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M A Pallansch

Publications and source records attributed to M A Pallansch.

At least 37 records · Page 2Linked to original sources

New-onset juvenile dermatomyositis: comparisons with a healthy cohort and children with juvenile rheumatoid arthritis.

OBJECTIVE: To determine, in a case-control study, if patients with new-onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups. METHODS: A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB). RESULTS: A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease-onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children < or =7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1-6 were normal. CONCLUSION: Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease-onset date, and young patients have elevated enteroviral titers, as do young geographic controls.

Animals↗

A theoretical framework for evaluating the sensitivity of surveillance for detecting wild poliovirus: I. Factors affecting detection sensitivity in a person with acute flaccid paralysis.

Surveillance for cases of acute flaccid paralysis provides a means for detecting circulating wild poliovirus in a population and therefore is crucial to the global polio eradication effort. An initial step toward developing a more general framework for understanding the sensitivity of the acute flaccid paralysis surveillance system is presented by first specifying four categories of sensitivity involved: laboratory sensitivity, specimen sensitivity, person sensitivity, and population sensitivity. Using this framework, estimates for specimen sensitivity (the probability that virus will be detected in a specimen collected from an infected person) and the prevalence of infection are derived and applied to surveillance data from three regions. On the basis of the framework, our analysis indicates that a second specimen may significantly increase person sensitivity under some circumstances but provides little improvement under others.

False Negative Reactions↗

A theoretical framework for evaluating the sensitivity of surveillance for detecting wild poliovirus: II. Factors affecting detection sensitivity in a population with circulating wild poliovirus.

A basic framework for describing sensitivity of surveillance to detect poliovirus is extended from individuals to general populations (population sensitivity). Using the mathematical formulations for population sensitivity, the theoretical behavior of surveillance sensitivity under various conditions is analyzed. As a region nears the elimination of poliovirus, population sensitivity falls to a value lower than the case-to-infection ratio, regardless of the system proficiency. Also, a second stool specimen makes a substantial contribution to population sensitivity only in regions with relatively low specimen sensitivity and then only over a narrow range of population infection incidence. Estimates of the mean numbers of infected and uninfected acute flaccid paralysis cases investigated in a season are derived. These may serve as additional indicators of system operation but require the collection of 2 specimens per case.

Feces↗

Duration of poliovirus excretion and its implications for acute flaccid paralysis surveillance: a review of the literature.

Timely investigation of children with acute flaccid paralysis, with collection of stool specimens for virus isolation, is the primary strategy used to detect wild poliovirus circulation. To determine the optimal timing of stool specimen collection, studies of wild and vaccine poliovirus excretion published between 1935 and 1995 were reviewed. Data were compiled from comparable studies, scatter plots of the data were created, and third-order regression lines were calculated. The data indicated that wild polioviruses were excreted by a majority of previously unvaccinated infants and young children for 3-4 weeks. The duration of viral shedding was reduced, however, among children who were previously vaccinated with inactivated poliovirus vaccine, who had preexisting antibodies to the infecting serotype, or who had previous intestinal infection with homologous poliovirus. These data suggest that the 14-day period after onset of paralysis is the interval with the highest probability of detecting wild poliovirus excretion in paralyzed children.

Disease Outbreaks↗

Increased immunogenicity of oral poliovirus vaccine administered in mass vaccination campaigns compared with the routine vaccination program in Jordan.

To compare the immunogenicity of routine versus mass campaign doses of oral poliovirus vaccine (OPV), serum neutralizing antibodies were measured in 254 children before and after two mass vaccination campaigns in Jordan. Precampaign seroprevalences to poliovirus types 1, 2, and 3 in children who had received three, four, or five routine doses of OPV were compared with postcampaign seroprevalences in children who had received one, two, or three routine doses plus two mass campaign doses. Seroprevalences were consistently higher in subgroups that received two doses through mass campaigns than in subgroups that received all doses through the routine program, especially for poliovirus type 3. Geometric mean titers were also consistently higher for mass campaign subgroups, particularly for poliovirus type 3. The findings suggest that adding further doses of OPV to the routine schedule is unlikely to have as great an impact on the immune state of children as administering the same number of doses during mass campaigns.

Child, Preschool↗

Sequential use of inactivated poliovirus vaccine followed by oral poliovirus vaccine in Oman.

