|Year : 2020 | Volume
| Issue : 1 | Page : 83-88
Prevalence of maternal measles antibody and its associated factors among infants in Coastal Karnataka, India
S Sathiyanarayanan1, Pawan Kumar2, Chythra R Rao2, Arun Kumar3, Asha Kamath4, Veena Kamath2
1 Department of Community and Family Medicine, All India Institute of Medical Sciences, Mangalagiri, Andhra Pradesh, India
2 Department of Community Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
3 Department for Virus Research, Manipal Academy of Higher Education, Manipal, Karnataka, India
4 Department of Statistics, Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, Karnataka, India
|Date of Submission||23-Jun-2019|
|Date of Acceptance||13-Dec-2019|
|Date of Web Publication||14-Jan-2020|
Dr. S Sathiyanarayanan
Department of Community and Family Medicine, All India Institute of Medical Sciences, Mangalagiri - 520 008, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The current recommendation in India to commence first dose of measles immunization is at 9 months of age. The effectiveness of measles vaccination is greatly impacted by the level of maternal measles antibody (MMA) during infancy.Objectives: To find the prevalence of MMA and to study the maternal and infant factors associated with persistence of MMA among the infants in a Indian rural community.Methodology: Dried blood spot sample was collected before vaccination among infants aged 9 months and above when they came for first dose of measles vaccine to assess measles-specific maternal IgG antibody titers by enzyme immunoassay. Maternal and child factors influencing persistence of MMA were collected by interviewing the mothers. Association between various factors affecting seropositivity was tested using univariate logistic regression analysis and strength of association is reported as risk ratio with 95% confidence interval.Results: Based on the qualitative estimation among all the recruited children (250) in the study, 4 (1.6%) infants showed the presence of MMA whereas 25 (10%) of children had MMA on quantitative estimation. The effect of maternal factors, child nutrition, and sociodemographic factors on the presence of MMA was not found to be statistically significant.Conclusion: The prevalence of persistent MMA (IgG titer ≥200 mIU/ml) among the infants aged 9–12 months was 10%. The choice of vaccinating infants at the end of 9 months for the first dose of measles vaccine is justified as the remaining (90%) of infants were susceptible for measles infection at this age.
Keywords: Infants, maternal antibodies, measles, persistence, prevalence, vaccine
|How to cite this article:|
Sathiyanarayanan S, Kumar P, Rao CR, Kumar A, Kamath A, Kamath V. Prevalence of maternal measles antibody and its associated factors among infants in Coastal Karnataka, India. Indian J Community Med 2020;45:83-8
|How to cite this URL:|
Sathiyanarayanan S, Kumar P, Rao CR, Kumar A, Kamath A, Kamath V. Prevalence of maternal measles antibody and its associated factors among infants in Coastal Karnataka, India. Indian J Community Med [serial online] 2020 [cited 2021 Jan 24];45:83-8. Available from: https://www.ijcm.org.in/text.asp?2020/45/1/83/275966
| Introduction|| |
Measles, one of the most contagious viral diseases, affected almost every child before the widespread use of the measles vaccine. About six million measles-related deaths were estimated to occur globally each year before the use of the live attenuated measles vaccine, which was licensed in 1963. Although measles deaths in industrialized countries are rare, measles is often fatal in developing countries with increased risk of deaths for children under 5 years of age, those living in overcrowded conditions, those who are malnourished (especially with Vitamin A deficiency), and those with immunological disorders, such as advanced HIV infection., India introduced a second dose of measles through routine immunization as recommended by the WHO at 18 months of age in 2010 in addition to first dose which is given at the end of 9 months of age since 1985.
The effectiveness of vaccination against measles is greatly impacted by the level of maternal antibody to measles virus (MMA) during infancy. Maternal antibodies interfere with immune response,, and antibody production. Nutritional status of pregnant mother, socioeconomic status, race and ethnicity,,, age, parity,, and rate of decay of maternal antibody after birth,, are some of the known factors influencing MMA levels in infants. While the recommended age for the first dose of measles in developed countries is 15 months, the choice of vaccination at 9 months in India was to balance between the need for early protection and the advantage of delaying it for best vaccine efficacy.,,
Therefore, estimation of MMA is important to determine the effectiveness of vaccination against measles. This study was conducted to find out the prevalence of MMA and to study the maternal and infant factors associated with persistence of MMA among the infants in a rural community in India.
| Methodology|| |
A cross-sectional study was conducted at the six Rural Maternity and Child Welfare (RMCW) homes in the study area which covers a population of 50,000 living in 8684 families spread out in 14 villages. All apparently healthy children <1 year of age coming to the RMCW homes for the first dose of measles vaccination were included in the study. Approval for the study was obtained from the Institutional Ethics Committee (IEC/60/2012-13).
