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Biomedical subjects

B J Cohen

Publications and source records attributed to B J Cohen.

At least 37 records · Page 2Linked to original sources

Salivary diagnosis of rubella: a study of notified cases in the United Kingdom, 1991-4.

Rubella infections, notified by general practitioners on the basis of a clinical diagnosis, were investigated by testing blood and saliva samples for specific IgM. Overall 52 (29%) of 178 cases with appropriately timed blood specimens were confirmed as recent rubella by IgM serology. Only 2 (3%) of 74 cases in children under 5 years were confirmed compared to 50 (48%) of 104 cases in older children and adults. The confirmation rate was lower (6%) in those with documented vaccination history than in those without (42%). The specificity of saliva rubella IgM testing compared to testing corresponding blood samples was 99%. The overall sensitivity of saliva rubella IgM testing was 81%. This rose to 90% if results from inappropriately timed specimens and specimens taking more than 1 week to reach the laboratory were excluded. A corresponding saliva rubella IgG test was 98% sensitive and 100% specific. Of 126 rubella IgM negative cases, 25 (20%) were positive for parvovirus B19 IgM. This study confirmed that rubella surveillance based on clinical reports is not specific. It also demonstrated that saliva samples, if taken 7-42 days after onset of illness and transported rapidly to the laboratory, are a feasible alternative to blood samples for rubella surveillance.

Adolescent↗

Immediate and long term outcome of human parvovirus B19 infection in pregnancy.

OBJECTIVE: To estimate more precisely the risk of fetal loss and congenital abnormalities after maternal parvovirus B19 infection, and to assess the long term outcome for surviving infants. DESIGN: Prospective cohort study of pregnant women with confirmed B19 infection with follow up of the surviving infants. The rate of fetal loss in the study cohort was compared with that in pregnant women with varicella. SETTING: Cases reported by laboratories in England and Wales between 1985-1988 and 1992-1995. SAMPLE: Four hundred and twenty-seven pregnant women with B19 infection and 367 surviving infants of whom 129 were followed up at 7-10 years of age. METHODS: Questionnaires to obstetricians and general practitioners on outcome of pregnancy and health of surviving infants. Maternal infection confirmed by B19-specific IgM assay and/or IgG seroconversion. RESULTS: The excess rate of fetal loss in women with B19 infection was confined to the first 20 weeks of gestation and averaged 9%. Seven cases of fetal hydrops followed maternal infections between 9 and 20 weeks of gestation (observed risk 2.9%, 95% CI 1.2-5.9). No abnormalities attributable to B19 infection were found at birth in surviving infants (observed risk 0%, upper 95% CI 0.86%). No late effects were found at 7-10 years. CONCLUSIONS: Around 1 in 10 women infected before 20 weeks of gestation will suffer a fetal loss due to B19. The risk of an adverse outcome of pregnancy after this stage is remote. Infected women can be reassured that the maximum possible risk of a congenital abnormality due to B19 is under 1% and that long term development will be normal.

Cohort Studies↗

Detection of IgG antibody to Epstein-Barr virus viral capsid antigen in saliva by antibody capture radioimmunoassay.

A 'G' antibody capture radioimmunoassay (GACRIA) to detect IgG to Epstein-Barr virus (EBV) viral capsid antigen (VCA) in saliva is described. The monoclonal antibody to EBV VCA used in the GACRIA bound non-specifically when testing saliva samples having a total IgG content of less than 2.0 mg/l, so giving false positive results. This problem was overcome by including 0.5% EBV-negative human serum in the monoclonal antibody diluent. The performance of the assay was then evaluated by comparing the GACRIA test on serum and saliva samples to indirect immunofluorescence assay (IFA) results on sera using a panel of paired serum/saliva samples. Compared to the corresponding serum IFA the saliva GACRIA had a sensitivity and specificity of 93.5 and 100%, respectively. Although less sensitive than IFA on serum samples, the saliva GACRIA is sufficiently sensitive to be used for epidemiological screening and will enable testing for anti-EBV VCA to be carried out easily and on a wide scale.

