MMR vaccination timing and long-term immunity among childhood cancer survivors.

Long-term seroprotection against the measles and mumps viruses has not been reported in childhood cancer survivor (CCS) who received two-lifetime doses of the measles, mumps, and rubella (MMR) vaccine. We performed a retrospective study of measles and mumps titers among 55 CCS who received standard chemotherapy and two MMR vaccinations at any time. Over 75% of CCS who received at least one MMR prior to their cancer diagnosis had a negative or equivocal titer to measles or mumps. In contrast, all CCS who received the MMR series following their cancer treatment demonstrated long-term seroprotection to both viruses at a mean of 8.2 years after their last vaccination.

Innovations in vaccine delivery: increasing access, coverage, and equity and lessons learnt from measles and rubella elimination.

Disease eradication and elimination programs drive innovations based on progress toward measurable objectives, evaluations of new strategies and methods, programmatic experiences, and lessons learned from the field. Following progress toward global measles elimination, reducing measles mortality, and increasing introductions of measles and rubella vaccines to national programs, the measles and rubella immunization program has faced setbacks in recent years. Currently available vaccine delivery methods have complicated logistics and drawbacks that create barriers to vaccination; innovations for easier, more efficient, and safer vaccine delivery are needed. Progress can be accelerated by new technologies like microarray patches (MAPs) that are now widely recognized as a potential new tool for enhancing global immunizations efforts. Clinical trials of measles-rubella vaccine MAPs have begun, and several other vaccine MAPs are in the pre-clinical development pathway. MAPs could significantly contribute to Immunization Agenda 2030 priorities, including reaching zero-dose children; increasing vaccine access, demand, coverage, and equity; and achieving measles and rubella elimination. With strong partnerships between public health agencies and biotechnology companies, translational novel vaccine delivery systems can be developed to help solve public health problems and achieve global health priorities.

Applying sequential surveillance methods that use regression adjustment or weighting to control confounding in a multisite, rare-event, distributed setting: Part 2 in-depth example of a reanalysis of the measles-mumps-rubella-varicella combination vaccine and seizure risk.

OBJECTIVE: In-depth example of two new group sequential methods for postmarket safety monitoring of new medical products. STUDY DESIGN AND SETTING: Existing trial-based group sequential approaches have been extended to adjust for confounders, accommodate rare events, and address privacy-related constraints on data sharing. Most adaptations have involved design-based confounder strategies, for example, self-controlled or exposure matching, while analysis-based approaches like regression and weighting have received less attention. We describe the methodology of two new group sequential approaches that use analysis-based confounder adjustment (GS GEE) and weighting (GS IPTW). Using data from the Food and Drug Administration's Sentinel network, we apply both methods in the context of a known positive association: the measles-mumps-rubella-varicella vaccine and seizure risk in infants. RESULTS: Estimates from both new approaches were similar and comparable to prior studies using design-based methods to address confounding. The time to detection of a safety signal was considerably shorter for GS IPTW, which estimates a risk difference, compared to GS GEE, which provides relative estimates of excess risk. CONCLUSION: Future group sequential safety surveillance efforts should consider analysis-based confounder adjustment techniques that evaluate safety signals on the risk difference scale to achieve greater statistical power and more timely results.

Outcomes for Nitazoxanide Treatment in a Case Series of Patients with Primary Immunodeficiencies and Rubella Virus-Associated Granuloma.

PURPOSE: Nitazoxanide was recently reported as having in vitro effectiveness against the rubella virus. Immunodeficiency-related vaccine-derived rubella occurs in some patients who have an inherited immunodeficiency and who received the MMR vaccine. This study investigated the in vivo effectiveness of nitazoxanide therapy. METHODS: This is a retrospective analysis of seven patients treated with nitazoxanide as salvage therapy for immunodeficiency-related vaccine-derived rubella infection. The patients were recruited from an ongoing rubella detection surveillance project. RESULTS: Seven patients with persistent rubella were treated with nitazoxanide and one demonstrated significant clinical improvement. Two additional patients exhibited diminished viral capsid production with one patient having transient slowing of progression. The cohort overall generally had low T cell counts and had a high burden of comorbidities. There were three deaths. Two deaths were from PML and one was related to hematopoietic stem cell transplantation. CONCLUSIONS: Nitazoxanide has limited in vivo anti-viral effects for immunodeficiency-related vaccine-derived rubella. Most patients did not exhibit clinical improvement.

