Measles vaccine immunogenicity and antibody persistence in 12 vs 15-month old infants.

HYPOTHESIS: Maternal measles immunity in the United States today is primarily vaccine induced, with corresponding lower antibody titers in infants, as compared to infants born in an earlier era to mothers with naturally acquired measles immunity. We hypothesized that, due to lower titer of passively transferred maternal measles antibody, administration of measles vaccine at 12 months of age would result in seroconversion and antibody persistence comparable to vaccination at 15 months of age. POPULATION: Children at both an urban hospital and a suburban clinic. METHODS: Informed consent was obtained from mothers for the infants to receive M-M-R(R)II vaccine at either 12 or 15 months and to have serum samples obtained before vaccination and 4 weeks post-vaccination (PV). Between 9 and 39 months PV, a third serum sample was obtained from 28% of seroconverters. A diary of adverse experiences was kept for 3 weeks PV. Sera were assayed by a microneutralization assay (NT) and an enzyme immunoassay (EIA) for measles antibody. RESULTS: Both age groups tolerated vaccination well with minor and transient side effects. Forty-four of 47 (94%) 12-month-old infants seroconverted by NT, compared to 45 of 46 (98%) 15-month-olds (p=NS). There was no statistically significant decline in median NT titers or EIA titers in nineteen 12-month-olds and thirteen 15-month olds followed for 9-39 months PV. CONCLUSION: This study showed comparable serologic responses in 12- vs 15-month-old infants born to measles vaccine-immune mothers; however, the sample size was too small to have adequate power and further study is indicated. Titers of antibody were constant in both the 12-month-old and the 15-month-old infants, over a 9-39 month period, suggesting that waning immunity over this period of time is not a problem in either age group.

Immune response to measles vaccine in 6-month-old infants of measles seronegative mothers.

Determinants of measles vaccine-induced immune response in infancy include maternal immune status and the infant's age at immunization. In a previously published study, 74% of 19 6-month-old infants developed neutralizing antibody. Two of the infants were born to measles seronegative mothers. In order to (1) assess the prevalence of measles seronegativity in a population of US mothers born after 1960 and (2) assess the immunogenicity of standard titer measles vaccine in 6-month-old infants of measles seronegative mothers, mothers with healthy term (> or = 37 weeks gestation) infants attending well child care clinics at MetroHealth Medical Center were prospectively screened for measles antibody by EIA. If negative, maternal samples were retested for neutralization (NT) antibody. Fifteen of 169 women were seronegative by both assays. Six-month-old infants of 9 of these 15 seronegative mothers were enrolled in the pediatric vaccine study. Serological response of these 9 infants to monovalent measles vaccine (Attenuvax) was compared to the responses of 17 6-month-old infants of seropositive mothers and 15 15-month-old toddlers from our previous study. All 9 infants of seronegative mothers became EIA seropositive after the vaccine compared to 9 of 17 6-month-old infants born to seropositive mothers (p = 0.02). Differences in NT seroconversion rates (100% vs 70.6%) were not statistically significant. The comparison group of 15-month-old vaccinees showed 100% seroconversion by both assays. The NT geometric mean titer (GMT) was higher in the 15-month-old toddlers than in the 6-month-old infants born to seronegative mothers (87.2 vs 33.9, p < 0.01), suggesting age-related differences in humoral immune response unrelated to passively transferred maternal antibody.

Serologic responses to hepatitis C virus in solid organ transplant recipients.

