Levels of rubella antibody among vaccinated and unvaccinated Portuguese mothers and their newborns

Maternal and cord sera (231 pairs) were tested to measure rubella IgG levels, using a commercial immunoassay method with final fluorescent detection (ELFA). One hundred and twenty-two women had been vaccinated against rubella. Geometric mean concentrations (GMC) were not associated with time since vaccination. GMC of rubella IgG among vaccinated and unvaccinated mothers were respectively 66.6 and 80.9IU/ml (p=0.29). The corresponding values for cord sera GMC were 140.6 and 140.2IU/ml (p=0.99). These GMC values seem to have been influenced by increased transplacental transport efficiency (TTE) among vaccinated mothers. This was observed if TTE was measured as difference or ratio of cord-maternal concentration of rubella IgG, but was only statistically significantly (p=0.02) for ratio. TTE also seemed to be higher when antibody levels in mothers were below <15IU/ml. There seemed to be some interaction between susceptibility and vaccination status, but these results should be seen with caution. We do not know of a proven biological reason to support differential TTE in vaccinated and unvaccinated mothers. The sensitivity of the lab assay might have influenced the results, such that very low antibody levels in some vaccinated mothers were underestimates of true concentrations. Our finding that 38 mothers had antibody levels considered to be below the threshold for protection highlights the importance of implementing policies to vaccinate susceptible women of childbearing age.     

Measles antibodies in cord blood in Portugal: Possible consequences for the recommended age of vaccination

The optimum age to give the first dose of measles vaccine must balance the risks of disease and vaccine failure. Both are influenced by the levels of transplacentally acquired maternal antibodies. This study was conducted in the Obstetric service of Portuguese hospital, in 2012–2013. Mothers were recruited after informed consent. Measles IgG was measured in 206 cord sera, using a commercial immunoassay. Geometric mean concentrations (and 95% CI) were 1849 mIU/ml (1196–2857) and 790 mIU/ml (618–1008) in cord sera of newborns from unvaccinated and vaccinated mothers respectively. Maternal age and vaccination status were both associated with the concentration in cord sera, but maternal age was the major predictor. The likely explanation is the same already mentioned in other studies: as a vaccination program progresses, vaccination coverage increases as measles incidence decreases. That results newborns from younger vaccinated mothers having less measles antibodies while the older mothers are more likely to have been infected with the wild virus. As the proportion of vaccinated mothers increase, developed countries tend to anticipate the recommended age of the first dose to 12 months of age. Models using hypothetical measles antibody decay rates in infancy were explored. Anticipating the first dose of MMR1 in Portugal to the age of 12 months might have not been the best decision but results were not conclusive, and arguments supporting or not the anticipation were discussed.     

Transplacental transfer of measles and total IgG.

This study was conducted to evaluate factors affecting the levels of total IgG (tIgG) and measles specific IgG (mIgG) in mother and cord sera, and the efficiency of transplacental transport of tIgG and mIgG. The study was conducted in four hospitals in Oporto, Portugal, where 1539 women and their newborns were enrolled. Measles IgG levels were lower among vaccinated mothers and respective cord sera than among vaccinated counterparts. Cord mIgG was strongly correlated with maternal levels in both vaccinated and unvaccinated groups. Transplacental transport efficiency (TTE) of mIgG decreased with increasing maternal levels, although almost one third of the observed effect was due to measurement error. The TTE was not affected by vaccination status. Monitoring maternal measles antibody levels and maternal vaccination status could be useful to determine when the age for measles vaccination can be reduced.     

Measles susceptibility in maternal-infant dyads—Bamako,Mali

Measles is endemic in Africa; measles mortality is highest among infants. Infant measles antibody titer at birth is related to maternal immune status. Older mothers are likelier to have had measles infection, which provides higher antibody titers than vaccine-induced immunity. We investigated the relationship between maternal age and measles susceptibility in mother-infant pairs in Mali through six months of infancy.We measured serum measles antibodies in 340 mother-infant pairs by plaque reduction neutralization test (PRNT) and calculated the proportion of mothers with protective titers (>120 mIU/mL) at delivery and the proportion of infants with protective titers at birth, and at three and six months of age. We explored associations between maternal age and measles antibodies in mothers and infants at the timepoints noted.Ten percent of Malian newborns were susceptible to measles; by six months nearly all were. Maternal and infant antibody titers were highly correlated. At delivery, 11% of mothers and 10% of newborns were susceptible to measles. By three and six months, infant susceptibility increased to 72% and 98%, respectively. Infants born to younger mothers were most susceptible at birth and three months. Time to susceptibility was 6.6 weeks in infants born to mothers with measles titer >120–<430 mIU/mL versus 15.4 weeks when mothers had titers ≥430 mIU/mL.Maternal and newborn seroprotective status were positively correlated. Improved strategies are needed to protect susceptible infants from measles infection and death. Increasing measles immunization coverage in vaccine eligible populations, including nonimmune reproductive-aged women and older children should be considered.     

