OUTBREAK INVESTIGATION

February 1, 2006

OUTBREAK INVESTIGATION

OUTBREAK INVESTIGATION
An ICPs Worst Nightmare

By Kathy Dix

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

ICPs are not the only interested parties. Private companies even have a role in outbreak prevention. TheAmerican Type Culture Collection (ATCC) is the worlds largest biologicalresource center, as it holds millions of disease cultures, used by scientists todevelop various vaccines for avian flu, for example. The ATCC is currentlyworking with the U.S. military to develop standards for preventing and handlingoutbreaks.

Jesus Soriano, ATCCs vice president for licensing,contracts, and compliance, explains, ATCC distributes biological materialsunder strict compliance with all regulations pertaining to the acquisition,storage, handling, and distribution of microorganisms and the technical datarelating to those biomaterials. ATCC has developed and implemented proprietaryprocedures and controls for distribution that ensure risk diversion and thefulfillment of licenses per delivered item and per destination.

The organization also enforces a strict hazardous materialreview process. Further, ATCC distributes biomaterials under a materialstransfer agreement (MTA) that must be agreed to by the end user prior to receiptof 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 recipientsof ATCC research standards undergo a comprehensive screening and registrationprocess that ensures that institutions ordering our materials have the legalright to do so and have in place appropriate bio-safety programs. While ATCC is not involved in the investigation or mitigationof an infectious disease outbreak, the organization supports, when possible,research related to such an outbreak by making research standards available tothe scientific community.

Multidrug-resistant Organisms

Maurice Ramirez, DO, is a certified medical review officer; afederal medical officer, through the National Disaster Medical System, DisasterMedical Systems Team, Florida Three; a full-time practicing emergency room physician in Sun CityCenter, Fla. and Sebring, Fla., and the founder and president of High Alert, aneducational corporation specializing in disaster preparedness and rapiddecision-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. Itsinteresting 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 ofhis pelvis, right above the belt line, on his right side, which is the areaknown as the anterior superior iliac spine. This area was about silverdollar-sized. It had no abscessed cavity at the time; it had not yet brokenopen. 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. Almostinvariably, when you hear that history, studies have shown, that is in factcellulitis, a skin infection, and most commonly, it will be Staphylococcusaureus, whether or not it is multi-resistant.

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

It was quite obviously not fully responding to our choice ofantibiotics; he was otherwise still feeling well. The presumption ofmulti-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 thefollowing 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 Staphylococcusaureus out of his culture, which was resistant tooxycillin, methicillin, but it was sensitive to Bactrim and rifampin.

However, Ramirez says, that is typical for community-acquiredstaphylococcus in that geographic area. Because of that, he says, the diagnosiswasnt just a wild guess; it is a scientific assumption. Thats notunusual for staphylococcus, to be partially resistant to single drug therapy,even though it appears to be sensitive. Its one of the ways doctors get introuble they look at the paper, and they say, Look, it should besensitive, not thinking about what the bug does.

Two days after the culture came back, and he came back fora follow-up and was told about cultures, in comes a young lady, and she has ared ulcerated lesion, which is slightly pussy on her left anterior superioriliac spine. She states that her fiancé, who is a third party, has a similarlesion 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 isalready on antibiotics. Patients B and C are placed on Bactrim and the lesionsare marked, they come back the following day and their lesions are worse. Theircultures are showing Staphylococcus aureus already; theyre placed on rifampin, and then, by the third day,their lesions are stable, and by the fourth day, theyre 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 iliacspine; its red, its ulcerated, its larger than any of thethree previous lesions. Shes put on both therapies because, of course, weknow what her husband has her lesion stabilizes, and it grows the samething.

All four cultures were sent for a genotype to determinegenetically if the physicians were dealing with the same bug, to see if thehospital was about to see a mini-outbreak. They are all identical, from thesame culture. As it turns out, the husband/wife pair, A and D, are bestman/matron of honor for B and C. And A and D and B and C had gone hot-tubbingtogether. Now exactly what had transpired to get As lesion to end up on B,and Bs lesion on C was it C or A that provided the lesion to D? isthe area subject to a lot of conjecture, because of course there is significant denial of anythingexcept B and C being together and A and D being together. In either event, wehave what are called kissing lesions two people whose lesions areanatomically capable of mating up, that are genetically identical, and passedbetween known contacts. All were sensitive to the same antibiotics. Thats amini-outbreak pedigree, fortunately carrying only four patients, he says.

