Waning of maternal antibodies against measles, mumps, rubella, and varicella in communities with contrasting vaccination coverage.
ABSTRACT: BACKGROUND: The combined measles, mumps, and rubella (MMR) vaccine has been successfully administered for >20 years. Because of this, protection by maternal antibodies in infants born to vaccinated mothers might be negatively affected. METHODS: ?A large cross-sectional serologic survey was conducted in the Netherlands during 2006-2007. We compared the kinetics of antibody concentrations in children and women of childbearing age in the highly vaccinated general population with those in orthodox Protestant communities that were exposed to outbreaks. RESULTS: ?The estimated duration of protection by maternal antibodies among infants in the general population, most of whom were born to vaccinated mothers, was short: 3.3 months for measles, 2.7 months for mumps, 3.9 months for rubella, and 3.4 months for varicella. The duration of protection against measles was 2 months longer for infants born in the orthodox communities, most of whom had unvaccinated mothers. For rubella, mothers in the orthodox communities had higher concentrations of antibodies as compared to the general population. CONCLUSION: ?Children of mothers vaccinated against measles and, possibly, rubella have lower concentrations of maternal antibodies and lose protection by maternal antibodies at an earlier age than children of mothers in communities that oppose vaccination. This increases the risk of disease transmission in highly vaccinated populations.
Project description:In 2013 and 2014, the Netherlands experienced a measles outbreak in orthodox Protestant communities with low measles-mumps-rubella vaccination coverage. Assessing total outbreak costs is needed for public health outbreak preparedness and control. Total costs of this outbreak were an estimated $4.7 million.
Project description:BackgroundChildhood vaccination schedules recommend vaccine doses at predefined ages.AimWe evaluated vaccination completeness and timeliness in Jerusalem, a district with recurrent vaccine-preventable disease outbreaks.MethodsVaccination coverage was monitored by the up-to-date method (vaccination completeness at age 2 years). Timeliness of vaccination was assessed in children (n = 3,098, born in 2009, followed to age 48 months, re-evaluated at age 7 years) by the age-appropriate method (vaccine dose timeliness according to recommended schedule). Vaccines included: hepatitis B (HBV: birth, 1 month and 6 months); diphtheria, tetanus, acellular pertussis, polio, Haemophilus influenzae b (DTaP-IPV-Hib: 2, 4, 6 and 12 months); pneumococcal conjugate (PCV: 2, 4 and 12 months); measles-mumps-rubella/measles-mumps-rubella-varicella (MMR/MMRV: 12 months) and hepatitis A (HAV: 18 and 24 months).ResultsOverall vaccination coverage (2014 cohort evaluated at age 2 years) was 95% and 86% for MMR/MMRV and DTaP-IPV-Hib4, respectively. Most children (94%, 91%, 79%, 95%, 92% and 82%) were up-to-date for HBV3, DTaP-IPV-Hib4, PCV3, MMR/MMRV1, HAV1 and HAV2 vaccines at 48 months, but only 32%, 28%, 38%, 58%, 49% and 20% were vaccinated timely (age-appropriate). At age 7 years, the median increase in vaccination coverage was 2.4%. Vaccination delay was associated with: high birth order, ethnicity (higher among Jews vs Arabs), birth in winter, delayed acceptance of first dose of DTaP-IPV-Hib and multiple-dose vaccines (vs MMR/MMRV). Jewish ultra-Orthodox communities had low vaccination coverage.ConclusionsConsiderable vaccination delay should be addressed within the vaccine hesitancy spectrum. Delays may induce susceptibility to vaccine-preventable disease outbreaks; tailored programmes to improve timeliness are required.
Project description:Background:Many measles cases in Tianjin, China, occur in infants whose mothers were born after widespread vaccination programs. We assessed age-specific decreases in maternal measles antibodies in infants and examined maternal and infant characteristics in relation to infant antibody titers. Methods:Infant and mother dyads were enrolled from a sample of immunization clinics in all Tianjin districts. Participants' antibody titers were measured from dried blood spots. A multivariable log-linear model regressed infant antibody titers onto infant and mother characteristics. Results:Among 551 infants aged ?8 months, protective levels of measles antibodies were observed in infants whose mothers had measles titers ?800 IU/mL (mean antibody titer, 542.5 IU/mL) or 400 to <800 IU/mL (mean, 202.2 IU/mL). Compared with infants whose mothers had no history of disease or vaccination, those with a history of disease had 1.60 times higher titers (95% confidence interval, 1.06-2.43). Conclusions:Limited vaccination programs in the 1980s have resulted in many Chinese women with inadequate protection against measles and an accordingly low efficiency of transplacental transmission to a fetus. Current vaccination programs, which target children aged 8 months through adolescence may be ineffective in controlling transmission of measles to infants.
