Short-term outcomes of the use of intraventricular ribavirin in Filipino patients with subacute sclerosing panencephalitis

@#<p style="text-align: justify;"><strong>Background.</strong> Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by prolonged persistent infection of the central nervous system with a measles virus mutant. Though various treatment modalities have been tried, there is no effective treatment to completely cure SSPE and new therapeutic strategies are needed.</p><p style="text-align: justify;"><strong>Objective.</strong> This is a prospective uncontrolled observational open label trial to describe the short-term outcomes and safety of intraventricular ribavirin in combination with oral isoprinosine in Filipino SSPE patients.</p><p style="text-align: justify;"><strong>Methods.</strong> Sixteen (16) unrelated SSPE patients between ages 3-26 years and in various clinical stages were included in this study. Demographic data were described. Intraventricular instillation of ribavirin (1-3 mg/kg/dose) through an Ommaya reservoir was given for a duration of 3-6 months in 13 patients. The duration of follow-up was 48 weeks. The clinical outcome was assessed before, during, and after treatment using the Neurological Disability Index (NDI), Brief Assessment Examination (BAE), and clinical staging using the Jabbour Classification. Adverse side effects from intraventricular ribavirin were enumerated.</p><p style="text-align: justify;"><strong>Results.</strong> Six of 13 (46.15%) patients mostly in Stage III illness had clinical improvement showing decreasing NDI and BAE scores during treatment and the clinical improvement was maintained or improved further during the 48-week follow-up period. Clinical improvement manifested as improved mental alertness, decrease in spasticity and reduction of seizures. The clinical staging of those who improved remained stable during and after treatment was discontinued. Five (38.46%) patients in Stage II disease worsened and progressed to Stage III despite ribavirin therapy including 1 (7.6%) patient who died after the treatment phase due to pneumonia and brainstem failure. The clinical course of two (15.38%) patients remained unchanged. Minor adverse side effects of ribavirin included transient fever, rash, oral sores, seizure episodes, drowsiness, bladder retention and mild increase in transaminases. Ommaya reservoir infection was a serious adverse event in 5 (31.25%) patients.</p><p style="text-align: justify;"><strong>Conclusion.</strong> There is still no definitive cure for SSPE. Although ribavirin may help alleviate some of the symptoms of SSPE and prolong life, it may not reverse or halt the progression of the disease. Long term follow-up of these patients and continuous use of intraventricular ribavirin will better clarify its role in modifying the fatal course of SSPE. The role of ribavirin in Stage I patients and a controlled clinical trial in Stage II SSPE needs further studies.</p>

The first outbreak of measles virus caused by imported genotype D8 in Jiangsu province of China

ABSTRACT Here we reported the outbreak of measles cases caused by the genotype D8 measles virus for the first time in Jiangsu province in China, which was possibly imported by a foreign student from Laos. Throat swab specimens were collected, and used to isolate virus. 634-bp fragment of the N gene and 1854-bp fragment of H gene were amplified by reverse transcription-PCR and sequenced, respectively. Phylogenetic results indicated that they belonged to genotype D8 measles virus. Further epidemiology investigation showed that the adults with D8 measles virus infection did not receive measles vaccine before having measles. In China, almost all D8 genotype MeV only infected those population without receiving measles vaccine immunization. Therefore, it is still necessary to implement the supplement activity of measles immunization target adult with immunity gap.

Molecular characterisation of the emerging measles virus from Roraima state, Brazil, 2018

Measles is a human infectious disease of global concern that is caused by the measles virus. In this study, we report the complete genome sequencing of one measles virus isolate, genotype D8, that was obtained directly from a urine sample in Boa Vista city, the capital of Roraima state in Brazil. Phylogenetic reconstruction grouped the genome described in this study with that of samples from Australia, South Korea, and Italy. To our knowledge, this is the first complete genome sequence of a wild-type measles virus reported from Latin America. Therefore, the present data strengthen the current knowledge on the molecular epidemiology of measles worldwide.