Based on an Indian study which found that 5%–10% of 9–11-month-old infants had persistent MMA, the sample size was calculated using the formula n = (Z2pq)/d2; with absolute precision as 4% and allowing 15% nonresponse, the sample size was 250. Children who were appropriately immunized for age, permanent residents of the area, and consenting parents of eligible children were included. Children with mental retardation/apparent physical deformities interfering with anthropometric measurements and children of adopted parents were excluded.
Children were recruited as and when they came for immunization between January and December 2013, and personal interview was conducted with each mother with a pretested semistructured questionnaire. Variables such as name, age, sex, birth order, birth weight, blood group, antenatal and perinatal history, age at pregnancy, neonatal history, gestational age at delivery, mode of delivery, history of infection with measles, duration of breast feeding, age at weaning, and complementary foods were recorded using the questionnaire, after verifying with their antenatal and birth records. Anthropometric measurements such as length and weight were recorded using standard weighing scales. Under sterile conditions, dried blood spot (DBS) sample was collected using Whatman 903 filter paper imprinted with a circle of diameter 12.5 mm. The dried blood spot was collected in a separate ziplock plastic bag and coded to ensure blinding of the samples [Figure 1].
|Figure 1: Drying of the blood samples collected by dried blood spot method|
Click here to view
The specimen was then transported in a vaccine carrier to the Department of Virus Research (DVR), Manipal Academy of Higher Education (MAHE), Manipal, on the same day, which was then stored at +2°C to +8°C. The measles-specific IgG antibody titers were assessed by an experienced lab technician in DVR using Dade Behring Enzygnost Anti-Measles Virus/IgG (measles IgG) manufactured by Siemens Healthcare Diagnostics Products GmbH, Marburg/Germany [Figure 2].
|Figure 2: Dispensing the samples in the ELISA well for measles IgG estimation|
Click here to view
For qualitative estimation, samples registering corrected optical density (OD) value ≥0.2 were considered to indicate protection against measles and thus defined as “positive by ELISA.” Quantitative estimation of IgG antibody titers was done using the α-method, and geometric mean titer (GMT) was presented as mIU/ml. Thus, seropositivity was defined as samples having measles IgG level ≥200 mIU/ml.
Data were entered and analyzed using Statistical Package for the Social Sciences (SPSS Inc., Released 2007, SPSS for Windows, version 16.0., Chicago, IL, USA). Sociodemographic details were presented using descriptive statistics. The proportion of infants with persistent MMA were presented as percentages. Association between various factors affecting seropositivity was tested using univariate logistic regression analysis, and strength of association was reported as risk ratio (RR) with 95% confidence interval (CI).
| Results|| |
Of the 250 recruited infants, 120 (48%) were male and 130 (52%) were female. The mean age (±standard deviation [SD]) of the infants was 9.59 (±0.76) months with a range of 9–14 months. Majority of them were Hindus (68%) followed by Muslims (29.2%) and the rest (2.8%) were Christians. Most of them (83.2%) belonged to middle socioeconomic status according to the Modified Udai Pareek Scale. It was observed in the present study that corrected OD value of 0.2 corresponds to 350 mIU/ml and corrected OD value of 0.1 corresponds to 150 mIU/ml in the quantitative estimation done for IgG antibodies. Seropositivity among the subjects based on the qualitative and quantitative estimation is shown in [Table 1].
|Table 1: Persistence of maternal measles antibody (IgG) among the study subjects (n=250)|
Click here to view
To study the effect of subject and maternal factors influencing persistent MMA using univariate logistic regression analysis, seropositivity based on quantitative estimation was considered. Among the 25 infants who showed persistent MMA levels at 9 months of age, 14 (10.8%) of them were female and 11 (9.2%) were male. It was observed that although the chance of female infants showing persistent MMA levels was higher as compared to male infants (RR = 1.20, 95% CI = 0.52–2.75); this was not statistically significant (P = 0.673). Children who did not cry immediately after birth had persistent maternal antibody (RR = 6.45, 95% CI = 1.02–40.52), which was statistically significant (P = 0.047). Furthermore, malnourished children had more chance of having maternal antibody (RR = 1.48 95% CI = 0.41–5.34), which was not statistically significant (P = 0.554). Initiation of supplementary feeds before 6 months, duration of exclusive breast feeding <4 months, history of fever with rash, and ≥3 episodes of diarrhea had more chance of having MMA levels, but these were not statistically significant. Initiating breast feeding after day 1, history of hospitalization, and neonatal jaundice had lesser chance of having MMA levels, but these were also not statistically significant [Table 2].
