A little bit of measles does you good
BMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7201.4 (Published 03 July 1999) Cite this as: BMJ 1999;319:4
All rapid responses
EDITOR
When discussing the hypothesis that standard dose Schwartz measles
vaccine reduces mortality from conditions other than measles(1) Shann
refers to the observations that while measles causes only10% of child
mortality the vaccine reduces mortality in developing countries by at
least 30% (2) and that immunised children who have not had measles have a
much lower mortality than unimmunised children who have not had measles
(2,3).
When I worked at Murgwanza Hospital in Tanzania from 1984-1991
measles vaccination was generally available in the community through the
maternal child health programmes. These programmes included an educational
component relating to nutrition, prevention of disease and early treatment
of febrile illnesses such as malaria. As the primary health care
programme gained momentum following the Alma Ata declaration which aimed
for "health for all by the year 2000" efforts to improve health awareness
intensified. It was distressing that children were not all immunised and
that outbreaks of measles still occurred. Often children with measles
presented late and had signs of other illnesses. We always assumed that
children who were not immunised against measles when this was available
were more likely to be poorly nourished and less likely to be brought for
early medical care if they had life threatening illnesses such as malaria
or gastro-enteritis.
It is true that a study in Benin (4,2) failed to
show that DTP and polio vaccination was associated with reduced mortality
from other conditions . However, this study was only relevant to a narrow
age band until the children were given measles vaccination.
I would
suggest that measles immunisation could be an indicator that parents in
developing countries are trying to give their children optimum care.
Therefore the improved mortality is not necessarily due to the vaccine
itself.
David Emerton
Accident & Emergency Consultant
North Tees General Hospital
Stockton on Tees
TS19 8PE
1 Shann F. A little bit of measles does you good. BMJ 1999;319:4-5.
2 Aaby P, Samb B, SimondonF, Coll Seck AM, KnudsenK, Whittle H. Non-
specific beneficial effect of measles immunisation : analysis of mortality
studies from developing countries BMJ 1995;311 481-5.
3 SambB, AaabyP, Whittle H, Coll Seck AM, Simondon F. Decline in measles
case fatality ratio after the introduction of measles immunisation in
rural Senegal. Am J Epidemiol 1997;145:51-7.
4 Velema JP, Alihonou EM, Gandaho T, Hounye FH Childhood mortality among
users and non-users of primary health care in a rural West African
community. Int J Epidemiol 1991;20,474-9.
Competing interests: No competing interests
Editor
I have just read the fourth editorial in today's BMJ (1) on measles
immunisation, and was interested to learn that "the vaccine itself may
reduce mortality from conditions other than measles."
I have read the rest of the article and it is not clear whether the
reduction in mortality is from:
a) all conditions other than measles
b) all infective conditions other than measles
c) specific infective conditions other than measles
d) specific non-infective conditions other than measles
Although I work as a hospital specialist, I enjoy the BMJ as a
generalist as it is a great help in keeping my knowledge-base broad.
Perhaps your contributor could have been more specific for the sake of
those readers who do not have the time to seek out all the articles by
Aaby and his numerous co-workers.
Clinton Buckoke
Consultant Anaesthetist
Southend Hospital
Westcliff-on-Sea
Essex SS0 0RY
1 Shann F, A little bit of measles does you good. BMJ 1999;319:4-5
Competing interests: No competing interests
Frank Shann's editorial 'A little bit of measles does you good' (1)
highlights several unexpected effects of mass measles vaccination. No
more satisfactory explanation has been advanced for an apparently marked
decline in the incidence of childhood esotropia (convergent squint) than
that it may be due to a large reduction in the incidence of measles.
Figures for the incidence of childhood esotropia, with a peak at age
3 to 4 years, are difficult to gather, but there is general agreement that
fewer cases present in the United Kingdom than a generation ago. More
easily verified is a marked decrease in the past 25 years in the number of
squint
operations performed. Previously about 2 squint corrections were done on
a typical 'general' ophthalmic operating list; now these operations are
becoming something of a rarity, though increased awareness of consecutive
divergence as a consequence of over-zealous squint correction has also
contributed to the decline in the number of operations.
The principal factors determining the onset of childhood esotropia
are genetic influences, refractive errors (usually hyperopia) and a high
accommodative convergence/accommodation ratio (2). The precipitating
cause of a child with normal, though fragile, binocular function
developing a squint has often been considered to be a systemic illness.
Measles used to be common at this age - now it is rare. Whether it is the
stress induced by
the illness or, more specifically, a subclinical encephalitis is unknown
(3), but the decline in measles and that of concomitant esotropia may be
connected.