Immunity against measles in populations of women and infants in Poland

During the 1997-1998 measles epidemic in Poland a high attack rate occurred in infants up to 1 year of age (24.6/100,000 in comparison with 5.5/100,000 in total population). Routine vaccination against measles for infants aged 13-15 months was introduced in Poland in 1975, and a second dose added in 1991. The recommended age for measles vaccination was based on information gathered in years when most mothers had a natural measles. Nowadays, many mothers have received measles vaccine. Early loss of passively acquired measles antibody may occur in infants of women who received measles vaccine, because measles vaccine induces lower antibody titres than does natural infection. Therefore, measles-specific antibody titres were determined among vaccinated and unvaccinated women as well as among infants, whose mothers were born after 1976 and likely were vaccinated (Group 1), and those, whose mothers were born before 1969 and likely have had a natural measles (Group 2). All women that were born in prevaccination era had significantly higher geometric mean titre (GMT) of measles antibody than those who were vaccinated (P<0.001). Also infants from Group 2 at every age had higher GMT of measles antibody than those of Group 1. The antibody decay was significantly faster among infants whose mothers acquired immunity by measles vaccination. Because nowadays the majority of women in childbearing age are vaccinated against measles, earlier vaccination in the infants should be considered.     

Follow-up of infants given measles vaccine at 6 months of age: antibody and CMI responses to MMRII at 15 months of age and antibody levels at 27 months of age

The worldwide elimination of measles is an important target. In developed countries, to control measles outbreaks, immunization from 6 months of age is recommended. In this study, infants (n = 290) who were (1) born to mothers with natural immunity or to vaccinated mothers and (2) previously immunized with Connaught (CLL) or AIK-C measles vaccine at 6 months of age, were evaluated for measles immunity before and after measles-mumps-rubella (MMRII at 15 months of age. Eight weeks after MMRII, 98.9% of infants were seropositive by enzyme immunoassay (EIA) and 70% demonstrated measles specific cellular immunity by blast transformation (BT) of lymphocytes. At 27 months of age, 98.4% of infants had protective antibody levels by plaque reduction neutralization (PRN) test. These results suggest that AIK-C and CLL vaccines elicit durable protective immunity in young infants when used in early immunization programs.     

Durability of passive measles antibody in Jamaican children

Measles antibody titres were determined by haemagglutination inhibition and by neutralization in 221 sets of serum collected from delivering mothers, umbilical cords, and infants when about six months of age. Radio-immunoassay was also used to measure antibody in 120 sera. Total IgG concentration was determined in the infant sera. All mothers had measles antibody and the mean titre was high. At the time of birth, measles antibody had been further concentrated in the infant. Nevertheless, many children lost protective titres before six months of age. The rate of loss was correlated with the infant's total serum IgG so that high IgG levels at six months correlated with rapid loss of measles-specific antibody. It is suggested that in homes where sanitation is poor, antibody is made to many agents at an early age. To maintain physiological balance, homeostatic mechanisms then increase the rate of catabolism of all IgG, including that passively acquired. In keeping with its stage of sanitary development, vaccination in Jamaica can profitably be given earlier than in the United States, but it must be later than in many African countries.     

Waning of measles maternal antibody in infants in measles elimination settings – A systematic literature review

IntroductionMost infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination.MethodsWe conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool.ResultsWe identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3–7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune.ConclusionAlthough limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.     