Antibodies, Viral↗

Detection of parvovirus B19-specific IgM by antibody capture radioimmunoassay.

A solid phase IgM-capture radioimmunoassay (MACRIA) for the detection of parvovirus B19-IgM is described (Cohen et al., 1983, J. Hyg. Camb. 91, 113-130). IgM from a dilution of patients serum is 'captured' onto a solid phase coated by anti-human IgM. To determine whether any of the IgM is specific for parvovirus B19, B19 antigen is added followed by a detector system. In the MACRIA described here the detector system comprises a mouse monoclonal antibody to parvovirus B19 and a 125I-labelled anti-mouse antibody. A calibration curve derived from a standard B19 IgM serum is used to quantify B19 IgM using a single dilution of test sera. The purpose of the protocol is the diagnosis of recent acute infection with parvovirus B19.

Animals↗

Chronic anemia due to parvovirus B19 infection in a bone marrow transplant patient after platelet transfusion.

BACKGROUND: Many reports document the transmission of human parvovirus B19 (B19) infection by clotting factor concentrates manufactured from large plasma pools. Transmission via other blood components originating from a single donor or a small number of donors, however, seems to occur only rarely. The study reported here identifies a B19 infection that was transmitted via a platelet donation. CASE REPORT: A multiply transfused allogeneic bone marrow transplant patient developed chronic anemia due to persistent B19 infection. The anemia responded to therapy with intravenous immunoglobulin. It was postulated that a transfusion was the source of the B19 infection. Archived sera from 90 implicated blood donors were tested for B19 IgM and DNA by the use of dot-blot hybridization and a nested polymerase chain reaction with primers from the B19 nonstructural gene. B19 DNA from patient and donor sera were sequenced. One of the 90 blood donors (Donor A) was B19 IgM positive and had a high level of B19 DNA. The patient was viremic 3 days after transfusion of platelets from this donor, and the sequence of B19 DNA from the patient exactly matched that of B19 DNA from the donor. A second blood donor (Donor B) had a low level of B19 DNA but was IgM negative. The patient showed no evidence of B19 infection after the transfusion of red cells from Donor B, and the sequence of this donor's B19 DNA was different from that in the patient. CONCLUSION: Blood Donor A with asymptomatic acute B19 infection was the source of B19 infection in the bone marrow transplant patient. Donor B with a low level of B19 DNA was not the source of infection.

Adult↗

Educators' responses to changes in the health care system.

A survey was conducted to identity programmatic/curricular changes made by New York state nursing schools in response to the changing health care environment and to identity the success of job placement for new graduates. Data were reported for 84 programs. Respondents indicated that innovative curriculum initiatives were employed, such as increasing community experiences and primary health care content. Opportunities for job placement were enhanced by a number of strategies, including resume writing and job interviewing workshops.

Curriculum↗

Sequence analysis of a parvovirus B19 isolate and baculovirus expression of the non-structural protein.

Serology for parvovirus B19 has been hampered by limited availability of antigen which has often had to be isolated from viraemic blood donations. We have determined the sequence of the genome of one such isolate (Stu). It is 99% similar to the sequences of two other isolates (Wi and Au) except at the far 5'-end, where it is more similar to the terminus of another isolate (Ala/Alb). Recombinant nonstructural protein, NS, was constructed. Antibodies to NS, as well as to the capsid proteins, VP1/2, were detected in patients with B19 infection.

Animals↗

A school outbreak of parvovirus B19 infection investigated using salivary antibody assays.

An outbreak of parvovirus B19 infection at a primary school was investigated using saliva samples. Antibody capture immunoassays for salivary B19 IgG and IgM were developed using a recombinant B19 antigen and monoclonal antibody to B19 virus. Evaluation of the salivary IgG assay using paired serum and saliva samples from 43 staff at St Thomas' Hospital showed that it had a sensitivity of 100% and a specificity of 95%. Evaluation of the salivary B19 IgM assay using 87 paired blood and saliva samples from a study of general practitioner rubella notifications showed it had a sensitivity of 60% and a specificity of 98%. Using the salivary assay the level of B19 IgG within 2 weeks of the start of the outbreak ranged from 5-33% in children and 29% in staff. By detecting salivary B19 IgM and/or B19 IgG seroconversions, attack rates of 8-50% in children in different classes and 47% in staff were observed. Household transmission was also studied and an attack rate of 45% was recorded in 11 susceptibles. After the outbreak, the level of B19 IgG in children with the highest attack rates was 60-70%, similar to that seen in adults in the UK. This study highlights the risk of B19 infection in an institutional setting and shows that saliva samples are a useful alternative to blood.