Seroprevalence and geometric mean titers (GMTs) were compared at 6 and 10 months after vaccination with monovalent type 1 oral poliovirus vaccine (OPV) at 6 months and trivalent OPV at 7 and 9 months. Group 1 had received 4 doses of OPV, group 2 OPV at birth and 3 doses of OPV and inactivated poliovirus vaccine (IPV), and group 3 placebo at birth and 3 doses of IPV. A total of 547 infants completed the study. At 10 months, seroprevalence to poliovirus type 1 was 98%, 99%, and 98% in groups 1, 2, and 3; 100%, 100%, and 98% to poliovirus type 2; and 80%, 96%, and 91% to poliovirus type 3. Differences in seroprevalence among the groups were significant for poliovirus type 3 (P < .001). Between 6 and 10 months, significant increases in seroprevalence and GMTs occurred for poliovirus type 1 but not for types 2 and 3. Two OPV doses following 3 IPV doses did not significantly increase seroprevalence or raise GMTs for poliovirus types 2 and 3; however, significant increases were found for poliovirus type 1, which may have benefitted from monovalent type 1 administration.

Antibodies, Viral↗

Comparison of a monoclonal antibody-based IgM capture ELISA with a neutralization assay for assessing response to trivalent oral poliovirus vaccine.

Monoclone-based IgM capture ELISAs were developed for each of the three poliovirus serotypes and compared with a neutralization assay for detecting response to trivalent oral poliovirus vaccine among 224 infants. The IgM-based response rates were significantly higher than the neutralizing antibody-based rates: 95% versus 83% to poliovirus type 1, 99% versus 94% to poliovirus type 2, and 89% versus 59% to poliovirus type 3. IgM responses to the first vaccine dose were significantly associated between serotypes, suggesting that some of the discordance may reflect a heterotypic IgM response. When the response rates in 4 vaccine formulation groups were compared, group differences using the two assays were similar for poliovirus types 1 and 2 but not for type 3. Therefore, IgM results using these assays may not be adequate substitutes for neutralizing antibody results when determining vaccine response.

Animals↗

Outbreak of paralytic poliomyelitis in a highly immunized population in Jordan.

Between November 1991 and March 1992, 37 cases of paralytic poliomyelitis occurred in Jordan, where none had been reported since 1988. Of these, 17 (50%) of 34 patients had received at least three doses of oral poliovirus vaccine (OPV3). The first and 2 subsequent case-patients were children of Pakistani migrant workers, and the first 8 and a total of 27 (75%) case-patients resided in or near the Jordan Valley. A seroepidemiologic study of 987 children in all regions of Jordan was performed to assess OPV3 coverage and immune response to OPV. Although OPV3 coverage by 12 months of age was high (96%) in the general population, coverage was lower among Pakistani (21%), Bedouin (63%), and Gypsy (9%) children (P < .001). Seroprevalences for poliovirus type 3 were 71% in the Jordan Valley versus 81% in other regions after 3 doses of OPV (P < .06) and 77% in the Jordan Valley versus 98% in other regions after 5 doses of OPV (P < .001). This outbreak demonstrates the importance of achieving high seroimmunity to infection in all geographic areas to prevent the reintroduction and spread of imported strains of wild poliovirus.

Case-Control Studies↗

Outbreak of poliomyelitis in Gizan, Saudi Arabia: cocirculation of wild type 1 polioviruses from three separate origins.

In 1989, a localized outbreak of 10 cases of poliomyelitis occurred in Saudi Arabia. Wild poliovirus type 1 was isolated from 5 patients. To determine the patterns of poliovirus circulation, partial nucleotide sequences of the poliovirus isolates were compared. These isolates were remarkably diverse. Two isolates were closely related to each other and to viruses isolated during the 1988 epidemic in Oman. Two other isolates were very similar to viruses found in Egypt. The fifth isolate was distantly related to the latter pair. The molecular data suggest that the 10 cases represented three separate outbreaks. The virologic findings underscore the potential for Saudi Arabia, which receives millions of guest workers and their families each year from countries in which polio is endemic, to be exposed to frequent importations of wild polioviruses. To restrict the circulation of imported polioviruses, Saudi Arabia must maintain high population immunity to poliovirus in all geopolitical divisions.

Child↗

The role of enteroviral infections in the development of IDDM: limitations of current approaches.

Enteroviruses have been examined for their possible role in the etiology of IDDM for nearly 40 years, yet the evidence remains inconclusive. The mechanism of acute cytolytic infection of beta-cells, proposed by earlier studies, appears to be incompatible with the long preclinical period of autoimmunity preceding IDDM. Advances in molecular biology have improved our understanding of enteroviral biology and of potential alternative pathogenic mechanisms through which enteroviruses may cause diabetes. The focus of future human studies will likely shift from people with IDDM to those with prediabetic autoimmunity to determine whether acute enteroviral infections can promote progression from autoimmunity to overt diabetes. We propose that such studies use assays to detect enteroviral RNA, in addition to IgM serology. RNA assays can overcome sensitivity and type-specificity limitations of IgM assays as well as identify diabetogenic strains of enteroviruses, if such exist. Evaluation of the role of enteroviruses in triggering beta-cell autoimmunity in humans will require large prospective studies of young children. The Diabetes Autoimmunity Study in the Young--one of very few such studies currently underway--is focusing on potential interactions between HLA class II genes and enteroviral infections. Future studies will likely examine interactions between viral infections and non-HLA IDDM candidate genes, including those that may determine beta-cell tropism of candidate viruses.

