Congress’s creation of federal agencies is clearly a huge achievement, and they’ve also periodically given new powers to already existing agencies. For instance, Mark Pendergrast tells the story of the Dalkon Shield, an IUD that turned out to cause infections while failing to prevent pregnancy in many of the women who used it; at least 17 pregnant women died with IUDs in their uteruses. The manufacturer, facing lawsuits, eventually took the product off the market, but the episode demonstrated the need to prevent similar problems in the future. Congress responded by passing the Medical Devices Amendment Act, which mandates that medical devices receive FDA approval before being marketed.

Agencies also rely on Congress for their annual appropriations, and public health isn’t often the top Congressional priority when it comes to dividing a limited pool of revenue. There are times when Congress responds to a growing health threat by giving an agency more money to address the problem; for instance, after several outbreaks of food-borne illnesses, Congress gave FDA’s FY 2010 budget a large increase to help it hire more food inspectors. It seems like more often, though, Congress makes funding decisions that run counter to the advice of public health professionals.

Of course, those of us in the public health field would like to see much larger amounts of money overall going to preventing death and disease – as Karen Starko pointed out in her post last week, public-health efforts bring enormous benefits, but are miserably underfunded compared to other areas. Then there are the problems with Congressional priorities, which can be shaped more by current news coverage or a small-but-vocal group of constituents than by a broad understanding of our nation’s health challenges. Inside the Outbreaks includes a few examples of this, including post-9/11 Congressional decisions to increase appropriations for bioterror while cutting other health-related budget items.

In addition to Congress and CDC having different ideas about the relative importance of different public health priorities, there can also be times when members of Congress flat out oppose a CDC effort to tackle a particular public health problem and eliminate funding for that area altogether. Mark Pendergrast gives this example in Chapter 18:

In November 1994, conservative Republicans had won both houses of the U. S. Congress, which spelled trouble for the CDC National Center for Injury Prevention and Control, where EIS alums Mark Rosenberg and Jim Mercy continued to study the impact of firearms. As their EIS officer for the incoming class of 1995, they recruited Etienne Krug, a 34-year-old Belgian.

“I grew up in Europe,” Krug said, “where firearms are not available at all. They are considered very unsafe to have in your home.” So he decided to compare the rate of firearms deaths in the United States with other developed countries. The results showed children under the age of 15 were twelve times more likely to be killed with a gun in the United States than in the other countries’ combined average rates. Krug’s study also pointed out that while the overall annual death rate for children in the United States had declined substantially since 1950, the child homicide rate had tripled.

When the MMWR published his findings in February 1997, Krug was interviewed on international TV and radio, resulting in an anonymous death threat. The Republican Congress had just passed a bill eliminating the $2.6 million Division of Violence Prevention budget for firearms research and ordering the CDC never to advocate gun control. Thus, when pressed by reporters about whether tougher laws should be passed, Krug answered, “That is up to legislators to determine based on the data.” The Congressional ban on CDC gun control advocacy remains in place.

This is troubling. If scientists think that Congress will eliminate research efforts that yield results Congress dislikes, they’re likely to steer clear of investigations that might draw Congressional ire, even if that research could save many lives. This was also something that my colleagues and I found in our Scientists in Government research, when we interviewed scientists from federal agencies to identify policies and practices that could be improved in order to strengthen federal science. In particular, several scientists from the National Institute for Occupational Safety and Health (which is part of CDC) told us that the 104th Congress’s threat to eliminate NIOSH still informs agency decisions about research topics, and that new initiatives have been “noticeably in non-controversial areas.”

Congress has a responsibility to exercise oversight over the agencies it has created, but its micro-managing has the potential to impede agencies in their work to carry out their Congressionally mandated missions – which in CDC’s case is “Collaborating to create the expertise, information, and tools that people and communities need to protect their health – through health promotion, prevention of disease, injury and disability, and preparedness for new health threats.” There will be times when the tools and information communities need to protect their health do not sit well with a group of voters, and Congressional (or presidential) pandering to those voters will impede disease prevention.

