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Dr. Venkat Mani

Dr. Venkat Mani is the chief of Infectious Disease at Southern Maryland Hospital in Clinton, Maryland. He treated postal worker Joseph Curseen before he died from inhalation anthrax. Excerpts from his conversation with Susan Dentzer follow.

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  • SUSAN DENTZER:

    Let's start by talking about, in general terms, about the appearance of anthrax and what it means here for the medical community which suddenly has had to confront a disease that most American physicians, most physicians, indeed, in many parts of the world, no longer have familiarity with. What has that been like?

  • DR. MANI:

    Up until October, the incidents of anthrax in United States were extremely rare. Looking at the literature, there were about 234 cases described since 1944, and most all of them were skin anthrax, not lung anthrax or, or inhalational anthrax that we are, we are dealing with now.

    So the data that we have, or the, or the information we have in the textbooks around the basis of, is the clinical presentation elsewhere in the world, a lot of it in the developing countries and some from the outbreak in Soviet Union, Iran.

    So the physicians trained here have not seen case of anthrax, both cutaneous and pulmonary. So since October, this first case that happened in Florida, and then we had cases here, there's a increased awareness of what the clinical presentation is going to be and how to recognize the disease, and start appropriate treatment to improve the outcome.

  • SUSAN DENTZER:

    Had you ever seen a case of anthrax, either cutaneous or inhalational?

  • DR. MANI:

    I have not. I went to medical school in India, graduated in '67. There used to be rare cutaneous anthrax cases diagnosed then. I have handled a specimen in the microbiology laboratory but I have not personally seen a case there. But not inhalational type.

  • SUSAN DENTZER:

    And of course since you came to the United States–

  • DR. MANI:

    No, we, we have not had a case of anthrax in this area at all.

  • SUSAN DENTZER:

    Now let's talk about the case of Mr. Curseen. You were able to look through his chart and understand what happened. Take it from the beginning. What happened in the case of that patient?

  • DR. MANI:

    When I was called in to see the patient on October 22nd, as I arrived looking at him, he was on a respirator, so I could not talk to him. I talked to his wife, both in the hospital and later in the, in the office. The history that I get is he was doing well until–now the 22nd is a Monday. The Tuesday before that, he was complaining of stomach pain and some nausea.

    He told her that he had some food poisoning. He took over-the-counter antacids, and he felt somewhat better, that he was able to go to work. He's a night shift worker.

    On Saturday, he was in the church, apparently had a brief passing-out spell. The rescue squad was called in. The paramedics arrived. By that time he has recovered quite well, felt well, and told them look, I'm–nothing's wrong with me, I have a little touch of upset stomach. I'm feeling well. You know, I'm not going to any hospital. And he drove himself then back home, apparently feeling well, and he drove to work Saturday, Saturday night.

    From work, he apparently called her and said I'm not feeling well, I got severe pain in the upper part of the stomach, and I'm nauseous, and he had loose stool. So he drove himself from there to the, to the hospital. I looked at his chart and I spoke to the emergency room physician who took care of him, who's a very–is a board-certified well-respected infectious disease doc. I mean, well-respected emergency room doctor who saw him.

    And looking at it, he, he was alert, he was not toxic, was complaining of upper abdominal pain, nausea, and history of having had diarrhea. His–he was clinically noted to be dehydrated. So he was given intravenous fluids to correct that.

    He had a chest x-ray done which was normal. He had blood tests done, which were nothing out of ordinary, and he was felt to have gastroenteritis, and, and gastritis, that is, gastritis, stomach part, enteritis is the intestinal part, and he was sent home. Apparently he was very anxious to go. "Look, I'm quite well. The doctor wrote an order for a pain medication. I don't need any pain medicine. I'm–you know–I'm getting better with all the fluids you have given." And he, he went home.

    He drove himself back from the emergency room to his house in Clinton. Apparently, later that night, he did not feel well, and the next morning his wife found him slumped in the bathroom, and she called the rescue squad and brought him to the hospital.

    When he, when he arrived there, he has a fast heart rate, he had low blood pressure and was breathing fast. At that time they strongly suspected that he had, he could have had anthrax, because he was giving a history, that he was a postal worker. And Sunday night, the local health authorities recognized that there [was a person hospitalized at Inova Fairfax Hospital] and was a worker at Brentwood, the diagnosis was confirmed, [and] they started treating patients with Cipro as of Sunday, Sunday evening.

    So when he came to the emergency room, he said look, you know, all–his colleagues were taking Cipro and he's working there, and he was concerned about this possibility.

