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2000 contents page
Coming to grips with the big one
A new plan to attack measles is gathering
widespread support, as Phyllida Brown discovers
MEASLES kills more children than
any other other vaccine-preventable disease. This year it will claim
the lives of about 880,000 children a staggering 30% of all
vaccine-preventable deaths and 40% of those in children. How can
this be, when an effective vaccine costing just 26 cents, including
safe injection equipment, has been widely available for more than
Its an easy enough question
to ask, but, predictably, the answer is tougher. Measles virus is
difficult to control because of its contagious nature and the characteristics
of the existing vaccine (see Box 1). Disagreements
about how best to tackle it have continued for a decade.
Box 1: Why measles is such a tough challenge
Measles is the most contagious
infection know to humans. It may cause fever, cough, rash,
conjunctivitis, diarrhoea, ear infections and pneumonia. A
less frequent but serious consequence of infection is encephalitis,
or inflammation of the brain. Measles can also cause permanent
disabilities such as blindness.
Measles accounts for fully
30% of all deaths from vaccine-preventable diseases including
adult deaths caused by hepatitis B (See Figure
1). Twenty countries account for 85% of the deaths, and
half of all deaths are concentrated in just four countries India,
Nigeria, Ethiopia and the Democratic Republic of Congo.
Complications of the disease
are much more common in low-income countries, and in malnourished
children, than in industrialized countries. However, in some
high-income countries, particularly in Europe, complacency
about measles has created situations where vaccination coverage
levels are lower than required to prevent outbreaks.
With the introduction of
measles vaccine to the majority of the worlds children,
the estimated yearly death toll has fallen by about 80% from
the pre-vaccine era. However, because measles is so contagious,
and because a small minority of those who are vaccinated do
not develop immunity, vaccination coverage levels need to
be very high above 90% to stop the transmission
of the virus.
Measles vaccine is given
no earlier than 9 months. Before this time, it fails to stimulate
immunity in the infant because the mothers antibodies to
the virus are still present. Thus, immunization against measles
must be delivered much later than the rest of the immunization
schedule of vaccines against tuberculosis (BCG), polio and
diphtheria, tetanus and pertussis (DTP). This means that,
even where coverage rates for BCG and DTP vaccines are at
80% or above, coverage for measles vaccine is usually lower
because a large number of parents do not maintain contact
with health workers after the first few months. Measles vaccine
is also more difficult to handle than some other vaccines:
it has to be reconstituted and is highly sensitive to heat.
Research to identify new
vaccines against measles, particularly those that could be
delivered earlier in life and/or by inhalation, is continuing.
The Americas have made dramatic
progress towards eliminating the disease. But some other regions
have seen their situation worsen steadily. Amid an overall stagnation
in immunization programmes, the percentage of children vaccinated
against measles worldwide appears to have actually fallen, from
80% in the early and mid-1990s to 72% in 1999. In many countries
in sub-Saharan Africa, coverage is much lower.
Determined to change the current
situation, the World Health Organization and UNICEF, together with
the US Centers for Disease Control and Prevention (CDC), developing
country health experts and others, have hammered out a consensus
on what should be done. A plan1 to be published
this month by WHO and UNICEF should be endorsed by the partner organizations
and finalised by the end of the year. The plan has two broad goals:
- To cut measles deaths by two-thirds, saving
3 million lives, by 2005; and
- To continue to prevent at least 600 000
deaths a year, sustainably, after 2005.
In addition, the plan sets a timetable
to collect data to indicate whether, after 2005, measles can feasibly
be eradicated worldwide.
The plan sets out details of how
these goals may be reached (see Box 2). The
core of the plan is to increase routine coverage with measles vaccine
and then use supplemental campaigns to cut the death toll further.
"We have an agenda now to substantially reduce measles mortality,"
says Ana Maria Henao-Restrepo, who coordinates measles activities
Box 2: Gaining the upper hand: a strategy
to reduce measles deaths worldwide
The WHO-UNICEF mortality
reduction strategy will be focused on the 20 countries that
account for 85% of all measles deaths. Initially, it is being
adopted by a subgroup of those countries that are already
free of endemic polio (Mozambique, Tanzania, Uganda, Indonesia
and Myanmar), allowing the remainder to concentrate first
on polio eradication. Countries will draw up 3 to 5-year plans
to achieve and sustain the targets.
Countries are advised to:
- Increase their routine coverage of
at least one dose of measles vaccine to at least 80% of
infants aged 9 months.
- Ensure a "second opportunity" for
measles vaccination, either through a supplemental campaign
or a routine second dose. The second opportunity is needed
both to increase the probability that everyone gets at least
one dose, and to increase the proportion of the population
that is successfully immunized. (At 9 months, up to 15%
of infants will not respond to a single dose of measles
vaccine, but will be protected after a second dose later.)
This advice is new and based on evidence that high measles
mortality is more frequently found in settings where children
have only one opportunity for measles vaccination.