Immunogenicity and safety of the combined vaccine for measles, mumps, and rubella isolated or combined with the varicella component administered at 3-month intervals: randomised study

BACKGROUND Field testing required to license the combined measles, mumps, and rubella (MMR) vaccine must take into account the current recommendation of the vaccine in Brazil: first dose at 12 months and second dose at 15 months of age in combination with a varicella vaccine. OBJECTIVES This study aimed to evaluate the clinical consistency, immunogenicity, and reactogenicity of three batches of MMR vaccine prepared with active pharmaceutical ingredients (API) from Bio-Manguinhos, Fiocruz (MMR-Bio), and compare it to a vaccine (MMR produced by GlaxoSmithKline) with different API. METHODS This was a phase III, randomised, double-blind, non-inferiority study of the MMR-Bio administered in infants immunised at health care units in Pará, Brazil, from February 2015 to January 2016. Antibody levels were titrated by immunoenzymatic assays. Adverse events were recorded in diaries. FINDINGS Seropositivity levels after MMR-Bio were 97.6% for measles, 84.7% for mumps, and 98.0% for rubella. After the MMRV vaccine, seroconversion rates and GMT increased substantially for mumps. In contrast, approximately 35% of the children had no detectable antibodies to varicella. Systemic adverse events were more frequent than local events. CONCLUSION The demonstration of batch consistency and non-inferiority of the Bio-MMR vaccine completed the technology transfer. This is a significant technological achievement with implications for immunisation programs.

A long-term subacute sclerosing panencephalitis survivor treated with intraventricular interferon-alpha for 13 years / 소아과

Subacute sclerosing panencephalitis (SSPE) is a rare, progressive, and fatal central nervous system disorder resulting from persistent measles virus infection. Long-term data are scarce, with a maximum follow-up period of 10 years. Interferon-alpha (IFN-α) is a protein that exerts its antiviral activity via enhancement of cellular immune response and is reported to be an effective drug for the treatment of SSPE. However, there is currently no consensus regarding the optimal duration of IFN-α therapy. Here, we present a case report of a patient with SSPE treated with long-term intraventricular IFN-α therapy, which facilitated clinical improvement and neurological stabilization without causing serious adverse effects. To the best of our knowledge, this is one of the longest follow-up studies investigating a patient with SSPE receiving intraventricular INF-α treatment. Further studies are necessary to validate the benefits and safety of long-term intraventricular IFN-α treatment in patients with SSPE.

Current and Prospect on Measles Outbreak / 대한내과학회지

Measles is a highly contagious infectious disease characterized by fever, rash, cough, coryza, and conjunctivitis. The causative organism is the measles virus transmitted via the respiratory route. Before the introduction of an effective vaccine, measles was one of most prevalent diseases worldwide. Mortality may occur in patients with complications, including pneumonia, which is the most common cause of measles-associated death. The diagnosis of measles is based on clinical symptoms and laboratory tests, including the detection of measles virus-specific antibodies or measles virus ribonucleic acid and cultured viruses. The treatment for measles is primarily supportive care. In Korea, availability of the measles vaccine has substantially reduced the incidence and mortality of the disease. The World Health Organization verified the elimination of measles in March 2014; however, small outbreaks continue to be reported. Although a large proportion of measles cases occur in infants less than 1 year old, the disease has been reported in young adults with a history of measles vaccination. Here, we review the current literature on measles and discuss the importance of measles prevention in Korean adults.

Measles - an old children's disease to remember / Sarampo - uma velha doença infantil a relembrar

Measles is a serious, highly contagious viral disease. The measles virus is a single-stranded, RNA virus of the genus Morbillivirus within the family Paramyxoviridae, transmitted by air, through droplets of aerosols or by direct contact with respiratory secretions of infected individuals. The infection is acquired through the mucosa of respiratory tract or conjunctiva. In 2005, the World Health Organization established that measles eradication in the European Region should be achieved by 2010, but despite the measures adopted by the various countries, measles re-emerged, with 10271 cases reported only in 2013 in 30 states of European Union, with more than 91% of them in Germany, Italy, Netherland and United Kingdom. In the beginning of 2017, Portugal was threatened with a measles outbreak, reporting in the first five months of the year 31 confirmed cases, 20 (65%) of them in adults (18 or older), of which 45% (13) were in health professionals. Because this measles outbreak had so many cases in adults, the authors decided to make a brief review, trying to remember an old infection, not so well known by younger doctors, and that can be overlooked in the approach of the adult patients. The authors also point out that measles virus could virtually be eradicated as there is an effective vaccine and there is no reservoir in nature for the virus other than humans (AU)

