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Biomedical subjects

M A Pallansch

Publications and source records attributed to M A Pallansch.

At least 55 records · Page 3Linked to original sources

Serologic evidence of an association between enteroviruses and the onset of type 1 diabetes mellitus. Pittsburgh Diabetes Research Group.

Serum was collected from 128 patients < or = 18 years of age admitted to the Children's Hospital of Pittsburgh with new-onset insulin-dependent diabetes mellitus (IDDM) and from 120 control-patients who were frequency-matched to case-patients for age, sex, and date of bleed. Serum was tested for IgM against 14 enterovirus serotypes: coxsackieviruses B1-B6 and A9, echoviruses 4, 6, 9, 11, 30, and 34, and enterovirus 71. Case-children 13-18 years of age were more likely than control-patients to be IgM-positive for 9 of 14 serotypes (P < or = .05 for each). In contrast, case-children 10-12 years of age and 1-9 years of age were each more likely than age-matched control-children to be IgM positive for 1 serotype (P < or = .05 for each). In addition, the association between IgM positivity and IDDM occurred earlier in girls than in boys. These data support an association between IDDM and enterovirus IgM positivity in older children.

Adolescent↗

Geographical genotypes (geotypes) of poliovirus case isolates from the former Soviet Union: relatedness to other known poliovirus genotypes.

A 150 nucleotide long region corresponding to adjoining segments of the genes encoding polypeptides VP1 and 2A of 84 poliovirus strains recently isolated from patients with paralytic poliomyelitis over the territory of the former Soviet Union (FSU) were characterized by sequencing and/or PCR amplification using specially designed primers. Eighteen isolates were found to be very closely related to one or another of the three Sabin vaccine strains. Three distinct classes of geographical genotypes (geotypes) were discerned among 42 wild-type (non-Sabin) strains of serotype 1. One such geotype (called A) was widely circulating in 1990-91 in the Caucasian (Azerbaijan and Georgia) as well as Asian (Kyrgyzstan and Turkmenistan) Republics; this geotype exhibited only weak relatedness to known strains isolated outside the FSU. On the other hand, a subset of strains belonging to another geotype (T) of serotype 1, which circulated in 1991 in Tajikistan, demonstrated very close relatedness to contemporaneous strains isolated in Pakistan, India and Jordan. Strains that were somewhat different, but belonging to the same T-geotype, were found also in Moldova and Georgia. Strikingly, the primary structure of the VP1/2A junction of certain T-geotype isolates differed from the corresponding region of Sabin 1 only in 13-15% of positions, thereby not reaching the upper limit accepted for a geotype. This observation raises, though does not prove, the possibility that at least the relevant segment of the T-geotype RNA originated from the vaccine strain. The third geotype of serotype 1 was represented by a single, perhaps imported, isolate. Four distinct subsets of a common geotype (C) were discerned among 24 wild-type isolates belonging to serotype 3. These strains exhibited a broad geographical distribution being found, in particular, in Armenia, Azerbaijan, Georgia, Turkmenistan and Tajikistan; on the other hand, the C-geotype strains exhibited only a relatively distant relatedness to a strain isolated outside of the FSU (in Oman).

Amino Acid Sequence↗

Comparative study of five methods for intratypic differentiation of polioviruses.

A coded panel of 90 poliovirus isolates, 30 of each of the three known serotypes, was used to evaluate five methods for the intratypic differentiation of polioviruses: (i) an enzyme-linked immunosorbent assay with polyclonal cross-absorbed antisera (PAb-E), (ii) a neutralization assay with type-specific monoclonal antibodies (MAb-N), (iii) a restriction fragment length polymorphism (RFLP) assay, (iv) a Sabin vaccine strain-specific PCR assay, and (v) a Sabin vaccine strain-specific cRNA probe hybridization (ProHyb) assay. Sequence analysis was used for the definitive characterization of the strains. The panel was distributed to five laboratories; each laboratory analyzed the strains by at least two methods. Each method was used by three or four laboratories. The total performance scores (percentage correct results per number of tests) of the five methods were 96.7% for PAb-E, 93.9% for MAb-N, 91.9% for RFLP assay, 93.3% for Sabin vaccine strain-specific PCR, and 97.4% for Sabin vaccine strain-specific ProHyb. Consistent results were obtained by each laboratory for 88 of 90 isolates (97.8%) examined by PAb-E, 81 of 90 isolates (90.0%) examined by MAb-N, 78 of 90 isolates (86.7%) examined by RFLP assay, 81 of 90 isolates (90.0%) examined by PCR, and 89 of 90 isolates (98.9%) examined by ProHyb assay. Six strains were classified differently by different methods. It is recommended that at least two methods be used for the intratypic differentiation of poliovirus isolates, and each method should be based on a different principle (i.e., antigenic properties and nucleotide sequence composition). If two assays yield discrepant results, further characterization, preferably by partial sequence determination, will be required for correct identification.

