Serological response to early measles vaccination

This study compares the persistence of measles IgG antibody in 239 children vaccinated at 6-8 months of age with 76 children vaccinated after 8 months of age. Among the children vaccinated prior to 9 months, 49 per cent of the children between 16 and 44 months and 33 per cent of children over 54 months had levels of measles IgG antibody conventionally considered protective. Among the children older than 48 months, 67 per cent of children vaccinated before 9 months and 13 per cent of children vaccinated after 8 months had antibody levels below the conventionally accepted protective levels of 0.2 IU/ml. Older children had lower antibody levels than younger children. Measles immunization before 9 months with the standard titer Edmonston-Zagreb vaccine has not provided a large proportion of under-five children with protective levels of measles IgG antibody. A significant proportion of children vaccinated at the currently recommended age also had suboptimal levels. It is difficult to protect the majority of the measles-susceptible population with a single dose regardless of the immunization schedule used. A second dose of measles vaccine may be necessary to increase the herd immunity.     

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.     

Prevalence of placentally transmitted antibodies for measles in infants 3 to 11 months old in an urban slum community

Upto 35% of infants aged between 6 and 11 months are infected with measles in India with its associated high morbidity and mortality. The objective of the study is to know the waning pattern of placentally transmitted antibodies (PTA) for measles so that the age at which children are likely to become susceptible to measles infection could be identified. A cross-sectional serological survey of children aged 3 to 11 months in one of the Integrated Child Development Service (ICDS) area in Madras city slums was done. Venous blood from 376 children was collected and was tested for Hemagglutination Inhibition (HI) antibodies by standard microtitration technique. Titre greater than or equal to 1:8 has been considered as protective. The proportion of children with immune level and the Geometric Mean Titre (GMT), declined to the least by 5 months which denotes that most of the infants become susceptible to measles infection from as early as 5 months of age. There is no significant difference in the waning pattern between different age groups, sex and nutritional status. A community study for effectiveness of measles vaccine at 6-8 months of age is needed to know the feasibility of immunization earlier than 9 months of age.     

Placental transfer and decay of maternally acquired antimeasles antibodies in Nigerian children

BACKGROUND: In developing countries vaccination against measles virus (MV) is generally administered at 9 months of age, although it is well-documented that protection of most infants by passively acquired maternal MV antibodies is waning before immunization is given. The purpose of this study was to investigate the decay of maternally derived MV antibodies in Nigerian infants as well as to compare a German and Nigerian cohort of paired mothers and newborns regarding the placental transfer efficiency of MV-specific IgG and total IgG antibodies. METHODS: MV-specific IgG antibodies were measured with a commercially available MV-enzyme-linked immunosorbent assay, a recombinant hemagglutinin enzyme-linked immunosorbent assay as well as a neutralization assay. Total IgG values were determined with a standard immunoturbidimetric test. RESULTS: Anti-MV IgG titers were twice as high in German newborns as in Nigerian newborns. An increased concentration of immunoglobulins transferred via the placenta was found only in the German cohort. High concentrations of total maternal IgG reduced the concentration of MV-specific as well as total IgG that crossed the placenta. Furthermore only 17% of the 4-month-old Nigerian infants were still protected against measles. Antibodies had a biologic half-life of 33 days and a biochemical half-life of 48 days. CONCLUSIONS: Our findings demonstrate that the decay of passively acquired MV antibodies occurred even more rapidly than expected resulting in susceptibility to MV in most of the 4-month-old infants in Nigeria. Furthermore transfer of maternal anti-MV IgG and total IgG antibodies to the newborn was more efficient in the German cohort compared with the Nigerian group. These findings suggest the use of alternative vaccination strategies in developing countries to possibly reduce the window of susceptibility against measles.     

The evaluation of vaccination against measles at nine months of age (report of an epidemic).

Sixteen measles cases were studied during an epidemic that broke out in Etimesgut district of Ankara. Eight of these children had never been vaccinated against measles while the remainder had been vaccinated at nine months of age. In the sera obtained during the course of the illness, anti-measles antibody was not detectable in six vaccinated children and in four unvaccinated children. Upon observing the siblings of the subjects, it was determined that one out of three who had not been vaccinated against measles and three out of seven who had been vaccinated at nine months of age contracted the disease within a month. However none of the siblings who had been vaccinated against measles at 15 months contracted the disease. In our cases, although vaccination at nine months of age could not prevent measles, it resulted in a milder form of the disease. It seems that measles vaccine administered to infants at around nine months of age does not prevent the occurrence of the disease in many children.     

Experience with a measles vaccine manufactured in India.