新生儿母传麻疹抗体水平与相关因素调查

目的:了解新生儿及其母亲麻疹抗体水平,探讨新生儿与母体抗体水平关系以及影响新生儿抗体水平的可能因素,为控制小月龄儿童麻疹发病提供有效建议。方法:采集孕妇产前静脉血和新生儿脐带血共156对,使用ELLSA方法进行麻疹IgG抗体水平检测。结果:母亲麻疹抗体几何平均浓度为546.48 mIU/ml,新生儿为746.64 mIU/ml,是母亲的1.37倍;母亲麻疹抗体对数浓度与新生儿的呈正相关,相关系数为0.883(P=0.000);母亲麻疹抗体水平与母亲年龄、户籍和出生地等因素的关系有统计学意义,30岁及以上组母亲的麻疹抗体几何平均浓度高于30岁以下组(t=-2.078,P=0.039),外省户籍母亲的麻疹抗体几何平均浓度高于北京市户籍组(t=-2.073,P=0.040),两两比较发现农村地区出生母亲的麻疹抗体几何平均浓度高于城市组(LSD法:P=0.005);胎传抗体能力与胎龄、母亲年龄的关系有统计学意义,两两比较发现胎龄38～40周的新生儿其胎传抗体能力高于胎龄小于38周的新生儿(LSD法:P=0.014),母亲年龄在30岁以下组的新生儿胎传抗体能力高于30岁及以上组(t=2.636,P=0.009)。结论:母亲麻疹抗体水平和胎传抗体能力是影响新生儿抗体水平的重要因素,育龄妇女加强免疫麻疹成分疫苗是现阶段控制小月龄麻疹发病的重要手段,早产儿和生育年龄过大母亲所生新生儿受到麻疹威胁时应考虑提前到6月龄接种麻疹疫苗。     

Measles immunity and response to revaccination among secondary school children in Cumbria.

The prevalence of antibody to measles virus in 759 children aged 11-18 years attending a secondary school in Cumbria was measured using a salivary IgG antibody capture assay. Serum IgG antibody levels were measured using a plaque reduction neutralization assay in subjects whose saliva was antibody negative. Vaccination histories were obtained from the child health computer and general practice record. A total of 662 pupils (87% of those tested) had detectable measles-specific IgG in saliva. Of the remaining 97, 82 provided blood samples and 29 had serum neutralizing antibody levels above 200 mIU/ml. Afer adjusting for non-participation rates, the proportion considered non-immune (no IgG in saliva and < or = 200 mIU/ml in serum) was 9% overall, ranging from 6% in vaccinated children to 20% in unvaccinated children. Measles-mumps-rubella vaccine was given to 50 children of whom 38 provided post-vaccination serum and 32 saliva samples. Thirty (79%) had a fourfold or greater rise in serum neutralizing antibody and 28 (88%) developed IgG antibody in saliva. Half of the children considered non-immune by antibody testing would have been overlooked in a selective vaccination programme targeted at those without a history of prior vaccination. A programme targeted at all school children should substantially reduce the proportion non-immune since a primary or booster response was achieved in three quarters of previously vaccinated children with low antibody levels and in all unvaccinated children. While it is feasible to screen a school-sized population for immunity to measles relatively quickly using a salivary IgG assay, a simple inexpensive field assay would need to be developed before salivary screening and selective vaccination could substitute for universal vaccination of populations at risk of measles outbreaks. The salivary IgG assay provided a sensitive measure of a booster response to vaccination.     

Placental transfer of measles antibodies: effect of gestational age and maternal vaccination status

Despite nationwide measles vaccination coverage in Israel of over 90%, repeated outbreaks of measles have spread from isolated communities with poor immunization uptake. Some severely affected individuals were children under 1 year of age, including premature infants. We evaluated the serological status of 195 newborn infants and their 161 mothers divided into four groups: vaccinated mothers (VMs) and premature infants, VM and full term infants, naturally immunized mothers (NIMs) and premature infants, NIM and full term infants. Maternal and cord blood measles antibody titers were determined by haemagglutination inhibition (HI) test and microneutralization test (mNT). Fewer than 40% of preterm infants of VM and less then 70% of preterm infants of NIM had protective titers at birth. The results of this study may aid in formulating new measles vaccination recommendations for preterm infants.     

Cell-mediated and antibody immune responses to AIK-C and Connaught monovalent measles vaccine given to 6 month old infants

Measles vaccination of infants younger than 1 year of age should be successful in populations with a high proportion of measles vaccinated mothers. Infants whose mothers were vaccinated are born with less maternal antibody which can interfere with vaccination compared with infants whose mothers had measles. AIK-C or Connaught (CLL) measles vaccine was given to 300 6 month infants born to mothers who had measles (group 1) or who were vaccinated against measles (group 2). Pre- and post-vaccination measles antibody was measured by EIA and PRN and cell mediated immunity (CMI) by blast transformation and production of interferon-gamma and interleukin-10. After vaccination, mean antibody level, seroconversion and blastogenesis were significantly lower for group 1 than group 2 (p < 0.05). Post-vaccination measles IgG was significantly higher for group 2 CLL vaccinees compared with group 2 AIK-C (p < 0.05); seroconversion rates were 73 and 63%, respectively. More than 93% of group 2 infants had elevated measles IgG after vaccination. About 89% of all children had some evidence of a blastogenic response. Lymphoproliferation correlated strongly with cytokine production and weakly with IgG. Not all seroresponders had a CMI response and vice versa. AIK-C and CLL vaccines induce strong measles specific T and B immunity in most 6 month infants of vaccinated mothers.     