Environmental Microbiology↗

Paralytic poliomyelitis in Romania, 1984-1992. Evidence for a high risk of vaccine-associated disease and reintroduction of wild-virus infection.

Although poliomyelitis due to wild-virus infection has virtually disappeared from Romania, with no cases having been documented between 1984 and 1989, vaccine-associated paralytic poliomyelitis has been reported at very high rates for over two decades. In November 1990, to decrease the risk of vaccine-associated paralytic poliomyelitis, oral poliovirus vaccine produced in Romania was replaced by imported oral vaccine made by a Western European manufacturer. To better quantify the risk of vaccine-associated paralytic poliomyelitis and the impact of the change in vaccine manufacturer, the authors reviewed clinical, epidemiologic, and laboratory data on poliomyelitis cases that occurred in Romania from 1984 to 1992. Poliovirus isolates were characterized at the US Centers for Disease Control and Prevention. During the period 1984-1992, 132 confirmed cases of paralytic poliomyelitis were reported in Romania, of which 13 were classified as wild-virus-associated, 93 as vaccine-associated, and 26 as "of unknown origin." Wild type 1 poliovirus was isolated during 1990-1992 from nine of 13 (69%) cases in an outbreak that occurred primarily among undervaccinated gypsy children. Vaccine-associated cases were epidemiologically and virologically distinct from wild-virus cases. Of the 93 vaccine-associated cases, 45 children were recipients and 48 were contacts. The overall risk of vaccine-associated paralytic poliomyelitis in Romania (1 case per 183,000 doses of oral poliovirus vaccine distributed) was 14-fold higher than the risk in the United States. The risks of recipient vaccine-associated paralytic poliomyelitis related to the first dose of oral vaccine were similar for Romanian and imported vaccine (1 case per 95,000 doses and 1 case per 65,000 doses, respectively), as were the total risks of vaccine-associated paralytic poliomyelitis. These findings definitively demonstrate a substantially elevated risk of vaccine-associated paralytic poliomyelitis in Romania which was not affected by a change in oral poliovirus vaccine manufacturer.

Child, Preschool↗

Enterovirus 71 infections and neurologic disease--United States, 1977-1991.

Since first described in 1974, enterovirus 71 infections have been associated with severe neurologic disease, and widespread infection was suspected in 1987. To investigate enterovirus 71 activity further, data were reviewed for isolations reported nationally during 1977-1991, virology laboratories were contacted regarding isolations during 1985-1989, and medical records were reviewed for respective patients, 1985-1989. From 1977 to 1991, 193 culture-confirmed enterovirus 71 infections were identified: > or = 1 isolate each year. In 1987, 45 persons in 17 states were infected compared with a maximum of 22 persons in 1-8 states in the other years. Of these 45, 27 (60%) had the following: paralysis (6), Guillain-Barré syndrome (1), meningitis (18), or encephalitis (2). Enterovirus 71 has been endemic in the United States since at least 1977, was identified more frequently in 1987 than in other years, and continues to be an occasional cause of severe neurologic disease.

Adolescent↗

Echovirus 30 infection and aseptic meningitis in parents of children attending a child care center.

In July 1992, 13 parents with children attending a child care center (CCC) developed aseptic meningitis (AM) due to echovirus 30 (E30). To determine the extent of illness and risk factors for transmission, survey and blood specimens were collected from CCC families and teachers and from adult and pediatric controls. Infection was defined as the presence of anti-E30 IgM antibodies. CCC parents (60%, 67/111) and children (75%, 79/105) had significantly higher infection rates than did teachers (14%, 3/22), adult controls (24%, 10/41), and pediatric controls (24%, 17/70). Infected CCC parents had more severe illness (18% [12/65] had AM; 11% [7/65] were hospitalized) than did infected CCC children (3% [2/79] had AM and 1% [1/79] were hospitalized). More frequent handwashing among teachers compared with parents and among mothers of toddlers was associated with significantly lower rates of infection (P < or = .05). Education of parents about good handwashing practices may reduce transmission of E30 and other infectious agents from children to adults.

Adult↗

Vaccine-preventable disease susceptibility in a young adult Micronesian population.