O sarampo é uma doença viral grave e altamente contagiosa. O vírus do sarampo é um vírus de ARN, cadeia simples, do gênero Morbillivirus, da família Paramyxoviridae, transmitido pelas vias aéreas, através de gotículas de aerossóis ou por contato direto com secreções respiratórias de indivíduos infectados. A infecção é adquirida pelo contato dessas gotículas com a mucosa do trato respiratório ou conjuntiva. Em 2005, a Organização Mundial de Saúde estabeleceu que o objetivo para a erradicação do sarampo na Região Europeia seria até 2010 mas, apesar das medidas adotadas pelos diversos países, o sarampo ressurgiu, com 10271 casos relatados somente em 2013 em 30 estados da União Europeia, com mais de 91% deles na Alemanha, Itália, Holanda e Reino Unido. No início de 2017, Portugal foi ameaçado por um surto de sarampo, relatando nos primeiros cinco meses do ano 31 casos confirmados, 20 (65%) em adultos (com idade igual ou superior a 18), dos quais 45% (13) foram em profissionais de saúde. Face a este surto de sarampo ter tantos casos em adultos, os autores decidiram fazer uma breve revisão, tentando relembrar uma infeção antiga, não tão conhecida pelos médicos mais jovens e que pode ser esquecida na abordagem de um doente adulto. Os autores salientam igualmente que o vírus do sarampo pode virtualmente ser erradicado, pois existe uma vacina eficaz e não existe na natureza nenhum reservatório para o vírus, além dos humanos (AU)

Características de la estructura molecular de las proteínas E del virus del Zika y E1 del virus de la rubéola y posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso / E-ZIKV and E1-RV proteins molecular structure and their potential implications in neurotropism and nervous system disorders

Resumen Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por ZIKV se ha asociado con un gran neurotropismo y con efectos neuropáticos, como el síndrome de Guillain-Barré en el adulto y la microcefalia fetal y posnatal, así como con un síndrome de infección congénita similar al producido por el virus de la rubéola (RV). Objetivo. Comparar las estructuras moleculares de la proteína de envoltura E del virus del Zika (E-ZIKV) y de la E1 del virus de la rubéola (E1-RV), y plantear posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso asociadas con el ZIKV. Materiales y métodos. La secuencia de aminoácidos de la proteína E-ZIKV (PDB: 5iZ7) se alineó con la de la glucopreteína E1 del virus de la rubéola (PDB: 4ADG). Los elementos de la estructura secundaria se determinaron usando los programas Vector NTI Advance®, DSSP y POSA, así como herramientas de gestión de datos (AlignX®). Uno de los criterios principales de comparación y alineación fue la asignación de residuos estructuralmente equivalentes, con más de 70 % de identidad. Resultados. La organización estructural de la proteína E-ZIKV (PDB: 5iZ7) fue similar a la de E1-RV (PDB: 4ADG) (70 a 80 % de identidad), y se observó una correspondencia con la estructura definida para las glucoproteínas de fusión de membrana de clase II de los virus con envoltura. E-ZIKV y E1-RV exhibieron elementos estructurales de fusión muy conservados en la región distal del dominio II, asociados con la unión a los receptores celulares de entrada del virus de la rubéola (glucoproteína de mielina del oligodendrocito, Myelin Oligodendrocyte Glycoprotein, MOG), y con los receptores celulares Axl del ZIKV y de otros flavivirus. Conclusión. La comparación de las proteínas E-ZIKV y E1-RV es un paso necesario hacia la definición de otros factores moleculares determinantes del neurotropismo y la patogenia del ZIKV, el cual puede contribuir a generar estrategias de diagnóstico, prevención y tratamiento de las complicaciones neurológicas inducidas por el ZIKV.