- Establish an effective system for
monitoring coverage and maintaining measles surveillance.
- Provide vitamin A supplements where
needed alongside vaccination.
- Improve the management of complicated
For more details, and for
separate guidelines for countries aiming to eliminate measles,
see reference 1.
The consensus underlying the plan
marks a welcome resolution to a protracted debate between key players
in global public health. The argument has not been about the need
to reduce the number of deaths after all, few would question
this but about whether the world should embark on a campaign
to eradicate measles, and if so, when. By deferring the eradication
decision until more data have been gathered, the plan allows the
opposing camps to move forward.
"The programme was at a standstill,"
says Edward Hoekstra, medical coordinator for measles activities
at UNICEF. "Now everyone is agreed."
The grounds for the debate have
shifted quickly. As recently as 1996 experts at a meeting held by
WHO, the Pan American Health Organization (PAHO) and the CDC concluded
that global measles eradication was feasible and that a target date
should be set for between 2005 and 20102. But
others were less certain. The World Bank, for example, has long
argued against embarking on an eradication campaign before the costs
of doing so including the diversion of resources from other
immunization efforts have been carefully weighed.
The Americas have almost eliminated
indigenous measles, but only through a highly aggressive and active
campaign. Elsewhere, in the poorest high-burden countries, such
tactics are currently "unthinkable", says Henao-Restrepo. Fifteen
countries, all but five of them in Africa, immunized less than half
of their one year-olds against measles in 1998. Measles is killing
children in these countries mainly because their routine immunization
programmes are struggling on all fronts.
"The consensus is building that
the world is not ready for a measles eradication campaign," says
Mark Kane, of the Bill and Melinda Gates Childrens Vaccine
Program. One reason, he believes, is that the Global Polio Eradication
Initiative has proved more labour-intensive and costly in its final
stages than most experts predicted. Even at a predicted cost of
US$2.5 billion spread over 20 years, the cost is likely to be dwarfed
by the predicted $1.5 billion annual savings that will flow from
polio eradication3; but, experts fear, before
that final goal is achieved, a second disease eradication initiative
could sap resources and attention from the critical final stages
of the polio campaign.
Finish off polio first
This view is also supported by
Ciro de Quadros, head of vaccines and immunization at the PAHO,
who is credited with being the driving force behind both the polio
and the measles elimination initiatives in the Americas. "It is
essential that we act to reduce measles mortality, but of course
we cannot think about global eradication of measles at this stage,"
he says. "The top priority must be to eradicate polio."
Also, it has become clear that
countries current needs are too diverse to be straitjacketed
into a single measles eradication campaign. Each has different pressures
In Pakistan, for example, Rehan
Hafiz, the national manager for the Expanded Programme on Immunization
(EPI), says the programmes resources are fully devoted to
the polio campaign at present, and any additional campaign on measles
should only be considered later and after careful thought. "Campaigns
are very labour-intensive," says Rehan. "The basis for a strong
programme should always be routine immunization."
In contrast, Uganda is under popular
pressure from parents to conduct measles campaigns. Issa Makumbi,
the national manager for the EPI in Uganda, says that there is strong
demand from ordinary people to act swiftly with mass vaccination
campaigns to protect infants from resurging outbreaks of measles.
Routine measles vaccination coverage is around 53%. "We cannot wait
to revitalise the routine programme while our people are dying,"
says Makumbi. "We have to do campaigns first to reduce morbidity
and mortality a bit and then put all our efforts into improving
routine coverage." Uganda, with support from UNICEF and WHO, is
currently doing mass campaigns in 20 districts. "We have to respond
to this demand," he says. "It is a reality."
As polios devastating effects
have begun to recede, the burden of measles has looked increasingly
unacceptable, and some in Uganda and in other countries in
Africa where polio is no longer endemic have questioned the
resources that polio attracts compared with the resources available
for measles control within routine programmes. "From the communitys
point of view, polio is not the priority," says Makumbi. "It is
measles that kills them every minute." Like some other countries,
Uganda has made a virtue of this situation by combining polio campaigns
with measles campaigns. In this way, staff resources are used efficiently
and the uptake for polio vaccine remains high, even though the threat
of the disease is less visible, because families have strong motivation
to get their children immunized against measles.
The new WHO-UNICEF plan recognizes
countries different needs and sets out a framework for good
practice. It is based on analyses of the evidence of what works,
says Henao-Restrepo. All countries, whatever their current measles
status, can use the plan to reduce their measles deaths, while countries
or regions that wish to be more ambitious, such as the Americas,
Europe and the Eastern Mediterranean, which have elimination plans,
can also work within the framework to achieve their aims.
