Enhancement in seroconversion to measles vaccine with simultaneous administration of vitamin A in 9-months-old Indian infants

The mutual interactions of measles vaccine and vitamin A dose when administered simultaneously to 9 month old infants are explored in this study. One hundred healthy infants of 9 months of age received EZ strain of measles vaccine in the routine immunization clinic along with either 100,000 IU of vitamin A or a placebo orally. Blood samples were collected before and 4 weeks after intervention. They were coded and analysed for serum retinol and Hemagglutination Inhibition (HI) antibodies to measles. Ninety five per cent of the infants were seronegative to measles prior to vaccination with a seroconversion rate of 63% in the control group and a significantly higher percent of 83.7% in the experimental group (P < 0.01). Seroconversion was not related to initial serum retinol levels in either of the groups. 42% of infants had serum retinol levels less than 20 ug/dl before administration of the vaccine and both the groups showed improvement in vitamin A status following intervention, the increase being significant in the experimental group (from 22.4 ± 1.32 to 26.0 ± 1.07; P < 0.05). The results indicate that majority of the infants at 9 months of age were seronegative to measles. Seroconversion to measles vaccine in the routine immunization clinics was low. Simultaneous administration of vitamin A and measles vaccine had beneficial effects on vitamin A status as well as seroconversion rates to the vaccine in 9 months old infants.     

Seroconversion after measles vaccination at nine and fifteen months of age

BACKGROUND: Despite high vaccination coverage, single dose measles immunization programs have been unsuccessful in eliminating the disease. Because seroconversion rates are lower in infants vaccinated before 12 months of age, a second dose of measles vaccine is recommended at 15 months. The aim of this study was to determine the seroconversion rates in children after the first and second doses of measles vaccinations at 9 and 15 months of age. METHODS: Study population comprised 116 infants attending the Well Baby Clinic of Istanbul University, Faculty of Medicine. Serum specimens were obtained from children before and 1 month after the first measles (Rouvax, Schwarz strain 1000 TCID(50)) vaccine given at 9 months. A second dose was given to 72 children at 15 months of age as measles-mumps-rubella (Trimovax, Schwarz measles strain, 1000 TCID(50); Urabe Am 9 mumps strain, 5000 TCID(50); Wister RA 27/3 rubella strain, 1000 TCID(50)). Third blood samples were collected 20 months after the second vaccine. RESULTS: Passive antibody positivity rate was 5.2% at the age of 9 months. Seroconversion rate was 77.6% after the first dose and 81.9% after the second dose of measles vaccine. Of 15 children who were seronegative, 13 (86.7%) became seropositive after the immunization at 15 months. Eleven children (19.2%) seroconverted from positive to negative after the second vaccine. CONCLUSION: The two dose schedule seems to increase the seropositivity rate. Our findings also indicate that increasing vaccination coverage and revaccination at 6 years of age are important even with the early two dose schedule.     

Comparison of high titer Edmonston-Zagreb, Biken-CAM and Schwarz measles vaccines in Peruvian infants.

In an effort to identify the optimal dose and strain of measles vaccination for early immunization, Peruvian infants were randomly assigned to receive one of three measles vaccines in varying doses at 5 to 6 or 8 to 9 months of age. Edmonston-Zagreb vaccines were significantly (P < 0.001) more immunogenic than equivalent or higher titers of Schwarz or Biken-CAM vaccines as determined by neutralization antibody response 3 months after vaccination. Eighty-two percent of infants who received high titer Edmonston-Zagreb vaccine at 5 to 6 months of age developed protective concentrations of measles antibody, a response rate similar to that observed after standard titer Schwarz (81%) or high titer Biken-CAM vaccine (81%) at 8 to 9 months of age. No significant differences in the rates of fever, rash or other adverse events were noted by vaccine group 10 to 14 days after vaccination. Although the high titer vaccines are more immunogenic in young infants than standard vaccines, long term safety must be assured before these vaccines can be put into widespread use.     

Diphtheria-tetanus-pertussis vaccination administered after measles vaccine: increased female mortality?

In low-income countries, children should receive 3 doses of diphtheria-tetanus-pertussis vaccine (DTP) at 6, 10 and 14 weeks of age, and measles vaccine at 9 months of age. However, there is often a delay in administering the vaccines, and DTP is often given after measles vaccine. Previous observations suggest that this practice is associated with increased mortality for female, but not for male children. Within a vitamin A trial in Guinea-Bissau, vaccination status was registered at the time of measles vaccination at 9 months; 141 (31%) of 455 children were missing 1 or more DTP vaccines and were likely to receive them afterward. We examined whether missing DTP vaccine at this time point was associated with sex-differential effects on mortality. In female children, missing DTP was associated with 3.55 (95% confidence interval: 1.23-10.26) times higher risk of dying before 36 months of age, whereas it made no difference in male children (0.97 [0.34-2.80]). The result supports that receiving DTP after measles vaccine affects female children negatively.     