Five hundred and twenty seven children between 7 months and 2 years of age were vaccinated with measles vaccine manufactured by the Serum Institute of India. The sero-conversion rate in children who had no antibodies previous to vaccination was 98.4% as tested in HI. Ninety per cent of children who had pre-vaccination measles antibodies showed a two-fold or more rise in HI antibodies. The side reactions of the vaccine were negligible.     

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).     

Seroconversion in different age groups after measles vaccination

Seroconversion following measles immunisation was studied in 439 children aged below 9 to 25 months. The anlaysis of age specific seroconversion rate revealed that only 78 · 9 per cent children in the age group below 9 months was seroconversion rate was not observed with further increase in the age of immunisation. The finding supports the recommendation that 9–12 months is the earliest age for satisfactory active immunisation against measles in India. The use of potent measles vaccine in the immunisation programme was monitored by potency testing of samples recalled from the field.     

Impact of multiple dose measles vaccination on measles transmission patterns in Gweru, Zimbabwe

Multiple dose measles vaccination was applied in Gweru, Zimbabwe in 1990-1996. This included (a) a vaccine administered to children at 9 months of age and revaccination of the same children at any point between the ages of 12 and 23 months, and (b) a single mass vaccination campaign targeted at children aged 12-119 months (who were vaccinated irrespective of vaccination status or disease history) run in early 1990. This study describes the impact of this schedule on measles transmission patterns. Using measles disease surveillance data the study compared measles transmission patterns under single dose vaccination in 1983-1989 and under multiple dose vaccination in 1990-1996. Median measles incidence rates were 261.0 and 19.0/100000 population in 1983-1989 and 1990-1996, respectively, and these were different (p = 0.002). Vaccinated cases (vaccine failures) among children aged 10-119 months significantly increased from 49.6 to 70.4 per cent of all reported cases in 1983-1989 and had a median incidence rate of 480.4/100000. In 1990-1996 the median incidence rate was 12.8 and these incidence rates were different (p = 0.002). Cases aged 60-119 months significantly increased from 14.3 to 62.2 per cent of all reported cases in 1983-1989 and had a median incidence rate of 654.1/100000. In 1990-1996 the median incidence rate was 21.4 and these incidence rates were different (p = 0.004). It was concluded that under multiple dose vaccination, lower measles incidence rates occurred most likely due to reduction of both vaccine failures and cases aged 60-119 months.     

Study of antibody titres after measles vaccination: fever within 7 days of vaccination and efficacy of booster doses

We investigated seroconversion rates in febrile children after measles vaccination. Among 6364 vaccinees, 501 children had a temperature of 37.5 degrees C or higher within 7 days of vaccination. The seroconversion rate assessed by a haemagglutination-inhibition assay was 76.6% in 501 febrile children but 95.2% in 84 afebrile controls. Measles vaccination has been reported to provide immunity in at least 95% of cases. The number of patients infected with measles has dramatically decreased since the introduction of measles vaccination. However, problems remain, including primary vaccine failure (PVF), failure to develop immunity after vaccination, and secondary vaccine failure (SVF), that is, the development of infection because of waning antibodies after vaccination. In this study, we investigated the effect of febrile upper respiratory tract infection (URTI) after vaccination and found a lower rate of seroconversion to measles and a lower mean antibody titre in those who developed a fever within 7 days of measles vaccination.     

Study of antibody titres after measles vaccination: fever within 7 days of vaccination and efficacy of booster doses.

We investigated seroconversion rates in febrile children after measles vaccination. Among 6364 vaccinees, 501 children had a temperature of 37.5 degrees C or higher within 7 days of vaccination. The seroconversion rate assessed by a haemagglutination-inhibition assay was 76.6% in 501 febrile children but 95.2% in 84 afebrile controls. Measles vaccination has been reported to provide immunity in at least 95% of cases. The number of patients infected with measles has dramatically decreased since the introduction of measles vaccination. However, problems remain, including primary vaccine failure (PVF), failure to develop immunity after vaccination, and secondary vaccine failure (SVF), that is, the development of infection because of waning antibodies after vaccination. In this study, we investigated the effect of febrile upper respiratory tract infection (URTI) after vaccination and found a lower rate of seroconversion to measles and a lower mean antibody titre in those who developed a fever within 7 days of measles vaccination.     