Review for Disease of the Year: Treatment of Viral Anterior Uveitis: A Perspective.

PURPOSE: To define a clinically tailored therapeutic strategy for the treatment of viral anterior uveitis (VAU). METHODS: A PubMed search spanning the past 5 years was conducted using the MesH-terms "viral anterior uveitis" and "therapy." RESULTS: The herpes simplex virus (HSV), the varicella zoster virus (VZV), and the cytomegalovirus (CMV) are the predominant pathogens in VAU. Other viruses, including rubella, chikungunya, and zika, have been linked with distinct forms of the disease. Depending on the causative agent and the host immunocompetence, the mainstay treatment for suspected VAU is a combination of topical or systemic antivirals and topical corticosteroids, supplemented with cycloplegics and intraocular-pressure-lowering medication. CONCLUSIONS: Oral acyclovir, valacyclovir, and famciclovir are the mainstay of treatment for HSV- and VZV-induced infections. Brivudin serves as an alternative in insufficiently responsive cases. CMV-induced infections respond well to valganciclovir. A 3- to 12-month course of prophylactic treatment against recurrences is worth considering.

Vacuna contra sarampión rubeola y paperas y su asociación con autismo: a 20 años de controversia / Vaccine against measles mumps and rubella and its association with autism: 20 years of controversy

Resumen En la presente revisión se ofrecen las pautas éticas que rigen el esquema con que debe ser aplicada la vacuna triple contra Sarampión Rubeola y Paperas. Se hace énfasis en la falta de datos clínicos que hayan asociado esta vacuna con el desarrollo de autismo en niños y se expone con base en evidencia científica los riesgos de la no vacunación en este grupo etario.

Abstract In the present review is offered the ethical guidelines that govern the scheme with which the triple vaccine against Measles Rubella and Mumps must to be applied. It emphasizes the lack of clinical data that have associated this vaccine with the development of autism in children and exposes based on scientific evidence the risks of non-vaccination in this age group.

Inhibition of rubella virus replication by the broad-spectrum drug nitazoxanide in cell culture and in a patient with a primary immune deficiency.

Persistent rubella virus (RV) infection has been associated with various pathologies such as congenital rubella syndrome, Fuchs's uveitis, and cutaneous granulomas in patients with primary immune deficiencies (PID). Currently there are no drugs to treat RV infections. Nitazoxanide (NTZ) is an FDA-approved drug for parasitic infections, and has been recently shown to have broad-spectrum antiviral activities. Here we found that empiric 2-month therapy with oral NTZ was associated in the decline/elimination of RV antigen from lesions in a PID patient with RV positive granulomas, while peginterferon treatment had no effect. In addition, we characterized the effects of NTZ on cell culture models of persistent RV infection. NTZ significantly inhibited RV replication in a primary culture of human umbilical vein endothelial cells (HUVEC) and Vero and A549 epithelial cell lines in a dose dependent manner with an average 50% inhibitory concentration of 0.35 µg/ml (1.1 µM). RV strains representing currently circulating genotypes were inhibited to a similar extent. NTZ affected early and late stages of infection by inhibiting synthesis of cellular and RV RNA and interfering with intracellular trafficking of the RV surface glycoproteins, E1 and E2. These results suggest a potential application of NTZ for the treatment of persistent rubella infections, but more studies are required.

[Adult-onset opsoclonus-myoclonus-ataxia syndrome revealing rubella meningoencephalitis]. / Syndrome opsoclonus-myoclonus-ataxie révélant une méningo-encéphalite rubéolique chez un adulte.

INTRODUCTION: Opsoclonus-myoclonus-ataxia (OMS) is a rare clinical syndrome, of paraneoplastic infectious, post-infectious, post-vaccinal or idiopathic origin. CASE REPORT: We report a 24-year-old young man who presented with gait disorder preceded by a febrile rash and retroauricular lymph nodes. Three days before admission, he had headache, vertigo, nausea and vomiting followed by gait unsteadiness and movement disorders of limbs and eyes. On examination, he had OMS syndrome. Brain MRI, total body scan, MIBG scintigraphy, tumor markers and onconeural antibodies were normal. Cerebro-spinal fluid (CSF) analysis showed lymphocytic meningitis. Positive serum and CSF immunoglobulin M antibody against rubella virus was demonstrated. He received acyclovir with full recovery within two weeks. We discuss the peculiarities of this association with a literature review. CONCLUSION: This observation enlarges the spectrum of neurological manifestations of rubella as well as that of OMS etiologies.