Measles related complications and the role of vitamin A supplementation

Purpose. Measles is associated with high rate of complications and contributes to a major proportion of childhood morbidity and mortality. The role of vitamin A supplementation (VAS) in the case management of measles and prevention of complications is partially understood and not sufficiently supported by epidemiological data. This paper analyses the possible role of vitamin A supplementation in prevention of measles related complications and associated fatality   Methods. A cross sectional study was carried out during an outbreak of measles in Shivpuri, India. A total population of 193,000 was covered by house to house visit and, the caregivers of total 1204 measles cases, including 214 cases with complications, were interviewed using a semi structured interview schedule. The analysis of data was done using Epi Info   Results. The attack rate of 6.7% and rate of complications at 17.8% were found in this investigation. The coverage with routine measles vaccine and the vitamin A supplementation was 18.3% and 28.9% respectively. The management of measles cases was poor with only 15.8% cases receiving therapeutic doses of vit A. Both complications and case fatality rate was higher amongst children who had not received vit A supplementation in previous 6 months (p<0.05). Measles vaccine also found to have preventive effect on development of complications (p<0.05)   Conclusions. Routine vitamin A supplementation and measles vaccination reduces the chances of complications amongst measles cases. The role of VAS becomes more important when the case management is poor. While, measles is frequently associated with complications in Indian setting, there is a need of enhancing the efforts to improve the delivery of vit A supplementation and measles vaccine to the children in rural areas       

Successful immunization of infants at 6 months of age with high dose Edmonston-Zagreb measles vaccine. Cite Soleil/JHU Project Team

A group of 2097 Haitian infants 6 to 11 months of age were randomized to receive Schwarz or Edmonston-Zagreb strain measles vaccines containing 10- to 500-fold more vaccine viral particles than standard potency vaccines. No unusual adverse reactions were noted. Edmonston-Zagreb vaccines were more effective than equivalent doses of Schwarz vaccines as measured by the proportion of vaccinated children with measles antibody concentrations greater than or equal to 200 mIU/ml 2 months after vaccination and the persistence of antibody at 18 to 24 months of age. High titer Edmonston-Zagreb vaccine administered at 6 months of age induced antibody concentrations greater than or equal to 200 mIU/ml in 83% of infants by plaque reduction neutralization and 93% of infants by enzyme-linked immunosorbent assay with high rates of antibody persistence at 12 to 24 months of age. The World Health Organization recommends high titer Edmonston-Zagreb measles vaccines for routine use at 6 months of age in areas where measles is an important cause of mortality in young infants.     

The effect of live measles vaccines on serum vitamin A levels in healthy children

Abstract Objective: Serum retinol levels have been shown to be depressed during measles infection. This study aims to demonstrate whether there is any decrease in serum vitamin A level following immunization with live viral vaccine and its relation with vaccine seroconversion in children with measles. Since many children receive measles vaccine alone or in combination with measles-mumps-rubella vaccine, we studied serum vitamin A levels and antibody levels in healthy, well-nourished children before and after immunization with monovalent and combined live attenuated measles vaccine.
Methods: The first group included 21 healthy children between the ages of9–11 months who received live measles (Schwarz) vaccine. There were also 21 healthy children (range14–20 months of age) who received measles-mumps-rubella Trimovax® (Pasteur Merieux) vaccine. All children were tested for serum vitamin A levels before vaccination, on days9–14 and30–42 following both vaccinations. Measles specific antibody levels were also measured on admission and30–42 days following vaccinations.
Results: In both vaccination groups, mean serum vitamin A levels reduced significantly on days9–14, but increased slightly on days30–42 in the measles-mumps-rubella vaccinated group (P < 0.05). The baseline and follow-up levels of mean serum vitamin A did not differ between seroconverted and nonseroconverted cases within the measles vaccinated group.
Conclusion: Serum vitamin A levels are reduced following vaccination with monovalent and combined live attenuated measles vaccines.     