BACKGROUND: Hepatitis C (HCV) infection is known to have been transmitted by both blood transfusion and donor organs. We sought to determine the historical incidence of donor- and transfusion-acquired HCV infection in kidney transplant (RTx) and heart transplant (HTx) recipients at our center and to study the kinetics of seroconversion to HCV. METHODS: A bank of sera collected from organ donors (388 RTx and 88 HTx) who received allografts between January 1984 and April 1992 was screened for anti-HCV using a third generation enzyme immunoassay. Recipient sera collected before transplant (preTx), at 1 year after transplant, and at last follow-up were tested. Fresh follow-up sera on all surviving anti-HCV-positive (+) RTx and HTx, all anti-HCV-negative (-) HTx, and a subset of 85 anti-HCV- RTx were assayed for HCV RNA using an reverse transcriptase-polymerase chain reaction assay. RESULTS: Twenty-four of 388 RTx (6.2%) and 2 of 88 HTx (2.3%) were anti-HCV+ preTx. Eight of 218 (3.7%) organ donors were anti-HCV+. Six of the seven (85.7%) anti-HCV+ donors with adequate recipient follow-up transmitted HCV infection to one or more recipients. Nineteen of 313 RTx (6.1%) and 8 of 72 HTx (11.1%) with follow-up > or =1 year seroconverted to anti-HCV. One of 85 (1.2%) anti-HCV- RTx and 3 of 44 (6.8%) anti-HCV-HTx were HCV RNA+ when tested at last follow-up. Five cases of de novo HCV infection occurred after the introduction of first generation anti-HCV screening of donors. Persistent viremia (HCV RNA+) at last follow-up was observed in 70.6% (12/17) RTx anti-HCV+ preTx. Fourteen of 15 (93.3%) RTx and 9 of 9 (100%) HTx with de novo HCV infection had persistent viremia. Seroconversion was more delayed in HTx than RTx (P=0.0572, log-rank Mantel-Cox statistic) although both groups demonstrated an impaired humoral response to HCV when compared with the immunocompetent host. CONCLUSIONS: Organ donor- and transfusion-acquired HCV infection was common in RTx and HTx transplanted before the introduction of second generation anti-HCV screening in 1992. Serologic responses to HCV are often delayed and sometimes absent in these patients. Assays for HCV RNA should be considered as a screening test for the detection of HCV infection in this population. Serologic responses to HCV were more impaired in HTx compared with RTx, which may reflect the more intensive immunosuppressive regimens given to HTx at our center.

Molecular analysis provides evidence for human to human transmission of Staphylococcus aureus endocarditis in non-drug abusers.

Two cases of invasive Staphylococcus aureus are reported in which human to human transmission resulted in primary bacteremia and endocarditis. The identity of the organism was confirmed by phage typing, antibiograms, coagulase gene polymorphisms and ribotyping. This is the first documented case of such transmission not involving an intravenous drug abuser.

Measles vaccine immunogenicity in 6- versus 15-month-old infants born to mothers in the measles vaccine era.

HYPOTHESIS: The low titer of measles antibody in infants of mothers with vaccine-induced immunity may allow immunization against measles before 15 months of age. METHODS: Six- and 15-month-old infants born to mothers < or = 30 years of age with no history of measles were recruited. Infants enrolled at 6 months of age were immunized with monovalent measles vaccine (Attenuvax), and maternal serum and infant pre- and postvaccination sera were obtained. Those enrolled for primary vaccination at 15 months of age received either Attenuvax (N = 12) or M-M-RII (N = 3). Six-month-old infants were revaccinated with M-M-RII at 15 months of age; pre- and postrevaccination sera were again obtained. Three antibody assays were used: a measles neutralizing assay (NT) and two enzyme immunoassays (EIA) for measles IgG and measles IgM. RESULTS: Among primary vaccinees, 14 of 19 infants aged 6 months (74%) developed NT antibody, as did 15 of 15 infants aged 15 months (100%). The reciprocal geometric mean titer of 6-month-old seroresponders was 23.3, significantly lower than that of the 15-month-old primary vaccinees (87.7, P < .001). Primary seroconversion rates by EIA were 53% for 6-month-old infants and 100% for those aged 15 months. Revaccination of infants who had received Attenuvax at 6 months of age resulted in 100% NT positivity; the geometric mean titer rose to equal that of the group given primary immunization at 15 months of age. Measles IgM antibody was detected in 10 of 14 infants tested 1 month after primary vaccination at 15 months, but was not detected in any of the revaccinated infants after the second dose at 15 months of age (P < .001). CONCLUSIONS: 1) Immunization with measles vaccine in infants born to vaccine-immune mothers at 6 months of age induced NT antibody in 74% of infants. 2) Revaccination of prior 6-month-old vaccinees at 15 months resulted in antibody titers equivalent to 15-month-old vaccinees. 3) Lack of an IgM response following revaccination suggests that even seronegative infants may be primed to respond on re-exposure to measles.