Inside the Outbreaks‘ description of CDC’s work on HIV/AIDS illustrates just how much is at stake when lawmakers, executives, and agencies themselves let political considerations interfere with research and prevention efforts. I knew the US had been too slow to respond to AIDS, but reading about multiple instances when EIS officers recommended specific actions but authorities declined to act was depressing. As early as 1982, EIS officer Jim Curran’s was recommending that blood donations from high-risk groups be deferred – and his advice wasn’t being heeded. Because of how AIDS is spread (sexual contact, injection drug use) and because it initially affected marginalized populations, many people were reluctant to discuss or investigate it, and then resisted the kinds of prevention efforts (condom distribution, needle exchanges, etc) that could best prevent its spread.

Aside from reminding Congress (and the White House) just how many lives are at stake from public health problems it would rather not acknowledge, what are good ways to ensure that Congressional actions towards health-related federal agencies don’t hinder agencies in fulfilling their Congressionally mandated missions?

Although Karen’s and subsequent CDC studies clearly demonstrated that giving children aspirin caused the vast majority of Reye syndrome cases, the CDC has no regulatory power. The FDA gave in to pressure from the aspirin industry and delayed a warning label on children’s medicine containing aspirin for five years, during which nearly 300 more children died of Reye syndrome in the United States.

He follows up the Reye’s Syndrome story by asking “Should the CDC have regulatory power?” In considering that question, it’s instructive to look at some of the many episodes in the book where EIS officers either were or weren’t able to use their discoveries about the source of disease outbreaks to get necessary large-scale changes made.

Because there’s such a range of causes of disease outbreaks, I’m going to confine my comments today to food. Food-borne diseases were a constant thread running through the book, and the EIS officers were usually able to identify a source, like a producer or food preparer failing to take proper sanitary precautions or a production facility being contaminated with bacteria. In many cases, an EIS officer to pinpoint a cause that was simple to fix – a food handler putting potato salad in containers that had held raw chicken, for instance. In other cases, as with an entire shipment of toxin-laden smoked whitefish or contaminated canned mushrooms from China, the FDA was able to issue a recall or ban importation. Our overall food safety system would be stronger if we devoted more resources to inspections and surveillance, but my impression when I finished the book was that a lack of regulatory authority isn’t the problem in these situations.

In terms of preventing food-borne illnesses, CDC findings on eggs that were described in the book also seemed to translate into policy with relative ease. After a string of mid-1960s salmonellosis cases being traced to products containing eggs, Philip Brachman, head of the Salmonella Surveillance Unit, sent recommendations to state health departments. Following his recommendations, FDA “passed regulations requiring that eggs be inspected (and diverted for pasteurization if cracked), then graded and sanitized on the outside.” This policy was based on the knowledge that cracked or soiled eggs could be contaminated with Salmonella-containing chicken feces. In the late 1980s, a multi-state outbreak of Salmonella eteritidis from products from a Rotanelli Foods plant sent EIS officer Mike St. Louis on the Salmonella trail:

EIS officers had made the egg-Salmonella link 25 years before, but past outbreaks had been traced to fecal contamination of cracked or soiled eggs. The modern Rotanelli plant had purchased unblemished large white eggs and then disinfected their exteriors. St. Louis buried himself in poultry research and found a 1944 article in the British Medical Journal stating that S. enteritidis could persist in the ovaries of chickens. Could the hens actually be depositing bacteria inside the intact eggs they laid? He published the suggestion in the Journal of the American Medical Association, raising a storm of protest from the egg industry.

Illinois-based EIS officer Sue Trock incubated whole eggs from an implicated farm, washed and flame-sterilized them, then cracked and cultured them. She found an abundance of S. enteritidis. Until then, eggs had been considered perfectly packaged natural products requiring no refrigeration. Illinois was the first state to demand chilled eggs (to prevent bacterial proliferation), even in transport, and the FDA soon followed suit.

Food on cruise ships is another recurring agent of disease outbreaks. Here’s how EIS officers went about tackling that:

In October 1973, 16 recently returned passengers from the S/S Statendam, operated by Holland-American Cruises, had experienced diarrheal illness due to Salmonella bareilly or S. senftenberg, both relatively rare serotypes. On December 19, 1973, the Statendam sailed on a nine-day Caribbean Christmas cruise, during which 55 of the 750 passengers complained of diarrhea. For the next five cruises, a CDC team, including EIS officers Mike Merson and Dale Lawrence, distributed a diarrhea questionnaire to all passengers. On each cruise, between six and ten percent reported a diarrheal illness. Swabs from crew members revealed ten salmonella varieties. Many of the afflicted crew worked in the ship’s galley.

