Update on Anthrax Investigations
with Dr. Bradley Perkins

November 9, 2001

CDC MODERATOR: Good afternoon. Today, Dr. Bradley Perkins will be the speaker for our telebriefing. Dr. Perkins is going to discuss an article that's no available online in CDC's Emerging Infectious Diseases Journal. It discusses the first ten cases of inhalational anthrax relating to a bioterrorism event.

Dr. Perkins?

DR. PERKINS: Good afternoon. The first ten cases of inhalational anthrax related to bioterrorism shares similarities with previously reported inhalational anthrax cases, but also has some important differences that are outlined in the article that's available online in the Emerging Infectious Diseases Journal. The article summarizes each of the ten cases and notes that the survival rate among the group of recent cases was higher than previously had been expected.

Prior to October 2001, the last case of inhalational anthrax in the United States occurred in 1976. Between October 4th and November 2nd, CDC, and state and local health officials confirmed ten cases of inhalational anthrax. Of these ten patients, 70 percent were male, and the average age was 56 years. Four of these individuals died. Previous studies indicated a survival rate of less than 15 percent for persons with inhalational anthrax. The survival rate in this group of ten patients is at 60 percent.

The combination of antibiotic therapy begun during the initial phase of illness and aggressive supportive care may have markedly improved the survival rate for the recent ten patients. All but one of the patients in this investigation were Postal workers, mail handlers, sorters or journalists who were known to be or believed to have processed, handled or received letters containing Bacillus anthracis spores.

We think this is critical information to urgently get out to the front-line clinicians that may be seeing future cases of anthrax in either its inhalational or cutaneous form and look forward to their continuous support in early identification and treatment of these individuals.

CDC MODERATOR: Okay, John, we're now ready for questions.

AT&T MODERATOR: Certainly. And once again, ladies and gentlemen, if you do have a question at this time, please press the one on your touch tone phone.

Our first question today is from the line of Sanjay Baht with the Palm Beach Post. Please go ahead.

QUESTION: Yes. Thank you for holding these briefings. I have two questions.

The first, in light of September 11th and the anthrax attacks, there's been a lot of discussion about expanding the laboratory response network and training at the local level. Is expanding the number of EIS officers also a priority and how big of an expansion would you like to see?

DR. PERKINS: I think that the EIS officers, during the conduct of this investigation, have been critical because they are a very highly trained, mobile and rapid--rapid-deployment force that can do essentially most all of the critical epidemiologic investigation functions that are needed to do these investigations.

I think consideration of expanding the class of the EIS officers has been discussed at CDC at the highest levels. I don't know that there have been any decisions made about expanding the EIS officer class, but they have been a critical asset of CDC during this investigation.

QUESTION: [Technical problem with phone line.] Can you tell us anything about the select agent registry, such as how many labs are registered with the CDC [inaudible] select [inaudible] or the direction of the changes the CDC would like to see in current shipping or storage rules?

DR. PERKINS: I'm sorry. I did not hear the beginning of your question.

QUESTION: Okay.

DR. PERKINS: Can you restate?

QUESTION: Yeah. Can you tell us anything about the select agent registry, such as how many labs are currently registered to mail select agents or what direction the CDC would like to see in the changes made to shipping or storage rules.

DR. PERKINS: No, I cannot comment on that question.

AT&T MODERATOR: Our next question is from the line of Gina Colloda with the New York Times. Please go ahead.

QUESTION: I have two questions. First of all, you may note that on Table 1 it's supposed to be ten patients and we can only see eight. I don't know why, but it seems like the last two were cut off. But I was really curious to know whether there's anything you can look at in the laboratory findings or anything else which would differentiate the people who lived from the people who died.

And, number two, I was wondering, when you talk about the numbers of people, the distribution of the patients, when you say that 70 percent were male, with an average of 56 years, that sort of is like a numerator, but we don't know what the denominator is. I mean, like were most of the people who were in that mail room males? Do they tend to be middle-aged or, in other words, is this a significant finding or not, in terms of the number of people who may have been exposed?

So those are my two questions.