    He had a chest x-ray done which showed wide mediastinum. That was not seen in the chest x-ray done 24 hours ago. Mediastinum is part of the chest between the two lungs. That is normally of a narrow size, and, in him, that was wider, and he had evidence of pneumonia on either side of the lung. His blood count showed increased white blood cell count, indicating there's an active infection that is going on.

    They have to intubate him, that is, put a tube in his throat, put him on a, on a respirator, and admit him to the intensive care unit.

    They have to give him medication to bring his blood pressure up. They have to give him fluids to bring his blood pressure up again.

    That's the time that I got to see him, and the diagnosis was suspected at that point. To make a quick, fairly definitive diagnosis, we did a gram stain of his blood smear. Staining the blood, looking for bacteria. Normally, in a patient with blood infection we do not see the bacteria on the smear, because there are not that many bacteria. You have to read for the culture, the next day, or the third day, because even small number of bacteria will multiply, and then we can culture and demonstrate the organism.

    In this case there were so many organisms on the smear, that we could directly see it. Generally, when that is seen, that means the person has overwhelming sepsis. So when I looked at that smear, it was certain in my mind that we are dealing with a case of pulmonary anthrax.

    There are bacteria which we call as gram positive and gram negative. We, in general practice, we almost never seen a gram positive bacterial infection. It is very unusual. So when I saw this, you know, it was clear to me that, that, you know, this is going to be a case of anthrax. I want to be sure that, you know, he is covered with antibiotics.

    When you have a person with a blood sepsis–blood infection, and you see the bacteria on the, on the blood smear, that patient will almost never survive. By that stage the bacteria is winning the battle.

    It's overwhelming the body with the toxin. You know, it was clear to me that this patient is not going to survive.

    The reason I'm mentioning that is because he had developed swelling of his abdomen, and we did a CAT scan, and that showed he had fluid in the abdomen, fluid in the lung. We were concerned that he may have gangrene of the bowel. If a person has gangrene of the bowel, one has to do surgery to remove that. But once we knew that this is a case of anthrax, at that point we said we are not going to operate on him. Of course he died about six hours after he came into the hospital.

  • SUSAN DENTZER:

    Let me back up and just ask you a bit more about the initial tests that were done when he came in on Sunday. You said a chest x-ray was taken of him.

  • DR. MANI:

    Right.

  • SUSAN DENTZER:

    And it showed everything was fine.

  • DR. MANI:

    That's right. The chest x-ray was normal. There was no lung shadows. The, the mediastinum that was later abnormal was normal. So it was a normal chest x-ray.

  • SUSAN DENTZER:

    And he was also given a blood culture at that point?

  • DR. MANI:

    Blood culture was not done. The reason for that is we do blood cultures if patient has fever, or if patient is suspected to have bacterial infection. This emergency room physician's clinical judgment was that this patient did not have those. So a blood culture was not done.

  • SUSAN DENTZER:

    And was he asked about his occupation at that point?

  • DR. MANI:

    I did not see a note made in the chart of, of documentation of what his occupation was, asked by the emergency room, room physician.

  • SUSAN DENTZER:

    So to all indications, it's not clear whether he was asked or not what his occupation was.–

  • DR. MANI:

    That's right.

  • SUSAN DENTZER:

    Where he worked; whether there was any possibility that he could be linked to anthrax?

  • DR. MANI:

    There was no mention made in the chart.

  • SUSAN DENTZER:

    Now going forward to Monday, after you've established that he is in the dire situation he's in, what happened at that point? How did he progress from the point you saw him to death?

  • DR. MANI:

    He–we could not keep his blood pressure up. We could not oxygenate him, that is, give, give him enough oxygen to maintain the blood oxygen level. He–his heart stopped. They, they, they worked on him to resuscitate. It was not successful.

  • SUSAN DENTZER:

    And so he died at about…?

  • DR. MANI:

    About 12:00 o'clock noon time.

  • SUSAN DENTZER:

    Looking back on this experience, what does it tell us? What are the lessons that you draw from this?

  • DR. MANI:

    You know, I happened to hear about the case that came into Greater Southeast Community Hospital, the other anthrax patient who died. There's a lot of similarities between these two cases. One conclusion that I came to here in these two is that initial presentation is very nonspecific, even though the patient that I took care of had x-ray evidence of pneumonia.

    He did not have any symptoms of cough, sputum production, chest pain. Those were common symptoms that we see in patients with pneumonia.