Robin Finlay
Consultant ophthalmic surgeon
Royal United Hospital
Bath BA1 3NG
1 Shann F. Editorial: A little bit of measles does you good. BMJ
1999;319:4-5.
2 Parks MM. Abnormal accommodative convergence in squint. Arch
Ophthal 1958;59:364-80
3 Taylor D. Paediatric ophthalmology, Blackwell Scientific
Publications, 1990;625
Competing interests: No competing interests
History has documented well for us the devastating effects of the
arrival of the measles virus from Europe several centuries ago (e.g.,
Iceland and the Americas). Some will also remember that when measles
vaccine became available on a large scale (late 60's), in the unpublished
and published experience (1970's) of a number of clinicians, the
relationship between measles and susceptibility to other diseases, notably
tuberculosis, was well established, at least in Amerindian and other
population groups living in poverty and not exposed to measles prior to
outbreaks recorded at the time. Studies published then documenting
effects of clinical measles on the immune response were accepted as a
reasonable explanation.
Thus, Dr. Shann's editorial, while no surprise, comes as a welcome
reminder of things forgotten. The implications for public health action
are clear - and not unrelated to the relationship between AIDS and
susceptibility to other diseases, which has cost so much money to "prove".
The point is one of public policy: how to maintain funding for
successful epidemiological activities once their goal has been attained
(in this case, the elimination or eradication of measles, hopefully just
around the corner).
The history of tuberculosis control, while somewhat "glorious" during
the post-World War II years related to strong social support (NGO sales of
stamps), has been a glaring example of successive failures in establishing
political priority for what once was the "disease of kings". It is only
fair to recognize the renewed efforts being made by WHO over the past 4 or
5 years, and the commitment expressed by their new Director General in
this regard. Unfortunately, the national response has yet to materialize
in the intensity and perspective required. More realistic approaches
need to be developed which take into account the financial and logistic
barriers still limiting access to general healthcare across the globe.
Although it is true that our most successful ventures have been in
the pursuit of one creature at a time (i.e., yellow fever, smallpox,
polio), how can we deal effectively with the long and growing list on the
table?
While there are many reasons to be optimistic, lip service to these
causes - and to their integration to the mainstream of primary healthcare
- is not enough. How long do we need to wait and how big a price should
we all pay for the consequences of our inertia? Have we learned the
lessons from our failure in controlling the AIDS epidemic in its early
stages? Are we really ready for another Ebola?
Or is this just a love affair with Mycobacteriae and other creatures that
share our planet and our bodies? Do we really care at all?
Competing interests: No competing interests
The hypotheis that measles immunisation provides nonspecific immune
stimulation sufficient to decrease mortality from other diseases is
interesting. However, I don't really believe the studies have ruled out
the more likely explanation that measles immunisation is just a marker for
other socioculturally determined health seeking behaviours. The fact that
similar effects are not seen for other vaccines does not exclude measles
immunisation from being correlated with health seeking behaviours. Measles
vaccination is different to other vaccines - in its timing and it is often
associated with national campaigns (including in some of the studies Dr
Shann references). Are there any data that rules out the confounding
effect of sociocultural determinants?
Competing interests: No competing interests
Measles immunisation and socioeconomic confounding
Measles immunisation causes a spectacular reduction of 30% to 86% in
child mortality in developing countries (1). The benefit is greatest in
the 6-12 months after immunisation, and in infancy (44% to 100%). Dr
Dalton (2nd July 1999) and Dr Emerton (20th July 1999) wonder whether the
apparent benefit from measles immunisation might be due to better
nutrition and better health care in children who receive measles vaccine
(socioeconomic confounding), rather than an effect of the vaccine. In the
absence of any large randomised controlled trials of measles vaccine in
developing countries, socioeconomic confounding cannot be excluded – but
it is highly unlikely, for several reasons.
First, in the only placebo controlled trial of measles vaccine in a
developing country (2), none of the 23 vaccinated children died compared
to 3 (12%) of the 25 unvaccinated children.
Second, in a natural experiment in Bissau (3), some children were
accidentally injected with an ineffective vaccine (given on five
consecutive vaccination days over a 3 week period). There was no
selection bias in this study because all the children were immunised.
From the time of vaccination to 3 years of age, the mortality rate was
4.5% in 124 children who seroconverted after active vaccine and 15.1% in
53 children given ineffective vaccine.
Third, in two large studies in Zaire (4) and Bangladesh (5),
confounding is unlikely because measles vaccine was made available in half
the study area and not in the other. The two areas had similar mortality
rates before immunisation. Immunisation reduced mortality by 42% in Zaire
and by 46% in Bangladesh.