There have been case reports of community- acquired Staphylococcusaureus, which is a completely different bug than themultiresistant MRSA that we see in hospitals, Ramirez explains. Even though they effectively cause thesame symptoms, they are totally genetically different subspecies of the sameorganism. They infer resistance differently; they are theoretically capable of exchanging resistancesbetween each other, and creating effectively a third subspecies, but that hasnthappened yet. Any time you place multiple bacteria, particularly with varyinglevels of resistance such as placing people with community-acquired MRSA ina hospital environment, where there is already hospital-acquired MRSA bydefinition then that possibility exists. As soon as that one patient becomesinfected with both strains of the diseases, they will start exchanging geneticmaterial.

He continues, Fortunately, we havent seen that in anymajor outbreaks or reports to date, but four years ago, we werent seeing anycommunity-acquired MRSA at all. Four years ago, we saw it in the westernconference college football, and there were some young men who ended uphospitalized, and one or two who died as a result of the MRSA. Again, this iscommunity-acquired, its a new thing for us, and it effectively wipes out theold standby drugs for the gee, its red and I think its infected on yourskin.

The staphylococcus is already on the skin of the carrier, andtransfers quite easily from person to person, because it grows so well on intactskin, and on that skin, does not cause disease. However, Ramirez adds, If youget it through intact skin, by abrasion, rubbing or puncture, its now apotent bacteria where it doesnt belong, and that invariably causes problems.

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

Ramirez is associated with the National Disaster Life SupportEducational Consortium and the educational foundation, which is agovernment/private and educational institute joint effort, with courses for boththe lay public and healthcare providers, to respond to all hazards related todisaster hurricanes, terrorism (bio, nuclear or chemical), or pandemic as isconcerned with avian flu or the Victoria A strain. Through the education,which is partly funded by the Department of Homeland Security, we do teach therole of the individual provider and the private healthcare institution in thatchain 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 surveillancethey need to be utilizing, he explains.

The big issues for surveillance of infectious disease arereally common patterns, and one of the things my company High Alert teaches,both to business and to healthcare, is pattern recognition. Common things arecommon, and experience builds series of patterns. Since the time you were born,you were born with the ability to recognize voices, faces, comfortableenvironments, and over time, you develop certain patterns of normal andabnormal. Within a particular profession, within a niche of thatprofession, you also develop patterns. Hence, in south Florida, when an internal medicine doctorencountered a patient with an unusual pneumonia, he looked at the chest Xray,and because of his experience overseas, he saw a pattern that even theradiologist did not recognize, because it was not in the radiologistsrepertoire of patterns, and the internist said, This is pulmonary anthrax.It turned out to be pulmonary anthrax from the American Publishing building, theattack on the National Enquirer. Similarly, in Arlington, Va., a physician atGeorge Washington looked at a chest X-ray of a young postal worker sufferingfever, chills, shortness of breath, respiratory distress, and said, Thislooks like a textbook picture I saw once of pulmonary anthrax. These are thekinds of surveillances, when you see something unusual, or when you see clustersof things even if theyre common, but theyre coming in uncommon numbers such as our cluster of four staph apparently kissing lesions, ifyou ignore the relationships, definitely kissing lesions, in a cohortof four within a week. Thats a mini-outbreak.

Recognizing these abnormal patterns led to the identificationof individual outbreaks of anthrax, West Nile, and Hantavirus. All of theseoutbreak recognitions occur because individual providers note that something newis in their environment, or that theyre seeing clusters of the same stuff,but a lot more of it and much closer together. That should cause that individualor healthcare group to move to the next step, which is to notify their publichealth, and the Centers for Disease Control and Prevention (CDC), and say, Ithink theres something different here. They may be wrong; thats OK, andthats one of the things we have to get healthcare providers and particularlyinstitutions past, that its OK to give a genuine alarm and have it turn outto be a series of coincidences, as opposed to what happened with the cruiseships two years ago out of Canaveral. With the first set of episodes, (theresponse was), Oh, its just a little diarrhea; its not a big deal,and it turns out to be Norwalk. By the time the next set of cruise ships docksfour days later, it is affecting four ships and everybody on them, and adverselyaffects the entire industry for a year. There were a lot of politics andbusiness decisions mixed in there, and a lot of business pressures that shouldnthave been there, that caused that first sentinel cases to be swept aside, but itsan example of what happens when the system fails to act on what is recognized,or fails to recognize the first warning signs, Ramirez says.

