Bernard Cohen

Persistent B19 Parvovirus Infection in Patients Infected with Human Immunodeficiency Virus Type 1 (HIV-1): A Treatable Cause of Anemia in AIDS

OBJECTIVEnTo determine the role of B19 parvovirus in red cell aplasia of patients infected with human immunodeficiency virus type 1 (HIV-1).nnnDESIGNnUncontrolled clinical trial, with assay of serum, peripheral blood cells, and bone marrow for virus using DNA hybridization and immunocytochemistry techniques; these assays were then correlated with clinical findings, results of immunoassays for antivirus antibodies, and with immunoglobulin (Ig) therapy.nnnSETTINGnGovernment medical referral center, and university and private hospitals.nnnPATIENTSnSeven patients with pure red cell aplasia and serologic evidence of infection with HIV-1.nnnMEASUREMENTS AND MAIN RESULTSnAll patients had giant pronormoblasts in the bone marrow (present in transient aplastic crisis caused by acute B19 parvovirus infection). High concentrations of B19 parvovirus were demonstrated in sera, in several cases in samples separated by weeks or months. Viral DNA and capsid protein were present in the bone marrow of three patients studied, and active viral replication was detected by southern analysis. There was no antivirus IgG in capture immunoassay and no or very low levels of antivirus IgM. The patients did not have symptoms of fifth disease, the illness caused by this virus in immunologically normal persons. Six patients were treated with a regimen of intravenous commercial immunoglobulin. In all cases, this therapy resulted in rapid reduction in serum virus concentrations and full recovery of erythropoiesis. Relapses in two cases were predicted by DNA hybridization studies, and these cases were successfully retreated.nnnCONCLUSIONSnThe B19 parvovirus is a remediable cause of severe chronic anemia in HIV-infected patients. Recognition of and therapy for parvovirus in this population will avoid erythrocyte transfusion and should prevent transmission of the virus to other persons, including immunosuppressed persons and women of child-bearing age.

Neonatal Measles Immunity in Rural Kenya: The Influence of HIV and Placental Malaria Infections on Placental Transfer of Antibodies and Levels of Antibody in Maternal and Cord Serum Samples

INTRODUCTIONnYoung infants are protected from measles infection by maternal measles antibodies. The level of these antibodies at birth depends on the level of antibodies in the mother and the extent of placental transfer. We investigated predictors of levels of measles antibodies in newborns in rural Kenya.nnnMETHODSnA total of 747 paired maternal-cord serum samples (91 from human immunodeficiency virus [HIV]-infected and 656 from HIV-uninfected mothers) were tested for measles immunoglobulin G antibodies. Placental malaria infection was determined by biopsy. Data on pregnancy history, gestational age, and anthropometric and socioeconomic status were collected.nnnRESULTSnInfants born to HIV-infected mothers were more likely (odds ratio, 4.6 [95% confidence interval {CI}, 2.2-9.7]) to be seronegative and had 35.1% (95% CI, 9.8%-53.2%) lower levels of measles antibodies than did those born to HIV-uninfected mothers. Preterm delivery, early maternal age, and ethnic group were also associated with reduced levels of measles antibodies. There was little evidence that placental malaria infection was associated with levels of measles antibodies in newborns.nnnCONCLUSIONnOur results suggest that maternal HIV infection may reduce levels of measles antibodies in newborns. Low levels of measles antibodies at birth render children susceptible to measles infection at an early age. This is of concern in sub-Saharan African countries, where not only is the prevalence of HIV high, but measles is the cause of much morbidity and mortality.

Revaccination of Children after Completion of Standard Chemotherapy for Acute Leukemia