Fourth, studies that have controlled for socioeconomic factors have
still found that measles immunisation reduced mortality by 36% to 90%(1).
Fifth, measles immunisation is unlikely to be merely a marker for
better health care because the reduction in mortality is greatest in the
12 months after measles immunisation (and the benefit of better health
care should persist), and diphtheria-tetanus-pertussis immunisation is not
associated with reduced mortality (6).
Measles immunisation causes a much greater fall in mortality than the
proportion of deaths attributed to measles, particularly in girls (1). Is
this because measles causes many more deaths than we realise (from delayed
effects of the disease, or from subclinical infection), or does the
vaccine reduce mortality from conditions other than measles?
The large reduction in mortality after immunisation is unlikely to be
due to the prevention of delayed deaths from measles because immunised
children who have not had measles have a much lower mortality than
unimmunised children who have not had measles (1). Subclinical measles
infection is certainly common in both immunised and unimmunised children
in developing countries, however such infections have no effect on
nutritional indices or mortality (7).
In randomised controlled trials in Guinea-Bissau (8) and Senegal (9),
children were given high-titre Edmonston-Zagreb (EZ) vaccine at 4-5 months
of age or standard Schwarz vaccine at 9-10 months. In the two trials,
girls given EZ vaccine had a mortality rate that was 1.95 and 1.76 times
respectively that of girls given Schwarz vaccine. This occurred despite
the fact that there is a good antibody response to high-titre EZ vaccine
at 4-5 months, and there was no increase in measles in the EZ group. Both
vaccines protected against measles, but the Schwarz vaccine also protected
girls against diseases other than measles. These were both randomised
trials, so socioeconomic confounding is very unlikely to be the
explanation for this remarkable finding.
It is crucial that the main message is not lost in the debate about
cause and effect. Measles immunisation clearly causes a spectacular
reduction in mortality in children in developing countries, and this
effect is probably enhanced by a two-dose schedule with immunisation at 6
and 9-12 months. Far greater effort should go into seeing that all
children receive measles vaccine and, if measles is ever eradicated,
controlled trials will be needed to see whether the vaccine should still
be given to children in countries with high child mortality rates.
Frank Shann.
Intensive Care Unit, Royal Children's Hospital,
Melbourne, Victoria 3052, Australia
Peter Aaby.
Department of Epidemiology Research, Statens Serum Institut,
Artillerivej 5, 2300 Copenhagen S, Denmark
1. Aaby P, Samb B, Simondon F, Seck AMC, Knudsen K, Whittle H. Non-
specific beneficial effect of measles immunisation: analysis of mortality
studies from developing countries. BMJ 1995;311:481-5.
2. Hartfield J, Morley D. Efficacy of measles vaccine. J Hygiene
(Camb) 1963;61:143-7.
3. Aaby P, Pedersen IBR, Knudsen K, da Silva MC, Mordhorst CH, Helm-
Petersen NC et al. Child mortality related to seroconversion or lack of
seroconversion after measles vaccination. Pediatr Infect Dis J 1989;8:197
-200.
4. Kasongo Project Team. Influence of measles vaccination on survival
pattern of 7-35-month-old children in Kasongo, Zaire. Lancet 1981;1:764-
767.
5. Koenig MA, Khan MA, Wojtyniak B, Clemens JD, Chakraborty J,
Fauveau V et al. Impact of measles vaccination on childhood mortality in
rural Bangladesh. Bull WHO 1990;68:441-7.
6. Velema JP, Alihonou EM, Gandaho T, Hounye FH. Childhood mortality
among users and non-users of primary health care in a rural West African
community. Int J Epidemiol 1991;20:474-9.
7. Bennett J, Whittle H, Samb B, Cisse B, Simondon F, Aaby P.
Seroconversions in unvaccinated infants: further evidence for subclinical
measles from vaccine trials in Niakhar, Senegal. Int J Epidemiol
1999;28:147-51.
8. Aaby P, Knudsen K, Whittle H, Lisse IA, Thaarup J, Poulsen A et
al. Long-term survival after Edmonston-Zagreb measles vaccination in
Guinea-Bissau: increased female mortality rate. J Pediatr 1993;122:904-8.
9. Aaby P, Samb B, Simondon F, Knudsen K, Seck AMC, Bennett J et al.
Sex-specific differences in mortality after high-titre measles
immunization in rural Senegal. Bull WHO 1994;72:761-770.
Competing interests: No competing interests