|Table 2: Univariate logistic regression for association between subject characteristics and persistence of maternalmeasles antibody (n=250)|
Click here to view
Among children whose mothers were ≥26 years of age during delivery, only 13 (8.7%) of them had persistent MMA levels at 9 months of age (RR = 0.71, 95% CI = 0.31–1.62), but this was not statistically significant (P = 0.416). Among 210 children born to mothers without a history of measles infection, 21 (10.0%) had persistent MMA levels whereas 5 (12.5%) out of 40 children born to mothers with a history of measles infection had persistent MMA levels at 9 months of age (RR = 1.00, 95% CI = 0.32–3.09). No significant association was found with other maternal factors such as antenatal complications, interpregnancy interval, gestational age, mode of delivery, and blood group in the present study [Table 3].
|Table 3: Univariate logistic regression analysis for the association between maternal factors and persistence of maternal measles antibody (n=250)|
Click here to view
| Discussion|| |
The present study was done among 250 rural children to find out the prevalence of MMA and the factors which determine the effectiveness of measles vaccination at the end of 9 months of age. The mean age (±SD) of the infants was 9.59 (±0.76) months with a range of 9–14 months with almost equal gender distribution.
Qualitative estimation of maternal measles antibody
DBS sample was used to calculate measles-specific IgG antibodies and samples registering corrected OD value ≥0.2 were considered seropositive. Based on this, 4 (1.6%) infants showed the presence of MMA. An Australian study used a similar method of sample collection and cutoff value (OD value ≥0.2 as protective) for interpretation of results and showed an overall sensitivity of 98.4% and specificity of 97.2% compared with the results of serum testing. It was observed in the present study that corrected OD value of 0.2 corresponds to 350 mIU/ml in the quantitative estimation done for IgG antibodies as against 300 mIU/ml and 130 mIU/ml reported in other studies.,
Quantitative estimation of maternal measles antibody
Infants with a titer ≥200 mIU/ml were considered protective against measles infection.,,, Based on this, 25 (10%) children had MMA, which means the prevalence of MMA among infants in the present study was 10%, which is similar to the results reported in an Indian study. Two other studies done abroad reported passive antibody positivity rate (MMA) as 5.2% and 8.1% at 9 months of age, respectively.,
Subject factors influencing maternal measles antibody among infants
Although female infants had persistent MMA compared to male infants, it was not statistically significant in contrast to other study done in 2009 where it was shown that girls lost maternal measles antibodies more rapidly than boys and well before 9 months of age. An Egyptian study found higher seropositive rate for MMR vaccine among infants of 1st or 2nd birth order in their family, with a significant decrease in the percentage seropositivity for infants ranked higher in the family birth order (P< 0.001). However, in the present study, it was observed that infants of third or more birth order were found to have persistent MMA levels (RR = 2.29, 95% CI = 0.74–7.01) compared to infants born of first and second order. Children who did not cry immediately after birth had persistent maternal antibody, which was statistically significant (P = 0.047). However, this might be due to very small number of children in this group. Religion and socioeconomic status were not found to have any association with persistence of MMA levels similar to other study which also found no difference in positive seroprevalence rate with respect to socioeconomic status, sibling size, and educational level of fathers.