Integration of vitamin A supplementation with the Expanded Programme on Immunization: lack of impact on morbidity or infant growth

Vitamin A deficiency is associated with increased morbidity and mortality from diarrheal disease, measles, and malaria. It has been proposed that vitamin A supplementation could be linked with childhood immunization programs to improve child health. We conducted a randomized, doubleblind, placebo-controlled clinical trial to evaluate the impact of linking vitamin A supplementation with the Expanded Programme on Immunization on morbidity and child growth. In West Java, Indonesia, 467 six-week-old infants were randomized to receive 7.5 mg retinol equivalent (RE), 15 mg RE, or placebo with childhood immunization contacts at 6, 10, and 14 wks and 9 mo of age. Child growth was assessed through anthropometry, and morbidity histories were obtained. Vitamin A supplementation had no apparent impact upon linear or ponderal growth or infectious disease morbidity in the first 15 mo of age when integrated with the Expanded Programme on Immunization.

Conclusion : Although improving vitamin A nutriture is of general importance in reducing diarrheal and measles morbidity and mortality in developing countries, this clinical trial showed no apparent benefit of vitamin A capsules for infant health when given through childhood immunization programs.     

Reimmunization following early immunization with measles vaccine: a prospective study

A prospective study was designed to determine the response of previously immunized infants following administration of measles vaccine at 15 to 18 months of age. Upon entry into the study at 7 to 12 months of age, 14 of 127 infants had measles antibody. Measles vaccine was administered to infants in the experimental group on the day of entry into the study. Prior to measles, mumps, and rubella vaccine administration at 15 to 18 months of age, six of 23 infants in the control group and 80 of 90 infants in the experimental group had detectable antibodies. Following the (re)vaccination at 15 to 18 months of age, 20 of 21 infants in the control group and 49 of 52 infants in the experimental group had detectable antibody. Early measles immunization in this study did not interfere with the ultimate response to immunization at 15 to 18 months of age. These results support the policy of early immunization for those infants at risk for exposure to measles and reimmunization at 15 months of age.     

Measles, mumps and rubella immunization at nine months in a developing country

The antibody responses and reactogenicity of a measles, mumps and rubella vaccine in 9-month-old and 15-month-old black children in South Africa were compared. The antibody response to the measles component was marginally better in the older group, but no differences were observed in the response to the mumps and rubella components. Reactogenicity was similar in the two age groups. Therefore it is possible that a trivalent measles, mumps and rubella vaccine can safely and effectively replace routine measles immunization at 9 months of age in this population. Whether routine immunization policy should incorporate such a vaccine depends on the extent of acceptance of measles vaccination. In urban populations of developing countries with high rates of measles immunization, routine vaccination at 9 months might interrupt circulating wild type rubella and provide sufficient herd immunity to protect susceptible women of childbearing age. It also should decrease significantly the complications associated with wild type mumps infection. The replacement of measles vaccine by a trivalent vaccine may be very cost-effective.     

Prevention in pediatrics in the Nord-Cotentin. Prospective study of 255 cases

Over a 4 month period, the medical records of 255 children with an age range of 6 months to 3 years and who had been admitted to the Cherbourg Hospital Department of Pediatrics were prospectively studied. Ninety-nine % had received BCG vaccination but only 71% had a positive skin test. Ninety-two % were vaccinated against diphtheria, tetanus, whooping cough and poliomyelitis and 61% against measles. Seventy-eight % of parents said that they had correctly administered vitamin D, at least up to 18 months of age. Seventy % of children were fed cow's milk during the second half of the first year and at least 35% had at least one hematological sign of iron deficiency. The promotion of routine immunizations as well as vaccination against rubella-mumps-measles seems to be desirable goals. There is a need for the widespread use of adapted milk formulas up to 1 year of age and for systematic iron supplementation of pregnant women and of infants presenting with evidence of iron deficiency or on cow's milk.     

High-titer measles vaccination before 9 months of age and increased female mortality: do we have an explanation?

In 1989, high-titer (HT) Edmonston-Zagreb measles vaccine with a titer more than 10(4.7) plaque-forming-units was recommended by the World Health Organization for use in areas with a high incidence of measles in children younger than 9 months. In 1992, the recommendation was rescinded following reports from Guinea-Bissau, Senegal, and Haiti showing an increased incidence of female mortality occurring after administration of HT Edmonston-Zagreb vaccination. We reviewed 9 studies of HT measles vaccines that reported data on mortality. These reports included 4 randomized trials comparing HT vaccine administered to children younger than 9 months with standard-titer (ST) vaccines (10(3.0) to 10(4.0) plaque-forming-units) given at 9 months of age. Five studies from Zaire, Haiti, Senegal, Rwanda, and Zaire had no control group receiving ST vaccine at 9 months of age, but investigators were able to examine the female-to-male mortality ratio within these HT studies. Investigators have hypothesized that HT vaccine had caused immune suppression similar to that of measles infection. The present review suggests first that the HT vaccine itself is unlikely to be the cause because the effect was not found in all studies. Second, the increased mortality started only after 9 to 10 months of age when controls received ST measles vaccine, and HT groups received the "control vaccine." It was not found in the studies that provided another measles vaccine instead of control vaccine. Third, because the HT studies with excess mortality rates showed increased female mortality rates, we need to find environmental or contextual conditions associated with increased female mortality rates in some studies to explain the problem associated with HT measles vaccination.     

