OUTBREAK INVESTIGATION

OUTBREAK INVESTIGATION
An ICP’s Worst Nightmare

Recent bioterrorism scares have shone a spotlight on emerging diseases and raised fears of outbreaks that are due to global enemies. Anthrax and smallpox were at the forefront of these scares, but even excluding these, there are enough organisms occurring naturally to keep an infection control practitioner (ICP) busy. Now, it is pandemic flu, avian flu, multi-drug-resistant organisms (MDROs), and pertussis taking precedence in the media.

ICPs are not the only interested parties. Private companies even have a role in outbreak prevention. The American Type Culture Collection (ATCC) is the world’s largest biological resource center, as it holds millions of disease cultures, used by scientists to develop various vaccines for avian flu, for example. The ATCC is currently working with the U.S. military to develop standards for preventing and handling outbreaks.

Jesus Soriano, ATCC’s vice president for licensing, contracts, and compliance, explains, “ATCC distributes biological materials under strict compliance with all regulations pertaining to the acquisition, storage, handling, and distribution of microorganisms and the technical data relating to those biomaterials. ATCC has developed and implemented proprietary procedures and controls for distribution that ensure risk diversion and the fulfillment of licenses per delivered item and per destination.

The organization also enforces a strict hazardous material review process. Further, ATCC distributes biomaterials under a materials transfer agreement (MTA) that must be agreed to by the end user prior to receipt of any biological material, and to which all recipients are contractually bound. The text of the MTA can be found at www.atcc.org/documents/mta/mta.cfm.

“Prior to receiving any biological material, all recipients of ATCC research standards undergo a comprehensive screening and registration process that ensures that institutions ordering our materials have the legal right to do so and have in place appropriate bio-safety programs. While ATCC is not involved in the investigation or mitigation of an infectious disease outbreak, the organization supports, when possible, research related to such an outbreak by making research standards available to the scientific community.”

Maurice Ramirez, DO, is a certified medical review officer; a federal medical officer, through the National Disaster Medical System, Disaster Medical Systems Team, Florida Three; a full-time practicing emergency room physician in Sun City Center, Fla. and Sebring, Fla., and the founder and president of High Alert, an educational corporation specializing in disaster preparedness and rapid decision-making for business and healthcare.

Ramirez presents a case study related to a common MDRO — methicillin-resistant Staphylococcus aureus (MRSA). “The case study I chose is actually a cohort of four,” he reports. “It’s interesting because the mechanism of transmission is still up in the air. A 26- year-old man presented to the emergency room with a red lesion on the front of his pelvis, right above the belt line, on his right side, which is the area known as the anterior superior iliac spine. This area was about silver dollar-sized. It had no abscessed cavity at the time; it had not yet broken open. There have been a number of studies looking at these kinds of lesions, particularly, in the history of, ‘I think I was bitten by a spider.’ Almost invariably, when you hear that history, studies have shown, that is in fact cellulitis, a skin infection, and most commonly, it will be Staphylococcus aureus, whether or not it is multi-resistant.

“This gentleman presented with, ‘I think I was bitten by a spider,’ with a lesion that was not at that time culturable, and of course, it would be presumptively Staphylococcus aureus. He was placed on a course of antibiotics, Bactrim® DS. The outer edge of the area was marked with an indelible marker and he was instructed to come back the following day. By the following day, he had an ulcer in this spot, the red was outside the marked area, and it was now something that could be cultured.

It was quite obviously not fully responding to our choice of antibiotics; he was otherwise still feeling well. The presumption of multi-resistant staphylococcus was made, and a second antibiotic was added, rifampin. The new area of red was marked, and he was instructed to come back the following day; by then, it had not gotten any better but had gotten no worse, and by the third day after the ulcer had formed, he had grown Staphylococcus aureus out of his culture, which was resistant to oxycillin, methicillin, but it was sensitive to Bactrim and rifampin.”