Major outbreak of pertussis in northern Alberta, Canada: analysis of discrepant direct fluorescent-antibody and culture results by using polymerase chain reaction methodology.

A major outbreak of 5,683 cases of pertussis occurred in northern Alberta, Canada, from December 1989 to January 1991. The outbreak highlighted a number of problems with current methods of pertussis diagnosis. In particular, an exceptionally high proportion of direct fluorescent-antibody (DFA)-positive, culture-negative specimens (88.4%) was identified. We took this opportunity to use polymerase chain reaction (PCR) methodology to examine whether the low culture rates were due to specimens containing dead organisms or whether the DFA results represented high numbers of false-positive results. A set of primer sequences within a Bordetella pertussis-specific repetitive element was used to amplify proteinase K extracts of B. pertussis DNA recovered from 279 submitted slides inoculated at the point of collection with nasopharyngeal material obtained from pernasal swabs. The PCR data corroborated the culture results: 84.6% of DFA-positive, culture-negative specimens were similarly PCR negative. At least three different bacterial species that were significantly cross-reactive with the commercial DFA reagent were identified in clinical specimens and in pure culture, providing one possible explanation for the false-positive DFA results. These results and other limitations of current diagnostic techniques underline the urgent need for a new DFA reagent with improved specificity and a standardized means of measuring the patient antibody response for the diagnosis of pertussis.

Reduced measles immunity in infants in a well-vaccinated population.

The recommended age for measles vaccination is based in part on information gathered when most mothers had natural measles. Nowadays many mothers have received measles vaccine. To assess this change measles antibody neutralization titers (NT) were determined for 278 mother-infant pairs. One hundred sixty-four mothers, born before 1958, likely had had natural measles (Group 1). Sixty mothers received one to three killed plus one attenuated measles vaccination (Group 2) and 54 received 1 attenuated measles vaccination only (Group 3). NT were determined for the mother and for the infant at birth and in the infant during the fourth and sixth months. Group 1 mothers and infants at every age had higher geometric mean NT than those in Groups 2 or 3 (P less than 0.05). By 7 months 65% of Group 1 infants and greater than 90% of Group 2 and 3 infants had an NT less than 1:10. The rate of antibody decay was significantly faster for Group 1 infants (P less than 0.05). Earlier vaccination in the infant should be considered.

Measles virus specific antibody in infants in a highly vaccinated society.

Measles virus specific antibody levels were measured in infants from 2 to 12 months of age. The sera were tested by hemagglutination-inhibition (HI), neutralization (NT), and enzyme immunoassay (EIA) methods. The results of this study indicate that in the population examined, infants at an early age have very low or no immunity of maternal origin to measles virus-93% of the infants were without detectable neutralizing antibody (NT titer less than or equal to 10) at 6 months of age, and by the end of the first year of life 100% had no neutralizing antibody.

Nuclear accumulation of measles virus nucleoprotein associated with a temperature-sensitive mutant.

A measles virus (MV) Lec strain conditional-lethal (temperature-sensitive) mutant, designated MV ts38, has been isolated from 5-fluorouracil-mutagenized stock. The mutant has been characterized with regard to growth characteristics at 32 degrees C (permissive temperature) and 39 degrees C (non-permissive temperature). Virus-specific RNA transcription and/or translation appeared to be blocked at the non-permissive temperature as no virus-specific products could be detected by biochemical or immunological procedures. Following initiation of viral replication at 32 degrees C, with subsequent shift-up to 39 degrees C, presynthesized nucleoprotein (NP) was transported to, and accumulated in the cell nucleus whereas other viral proteins could not be detected there. A corresponding accumulation of NP in the nucleus is most often seen in association with MV neurotropic subacute sclerosing panencephalitis isolates in vivo and in vitro.