Immunization Focus - the GAVI quarterly

SPECIAL FEATURE - November 2000

Swift action: measles vaccination campaigns, like this one in East Timor, can only supplement a good routine programme

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 20 years?

It’s 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 world’s 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 mother’s 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 plan 1 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 at WHO.

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 measles cases.

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 2010 2 . 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 Children’s 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 eradication 3 ; 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 and priorities.

In Pakistan, for example, Rehan Hafiz, the national manager for the Expanded Programme on Immunization (EPI), says the programme’s 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 polio’s 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 community’s 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, it’s 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 year’s 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 GAVI’s 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, GAVI’s 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 GAVI’s 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 Fund’s 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 partner grants.

"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 today’s atmosphere of consensus, next year’s one year-olds could be the first to see progress.

Footnote

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.

References

1. Global Measles Mortality Reduction and Regional Elimination: Strategic plan 2001-2005. WHO/UNICEF November 2000.
Contact: Dr. A. Henao-Restrepo ( henaorestrepoa@who.int )

2. Morbidity & Mortality Weekly Report. June 13 1997, 46 (RR11) 1-20
http://www.cdc.gov/mmwr/preview/mmwrhtml/00047959.htm

3. Immunize Every Child, GAVI Policy Paper, February 2000.

Immunization Focus November 2000 - Contents