However, Ramirez says, that is typical for community-acquired staphylococcus in that geographic area. Because of that, he says, the diagnosis “wasn’t just a wild guess; it is a scientific assumption. That’s not unusual for staphylococcus, to be partially resistant to single drug therapy, even though it appears to be sensitive. It’s one of the ways doctors get in trouble — they look at the paper, and they say, ‘Look, it should be sensitive,’ not thinking about what the bug does.

“Two days after the culture came back, and he came back for a follow-up and was told about cultures, in comes a young lady, and she has a red ulcerated lesion, which is slightly pussy on her left anterior superior iliac spine. She states that her fiancé, who is a third party, has a similar lesion on his right anterior superior iliac spine, and neither had been treated. So we now have Patient B, the lady, and patient C, another male. Patient A is already on antibiotics. Patients B and C are placed on Bactrim and the lesions are marked, they come back the following day and their lesions are worse. Their cultures are showing Staphylococcus aureus already; they’re placed on rifampin, and then, by the third day, their lesions are stable, and by the fourth day, they’re starting to improve.

“Lo and behold, in comes a fourth, Patient D, a young lady, the wife of patient A. She has a lesion on her left anterior superior iliac spine; it’s red, it’s ulcerated, it’s larger than any of the three previous lesions. She’s put on both therapies — because, of course, we know what her husband has — her lesion stabilizes, and it grows the same thing.”

All four cultures were sent for a genotype to determine genetically if the physicians were dealing with the same bug, to see if the hospital was about to see a mini-outbreak. “They are all identical, from the same culture. As it turns out, the husband/wife pair, A and D, are best man/matron of honor for B and C. And A and D and B and C had gone hot-tubbing together. Now exactly what had transpired to get A’s lesion to end up on B, and B’s lesion on C — was it C or A that provided the lesion to D? — is the area subject to a lot of conjecture, because of course there is significant denial of anything except B and C being together and A and D being together. In either event, we have what are called ‘kissing lesions’ — two people whose lesions are anatomically capable of mating up, that are genetically identical, and passed between known contacts. All were sensitive to the same antibiotics. That’s a mini-outbreak pedigree, fortunately carrying only four patients,” he says.

“There have been case reports of community- acquired Staphylococcus aureus, which is a completely different bug than the multiresistant MRSA that we see in hospitals,” Ramirez explains. “Even though they effectively cause the same symptoms, they are totally genetically different subspecies of the same organism. They infer resistance differently; they are theoretically capable of exchanging resistances between each other, and creating effectively a third subspecies, but that hasn’t happened yet. Any time you place multiple bacteria, particularly with varying levels of resistance — such as placing people with community-acquired MRSA in a hospital environment, where there is already hospital-acquired MRSA by definition — then that possibility exists. As soon as that one patient becomes infected with both strains of the diseases, they will start exchanging genetic material.”

He continues, “Fortunately, we haven’t seen that in any major outbreaks or reports to date, but four years ago, we weren’t seeing any community-acquired MRSA at all. Four years ago, we saw it in the western conference college football, and there were some young men who ended up hospitalized, and one or two who died as a result of the MRSA. Again, this is community-acquired, it’s a new thing for us, and it effectively wipes out the old standby drugs for the ‘gee, it’s red and I think it’s infected on your skin’.”

The staphylococcus is already on the skin of the carrier, and transfers quite easily from person to person, because it grows so well on intact skin, and on that skin, does not cause disease. However, Ramirez adds, “If you get it through intact skin, by abrasion, rubbing or puncture, it’s now a potent bacteria where it doesn’t belong, and that invariably causes problems.”

Simply rubbing skin on skin could cause micro-abrasions and allow the staphylococcus to enter through these very small breaks.

