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- Infection of mice, ferrets, and rhesus macaques with a clinical mumps virus isolate. [JOURNAL ARTICLE]
- J Virol 2013 May 15.
In recent years, many mumps outbreaks have occurred in vaccinated populations worldwide. The reasons for these outbreaks are not clear. Animal models are needed to investigate the causes of outbreaks, as well as to understand the pathogenesis of mumps virus. In this study, we have examined the infection of three animal models with an isolate of mumps virus from a recent outbreak (MuV-IA). We have found that while both ferrets and mice generated humoral and cellular immune responses to MuV-IA infection, no obvious signs of illness were observed in these animals; rhesus macaques were most susceptible to MuV-IA infection. Infection of rhesus macaques via both intranasal and intratracheal routes with MuV-IA led to typical mumps clinical signs at 2 weeks to 4 weeks post-infection. However, none of the infected macaques showed any fever or neurologic signs during the experimental period. Mumps viral antigen was detected in parotid glands by immunohistochemistry (IHC). Rhesus macaques represent the best animal model for the study of mumps virus pathogenesis.
- Waning of Maternal Antibodies Against Measles, Mumps, Rubella, and Varicella in Communities With Contrasting Vaccination Coverage. [JOURNAL ARTICLE]
- J Infect Dis 2013 May 8.
Background.The combined measles, mumps, and rubella (MMR) vaccine has been successfully administered for >20 years. Because of this, protection by maternal antibodies in infants born to vaccinated mothers might be negatively affected.Methods. A large cross-sectional serologic survey was conducted in the Netherlands during 2006-2007. We compared the kinetics of antibody concentrations in children and women of childbearing age in the highly vaccinated general population with those in orthodox Protestant communities that were exposed to outbreaks.
Results.The estimated duration of protection by maternal antibodies among infants in the general population, most of whom were born to vaccinated mothers, was short: 3.3 months for measles, 2.7 months for mumps, 3.9 months for rubella, and 3.4 months for varicella. The duration of protection against measles was 2 months longer for infants born in the orthodox communities, most of whom had unvaccinated mothers. For rubella, mothers in the orthodox communities had higher concentrations of antibodies as compared to the general population.
Conclusions.Children of mothers vaccinated against measles and, possibly, rubella have lower concentrations of maternal antibodies and lose protection by maternal antibodies at an earlier age than children of mothers in communities that oppose vaccination. This increases the risk of disease transmission in highly vaccinated populations.
- [Measles vaccination campaign among vulnerable populations during the peak of the 2011 epidemic in Marseilles.] [JOURNAL ARTICLE]
- Rev Epidemiol Sante Publique 2013 May 6.
BACKGROUND:From 2008 to the end of 2011, Europe experienced a major outbreak of measles. The outbreak hit France especially hard, with measles hotspots in the South-East of France. It is known that people living in precarious socio-economic conditions are more exposed to infectious diseases. Regarding the local situation, the NGO "MdM-Marseille" decided to conduct a vaccination campaign among the Roma community living in camps.
METHODS:The campaign was planned with two injections of a combined measles, mumps and rubella vaccine (MMR) in a one month interval for all young people born since 1980 and over the age of one year, regardless of antecedents. Twenty-four camps were selected. The target population was estimated at 720 people. Each site was the subject of an information visit. A letter was sent to the Prefecture to inform them and ask for a moratorium on evictions for the identified camps.
RESULTS:Between May 15th and September 15th 2011, 326 primary immunizations were performed during 34 visits (covering 45.3% of the target population). Over the same period, almost all the camps were evacuated, forcing teams to stop the vaccination campaign. The second injection campaign covered only 37 persons.
CONCLUSION:The vaccination campaign among Roma populations in Marseilles was organized in a context of a major national outbreak of measles in the general population. Although the Prefecture was informed, camp evictions were not interrupted. This highlights the discrepancy between public health policy and security policy. In the context of an epidemic, innovative actions should be focused on vulnerable populations in partnership with health authorities. The main objective is to find procedures that can protect populations at risk in the event of a health crisis but which are also useful for routine prevention.
- Estimation of vaccine efficacy and critical vaccination coverage in partially observed outbreaks. [Journal Article]
- PLoS Comput Biol 2013 May; 9(5):e1003061.