Childhood survival in Haiti: protective effect of measles vaccination

To evaluate the impact of measles vaccination on survival of children residing in a periurban slum in Haiti, a total-population survey was conducted 2.5 years after completion of a one-time study of the serologic response to measles vaccine administered in the same population. Pregnancy histories from the 16,400 women in the population revealed that 1499 children had been born during a 7-month interval that would have made them eligible for participation in the measles vaccine program. Of these children, 1381 (92.1%) survived to 9 months of age, the median age that measles vaccine had been administered. Seventy-three infants had died between 9 and 39 months of age. Mortality of infants who were seronegative before receiving measles vaccine was significantly lower (P = .0013) than that of unvaccinated infants (3/235 vs 70/1056, respectively). Other factors positively associated with survival between 9 and 39 months of age included socioeconomic status (P = .0002), maternal literacy (P = .0020), maternal knowledge and use of oral rehydration solution (P = .0002), and an interval of greater than 24 months to the birth of the next younger sibling (P = .0012). Multivariate stepwise logistic regression analysis was used to evaluate the independent association of measles vaccination by adjusting for other factors that also correlated with survival and that might have been associated with maternal seeking of vaccinations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measles Vaccination V. The Booster Effect of Purified Hemagglutinin in Children Previously Immunized with this Product or Formalin-Killed Vaccine

Two groups of children immunized at the age of 6 months to two years with three monthly doses of either formalin-killed (FK) or Tween-ether (TE) measles vaccine were submitted to clinical and serological follow-up analysis up till 17 months after vaccination and then given a booster of TE vaccine of moderate potency. Among 8 cases of clearcut exposure to measles before the booster 6 responded with mild clinical symtoms; 3 without and 3 with a faint rash. An increase in HI serum titer was recorded in 3 out of the 6 cases. All of them had received FK vaccine. Between 11 and 17 months after vaccination no change in HI titers was demonstrable. After the booster the geometric mean HI titer increased 20 times in children primarily vaccinated with TE vaccine and 83 times in children given FK vaccine. In the pre-booster serum samples only 75 antibodies were detectable, where-as the post-booster serum samples in addition to 75 antibodies contained 1 to 3% 19S 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.     

Effect of monovalent measles and trivalent measles-mumps-rubella vaccines at various ages and concurrent administration with hepatitis B vaccine

To determine the most suitable vaccination schedule in developing countries, a study was conducted to reevaluate the immunogenicity of monovalent measles vaccine and trivalent measles-mumps-rubella vaccine at different ages. The success rate of measles vaccination was 84% at 9 months, 88% at 12 months and 100% at 15 months of age. Vaccination with measles vaccines at 9 and 15 months of age was also 96% immunogenic. Most vaccinees (16 of 17) not responding to the first measles vaccine before 1 year of age developed measles antibody with another shot of vaccine after 15 months of age. Trivalent measles-mumps-rubella vaccine worked well in children ages 14 to 18 months. Administering trivalent vaccine and hepatitis B vaccine concurrently at 1 year of age, rubella and mumps antibodies developed in more than 95% of vaccinees, while measles antibody was detected in 88%. Responses to hepatitis B vaccine in this situation were good; 89% of vaccinees developed antibody against hepatitis B surface antigen (greater than or equal to 10 mIU/ml) and the geometric mean titer was 362.49 mIU/ml. In summary vaccination twice at 9 and 15 months is effective and is a useful regimen in developing countries where measles is still endemic. Trivalent vaccine and hepatitis B vaccine will not interfere with each other when given together at 1 year of age.     