[A case of rubella encephalitis presenting as clinically mild encephalitis/encephalopathy with a reversible splenial lesion].

A 26-year-old male was admitted because of a fever, headache and disturbance of consciousness with lymph node swelling of the neck two days after developing a rash. A neurological examination revealed restlessness with irritability in response to sensory stimuli, such as an injection. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed a hyperintense ovoid lesion in the splenium of the corpus callosum, which showed a low coefficient in the ADC map: the lesion disappeared after 22 days. An enzyme immunoassay (EIA) of the serum and cerebrospinal IgM were positive for rubella virus. The patient was therefore diagnosed with rubella encephalitis. He recovered gradually and was discharged on day 19 after the onset of symptoms without any sequelae. To our knowledge, this is the first case of rubella encephalitis presenting as clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). Although the exact mechanism underlying the development of rubella encephalitis is not well established, this case indicated that our patient had an immune-mediated secondary encephalitis. According to the survey of the pandemic of rubella from 2012 to April 2013 in Japan, the incidence of rubella encephalitis is thought to be relatively higher than was previously noted. This emphasizes the importance of vaccination for preventing encephalitis.

[Influence of TORCH-infections on the spermatogenesis of men].

The purpose of the given study was to reveal causal relations between infection of the urino-genital tract by intracellular parasites, the so-called TORCH-infections, and the decrease of spermatogenesis. For observation 182 men of reproductive age (from 22 to 38 years) with oligozoospermia and aspermia, without any complaints or clinical symptoms indicating existence of infections of urino-genital tracts, were selected. Out of those, 131 revealed oligozoospermia, i.e. the quantity of spermatozoons was no higher than 20 mln in 1 ml of ejaculate, and 51 revealed - aspermia. For examination of some TORCH infections, medical doctors in charge directed 44 oligozoospermia patients and 15 aspermia patients, who respectively constituted group I and group II. Examinations were carried out for Chlamydia trachomatis--(Ch.t), Herpes simplex virus--(HSV), Ureaplasma urealiticum--(U.u.), Cytomegalovirus--(CMV), and Mycoplasma hominis--(M.h.). In the group with oligozoospermia, cases of infections by Chlamydias (41.5%) and Herpes virus (51.3%) were frequent, but Ureaplasma (56,5%) was more frequent than any infections. Cytomegalovirus occurred in the least number of cases. Making any conclusions on the frequency of infections by M.h. is difficult due to the low number of examinations. Similar picture was observed in Group II as well. Following successful treatment of infections in Group I, 8 patients with Ch.t. and 8 patients with U.u. showed an improved spermogram after several months. Treatment of other infections did not yield tangible results. In Group II spermatogenesis remained without any changes.

Fetal infections and brain development.

Current microbial diagnostics enable rapid and specific identification of the agents causing intrauterine and perinatal infections, and CT and MRI allow precise characterization of the central nervous system effects of these pathogens. Although infections with Toxoplasma gondii, Toxoplasma pallidum, Toxoplasma cruzi, and cytomegalovirus cannot currently be prevented by immunization, postnatal therapy of infected neonates can substantially improve outcome. Therapy with acyclovir should be initiated whenever perinatal herpes simplex virus encephalitis is suspected. Despite these strategies, intrauterine and perinatal infections remain major causes of permanent deafness, vision loss, cerebral palsy, and epilepsy among children throughout the world.

[Clinical and experimental study on effects of huanglan granule in inhibiting rubella virus].

OBJECTIVE: To explore the therapeutic effect and acting mechanism of Huanglan Granule (HLG) on rubella virus (RuV). METHODS: Sixty patients with positive RuV-IgM were randomly assigned to two groups equally, the treatment group was medicated by HLG (one dosage per day, containing milkvetch root, isatis root and basket fern, each 30 g), while the control group by ribavirin (0.2 g, three times per day) for 20 days. The negative conversion rate of RuV-IgM and the serum levels of interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) were observed before and after treatment. Moreover, the in vitro inhibitory activity of HLG against RuV Gos line on cultured Vero cells was determined by cytopathic inhibition method. RESULTS: The difference of negative conversion rate between the two groups after one course treatment was significant (86.7% vs 63.3%, P <0.05). However, it turned to insignificant after two courses of treatment (100% vs 86.7%, P >0.05). The serum level of IL-2 was lower and TNF-alpha was higher significantly in patients with positive RuV-IgM as compared with the normal range, and the two indexes returned to the normal range rapidly after HLG treatment. In vitro study showed that the inhibitory effect of HLG on RuV caused cellular change was evident. CONCLUSION: HLG has obvious inhibitory effect on RuV, both in vitro and in vivo, it can also raise the immunity of organism and thus it serves as a safe and effective Chinese medicine for treatment of active RuV infection.