Classical approaches to estimate vaccine efficacy are based on the assumption that a person's risk of infection does not depend on the infection status of others. This assumption is untenable for infectious disease data where such dependencies abound. We present a novel approach to estimating vaccine efficacy in a Bayesian framework using disease transmission models. The methodology is applied to outbreaks of mumps in primary schools in the Netherlands. The total study population consisted of 2,493 children in ten primary schools, of which 510 (20%) were known to have been infected, and 832 (33%) had unknown infection status. The apparent vaccination coverage ranged from 12% to 93%, and the apparent infection attack rate varied from 1% to 76%. Our analyses show that vaccination reduces the probability of infection per contact substantially but not perfectly ([Formula: see text] = 0.933; 95CrI: 0.908-0.954). Mumps virus appears to be moderately transmissible in the school setting, with each case yielding an estimated 2.5 secondary cases in an unvaccinated population ([Formula: see text] = 2.49; 95%CrI: 2.36-2.63), resulting in moderate estimates of the critical vaccination coverage (64.2%; 95%CrI: 61.7-66.7%). The indirect benefits of vaccination are highest in populations with vaccination coverage just below the critical vaccination coverage. In these populations, it is estimated that almost two infections can be prevented per vaccination. We discuss the implications for the optimal control of mumps in heterogeneously vaccinated populations.
- Circulation of Two Mumps Virus Genotypes in an Unimmunized Population in India. [JOURNAL ARTICLE]
- J Med Virol 2013 May 8.
Two separate outbreaks of fever with parotitis were reported from the Apsinga and Pimpla villages in the Osmanabad district of the Maharashtra State, India during February and March 2012. Meningo-encephalitis was noted in two patients resulting in the death of an 11-year male. Samples of blood and throat swabs were collected from patients with fever and parotitis. Serum samples from suspected (n = 62) and convalescent (n = 19) patients were tested for mumps virus specific IgM and/or IgG antibodies. Mumps virus specific IgM antibodies were detected in 44 of 62 serum samples (71%). Of the 19 convalescent phase sera 16 had both, anti-mumps virus IgM and IgG antibodies. Twenty-eight throat swabs collected from patients with parotitis were tested by RT-PCR for the SH gene. Twenty-three specimens were found to be positive and nucleotide sequencing of the amplified PCR products revealed circulation of two distinct genotypes that were village specific. Mumps virus genotype C (n = 18) was detected in Apsinga village and genotype G (n = 5) in Pimpla village. Two mumps virus isolates were also obtained using Vero cells. This is the first report from India confirming simultaneous circulation of mumps virus genotype C in one village and the G genotype in another village only 37 km away. J. Med. Virol. 9999:XX-XX, 2013. © 2013 Wiley Periodicals, Inc.
- The novel human polyomaviruses HPyV6, 7, 9 and beyond. [JOURNAL ARTICLE]
- APMIS 2013 May 8.
Since the discovery of Merkel cell polyomavirus and its causative association with Merkel cell carcinoma (MCC), six human polyomaviruses (HPyVs) have been identified that, so far, lack any disease association, which include the human polyomaviruses (HPyV) 6, 7, 9, 10 and 12 as well as the Saint Louis polyomavirus (STLPyV). PCR studies revealed that HPyV6 and HPyV7 are shed from the skin of healthy subjects and of patients suffering from various skin tumours. HPyV6, 7 and 9 were sporadically detected in body fluids and excretions of immunocompromised patients and healthy subjects. HPyV10 was identified in papillomavirus-induced anal condylomas, and variants of HPyV10, named MWPyV and MX polyomavirus (human) (MXPyV), as well as STLPyV were detected in faeces of diarrheal and healthy children. HPyV12 was discovered in organs of the digestive tract of patients suffering from various malignant diseases. Serological studies using capsomer-based or virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA) revealed that HPyV6, 7, 9 and 12 are circulating in the human population. As all other HPyVs, the novel polyomaviruses encode small and large T antigens and thus are potentially oncogenic. However, several studies have revealed a lack of association of HPyV6, 7 and 9 with numerous human tumours. In the future, it will be important to unravel the cell types and body compartments of the novel HPyVs' reservoir and to search for possible associations with cancer and non-malignant diseases.
- Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine (HibMenCY-TT; MenHibrix(®)): A Review. [JOURNAL ARTICLE]
- Drugs 2013 May 7.
The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6 weeks-18 months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6 weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15 months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6 months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15 months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the HibMenCY-TT vaccine in infants and toddlers in the phase III trial was considered to be clinically acceptable and comparable to that of the Hib conjugate vaccines received by the control group.
- Design and Characterization of a Fully Differential MEMS Accelerometer Fabricated Using MetalMUMPs Technology. [Journal Article]
- Sensors (Basel) 2013; 13(5):5720-36.