育龄妇女接种麻疹疫苗对婴儿麻疹发病影响的研究

目的研究育龄妇女接种麻疹疫苗（measles attenuated live vaccine,MV）对婴儿麻疹发病的影响,为降低婴儿麻疹发病提供参考。方法分析2006-2012年枣庄地区婴儿麻疹发病状况,采用酶联免疫吸附试验,检测育龄妇女接种MV后母婴麻疹抗体。用SPSS 11.5软件进行统计分析,分析方法运用χ2检验、t检验、F检验,以P〈0.05为差异有统计学意义。结果育龄妇女接种MV后（2010-2012年）婴儿年均麻疹发病率降至34.08/10万;病例以母亲孕前≥24个月接种MV者最高,占婴儿病例的50.00%（19/38）,其中〈8月龄占42.11%（16/38）;育龄妇女抗体阳性率、几何平均倒数滴度（GMRT）分别为95.72%和1 300.52,随时间推移到孕前24个月迅速下降至82.05%和521.35,接近免前水平（82.72%、419.78）。孕前3-6个月、8-12个月内接种,其婴儿（0-8月龄）麻疹抗体阳性率、GMRT明显高于相应对照（χ^2=27.92、24.41;t=10.23、9.78;均P〈0.01）,而其8月龄婴儿免疫成功率（76.19%-90.00%）、GMRT（672.24-712.56）差异均无统计学意义（χ^2=1.54,F=0.47,P〉0.05）。结论育龄妇女孕前3-12个月内接种MV,可显著提高母婴抗体水平,减少婴儿初免前暴露;同时不影响基础免疫成功率和GMRT水平,对降低婴儿麻疹发病,实现消除麻疹具有重要意义。     

Antikörper gegen impfpräventable Erkrankungen bei Schwangeren und deren Neugeborenen

In the eastern part of Germany, the age of primigravid women has clearly increased since 1990. This may change the protection provided by antibodies in pregnant women as well as their newborns. The objective of the present study was to assess antibodies against vaccine-preventable viral infectious diseases in pregnant women and their offspring to draw conclusions about their protection. Maternal and cord blood samples of 290 women from the eastern part of Germany with a mean age of 28 years were analyzed for antibodies against measles, mumps, rubella, poliomyelitis, and varicella. The study showed that the pregnant women had detectable levels of antibodies against measles virus in 79%, against mumps virus in 96%, against rubella virus in 87%, against polioviruses types 1-3 in 62-64%, and against varicella-zoster virus (VZV) in 97% of the cases. The seroprevalence of the antibodies in the newborns were not significantly different from those of their mothers. When antibody titers of mothers and newborns were compared, significantly higher titers to VZV could be detected in the cord blood sera of newborns. It is suggested that the prevalence of antibodies against measles and poliomyelitis is insufficient to protect the newborns efficiently. An immunity gap of 13% against rubella in mothers results in a potential risk for a congenital rubella syndrome in newborns. Despite the high seroprevalence of rubella and chickenpox, there is considerable potential for infections during pregnancy and neonatal period.     

母亲外周血与脐带血麻疹抗体水平研究

目的研究母亲、新生儿麻疹抗体水平与麻疹发病的关系。方法采集60名妊娠母亲外周静脉血与脐带血分离血清,采用ELISA法检测麻疹IgG抗体水平。结果妊娠母亲外周静脉血、脐带血麻疹IgG抗体浓度分别为(4.883±4.687)ng/ml、(7.280±6.061)ng/ml;妊娠母亲麻疹IgG抗体浓度同正常育龄妇女(P﹥0.05);母亲平均血清麻疹IgG浓度低于新生儿(P﹤0.05);母血与脐血麻疹IgG抗体水平呈正的直线相关关系(r=0.946,P=0.000);曾有麻疹感染史的母亲静脉血麻疹IgG抗体浓度明显增加(β=0.259,t=2.058,P=0.044);自然感染麻疹母亲的脐血麻疹IgG浓度显著高于曾接种麻疹疫苗母亲的脐血麻疹IgG(P﹤0.05)。结论母亲麻疹IgG抗体水平是影响婴儿麻疹发病率的重要原因。     

Mumps antibodies in the cord blood: Association with maternal recall of mumps. Possible consequences for vaccination strategies

