Childhood immunization in rural Malawi: time of administration and predictors of non-compliance

A cohort of 760 newborns was followed prospectively for 2 years to ascertain the time of administration of childhood vaccinations in rural Malawi and to study predictors of non-compliance with national vaccination recommendations. At 1 year of age, 99% of the infants were fully vaccinated against tuberculosis, 91% against polio, 90% against diphtheria, pertussis and tetanus and 64% against measles. At 2 years, the corresponding vaccination coverages were 99%, 93%, 93% and 84%. On average, all vaccinations were given 1-3 months later than recommended. Many of the delayed measles vaccinations were given during a separate vertical campaign, during which 25% of previously unvaccinated 21-23-month-old children were identified and immunized. Non-compliance with vaccination recommendations was associated with living in villages with no access to mobile vaccination teams, birth between April and June and birth at home. In this rural Malawian area, most vaccination services were functioning well. To increase measles vaccination coverage, regular outreach activities should be encouraged.     

Passive immunity to measles in the breastmilk and cord blood of some nigerian subjects

Maternal and cord blood collected from 33 Nigerian mother-child pairs were tested for measles-sepcific IgG. All 33 had protective measles antibodies at the time of delivery with a positive correlation of r = 0.87. Determination of the rate of waning of these antibodies revealed that 58 per cent of these children had lost the protective maternal antibody by the age of 4 months and only 3 per cent of the children had enough antibody to protect them between the ages of 6-9 months. Fifty-five colostrum samples from the same mothers and 347 breastmilk samples collected at various periods of breastfeeding also showed that anti-measles IgA had dropped below the protective cut-off within the first 2 weeks of birth. It is evident that the Nigerian child is born with solid anti-measles antibody but the rate of waning has left a large number unprotected before the first dose of the vaccine. There is an urgent need to review the measles vaccination programme in Nigeria to protect these susceptible infants.     

Meningococcal antibody titres in infants of women immunised with meningococcal polysaccharide vaccine during pregnancy.

Seventy five Gambian women were immunised with a single dose of a group A+group C meningococcal polysaccharide vaccine during the last trimester of pregnancy. IgG antibody titres were measured in mothers and in their infants by an enzyme-linked immunosorbent assay (ELISA). All women had a good response to vaccination and maternal antibodies were high at the time of delivery (23.2 micrograms/ml for group A antibodies and 14.3 micrograms/ml for group C antibodies). However, only a proportion of this antibody crossed the placenta; cord blood:maternal antibody ratios were 30% for group A antibody and 44% for group C antibody, respectively. Considerable variability in cord blood:maternal blood ratios was seen between individuals. This could not be related to age, parity, or ethnic group. Mean group A and group C cord blood:maternal blood ratios were lower in women with serological evidence of syphilis than in seronegative women, and diminished transfer of group A antibody was noted in women with active malarial infection of the placenta. Antibody titres declined rapidly in infants and by the age of 3-4 months these had reached control values. Maternal immunisation may give infants some protection against group A and group C meningococcal disease but only during the first few months of life.     

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??Abstract: Objective??Evaluate the level of measles’ IgG in healthy lying-in mothers and non-measles infants to assess their protective competence to measles. Methods??We collected blood samples from 100 healthy lying-in mothers?? 52 non-measles newborns and 52 non-measles infants of 2??6 months old?? and Enzyme Linked ImmunoSorbent Assay ??ELISA?? was applied to detect the levels of MV IgG. Results??Totally 47 out of the 100 ??47.0%?? healthy lying-in mothers had protective competence and only 9 of them ??9.0%?? had the obvious protective competence. In the 52 newborns and 52 infants of 2??6 month 20 ??38.46%?? and 6 ??11.54%?? cases respectively had protective competence and only 5 of the newborns ??9.61%?? had the obvious protective competence to prevent them from being infected by measles virus. Conclusion??The levels of measles’ IgG in these people are low. There is some kind of correlation between lying-in mothers and newborns and the levels in 2??6-month old infants are lower.     

Transplacentally acquired immunoglobulin G antibodies against measles, mumps, rubella and varicella-zoster virus in preterm and full term newborns

IgG antibody values against measles, mumps, rubella and varicella-zoster virus in 71 full term and 101 preterm infants and their 152 mothers and the decay of maternally acquired antibodies during infancy were studied. Both magnitude of transplacental antibody passage and cord blood antibody values correlated with gestational age. After 6 months preterm infants born before 32 weeks of gestation had lost maternal antibodies.     

