Humoral and cell-mediated immune responses to an early 2-dose measles vaccination regimen in the United States

BACKGROUND: Shifts in peak measles incidence to children <12 months old and the associated high mortality support the study of an early 2-dose measles vaccine regimen. METHODS: Fifty-five infants were vaccinated with measles vaccine at age 6 (n=32) or 9 (n=23) months, followed by measles-mumps-rubella (MMR)-II vaccine at age 12 months. A control group received MMR-II only at age 12 months. Measles-specific humoral and cell-mediated immunity were evaluated before, 12 weeks after measles immunization, and 24 weeks after MMR-II. RESULTS: Measles-specific T cell proliferation after both doses of vaccine was equivalent, regardless of age or the presence of passive antibodies. Seroconversion rates, geometric mean titers, and the percentage of infants with antibody titers >120 mIU after the first measles vaccine were lower in infants vaccinated at age 6 months, regardless of the presence of passive antibodies, but measles humoral responses increased after the administration of MMR-II vaccine in children initially vaccinated at age 6 or 9 months. CONCLUSION: Measles vaccination elicits T cell responses in infants as young as 6 months old, which may prime the humoral response to the second dose. Initiating measles vaccination as an early 2-dose regimen results in an immunologic response that is likely to have clinical benefits in developed and developing countries.     

Short report: assessing field vaccine efficacy for measles in famine-affected rural Ethiopia

Measles is a major cause of mortality in complex emergencies. Both high vaccination coverage and vaccine efficacy are required to prevent major epidemics of measles in such situations. Evaluation of field vaccine efficacy is a critical but underutilized component of program monitoring in emergencies, and is particularly important in rural areas where the integrity of the cold chain is difficult to guarantee. In July 2000, we evaluated the field vaccine efficacy for measles vaccination by comparing the incidence of cases in vaccinated and unvaccinated groups during a two-stage cluster survey of 563 children in Ethiopia. Approximately 30% of the measles cases occurred in vaccinated children. Estimated field vaccine efficacy for measles was 66.9% in children 9-36 months old. The finding of a field vaccine efficacy for measles less than 80% warrants formal assessment of measles vaccine efficacy, particularly in famine emergencies where measles is associated with a high case fatality rate.     

Comparison of vaccination with measles-mumps-rubella vaccine at 9, 12, and 15 months of age

To determine seroconversion rates with measles-mumps-rubella vaccine administered to children at 9, 12, or 15 months of age, we undertook a prospective randomized trial. Among children vaccinated at 15 months of age, 98% seroconverted to measles, compared with 95% of those vaccinated at 12 months of age and 87% of those vaccinated at 9 months of age. In each age group, children of mothers born in or before 1963 had lower rates of seroconversion against measles, with the lowest rate in children vaccinated at 9 months. The seroconversion rate of rubella paralleled that of measles, with the lowest seroconversion rates in children vaccinated at 9 months of age whose mothers were born in or before 1963. The response to mumps varied little by age of the child or birth year of the child's mother. These results support the recommended age for first vaccination with measles-mumps-rubella at 12-15 months.     

Field trial of a heat-stable measles vaccine in Papua New Guinea

In Papua New Guinea, consideration has been given to the introduction of measles vaccination, and a trial was conducted to determine the optimum age for vaccination and the suitability of a heat-stable measles vaccine (Rimevax) for countrywide use. As much of the vaccination programme is carried out by MCH teams on foot patrols, the trial was designed to determine immunogenicity of the vaccine after being transported and used for a week in a standard issue vaccine Esky by MCH staff. A study of the relevant literature having indicated 9 months as the probable best minimum age for measles vaccination, younger children were not included. The study was carried out on 313 infants and children aged nine to 24 months. An overall seroconversion rate of 96.6% was achieved using initially potent vaccine kept under field conditions for up to 102h. Ninety-seven percent of the vaccinees less than 11 months and 15 days of age seroconverted, as did all 15 children who were less than 70% of the Harvard standard weight for age. All 35 children who had seroconverted and who were retested six months after vaccination had detectable measles antibodies in their serum. Parental recollection of past measles infection was found unreliable as was reporting of post-vaccination reactions by parental recall since the incidence of reported 'reactions' in initially seronegative and seropositive vaccinees were similar. It is concluded that use of this heat-stable vaccine is possible with existing cold chain facilities in PNG and that infants can be vaccinated from the age of 9 months.     