BACKGROUNDnAfter the treatment of patients with acute leukemia, there is a decrease in vaccine-specific antibody and an increased susceptibility to certain vaccine-preventable diseases. A simple revaccination schedule is warranted.nnnMETHODnFifty-nine children (age, 1-18 years) who had completed standard chemotherapy in accordance with Medical Research Council of United Kingdom protocols were recruited. All children received a single dose of Haemophilus influenzae type b (Hib), tetanus, diphtheria, acellular pertussis, meningococcus C, polio, measles, mumps, and rubella vaccines > or = 6 months after completion of treatment. Antibody concentrations were measured before vaccination and 2-4 weeks and 12 months after vaccination.nnnRESULTSnPrevaccination antibody levels were protective for all patients for tetanus (geometric mean concentration [GMC], 0.13 IU/mL; 95% CI, 0.1-0.17 IU/mL), for 87% for Hib (GMC, 0.5 microg/mL; 95% CI, 0.37-0.74 microg/mL), for 71% for measles (GMC, 301 mIU/mL; 95% CI, 163-557 mIU/mL), for 12% for meningococcus C (geometric mean titer [GMT], 1:2.9; 95% CI, 1:2.2 to 1:3.9), and for 11% for all 3 poliovirus serotypes. Revaccination resulted in a significant increase in levels of antibody to each vaccine antigen, with 100% of patients achieving optimal antitetanus antibody concentrations (defined as > 0.1 IU/mL; 1.5 IU/mL; 95% CI, 1.1-2.1 IU/mL), 93% achieving optimal antibody concentrations to Hib (defined as > 1.0 microg/mL; 6.5 microg/mL; 95% CI, 5.1-8.2 microg/mL), 94% achieving optimal antibody concentrations to measles (defined as > or = 120 mIU/mL; 2720 mIU/mL; 95% CI, 1423-5198 mIU/mL), 96% achieving optimal antibody concentrations to meningococcus C (defined as > or = 1:8; 1:1000; 95% CI, 1:483-1:2064), and 85% achieving optimal antibody concentrations to all the 3 poliovirus serotypes (defined as > or = 1:8). For the majority of subjects, protection persisted for at least 12 months after vaccination.nnnCONCLUSIONnRevaccination of children after standard chemotherapy is important, and protection can be achieved in the majority of these children using a simple schedule of 1 vaccine dose at 6 months after completion of leukemia therapy.

Revaccination with Measles, Tetanus, Poliovirus, Haemophilus influenzae Type B, Meningococcus C, and Pneumococcus Vaccines in Children after Hematopoietic Stem Cell Transplantation

BACKGROUNDnThere is a decrease in antibody levels after hematopoietic stem cell transplant (HSCT), and such patients may be at increased risk of acquiring vaccine-preventable infection. A simple and validated revaccination schedule is required. The aim of this study was to evaluate the immunogenicity of a revaccination schedule for pediatric HSCT recipients.nnnMETHODSnThirty-eight children (age, 1-18 years) who had undergone autologous or allogeneic HSCT for malignant diseases were recruited. All children received vaccinations in accordance with a predefined schedule. Antibody concentrations were measured before and 2-4 weeks after vaccination against tetanus; Haemophilus influenzae type b (Hib); meningococcus C; measles; poliovirus serotypes 1, 2, and 3; and 9 pneumococcus serotypes.nnnRESULTSnBefore vaccination, protective antibody levels were found for tetanus in 95% of patients (geometric mean concentration [GMC], 0.07 IU/mL; 95% CI, 0.05-0.1 IU/mL), for Hib in 63% (GMC, 0.34 microg/mL; 95% CI, 0.21-0.57 microg/mL), for measles in 60% (GMC, 102 mIU/mL; 95% CI, 41-253 mIU/mL), for meningococcus C in 11% (geometric mean titer [GMT], 1:4; 95% CI, 1:2-1:8.4), for all 3 poliovirus serotypes in 29%, and for all 9 pneumococcal serotypes in 0%. Vaccination resulted in a significant increase (P < or = .05) in antibody levels to each vaccine antigen studied, with 100% of patients achieving protection against tetanus (GMC, 2.2 IU/mL; 95% CI, 1.8-2.7 IU/mL), 100% achieving protection against Hib (GMC, 8.4 microg/mL; 95% CI, 7.6-9.3 microg/mL), 100% achieving protection against measles (GMC, 2435 mIU/mL; 95% CI, 1724-3439 mIU/mL), 100% achieving protection against meningococcus C (GMT, 1:5706; 95% CI, 1:3510-1:9272), 92% achieving protection against the 3 poliovirus serotypes, and > or = 80% achieving protection against each of the heptavalent pneumococcal conjugate vaccine-associated serotypes. No factors relevant to age, underlying disease, or treatment type were found to significantly influence responses.nnnCONCLUSIONnRevaccination of pediatric HSCT recipients in accordance with this revaccination schedule provides a high level of protection against these vaccine-preventable diseases.