Placental transfer of tetanus antibodies and protection of the newborn

The aim of the study was to compare the placental transfer of tetanus toxoid antibodies (TTAB) and total IgG in Africa, where we had previously demonstrated a lack of transmission from mother to the newborn of measles antibodies. Two series of mother-child pairs, 45 in Paris and 134 in Libreville, Gabon, Central Africa, were measured after full-term pregnancies and normal deliveries. Means of ratios of cord/mother concentrations for TT AB and IgG were, respectively, 2.52 and 1.28 in Paris and 0.98 and 0.82 in Gabon. In 11 pairs from Libreville no TT AB were found in mother and cord blood, but in four other African newborns (3 per cent), the mother transmitted TT AB which were lower than protective level against tetanus. Other data (negative correlation between mother IgG and cord/mother ratio of corresponding TT AB concentrations, and better transmission of TT AB in the low range of maternal IgG) indicate that the limitation of active placental transfer of antibodies is related to the high maternal IgG level common in Africa.     

Effect of a prepregnancy pertussis booster dose on maternal antibody titers in young infants

To examine the influence of a pertussis booster vaccination on the transfer of maternal antibodies, 24 nonpregnant women received a tetanus, diphtheria, acellular pertussis booster vaccine between 2 consecutive pregnancies. Blood was drawn from mothers and off-spring. Efficient transplacental antibody transfer and significantly higher antibody titers against 3 pertussis antigens were observed in cord blood and in blood of 1-month-old infants born after a maternal booster vaccination compared with results in their siblings born before the booster administration.     

Maternal-fetal transfer of pneumococcal capsular polysaccharide antibodies

Maternal-fetal transfer of IgG antibodies is an important host defense for newborns, who have an increased incidence of bacterial infections. To study the transfer of specific pneumococcal capsular polysaccharide (PPS) antibodies, we measured the concentrations, in 30 paired maternal and cord serum samples, of IgG and IgM by radial immunodiffusion, of serotype 7F Streptococcus pneumoniae PPS antibodies by radioimmunoassay and enzyme immunoassay, and of opsonic activity to that organism by a radiolabeled bacterial uptake assay. Cord serum had significantly greater total IgG, yet significantly less type 7F PPS IgG antibodies and opsonic activity than maternal serum. Cord serum had low concentrations of total IgM and no IgM type 7F-specific antibodies. Reduced transport of specific IgG antibodies and absent transfer of IgM may contribute to the susceptibility of newborns to bacterial infection.     

Passive immunity of premature infants against measles during early infancy

The aim of this study was to evaluate the presence of transferred measles antibodies and seronegativity rates during early infancy in premature newborns whose mothers had infection-induced immunity. The premature group was composed of 22 and 35 newborns of gestational ages < 32 wk and > 32 wk, respectively, and the control group consisted of 28 term newborns. Enzyme-linked immunosorbent assay (ELISA) was used for the qualitative detection of IgG antibodies to measles virus. Mean cord blood relative values were significantly lower in both premature groups, < or = 32 wk (p < 0.0001) and > 32 wk (p < 0.001), when compared with term infants. No seronegative infant was found in the premature group at 2 mo of age. At 4 mo, the seronegativity rate was 27% for premature infants < or = 32 wk and 35% for those > 32 wk. At 6 mo, seronegativity increased to 86% and 74% for premature infants born at gestational ages < or = 32 wk and > 32 wk, respectively. Forty-six percent of the term infants became seronegative at that age. The differences between term infants and those in the two premature groups were statistically significant (p < 0.05 and p < 0.005). Premature infants, regardless of their prematurity degree, were thought to be more susceptible to measles infection than term ones at the age of 6 mo. Policies for their protection from measles infection are still to be investigated.     

