There was a significant association between caregivers' educational status, age, tribe and marital status and their knowledge of measles; however, tribe was the only significant predictor of knowledge after regression analysis. Caregivers from other tribes were 3.3 times more likely to have good knowledge of measles than Yoruba caregivers. Caregivers who were 35 years and older compared to those younger than 35 years (OR: 0.625; 95% CI: 0.425­0.921) and those who were not currently married compared to those married (OR: 0.455; 95% CI: 0.273­0.758) had lower odds of having good knowledge of measles, respectively. Conclusion: Home treatment by caregivers of children with measles is high. Health education on the cause, prevention and treatment of measles should be provided for caregivers