The influence of HIV-1 exposure and infection on levels of passively acquired antibodies to measles virus in Zambian infants.

BACKGROUND: The age at which passively acquired antibodies are lost is critical to determining the optimal age for measles vaccination. Little is known about the influence of human immunodeficiency virus type 1 (HIV-1) infection on levels of prevaccination antibodies to measles virus. METHODS: Antibodies to measles virus were measured by plaque reduction neutralization assay in HIV-1-infected, HIV-seropositive but uninfected, and HIV-seronegative Zambian infants aged 6 weeks to 9 months. Regression models were used to estimate age-specific antibody concentrations. RESULTS: Neutralizing antibodies to measles virus were measured in 652 plasma samples collected from 448 infants, of whom 61 (13.6%) were HIV-1 infected, 239 (53.4%) were HIV seropositive but uninfected, and 148 (33%) were HIV seronegative. The best fitting model suggests that HIV-1-infected infants have lower levels of passively acquired antibodies to measles virus at birth than do HIV-seronegative infants, but their antibody levels decrease more slowly. By 6 months of age, 91% (95% confidence interval, 83%-99%) of HIV-1-infected infants, 83% (95% confidence interval, 77%-89%) of HIV-seropositive but uninfected infants, and 58% (95% confidence interval, 51%-64%) of HIV-seronegative infants were estimated to have antibody levels that were unlikely to affect immune responses to measles vaccine (cutoff value for immune response, <50 mIU/mL). By 9 months of age, 99% of all infants had antibody levels <50 mIU/mL. CONCLUSIONS: Infants born to HIV-1-infected women are less likely to have passively acquired antibodies that would neutralize measles vaccine virus and, thus, have an increased risk of measles prior to the age of routine vaccination. Protection could be achieved by administration of the first dose of measles vaccine prior to 9 months of age.     

Control of measles in Czechoslovakia (CSSR)

Mass immunization against measles in the Czechoslovak Socialist Republic (CSSR) began in 1969 and utilized the Czechoslovak vaccine, which corresponds in its parameters to the further-attenuated measles vaccines. The immunization rate for relevant age groups of the population (i.e., children born in 1968-1980) is already 98%-99% in 1982. Measles morbidity decreased to less than 2% of the incidence before the introduction of immunization, and the mortality now is practically negligible. The decade 1972-1982 produced significant changes in epidemiologic characteristics of measles. Of importance is the gradual shift in the age distribution of affected children to older, nonimmunized age groups. Results of yearly immunologic surveys of a broad, randomly selected population sample have become the decisive criteria for evaluation of vaccine efficacy. The program of revaccination of all children was chosen as the optimal strategy for maintaining measles elimination. This program aims at ensuring a level of herd immunity in the whole population of greater than or equal to 95%.     

Immunogenicity of measles and rubella vaccines in Oman: a prospective clinical trial

A prospective immunogenicity trial of measles and rubella vaccines was conducted in Oman. Children received measles vaccine at age 9 months and measles-rubella vaccine at age 15 months. Serum specimens were tested for measles-specific IgG and rubella-specific IgG. Of 1025 eligible infants, 881 (86.0%) returned for all five visits and had adequate serum samples for testing. Seroconversion to measles after vaccination at 9 months was 98.1%. At 15 months, 47 (5.3%) of the 881 children were seronegative for measles; of these, 44 (93.6%) seroconverted. At 16 months, 99% of the children seronegative at age 9 months seroconverted after receiving two doses of measles vaccine. At age 15 months, 684 (77.6%) children were seronegative for rubella. Of these, 676 (98.8%) seroconverted by age 16 months. One dose of measles vaccine at age 9 months was highly immunogenic. One dose of measles-rubella vaccine at age 15 months closed the remaining measles immunogenicity gap and resulted in a high rate of rubella seroconversion.     