Measles and mumps antibody concentrations in newborns and their mothers--follow up first year of life

BACKGROUND: During the last twenty years the incidence of measles and mumps decreased after introduction of vaccinations in the industrial nations. The vaccination rate of the population in Germany lies currently under the required elimination rate. The epidemiological situation has changed altogether. The illness age has on the one hand moved up, teenager and adult suffer more frequent these so-called children's diseases with an increased complication rate. On the other hand illness cases in infancy seeming to increase. It was aim of this study to examinate the current serological situation for measles and mumps antibody status in women in childbed and their healthy newborns at birth time and during the first seven to nine life months. PATIENTS AND METHOD: 237 healthy newborns, born in 1999 in Bochum, West-Germany and their mothers were included. The mothers were asked if and when they did suffer from measles and mumps or were questioned to active vaccinations against these diseases. Immediately antepartal from all mothers was taken a venous blood sample. Immediately postpartal from all newborn childs umbilical cord blood was taken and again a blood sample in the age of six to eight months. In the serum tests the measle and mumps IgG antibody concentrations were examined quantitatively with ELISA methods. In cases with negative or borderline positive values the plaque neutralization test was also used for measuring of the measle antibodies. CONCLUSIONS: Between the maternal and neonatal titers results the knownly positive correlation. Maternal lending immunity against measle and mumps lasts more less into infancy as generally suspected. An earlier first active immunization against measles and mumps could be discussed. The strict realisation of the present vaccinating recommendations should be operated as a matter of priority to lead to the desired measles and mumps eradication.     

Placental antibody transfer: influence of maternal HIV infection and placental malaria

AIM: To determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer. METHODS: One hundred and eighty materno-neonatal pairs from a Malawian population were assessed. Cord and maternal serum samples were tested for total serum IgG antibody titres using nephelometry, and for specific IgG antibody titres to Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme linked immunosorbent assay (ELISA). RESULTS: Multiple regression analyses showed that placental malaria was associated with a decrease in placental IgG antibody transfer to S pneumoniae and measles to 82% and 81%, respectively. Maternal HIV infection was associated with a reduction in IgG antibody transfer to S pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S pneumoniae and measles IgG antibody transfer reduction to 86% and 87%, respectively. No effect was seen with tetanus toxoid antibody transfer. CONCLUSION: The combined influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia seems to be linked to the low transplacental antibody transfer observed in the Malawian population.     

Immunologic findings in oral pertussis vaccination

Whooping cough specific surface IgA antibodies, agglutinating serum IgG antibodies and the in vitro lymphocyte reactivity to Bordetella pertussis germs were investigated in newborns and infants both unvaccinated and parenterally and orally immunized against whooping cough. Furthermore the E-rosette formation and the lymphocyte reactivity to phytohaemagglutinin, pokeweed mitogen and concanavalin A were studied. Only oral pertussis immunisation effected a local immune reaction with formation of secretory surface IgA antibodies in the saliva and prevented the postnatal disappearance of the Bordetella pertussis specific IgG antibodies seen in unvaccinated infants. From the third month of life the lymphocyte reactivity to a Bordetella pertussis germ suspension resulted in measurable stimulation following oral whooping cough vaccination. After the third month of life the pertussis stimulation indices of the orally immunized infants remained above the values for adults with a history of whooping cough and were equivalent to those for the parenterally immunized infants.     

Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A vaccination starting at 2-month-old children

Active immunization with hepatitis A vaccine has been shown to provide long-term protection against hepatitis A virus (HAV) infection. However, few data are available regarding use of the hepatitis A vaccine in children under two years of age. The present study was conducted to test the safety and immunogenicity of inactivated hepatitis A vaccine administered to infants, and to evaluate the correlation between mother and infant anti-HAV antibodies. A total of sixty healthy children, two months of age, were enrolled in this study and immunized with 360 EU of inactivated hepatitis A vaccine (Havrix) according to the two, four and six months of age schedule. Blood sampling was performed prior to the first vaccination and one month after the third vaccination at seven months. Venipuncture was also done on mother on admission. The reactogenicity was expressed as the percentage of reported local and systemic reactions. The most common side effects were erythema on the injection site and fever. Infants with passively transferred maternal anti-HAV antibodies had a reduced anti-HAV GMT after vaccination. On admission, only one infant and his mother were seronegative and seroconversion was only detected in this infant. One month after the third dose seven infants (12.3%) were found to be seronegative. The infant without passively acquired maternal anti-HAV had the protective levels with a GMT of 3176 mIU/ml one month following the third dose. There was a significant positive correlation between the titers of mother and infant anti-HAV antibodies (n = 0.96, p < 0.001) on admission. Hepatitis A vaccine showed no immunogenicity in infants with presence of maternal antibodies. Hepatitis A vaccine is safe but it should be used after the disappearance of maternal antibodies.     