This paper presents a fully differential single-axis accelerometer fabricated using the MetalMUMPs process. The unique structural configuration and common-centriod wiring of the metal electrodes enables a fully differential sensing scheme with robust metal sensing structures. CoventorWare is used in structural and electrical design and simulation of the fully differential accelerometer. The MUMPs foundry fabrication process of the sensor allows for high yield, good process consistency and provides 20 μm structural thickness of the sensing element, which makes the capacitive sensing eligible. In device characterization, surface profile of the fabricated device is measured using a Veeco surface profilometer; and mean and gradient residual stress in the nickel structure are calculated as approximately 94.7 MPa and -5.27 MPa/μm, respectively. Dynamic characterization of the sensor is performed using a vibration shaker with a high-end commercial calibrating accelerometer as reference. The sensitivity of the sensor is measured as 0.52 mV/g prior to off-chip amplification. Temperature dependence of the sensing capacitance is also characterized. A -0.021fF/°C is observed. The findings in the presented work will provide useful information for design of sensors and actuators such as accelerometers, gyroscopes and electrothermal actuators that are to be fabricated using MetalMUMPs technology.
- Clinical presentation, etiology, and survival in adult acute encephalitis syndrome in rural Central India. [JOURNAL ARTICLE]
- Clin Neurol Neurosurg 2013 May 1.
BACKGROUND:Acute encephalitis syndrome (AES) is a constellation of symptoms that includes fever and altered mental status. Most cases are attributed to viral encephalitis (VE), occurring either in outbreaks or sporadically. We conducted hospital-based surveillance for sporadic adult-AES in rural Central India in order to describe its incidence, spatial and temporal distribution, clinical profile, etiology and predictors of mortality.
METHODS:All consecutive hospital admissions during the study period were screened to identify adult-AES cases and were followed until 30-days of hospitalization. We estimated incidence by administrative sub-division of residence and described the temporal distribution of cases. We performed viral diagnostic studies on cerebrospinal fluid (CSF) samples to determine the etiology of AES. The diagnostic tests included RT-PCR (for enteroviruses, HSV 1 and 2), conventional PCR (for flaviviruses), CSF IgM capture ELISA (for Japanese encephalitis virus, dengue, West Nile virus, Varicella zoster virus, measles, and mumps). We compared demographic and clinical variables across etiologic subtypes and estimated predictors of 30-day mortality.
RESULTS:A total of 183 AES cases were identified between January and October 2007, representing 2.38% of all admissions. The incidence of adult AES in the administrative subdivisions closest to the hospital was 16 per 100,000. Of the 183 cases, a non-viral etiology was confirmed in 31 (16.9%) and the remaining 152 were considered as VE suspects. Of the VE suspects, we could confirm a viral etiology in 31 cases: 17 (11.2%) enterovirus; 8 (5.2%) flavivirus; 3 (1.9%) Varicella zoster; 1 (0.6%) herpesvirus; and 2 (1.3%) mixed etiology); the etiology remained unknown in remaining 121 (79.6%) cases. 53 (36%) of the AES patients died; the case fatality proportion was similar in patients with a confirmed and unknown viral etiology (45.1 and 33.6% respectively). A requirement for assisted ventilation significantly increased mortality (HR 2.14 (95% CI 1.0-4.77)), while a high Glasgow coma score (HR 0.76 (95% CI 0.69-0.83)), and longer duration of hospitalization (HR 0.88 (95% CI 0.83-0.94)) were protective.
CONCLUSION:This study is the first description of the etiology of adult-AES in India, and provides a framework for future surveillance programs in India.
- Genetic Variation in the HN and SH Genes of Mumps Viruses: A Comparison of Strains from Mumps Cases with and without Neurological Symptoms. [Journal Article]
- PLoS One 2013; 8(4):e61791.
It is known that mumps virus (MuV) strains may vary in their neurovirulent capacity, and certain MuV strains may be highly neurotropic. In animal models and epidemiological studies, mutations at specific amino acids (aa) have been proposed to be associated with neurovirulence. To assess whether these genetic variations can be observed in clinical samples from patients and if they correlate with neurovirulence as determined by clinical symptoms, 39 mumps patients with or without neurological symptoms were investigated.Respiratory samples, oral fluids, throat swabs, and neurological and cerebrospinal fluid samples were tested by RT-PCR and products sequenced. Sequences of the entire small hydrophobic (SH) gene and the partial hemagglutinin-neuraminidase (HN) gene were compared.The results showed there was no significant difference between the samples of the two groups of patients at the aa sites in either the HN protein or the SH protein, which have previously been hypothesized to be associated with neurovirulence or antigenicity. The occurrence of neurological symptoms of mumps does not appear to be due to a single point mutation in either the HN or SH gene.