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Measles Antibodies in Children Aged 5-7 Years in Karachi.

Byline: Sultana Habibullah

Abstract

Objectives: To assess the presence of antibodies in children aged between 5-7 years and correlate it with the vaccination and previous exposure to measles and also assess the need for a booster dose of vaccine.

Subjects and Methods: A serological cross-sectional survey was conducted in school children age 5-7 years, selected using convenient sampling technique from Saddar town, Karachi. Variables included age, gender, immunization status, past history of clinical measles and the age at time of disease. Measles specific IgG antibody titers were estimated by ELISA at PMRC, Shaikh Zayed Hospital, Lahore. Consent was obtained from guardians of the children. Study was analyzed on SPSS version 15.

Results: A total of 500 children were studied with 278(55%) aged between 6.1-7 years and equal male to female ratio. Of the total, 415(83%) children had received measles vaccination in the past amongst whom 68(16%) had history of suffering from measles in the past. IgG antibodies were found in 401(80%) with majority (58% n=231) aged between 6.1-7 years and more females showed protection (M:F ratio 43:57). Despite receiving vaccination 42 children suffered from clinical measles between 1-7 years of age while another 22 suffered from measles before their first birthday.

Conclusions: Protective antibodies were found in 80% school children while 20% were still un-protected with the current regime of measles vaccination.

Policy statement: Vaccination strategy for measles needs to be reviewed for two dose vaccination schedule.

Key words: Measles vaccination, disease, seroprevalence.

Introduction

Measles is a leading vaccine-preventable killer of children worldwide and was estimated to cause 614,000 global deaths in 2002 with 50% occurring in Sub-Sahara Africa. Its vaccination has been an extremely successful public health intervention resulting in elimination of measles in most areas of the globe while, in some areas it still remains an important public health problem1,2. Successful measles immunization depends on the absence of maternal antibodies at the time of vaccination which are transferred via placenta during the first trimester of pregnancy and gradually wane in the first year of life3. The optimum age for measles vaccination varies from country to country and there is no standardized vaccination schedule. A study conducted in Mozambique showed measles antibodies in children between 6-9 months age4.

However, determining the optimal age for measles vaccination program in developing countries is crucial because the virus transmission is very efficient and disease of measles at an early age is so great that children must be vaccinated soon after they lose maternal protection5. Though WHO recommends age of measles vaccination in developing countries at nine months6.

Despite universal use of measles vaccines in recent decades, epidemics of the disease continued to occur. Understanding the role of primary vaccine failure (failure to sero-conversion after vaccination) and secondary vaccine failure (waning immunity after sero-conversion) in measles epidemic is important for the evaluation of measles control programmes in developing countries7.

In Pakistan measles vaccine is given free as a single dose through EPI at 9 months, while many affording parents take it through private pediatricians by paying for vaccination. Considering these facts this study was conducted to (i) determine the presence of antibodies in children aged between 5-7 years and (ii) correlate it with the vaccination and previous exposure to measles and also assess the need for a booster dose of vaccine.

Subjects and Methods

This is a secondary data analysis from a national sampling for serological survey of measles antibodies in

Table I: Vaccination status, gender, age and disease status.

Vaflables###Vaccination status###Total###95% C.I###p value

###Yes###No###n=500

Gander

Male###188(45%)###50(59%)###238###1.15-1.26###0.238

Female###227(55%)/415###35(41%)85###262/500###1.09-1.17

Age groups

Upto 5 yeas###45(11%)###4(5%)###49###1.0-1.16###0.000

5-1-6 years###144(35%)###29(34%)###173###1.11-1.22

6-1-7 years###226(54%)415###59(61%)/85###278/500###1.14-1.23

Disease status

Yes###68(16%)###15(18%)###83###1.09-1.26###0.000

No###347(84%)415###70(82%)/85###417/500###1.13-1.20

Table 2: Distribution of antibodies in relation to gender, age and disease status.