The targets for saving lives can
be pursued by all countries immediately and the economic arguments
for doing so are convincing. Preliminary estimates of the cost of
achieving the mortality reduction goals in the twenty highest-burden
countries are $150 million a year, says Hoekstra, a relatively modest
sum. What is more, WHO and UNICEF say that governments can achieve
the goals extremely cost-effectively. In high-burden countries,
improving coverage from 50% to 80% is estimated to cost around US$2.50
for each life-year gained. In general, health interventions that
can be delivered in low-income countries for less than US$25 per
year of life gained are considered to be excellent "buys" for governments,
so this represents exceptionally good value for money.
The core of the plan is to increase
routine immunization coverage with measles vaccine to 80% by 2005.
But WHO and UNICEF recognize that this will be only a first step.
Even when fully implemented, routine coverage of 80% would still
result in more than 250,000 children dying of measles each year.
To reduce the worldwide death toll
beyond this level, supplementary campaigns will be needed, implemented
as part of a long-term and comprehensive strategy.
The recommendations are based
on the results of models devised by Nigel Gay and colleagues at
the Public Health Laboratory Service in London, England. Using real
data from a typical high-burden country where measles vaccination
coverage is only 30%, Gay and his colleagues modelled the impact
on mortality of increasing coverage to 80%, enacting one-off campaigns,
and doing both. Their results are shown in Figure
2. If coverage is increased to 80%, the number of deaths will
fall by two-thirds over five years, then plateau. If, on the other
hand, the country attempts to reduce measles deaths with a one-off
campaign, deaths will fall sharply but transiently, returning to
the previous high level within a couple of years. If, however, routine
coverage is increased to 80% and a supplemental campaign is added,
deaths will be sharply and sustainably reduced.
Figure 2: Models
used by WHO and UNICEF show the expected impact of different
approaches to vaccination
"You have to do both things,"
says Hoekstra. "With high coverage and a campaign, its a few
years before the number [of deaths] goes up again, so you have a
longer period to work on improving routine immunization." Repeated
campaigns will, of course, reduce the death toll further. "Measles
campaigns could not replace routine immunization programmes," says
Hoekstra. "They can only be in addition."
One critical issue is the supply
of vaccine: officials estimate that it will take up to two years
for the manufacturers of measles vaccine some 12 companies
in all to scale up production to a level needed for countries
to carry out the recommended steps in the mortality reduction strategy.
The targets in the WHO-UNICEF plan take these delays into account.
"We are watching the situation closely and will review it every
3-6 months," says Henao-Restrepo.
Action by the years end
WHO and UNICEF are keen to move
ahead quickly with seeking endorsement for the plan from their technical
experts, then implementing it. This month, the GAVI Board will also
be asked to decide on the role that the Alliance and its partners
should play. As well as declaring measles a high priority, GAVI
will be asked to help in practical ways.
One of GAVIs key milestones
is to increase routine immunization coverage to 80% by 20053, putting
it firmly in line with a central goal of the measles plan. Also
in line with the plan, GAVIs partners are already working
with countries to improve the systems used to monitor vaccine coverage
and safety. At present, measles vaccine coverage is not included
in GAVIs monitoring system, with the main indicator being
the percentage of children who receive diphtheria, tetanus and pertussis
(DTP) vaccine. In future, measles coverage may be added to the indicators.
Decisions about whether or how
the Vaccine Fund might provide support for the measles strategy
will be made in the near future. One of the Vaccine Funds
three sub-accounts provides support for countries to improve their
routine immunization services so, in principle, this could be used
in part to help improve routine measles vaccination coverage. A
more controversial question is whether the Vaccine Fund might also support
supplemental measles campaigns or even buy vaccine supplies. Different
experts hold different views. For example, Kane, a member of the
GAVI Working Group, says that he personally does not believe that
the limited resources of the Vaccine Fund should be used for buying
measles vaccine or paying for campaigns today. But in 2-3 years
time, if routine coverage and monitoring has improved in the high-burden
countries, he personally believes that the GAVI Board may want to
consider using Global Fund resources for well-planned supplemental
campaigns, if other support is not available. Hoekstra, meanwhile,
argues that the Vaccine Fund should be used, for example to make
strategic grants valued at, say, one-third the size of individual
Swift action: measles vaccination
campaigns, like this one in East Timor, can only supplement a good
"Measles is the number one public
health problem among vaccine-preventable diseases of children,"
says Hoekstra, "and GAVI now has the opportunity to bring it under
the umbrella of its programme." In todays atmosphere of consensus,
next years one year-olds could be the first to see progress.
Measles elimination is defined
as a situation where endemic transmission has stopped over a wide
geographic area and secondary spread from imported cases will end
naturally, but continued intervention is needed.
Measles eradication is defined
as the interruption of transmission worldwide.
1. Global Measles
Mortality Reduction and Regional Elimination: Strategic plan 2001-2005.
WHO/UNICEF November 2000.
Contact: Dr. A. Henao-Restrepo (email@example.com)
2. Morbidity &
Mortality Weekly Report. June 13 1997, 46 (RR11) 1-20
3. Immunize Every
Child, GAVI Policy Paper, February 2000.
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