Abstract Introduction: Zika virus (ZIKV) is an enveloped flavivirus transmitted to humans mainly by Aedes aegypti. ZIKV infection has been associated with high neurotropism and neuropathic effects such as the Guillain-Barré syndrome in adults, and fetal and postnatal microcephaly and the congenital Zika virus syndrome similar to that produced by rubella virus (VR). Objective: To compare Zika virus membrane protein E (E-ZIKV) and rubella virus membrane protein E1 (E1-RV), and to propose possible implications for neurotropism and nervous system disorders associated with ZIKV infections. Materials and methods: The amino acid sequence of E-ZIKV protein (PDB: 5iZ7) was aligned to that of rubella virus glycoprotein E1 (PDB: 4ADG). The secondary structure elements were determined using the programs Vector NTI Advance®, DSSP, and POSA, and integrated data management tools (AlignX®). One of the main comparison and alignment criteria was the allocation of structurally equivalent residues with more than 70% identity. Results: E-ZIKV structural organization (PDB: 5iZ7) was similar to that of E1-RV (PDB: 4ADG) (70%-80% identity), and it was consistent with relevant structural features of viral membrane class II fusion glycoproteins. E-ZIKV and E1-RV exhibited highly conserved fusion structural elements at the distal region of domain II, which has been associated with the RV myelin oligodendrocyte glycoprotein and Axl cell receptors in ZIKV and other flaviviruses. Conclusion: The comparison of E-ZIKV and E1-RV proteins constitutes an essential step towards the definition of ZIKV neurotropism and pathogenesis molecular determinants, and for the adoption of diagnosis, prevention and treatment strategies against neurological complications induced by ZIKV infection.

Epidemiological Investigation of a Measles Outbreak in Seoul, 2013~2014

Korea declared in 2006 that measles had been eliminated; however, a measles outbreak occurred in the southeastern area of Korea in 2011. Active surveillance of measles patients was conducted in Seoul 3 cases were detected in 2013 and 103 cases in 2014. Of 106 confirmed measles patients, 32 cases were within one university in Seongbukgu, and 23 were within three schools in Yongsangu. Students 14~29 years old comprised 78.3% (83/106) of the cases, and 75.5% (80/106) of the measles viruses were of genotype B3. One foreign traveler played an important role in the measles outbreak in Seoul. This measles outbreak in Seoul may provide useful data for future epidemiological studies of measles.

Advances in measles virus for cancer therapy / 浙江大学学报·医学版

Oncolytic virotherapy is a novel cancer therapy. Vaccine-attenuated strains of measles virus(MV)is an ideal candidate for oncolytic virotherapy which has an excellent safety record. Vaccine-attenuated MV uses CD46 and Nectin-4 molecule as major entry receptors into cells. Vaccine-attenuated MV can selectively infect and kill a wide variety of cancer cells in vitro and in vivo. With the development of molecular cloning, scientists have successfully rescued cDNA of vaccine-attenuated MV and increased its oncolytic efficiency with molecular engineering techniques. Phase I clinical trials of virotherapy for ovarian cancer and multiple myeloma with vaccine-attenuated MV are underway. The preliminary results indicate the promising antitumor potential of vaccine-attenuated MV.