    So it's a very rapidly-progressing disease with nonspecific presentation. In layman's terms, the presentation is vague, so it's not pointing to one system in the body that is, is involved, implying that we have to be aware of this clinical entity, and if in the community there is an outbreak, or the person happened to work in an area where there is an outbreak, we should have a higher awareness in starting diagnosis and treatment on these patients.

  • SUSAN DENTZER:

    So patients will walk in, and it will look just like the flu, or just like gastroenteritis?

  • DR. MANI:

    These patients can [appear to have] very common, common illnesses like flu and gastroenteritis. They may well have anthrax, in the early stage.

  • SUSAN DENTZER:

    And so it sounds like what you've learned from this, besides the fact that the symptoms can be very unspecific, is that the progression is very, very rapid.

  • DR. MANI:

    That's correct. Very, very rapid clinical progression. I mean, I was there for the last three hours of this patient. It's very dramatic, how rapidly he was dying, that we couldn't do much.

  • SUSAN DENTZER:

    And given what the emergency room physicians had seen the day before, versus what you were seeing at that point, just 24 hours later–

  • DR. MANI:

    It's very different, much different. Here is a patient who drove into the emergency room, wanted to go home, felt, you know, "I don't want any pain shots." He was offered an injection of Toradol [ph] which is a pain shot. He said, "My pain is better after the fluids you gave me, I'm feeling well, I want to go home."

  • SUSAN DENTZER:

    And drove himself home?

  • DR. MANI:

    That's correct.

  • SUSAN DENTZER:

    And 24 hours later, he was dead.

  • DR. MANI:

    Was dead.

  • SUSAN DENTZER:

    What, what do you think is the lesson, now, for the medical community, in general? It sounds as if now, at least in this area, no one is going to make a mistake about not asking anybody about an occupation.

  • DR. MANI:

    We have, at Southern Maryland, had about 25 patients who were admitted for at least one-day observation, who had worked in the mentioned postal facility, or in the area, had flu-like symptoms, so we culture them, put them on antibiotic, observe for 24 hours, the cultures come back negative or they are stable, they are sent home to continue the antibiotic pill they were taking.

  • SUSAN DENTZER:

    So the the protocol changed, dramatically–

  • DR. MANI:

    That's correct. Keep in mind, you know, this is a learning experience for everybody in the health care field, probably [even the] officials in CDC, locally, and we, at the local, local hospitals. It's constantly changing, in terms of where the outbreak is happening, how best to handle it. What we are doing today is not what we did five days ago. It is different, because we know more about this.

  • SUSAN DENTZER:

    This case became the basis of a presentation at the Society for Infectious Disease meeting. Let's talk about this.

  • DR. MANI:

    We wanted all the–or many physicians around the country know how this case presented to us, so they will have an idea of how this could present, if it happens to be in their area. So we were, we contacted the IDSA, that is, Infectious Disease Society of America, because a national convention was going on last weekend in San Francisco. So they arranged for one of the fellows to, you know, fly from here to there, and present this case in their plenary session yesterday morning.

    There was a lot of interest, and, you know, numerous questions about, you know, how this case presented, looking at the pictures, looking at gram stain, x-ray pictures.

  • SUSAN DENTZER:

    And how common do you think it is for a case to happen on day one and be presented at a major medical society six days later?

  • DR. MANI:

    It–well, this is one of a kind. We, we don't have any track record for this. But it is–it's kind of sad, we have to be in the situation, but, you know, I'm glad that we are able to spread the information to physicians around, about the clinical picture, so they can handle it.

  • SUSAN DENTZER:

    Do you have any criticisms of the Centers For Disease Control or of the Postal Service for not having moved quicker to identify this possibility that more workers could have become infected?

  • DR. MANI:

    I think it's very unfair to blame them, because what we know today is a lot more than what we knew on Sunday. By that I mean before we felt if there is a closed envelope with spores in it, somebody touches it or comes in contact with it, that person will not develop anthrax. We believed, up until that point, only those who have inhaled the spores directly will develop the disease.

    Now the data suggests that perhaps the spores can be coming out of the envelope and a person who's handling it can, can inhale, and the information is constantly evolving. The first patient got admitted to, you know, Fairfax Hospital, on Friday. But that patient had a chest x-ray that is abnormal and he was started on treatment. The diagnosis was confirmed only on Sunday.

    So until then it was kind of a, you know, suspicion of a case of patient with pneumonia. So the concept is evolving. I wish we knew then what we know now, but I'm not sure how that could happen.

  • SUSAN DENTZER:

    And so the CDC and the public health authorities have been in the same boat.