Project description:New methods to increase measles and rubella (MR) vaccination coverage are needed to achieve global and regional MR elimination goals.Here, we developed microneedle (MN) patches designed to administer MR vaccine by minimally trained personnel, leave no biohazardous sharps waste, remove the need for vaccine reconstitution, and provide thermostability outside the cold chain. This study evaluated the immunogenicity of MN patches delivering MR vaccine to infant rhesus macaques.Protective titers of measles neutralizing antibodies (>120 mIU/mL) were detected in 100% of macaques in the MN group and 75% of macaques in the subcutaneous (SC) injection group. Rubella neutralizing antibody titers were >10 IU/mL for all groups. All macaques in the MN group were protected from challenge with wild-type measles virus, whereas 75% were protected in the SC group. However, vaccination by the MN or SC route was unable to generate protective immune responses to measles in infant macaques pretreated with measles immunoglobulin to simulate maternal antibody.These results show, for the first time, that MR vaccine delivered by MN patch generated protective titers of neutralizing antibodies to both measles and rubella in infant rhesus macaques and afforded complete protection from measles virus challenge.
Project description:Immunization and nutritional interventions are mainstays of child health programs in sub-Saharan Africa, yet few published data exist on their interactions. HIV-exposed (but uninfected) infants enrolled in a randomized placebo-controlled trial of multivitamin supplements (vitamins B complex, C, and E) conducted in Tanzania were sampled for an assessment of measles IgG quantity and avidity at 15 to 18 months. Infants were vaccinated between 8.5 and 12 months of age, and all mothers received high-dose multivitamins as the standard of care. Of 201 HIV-exposed infants who were enrolled, 138 (68.7%) were seropositive for measles. There were no effects of infant multivitamin supplementation on measles seroconversion proportions, IgG concentrations, or IgG avidity (P > 0.05). The measles seroconversion proportion was greater for HIV-exposed infants vaccinated at 10 to 11 months of age than for those vaccinated at 8.5 to 10 months (P = 0.032) and greater for infants whose mothers had a CD4 T-cell count of <200 cells/?l than for infants whose mothers had a CD4 T-cell count of >350 cells/?l (P = 0.039). Stunted infants had a significantly decreased IgG quantity compared to nonstunted infants (P = 0.012). As for measles avidity, HIV-exposed infants vaccinated at 10 to 11 months had increased antibody avidity compared to those vaccinated at 8.5 to 10 months (P = 0.031). Maternal CD4 T-cell counts of <200 cells/?l were associated with decreased avidity compared to counts of >350 cells/?l (P = 0.047), as were lower infant height-for-age z-scores (P = 0.016). Supplementation with multivitamins containing B complex, C, and E does not appear to improve measles vaccine responses for HIV-exposed infants. Studies are needed to better characterize the impact of maternal HIV disease severity on the immune system development of HIV-exposed infants and the effect of malnutrition interventions on vaccine responses. (This study has been registered at ClinicalTrials.gov under registration no. NCT00197730.).
Project description:BACKGROUND:Measles is endemic in the Democratic Republic of the Congo (DRC), and 89-94% herd immunity is required to halt its transmission. Much of the World Health Organization African Region, including the DRC, has vaccination coverage below the 95% level required to eliminate measles, heightening concern of inadequate measles immunity. METHODS:We assessed 6706 children aged 6-59?months whose mothers were selected for interview in the 2013-2014 DRC Demographic and Health Survey. History of measles was obtained by maternal report, and classification of children who had measles was completed using maternal recall and measles immunoglobulin G serostatus obtained from a multiplex chemiluminescent automated immunoassay dried blood spot analysis. A logistic regression model was used to identify associations of covariates with measles and seroprotection, and vaccine effectiveness (VE) was calculated. RESULTS:Out of our sample, 64% of children were seroprotected. Measles vaccination was associated with protection against measles (OR: 0.15, 95% CI: 0.03, 0.81) when administered to children 12?months of age or older. Vaccination was predictive of seroprotection at all ages. VE was highest (88%) among children 12-24?months of age. CONCLUSION:Our results demonstrated lower than expected seroprotection against measles among vaccinated children. Understanding the factors that affect host immunity to measles will aid in developing more efficient and effective immunization programs in DRC.
Project description:Immunity to measles, mumps, rubella, and varicella-zoster viruses (VZV; MMRV) is a common condition of employment for health care workers (HCWs) to ensure compliance with national standards and state laws. When documentation of complete vaccination or laboratory-confirmed infection is not available, Advisory Committee on Immunization Practices (ACIP) criteria are used to guide vaccination or anti-MMRV IgG testing. We assessed the performance of the BioPlex 2200 MMRV IgG multiplex flow immunoassay (MFI; Bio-Rad Laboratories, Hercules, CA) and matched immunofluorescence assays (IFAs; MBL Bion, Des Plaines, IL) in 220 HCWs categorized by ACIP criteria for presumptive immunity to MMRV. Among HCWs presumptively immune to measles, mumps, rubella, and VZV, the Bio-Rad MFI was positive in 77.3, 85.4, 84.3, and 91.1% of HCWs, respectively. Comparatively, the Bion IFA was positive in 92.9, 91.1, and 93.5% of HCWs presumptively immune to measles, mumps, and VZV (a rubella IFA was unavailable). Among HCWs fully vaccinated against measles, mumps, and VZV, Bio-Rad MFI/Bion IFA positivity rates were 77.4%/93%, 84.8%/90.7%, and 54.5%/90.9%, respectively. The Bio-Rad MFI was positive in 83.7% of HCWs fully vaccinated against rubella. For HCWs whose last vaccination event occurred within 15?years of enrollment, 83.3, 93.3, and 74.2% were positive by the Bio-Rad measles, mumps, and rubella IgG MFIs, respectively. We show significantly decreased Bio-Rad MFI sensitivity for detection of anti-measles and anti-mumps IgG-class antibodies in presumptively immune or fully vaccinated HCWs. Although negative results typically prompt revaccination, failure to recognize presumptive immunity in individuals unable to receive live, attenuated vaccines may have employment implications.