Variables###Antibody status###Total###95% C.I###p value

###n=500

###Yes###No

Gender

Male###187(47%)###51(51%)###238###1.16-1.26###0.238

Female###214(53%)/401###48(49%)/99###262//500###1.13-1.23###

Age groups

Upto5 years###36(9%)###13(13%)###49###1.13-1.39###0.000

5.1-6 years###134(33%)###39(39%)###173###1.16-1.28

6.1-7 years###231(58%)/401###47(47%)/99###278/500###1.12-1.21

Disease status

Yes###79(20%)###4(4%)###83###1.00-1.09###0.000

No###322(80%)/401###96(95%)/99###417/500###1.18-1.26

school going children aged between 5-7 years8. Total sample size of the primary study was 2500 while the present analysis is an in depth analysis of 500 children from Karachi.

Variables of the study were age, gender, immunization status, past history of suffering from clinical measles, age at the onset of disease and the presence of measles specific IgG antibodies.

Children suffering from any chronic illness and recent history of acute illness like fever, skin rash, parotid enlargement and joint pains were excluded from the study.

Proformas were filled by Co-investigator and one data collector. Blood samples were collected by trained phlebotomists. Sera were separated and frozen, which were later transported in cold chain to Pakistan Medical Research Council, National Health Research Complex Shaikh Zayed Hospital, Lahore, where test for measles (IgG) antibodies were done using commercially available Enzyme-linked Immunosorbant Assay (ELISA) kits (IBL International Germany). According to the manufacturer's guidelines when concentration of IgG antibody was less than 200 m IU, it was considered negative (non-protective), levels between 200-300 m IU were border line and greater than 300 m IU were positive.

Permission was obtained from Federal Ministry of Education, Executive District Officers (Education) and principals of selected schools. Consent was taken from the parents. The child was called on pre-fixed day for blood sample collection.

Statistical package for Social Sciences (SPSS) version 15 was used for data analysis. Results were expressed in percentages, where appropriate, chi-square at 0.05 alpha level was applied for test of significance.

Results

Secondary data analysis was done on 500 children from Karachi. Majority i.e. 278(55%) children were between 6.1-7 years of age with a male to female ratio of 48:52.

As per parent's recall, 415(83%) children had received one dose of measles vaccine. The male to female ratio of vaccinated children was 45:55 and majority i.e. 226(54%) were 6.1-7 years old. Out of 500 children, 83 had history of suffering from measles in the past. When vaccination status of these children was checked, it was found that 68 were vaccinated while 15 were not vaccinated Table-1.

Protective antibodies ( greater than 300 m IU) were found in 401(80%) with no gender discrimination. Majority i.e. 231(58%) of children with protective antibodies were between 6.1-7 years of age. Out of 401 children with protective antibodies 79(20%) had history of suffering from clinical measles in the past (Table-2).

Out of 79(20%) children who suffered from clinical measles disease 64(16%) were vaccinated and 15(4%) were not vaccinated. Out of 64 children, 22 suffered before their first birthday while 42 suffered between 1-7 years of age (Table-3).

Table 3: Distribution of antibody in relation to vaccination and age at disease.

Age at clinical###Presence of protective antibody###Total

measles disease###Vaccination status

###Yes###N

Year one###22###3###25

Year two###11###2###13

Year three###12###2###14

Year four###7###3###10

Year five###7###3###10

Year six###4###1###6

Year seven###1###1###2

Total###64(16%)###15(4%)###79(20%)

Out of 99 children who did not have protective antibodies, 4 had a history of suffering from clinical measles disease and vaccination in the past. Of these 2 developed disease before first birthday and one each at the age of four and five years.