Amino Acid Sequence↗

Sites other than nucleotide 234 determine cardiovirulence in natural isolates of coxsackievirus B3.

The genetic site(s) that naturally determine the cardiovirulence phenotype of coxsackievirus B3 (CVB3) have yet to be mapped. Using two closely related CVB3 strains that differed in terms of cardiovirulence phenotype in mice, we previously reported the difference in phenotype mapped to a single site, nucleotide 234 (nt234) in the 5' non-translated region (NTR) of the CVB3 genome. When nt234 was C, the virus was attenuated and when U, the virus was cardiovirulent. To determine whether this finding was applicable to other strains of CVB3, we examined 13 different naturally occurring CVB3 strains isolated in different years in the United States. We determined that only two isolates induced severe inflammatory heart muscle disease in C3H/HeJ male mice. Using PCR products as sequencing templates, we determined the 5' NTR sequence from each viral genome. Alignment of these sequences and other published CVB3 5' NTR sequences suggests as many as four separate lineages, with commonly used laboratory strains clustering closely in one branch. An examination of the sequences showed that regardless of cardiovirulence phenotype, nt234 was invariably uridine. Thus, the previously reported cytidine at nt234 is most likely the result of a rare mutation and is not a naturally occurring variation and other sites must account for the variance in virulence seen in natural isolates of CVB3.

Animals↗

Seroprevalence of antibody against poliovirus in inner-city preschool children. Implications for vaccination policy in the United States.

OBJECTIVES: To assess susceptibility to poliomyelitis in selected inner-city preschool children in the United States and to estimate the contribution of secondary spread of live attenuated oral poliovirus vaccine virus to type-specific immunity. DESIGN: Cross-sectional seroprevalence study. METHODS: Serum neutralizing antibody levels against poliovirus types 1, 2, and 3 were analyzed according to vaccination status, age, and other sociodemographic variables. SETTING: Hospital and satellite clinics serving inner-city populations in Houston, Tex, and Detroit, Mich, 1990 to 1991. PARTICIPANTS: A total of 526 children aged 12 to 47 months seeking medical care were enrolled in the seroprevalence study; 144 children aged 12 to 35 months without a history of previous oral poliovirus vaccination were enrolled in the secondary spread study. RESULTS: Seropositive rates were similar in children in both cities, ranging from about 80% for types 1 and 3 in 12- to 23-month-old children to more than 90% in those aged 36 to 47 months. The most important predictor of seropositivity was the number of doses of oral poliovirus vaccine received (P < .01), with levels approximately 90% for all 3 serotypes among children who had received 3 or more doses. In children likely to have been unvaccinated, seropositive rates ranged from 9% to 18% for poliovirus types 1 and 3 and from 29% to 42% for type 2; secondary spread of vaccine virus appeared to have occurred among children who had previously received 1 dose or less but not those with 2 or more doses. CONCLUSIONS: Levels of immunity to poliovirus among inner-city preschoolers are high and may be predicted by the number of doses of oral poliovirus vaccine received. Secondary spread of the vaccine virus plays a modest role in increasing polio immunity in inner-city populations, especially against types 1 and 3. This role will decrease in importance if the recently attained high levels of immunization coverage in the United States are sustained and if the risk of importation of wild poliovirus continues to diminish.

Antibodies, Viral↗

Coxsackievirus B3 clinical isolates and murine myocarditis.

Fifteen clinical coxsackievirus B3 (CVB3) isolates were assessed for cardiopathologic capabilities in adolescent male CD-1 mice in comparison to two well characterized cardiovirulent CVB3 strains. One isolate was cardiovirulent, one minimally cardiovirulent and the remaining 13 isolates were noncardiovirulent. The two cardiovirulent isolates and one well characterized cardiovirulent strain, established higher viremic titers, in comparison to five noncardiovirulent isolates that were examined. The two cardiovirulent isolates and one well characterized cardiovirulent strain replicated to significantly higher titers than five noncardiovirulent isolates in primary cultures of murine neonatal or adolescent cardiac fibroblasts. Nucleotide sequence analysis of an area defined by nucleotides(N)300-N599 in the 5'-nontranslated region were performed on the two well characterized cardiovirulent CVB3 strains, the two cardiovirulent isolates and 12 noncardiovirulent isolates. The data detected a single discriminatory nucleotide position. An A was present at N565 in three of four cardiovirulent CVB3, whereas a U or C was present in this position in 12 of 12 noncardiovirulent CVB3. In toto, these data are compatible with the hypothesis that the type of the nucleotide at N565, a position within the internal ribosome entry site, is associated with capacity of a CVB3 for replication in vivo and in vitro and this capacity for vigorous replication is associated with cardiovirulence.