The present study aims to contribute to the evaluation of the serological impact of vaccination against mumps in Portugal, measuring anti-mumps IgG (MuIgG) levels in cord sera and the corresponding proportions of seropositive newborns, and their association with potential predictive variables. The data from this study came from 198 umbilical cord sera. Detailed vaccination records were available for all mothers. MuIgG were measured in the sera, using a commercial immunoassay. The geometric mean concentration (GMC) of MuIgG was 31.7 RU/ml. Seropositive/immune sera (concentration ≥16 RU/ml) were 75.3%. While 49 mothers were “unsure” about ever having had mumps, 46 said they had had the disease and 103 said they had not had it. Eighty eight women did not receive a single dose of MMR while the other received 1 or 2 doses, with different combinations of vaccine strains. This study found that recalling mumps was predictive of higher MuIgG GMC and seropositivity. Maternal age and vaccination status were not associated with GMC or seropositivity. Nevertheless, in the small subset of newborns from vaccinated mothers not recalling mumps, receiving two doses was predictive of higher GMC than just receiving one. Maternal recall of mumps is highly predictive of seropositivity while not recalling the disease results in numerous false-negatives. This is consistent with other studies and with the fact that infection with mumps virus can result in a wide range of clinical manifestations. We agree on the need for further research to support a recommendation of a three (or more)-dose MMR strategy but we also believe that evidence is fast accumulating in favour of a higher dose strategy. The issue of waning immunity due to vaccines when vaccination succeeds in controlling (and nationally eliminating) target diseases like measles and mumps must be urgently taken into account.     

Susceptibility to tetanus and missed vaccination opportunities in Portuguese women

Maternal and cord sera (96 pairs) were tested to measure antitetanus toxin IgG (ATT IgG) levels, using a commercial enzyme immunoassay. One mother had no detectable antitetanus antibody and four more had levels below those considered to be reliably protective (<160 mIU/ml). All five had been eligible for vaccination during pregnancy according to Portuguese guidelines, although one had received seven lifetime doses of TT. In maternal and cord sera, ATT IgG levels among those not vaccinated during the current pregnancy were significantly lower than among vaccinees (p < 0.0001), but there was no difference between those vaccinated once or twice during pregnancy. Among those not vaccinated during pregnancy, levels of ATT IgG decreased with time since last dose of vaccine (P = 0.0001). The total number of doses of vaccine was not significantly associated after controlling for time since last dose. Missed immunization opportunities occurred among half the women studied. Efforts to sustain protection against tetanus must be intensified.     

Supplemental measles vaccine antibody response among HIV-infected and -uninfected children in Malawi after 1- and 2-dose primary measles vaccination schedules

BackgroundThe long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented.MethodsMeasles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations.ResultsOf 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV-infected children who received two doses of MV at ages 6 and 9 months. Among HIV-uninfected children, protective levels of antibody were found post sMV in 90–99% through ages 24–36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV.ConclusionsOur findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs.     

Antibody against viruses in maternal and cord sera: specific antibody is concentrated on the fetal side of the circulation.

Paired maternal and cord sera from 100 pregnancies were tested for antibodies against herpes simplex virus, measles virus and respiratory syncytial virus by complement fixation and for antibodies against rubella virus, influenza A virus and influenza B virus by haemagglutination-inhibition. For four viruses (herpes simplex, measles, respiratory syncytial and rubella) higher levels of antibody were found in cord than in maternal sera. There was no difference between maternal and cord serum titres against influenza B virus but significantly higher levels of antibody against influenza A virus were found in maternal sera than in cord sera. This discrepancy was investigated by measuring antibodies against the surface antigens of influenza A by a complement fixation technique, and by single radial haemolysis. Both methods showed a preponderance of virus-specific antibody in cord sera. We conclude that IgG antibodies against most, if not all, viruses are concentrated on the fetal side of the circulation, but the conventional haemagglutination-inhibition techniques may fail to detect this difference.     

70对母婴麻疹野病毒中和抗体检测结果分析

[目的]了解母婴的麻疹野病毒中和抗体水平及其相关性。[方法]采用中和试验的方法直接检测孕妇及新生儿的麻疹野病毒中和抗体水平并进行相关分析。[结果]孕妇及新生儿的麻疹野病毒中和抗体阳性率分别为91．52％和88．57％,平均几何滴度（GMT）分别为61．32和58．17;配对母婴的麻疹野病毒中和抗体水平呈高度正相关（r=0．899,P〈O．01）。当母体的抗体滴度≥l：16时,其子代抗体的阳性率可达100．00％。[结论]母婴的麻疹抗体水平密切相关,提高母源麻疹抗体水平应是控制低月龄小儿麻疹发病的重要措施之一。