The duration of maternal measles antibodies in children

The most important factor affecting the success of measles immunization is the disappearance of maternal anti-measles antibodies. In order to determine the optimum age for measles vaccination and to contribute towards the Expanded Programme on Immunization as currently applied in Turkey, we investigated the rate of disappearance of anti-measles antibodies. The study population consisted of 124 healthy infants aged 1-15 months from Erzurum, Erzincan, and Kars. The overall proportion of seropositivity, which is the result of the presence of maternal anti-measles antibodies, was 67/124 (54 per cent). The proportion of infants with detectable antibodies declined progressively with increasing age. The distribution of maternal antibody levels with respect to age showed a progressive reduction with increasing age from 7 months to 15 months. Thus the proportion of antibody-positive infants declined from 50 per cent at 7-9 months to 10 per cent at 13-15 months. While an evident decrease occurred during these months, no important decline was observed up to 9 months of age. The results of this study show that the minimum proportion of antibody-positive infants (10 per cent at 13-15 months of age) is still higher than the optimum proportion (5 per cent). The Schwarz vaccine, which is used mostly in measles immunization, seems not to be effective to obtain a high seroconversion rate in our infants. Edmonston-Zagreb vaccine strain should be given to children under the age of 15 months in eastern Turkey. In addition, serological studies should be performed periodically, and vaccination programmes appropriate for our country should be determined according to these data.     

Measles seroprevalence in Izmir with special emphasis on measles vaccination policy for Turkey

BACKGROUND: Measles outbreaks seem to occur every 2- to 3-year intervals in Turkey. However, sero-epidemiological studies are limited. Knowing the prevalence of measles susceptibility as measured either by serologic markers of immunity or surveys of vaccination coverage is an important tool to assess the risk for measles outbreaks. METHODS: In order to determine the seroprevalence of measles antibodies among a 1 to 29-year-old population in Izmir (Turkey) and to develop the best vaccination policy for measles, a total of 600 people aged from 1 to 29 were selected for the study with cluster sampling. The information on sociodemographic characteristics, vaccination status and measles history was gathered for each participant. Measles-specific IgG antibodies were screened qualitatively by using microenzyme immune assay for 595 subjects. RESULTS: Of the 595 participants screened for the measles antibodies, 56 (9.4%) were seronegative. The proportion of the susceptible individuals in the age groups of 1-4, 5-9, 10-14, 15-19 and 20-29 was 20.0, 10.4, 6.0, 10.3 and 3.0%, respectively. The logistic regression analysis showed that none of the independent characteristics (sex, socioeconomic status, past measles history, vaccination status) with the exception of age group, was significantly associated with measles seronegativity. CONCLUSION: The optimal measles vaccination policy for Turkey may be to increase vaccination coverage above 90%, to conduct a catch-up campaign covering persons aged 1-19, regardless of previous vaccination status. Another factor to consider is to adopt a routine two-dose vaccination, giving the first dose at 12-15 months of age and the second dose at school entry.     

Factors affecting antibody response of newborns to repeated administrations of the rotavirus vaccine RIT 4237

The safety and immunogenicity of repeated doses of RIT 4237, an oral live attenuated rotavirus vaccine of bovine origin, as well as the influence of gastric acidity and maternal antibodies on the vaccine "take rate" were studied in newborns. The vaccine was given orally on the first day of life, at 1 month, and at 2 months of age. Fifty-seven newborns entered the study but only 36 completed the trial. No adverse reaction was observed after vaccination. Immune responses were evaluated by titrating pre- and postvaccination serum antibodies to RIT 4237 by a neutralization technique. Eight of 43 (18.6%) tested infants responded to the first dose of vaccine. Subsequently another six and 11 infants responded to the second and third dose, respectively. The total cumulative response after the third dose was 23 of 36 vaccinees (63.9%). The geometric mean neutralizing antibody titers was lower in responders than in nonresponders before the first dose of vaccine indicating that maternal antibodies interfered with vaccine "take." Since the RIT 4237 strain is acid sensitive, gastric pH was measured at the time of each vaccination. Mean pH values in responders were not significantly different than those found in nonresponders. Therefore, vaccine failures cannot be due to inactivation of the rotavirus vaccine in the stomach but instead they can be attributed to high levels of maternal antibodies. At each vaccination, additional subjects seroconverted. Therefore, a multiple dose scheme is advisable to obtain an optimal immune response.     