Adult↗

Outbreak of vertigo in Wyoming: possible role of an enterovirus infection.

An epidemiologic investigation was conducted to characterize and evaluate the possibility of a viral aetiology of an outbreak of acute vertigo in Hot Springs Country, Wyoming, during autumn 1992. Case-finding identified Hot Springs County residents who sought medical attention for new onset vertigo during 1 August, 1992-31 January 1993. Thirty-five case-patients and 61 matched controls were interviewed and serum specimens were obtained during January 1993. Case-patients were more likely than controls to report symptoms (e.g. fatigue, sore throat, fever, diarrhoea) of antecedent acute illness. Case-patients did not have a significantly greater prevalence or mean titre of IgG antibodies to respiratory syncytial virus, parainfluenza viruses, Epstein-Barr virus, and cytomegalovirus than controls. Serologic evidence of recent enterovirus infection (IgM antibodies) was found for 74% of case-patients compared with 54% of controls (P < 0.05), suggesting a possible association between vertigo and enterovirus infection. Future studies are needed to define the role of enteroviruses in innerear diseases.

Adolescent↗

Group-specific identification of polioviruses by PCR using primers containing mixed-base or deoxyinosine residue at positions of codon degeneracy.

We have developed a method for differentiating polioviruses from nonpolio enteroviruses using PCR. A pair of panpoliovirus PCR primers were designed to match intervals encoding amino acid sequences within VP1 that are strongly conserved among polioviruses. The initiating primer hybridizes with codons of a 7-amino-acid sequence that has been found only in polioviruses; the second primer matches codons of a domain thought to interact with the cell receptor. The panpoliovirus PCR primers contain mixed-base and deoxyinosine residues to compensate for the high degeneracy of the targeted codons. All RNAs from 48 vaccine-related and 110 wild poliovirus isolates of all three serotypes served as efficient templates for amplification of 79-bp product. None of the genomic sequences of 49 nonpolio enterovirus reference strains were amplified under equivalent reaction conditions. Sensitivities of poliovirus detection were as low as 100 fg (equivalent to approximately 25,000 genomic copies or 25 to 250 PFU) when the amplified products were visualized by ethidium bromide fluorescence. These degenerate PCR primers should aid in the detection of all polioviruses, including those wild poliovirus isolates for which genotype-specific reagents are unavailable.

Amino Acid Sequence↗

Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: poliovirus vaccination.

Inactivated and trivalent oral poliovirus vaccines contain either formalin-inactivated or live, attenuated poliovirus, respectively, of the three serotypes. Interference among the three attenuated poliovirus serotypes was minimized with a "balanced-formulation" vaccine, and serologic responses after IPV were optimized by adjusting the antigenic content of each inactivated poliovirus serotype. Seroconversion is dependent on both the relative content as well as the absolute quantity of virus in the vaccine. The "gold standard" method to assess humoral antibody responses following vaccination is the neutralization assay. Any detectable titer of neutralizing antibody against poliovirus is considered protective against clinical paralytic diseases. Recently, standard procedures were adopted for conducting neutralization assays. Efforts are being undertaken now to develop a combined diphtheria and tetanus toxoids and pertussis vaccine and IPV vaccine in the United States using a dual-chambered syringe that mixes the content of both vaccines at the time of injection; this approach is necessary to overcome the potential detrimental effect of thimerosal on IPV (the preservative in DTP). Other vaccines that combine DTP and/or Haemophilus influenzae type b and/or hepatitis B with IPV appear feasible but require further investigation. New combination vaccines should induce similar or superior levels of neutralizing antibody in serum for individual protection against paralytic disease and mucosal immunity that effectively decreases viral replication in the intestine and pharynx for population protection against transmission of poliovirus.

Antibodies, Viral↗

Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus.

Enterovirus 71 (EV71) is capable of causing paralytic disease indistinguishable from poliomyelitis due to poliovirus. To determine the relationship of EV71 to poliovirus and other enteroviruses, two strains of EV71 have been cloned and sequenced. The EV71 strains had only 46% amino acid identity with the polioviral P1 capsid region and 55% with the entire polyprotein. There were no regions of high similarity that might account for their respective ability to cause paralytic disease. The two strains, a neurovirulent isolate (EV71/7423/MS/87) and the prototype strain (EV71/BrCr), share 81% nucleotide identity and 95% amino acid identity. Sequence comparisons in the coding region between the two EV71 strains and other picornaviruses indicate that EV71, coxsackievirus A16 and coxsackievirus A2 comprise a distinct genetic group within the enteroviruses.

Base Sequence↗