International measles incidence and immunization coverage

Measles is exquisitely sensitive to immunization programs. We investigated the decline in measles incidence after immunization with 1 or 2 doses of measles-containing vaccine (MCV), with or without supplementary immunization activities (SIAs). Using data from the World Health Organization, we modeled the impact of measles immunization using a negative binomial regression model. All countries offer measles immunization, and 192 of 193 countries offer a second dose of MCV (MCV2), using either a routine second dose, SIAs, or both. The incidence of measles fell from a median of 70.9 cases/100,000/year when coverage with a first dose of MCV (MCV1) was in the range of 0%-39% to a median of .9 cases/100,000/year when MCV1 coverage was 90%-100%, in both cases with no MCV2. Further reductions followed the introduction of MCV2 and SIAs. Modeling showed that each 1% increase in MCV1 coverage was followed by a 2.0% decrease in incidence in the same and following years (95% confidence interval [CI], 2.0%-1.9%, and 2.1%-1.9%, respectively). For a second dose, a rise of 1% in MCV2 coverage was followed by a decrease in measles incidence by .4% (95% CI, .3%-.5%) in the same year and .3% (95% CI, .2%-.5%) in the following year. SIAs were followed by decreases of measles incidence by 40.3% (95% CI, 46.3%-33.8%) in the same year and 45.2% (95% CI, 51.1%-48.7%) in the following year. A herd immunity effect was demonstrated with MCV1 coverage of >80%, and SIAs are an extraordinarily effective strategy for measles control.     

Effectiveness of 1 dose of 2009 influenza A (H1N1) vaccine at preventing hospitalization with pandemic H1N1 influenza in children aged 7 months-9 years

The availability of a well-established immunization registry to provide vaccination information, a school-located vaccination campaign followed by continued 2009 influenza A (H1N1) (pH1N1) activity, and a requirement to report hospitalized influenza cases provided an opportunity to estimate vaccine effectiveness (VE) of an initial dose of pH1N1 monovalent vaccine in children aged 7 months-9 years. Seventy-eight case children and 729 date-of-birth- and zipcode-matched controls were studied. The VE of a single vaccine dose in preventing pH1N1 hospitalization ≥ 14 days after vaccination was 82% (95% confidence interval [CI], 0%-100%; P = .04) in children aged 3-9 years but was zero (-3%; 95% CI, <0%-75%) in children aged 7-35 months. These findings are consistent with those from prelicensure immunogenicity studies and have implications for interpretation of immunogenicity studies and setting priorities for vaccination of young children in future pandemics. Immunization registries can provide a simple, rapid assessment of VE to evaluate and inform vaccination policy.     

Impact of alternative approaches to accelerated measles control: experience in the African region, 1996-2002

From 1996 to 2000, several African countries accelerated measles control by providing a second opportunity for measles vaccine through supplemental campaigns. Fifteen countries completed campaigns in children aged 9 months to 14 years. Seven countries completed campaigns in children aged 9-59 months. In almost all countries that conducted campaigns in children aged 9 months to 14 years, measles deaths were reduced to near zero. In six countries, near-zero measles mortality has been maintained for 4-6 years. Supplemental immunization in children <5 years old was only partially effective (range, 0-67%) in reducing mortality. Measles cases decreased by 50% when routine vaccination coverage increased from 50% to 80%. Initial measles campaigns in children aged 9 months to 14 years, follow-up campaigns in those aged 9-59 months every 3-5 years, and increased routine coverage to 80% will be needed to reduce and maintain measles deaths in African countries at near zero.     

Measles epidemic in the Netherlands, 1999-2000

In 1999-2000, a measles epidemic occurred in The Netherlands, with 3292 reported cases; 94% of the affected patients had not been vaccinated. Only 1 patient had received 2 doses of vaccine. Three patients died, and 16% had complications. For the unvaccinated population, the incidence per 1000 inhabitants 15 months to 14 years old increased from 83 (95% confidence interval [CI], 53-113), in municipalities with vaccine coverage rates < or =90%, to 200 (95% CI, 153-247), in municipalities with coverage rates >95%; for the vaccinated population, the incidence increased from 0.2 (95% CI, 0.1-0.4) to 1.4 (95% CI, 0.9-1.9). Unvaccinated individuals were 224 times (95% CI, 148-460 times) more likely to acquire measles than were vaccinated individuals; the relative risk increased with decreasing vaccine coverage. Herd immunity outside unvaccinated clusters was high enough to prevent further transmission. More case patients came from the vaccine-accepting population living among unvaccinated clusters than from individuals who declined vaccination and who lived among the vaccine-accepting population.     