Analysis on clinical and epidemioloical characteristics of measles in hospitalized children in Shanghai in 2012 / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the main factors that influence measles morbidity and the genotype of measles virus, so as to provide evidence for scientific decision making to further control the prevalence of measles.</p><p><b>METHOD</b>A retrospective analysis included 182 children in Children's Hospital of Fudan University, diagnosed with measles from January 1, 2012 to December 31. The clinical and epidemiological characteristics, including the gender, age, the incidence of seasonal trends, measles vaccine vaccination history, contact history and other clinical manifestations, laboratory test results, and so on were analyzed. And the reverse transcription PCR (RT-PCR) was adopted to detect sputum specimens from suspected patients with measles,who were selected randomly,the sequence of the part of the PCR products was analyzed.</p><p><b>RESULT</b>(1) Clinical and epidemiological data: Totally were 182 children with measles (125 males, 57 females) were enrolled into this study. The age of the patients ranged from 3 months to 89 months, 127 cases were younger than 9 months (69. 8%). The prevalence season was from April to August, while the peak month was April and May (22. 5%, 23. 1%). Among 182 hospitalized children, only 11 cases underwent measles vaccination (6. 0%), and among them 5 cases were within 2 weeks before disease onset. A total of 167 cases (91. 8%) had not been vaccinated, most of whom were immigrants, and the measles vaccination history of the remaining 4 cases were unknown. There was a positive correlation between the measles vaccination ratio in children of the floating population (8. 45%, 6/71) and the settled children (29.4%, 5/17, χ =8. 11 P =0. 004). In total, 24 cases (13. 2%) had definite measles exposure history, with 153 cases (84. 1%) of unknown origin,5 cases (2.7%) without any history of contact. (2) Clinical manifestations: All the 182 patients had fever (100%) and obvious rashes (100%), among them 145 cases had body temperature higher than 39 °C (79. 7%). The fever period ranged from 2 to 38 days. Among 182 hospitalized children,165 cases (90. 7%) had typical measles,17 cases had atypical measles. Among the 17 cases, two had severe measles, one had heterotypic measles. (3) The common complica tions: 96 cases had pneumonia (52. 8%), 80 had laryngitis (44. 0%), 38 had bronchitis (20. 9%),15 had hepatic dysfunction (8. 2%), 11 had myocardial damage (6. 0%), 3 had febrile seizures (1. 6%), and no patient had encephalitis. Of the 96 cases with pneumonia, 92 received sputum test; 38 were sputum culture positive (41%). The dominant pathogens were Streptococcus pneumoniae(11/38,29%), Haemophilus influenzae (6/ 38,16%), Moraxella catarrhalis (4/38, 11%), Escherichia coli (4/38, 11%), Candida albicans (4/38, 11%), Mycoplasma pneumoniae (4/38, 11%) and Staphylococcus aureus (3/38, 8%). (4) The H1a genotype was the only one genotype in the detected sequence of 54 measles virus strains.</p><p><b>CONCLUSION</b>Measles was more often seen in the children under the age of 9 months from the floating population. The morbidity peak month was from April to May in Shanghai. The H1a genotype was the only one genotype. We should try to improve vaccination coverage rate in the children who are at the age for vaccination, so as to prevent measles outbreak.</p>

Genetic Characterization of Hemagglutinin on Measles Virus Epidemic Strain Genotype H1a in Liaoning Province (China) from 1997 to 2014 / 病毒学报

To wished to characterize the hemagglutinin (H) gene of the measles virus epidemic strain H1a in Liaoning Province (China) from 1997-2014 to provide a basis for the control and elimination of measles. All 63 measles virus strains were the H1a genotype. Fragments of the H gene (1854 nucleotides) and nucleoprotein (N) gene (450 nucleotides) were amplified by reverse transcription-polymerase chain reaction (RT-PCR) and the PCR products sequenced and analyzed. Phylogenetic-trees were constructed with reference strains of the genotype-H measles virus downloaded from GenBank, including Chinese measles virus strains isolated in 1993-1994 and the vaccine reference strains S-191 and C-47. Sixty-three strains of the measles virus in 1997-2014 belonged to genotype H1a. The mean evolutionary rate for gene N-450 was higher than that for the H gene. All 63 strains of the measles virus were mutated from: serine (Ser S) to asparagine (Asn N) in the 240th amino acid; arginine (Arg R) to glycine (Gly G) in the 243th; and tyrosine (Tyr Y) to Asn N in the 481th amino acid. All measles virus strains in cluster 2 were mutated from proline (Pro P) to leucine (Leu L) in the 397th amino acid. The other neutralization sites showed no apparent difference when comparing the nucleotides/amino acids of the H gene of S191 vaccine strains.