Current US military recruit vaccination policy presumes that recruits have had a complete childhood immunization series. This assumption may not be appropriate for recruits from Micronesia, who may have had limited access to modern health care, including immunization programs. During 1988 and 1990, a cross-sectional serosurvey was conducted among 66 US military recruits, 56 from the Federated States of Micronesia and 10 from the Republic of the Marshall Islands, collectively referred to as Micronesia. Antibody seronegativity levels for 12 vaccine-preventable (or potentially so) diseases were: measles (52%), mumps (14%), rubella (21%), varicella (38%), diphtheria (39%) tetanus (0%), polio type 1 (4%), polio type 2 (0%), polio type 3 (14%), hepatitis A (9%), hepatitis B (17%), and hepatitis C (98%). Compared with Army recruits in general, Micronesian recruits were significantly more likely to be seronegative for measles and varicella and seropositive for hepatitis types A and B. Personal histories of disease were felt to be inadequate in predicting antibody status.

Adult↗

Immunogenicity of a supplemental dose of oral versus inactivated poliovirus vaccine.

In many developing countries, the immunogenicity of three doses of live, attenuated, oral poliovirus vaccine (OPV) is lower than that in industrialised countries. We evaluated serum neutralising antibody responses in 368 children aged 6 months and 346 children aged 9 months in Côte d'Ivoire who had previously received three doses of OPV at 2, 3, and 4 months of age, and who were then randomised to receive a supplemental dose of OPV or enhanced-potency inactivated poliovirus vaccine (IPV) at the time of measles vaccination. Although both vaccines increased seroconversion to all three poliovirus types, antibody responses were greater in the IPV group. Among children with no detectable antibody at baseline, IPV was 2 to 14 times more likely than OPV to induce seroconversion (type 1, 80% vs 40% at 6 months [p < 0.001] and 81% vs 14% at 9 months [p < 0.001]; type 3, 76% vs 22% at 6 months [p < 0.001], and 67% vs 5% at 9 months [p < 0.001]. Among children with detectable antibody at baseline, IPV was 1.4 to 7 times more likely than OPV to elicit 4-fold or more rises in antibody titre (p < 0.01). Geometric mean titres (GMTs) to all three poliovirus types were also consistently higher among IPV recipients than in OPV recipients when measured 4-6 weeks and 13-17 months after vaccination. Administration of a supplemental dose of IPV or OPV, which requires no additional visits or changes in the existing immunisation schedule, might improve protection against paralytic poliomyelitis in communities with suboptimum seroconversion rates after three doses of OPV.

Antibodies, Viral↗

Multiple primer pairs for polymerase chain reaction (PCR) amplification of human parvovirus B19 DNA.

Human parvovirus B19 is the etiologic agent of erythema infectiosum and transient aplastic crisis in patients with hemolytic anemias and has been associated with fetal death, arthritis, and chronic anemia. Acute B19 infection is best diagnosed by detection of IgM antibodies, whereas the diagnosis of chronic infection often requires the sensitivity of PCR to demonstrate presence of virus over time. To improve our ability to detect B19 DNA by polymerase chain reaction (PCR), we evaluated 19 primers combined into 16 different primer pairs for their ability to detect temporally and geographically diverse B19 isolates. All 16 pairs reacted with all isolates tested but with different sensitivity. Sequence analysis showed few nucleotide changes compared with published sequences. These changes did not explain observed differences in sensitivity between primer pairs. The most sensitive primer pairs detected 350 to 3500 DNA copies after 35 cycles. A second amplification cycle with nested primers improved the sensitivity 100-fold. These 16 primer pairs provide the diagnostic virologist with multiple options for B19 PCR assays.

Acute Disease↗

Paralytic poliomyelitis in Oman: association between regional differences in attack rate and variations in antibody responses to oral poliovirus vaccine.

Variation in attack rates of paralytic disease by region during the 1988-1989 epidemic of type 1 poliomyelitis in Oman provided the stimulus to test the hypothesis that these observations were due to regional differences in the response of infants to trivalent oral poliovirus vaccine (OPV). Seroprevalence studies of 394 children born during the outbreak were conducted in six different regions of Oman and in two socioeconomic status (SES) groups in the capital city of Muscat; a seroconversion study was also carried out in 105 infants born after the outbreak. Seroprevalence rates by region after receipt of at least three doses of OPV ranged from 90% to 100% (median 94%) to poliovirus type 1, and from 86% to 100% (median 97%) to type 2, and from 47% to 79% (median 72%) to type 3, with the lowest rates observed in regions with the highest incidence of type 1 paralytic disease. In Muscat, seroprevalence rates were also significantly lower in low versus high SES groups (type 1: 84% versus 98%, respectively [P = 0.006]; type 3: 59% versus 86%, respectively [P = 0.001]). In the seroconversion study conducted after the outbreak, 89%, 100% and 50% of infants had detectable antibodies to types 1, 2, and 3, respectively, after four doses of OPV. Low responses to type 3 were also associated with the occurrence of sporadic cases of type 3 poliomyelitis in 1991, in spite of high rates of coverage with at least four doses of OPV (> 96%) throughout the country.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Viral↗

Coxsackievirus B2 infection and aseptic meningitis: a focal outbreak among members of a high school football team.