Adolescent↗

Transmission of symptomatic parvovirus B19 infection by clotting factor concentrate.

The risk of acquiring diseases from transfusion of blood and blood products is well recognized and the issue of parvovirus in haemophiliacs is not a new one. We report two patients with haemophilia acquiring iatrogenic parvovirus B19 infection, resulting in life-threatening sepsis in one, and immunocompetent adult. Over the last 10 years there has been great progress in manufacturing safer products with regard to enveloped viruses such as HIV, hepatitis B and C. A recent outbreak across Europe of hepatitis A in haemophiliacs treated with plasma-derived factor VII concentrates has made haemophilic treaters concerned about the known (parvovirus B19 and hepatitis A) and the unknown non-lipid enveloped viruses that may be contained in the clotting factor concentrates, because these are resistant to the existing viral inactivating techniques. The possibility of HIV itself mutating into a non-lipid enveloped virus emphasizes the need to seek and use safer products.

Adult↗

Diagnosis of parvovirus B19 infection by detection of specific immunoglobulin M antibody in saliva.

Serum and saliva samples were simultaneously collected from patients with B19 infection. Specimens were collected in a period of 1 to 18 days after the onset of symptoms. Saliva samples were collected with a commercial device, OraSure. The quality of these samples was evaluated by determining the concentration of total immunoglobulin G (IgG) by an enzyme immunoassay. The concentration of IgG in these samples ranged from 4.8 to > 250 mg/liter. B19 infection was confirmed for 20 patients by testing sera in a 1: 100 dilution by an IgM capture enzyme immunoassay (MACEIA) and an IgM capture hemadherence test (MACHAT). Saliva samples from these IgM-positive patients were tested neat by MACEIA and MACHAT. IgM could be detected in 11 of 20 (55%) samples by MACEIA and in 15 of 18 (83%) samples by MACHAT. Serum and saliva samples from a further 17 patients with rash were also tested. All of these specimens were unreactive by both assays. These results show that saliva may be a convenient alternative to serum for the diagnosis of recent B19 infection.

Antibodies, Viral↗

Evaluation of 4 commercial test kits for parvovirus B19-specific IgM.

Four commercial test kits for parvovirus B19 IgM were evaluated by testing 491 sera assembled into 7 panels. The serum panels were designed to assess sensitivity and specificity of the commercial assays and to reflect the various clinical settings in which acute B19 infection forms part of the differential diagnosis. A mu-capture radioimmunoassay (MACRIA) was used as the reference test. With respect to MACRIA, the commercial B19 IgM assays showed an overall sensitivity of 70.1-84.1% and specificity of 92.2 to 97.4%. Assay performance varied in different clinical situations. In sera from adults with acute B19 arthropathy, all 4 assays were 100% sensitive, but in children with fifth disease, the sensitivity ranged from 44.1 to 88.6%. The sensitivity of all 4 assays was also low when testing samples collected more than 6 weeks after onset of symptoms and in women with B19-associated embryopathy. Specificity was greater than 97% in healthy blood donors, but varied from 70.9 to 83.3% in patients acutely infected with other viruses, including rubella. Although the IgM test kits here evaluated may be usefully introduced for B19 diagnosis in certain settings, knowledge of their limitations will be important when results have been interpreted.

Acute Disease↗

Accurate serodiagnosis of B19 parvovirus infections by measurement of IgG avidity.

