ATSDR Investigates Disease Cluster Mystery in Pennsylvania

Several residents of a rural community contract a rare disease, and no one knows why. Is it hereditary? Could it be caused by something in the water or the air? Local citizens become more uneasy as doctors diagnose other community members with the same illness.

Even though these events sound like the plot for a medical mystery, they actually happened in northeastern Pennsylvania in 2004.  Residents of Carbon, Luzerne, and Schuylkill Counties learned that several of their neighbors had been diagnosed with polycythemia vera (PV), a rare blood disease with no known cause or cure.  Even more concerning, four of these residents lived along the same rural road.  Two of them were husband and wife. “That was the stunner,” said Lora Siegmann Werner, regional representative for the Agency for Toxic Substances and Disease Registry (ATSDR) in Pennsylvania.

In PV, bone marrow cannot stop producing red blood cells. These extra cells are normal, but they thicken the blood, causing clots, heart attacks, and strokes. Although PV is now considered a type of cancer, it did not become reportable to state cancer registries until 2001. PV is also difficult to diagnose because many other conditions can produce similar symptoms and can increase the number of red blood cells. 

PV is rare. The National Cancer Institute estimates that it occurs in only one of 100,000 people yearly.  So when residents of the tri-county area learned that a number of their neighbors had been diagnosed with the disease, they went to the Pennsylvania Department of Health (PADOH) to ask for help.  They wanted to find out if the cancer rate, particularly for PV, was higher in their counties than in the rest of Pennsylvania.

PADOH searched the state cancer registry first for total cancer cases in the region from 1996 to 2002, and then a second time for cases from 2003-2004. They compared these numbers to the overall number of cases found elsewhere in the state.
The PADOH team issued its first report in December 2005. They found that the number of cancer cases in the tri-county area was similar to numbers elsewhere in the state.  However, the number of PV cases reported to the state from Luzerne County from 2001-2004 was 4 times the rate in the rest of Pennsylvania and from Schuylkill County, 3 times the rate. In late 2006, PADOH met with the community and acknowledged a “disease cluster“  in the region.

Residents of the region were not satisfied with this label. They wanted to understand why the disease was so widespread in their communities and if others were in danger of contracting it. They suspected an environmental cause.
For many years, Carbon, Luzerne, and Schuylkill Counties were home to mining, manufacturing, and recycling industries. In 1983, the U.S. Environmental Protection Agency (EPA) began identifying toxic industrial sites in these counties and cleaning up soil and groundwater contamination.

Even so, area residents were still concerned about possible remaining contaminants. They also worried about 7 local waste coal power plants and the coal fly ash the plants dump into abandoned mines.  Community leader Joseph Murphy, already disturbed by the number of disease cases occurring locally, led the grass roots movement seeking possible connections between the environment and PV.

PADOH requested support from ATSDR for further evaluation of the disease cluster. The agency agreed and   assembled a team of scientists to begin a new phase of the investigation. They faced an enormous challenge. Investigations of disease clusters are complex and rarely do they prove a direct link between a contaminant and a specific disease, especially when the cause of the disease is unknown.

“If the disease had an environmental trigger or link,” said team leader Dr. Vincent Seaman, “the exposure would have occurred 15 to 20 years earlier, based on the amount of time experts believe it takes for PV to surface.”  If so, he added, the question now was, “Is this still happening?  Are people in the community currently in danger of exposure?” 

First, Seaman contacted Dr. Ronald Hoffman, a renowned PV researcher now at New York City’s Mt. Sinai Hospital.  Hoffman welcomed the opportunity to partner with ATSDR to evaluate the disease. He told Seaman about a scientific breakthrough that could help identify people who had it.  In 2004, scientists had discovered a gene mutation, known as JAK2, which occurs in about 95% of all PV patients and can be detected by a blood test. The team could use this new tool to help identify and confirm PV cases in the tri-county area.

From 2006 through 2007, the PV investigation team traveled to Pennsylvania many times to visit individual members of the community and hold meetings to keep residents informed about the progress of the investigation.  “Having a good relationship with the community is paramount. You have to have more than just facts,” said Seaman, whom Werner called, “an amazing communicator.”

During their investigation, the team reviewed medical records, administered JAK2 blood tests, and interviewed patients.  In all, 33 cases of PV were confirmed. Fifteen of the cases were located where Carbon, Luzerne, and Schuylkill Counties meet, now called the Tamaqua cluster. There the disease was 4 times more common than in the rest of the tri-county area.  However, interviews revealed no common residence locations, lifestyles, or employment among the patients, so investigators could not make a connection between PV and the environment.

Community members were disappointed that the investigation did not uncover this link. But Seaman told them, “We have to have evidence and facts to support conclusions.”  The residents were not ready to give up.  “This was a core group of very committed residents and local physicians that advocated for more investigation,” said Werner. “These community members were willing to work with the agency and put their faith in the scientific process.”

Murphy praises the ATSDR team, calling them “fair” and “up front.” He adds, “I think that Vince and Lora typify the mission statement of ATSDR. The investigation could not have come about if the agency didn’t have a good group on the ground—level heads and good minds. They wanted to get to the truth and find the answers.”

At Seaman’s suggestion, in 2008, ATSDR and PADOH called a meeting of experts in Philadelphia. Medical, environmental, and public health specialists reviewed findings of ATSDR’s 2007 investigation and evaluated research needs.  As a result of support from then Senator Arlen Specter, Congress gave ATSDR special appropriations totaling $8 million over the next two years. These appropriations funded more than 15 research projects that will help scientists better understand the Tamaqua cluster and PV. One of those projects was a second round of JAK2 screening conducted by ATSDR in 2009.  Unlike most screenings, this one, coordinated by research scientist Dr. Ken Orloff, was open to anyone in the study area.  Team member and medical officer Dr. Bruce Tierney explained, “JAK2 testing is expensive and is not routine.  People in rural areas with limited healthcare ordinarily would not have the opportunity to be tested.” Team members, residents, and PADOH registered nurse Barbara Allerton and epidemiologist Kim Warren worked tirelessly to publicize the screenings, find locations, recruit participants, and conduct the testing.

In all, 1170 people were tested, the largest number tested in an exposure investigation to date.  Results included 5 known PV cases and 14 more people who had the JAK2 mutation. Two other projects are aimed at determining the rate of the mutation in the general population so that researchers can put the screening results into context. So far the research projects have not linked PV to any environmental or other cause.

Both Werner and Murphy acknowledge the powerful results of the alliance of concerned citizens, ATSDR investigators, research partners, and Congressional support and the timing that brought them together.  As a result of their collaboration, PV research is moving further than it has ever gone before.  Seaman said, “It was extremely rewarding to do the work. We felt like we were challenged in every area.”  Orloff added, “I really believe this is one of the best things ATSDR has done.”