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Sixteen people — including one who died — acquired hepatitis C virus at three different clinics in Maryland after being injected with a contaminated radionuclide solution used in cardiac imaging, an epidemiologist reported recently in Los Angeles at the annual meeting of the Society for Healthcare Epidemiology of America (SHEA).

SHEA Conference: HCV outbreak linked to nuclear cardiac imaging

SHEA Conference

HCV outbreak linked to nuclear cardiac imaging

Lot prepared at pharmacy infects 16 people

Sixteen people — including one who died — acquired hepatitis C virus at three different clinics in Maryland after being injected with a contaminated radionuclide solution used in cardiac imaging, an epidemiologist reported recently in Los Angeles at the annual meeting of the Society for Healthcare Epidemiology of America (SHEA).

"The potential for blood contamination of sterile radio pharmaceuticals within pharmacies has not been previously recognized," said Kirsten Larson, MPH, an epidemiologist with the Maryland Department of Health and Mental Hygiene in Baltimore. "Cross-contamination likely resulted from blood processing equipment reused during radionuclide preparation at the pharmacy."

The case was certainly not that cut and dry, however, because no blood products are used in radionuclide cardiac imaging. Saline from multidose vials also was implicated but may have been a red herring. The outbreak initially was discovered, in part, because the spouses of two of the first patients knew each other. The patients had visited the same cardiac imaging clinic on Oct. 15, 2004, then subsequently had symptomatic onset of hepatitis.

"Both men were symptomatic with onset of jaundice on Nov. 7, 2004," Larson said. "Both had elevated liver function tests and positive anti-HCV [test results]. Neither had any identifiable traditional risk factors for HCV."

Tracer used to assess heart

Cardiac nuclear imaging studies are common diagnostic tests in outpatient clinics and hospitals. The procedure is used to assess myocardial perfusion at rest and under stress, Larson explained at SHEA.

The procedure involves the use of an injectable radionuclide tracer. The tracer has a short half-life, so it typically is used within hours of preparation at a pharmacy. The first thought, however, was that the contamination could have occurred at the clinic where the two men were patients.

"We conducted an on-site [clinic] visit and obtained a patient list for the 15th of October," Larson continued. "We also conducted additional case finding through active surveillance and reports from physicians and laboratories. Patients and employees were tested for anti-HCV and HCV RNA. We also reviewed procedures as well as possible activities for HCV transmission including injections of the radio label tracer and saline," she said.

A total of nine patients had undergone cardiac nuclear imaging studies on the date in question. Of those nine, eight — including the two index cases — had symptoms and laboratory evidence of HCV infection. No additional cases of HCV were identified among patients who underwent imaging studies on the dates preceding and following Oct. 15.

Four clinic employees were tested for HCV and were negative. Of the eight cases of HCV from Oct. 15, all received saline flushes, which were drawn up individually from a common bag of saline. That breach could explain at least some of the transmission, but later findings would point straight back to the pharmacy where the nuclear medicine was prepared.

"No other risk factors were common among the eight, except that all eight had received a resting dose of a radio label tracer from the same lot, Lot X,’ Larson said. "Interestingly enough, the ninth patient, who did not develop HCV infection, received a resting dose of a radio label tracer from a different lot."

Recipe for infection

The investigation turned toward the pharmacy, and that is where things got really interesting during a number of site visits before the facility shut down.

"Though there were a number of safeguards in place to prevent employee and customer exposure to radioactivity, the safeguards for potential bloodborne pathogen exposures were not as evident," Larson said. "Syringes were heavily used in preparation, and many of the products were bought in bulk, unwrapped, and placed in cups and containers on counter tops throughout the pharmacy. Needlesticks were not well reported."

Of 24 pharmacy employees tested for HCV, 23 were negative and one had evidence of past infection with a different strain of the virus. That rules out a carrier as the source, so the investigators again looked at the preparation process. It wasn’t pretty.

"Work areas were poorly defined, and that may have been important," Larson said. "The containers used to transport the radio label doses to clinics and return the empty syringes to the pharmacy were not cleaned for potential bloodborne pathogen contamination."

Due to the large volume of orders, some 300 doses of radionuclide were being prepared daily. The process involves combining a powder with saline and a radio isotope. The mixture is cooked for 10 minutes and then additional saline is added before it is packaged into individual doses and distributed in syringes to clinics and hospitals.

Lot X was the first lot prepared on Oct. 15 at about 1 a.m. in the morning. Sixteen individual doses were prepared from the lot and were distributed to three separate cardiology clinics. The attack rate was extremely efficient, with 100% (16) of the patients who received Lot X acquiring acute hepatitis C infection.

"No people who received doses from other lots had acute HCV infection, and no pharmacy employees had evidence of active HCV infection either," Larson said. "No other associated cases were identified through statewide surveillance.

So what happened? "Importantly, we discovered that the pharmacy also radio labeled other products," she said, highlighting a breakthrough in the investigation. "One product prepared by the pharmacy involved the radio labeling of white blood cells [to] assist in the diagnosis of occult infections."

The white blood cell work was done about 12 hours prior to assembly of the contaminated lot, suggesting some of blood got into the radio tracing solution. Indeed, the source of the blood was identified as having chronic HCV infection with the matching A genotype.

Though the ultimate source for the HCV-infected blood was determined, the mechanism of contamination of the radio tracer is not completely clear. There were multiple opportunities for contamination, but the most likely answer may be that syringes containing the blood product were inadvertently used in assembling the radio tracer product.

"The same size syringes were used in the blood labeling and radionuclide preparation," Larson said. "Based on the way syringes are distributed throughout the pharmacy, it would be very difficult to distinguish a used syringe and needle from an unused one. This is an entirely possible — maybe even likely — scenario for this contamination.

Other aspects of pharmacy work may have been important as well. Saline-based vials used in a number of pharmacy products were repeatedly accessed and not discarded between preparations. Also there was some overlap in the work areas where the white blood cell radio labeling and radio nucleotide preparation was done, which could have facilitated cross-contamination."

Based on the outbreak, public health investigators recommended three actions:

  1. Any medical procedures involving injectable products should be considered as a potential risk for hepatitis C virus.
  2. Pharmacies handling blood products should maintain absolute separation of blood from other products.
  3. Pharmacies that handle blood should be regulated to ensure proper infection control procedures are followed.