Discussion

The overall prevalence of protective antibody against measles virus in primary school children in Saddar town, Karachi was 80% while 16% (64 cases) suffered from measles despite receiving vaccine with maximum cases suffering before one year of age. The presence of protective antibody indicates that an individual would be protected from clinical disease if exposed to wild virus9. Elimination of measles require continued commitment to increase vaccination coverage levels, the genetic analysis of circulating strains and sero-survey of vaccinated individuals to establish the population at risk of contracting the infection10,11. In the present study 16% vaccinated children developed measles disease but whether it was due to primary vaccine failure or due to waning of specific antibody could not be evaluated here though it was reported in other study7.

The frequency of primary vaccine failure varies with the immune function at the time of vaccination, number of doses, immunogenicity of virus used to manufacture the vaccine and the geographical region12. However, it is reported that in highly vaccinated population, measles outbreak occurs due to secondary vaccine failure13. The test for the assessment of IgG antibody avidity is a reliable tool for differentiating between the immune response occurring in immunologically naive patient (primary vaccine failure) and the immune response that occur in patients with a pre-existing B cell memory (secondary failure)14. The test uses the fact that in primary infection, the specific IgG antibody response begins with IgG antibody that binds weakly with antigen (low avidity), in the secondary infection the rapid antibody response characterized the production of high avidity antibody15. In the present study 16% children had high titers of measles specific antibody (IgG greater than5000mIU).

The present study showed that antibody titer was more in children aged between 6.1-7 years as compared to those aged less than 6 years of age. Despite vaccination 6% children suffered from measles before their first birthday indicating that our children lose their maternal antibody at an early age and therefore, are more vulnerable to disease at an early age. Older children are more protected as compared to younger children and same finding was reported in other studies from Pakistan16,17.

To achieve high rates of sero-conversion, vaccination programmes in developing countries are designed by vaccinating at an age when maximum number of children have neither maternal antibodies nor antibodies acquired through natural infection the 'window period'18. The window period can be overcome by adopting a two-phase vaccination programme in which vaccination is initially targeted at an early age 6-9 months and then at school going age i.e. 4-7 years when the second dose will boost the immunity as well as maintain it for a long time19,20.

The present study shows that 20% children are unprotected with the current regime of measles immunization and to give full protection they need a second dose of vaccine later.

Acknowledgement

The study was funded by Pakistan Medical Research Council vide grant No.4-5/08/RDC/Multi-centre/NIH, Islamabad. We acknowledge Education department, Principals of schools, parents and guardians of children who gave their consent to include their children in this study.

References

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13. Edmonson MB, Addiss DG, McPherson JT, Berg JL, Circo SR, Davis JP. Mild measles and secondary vaccine failure during a sustained outbreak in a highly vaccinated population. JAMA 1990; 263:2467-71.

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15. Paunio P, Hedman K, Davidkin I, Peltola H. IgG avidity to distinguish secondary from primary measles vaccination failures: prospects for a more effective global measles elimination strategy. Expert Opin Pharmacother 2003; 4:1215-25.

16. Ali G, Zaidi SSZ, Zaman N. Seroprevalence of measles antibodies in children at school going age in Islamabad, Pakistan. Pak J Med Res 2009;48:31-4.

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18. Nates SV, Giordano MO, Medeot SI, Martinez LC, Baudagna AM, Naretto E, et al. Loss of maternally derived measles immunity in Argentine infants. Pediatr Infect Dis 1998;17:313-16.

19. Mc Lean AR, Anderson RM. Measles in developing countries: Part II. The predicted impact of mass vaccination. Epidemiol Infect 1987; 100:419-41

20. Black FL. The role of herd immunity in control of measles. Yale J Biol Med 1982; 55:251-60.

PMRC Research Centre, Dow Medical College, Karachi.

Corresponding Author: Sultana Habibullah PMRC Research Centre, Dow Medical College Karachi., Email: s.habib@duhs.edu.pk
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Publication:Pakistan Journal of Medical Research
Article Type:Report
Geographic Code:9PAKI
Date:Sep 30, 2012
Words:2441
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