Project description:The burden of rotavirus morbidity and mortality is high in children aged <5 years in developing countries, and evaluations indicate waning protection from rotavirus immunization in the second year. An additional dose of rotavirus vaccine may enhance the immune response and lengthen the period of protection against disease, but coadministration of this dose should not interfere with immune responses to concurrently given vaccines.A total of 480 9-month-old participants from Matlab, Bangladesh, were enrolled in a study with a primary objective to establish noninferiority of concomitant administration of measles-rubella vaccine (MR) and a third dose of human rotavirus vaccine (HRV; MR + HRV), compared with MR given alone. Secondary objectives included noninferiority of rubella antibody seroconversion and evaluating rotavirus IgA/IgG seroresponses in MR + HRV recipients.Two months after vaccination, 75.3% and 74.3% of MR + HRV and MR recipients, respectively, had seroprotective levels of measles virus antibodies; 100.0% and 99.6%, respectively, showed anti-rubella virus immunoglobulin G (IgG) seroprotection. In the MR + HRV group, antirotavirus immunoglobulin A and IgG seropositivity frequencies before vaccination (52.7% and 66.3%, respectively) increased to 69.6% and 88.3% after vaccination.Vaccine-induced measles and rubella antibody responses are not negatively affected by concomitant administration of HRV. The HRV dose increases antirotavirus serum antibody titers and the proportion of infants with detectable antirotavirus antibody.NCT01700621.
Project description:Over the last years, an increasing number of outbreaks of vaccine-preventable infectious diseases has been reported. Besides elderly and immunocompromised individuals, newborns and small infants are most susceptible to infections, as their immune system is still immature. This vulnerability during infancy can be mitigated by the transplacental transfer of pathogen-specific antibodies and other mediators of immunity from mother to the fetus during pregnancy, followed postnatally by breast milk-derived immunity. Since this largely antibody-mediated passive immunity can prevent the newborn from infections, neonatal immunity depends strongly on the maternal concentration of respective specific antibodies during pregnancy. If titers are low or wane rapidly after birth, the protection transferred to the child may not be sufficient to prevent disease. Moreover, emerging concepts propose that mothers may transfer active immunity to the newborns via vertical transfer of pathogen-specific T cells. Overall, a promising strategy to augment and prolong neonatal immunity is to vaccinate the mother before or during pregnancy in order to boost maternal antibody concentrations or availability of specific T cells. Hence, a large number of pre-and postconceptional vaccine trials have been carried out to test and confirm this concept. We here highlight novel insights arising from recent research endeavors on the influence of prenatal maternal vaccination against pathogens that can pose a threat for newborns, such as measles, pertussis, rubella and influenza A. We delineate pathways involved in the transfer of specific maternal antibodies. We also discuss the consequences for children's health and long-term immunity resulting from an adjustment of prenatal vaccination regimes.
Project description:Measles and rubella are highly contagious viral diseases transmitted via respiratory secretions and aerosolized droplets. Thailand has implemented universal vaccination against measles using the monovalent measles (M) or the trivalent measles-mumps-rubella (MMR) vaccine for the past 30 years. Nevertheless, incidence of measles and rubella remains in some parts of the country. We conducted a seroprevalence study to evaluate the antibodies to measles and rubella virus among Thais of all ages and to determine pre-existing immunity resulting from either vaccination and/or natural exposure. A total of 1,781 serum samples collected in 2014 was tested for IgG to measles and rubella virus by commercial enzyme-linked immunosorbent assays (ELISA). Percentages of individuals with protective antibody levels and the geometric mean concentrations (GMC) of IgG in each age group were analysed. The GMC of anti-measles IgG and anti-rubella IgG were 653.7 IU/L (95% confidence interval (CI); 555.9-751.4) and 39.5 IU/mL (95% CI;35.0-43.9), respectively. Thais between the ages of six months and 25 years did not demonstrate sufficient protective herd immunity for measles. This observation is consistent with the recent measles outbreaks in this age group. Lower prevalence of immunity against rubella was found among children ages 5-6 years who may not have completed vaccination as infants. Our findings identify gaps in rubella and measles immunity in specific age groups and support recommendations for catch-up MMR vaccination in individuals 30 years of age or younger.