Molecular epidemiology of measles virus infection in Shanghai in 2000–2012: the first appearance of genotype D8

Purpose: The purpose of this study was to identify measles virus in Shanghai in 2012 and study the genotype trend of measles virus epidemic strains during 2000–2012. Methods: Nose and throat swab specimens were collected from 34 suspected measles cases in Shanghai. Measles virus was isolated using Vero-SLAM cells (African green monkey kidney cells/lymphoid signal activating factor-transfected African green monkey kidney cells). The 450 bp of C terminus of the N gene and the entire hemagglutinin gene sequence was amplified using RT-PCR. Phylogenetic analysis was performed by comparing the seven measles strains in Shanghai with the reference strains for H1a, H1b and D8 genotypes, as well as the Chinese measles virus vaccine strain. Results: Seven measles viruses strains were isolated from the 34 throat swap specimens. Six strains were genotype H1a, which is the predominant strain in China and one strain was genotype D8, which is the first imported strain since 2000. All these seven strains maintained most of the glycosylation sites except subtype H1a, which lost one glycosylation site. Conclusion: Since 2000, measles virus strains in Shanghai are consistent with measles virus from other provinces in China with H1a being the predominant genotype. This study is also the first report of genotype D8 strain in Shanghai. All strains maintained their glycosylation sites except H1a that lost one glycosylation site. These strains could still be neutralized by the Chinese measles vaccine. We suggest that Shanghai Center for Disease Control laboratories should strengthen their approaches to monitor measles cases to prevent further spread of imported strains. .

Panorama atual do sarampo no mundo: Risco de surtos nos grandes eventos no Brasil / Current landscape of measles in the world: risk of outbreaks in major events in Brazil

O sarampo é considerado uma das doenças infecciosas mais contagiosas do mundo (1), capaz de atingir todos os grupos etários, com risco particular em menores de cinco e naqueles entre 15 e 29 anos de idade (2), sendo uma das principais causas de morte evitáveis por vacina entre crianças (3). Frente aos recentes surtos de sarampo ocorridos no mundo, estaria o Brasil, que desde 2000 conseguiu eliminar a circulação do sarampo e na atualidade vem lidando apenas com surtos de pequena monta de casos importados, sob risco de grandes surtos durante a Copa do Mundo de 2014 e as Olimpíadas de 2016? Através de análises dos últimos surtos ocorridos em todo o mundo e pesquisa da cobertura vacinal no Brasil, os autores respondem a estas questões.

Measles is considered one of the most contagious diseases in the world (1). It’s able to reach all of age groups with particular risk in under five and 15-29 years old (2). It’s one of the main causes for evitable deaths for vaccine between children (3). According to recents measles outbreaks occurred in the world, Brazil is included in it, since 2000 has eliminated measles circulation and actually has been dealing with outbreaks of little dimension of imported cases, at risk of large outbreak during the World Cup 2014 and The Olympics Games 2016? Through analysis of the latest outbreaks ocurred all over the world and research of vaccine coverage in Brazil, the authors will answer to these questions.

Molecular detection of measles virus from children during a sporadic outbreak in two semi-urban areas in Nigeria

Background: According to the World Health Organization (WHO); African region accounts for 36 of deaths caused by measles worldwide. Nigeria has; over the years; recorded the highest average annual measles incidence per 100;000 populations in Africa. Measles epidemics have consistently been reported in northern Nigeria; but not in the South; reports of reduced protective haemagglutination inhibition antibody titers among children in Ibadan; southern Nigeria was made. Investigation of the viral agent responsible for the disease outbreak among children presenting with rash in two semi urban areas in southern Nigeria was carried out to confirm the etiology of the disease. Methodology: Twenty six throat swabs (TS); and nineteen urine samples were collected from twenty six children residing in Onireke and Sabo areas of Ibadan following the report of an outbreak of rashes among children. Active case finding with the support of community leaders was used to locate the affected children. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR); was used to identify the agent. Results: 21 of the 26 children screened tested positive for measles virus; but none was positive for Rubella virus. There was significant association between measles infection; and households with higher number of persons. Conclusion: Mass measles vaccination that targets overcrowded; rural and inaccessible areas is needed to increase herd immunity. Public health enlightenment on the benefits of vaccination is encouraged