Evaluation of a measles vaccine campaign in Ethiopia using oral-fluid antibody surveys

We undertook a study to demonstrate the potential contribution of oral-fluid (OF) antibody prevalence surveys in evaluating measles vaccine campaigns. In Asela town, southern Ethiopia, oral fluids were collected from 1928 children aged 9 months to 5 years attending for campaign immunization in December 1999 and 6 months later, from 745 individuals aged 9 months to 19 years, in the same location. Measles antibody status was determined by microimmune measles specific IgG enzyme immunoassay (EIA). Antibody prevalence was estimated at 48% in children attending for vaccination (pre-campaign), and 85% post-campaign in the comparable age group. The estimated reduction in the susceptible proportion was 75%. In older children the proportion antibody negative post-campaign was 28% in 7-9 year olds, and 13% in 10-14 year olds levels of susceptibility which raise concern over continued measles transmission. This is the first evaluation of a measles vaccine campaign based on oral-fluid seroprevalence surveys and it demonstrates the merit of oral-fluid surveys in informing health authorities about vaccination strategy refinement.

Kinetics of Decline of Maternal Measles Virus-Neutralizing Antibodies in Sera of Infants in France in 2006

ABSTRACT The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (≥120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.

Comparison of plaque reduction neutralisation test (PRNT) and measles virus-specific IgG ELISA for assessing immunogenicity of measles vaccination.

BACKGROUNDnPlaque reduction neutralisation test (PRNT) is a gold standard assay for measles antibodies. PRNT, however, is time-consuming and more difficult to standardise than ELISA.nnnMETHODSnPRNT results were obtained on pre- and post-vaccination sera from 501 measles-vaccinated infants. From this cohort a sub-set of 210 infants were selected for testing by ELISA, which was performed either manually or by an automated processor. Results were corrected for sampling proportion before comparing the assays.nnnRESULTSnSeroconversion was detected by PRNT in 454 infants of whom 324 were estimated to have seroconverted by manual ELISA and 191 by automated ELISA It is recommended that ELISA negative post-vaccination samples are re-tested by PRNT to detect all seroconversions.

SUBDURAL HEMATOMA RELATED TO ANTICOAGULATION THERAPY

Excerpt Spontaneous subdural hematoma is relatively rare. It has been reported as a complication of blood dyscrasias and, more recently, in association with ruptured aneurysm.1Although bleeding int...

Laboratory methods for assessing vaccine potency retained in aerosol outputs from nebulizers: application to World Health Organization measles aerosol project.

BACKGROUNDnLaboratory methods for measuring vaccine potency of nebulized aerosol are required to support clinical trials of measles aerosol vaccination.nnnMETHODSnMeasles vaccine containing the Edmonston Zagreb virus strain was reconstituted in sodium fluoride as tracer and nebulized from three devices. Emitted aerosol was collected using an impinger. Aliquots were removed from the impinger chamber for vaccine virus plaque assay and for fluoride measurement to determine aerosol output.nnnRESULTSnVaccine potency retention results were adjusted to take into account the effect of aerosol output on estimates. Adjusted potency of nebulized vaccine ranged from 88% to 102%.nnnCONCLUSIONSnNew laboratory methods to measure aerosol vaccine potency retention were reliable and accurate. The results demonstrated that Edmonston Zagreb vaccine remains robust during aerosolisation and imply that this is a viable candidate for further evaluation in the measles aerosol project.

Parvovirus B19 Infection in Pregnancy

Parvoviruses are widespread in nature, with a diversity of virus types affecting many animal species, usually in a species-specific manner. Some members of the parvovirus family give rise to asymptomatic infections but others are highly pathogenic, causing disease not only in adults but also in the young, the newborn and in the fetus. Parvoviruses of animals have for long been regarded as agents of reproductive failure and parvovirus B19 was recognised as a cause of fetal loss in humans in the 1980s. Moreover, following the control of congenital rubella by pre-pubertal and child vaccination, parvovirus B19 infection has emerged as probably the leading cause of viral embryopathy. This review will focus on the laboratory diagnosis of parvovirus B19 infection following exposure in pregnancy. The indications for testing maternal and fetal samples and the interpretation of test results will be discussed and a section is included on clinical management of the infection in pregnancy. The obstetric outcome in pregnant women who seroconvert will be reviewed.