DR. PERKINS: Taking your second question first, we're working to compare the age distribution, the demographic comparisons between the cases and the occupational groups that they represent, working with the Post Office to do that, primarily, and that information is not completely together or known.

I will say that, anecdotally, working with the Postal Service and being in these environments that the age distribution of the inhalational cases we've seen is slightly older than what you would expect based on what's been observed in those settings, but we're working to get more quantitative comparisons to draw that conclusion more firmly.

Your question, I'm not sure, can you restate that?

QUESTION: The age distribution is slightly older than what you'd expect based on what's been observed, but what about the gender distribution, were they mostly men in these Postal facilities?

DR. PERKINS: Yes, men are disproportionately represented in some of the settings where cases have occurred, and again that's part of the demographics comparison that we're carrying out.

AT&T MODERATOR: We'll go to the next question from--

CDC MODERATOR: John, I'm sorry. Let me interrupt you for a minute. Gina had a question about the tables on the other cases.

QUESTION: Yes.

CDC MODERATOR: Gina, it has the day with the way you printed it. The table was set up in a Landscape format. You probably printed the text. That's in Portrait. Simply change it to Landscape on your printer, and you'll get all of the--

QUESTION: Okay. But my question was beyond that. The question was can you tell the difference, in looking at this data, between those who lived and those who died? In other words, were there any distinguishing or other findings in the people who survived this inhalational anthrax as compared to those who died of it?

DR. PERKINS: In general, the persons that did poorly and died presented for medical attention, at least at the time of admission, with more critical illness than those that survived, suggesting that early identification and prompt treatment was important to the increased survival rate that we saw given the experience with the patients that have been treated, do we have a preferred treatment when we think we have meningitis? And the other question is do we have a sense of the role of the protein inhibitors like Clindamycin in treatments of serious cases?

DR. PERKINS: Yes. Those are both very good questions. We think that treatment with multiple drugs containing at least one chloroquinolone class drug is important, and that the selection of particular agents should be driven by considerations of involving the use of at least one drug that may be--may have activity in inhibiting the production of anthrax toxins, such as Clindamycin as a representative of that group.

We also feel like that in cases where meningitis is suspected or demonstrated that choosing appropriate antibiotics that penetrate into the cerebral spinal fluid is also an important clinical consideration because among the antibiotics that could be chosen from, there is variable penetration into that protected central nervous space.

The other, I think, critical factor to recognize is that cephalosporin should not be used for treatment of anthrax because of the innate capability that Bacillus anthraces has to produce a cephalosporinase that inhibits the antibacterial activity of the cephalosporin such as stef-triaxon.

AT&T MODERATOR: Thank you. Our next question is from Pete Williams with NBC. Please go ahead.

QUESTION: Dr. Perkins, can you tell us how old the Ames strain is? There's some indication that it's been around since the early 1900s, some indication that it was isolated later. How long has it been around?

DR. PERKINS: The Ames strain has been certainly through the most recent decades a strain of preference among researchers working on a variety of aspects in anthrax, either in animal models or in other research settings. I do not know the precise date that that isolate was obtained, but certainly for the last two decades it has been a strain of choice among researchers working in this area.

AT&T MODERATOR: Thank you. Our next question is from Miriam Selko with CNN. Please go ahead.

QUESTION: Hi. Thank you for these teleconferences. Can you tell us if the CDC told Iowa State University to destroy their strain of the Ames anthrax, and if so, why?

DR. PERKINS: I cannot tell you that. I know that I have not been in any way involved in making any such recommendations.

CDC MODERATOR: Next question.

AT&T MODERATOR: Thank you, and that's from the line of Jeremy Meniere with The Chicago Tribune. Please go ahead.

QUESTION: Hi. Thanks very much. Let's talk a little bit--two questions. One is in addition to antibiotics, you mentioned aggressive treatment as a factor in [inaudible]. Would you talk about some of what doctors have been able to do in that respect that they might not have done in cases decades ago? Are we talking about chest tubes or other things like that that might have been a factor?

Also I'd like you to talk a little bit about the incubation time which seems to be maybe less here than some studies have indicated in the past.

