The data is collected by a statistician who enters it in a computerized database and verifies and corrects the information provided by health aides. If there are similar cases epidemiologically linked, the diagnosis is considered probable. The child is visited by the public health nurse or doctor and the clinical diagnosis is confirmed. No serological confirmation is sought.
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Care is taken to ensure that the diagnosis of measles is done blind to the immunization status. The nurse or doctor visiting the village determines the cause of death by a simple verbal autopsy. If hospital records are available, they are checked for the cause of death. All children born to residents of the area between January 1 and December 31 were included in the study.
Children who had migrated out of Kaniyambadi block without a date of migration were excluded. The incidence of measles and death during the first five years of life conditional on surviving the first year was calculated according to the age at immunization using the actuarial method. The probability of measles and death was separately estimated for those who received measles vaccination and those who were unimmunized. While calculating the risk of death or disease for unimmunized children, those who subsequently received immunization were censored at the time of immunization.
For vaccinated children, the probability of disease was estimated separately for those vaccinated between 6 and 8 months and those vaccinated between 9 and 11 months. The primary focus of the study were differences between infants vaccinated at 6—8 months and those vaccinated at 9—11 months.
In the period under study 16 births were registered, of which children were excluded from the study as they left the study area soon after birth to return to their father's house. In this region, pregnant women, especially primigravidae, come to their parental home for their delivery and then return to the husband's home after 6 weeks. Of the vaccinated children, were vaccinated at 6—8 months, at 9—11 months and children after 12 months of age. There was no significant difference in risk of disease by age of vaccination or type of vaccine used Tables 1 and 2.
There was no significant difference in mortality between those who were vaccinated between 6 and 8 months and those vaccinated between 9 and 11 months Table 3. The majority of unimmunized children belonged to landless families and had uneducated parents. This difference was statistically significant Table 6. Our study does not permit us to measure the true protective effect of the vaccine directly because of the low incidence of disease among the few unimmunized subjects due to herd immunity. There was no noticeable difference in vaccine efficacy according to age at vaccination.
The strategy of giving vaccination at 6 months has been beneficial. If the strategy of vaccinating prior to 9 months had not been effective, there would have been an accumulation of susceptible children in the population over the last five years, resulting in outbreaks. The total benefit of vaccinating prior to 9 months needs to be evaluated based on the number of cases prevented during early infancy. A significant proportion of these early cases are likely to have developed serious or fatal complications Hull et al.
It is conceivable that in children vaccinated before 9 months of age, protection could wane in the course of several years and that these children may develop clinical measles when they are older. In developing countries the consequences of measles are serious among the very young, and the immediate objective of the vaccination strategy must be to offer protection as early as possible.
Vaccinated children who develop measles at an older age are less likely to suffer from the serious complications commonly seen in younger children.
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Since this would reduce the morbidity and mortality due to measles, waning immunity later in life need not be considered a serious problem. An equal number of boys and girls each received early MMR vaccination during this campaign. Furthermore, we found no differences between the age groups in day care attendance, underlying disease in the infant, duration of pregnancy, presence of older siblings, vaccination refusal on the basis of life philosophy eg, anthroposophy, homeopathy, or alternative medicine or religion, maternal educational level, maternal vaccination status, and past maternal measles virus infection.
Redness 53 infants [5. Parents of 8 infants 0. Parents of infants Overall frequencies were Among the infants aged 6—8 months, the frequency of any systemic AE was higher in the early responders than in the late responders Likewise, among the infants aged 9—11 months, For one of these infants, fever started within the risk window 5—12 days after vaccination.
After entering all possible confounders in the multivariable logistic regression, for both outcomes stepwise backward selection led to removal of all covariates ie, no adjustment was necessary. For any AE, ORs were not statistically significant in infants aged 8 months and those aged 14 months, whereas for systemic AEs occurring 5—12 days after vaccination, ORs were nonsignificant in infants aged 7, 8, 12, or 14 months.
We showed that this early MMR vaccination was well tolerated and that AEs in infants receiving their first MMR vaccine dose at 6—8 months of age were less frequent than AEs in infants aged 14 months, the age when routine MMR1 vaccination is scheduled in the Netherlands. We found that the occurrence of AEs is age dependent. Frequencies of all local and most systemic AEs were lower in the youngest age group of 6—8 months, compared with older age groups.
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For both local as well as most systemic AEs, frequencies were lowest in the youngest age category. However, only the frequencies of rash and all systemic AEs combined differed statistically significant between the age groups. Studies performed in Uzbekistan and Malawi found no influence of age on the occurrence of specific AEs among infants who received measles—containing vaccines at 6 and 9 month of age [ 12 , 13 ]. AEs were reported during an interview in the home in the second week after vaccination.
In the study by Helfand et al, parents recorded AEs in a daily log for 21 days after vaccination. The differences between the frequencies of AEs in these studies and the frequencies in our study may be attributed to varying methods of AE ascertainment.
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Furthermore, Bolotovski et al and Helfand et al presented no case definition of or cutoff temperature for fever, possibly leading to different numbers of cases with fever, which perhaps partly explains the differences. Another possible explanation for the lower frequencies of AEs in younger infants is the presence of maternal antibodies against measles virus that prohibit replication of vaccine virus and thereby prevent the occurrence of AEs. Among children born to orthodox reformed Protestant mothers who in general were naturally infected, the duration of protection was approximately 2 months longer [ 10 ].
Therefore, we think the influence of maternal antibodies is limited. However, we cannot exclude a possible influence of nondetectable, residual maternal antibodies. Furthermore, young infants are immunologically immature, which may also lead to less reactogenicity. Two other Dutch surveys on the tolerability of MMR1 vaccination given at age 14 months found different frequencies of local and systemic AEs than we observed among infants aged 12—14 months in our study [ 20 , 21 ].
The lower frequencies we found may be explained by study logistics: study participation was requested 4 weeks after the invitation for vaccination, and parents of infants who received the vaccination before completion of the survey might not have remembered all AEs, particularly the less severe symptoms.
Another possible explanation for the lower frequency of AEs found in our study is that our primary aim was to assess vaccine effectiveness, with additional questions on AEs, while both MMR1 surveys exclusively assessed tolerability. Therefore, the frequencies we found were probably less likely to have been affected by overreporting, compared with the 2 tolerability surveys.
Apart from this survey, parents were asked to report AEs after vaccination to the Dutch Pharmacovigilance Center, Lareb. Lareb received 11 reports, of which 2 involved serious systemic AEs 1 infant had febrile convulsion and 1 experienced crying and dehydration.noroi-jusatsu.info/wp-content/2020-07-10/2936-pirater-sms-samsung.php
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Our study has several limitations. These percentages do not differ very much. Therefore, we think the risk of bias is low, despite the low response rate. Furthermore, the sex distribution in our study is comparable to the distribution in the general population. This possibly influenced the reported AEs, resulting in an underestimation. However, because the age group in which this interval was shortest also had the lowest AE frequencies, recall bias may be limited.
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Because this outbreak occurred in a high-income country, results may be less applicable to developing countries. The latter countries often have a less developed healthcare system and a greater prevalence of malnutrition, possibly 1 resulting in an impaired immune response and 2 influencing the occurrence of AEs. Furthermore, all AEs were self-reported without additional validation. This may have led to an overestimation of AE frequencies. Since we did not compare results with the occurrence of symptoms in age-matched unvaccinated children, we could not assess causality.
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