Evaluation of urban measles mass campaigns for children aged 9-59 months in Mali

There are an estimated 234,000 cases of measles and 13,851 measles-related deaths per year in Mali. In 1998 and 1999, 548,309 children aged 9-59 months were vaccinated against measles during mass campaigns in urban centers across Mali. After the first campaign, measles incidence decreased by 95% in districts encompassing vaccinated urban centers and by 41% in nonvaccinated districts. There was no shift in the proportion of cases by age group in vaccinated centers. Measles in vaccinated districts after the campaign was likely related to persistent transmission in age groups not targeted for vaccination and among children living in nonvaccinated districts. The second campaign (1999) did not change the incidence of measles in vaccinated compared with nonvaccinated centers. Urban mass measles vaccination probably did not affect overall measles transmission in Mali. Mass vaccination of all children in Mali, targeting a larger age group, will be necessary to reach measles control objectives.     

Long-term protection against carriage of hepatitis B virus after infant vaccination

BACKGROUND: Carriage of hepatitis B virus (HBV) is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Infant vaccination has been effective in preventing horizontal transmission during early childhood. It is unknown whether protection is maintained into early adulthood. METHODS: In 1984, early childhood vaccination was introduced in 2 rural Gambian villages. In 2003, serological assessment of 81.5% of 1,350 eligible participants 1-24 years old was done, to determine vaccine efficacy against infection and carriage. RESULTS: Overall vaccine efficacy against infection and carriage was 83.4% (95% confidence interval [CI], 79.8%-86.6%) and 96.5% (85% CI, 93.9%-98.9%), respectively. Vaccine efficacy against infection was similar when restricted to primary responders (85.3%), but a significant effect of peak antibody concentration was found. Both vaccine efficacy and levels of hepatitis B surface antibody (anti-HBs) decreased with age, resulting in a vaccine efficacy against infection and carriage among 20-24-year-old participants of 70.9% (95% CI, 60.4%-80.5%) and 91.1% (95% CI, 75.8%-100%), respectively. Fifteen years after vaccination, fewer than half of the vaccinees had detectable anti-HBs. The prevalence of carriage in the unvaccinated population was similar to the prevalence 20 years earlier. CONCLUSIONS: HBV vaccination early during life can provide long-lasting protection against carriage, despite decreasing antibody levels. The role played by subclinical boosting and the necessity of a booster need to be evaluated.     

Measles vaccination coverage during poliomyelitis national immunization days in Burkina Faso, 1999

In 1999, Burkina Faso added measles vaccine during the second round of its poliomyelitis national immunization days (NIDs). A cluster survey was conducted in each of the country's 53 health districts to assess vaccination coverage achieved by the campaign. Forty-four percent of children aged 9-59 months had a documented prior measles vaccination, and 88% were vaccinated during NIDs. Eighty-five percent of children not previously vaccinated received measles vaccine during the campaign. Although routine vaccination coverage varied substantially among children from various socioeconomic groups, the campaign appeared to almost equally reach all groups of children surveyed. Poliovirus vaccine coverage was 90% when measles vaccine was added to the campaign, compared with 88% during the first round. In Burkina Faso, the addition of measles vaccine to poliomyelitis NIDs achieved greater equity in measles vaccination coverage according to a number of socioeconomic factors without compromising the coverage of poliovirus vaccination.     

Measles vaccine coverage and immune response in children of Caiabi and Metuktire Indian tribes living in malarial endemic area: Parque indígena do Xingu, Central Brazil.

Measles vaccination efficiency was evaluated in children from two Indian tribes - Caiabi and Metuktire - living in the Amazon region, in the Parque Indigena do Xingu (PIX).The population sample, selected at random, made up 37 Caiabi and 28 Metuktire children, aged from 20-75 months (40%). For operational and epidemiological reasons, measles vaccine is given from 6 months of age.The average age of children when they received the vaccine was 11.5 months for the first dose and 20 months for the second.The search for IgG antibodies against measles virus and Plasmodium falciparum was made through immunofluorescence assay (IFA). Measles vaccine coverage has reached 60% at 12 months of age and 92% at 18 months, whereas post-vaccine serum conversion was 95% in Caiabi children (geometric mean of titres (GMT) 126) and 89% in Metuktire (GMT 109).The difference in GMT is not statistically significant. Seventy-three per cent of Caiabi children (GMT 101) and 100% of Metuktire children (GMT135) were plasmodium antibody positive, showing they had been exposed to malarial infection. Despite the differences detected, the immune response to measles vaccine was satisfactory in both groups, with a positive percentage consistent with that achieved in non-malarial areas in Americas.The results show the efficiency of a vaccination programme in an indigenous area despite the difficulties in reaching the villages and maintaining the cold chain, and also despite the malaria endemicity.     