Pathobiology of Paget's Disease of Bone

Paget's disease of bone is characterized by highly localized areas of increased bone resorption accompanied by exuberant, but aberrant new bone formation with the primary cellular abnormality in osteoclasts. Paget's disease provides an important paradigm for understanding the molecular mechanisms regulating both osteoclast formation and osteoclast-induced osteoblast activity. Both genetic and environmental etiologies have been implicated in Paget's disease, but their relative contributions are just beginning to be defined. To date, the only gene with mutations in the coding region linked to Paget's disease is sequestosome-1 (SQSTM1), which encodes the p62 protein, and these mutations lead to elevated cytokine activation of NF-B in osteoclasts but do not induce a "pagetic osteoclast" phenotype. Further, genetic mutations linked to Paget's appear insufficient to cause Paget's disease and additional susceptibility loci or environmental factors may be required. Among the environmental factors suggested to induce Paget's disease, chronic measles (MV) infection has been the most studied. Expression of the measles virus nucleocapsid gene (MVNP) in osteoclasts induces pagetic-like osteoclasts and bone lesions in mice. Further, mice expressing both MVNP in osteoclasts and germline mutant p62 develop dramatic pagetic bone lesions that were strikingly similar to those seen in patients with Paget's disease. Thus, interactions between environmental and genetic factors appear important to the development of Paget's disease. In this article we review the mechanisms responsible for the effects of mutant p62 gene expression and MVNP on osteoclast and osteoblast activity, and how they may contribute to the development of Paget's disease of bone.

Genetic characteristics of hemagglutinin in measles viruses isolated in Henan Province, China / 病毒学报

This study aims to investigate the genetic characteristics of hemagglutinin in wild-type measles viruses in Henan Province, China and to provide a basis for measles control and elimination. Specimens were collected from suspected measles cases in Henan during 2008-2012. Cell culture was performed for virus isolation, and RT-PCR was used to amplify hemagglutinin gene. The PCR products were sequenced and analyzed, including construction of phylogenetic tree and analysis of the distance between the isolated virus and the reference virus; then, the variations in predicted amino acids were analyzed. The results showed that 12 measles viruses were isolated in Henan Province and identified as H1a genotype; the nucleotide and amino acid homologies were 98.0%-100% and 97.2%-99.8%, respectively. One glycosylation site changed in all the 12 sequences because of the amino acid mutation from serine to asparagine at the 240th site, as compared with Edmonston-wt. USA/54/A. Overall, the wild-type measles virus genotype circulating in Henan Province from 2008 to 2012 was H1a, with high homology between strains; there were some variations in amino acid sequences, resulting in glycosylation site deletion.

Genetic characterization of the isolates of measles viruses in Hongkou district of Shanghai, China in 2012 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To ascertain the genotype of measles viruses isolated in 2012 and genetic characterization of measles viruses in Hongkou district of Shanghai during 2000-2012.</p><p><b>METHODS</b>Measles virus was isolated from throat swab specimens collected from suspected measles cases and 450 bp fragment of C terminus on nucleoprotein (N) gene was amplified by RT-PCR. Sequence analysis was conducted to ascertain the genotype and to compare the difference of nucleotide with other measles virus strain announced by GenBank during 2000-2012. Measles virus genotype was analyzed. Epidemiological investigation was conducted.</p><p><b>RESULTS</b>Phylogenetic analysis showed that 7 measles virus samples were isolated from 34 throat swab specimens with 6 of them belonged to H1 genotype, 1 belonged to D8 genotype of H1 genotype. H1a appeared the main part of Shanghai measles virus. Epidemiological survey showed that D8 was an imported case, also the first case detected since 2000.</p><p><b>CONCLUSION</b>The genotype distribution of measles virus in Hongkou was identified the same as elsewhere in Shanghai. D8 was an imported case, detected for the first time since 2000. The results suggested that viral gene sequencing and genotyping should be regularly conducted at the measles laboratories in Shanghai to strengthen the networking monitoring program of the disease.</p>