February 2001
TORONTO - Inspired by the near eradication of polio, global health officials are evaluating whether measles can be the next target for worldwide eradication.
Walter A. Orenstein, MD, Director of the National Immunization Program at the Centers for Disease Control and Prevention, Atlanta, said three of the six regions of the World Health Organization (WHO) have announced goals to eliminate measles, and "if these efforts are successful, and polio eradication can be achieved, I think momentum will be built for measles eradication."
Even today, measles causes nearly 1 million deaths in children younger than 5, Orenstein said, primarily in the developing world, while prevaccination era estimates were as high as 6 million annual deaths. Annually, the United States spends $45 million for measles vaccination, and worldwide about $1.5 billion is spent on vaccination and treatment. Also, the cost of a case of measles in the United States is about $1,000. "Measles eradication, with stoppage of vaccination, would save those lives and eliminate those costs in perpetuity," he said.
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Speaking here at the 40th Interscience Conference on Antimicrobial
Agents and Chemotherapy, Orenstein said measles eradication is possible, as
measles meets the criteria for a disease to be considered eradicable: humans
must be critical to circulation of the organism; "sensitive and specific"
diagnostic tools must be available; an effective intervention must be
available; and prolonged interruption of transmission in a large area must be
demonstrated.
First, humans are the only known reservoir for the virus, and the virus can only survive in the environment for several hours, said Orenstein, a member of the Infectious Diseases in Children Editorial board. The major cell receptor for measles virus, CD46, is found only in primate cells (except transgenic laboratory animals) and serological evidence of measles is uncommon in non-human primates that have had limited contact with humans. "Humans are critical to the maintenance of measles virus transmission," he said.
Sensitive and specific diagnostic tools for measles exist, Orenstein said. The CDC has developed tests for immunoglobulin M (IgM) serum that are 95% specific and at least 90% sensitive. Most cases are positive before 72 hours of rash onset, and all cases are positive between 72 hours and 11 days. This is the reference assay in the Americas. Commercial kits are less available.
"Thus, sensitive and specific serologic and salivary assays are available for the reliable diagnosis of measles," he said. Also, virus can normally be isolated within five days from nasopharyngeal swabs and urine. Genotyping of the isolates is used to determine the source of infection.
The third criterion, Orenstein said, is an effective intervention. The level of protection conferred by a single dose of measles vaccine is effective, but is not enough to interrupt transmission. Mathematical models show that a two-dose measles vaccine strategy allows immunity levels of 95% or more to be reached, a level that should be adequate. All countries attempting to eliminate measles have used two doses, he added.
Finally, Orenstein cited several successful large-scale measles elimination efforts. The United States began aggressive measles eradication in the 1960s, based on a multifaceted strategy: achieving high levels of coverage in 1-year-olds; vaccinating remaining children upon school entry; careful surveillance; and aggressive response to outbreaks. In 1978, emphasis was placed on high immunity levels among school-age children, and in 1989 a second dose was recommended.
Since 1993, fewer than 1,000 cases have been reported in the United States, Orenstein said, and since 1997 the incidence rate has been less than one case per 1 million. Also, during extended periods all cases were associated with international importations of virus. In 1999, only 100 cases were reported, most linked to international importations.
"Thus the available data suggests measles has been eliminated as an endemic disease in the United States," he said.
Also, Orenstein said in 1994 the Pan American Health Organization (PAHO) established the goal of eliminating measles from the Western Hemisphere by the end of 2000 with a three-part strategy. The first was "Catch-up," one-time vaccination campaigns covering all children from 9 months to 14 years old. Second was "Keep-up," which involved sustaining high coverage with routine immunization. The third part was "Follow-up," which was subsequent mass campaigns covering all children — regardless of prior vaccination status — born since the previous campaign strategy.
"In practice, this usually means campaigns every three to five years," he said.
Reported measles cases dropped from 250,000 in 1990 to 2,000 cases in 1996, and most countries reported almost no cases, Orenstein said. "Most of the region was free of measles circulation."
Also, measles cases imported from Latin America to the United States dropped significantly. "These data strongly suggest," he said, "that measles transmission can be interrupted, at least transiently, in large populations in large geographic areas, including both in developed and developing countries."
Impediments to measles elimination do exist, Orenstein said,
including transmission among adults, increasing urbanization of the world,
favoring transmission at very young ages; the HIV epidemic; and, most
importantly, political will. However, each of these obstacles can be overcome,
he added.
Outbreaks show that adults may not be able to sustain an epidemic. In Brazil in 1997 (in one of the few South American epidemics in the 1990s), major outbreaks, particularly in São Paulo, hit young adults particularly hard. However, widespread transmission was not sustained, "suggesting that adults may fuel an epidemic but may not sustain transmission," Orenstein said.
Dense urban settings "are ideal for prolonged measles transmission even with a strong immunization program," Orenstein said, and vaccination programs will be challenged to immunize quickly "before susceptibles accumulate and fuel epidemics." However, the success of vaccination in populous cities such as Mexico City, New York, London and Los Angeles indicate urbanization is not insurmountable. The highly dense cities of Africa and Asia will pose the stiffest challenge yet, he cautioned.
HIV is a major problem worldwide, and in many areas of the world up to 10% of newborns are infected with HIV, causing a variety of problems for measles eradication, Orenstein said. However, data from South Africa, which has a high HIV prevalence, shows measles can still be eliminated with wide reaching vaccination activities.
Politics may be the biggest obstacle to measles elimination and eradication. "Probably the greatest impediment to eradication is political will, particularly in the developed world, where measles may not be seen as a problem," he said. Some of the lowest vaccine coverage rates are in the richest countries. "Measles eradication will require the buy-in of the developed world. Developed countries must realize that measles is worth preventing in their own countries so they do not become reservoirs of virus," he said, and developed countries must help finance efforts for measles eradication in developing nations.
So impediments do exist, Orenstein said. "The world is not yet ready for a global measles eradication initiative," he said. "Nevertheless, the available scientific and programmatic information is encouraging, and we believe someday there will be a goal for measles eradication."
For more information:
- Orenstein W. After polio: global eradication of measles? Symposium 36. Presented at the 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Sept. 17-20, 2000. Toronto.
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