  • DR. MANI:

    They are learning. They were in contact with us, you know, every few hours, and said are you sure the smear that you looked at–because all we knew then was a person with pneumonia and a positive blood culture smear, and to ensure that this is indeed a case of anthrax, and by 10:30 that morning, you know, after I talked with them, they felt certain that this is going–even though they cannot officially confirm it because the culture takes two days to come back, but at that point it became clear to them this is a case of inhaled anthrax.

    By that time they knew the, the Fairfax case was a case of anthrax. That was 48 hours after the patient came in. But the x-ray picture of those patients were different when the patient first came in, than our patient when he came on Sunday morning. Sunday morning, his x-ray was normal.

  • SUSAN DENTZER:

    Did you speak with the family of Mr. Curseen?

  • DR. MANI:

    Yes. I did. They were distraught. They, they are very deeply religious people, and they had some concerns about, you know, wished they had given antibiotic earlier, or the postal, postal authorities have done something different than what was done. But they were–I mean, they were coming to closure on the basis of faith that they were expressing.

    His wife came to my office two days ago. She's taking Cipro. She just wants to know if she should take it, how long should take it. So she came for a consultation.

    I advised that she would not need to take it, because there is no case of spread of anthrax from person to person.

  • SUSAN DENTZER:

    Let's talk about drug treatment for persons presumed to have been exposed to anthrax bacteria. At first, people were not given the antibiotics, prophylactically. Then it was decided that people generally would all be given antibiotics, prophylactically, and now we're, essentially now in the third stage, which is we've pulled back from Cipro and moved on to Doxycycline.

    How else have the protocols with respect to antibiotics treatment evolved, just in this very short time frame?

  • DR. MANI:

    When the outbreak was first recognized, we want to cover all, or more strains of anthrax organisms. So Cipro was chosen because we know that that is a broad spectrum antibiotic, and most all strains of anthrax bacteria were sensitive.

    Once the organisms were tested in the lab, we knew what other antibiotics one can use as well, and it became clear that all the organisms that were grown so far were all sensitive to Ciprofloxacin, were sensitive to Doxycycline, and sensitive to penicillin as well.

    When a person has a documented infection, or has a significant exposure to the spore, they should be on antibiotic for 60 days. The reason for that is if it is not, they could develop, relapse. This is mostly on animal data. We, we don't have human data to challenge them. That Rhesus monkeys, where they have challenged them with anthrax spores, and created a illness, and various treatment were given to them, when it is not continued until 60 days, or stopped in 30 days, there was certain number of monkeys developing relapsing infection.

    Also when they examined the mediastinum lymph node, they have found the organisms still there, up to 60 days. That's why it is recommended, now, those persons should take the antibiotic for a total of 60 days.

    You have to keep in mind, when a person takes an antibiotic for 60 days, one can see certain side effects from it. With any antibiotic, one can develop diarrhea, and some form of diarrhea can be quite severe. One can become allergic to the antibiotic and develop rash, difficulty breathing, can be even serious. With Cipro, particularly, when it's taken longer than four weeks, one can develop tendon rupture.

    There has been case reports of Achilles tendon rupture in the heal or biceps tendon rupture, and I happen to take care of a patient with an Achilles tendon rupture and it is quite a difficult clinical condition to operate on and to get them well.

    Fortunately, we know that this organism is sensitive to all antibiotics, so the current recommendation is to switch from Cipro to Doxycycline, and continue the course to complete 60 days of therapy.

    In general, Doxycycline has fewer side effects than Cipro. We have more experience treating a person with a long period of Doxycycline than with a long period with Cipro.

    We are learning and we have more data available, and then we say this is the safest approach.

    Let me make one other comment about the nasal swab. The nasal swab, that is, putting a swab in the na–nose and culturing it, is not very helpful in making a diagnosis or excluding a diagnosis in a particular person.

    It is useful as an epidemiological data collection. It appears that when a person inhales, they may have a few spores in the nostril for a short period of time and then it goes away.

    For example, Mr. Curseen, the patient I took care of, his nasal swab was negative, did not show presence of bacillus anthracis. So a negative nasal swab does not mean that person is not at risk of developing anthrax.

  • SUSAN DENTZER:

    And his nasal swab was negative when he first came in?

  • DR. MANI:

    When he came in the second time, when we suspected he had anthrax and swabbed his nose. His blood culture was positive, his sputum was positive, but not the nasal swab. We should not be lulled into the reassurance, look, I had a nasal swab done, that's not showing the spores, so I'm not at a risk of developing anthrax.

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