Maternal factors influencing maternal measles antibody among infants
Increasing maternal age was found to have lower persistent MMA, but was not statistically significant. Previous studies found a relationship between increasing age, parity of mothers, and lower GMTs., The present study did not find significant association with maternal history of measles infection with persistent MMA, but studies done in Europe and China concluded that infants born to mothers with a history of measles had higher antibody levels at birth and at 6 months than infants of vaccinated mothers.,, Children born of preterm delivery had higher persistent MMA (12.0%) compared to term infants (9.1%), but it was not statistically significant. However, other studies found that preterm infants receive significantly fewer antibodies compared to term infants.,
Persistence of maternal measles antibody in infants
A study done in India found that the GMT of MMA in the infants blood showed a statistically significant reduction with an increase in age during the early part of the infancy and touched the lowest by 7th month and thereafter remained in the vicinity of 125 mIU/ml. In another study done in 2003, the proportion of antibody-positive infants declined from 50% at 7–9 months to 10% at 13–15 months. A similar study done among French infants found that MMA decreases dramatically by 6 months of age and that 90% of infants are not protected against measles after 6 months of age. However, in an African study, the immune response to measles vaccine in 6-month-old infants were studied and found that out of 140 infants studied, no infant had more than 150 mIU/ml antibodies. To summarize, studies across the world have proven that only 5%–10% of infants have MMA at 9 months of age, which is concurrent with the present study findings. No clear consensus about the protective range of antibody levels or cutoff value for seropositivity might be a limitation of this study.
| Conclusion|| |
The prevalence of persistent MMA (IgG titer ≥200 mIU/ml) among the infants aged 9–12 months was 10%. The choice of vaccinating infants at the end of 9 months for the first dose of measles vaccine in India is justified as remaining 225 (90%) of infants were susceptible for measles infection at 9–12 months of age. Hence, the current timing of first dose of measles vaccination at the end of 9 months is appropriate and needs to be continued. The effect of maternal factors, child nutrition, and sociodemographic factors on the presence of MMA was not found to be statistically significant.
Financial support and sponsorship
Indian Council of Medical Research (ICMR) – Proposal ID: 2012-0464.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Clements CL, Hussey GD. Measles. In: Murray CJ, Lopez AD, Mathers CD, editors. Global Epidemiology of Infectious Diseases. Geneva: World Health Organization; 2004.
Perry RT, Halsey NA. The clinical significance of measles: A review. J Infect Dis 2004;189 Suppl 1:S4-16.
Wolfson LJ, Grais RF, Luquero FJ, Birmingham ME, Strebel PM. Estimates of measles case fatality ratios: A comprehensive review of community-based studies. Int J Epidemiol 2009;38:192-205.
World Health Organization. Measles vaccine: WHO position paper. Wkly Epidemiol Rec 2004;79:131-42.
Middleton E Jr, Kandaswami C. Effects of flavonoids on immune and inflammatory cell functions. Biochem Pharmacol 1992;43:1167-79.
John TJ. The optimum age for measles vaccination. Indian Pediatr 1982;19:455-6.
Job JS, John TJ, Joseph A. Antibody response to measles immunization in India. Bull World Health Organ 1984;62:737-41.
Bendich A. Antioxidant vitamins and human immune responses. Vitam Horm 1996;52:35-62.
Kamar S, Chowdhury OA, Murshed M, Hasan R. Effect of gestational age and nutrition on transplacental transfer of measles antibody. Med Today 2010;22:1-5.
Goncalves A. Passive Immunity Against Measles [Dissertation]. London: University of London; 1996. p. 227.
Markowitz LE, Albrecht P, Rhodes P, Demonteverde R, Swint E, Maes EF, et al
. Changing levels of measles antibody titers in women and children in the United States: Impact on response to vaccination. Kaiser permanente measles vaccine trial Team. Pediatrics 1996;97:53-8.
Rager-Zisman B, Bazarsky E, Skibin A, Tam G, Chamney S, Belmaker I, et al
. Differential immune responses to primary measles-mumps-rubella vaccination in Israeli children. Clin Diagn Lab Immunol 2004;11:913-8.
Umlauf BJ, Haralambieva IH, Ovsyannikova IG, Kennedy RB, Pankratz VS, Jacobson RM, et al
. Associations between demographic variables and multiple measles-specific innate and cell-mediated immune responses after measles vaccination. Viral Immunol 2012;25:29-36.
de Francisco A, Hall AJ, Unicomb L, Chakraborty J, Yunus M, Sack RB. Maternal measles antibody decay in rural Bangladeshi infants-implications for vaccination schedules. Vaccine 1998;16:564-8.
Sinha NP. Measles in children under six months-of age: An epidemiological study. J Trop Med Hyg 1980;83:255-7.
Kiliç A, Altinkaynak S, Ertekin V, Inandi T. The duration of maternal measles antibodies in children. J Trop Pediatr 2003;49:302-5.