DR. PERKINS: Yeah. Those are--that's a good question. I think that the--there's a range of things that may have not been done the same over the last century that are now common practice in settings of severe infectious diseases like anthrax, and they range from aggressive intravenous hydration therapy, the availability of pressor drugs that allow the maintenance of a normal blood pressure in the setting of severe infections.

In addition, there's mechanical ventilatory support, intubation with machines to assist in breathing.

The other thing that looks like it probably was critical that would not have been routinely practiced, certainly in the earlier parts of the last century, was the aggressive use of pleurosynthesis to remove bloody fluid that we saw collect in the lung space of many of these individuals, and that had to be done on a number of occasions with some of these folks. And if that's not done, that obviously mechanically compresses the lung tissue and further compromises respiratory function. So I think that was also important.

In one case, although there's not a lot of data to base this on that would be reasonable clinical consideration, one of the patients underwent plasmapheresis in an effort to try remove some of the toxin that may have been in the blood.

So I think it's probably a variety of things, but I think the hypothesis that improved technology to support people with serious infectious diseases as the body recovers from the infection resulting in improved survival is quite a valid hypothesis based on, you know, a number of technologies that are currently available.

CDC MODERATOR: Next question.

AT&T MODERATOR: Thank you. And that's from Steph Warrenstein with Knight Ridder. Please go ahead.

QUESTION: Yes. Looking at your--thanks again for having these. Looking again at your article, and I know you were meeting last week and continuing to meet about research that has to be done not in the field, but in the lab, to better understand anthrax and the way--why some people get exposed. Does this--especially looking at why some people died and also why some people got infected and others did not, what specific research questions do you want to look at in the lab resulting from your quick studies here?

In other words, in the lab, what are you specifically looking for right now?

DR. PERKINS: I think one of the hypotheses that's critical and lends itself very well to further laboratory research is the utility of this classes of antibiotics that inhibit protein synthesis and may thereby decrease production of the toxins through which anthrax does its damage. And we've already been in contact with a number of experts in this area, and I think that that's a critical research question in the context of therapy.

Another thing that we're actively exploring in terms of additional adjunctive therapy is the use of antiserum which is a preparation that would contain antibodies directed against the specific toxin components of the B. anthraces. And this is a time-proven approach to adjunctive therapy in toxin-mediated diseases such as anthrax, and we're aggressively pursuing research to support that modality as adjunctive therapy in cases of serious disease that don't look like they're going to respond to aggressive antibiotic use alone.

AT&T MODERATOR: Thank you. Our next question is from Maggie Fox with Reuters. Please go ahead.

QUESTION: Thanks again. Can I follow up on that? Can you tell us a bit more about this antiserum in lay language and also I got very excited about the gastrointestinal symptoms of some of the patients that are outlined in your paper until I read farther down and found out that that was also common in the Sverdlovsk incident.

But can you tell us in lay terms about how the bacteria moved into the gastrointestinal system and caused those problems?

DR. PERKINS: I think, and there's not a huge amount of data addressing this issue, but I think that the gastrointestinal symptoms that we're seeing are likely to be a manifestation of severe, diffuse toxemia. And when these toxins get into the blood, and there's two toxins, there's a lethal toxin which causes cell death and an edema toxin which causes swelling of tissues, when those get into the blood, they obviously move throughout the entire system and create symptoms throughout the body.

And so I don't think it's a phenomenon of the bacteria preferentially affecting the gastrointestinal system. I think what we're seeing is the impact of widespread toxemia, of widespread toxins circulating in the blood, and you've got that edema factor or edema toxin and lethal toxin exerting its disease-producing tendency on the gastrointestinal system at the same time it's doing that on the heart, and on the lungs, and a number of the major organs in the body.

What specific question did you have regarding the--

QUESTION: The antiserum. What is this stuff? What's it called, and is it something that is used? I have not heard this, except as theoretical, but you said it was a time-proven approach to adjunctive therapy.

