Healthcare Infection Prevention-Fatal infections hit defenseless military after vaccine loss
Healthcare Infection Prevention-Fatal infections hit defenseless military after vaccine loss
Some 10,000 preventable infections annually in new recruits
It is perhaps too harsh to say that the recently reported deaths of two young military recruits due to adenovirus infections can be traced to a bungled economic decision in the mid-1990s that let a highly effective vaccine fall out of production. But the bottom-line question remains: Would the vaccine have saved their lives?
"It is really impossible to say for sure, but that is what we suspect," says Margaret Ryan, MD, MPH, an investigator in the case and director of the Center for Deployment Health Research at the Naval Health Research Center in San Diego. "That is obviously why we care [about restoring the vaccine] because that is quite possibly true. I’ve talked to the families at length. I can’t tell them for sure that this wouldn’t have happened to these young people. We’ll never know for sure. But it is possible that vaccine could have prevented this."
The two unrelated cases involved two males: an 18-year-old and a 21-year-old who contracted adenovirus last year while undergoing Navy basic training in Great Lakes, IL. (See case reports, p. 2.) The Centers for Disease Control and Prevention expressed some caveats in ascribing the cause of the deaths, but concluded that "lack of identification of other viral pathogens, and [polymerase chain reaction] evidence support the diagnoses of adenovirus-related illnesses."1
Though adenovirus infections can be mild or even asymptomatic, the cases underscore that severe morbidity and mortality are possible from adenovirus infections in previously healthy young adults. Such serious adenoviral infections were reported in the U.S. military before vaccines were developed and in unvaccinated civilians.
The military has been hard hit by respiratory outbreaks of adenovirus stereotypes 4 and 7 over the years. During the 1950s and 1960s, up to 10% of recruits were infected with adenovirus, and the pathogen was responsible for approximately 90% of pneumonia hospitalizations.2 Living in close quarters under extreme stress of basic training are thought to be factors in the viruses’ history of infecting the military population. Another aspect of that could be surveillance artifact, Ryan notes.
"I think that it is a possible that there is something unique about the military that makes adenovirus such a dominant pathogen," Ryan says. "But there is also a little bit of surveillance artifact. Because we look for it, we know how much we have. Other people don’t know how much they have, because they don’t look. But adenovirus is not a uniquely military problem."
Indeed, an outbreak of adenovirus infection in Chicago involved residents of a pediatric chronic care facility.3 In the pediatric facility, 31 of 93 residents had adenovirus infection, and eight died.
"When a few deaths happen, it gets better described, but frankly if you look among the general viral respiratory illnesses in day care, schools, and colleges, adenovirus is a big player," Ryan says. "It is a very common pathogen if you look for it. But you need special viral culture techniques to do that."
The making of an orphan
While the original adenovirus vaccine was aimed primarily at the military, possible secondary markets in other patient populations may help entice a manufacturer to make the vaccine again. The recurrent problems in the military led to the development of a highly effective vaccine in 1971 that Ryan unabashedly recalls as "cool." That’s because there were no shots necessary; recruits swallowed enteric-coated pills that contained live attenuated virus.
The sole producer was Wyeth-Lederle Vaccines in St. David, PA. But Wyeth and the Pentagon had a falling out over some disputed multimillions needed to upgrade production facilities, and vaccine production was halted 1996. Limited amounts of vaccine remained available from 1997 through 1999, but the stock was totally depleted by mid-1999. The loss of the vaccine - after all is said and done and a new vaccine is ramped up - should well exceed whatever expenditure would have been necessary to maintain production.
"Without even the severe morbidity or mortality there is compelling evidence for adenovirus vaccine for this particular population," Ryan says.
"There has been two cost-effective analyses - one by the army and one by the navy - that clearly show the benefit of reestablishing adenovirus vaccine supply [even] in the absence of severe morbidity or mortality," she explains.
The military has requested proposals for a new adenovirus vaccine manufacturer, but pharmaceutical companies are not exactly elbowing each other aside to get the contract.
"There has been movement in that direction for years, but the progress is frustratingly slow," Ryan says. "Reestablishing the vaccine will likely be an expensive prospect. But it is not simply money, it is also finding a manufacturer who is willing to make it. The vaccine is hard to make. Right now, the military is the only group saying it wants it. Although other markets could clearly be developed, identifying a manufacturer right now is a particular challenge."
Virus reemerging in susceptible population
In the interim, with some 200,000 people entering the U.S. military each year; clinicians should consider adenovirus infection in severely ill young people in the military. That’s because the viral strains are reemerging in a susceptible population. Since 1999, approximately 10% to 12% of all recruits have become ill with adenovirus infection in basic training - a level similar to the pre-vaccine era, according to the CDC.
Other researchers documented a reappearance of adenotype 4 in 57% of isolates and adenotype 7 in 25% of isolates from throat cultures of trainees with respiratory disease. Of 3,413 throat cultures performed for recruits with febrile respiratory illness, 53% have yielded adenoviruses.4
With adenovirus now feeding on a susceptible military population, the study estimated that the loss of the vaccine will result in 10,650 preventable infections, 4,260 medical clinic evaluations, and 852 hospitalizations annually among U.S. Armed Services recruits.
Such a disease burden is expected to result in some $26 million in estimated annual medical and training costs for the army alone.5 With actual vaccine production not expected until years after a deal is struck with a manufacturer, some warn that military readiness may be in jeopardy.
And as the two most recent cases underscore, the toll will also be measured in lost lives. "The deaths serve to emphasize a point all preventive medicine folks in the military have been saying for years," Ryan says. "We need this vaccine."
Reference
1. Centers for Disease Control and Prevention. Two fatal cases of adenovirus-related illness in previously healthy young adults - Illinois, 2000. MMWR 2001; 50:553-555.
2. Buescher EL. Respiratory disease and the adenoviruses. Med Clin North Am 1967; 51:769-779.
3. Gerber SI, Erdman DD, Pur SL, et al. Outbreak of adenovirus genome type 7d2 infection in a pediatric chronic-care facility and tertiary-care hospital. Clin Infect Dis 2001; 32(5):694-700.
4. Gray GC, Goswami PR, Malasig MD, et al. Adult adenovirus infections. Loss of orphaned vaccines precipitates military respiratory disease epidemics. Clin Infect Dis 2000; 31:663-670.
5. Howell M, Nang R, Gaydos C, et al. Prevention of adenoviral acute respiratory disease in Army recruits: Cost-effectiveness of a military vaccination policy. Am J Prev Med 1998; 14:168-175.