Ramirez is associated with the National Disaster Life Support Educational Consortium™ and the educational foundation, which is a government/private and educational institute joint effort, with courses for both the lay public and healthcare providers, to respond to all hazards related to disaster — hurricanes, terrorism (bio, nuclear or chemical), or pandemic as is concerned with avian flu or the Victoria A strain. “Through the education, which is partly funded by the Department of Homeland Security, we do teach the role of the individual provider and the private healthcare institution in that chain of discovery and reporting — how they integrate both into public health, which for some states is written into law, as well as what kind of surveillance they need to be utilizing,” he explains.

“The big issues for surveillance of infectious disease are really common patterns, and one of the things my company High Alert teaches, both to business and to healthcare, is pattern recognition. Common things are common, and experience builds series of patterns. Since the time you were born, you were born with the ability to recognize voices, faces, comfortable environments, and over time, you develop certain patterns of normal and abnormal. Within a particular profession, within a niche of that profession, you also develop patterns. Hence, in south Florida, when an internal medicine doctor encountered a patient with an unusual pneumonia, he looked at the chest Xray, and because of his experience overseas, he saw a pattern that even the radiologist did not recognize, because it was not in the radiologists’ repertoire of patterns, and the internist said, ‘This is pulmonary anthrax.’ It turned out to be pulmonary anthrax from the American Publishing building, the attack on the National Enquirer. Similarly, in Arlington, Va., a physician at George Washington looked at a chest X-ray of a young postal worker suffering fever, chills, shortness of breath, respiratory distress, and said, ‘This looks like a textbook picture I saw once of pulmonary anthrax.’ These are the kinds of surveillances, when you see something unusual, or when you see clusters of things — even if they’re common, but they’re coming in uncommon numbers — such as our cluster of four staph apparently ‘kissing lesions,’ — if you ignore the relationships, definitely ‘kissing lesions,’ — in a cohort of four within a week. That’s a mini-outbreak.”

Recognizing these abnormal patterns led to the identification of individual outbreaks of anthrax, West Nile, and Hantavirus. “All of these outbreak recognitions occur because individual providers note that something new is in their environment, or that they’re seeing clusters of the same stuff, but a lot more of it and much closer together. That should cause that individual or healthcare group to move to the next step, which is to notify their public health, and the Centers for Disease Control and Prevention (CDC), and say, ‘I think there’s something different here.’ They may be wrong; that’s OK, and that’s one of the things we have to get healthcare providers and particularly institutions past, that it’s OK to give a genuine alarm and have it turn out to be a series of coincidences, as opposed to what happened with the cruise ships two years ago out of Canaveral. With the first set of episodes, (the response was), ‘Oh, it’s just a little diarrhea; it’s not a big deal,’ and it turns out to be Norwalk. By the time the next set of cruise ships docks four days later, it is affecting four ships and everybody on them, and adversely affects the entire industry for a year. There were a lot of politics and business decisions mixed in there, and a lot of business pressures that shouldn’t have been there, that caused that first sentinel cases to be swept aside, but it’s an example of what happens when the system fails to act on what is recognized, or fails to recognize the first warning signs,” Ramirez says.

Gregory Huhn, MD, MPHTM, is associate director for infectious diseases at ACCESS Community Health Network, Chicago, and a consulting physician for the Cook County Bureau of Health, at the John H. Storjer Jr. Hospital. Huhn reports on an outbreak of pertussis, the incidence of which has increased dramatically over the past two decades.

In this outbreak, which occurred at an oil refinery in Illinois and was reported in the CDC’s Morbidity and Mortality Weekly Report, 24 patients were involved. Seventeen of them were directly linked to the oil refinery — either workers or their family members — and seven cases in the community. (The MMWR report can be viewed at www.cdc.gov/mmwr/preview/mmwrhtml/mm5201a1.htm.) “Out of the 24 cases, 21 were actually in adults, older than age 20,” Huhn adds. “It is unusual to identify an outbreak (of pertussis) primarily in adults. Before the mid-1990s, primarily pertussis was recognized in infant and toddler populations, and now we’ve had quite a dramatic shift in the epidemiology, with two-thirds of cases identified in adolescents and adults.”