Impact of revaccinating children who initially received measles vaccine before 10 months of age

Two hundred fifty-four infants who had received measles vaccine at less than 10 months of age were revaccinated at greater than or equal to 15 months of age, and their immune responses were compared with 129 control infants who received their first doses of measles vaccine at greater than or equal to 15 months of age. Sera were collected at the time of revaccination (study infants) or primary vaccination (control infants), 3 weeks, and 8 months later and tested for antibody by hemagglutination inhibition (HI), enzyme-linked immunosorbent assay (ELISA), and cytopathic effect neutralization (CPEN). Of the 121 study infants who were initially HI negative, 116 (95.9%) made HI antibody 3 weeks postrevaccination compared with 126 (99.2%) of 127 control infants (P = 0.19). Of the 63 study infants with no initial detectable antibody by any of the three tests, 14 (22.2%) had a measles-specific IgM response 3 weeks postrevaccination compared with 37 of 50 (74.0%) randomly chosen control infants. By 8 months after revaccination, the 121 initially HI-negative study infants were significantly less likely to have detectable HI antibodies than control infants (52.1% v 97.6%) (P less than .001). However, 96.7% of these 121 study infants had detectable neutralizing antibody 8 months postrevaccination, an antibody thought to correlate best with protection. This study confirms the altered immune response to revaccination in infants first vaccinated prior to 10 months of age; however, the data suggest that most of these infants were successfully primed and are probably protected after revaccination.     

The pneumococcal conjugate vaccine

Streptococcus pneumoniae is the most frequent cause of otitis media, sinusitis, and pneumonia in children. It is also one of the most common causes of invasive bacterial infections in children including bacteremia and meningitis. One of the current issues regarding S. pneumoniae is the emergence of pneumococcal strains resistant to penicillin and other antibiotics. Children less than two years of age suffer an increased incidence of invasive pneumococcal disease but fail to respond to the 23-valent polysaccharide vaccine because of the immaturity of the T-cell independent immune function. Covalently conjugating the polysaccharide antigen to a carrier protein improves the immune response by permitting the host to utilize a T-cell dependent immune response that is adequately mature in children less than two years of age. Immunogenicity studies of the currently licensed heptavalent conjugated polysaccharide vaccine, (Prevnar, marketed by Wyeth Lederle Vaccines) demonstrated that infants vaccinated with three doses 2 months apart at 2, 4, and 6 months of age successfully developed antibodies to all 7 serotypes; booster doses at 12-15 months demonstrated an amnestic response for each serotype. Immunogenicity studies have similarly demonstrated successful responses in children with sickle cell disease and human immunodeficiency virus infection. An efficacy trial involving nearly 38,000 subjects demonstrated the vaccine's effectiveness in healthy children against invasive pneumococcal disease as well as against pneumonia and otitis media. Currently the US Advisory Committee on Immunization Practices (ACIP) recommends that all infants and children under 24 months of age receive the vaccine. The ACIP recommends that infants receive the vaccine routinely at 2, 4 and 6 months with a fourth dose at 12 to 15 months of age. Infants may receive the first dose as early as 6 weeks of age. The vaccine is also indicated for children 24 to 59 months of age who are at high risk for pneumococcal infection. Adverse events include local reactions in the first two days following vaccination such as approximately 10% reporting erythema, 10% induration, and 20% tenderness. Fever of 38 degrees C or higher occurred in 15% to 25% of children in the first two days following vaccination. Follow-up studies should address important questions regarding the use of pneumococcal conjugate vaccine and other age groups.     

Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia.

We performed a randomized, double-blind, controlled trial to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to receive either 2000 IU retinyl palmitate (n = 27) or saline placebo (n = 22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48%, placebo group 55%; p = 0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 micrograms/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 micrograms/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease.     

Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age

OBJECTIVE: The objective was to study the effects of iron supplementation on hemoglobin and iron status in 2 different populations. Study design: In a randomized, placebo-controlled, masked clinical trial, we assigned term Swedish (n = 101) and Honduran (n = 131) infants to 3 groups at 4 months of age: (1) iron supplements, 1 mg/kg/d, from 4 to 9 months, (2) placebo, 4 to 6 months and iron, 6 to 9 months, and (3) placebo, 4 to 9 months. All infants were breast-fed exclusively to 6 months and partially to 9 months. RESULTS: From 4 to 6 months, the effect of iron (group 1 vs 2 + 3) was significant and similar in both populations for hemoglobin, ferritin, and zinc protoporphyrin. From 6 to 9 months, the effect (group 2 vs group 3) was significant and similar at both sites for all iron status variables except hemoglobin, for which there was a significant effect only in Honduras. In Honduras, the prevalence of iron deficiency anemia at 9 months was 29% in the placebo group and 9% in the supplemented groups. In Sweden, iron supplements caused no reduction in the already low prevalence of iron deficiency anemia at 9 months (<3%). CONCLUSION: Iron supplementation from 4 to 9 months or 6 to 9 months significantly reduced iron deficiency anemia in Honduran breast-fed infants. The unexpected hemoglobin response at 4 to 6 months in both populations suggests that regulation of hemoglobin synthesis is immature at this age.