Early waning of maternal measles antibodies in era of measles elimination: longitudinal studyBMJ 2010; 340 doi: https://doi.org/10.1136/bmj.c1626 (Published 18 May 2010) Cite this as: BMJ 2010;340:c1626
All rapid responses
Leuridan et al.(1) describe early susceptibility to measles amongst
210 infants of vaccinated and naturally immune mothers in Belgium. The
authors report the median time to ‘immunity loss’ was 3.78 months for
infants of naturally immune women and 0.97 months for infants of
vaccinated women. These findings are based on measles IgG antibody levels
measured by ELISA and rely on an estimated protective threshold rather
than the internationally agreed protective threshold of 120mIU/ml as
measured by the gold standard plaque reduction neutralisation test (PRNT)
using.(2;3) Although the authors acknowledge the limitation of using ELISA
to determine protection in their study, the use of PRNT to assess maternal
measles antibody decay has already been studied in a number of different
settings and is more informative.(4-6)
Protection afforded by maternal antibodies in countries with
historically good measles control has been shown to wane prior to 6 months
of age in a number of studies.(4;5;7) A 2009 review concluded that many
infants in the UK will become susceptible to measles before 6 months of
age and will be able to respond to vaccine between 6 and 9 months of
age.(8) As a consequence, in May 2009 measles post-exposure prophylaxis
guidelines in England were revised.(9) The decision to recommend post-
exposure prophylaxis now requires an individual risk assessment based on a
range of factors including maternal age, maternal status (reliable history
of infection or vaccination) and age of infant.
It is important to stress however, that despite this susceptibility
gap now described in several studies, developed countries which have
experienced rising measles incidence have not seen a proportionally higher
burden of disease in infants.(10) The re-emergence of endemic measles
transmission in England and Wales in 2008(11) was accompanied by a rise in
confirmed cases amongst infants but the proportion of cases confirmed in
infants has remained low (7/78 (9%) in 2005 compared with 118/1388 (8.6%)
in 2008). In addition, the distribution of cases in the first year of life
has not altered significantly with more than 75% (295/375) of infant cases
during 2005-2009 occurring in those over 6 months of age. In the peak year
of 2008, only 6 (5%) confirmed infant measles cases occurred in children
below 3 months of age. Analysis based on models of maternal antibody
decline in the Netherlands suggested that adding an additional vaccination
at the age of 6 or 9 months or bringing forward the age of the first dose
(from 14 to 11 months) would have a relatively modest impact on disease
incidence, particularly when compared to bringing forward the age of the
second dose (from 9 to 4 years).(12) As the UK already gives the first
dose of MMR at 12 months and the second dose of MMR at around 3½
years,(13) the critical factor in protecting infants at high risk of
complications is to optimise measles control through high and timely
vaccine coverage of the routine childhood immunisation programme.
(1) 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.
(2) Chen RT, Markowitz LE, Albrecht P, Stewart JA, Mofenson LM,
Preblud SR et al. Measles antibody: reevaluation of protective titers. J
Infect Dis 1990; 162(5):1036-1042.
(3) Cohen BJ, Audet S, Andrews N, Beeler J. Plaque reduction
neutralization test for measles antibodies: Description of a standardised
laboratory method for use in immunogenicity studies of aerosol
vaccination. Vaccine 2007; 26(1):59-66.
(4) 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(3):519-524.
(5) Chui LW, Marusyk RG, Pabst HF. Measles virus specific antibody
in infants in a highly vaccinated society. J Med Virol 1991; 33(3):199-
(6) Gagneur A, Pinquier D, Aubert M, Balu L, Brissaud O, De Pontual
L et al. Kinetics of decline in maternal mesales neutralising serum
antibodies in infants in France in 2006. Vaccine 2008.
(7) van den HS, Berbers GA, de Melker HE, Conyn-van Spaendonck MA.
Sero-epidemiology of measles antibodies in the Netherlands, a cross-
sectional study in a national sample and in communities with low vaccine
coverage. Vaccine 1999; 18(9-10):931-940.
(8) Manikkavasagan G, Ramsay M. Protecting infants against measles
in England and Wales: a review. Arch Dis Child 2009; 94(9):681-685.
(9) Ramsay ME, Manikkavasagan G, Brown K, Craig L. Post exposure
prophylaxis for measles: Revised HPA Guidance. 2009.
(10) Muscat M, Bang H. Measles surveillance Annual Report 2009.
EUVAC.NET . 2009. 2-6-2010.
(11) Health Protection Agency H. Confirmed measles cases in England
and Wales - an update. Health Protection Report 2. 23-5-2008. 1-6-
(12) van den HS, Wallinga J, Widdowson MA, Conyn-van Spaendonck MA.
Options for improvement of the Dutch measles vaccination schedule. Vaccine
(13) Salisbury D, Ramsay M, Noakes K. Immunisation against
Infectious Disease. Fourth ed. The Stationery Office, 2006.
Competing interests: No competing interests
The authors are to be complemented for their very important
observations.In a similar study by me from India
published in 2002, I had compared the IgG antibody levels in babies at 6 -
9 months and 9-12 months of age. While 66% in the 6-9 months age group had
protective levels of antibodies, none in the 9-12 month group recorded
protective levels, indicating a rapid decline in the levels of antibodies.
The reasons for this could be because of lower levels of antibodies
in mothers due to waning in protection or due to an increase in numbers of
unvaccinated mothers. Malnourished mothers in developing countries also
may not have high levels of antibodies.
The implications of this observation include early presentation of
measles infection in infancy with its associated morbidity.The following
interventions may need consideration - Measles vaccines within the first
year of life as is the norm in developing countires followed by a booster
in the second year(usually MMR). Adolescents also may need MMR vaccine so
as to boost their antibody levels.
1.Optimal age for measles vaccination. Vidyashankar C
J Indian Med Assoc. 2002 Jan;100(1):24-6.
Competing interests: No competing interests