DR. PERKINS: Yes, it is. There's a variety of antitoxins that have been used over a long period of time. I mean, treatment for botulism, for example, botulism is a toxin-mediated disease for which the primary therapy is an antitoxin, which is an antibody that goes in and finds the toxin, neutralizes it, in some instances, and prepares it to be cleared by other inflammatory cells in the body, and these antibodies can be produced in a variety of ways.

Using human cells in culture, for example, you can produce large amounts of monoclonal antibodies. These are antibodies that have very specific activities, and they're all the same, and you can produce those and you can use them as adjunctive therapy. This is something that has been a major area of research for a long period of time.

AT&T MODERATOR: Thank you. Our next question is from Laura Mechler with the Associated Press. Please go ahead.

QUESTION: Thanks. I have a couple of questions for you.

First, in the New York City investigation, I understand there's a plan to test the subway routes along which the hospital worker traveled, but they hadn't yet determined how they were going to do that. Can you tell us anything about that?

And related to that, what else do you plan in terms of the investigation this weekend? Are there new routes to your planning?

And, finally, we're hearing that there may be a new case in New York City. Do you know anything about that?

DR. PERKINS: Certainly, we are not aware of any new cases in New York City at this time. Folks from CDC continue to vigorously support the investigation of the possible circumstances of exposure that's resulted in the inhalational case in New York City, but specifics regarding plans for additional environmental sampling at this time would need to be directed to the New York City Health Department.

Next question?

AT&T MODERATOR: Thank you. That's from the line of Kim Dixon with Bloomberg News. Please go ahead.

QUESTION: Hi. Thanks. I have two questions.

The first is about the widespread, I guess, availability of the Ames strain. I know you said it was the choice among researchers for the past two decades. Can it be estimated how many labs actually contain the Ames strain? There's some reports that there are really like less than 10 that actually would have this particular infectious strain.

And, two, could you comment about what the CDC is doing to look at the possible mortality rate associated with the smallpox vaccine in light of the fact that the government is ramping up and asking drug makers to come in and help it make more vaccine?

DR. PERKINS: I cannot comment on the smallpox issue. That's not my area of expertise. I lead the group that has responsibility for anthrax. Smallpox is done by other folks here.

In regard to the number of laboratories that may have the Ames strain, I do not know the answer to that question. CDC monitors the movement of select agents as they're moved from laboratory to laboratory, but we do not know the number of laboratories that actually have this strain in their collection of bacterial strains in their laboratory.

AT&T MODERATOR: Thanks. Our next question is from Laurie Garrett with News Day. Please go ahead.

QUESTION: Thank you. My question has to do with dose.

We've been hearing every imaginable possible dose described as necessary inhalation dose for anthrax from 9 or 3 spores all the way to 55,000. Did close examination of these ten cases offer any further elucidation on this? Is there a safe dose? Is there such a thing as a threshold dose for exposure? Do you believe in threshold theory?

DR. PERKINS: The ten cases that are reporting in the Emerging Infectious Diseases Journal really don't offer any opportunity to better clarify the number of anthrax spores that may be required for infection.

The variability that you hear among anthrax experts or other scientists as to the number of spores requires I think reflects a number of things. Paramount among those things are probably that for different people, a different infectious dose may be required, and that is seen with normal biologic phenomena with many infectious diseases. Obviously, it will be extremely difficult to establish with great certainty what the average amount of spores needed to cause inhalational anthrax is in a human.

What we do know is that there are environments with some level of spores present, particularly outdoor environments in areas where animal epidemics occur of anthrax, and we know that in those environments, we do not see inhalational anthrax among persons that worked routinely in those environments. So there clearly is a safe level of anthrax spore contamination. These spores are widely distributed really across the globe in many different locations where we don't see inhalational anthrax.

Extrapolating those data to the safe level of contamination in occupational settings is an area of active and vigorous pursuit here at CDC and among all of our partners. We know that some level is likely to represent a negligible human health risk. Defining that level and relating it to the occurrence of cutaneous and inhalational disease is something we're working very aggressively to try to do right now based on all available data.

AT&T MODERATOR: Thank you. Our next question is from Claus Marr with Inside Washington. Please go ahead.