Vaisberg A, Alvarez JO, Hernandez H, Guillen D, Chu P, Colarossi A. Loss of maternally acquired measles antibodies in well-nourished infants and response to measles vaccination, Peru. Am J Public Health 1990;80:736-8.
Singh J, Datta KK. Measles vaccine efficacy in India: A review. J Commun Dis 1997;29:47-56.
Siemens Healthcare Diagnostic Products GmbH. Enzygnost Anti-Measles Virus/IgG [Package Insert]. Germany: Siemens Healthcare Diagnostic Products GmbH; 2011.
Riddell MA, Byrnes GB, Leydon JA, Kelly HA. Dried venous blood samples for the detection and quantification of measles IgG using a commercial enzyme immunoassay. Bull World Health Organ 2003;81:701-7.
Leuridan E, Hens N, Hutse V, Ieven M, Aerts M, Van Damme P. Early waning of maternal measles antibodies in era of measles elimination: Longitudinal study. BMJ 2010;340:c1626.
Novello F, Ridolfi B, Fiore L, Buttinelli G, Medda E, Favero A, et al
. Comparison of capillary blood versus venous blood samples in the assessment of immunity to measles. J Virol Methods 1996;61:73-7.
Brugha R, Ramsay M, Forsey T, Brown D. A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women. Epidemiol Infect 1996;117:519-24.
Argüelles MH, Orellana ML, Castello AA, Villegas GA, Masini M, Belizan AL, et al
. Measles virus-specific antibody levels in individuals in Argentina who received a one-dose vaccine. J Clin Microbiol 2006;44:2733-8.
Khalil MK, Nadrah HM, Al Yahia OA, ElGhazali G. Seroresponse to the second measles vaccine dose at school entry in Qassim province, Saudi Arabia. East Mediterr Health J 2011;17:191-5.
Işik N, Uzel N, Gökçay G, Kiliç A, Yilmaz G, Sadikoǧlu B, et al
. Seroconversion after measles vaccination at nine and fifteen months of age. Pediatr Infect Dis J 2003;22:691-5.
Ceyhan M, Kanra G, Erdem G, Kanra B. Immunogenicity and efficacy of one dose measles-mumps-rubella (MMR) vaccine at twelve months of age as compared to monovalent measles vaccination at nine months followed by MMR revaccination at fifteen months of age. Vaccine 2001;19:4473-8.
Martins C, Bale C, Garly ML, Rodrigues A, Lisse IM, Andersen A, et al
. Girls may have lower levels of maternal measles antibodies and higher risk of subclinical measles infection before the age of measles vaccination. Vaccine 2009;27:5220-5.
Abbassy AA, Barakat SS, Abd El Fattah MM, Said ZN, El Metwally HA. Could the MMR vaccine replace the measles vaccine at one year of age in Egypt? East Mediterr Health J 2009;15:85-93.
Altinkaynak S, Ertekin V, Güraksin A, Kiliç A, Yiǧit N. The sero-epidemiology of measles in children from Eastern Turkey. West Indian Med J 2005;54:236-7.
Zhao H, Lu PS, Hu Y, Wu Q, Yao W, Zhou YH. Low titers of measles antibody in mothers whose infants suffered from measles before eligible age for measles vaccination. Virol J 2010;7:87.
Linder N, Tallen-Gozani E, German B, Duvdevani P, Ferber A, Sirota L. Placental transfer of measles antibodies: Effect of gestational age and maternal vaccination status. Vaccine 2004;22:1509-14.
Leineweber B, Grote V, Schaad UB, Heininger U. Transplacentally acquired immunoglobulin G antibodies against measles, mumps, rubella and varicella-zoster virus in preterm and full term newborns. Pediatr Infect Dis J 2004;23:361-3.
Arunkumar G, Rajeev J, Jai Prakash R, Nalini B, Shivananda PG. Decay of measles maternal antibody in infancy in Indian children. Abstract: 6th
Asia Pacific Congress of Medical Virology, 7-10 December 2003, Kuala Lumpur, Malaysia. J Clin Virol 2003;9 (Suppl 1):206.
Gagneur A, Pinquier D, Aubert M, Balu L, Brissaud O, De Pontual L, et al
. Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of infants in France in 2006. Clin Vaccine Immunol 2008;15:1845-50.
Kurubi J, Vince J, Ripa P, Tefuarani N, Riddell M, Duke T. Immune response to measles vaccine in 6 month old infants in Papua New Guinea. Trop Med Int Health 2009;14:167-73.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]