Pertusiss: A Growing Concern

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

In this outbreak, which occurred at an oil refinery inIllinois and was reported in the CDCs Morbidity and Mortality Weekly Report,24 patients were involved. Seventeen of them were directly linked to the oilrefinery either workers or their family members and seven cases in thecommunity. (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 (ofpertussis) primarily in adults. Before the mid-1990s, primarily pertussis wasrecognized in infant and toddler populations, and now weve had quite adramatic shift in the epidemiology, with two-thirds of cases identified inadolescents and adults.

There are several reasons why the disease epidemiology ischanging; first of all, Huhn reports, In 1995, the case definition changedfor the laboratory identification of pertussis, that incorporated polymerasechain reaction (PCR). Its a very sensitive and specific test, which issomewhat easier to obtain with specimen collection with a Dacron swab from thenasopharynx, and its actually a 48-hour turnaround, at least in the IllinoisDepartment of Public Health, so with the faster turnaround, much easier toidentify than growth by bacterial culture. Therefore, with the change in thecase definition also greater awareness of pertussis in these olderpopulations of adolescents and adults and probably a true increase inactually circulating infection, those are the responsible factors for theincrease 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 tovaccinate against pertussis, the last shot is given between ages 5 and 7, andimmunity wanes within five to 10 years after that last shot.

Until this year, we have not targeted these olderpopulations for effective vaccination, and now, these adolescents and adults dorepresent the reservoir pool for circulating pertussis, and serve as a sourcefor transmission to vulnerable infants, who bear the vast burden of morbidityand mortality. In order to curb these rising numbers, broad-based vaccinationfor adolescents and adults is necessary in order to make an impact to reducethis reservoir pool, and then to reduce transmission to vulnerable infants,Huhn explains.

CDC through the Advisory Committee on ImmunizationPractices (ACIP) has made recommendations, on June 30, 2005, for adolescents,and October 26, 2005, for adults, that they should receive at least one boostervaccine. We would have waning immunity even with those booster vaccines,probably over a five to ten year period, so its reasonable to assume that inorder to eliminate that circulating pool of pertussis in those olderpopulations, that they would have to be revaccinated, likely every ten years.

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

Pertussis incidence has increased shockingly since 1980, whenthe number of cases throughout the United States numbered 1,730. The incidencein 2004 reached 25,827 cases. This rise in pertussis has occurred in certainareas, particularly in Massachusetts, where they have enhanced pertussissurveillance, and they use a serologic test for diagnosis. Then there was an outbreak in Wisconsin last year thataccounted for a good proportion of these cases. Here in Illinois, weve hadthe highest numbers also reported since 1959, a 45-year high, and I believe ournumbers were 1,535. Its not a disease focused on urban populations. It can happen in any communities where there are schools, daycare centers so really, it can happen across the board whether its urbanor 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. Withinthe close contact of a person with an active illness, with paroxysms of cough,80 percent surrounding that source may be infected. If youre in a confinedspace greater than one hour, CDC would consider that a close contact, so in daycare settings, classroom settings, we actually do see quite a few cases. Once aperson has been identified with a prolonged cough illness, usually over atwo-week period, others around them, if they are not immune, and particularlythose in that adolescent age group, which does have waning immunity, arecertainly at risk for infection.

Because its early symptoms often mimic those of an upperrespiratory infection or viral infection, pertussis can often go undiagnoseduntil well into its later stages. The classic symptoms include paroxysms of coughing, often accompanied by awhooping sound, then post-tussive vomiting.

For a disease for which universal childhood vaccination isrecommended, it is the only disease in the past 20 to 25 years that is actuallyrising in numbers. It is truly a regrettable consequence for a disease that ispreventable, that we still have infant deaths from this disease, Huhn concludes.