In an investigation of a school outbreak of enterovirus-like illness and aseptic meningitis, an IgM antibody assay was used to identify persons with evidence of recent coxsackie virus B2 infection. During September and October 1989, 81 (25%) of 319 students and staff reported an enterovirus-like illness; of these, 17 (21%) also had aseptic meningitis. Attack rates for enterovirus-like illness were highest among varsity football team members (53%), and most of this illness occurred between 6 and 15 October. Coxsackie virus B2 was isolated from 2 varsity football players. IgM antibody studies confirmed that coxsackie virus B2 was the cause of the outbreak in the varsity football team and suggested it was not responsible for much of the disease in other students and staff: 63% of football team members were seropositive compared with 12% for other students in grades 6-12. This report illustrates the value of an IgM antibody assay in the investigation of enterovirus outbreaks to distinguish infection from illness.

Adolescent↗

Distribution of wild type 1 poliovirus genotypes in China.

Poliomyelitis remains an important public health problem in China. Most cases and outbreaks are associated with wild type 1 polioviruses. To obtain an overview of type 1 poliovirus transmission in China, partial genomic sequences were compared for 24 case isolates from 12 provinces. Because polioviruses evolve rapidly during infection of humans, the genetic relationships among isolates provide a measure of the extent of epidemiologic linkage among cases. The observed genetic relationships were complex: six different genotypes, apparently derived from five separate endemic origins, were found. One genotype was recombinant, having noncapsid sequences derived from the Sabin type 1 vaccine strain and capsid sequences derived from a genotype indigenous to several northern and eastern provinces. Some isolates from geographically separate provinces were closely related; other isolates were related to wild polioviruses found in neighboring countries. The combination of epidemiologic and virologic analyses may facilitate the development of more effective strategies for poliomyelitis eradication.

Base Sequence↗

Acute hemorrhagic conjunctivitis due to enterovirus 70 in American Samoa: serum-neutralizing antibodies and sex-specific protection.

Acute hemorrhagic conjunctivitis due to enterovirus 70 has caused extensive outbreaks in tropical areas since 1969. Between December 1, 1990, and March 4, 1991, an outbreak of acute hemorrhagic conjunctivitis due to enterovirus 70 occurred in American Samoa, where an outbreak due to the same agent had occurred in 1981. A survey of 5% of the households (134 households, 1,095 individuals) was conducted throughout the island of Tutuila. The outbreak affected 58% of the population, with age-specific attack rates greater than 50% for all age groups except children younger than 2 years. Attack rates were significantly higher for children 2-10 years old (65%) than in the remainder of the population. Women aged 21-40 years had higher rates than did men the same age (66 vs. 49%), possibly because of the close association of women and young children. At higher preepidemic titers, there was evidence of protection from clinical disease among males but not among females. Enterovirus 70 can cause large outbreaks even in a population already exposed in a previous large outbreak; protection due to previous infection is only partial.

Antibodies, Bacterial↗

Using the virus challenge dose in the analysis of virus neutralization assays.

We propose a new basis for adjusting the results of virus neutralization assays. These assays consist of two separate experiments performed in parallel: a virus titration experiment and a serum dilution assay. In the virus titration experiment, one estimates the amount of virus used in the assay (the virus challenge dose). In a typical virus neutralization assay, the virus challenge dose may range over an order of magnitude. In the serial dilution assay, one measures the serum neutralizing activity against a particular virus. Most standard methods use the virus titration results only to ensure that the overall experiment is acceptable; the specific results of the virus titration experiment are not used to adjust the estimate of serum neutralizing activity. Although adjustment based on calibration with reference sera could be done, this seldom occurs in practice. We use results from recent studies of the kinetics and stoichiometry of polio virus neutralization with monoclonal antibodies to develop a method to use results from the virus titration experiment to adjust the serum neutralizing activity directly. Our results also indicate that a simple ad hoc procedure can improve the accuracy of the estimated serum neutralizing activity.

Antibodies, Monoclonal↗

Genotype-specific in vitro amplification of sequences of the wild type 3 polioviruses from Mexico and Guatemala.