There are several reasons why the disease epidemiology is changing; first of all, Huhn reports, “In 1995, the case definition changed for the laboratory identification of pertussis, that incorporated polymerase chain reaction (PCR). It’s a very sensitive and specific test, which is somewhat easier to obtain with specimen collection with a Dacron swab from the nasopharynx, and it’s actually a 48-hour turnaround, at least in the Illinois Department of Public Health, so with the faster turnaround, much easier to identify than growth by bacterial culture. Therefore, with the change in the case definition — also greater awareness of pertussis in these older populations of adolescents and adults — and probably a true increase in actually circulating infection, those are the responsible factors for the increase in reported cases.”

Waning immunity does contribute as well. However, it is not responsible for all of the new cases. Although it is recommended that children receive a series of five shots to vaccinate against pertussis, the last shot is given between ages 5 and 7, and immunity wanes within five to 10 years after that last shot.

“Until this year, we have not targeted these older populations for effective vaccination, and now, these adolescents and adults do represent the reservoir pool for circulating pertussis, and serve as a source for transmission to vulnerable infants, who bear the vast burden of morbidity and mortality. In order to curb these rising numbers, broad-based vaccination for adolescents and adults is necessary in order to make an impact to reduce this reservoir pool, and then to reduce transmission to vulnerable infants,” Huhn explains.

“CDC through the Advisory Committee on Immunization Practices (ACIP) has made recommendations, on June 30, 2005, for adolescents, and October 26, 2005, for adults, that they should receive at least one booster vaccine. We would have waning immunity even with those booster vaccines, probably over a five to ten year period, so it’s reasonable to assume that in order to eliminate that circulating pool of pertussis in those older populations, that they would have to be revaccinated, likely every ten years.”

There is now an adult booster tetanus/diphtheria toxoids vaccine that incorporates the acellular pertussis vaccine as well; it is recommended that adults receive this booster every ten years. The recommendations for adolescents can be viewed at www.cdc.gov/nip/vaccine/tdap/tdap_child_recs.pdf, and the recommendations for adults at www.cdc.gov/nip/vaccine/tdap/tdap_adult_recs.pdf.

Pertussis incidence has increased shockingly since 1980, when the number of cases throughout the United States numbered 1,730. The incidence in 2004 reached 25,827 cases. “This rise in pertussis has occurred in certain areas, particularly in Massachusetts, where they have enhanced pertussis surveillance, and they use a serologic test for diagnosis. Then there was an outbreak in Wisconsin last year that accounted for a good proportion of these cases. Here in Illinois, we’ve had the highest numbers also reported since 1959, a 45-year high, and I believe our numbers were 1,535. It’s not a disease focused on urban populations. It can happen in any communities where there are schools, day care centers — so really, it can happen across the board whether it’s urban or rural,” says Huhn.

The disease is spread via droplets and is highly contagious, he adds — there is a documented secondary case attack rate of 80 percent. “Within the close contact of a person with an active illness, with paroxysms of cough, 80 percent surrounding that source may be infected. If you’re in a confined space greater than one hour, CDC would consider that a close contact, so in day care settings, classroom settings, we actually do see quite a few cases. Once a person has been identified with a prolonged cough illness, usually over a two-week period, others around them, if they are not immune, and particularly those in that adolescent age group, which does have waning immunity, are certainly at risk for infection.”

Because its early symptoms often mimic those of an upper respiratory infection or viral infection, pertussis can often go undiagnosed until well into its later stages. The “classic” symptoms include paroxysms of coughing, often accompanied by a “whooping” sound, then post-tussive vomiting.

“For a disease for which universal childhood vaccination is recommended, it is the only disease in the past 20 to 25 years that is actually rising in numbers. It is truly a regrettable consequence for a disease that is preventable, that we still have infant deaths from this disease,” Huhn concludes.