Nutritional and clinical status of children admitted to the malnutrition ward, Maputo central hospital: a comparison of data from 2001 and 1983

Malnutrition is the fourth commonest reason for hospital admission to the paediatric department of the Central Hospital, Maputo and has the second highest death rate (20 per cent). A study from 1995 into mortality at this paediatric department, suggested an increase in severe malnutrition. Recent studies have shown that the global burden of undernutrition in the world is declining; however, data for Eastern Africa shows a deterioration. The current study was aimed at describing and comparing the patients on the malnutrition ward, in 2001 and 1983. The study gathered indices of nutritional status and secondary diagnoses from the notes of all children (aged between 6 months and 5 years) discharged from the malnutrition ward for a period of l year (January-December 2001), and from data (collected in January-December 1983) for the malnutrition ward. Data was entered and analysed using Epi-Info 6 and SPSS statistics package. The ethics committee of the hospital approved the study. Data was collected for 558 children in 2001 and 833 in 1983. There was no gender difference, average age was 21.7 months in 2001 and 23.8 months in 1983 and the average hospital stay was 13.1 and 14.3 days, respectively. In 2001, 33 per cent had kwashiorkor, 26 per cent marasmus, and 28 per cent marasmic kwashiorkor. Three hundred and twenty children (82 per cent) were <2 Z-scores below the median weight-for-age and 252 children (65 per cent) were <3 Z-scores. Forty per cent had malaria, 65 per cent anaemia, 53 per cent bronchopneumonia, 14 per cent TB, 36 per cent diarrhoea, and 12 per cent HIV/AIDS. In 1983, 49 per cent had kwashiorkor, 17 per cent marasmus, and 11 per cent had marasmic kwashiorkor. A total of 494 children (81 per cent) were <2 Z-scores below the median weight-for-age and 335 children (55 per cent) were <3 Z-scores. Eighteen per cent had malaria, 37 per cent anaemia, 28 per cent bronchopneumonia, 6 per cent TB, 8 per cent diarrhoea, and 4.4 per cent measles/post-measles. A comparison between the clinical status of 1983 with that of 2001 shows little difference in age, gender or length of stay. There were fewer admissions in 2001, although a higher percentage of severely underweight children and the 2001 group had more secondary infections, especially malaria, bronchopneumonia and anaemia. Clinical malnutrition at a referral hospital level, in spite of the remarkable Mozambican economic growth, shows signs of following the depressing pattern for much of Eastern Africa. A prospective study including HIV tests and anthropometric data for this and the city's other hospitals is warranted. Discussion needs to be prompted on a local level about malnutrition and the use of guidelines.     

Measles in Equatoria region--south Sudan

A retrospective analysis of 208 cases of measles admitted to Sabbah Children's Hospital, Juba is presented. Seventeen per cent of the children were less than 10 months of age. The overall case fatality rate was 23%. The death rate was lowest in the first 9 months of life and increased with age, as did the incidence of malnutrition. It is recommended that measles vaccination should commence at 6 months of age in the Juba area, and that intensive health education about the dangers and management of measles be instituted.     

Moderate immunization coverage levels in East Delhi: implications for disease control programmes and introduction of new vaccines

A vaccination coverage survey conducted in East Delhi in September 1999 showed that only 58.6 per cent of the children aged 12-23 months had received the full course of the vaccines recommended under the national immunization programme. Coverage with the third dose of DTP and oral polio vaccines was around 71 per cent, and with BCG and measles vaccines was 83 and 59 per cent, respectively. Drop-out rates between DTP1 and DTP3 and between DTP1 and measles immunization were 13.8 and 28.7 per cent, respectively. Nine per cent of the children had not received a single dose of any vaccine. The main reason for failure to immunize was lack of information. There was a marginal increase in DTP3 and OPV3 immunization coverage levels as recorded through a previous survey in 1996, a drop in coverage with measles vaccine from 64.3 to 59 per cent, and a significant increase in tetanus toxoid immunization coverage of pregnant women from 79.4 to 93 per cent. The percentage of children who had not received any vaccine declined from 13 to 9 per cent in the period between the two surveys. Coverage with hepatitis B vaccine at 14 per cent was only marginally higher than the baseline rate of 9 per cent before the vaccine was made available, free of cost, through government and municipal corporation health facilities.     

Measles revaccination. Persistence and degree of antibody titer by type of immune response

During a measles immunization campaign 203 children were enrolled in an antibody response study. Of this group, follow-up clinical data and sera samples were available from 125 children three weeks after immunization and from 90 children ten months later. Seventy-six of the children had been previously vaccinated, ten had a history of measles and 39 denied vaccination or illness. Twenty-six of the children had prevaccination hemagglutination inhibiting antibody titers of less than 5. Of this group 12 had a primary immune response (IgM measles antibody) with geometric mean titers (GMT) of 90 and 40 three weeks and ten months respectively after vaccination. In contrast, the other 14 children with initial titers of less than 5 had secondary immune responses (only IgG measles antibody) with GMTs of 28 and 9 three weeks and ten months after vaccination. Since the antibody responses in these children who had previously been stimulated by measles antigen were modest and transient, it is suggested that booster immunization may not be effective in preventing future secondary vaccine failures. Also noted in this study was a poor correlation between historical data and actual measles antibody.     

Effect of second dose of measles vaccine on measles antibody status: A randomized controlled trial

Objective

To evaluate the effect of the second dose of measles vaccine on measles antibody status during childhood.