In an attempt to improve diagnosis of illnesses caused by parvovirus B19 and to discriminate primary from secondary infections, a protein-denaturing assay for avidity of parvovirus-specific IgG antibodies was developed. The assay used three types of purified recombinant antigens: a fusion protein containing the unique portion of the structural protein VP1, entire capsids made up of the major structural protein VP2 alone, or VP2 plus VP1. The avidity assays were evaluated by testing sequential acute-phase serum samples from 61 well-characterized patients (34 were followed > or = 6 months), sera from 38 controls with evidence of past infection, and sera from 388 seropositive patients studied for evidence of B19 infection during an epidemic. Parvovirus capsids consisting of VP2 alone yielded unusual IgG avidity and IgG antibody responses. Three different IgG avidity assays based on VP1 protein antigens were highly sensitive and specific and were considered suitable for identification of recent primary infections by human parvovirus B19.

Antibodies, Viral↗

Morphology and antigenicity of recombinant B19 parvovirus capsids expressed in transfected COS-7 cells.

COS-7 cells transfected with parvovirus B19-simian virus 40 (SV40) hybrid vectors have previously been shown to express B19 structural proteins. In this study the morphology and antigenicity of B19 proteins expressed in these cells were investigated. At 84 h after transfection, approximately 10% of the COS-7 cells expressed B19 antigen, and the yield was equivalent to 2 x 10(3) to 2 x 10(5) B19 particles/transfected cell. The B19 proteins self-assembled into capsids that were morphologically and antigenically similar to native B19 virions, and could substitute for native antigen in a B19 IgM assay. Recombinant capsids lacking the recently described 11 kDa protein also resembled native virions.

Animals↗

A simple and sensitive DNA hybridization assay used for the routine diagnosis of human parvovirus B19 infection.

A dot blot hybridization assay for parvovirus B19 diagnosis was developed by using a PCR-generated probe, digoxigenin labelling, and chemiluminescence detection. Different labelling techniques and hybridization solutions were evaluated. From this analysis a protocol was devised for routine diagnostic use. The protocol enabled 1 pg of B19 DNA to be detected. The results of applying this method to 8,369 diagnostic samples collected during 1994 and 1995 are given.

Base Sequence↗

Anticomplementary activity in serum samples from patients with acute parvovirus B19 infection.

Of 65 serum samples submitted for diagnostic purposes which proved to be anti-complementary by complement fixation test, 49 were parvovirus B19 IgM positive. Forty four of the 49 serum samples were from patients with arthropathy. Acute parvovirus B19 infection should be suspected when a patient has symptoms of disease of the joints and the serum is anticomplementary.

Acute Disease↗

Successful treatment of parvovirus B19 infection and red cell aplasia occurring after an allogeneic bone marrow transplant.

Chronic parvovirus B19 infection in the immunocompromised host may cause severe anaemia secondary to failure of erythropoiesis. This has been previously documented in patients with the Acquired Immune Deficiency Syndrome (AIDS), congenital immunodeficiencies and in children with acute lymphoblastic leukaemia during maintenance chemotherapy. We describe persistent parvovirus infection in a 14-year-old boy after HLA-matched sibling allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in second remission.

Adolescent↗

Age specific antibody prevalence to parvovirus B19: how many women are infected in pregnancy?

Infection with parvovirus B19 is an important cause of late fetal mortality in the second trimester, and many infections in pregnancy remain undiagnosed. A serological survey stratified by age has been used to estimate the incidence of maternal infection with parvovirus B19 in pregnancy. Serum remaining from specimens submitted for diagnosis from 6864 people of all ages to seven public health laboratories in England was tested for antibody to parvovirus B19. The antibody prevalence rose with age to 45% at 10 years and 60% to 70% in adults. The age specific force of infection was highest in children aged less than 10 years and lowest in adults. Maternal infection with parvovirus B19 is estimated to occur in approximately one pregnancy in 400. It has been estimated that fetal death occurs in 9% of these cases, which suggests that parvovirus B19 may cause more than 150 fetal deaths in England and Wales each year. Testing for evidence of recent infection with parvovirus B19 should be considered for unexplained cases of fetal hydrops in the second trimester, especially in years of parvovirus B19 epidemics.

Adolescent↗