Rubella in pregnancy.

OBJECTIVE: To provide an update on rubella and pregnancy so that health professionals remain aware of the potentially devastating effects on the developing fetus. OUTCOMES: Rubella vaccination has been effective in virtually eliminating congenital rubella syndrome in Canada. EVIDENCE: Medline, PubMed, and Cochrane Database were searched for articles published between 1985 and 2007. VALUES: The quality of evidence was rated using the criteria described in the report of the Canadian Task Force on Preventive Health Care. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.

Viral arthritis.

The role of viruses in the development of acute and chronic arthritis is complex, because viruses are ubiquitous, and all human beings are occasionally afflicted by viral infections. In general, most viral infections are acute and self-limiting and survive by infecting one susceptible host, then moving on to another. Some viruses establish prolonged latency in the host after acute infection, whereas other agents produce chronic infections following the primary stage. The mechanisms whereby these infections produce arthritis are diverse and still poorly understood, but are clearly influenced by both host and viral factors. This review addresses these and other common forms of viral arthritis, such as that caused by parvovirus B19.

Therapy of other viral infections: herpes to hepatitis.

Over the past several years, there has been an increase in knowledge pertaining to the diagnosis and management strategies for the herpes family (Types 1-8), the pox viruses, mumps, measles, rubella, and parvovirus B19 as well as the viral etiologies of hepatitis. Various antiviral treatments, such as nucleoside analogs and interferon therapy, have been available to reduce the signs and symptoms of these common viral infections. This article summarizes the preferred treatment strategies to be employed for each of the viruses for reducing severity, duration, recurrences (notably in the herpes family), transmission rates, as well as preventive alternatives. The majority of the therapeutic options attenuate the course of disease. Treatment decisions are driven by knowledge of the natural history and often are tailored to incorporate clinical circumstances for individual patients. Promotion of community awareness and the development of vaccines should be emphasized in the battle against these common viruses, particularly the herpes simplex viruses, the pox viruses, and hepatitis B.

Encephalitis and polyradiculoneuritis following rubella virus infection--a case report.

Amongst neurological complications of rubella virus infection, polyradiculoneuritis as well as encephalitis is very rare. Only one case of postrubella polyradiculoneuritis combined with encephalitis has been reported to our knowledge. A 17-years-old male presented with suspected meningoencephalitis in a recent epidemic of rubella in a southern district of Korea. He developed symmetrical hyporeflexic weakness of all four extremities with urinary disturbance several days later. Rubella IgM antibody titer (enzyme linked immunosorbent assay) was 58 AU/mL in serum and 12 AU/mL in cerebrospinal fluid. Electrophysiologic studies showed peripheral polyradiculoneuropathy with multifocal conduction block. Considering the involvement of the central nerve as well as the peripheral nerve in an adult patient, this case is thought to be valuable in view of the pathophysiology of neurologic complication in rubella virus infection.

Antiviral activity of natural and semisynthetic polysaccharides on the early steps of rubella virus infection.

The natural and semisynthetic carbohydrates scleroglucan, locust bean gum, tamarind gum (glyloid) and its three sulphate derivatives (GP4311, GP4327 and GP4324), glycogen and its two sulphate derivatives (GP4427 and GP4435), alginic acid and dextran sulphate, were investigated for their inhibitory effect on rubella virus (RV) infection of Vero cells. The neutral polymer scleroglucan and two highly negatively charged compounds, glyloid sulphate 4324 and dextran sulphate, had the highest inhibitory effect on RV antigen synthesis. The antiviral properties of active molecules appears to be dependent on the shape of the macromolecule and/or on the electric charge, while saccharide units play a minor role. The results indicated that polysaccharides blocked a step in virus replication subsequent to virus attachment, such as internalization and/or uncoating. Confirmation that the inhibitory activity of the compounds was directed at the early steps of RV multiplication, was that none of the polysaccharides had any effect on infection initiated by transfection of cells with RVRNA.