QUESTION: Thank you. I have a couple of questions for you. One is regarding an interim guideline for investigation of and response to anthrax exposures that was released today. It says here that "closing of a facility should not be done based only on the identification of anthrax from samples of environmental surfaces or based only on the identification of cutaneous anthrax." I was just wondering why CDC decided not to close buildings when people get skin anthrax.

The second is a question regarding respirators that workers are being asked to use. On October 24th, CDC said workers should use respirators with a 99.7-percent efficiency and a week later that was changed to respirators that are not as efficient, that only have a 95-percent efficiency, and I was just wondering what that decision was based on to change this.

DR. PERKINS: There are folks here at CDC that have been working with a variety of partners, including the U.S. Postal Service to try to establish the right mask to recommend in the Postal settings that we have the most concern about in regard to inhalational anthrax. And this has been an area of intensive focus by CDC, and there were a variety of technical and practical aspects that went into making specific recommendations. I don't know all of those aspects, but those decisions were based on the soundest science available regarding the risk and the ability of the Postal Service to implement those prevention modalities.

I think you should also recognize that these are interim guidelines, and we will be constantly reevaluating and assessing the effectiveness and the degree to which these recommendations can be implemented in an effective manner.

Your other question regarded when the CDC interim recommendations regarding building closure. Can you restate that question?

QUESTION: Yes. It says here that--it was from today, Interim Guidelines for Investigation of and Response to Anthrax Exposures. And it says,
"closing a facility" or "facilities should not be done based only on the identification of anthrax from samples of environmental surfaces and based only on the identification of cutaneous anthrax cases."

DR. PERKINS: Right. We recognize that as a result of the bioterrorism attacks that have occurred since early October that there has been contamination of a number of places in the mail system. A kind of cross-contamination that we think has occurred is resulting in very low levels of spores in potentially a very large number of places. We don't know how many places are going to end up having some low level of contamination, but we know of many at this point.

And also during this period of time we've done intensive surveillance, looking for cases of cutaneous or inhalational anthrax, and what we can conclude by observing that there's fairly extensive environmental contamination as a result of these incidents, but a very limited number of cases of cutaneous disease is that the risk is extremely low, and that we think that that risk can be mitigated by cleaning up these areas of environmental contamination and practicing vigilant mail-handling practice, looking for suspicious mail.

Of course, if there's cross-contamination, it may not be suspicious, but good handwashing following handling of mail should mitigate the very low risk that we recognize may be there as a result of cross-contamination. We don't think that that situation requires the closure of a building.

AT&T MODERATOR: Thank you. Our next question is from the line of Jill Carroll with The Wall Street Journal. Please go ahead.

QUESTION: Hi. Thank you for holding these briefings. They're very helpful.

Two questions. One is in the research that you're looking at, different environments, now that anthrax can be spread like indoors, I want to know what things you've learned from that so far. And also from the 10 cases, anything that showed up in the 10 cases that showed a new way anthrax could be spread, or some people have a lower tolerance? It might help either in the Kathy Nguyen case in New York City or in general understanding how anthrax infects.

DR. PERKINS: I wish I could tell that that kind of finding was clearly evident from the 10 cases we're reported, but really the most striking finding is that the risk was focused in very tightly-defined occupational groups that were the focus, either intentionally or unintentionally, of these current bioterrorism attacks.

That kind of occupational risk is traditionally quite helpful to physicians who are seeing patients that, you know, that could have anthrax, but in this case where, you know, it's unclear that these attacks will continue in this manner or whether they might change in some manner, it's potentially less useful than in many traditional public health investigations.

Your other question was?

QUESTION: On the research you're doing in other, you know, indoor settings, that kind of thing, where anthrax--how it's going, anything you're learning right now that's new on how anthrax can be spread or infected?

DR. PERKINS: I think the most important thing that we're currently learning is that there are many sites of environmental contamination in occupational studies that are not related to occurrence of human disease. That's good news and bad news. I mean we don't want our environments, our occupational environments or any other environments contaminated with B. anthraces spores. I would rather not have them there. You know, that's the bad news.