The extensive nucleotide sequence heterogeneity among independent genotypes of wild polioviruses permits the systematic design of genotype-specific molecular reagents. We have prepared two sets of polymerase chain reaction (PCR) primer pairs specific for the genotype of wild poliovirus type 3 recently endemic to Mexico and Guatemala. Nucleotide sequences of a representative wild type 3 virus isolated in Mexico in 1989 differed from the corresponding Sabin 3 (Leon 12 a1b) sequences at 167 of 900 positions within the VP1 region. From the sequence data, wild virus-specific primer pairs were designed to complement regions of high mismatch (greater than 33%) with Sabin 3 templates. Primer binding sites were spaced along the genome so that the predicted amplification products (142 bp and 163 bp) could be easily resolved electrophoretically from the products generated with our Sabin strain-specific primers (Sabin 1: 97 bp; Sabin 2: 71 bp; Sabin 3: 53 bp). RNAs of all wild type 3 poliovirus isolates from Mexico and Guatemala obtained over a 13-year period (1977-1990) served as efficient templates for amplification of the 142-bp and 163-bp products. Genomic templates derived from vaccine-related polioviruses and most heterologous wild polioviruses were inactive under equivalent reaction conditions. Amplifications generating a 114-bp product with a broadly reacting primer pair, matching highly conserved sequences in the 5'-noncoding region, provided a positive control for the presence in samples of poliovirus (or enterovirus) RNAs. Selective amplification of wild Mexico-Guatemala type 3 poliovirus sequences was obtained with either primer set in reactions containing large stoichiometric excesses (up to 10(6)-fold) of vaccine-related RNAs. We have used wild genotype-specific PCR primer sets to facilitate identification of wild polioviruses present in both clinical and environmental samples.

Amino Acid Sequence↗

Epidemiology of poliomyelitis in the United States one decade after the last reported case of indigenous wild virus-associated disease.

Poliomyelitis caused by wild poliovirus has been virtually nonexistent in the United States since 1980, and vaccine-associated paralytic poliomyelitis (VAPP) has emerged as the predominant form of the disease. We reviewed national surveillance data on poliomyelitis for 1960-1989 to assess the changing risks of wild-virus, vaccine-associated, and imported paralytic disease; we also sought to characterize the epidemiology of poliomyelitis for the period 1980-1989. The risk of VAPP has remained exceedingly low but stable since the mid-1960s, with approximately 1 case occurring per 2.5 million doses of oral poliovirus vaccine (OPV) distributed during 1980-1989. Since 1980 no indigenous cases of wild-virus disease, 80 cases of VAPP, and five cases of imported disease have been reported in the United States. Three distinct groups are at risk of vaccine-associated disease: recipients of OPV (usually infants receiving their first dose), persons in contact with OPV recipients (mostly unvaccinated or inadequately vaccinated adults), and immunologically abnormal individuals. Overall, 93% of cases in OPV recipients and 76% of vaccine-associated cases have been related to administration of the first or second dose of OPV. Our findings suggest that adoption of a sequential vaccination schedule (inactivated poliovirus vaccine followed by OPV) would be effective in decreasing the risk of VAPP while retaining the proven public health benefits of OPV.

Humans↗

Outbreak of paralytic poliomyelitis in Oman: evidence for widespread transmission among fully vaccinated children.

From January, 1988, to March, 1989, a widespread outbreak (118 cases) of poliomyelitis type 1 occurred in Oman. Incidence of paralytic disease was highest in children younger than 2 years (87/100,000) despite an immunisation programme that recently had raised coverage with 3 doses of oral poliovirus vaccine (OPV) among 12-month-old children from 67% to 87%. We did a case-control study (70 case-patients, 692 age-matched controls) to estimate the clinical efficacy of OPV, assessed the immunogenicity of OPV and extent of poliovirus spread by serology, retrospectively evaluated the cold chain and vaccine potency, and sought the origin of the outbreak strain by genomic sequencing. 3 doses of OPV reduced the risk of paralysis by 91%; vaccine failures could not be explained by failures in the cold chain nor on suboptimum vaccine potency. Cases and controls had virtually identical type 1 neutralising antibody profiles, suggesting that poliovirus type 1 circulation was widespread. Genomic sequencing indicated that the outbreak strain had been recently imported from South Asia and was distinguishable from isolates indigenous to the Middle East. Accumulation of enough children to sustain the outbreak seems to have been due to previous success of the immunisation programme in reducing spread of endemic strains, suboptimum efficacy of OPV, and delay in completing the primary immunisation series until 7 months of age. Additionally, the estimated attack rate of infection among children aged 9-23 months exceeded 25% in some regions, suggesting that a substantial proportion of fully vaccinated children had been involved in the chain of transmission.

Case-Control Studies↗