Presence of non-maternal antibodies in newborns of mothers with antibody deficiencies.

To explain the mechanism for induction and production of specific antibodies found in the newborn already at birth, without previous known exposure to the antigen, we chose a model that presumably excluded the possibility of specific antibodies being transferred from the mother to the fetus. Specific IgG, IgA, and IgM antibodies against Escherichia coli and poliovirus antigens were determined with ELISA in serum, saliva, and amniotic fluid from hypogammaglobulinemic and IgA-deficient mothers as well as in cord serum, saliva, and meconium from their offspring. All the mothers lacked IgA and some also lacked IgM antibodies, which were found in their healthy newborns. The amniotic fluid from a hypogammaglobulinemic mother lacking IgA contained small amounts of IgA antibodies, which were also found in the neonate, suggesting a fetal origin. There was evidence for the presence of antiidiotypic antibodies to poliovirus in the cord sera. We propose that idiotypic and/or antiidiotypic IgG antibodies transferred via the placenta from the mother to the fetus can initiate specific immune responses seen in the newborn. Thus, it may be that transplacental IgG not only passively protects the newborn, but also actively primes the fetus during fetal life via its content of idiotypic and/or antiidiotypic antibodies.     

Transplacental immunity and waning of maternal antibody in measles

Since transplacental immunity and waning of maternally derived measles specific antibodies play an important role in determining the optimum age for vaccination of infants against measles, a study was carried out in which 150 paired samples and 581 infant serum samples were tested for measles specific antibodies. Out of these paired samples, 132 pairs showed measles antibodies in both mother and cord. HAI antibody was absent in 3 paired samples whereas, 5 mothers could not pass on the antibodies in the cord samples. In the remaining 10 serum samples only cord blood showed the presence of antibodies without the detectable level of antibodies in mother. Statistically no significant difference between the mother and cord blood titers was observed by applying the student ‘t’ test for comparison of the mean (t=0.01). Analysis of 581 infant serum samples for prevalence of maternal antibodies indicated that 83% of the samples at the age of 3 months or below had measles antibodies but with the increase in age there was tremendous loss with only 19–20% at the age of 6–7 months. After 7 months the percentage of infants which had antibody varied from 11–13%. There was negative correlation between age and seropositivity (r=−0.72) which was highly significant (p<0.05).     

Response to RIT 4237 oral rotavirus vaccine in human milk, adapted-and soy-formula fed infants

During the first month of life 28 full-term newborns were breast-fed (18 males and 11 females). Thereafter 8 infants continued breast-feeding while the remainder were randomly fed on either an adapted milk formula (n=13) or a soy-formula (n=7). At five months, after an oral dose of RIT 4237 rotavirus vaccine of bovine origin was given, growth and IgM/IgG type antibodies against rotavirus were measured. Weight gain was similar in all infants. There were 2 IgM and 1 IgG responders out of 7 soy fed infants, compared with 4 out of 8 human milk fed (both IgM and IgG) and 7 out of 13 IgM and 6/12 IgG formula fed infants responding to vaccination. This observation confirms previous results obtained with polio, diphtheria tetanus and pertussis vaccines indicating that soy-protein formulas may interfere with immunization processes.     

Response to RIT 4237 Oral Rotavirus Vaccine in Human Milk, Adapted- and Soy-Formula Fed Infants

ABSTRACT. During the first month of life 28 full-term newborns were breast-fed (18 males and 11 females). Thereafter 8 infants continued breast-feeding while the remainder were randomly fed on either an adapted milk formula ( n =13) or a soy-formula ( n =7). At five months, after an oral dose of RIT 4237 rotavirus vaccine of bovine origin was given, growth and IgM/IgG type antibodies against rotavirus were measured. Weight gain was similar in all infants. There were 2 IgM and 1 IgG responders out of 7 soy fed infants, compared with 4 out of 8 human milk fed (both IgM and IgG) and 7 out of 13 IgM and 6/12 IgG formula fed infants responding to vaccination. This observation confirms previous results obtained with polio, diphtheria tetanus and pertussis vaccines indicating that soy-protein formulas may interfere with immunization processes.