The good news is that there's clearly going to be a level of environmental contamination that does not represent a health risk for cutaneous disease or for inhalational disease.

AT&T MODERATOR: Thank you. Our next question is from Ellen Beck with The United Press International. Please go ahead.

QUESTION: Thank you very much. Are you, given the fact that you're still actively investigating in the New York area, and I'm sure in the other key areas as well, are you at any point considering pulling back the number of people that you have in the field in Washington, New York, New Jersey, et cetera? Or have you pulled back the number of field investigators or technicians that are actively pursuing this?

DR. PERKINS: We're continuing to vigorously support local and state health department needs in all four of the major sites of the investigation, and in some cases our efforts are, and our focus, are shifting a little bit.

One of the current things that we're shifting additional people to work on are monitoring people that have been recommended for prolonged courses of antibiotics, 60 days of antibiotics for prevention of inhalational disease. We want to know if there's any adverse event or adverse impacts that occur because of them taking those antibiotics because it's unusual that you have this large a number of people on these antibiotics for this long a time, and we want to be aware of any adverse events that occur.

The other thing that we're trying to make sure happens is that all of the people that we recommended take 60 days of antibiotics actually take 60 days of antibiotics. So we're looking for strategies to promote adherence to those recommendations because we think it's critical that they complete that course so that they don't get sick.

AT&T MODERATOR: Thank you. Our next question is from the line of Dan Fergano with USA Today. Please go ahead.

QUESTION: Hi. Thanks again for having these briefings. A couple of questions about recognizing anthrax. Are you recommending chest x-rays as sort of first and best way to identify anthrax when people come into it? And I also had a question about the patient histories you put together. I'm reading that eight of 10 patients first came in, received antibiotics. The six who received fluoroquinolones were the ones who survived. Is that a common denominator in these folks?

DR. PERKINS: Let me take your first, your chest x-ray question first. This is a little tricky because I think what the paper clearly shows is that all of these cases had abnormal chest x-rays and that gives you--that does give the clinician something to work with.

However, you know, the early prodrome for these patients is typical for many respiratory diseases that physicians might not usually get a chest x-ray for. And so weighing--it's still going to be a challenge for the clinician to weigh the need to obtain chest x-rays in persons that may have anthrax among the range of diagnostic possibilities. And obviously respiratory disease like the kind that is seen and can have the symptoms of early anthrax is extraordinarily common in the United States. And we want to balance the use of chest x-rays carefully as we try to pick the needle out of the haystack here for early identification of patients that might have anthrax. So it's useful information that all the chest x-rays are abnormal in these patients, but it has to be in the clinical setting when you're looking at a specific patient, that information has to be balanced very carefully against the frequency of other respiratory disease.

And your question about the use of fluoroquinolones, I think that we do consider fluoroquinolones to be a foundational therapy for the treatment of severe illness resulting from Bacillus anthraces infection, and I think the cases, as you mentioned, suggest that that's true.

You know, that should be just the foundation, though, and there should be serious consideration of adding at least one or two different antibiotics to that foundation based on whether the presentation is consistent with meningitis or not, and the opinion about the need for a class of antibiotics that might exhibit protein synthesis and decrease the level of toxins in the blood.

CDC MODERATOR: John, we have time for one more question.

AT&T MODERATOR: Thank you. And that will be from the line of Rod Hendin with CBS News. Please go ahead.

QUESTION: Thank you very much for the conference call. Just a follow-up. You mentioned about--the question about how many labs have the Ames strain. My question is under Federal law and guidelines, is it required that anyone who transports or possesses anthrax in any form, in any amount, for any reason, must register that with the CDC.

DR. PERKINS: I'm not an expert in the select agent rule, but I think that is the general concept behind the select agent rule is that it monitors the transport of these select agents from laboratory to laboratory.

CDC MODERATOR: Thank you, ladies and gentlemen, for participating in today's telebriefing. A transcript will be available online.

AT&T MODERATOR: And, ladies and gentlemen, that does conclude your conference for today. We thank you for your participation, and you may now disconnect.

[End of conference call.]

Listen to the telebriefing

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U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES