Guarding HIV-positives against vaccine reaction in the age of bioterror

Scant medical data spur policy debate

Four days before President George W. Bush announced a national smallpox vaccination plan last month, a group of public health experts heaved a sigh of relief. In a meeting with Vice President Dick Cheney, they had finally managed to convince the administration not to follow a policy of mass, pre-emptive smallpox inoculation.

Those experts had argued that that a policy of mass inoculation of all Americans could produce casualties to HIV-infected people and others with damaged immune systems that would far outweigh any gains to be made from inoculations, at least in the absence of a clear terrorist threat.

"If this were a vaccine free of adverse events, the discussion would be moot," says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID). "But it’s the most dangerous vaccine we have, and the adverse events from it are well-known."

Calculating the risks of widespread serious reactions from smallpox vaccinations is devilishly hard, because most data on the subject predate the era of AIDS. With so many more people living today with suppressed immune systems, some experts fear there will be more serious problems associated with the vaccine than in the past.

Also worrisome is the way that recently vaccinated people shed virus from their vaccine site for up to four weeks. That means they can inadvertently infect others, in a phenomenon known as contact vaccinia.

The key, experts say, is to carefully screen vaccination volunteers for HIV and cover the vaccination site with an occlusive dressing. By taking those steps, most problems with serious reactions and contact vaccinia can be avoided.

Still, as one hospital executive says, someone’s occlusive bandage is bound to fall off, and someone with advanced HIV is bound to be vaccinated by mistake.

That’s part of the difficult calculus public health experts must perform as they weigh one unknown — the extent of vaccine complications — against an even bigger unknown, the scope of a bioterrorist threat.

"It’s a delicate balancing act," says Julie Gerberding, MD, MPH, director of the Centers for Disease Control and Prevention in Atlanta. "The more people we immunize, the more deaths and life-threatening complications we are going to see. We have a risk of smallpox, but we can’t really quantify it."

Who’s at risk?

By Fauci’s estimate, for every million people vaccinated, there will be at least one to two deaths; 15 to 50 life-threatening complications; and up to 900 serious but non-life-threatening complications. Complications range from the widespread but merely unpleasant to the rare but often fatal.

By some estimates, as many as 60 million people in the United States are at risk for serious side effects from the vaccine. According to the CDC, these risk groups include:

  • the 506,154 U.S. residents known to be living with HIV, as well as an estimated 300,000 more who are infected but don’t know it;
  • pregnant women and nursing mothers;
  • children less than 12 months old;
  • the 1.2 million people diagnosed each year with non-skin cancers;
  • the 2.1 million people with rheumatoid arthritis treated with corticosteroids;
  • the tens of thousands of recipients of bone-marrow and solid-organ transplants who are receiving immunosuppressive therapy;
  • the nation’s 14 million asthma sufferers, some of whom use steroids intermittently;
  • the 15% of the population that either has atopic dermatitis (also known as eczema) or that has a history of the condition. At similar risk are others with skin disorders, including burns, shingles, severe acne, impetigo, or chickenpox;
  • tens of thousands of newborns and patients on intensive care wards.

When people are vaccinated for smallpox, even those in perfectly good health should expect to suffer from several nuisance-type reactions. Almost everyone will have a sore, itchy arm at the vaccination site. In recent trials of Dryvax, the vaccine that will be used in the first wave of inoculations, half the subjects got muscle aches, says Fauci. About one in 10 had fever. A third of recipients felt so bad they skipped work or otherwise cut back on daily activities for a day or so.

The biggest threat: Progressive vaccinia

None of these, of course, are big worries for those with healthy immune systems. For these people, the most common complication to be feared is progressive vaccinia (also known as vaccinia necrosum and vaccinia gangrenosum).

In this condition, lesions at the original inoculation site expand and spread to other sites, and vaccinia virus proliferates in the skin, internal organs, and bloodstream. Patients must be hospitalized and treated with surgical debridement.

Though the condition is often fatal, optimal therapy probably consists of highly active antiretroviral therapy and vaccinia immune globulin (VIG), with perhaps cidofir thrown in for good measure, says John Bartlett, MD, director of the Department of Infectious Diseases at the Johns Hopkins University School of Medicine in Baltimore, and a senior core faculty member of the school’s Center for Civilian Biodefense Strategies.

Supplies of VIG (which is recovered from the blood of someone who has received the smallpox vaccine) are currently limited to about 600 doses, but more should become available once the vaccination program gets under way.

Because smallpox vaccination of the American public was halted in 1972, before various groups of people living with some degree of immune impairment became relatively common, there are few cases of progressive vaccinia recorded in medical literature. Probably because inactivated vaccinia virus often is a vector of choice for experimental AIDS vaccines, there are a handful of other instances where progressive vaccinia led to the death of HIV-infected people.

By reaching back to the pre-AIDS era, it’s also possible to find a few reports of people with compromised immune systems who contracted progressive vaccinia.

One case that has caused concern is that of a 19-year-old military recruit. At the time he was vaccinated, in the late 1980s, he was infected with undetected HIV. As a result of the vaccination, the recruit fell sick with progressive vaccinia. He was treated with VIG, and after a complicated course of illness, he recovered. However, he died several months later of AIDS.

At about the same time, as many as 400 other military recruits with undetected HIV were also vaccinated for smallpox, but none fell sick — presumably because their immune systems were not as damaged as the first soldier’s.

What does the case of the 19-year-old tell us about HIV and smallpox vaccinations? Not a thing, argue some, given that the young man died of complications due to AIDS, not the smallpox vaccine. Others contend that the case may offer not one, but two lessons: first, that immune damage caused by HIV places a person at elevated risk for progressive vaccinia; and second, perhaps, that vaccinia speeds HIV replication, hastening the onset of AIDS.

There are other possible serious side effects from the smallpox vaccine, but having an impaired immune system doesn’t appear to correlate with experiencing them. These include postvaccinial encephalitis and postvaccinial encephalopathy, two dangerous neurological complications, and eczema vaccinatum, an often-fatal complication afflicting those with active eczema or a history of eczema.

Although public health experts are generally relieved to see that the Bush plan does not call for mass pre-emptive vaccinations, many are surprised to hear the president announce that individuals who want to be vaccinated will be allowed to do so.

"I don’t think the vaccine should be made available to the public any more than I think a person should be able to walk into a pharmacy and ask for tetracycline or penicillin," says Randall Larsen, director of the ANSER Institute for Homeland Security in Washington, DC. "If a bunch of people start taking it and you have a fifth-grader who dies, it’ll be on the tube 24/7, and then people will stop taking it."

There are two other less controversial elements of the plan as well. To start with, military recruits who may see action in Iraq in the event of war will be vaccinated. As it happens, all recruits are already tested for HIV upon entry to the service, and periodically thereafter. Even so, as the military phase of the vaccine campaign cranks up, early reports have it that fully one-third of recruits are exempted from vaccination on various grounds.

"We’re paying a whole lot more attention to screening," says Assistant Secretary for Defense of Health Affairs William Winkenwarder, comparing the current efforts to less risk-averse times.

In the final piece of the plan, the vaccine is to be offered to the nation’s approximately 10 million health care workers. The half-million or so expected to volunteer for inoculation will make up the nation’s "smallpox responder teams."

Some hospitals won’t participate

After weighing the risks to patients and employees, some hospital administrators have decided to opt out of the first-responder plan. "I don’t like to cause disease," says Carlos del Rio, MD, chief of medicine at Grady Memorial Hospital and an infectious disease specialist at Emory University, both in Atlanta. "If, say, a patient with AIDS became infected [with vaccinia], that would be a disaster."

At the CDC, Gerberding says she expects most hospitals will take part in the vaccination program, and adds that she isn’t troubled by the decision of some not to take part.

If and when a case of smallpox is identified, the CDC strategy is first to deploy a "ring vaccination" response, that is, identifying the source case and then finding and vaccinating contacts. The plan calls for adding mass vaccinations if the initial number of cases or outbreak locations is large or if new cases fail to decline over time.

Critics of this plan argue that a broader, mass-inoculation approach would result in fewer deaths and faster epidemic eradication. They also say that in our mobile society, an epidemic could outrun the vaccinators.

As for the HIV-positive and other immune-impaired people, a strategy of inoculating everyone ahead of time leaves more room for careful screening for HIV, says William Bicknell, MD, from the Boston University School of Public Health. Plus, raising levels of so-called herd immunity will create a buffer for those whose damaged immune systems leave them at higher risk for smallpox.