Evolution of the measles vaccination program in Costa Rica

The vaccination program instituted in Costa Rica in 1967 has had a great impact on measles. Since 1973 the downturn in its incidence and in mortality due to the disease are due solely to the continued vaccination of susceptible children throughout the country. An epidemic outbreak occurred in 1977. Since the vaccine was given primarily to children of school age, this outbreak probably was the result of an accumulation of susceptible subjects. There was little change in the mortality rates. Programs resulting in a coverage of 70% attempted to prevent a new outbreak in 1979, but failed. Because the vaccine was routinely administered to children one year of age and older, most of the cases were in the group younger than that age. At present, the incidence of measles is minimal, and no fatalities occurred in 1981. Vaccination coverage for children two years of age exceeds 90%, and Costa Rica's goal is the complete eradication of the disease.     

Vaccination levels associated with lack of measles transmission among preschool-aged populations in the United States, 1989-1991

Knowledge of the minimum level of vaccination capable of preventing measles transmission in an age group is helpful for establishing program targets for measles elimination. In 1990, during the measles resurgence in the United States, one-half of cases occurred in children aged <5 years. Although estimated population immunity among persons >or=6 years of age was 93%, immunity was lower and varied widely among preschool-aged children. To examine the association of vaccine coverage at 2 years of age and measles incidence among preschool-aged children, we analyzed ecological studies of measles incidence in Milwaukee (Wisconsin) census tracts, Dallas (Texas) ZIP code areas, and selected cities during the 1989-1991 measles resurgence. In each study area, measles incidence decreased rapidly with increasing measles vaccine coverage and became low or negligible when coverage was >or=80%. Regression analysis also suggested that measles would not be transmitted when vaccine coverage was at least 79%. A minimum vaccine coverage of approximately 80% at the second birthday in census tracts, ZIP code areas, and cities in the United States may be sufficient to prevent measles transmission among preschool-aged children if population immunity is >or=93% among persons >or=6 years of age.     

Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: an observational study

BACKGROUND: Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1-infected children may be less likely to respond to or maintain protective antibody levels after vaccination. METHODS: We conducted a prospective study of the immunogenicity of standard-titer measles vaccine administered at 9 months of age to HIV-1-infected and uninfected children in Lusaka, Zambia. RESULTS: From May 2000 to November 2002, 696 children aged 2-8 months were enrolled. Within 6 months of vaccination, 88% of 50 HIV-1-infected children developed antibody levels of >or=120 mIU/mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV-seropositive but uninfected children (P=.3). By 27 months after vaccination, however, only half of the 18 HIV-1-infected children who survived and returned for follow-up maintained measles antibody levels >or=120 mIU/mL, compared with 89% of 71 uninfected children (P=.001) and in contrast with 92% of 12 HIV-1-infected children revaccinated during a supplemental measles immunization activity. CONCLUSIONS: Although HIV-1-infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence.     

Spectrum of complications of measles in Afghanistan: a study of 784 cases

Seven hundred and eight-four patients with measles admitted to the Institute of Child Health, Kabul (Afghanistan) between April 1980 and March 1982 were studied. Almost three-quarters (73.6%) of children (4 months to 12 years) with measles were below the age of 3 years. The maximum number of cases occurred in the 1 to 2 years age group (43.1%). Eighty-nine patients (11.3%) contracted the disease before 1 year of age whereas only 13 infants had developed measles before the age of 7 months. Measles occurred throughout the year and there was no significant seasonal variation. Bronchopneumonia was the commonest complication (85.4%) followed by enteritis (30.2%) and laryngotracheobronchitis (22%). The overall mortality was 10.8%. Respiratory complications including bronchopneumonia and laryngotracheobronchitis were the commonest causes of death followed by encephalitis and gastroenteritis. However, the case fatality rate was highest among patients who suffered from encephalitis and laryngotracheobronchitis. In our study, there was no significant difference in the incidence of mortality between well-nourished and moderately undernourished children. It is recommended that in developing countries measles vaccination should be given around 8-9 months of age and must be completed before the age of 1 year.