Setting

Immunization centre of Under-five Clinic of the Department of Community Medicine at a tertiary-hospital.

Design

Randomized Controlled trial.

Methods

Blood samples were collected from all subjects for baseline measles serology by heel puncture at 9–12 months of age. All subjects were given the first dose of measels vaccine. At second visit (3–5 months later), after collecting the blood sample from all, half the children were randomized to receive the second dose of measles vaccine (study group), followed by collection of the third sample six weeks later in all the subjects.

Results

A total of 78 children were enrolled and 30 children in each group could be analyzed. 11(36.6%) children in the study group and 13 (43.3%) children in the control group had protective levels of measles IgG at baseline. Around 93.3 % of children in the study group had protective measles antibody titers as against 50% in the control group at the end of the trial. The Geometric Mean Titre (GMT) of measles IgG increased from 14.8 NTU/mL to 18.2 NTU/mL from baseline to six weeks following receipt of the second dose of the vaccine in the study group, as compared to a decrease from 16.8 NTU/mL to 12.8 NTU/mL in the control group.

Conclusions

A second dose of measles vaccine boosts the measles antibody status in the study population as compared to those who receive only a single dose.     

Immune status following measles vaccination in infants and evaluation for the need of revaccination

In this prospective study, immune status of children vaccinated in infancy was determined at age 12-18 months. In 200 children, preimmunization protective measles hemagglutination (HI) antibody titres (greater than or equal to 1:8) were present in 38.5% of children of 6-8 months, the frequency decreased to 17.6 and 14.3% in age groups 9-11 and 12-18 months, respectively followed by an increasing incidence of 52.5% in those more than 18 months of age. Paired measles HI titre was estimated in 56 children, the post vaccination sample was taken at age 12-18 months, 3-9 months after measles vaccination. Most of the children (98.0%), with no detectable antibody titre, had a protective titre. Again a significant number (p less than 0.001) of children aged 12-18 months had protective HI titres compared to non-vaccinated. These findings suggest that when vaccinated at 9-11 months in our country, there is no need for revaccination later.     

Immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease.

OBJECTIVE--To determine the safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease. RESEARCH DESIGN--Prospective, nonrandomized, nonblinded study. SETTING--Hospital-based, comprehensive sickle cell center. PATIENTS--Children with sickle cell disease aged 18 months to 18 years who were previously unvaccinated or had an inadequate or waning response to H influenzae type b polysaccharide vaccine. SELECTION PROCEDURES--Consecutive eligible patients. INTERVENTIONS--Vaccination and observation for adverse effects. Blood samples were taken before and 1 to 2 and 6 months after vaccination to measure anticapsular antibody levels. MEASUREMENTS AND RESULTS--Vaccination was well tolerated. One hundred percent and 96% of the 31 immunized children had postvaccination anticapsular antibody concentrations of greater than 0.15 and 1.0 mg/L, respectively. Six months after vaccination, 100% and 89% of children had these antibody concentrations. CONCLUSIONS--H influenzae type b conjugate vaccines are safe and highly immunogenic in children with sickle cell disease. It is likely that these vaccines will be protective against invasive H influenzae type b disease.     

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.     

Antibody titers and immune response to diphtheria-tetanus-pertussis and measles-mumps-rubella vaccination in children treated for acute lymphoblastic leukemia

The objective of this study was to investigate the diphtheria-tetanus-pertussis and/or measles-mumps antibody titers before and after vaccination at various time points of acute lymphoblastic leukemia (ALL) therapy and to suggest an appropriate vaccination approach for ALL patients. The authors studied 37 ALL patients and 14 healthy control subjects, divided into three groups. In group 1 (newly diagnosed patients), baseline anti-diphtheria, anti-tetanus, and anti-pertussis titers were determined. Patients in group 2 (on maintenance chemotherapy) and group 3 (patients not receiving therapy for 3-6 months) were vaccinated with diphtheria-tetanus with or without acellular pertussis; group 3 and control subjects were also given measles-mumps-rubella vaccine. Preimmunization and 1-month postimmunization titers were drawn. Preimmunization anti-diphtheria and anti-tetanus antibody titers between the groups and the controls were statistically similar. The seropositivity rate for anti-measles antibody in group 3 was significantly lower than controls. After vaccination, all of the patients developed protective anti-diphtheria and anti-tetanus antibody titers. The seroconversion rates of group 3 and controls for anti-measles and anti-mumps antibodies were statistically similar. The results showed that patients on maintenance therapy and after cessation of therapy made good antibody responses to diphtheria and tetanus toxoids, but response to measles and mumps vaccines was not as sufficient as toxoid vaccines. Children with ALL can receive the appropriate vaccines during and after maintenance treatment.