Food preparation methods were alarming. Raw and cooked poultry were cut on the same butcher block with the same knives. Food handlers rarely washed their hands. Food was left at room temperature for two or three hours for breakfast and lunch buffets, then returned to the refrigerator. Leftovers were reworked and set out again for a midnight buffet. Once the problems were addressed, the number of Salmonella isolates declined, but on the eighth monitored cruise, there were still two senftenberg rectal isolates, and nine percent of the passengers reported illness.

EIS officers boarded nine other cruise ships at random during January and February 1974, administering questionnaires. The diarrhea rate ranged from 1.9 percent to 10.2 percent of the passengers, averaging 5.7 percent — not much different from the Statendam‘s record.

“We recommended that shipboard disease data be made public to put pressure on the cruise companies,” Merson recalled. The New York Times and Miami Herald ranked ships by illness records. Swiftly, the ships changed their food preparation and water storage practices, but cruise outbreaks have continued to plague tourists periodically.

This wasn’t the only instance in the book where a publicity campaign proved a swift and effective way to get companies whose products were implicated in disease outbreaks to improve their practices.

Between CDC’s ability to draw media attention to health problems and its apparently effective working relationship with FDA, it’s succeeded in addressing lots of food-related illnesses. However, Inside the Outbreaks includes plenty of examples where CDC wasn’t able to translate its findings into prevention, and the case of antibiotic use in livestock is one of those.

In 1983 EIS officer Scott Holmberg found victims in Minnesota and South Dakota to be suffering from a strain of Salmonella that was resistant to several antibiotics. He traced it to a farmer who “told Holmberg that he always threw in a handful of tetracycline per ton of feed to promote growth and prevent disease in his livestock.” Holmberg’s discovery spurred a push for regulation:

This outbreak was proof that resistant organisms developed in animals fed antimicrobials (primarily to fatten them faster) and then caused disease in humans. Holmberg documented that the fatality rate for people infected with drug-resistant Salmonella was 21 times greater than for regular strains. His investigation spurred FDA hearings and calls for a federal ban on adding antibiotics to animal feed. Although some breeders voluntarily stopped the practice, there is still no regulation in place. “If you want to buy antibiotics for yourself,” Holmberg observed, “you need a prescription, but not if you go to the feed store.”

More than a decade later, EIS officer Fred Angulo created a surveillance system whose information then spurred FDA action on a single antibiotic used for livestock:

In 1995, the FDA authorized the use of fluoroquinolones (i.e., Cipro) in chickens and turkeys, to promote growth and prevent disease. In response, Angulo created the National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS). Launched in 1996, it documented an alarming increase in fluoroquinolone resistance in the ensuing years. The FDA finally reversed its approval of the drug for poultry, but limiting antibiotic use in U. S. food animals remained a challenge.

When it comes to limiting the use of antibiotics in livestock in order to reduce the risk of antibiotic-resistant infections in humans, FDA probably gets more pressure from livestock producers – and the members of Congress who look after their interests – than from the public health community. FDA has the regulatory authority to withhold or revoke approval of antibiotics for routine use in livestock (as opposed to targeted use to combat actual infections), but the political environment is another matter.

There book contains many other examples of problems that CDC has identified but been unable to solve, for a wide range of reasons. Within CDC itself, a director’s reluctance to address sexually transmitted diseases can hobble prevention efforts recommended by agency staff. It may be up to another regulatory agency to ban or recall a product CDC has identified as being dangerous, and the agency may want to avoid the wrath of manufacturers. In some cases, Congress forbids an agency from tackling a particular issue – like refusing to let FDA regulate herbal supplements – or from making recommendations that would upset an interest group, like prohibiting CDC from advocating for gun control.

To return to Mark’s question, I doubt that giving CDC regulatory authority would make the agency dramatically more effective at solving the problems it identifies. For all of the examples I can think of, there’s another agency that does have the power to regulate the product or practice in question, but political or budgetary pressures keep them from doing so. Would CDC be any less subject to such pressures?

The public-health professionals who join the EIS – usually for two-year stints, though some stay longer – are often young and willing to take risks, from giving smallpox vaccinations in a war zone to taking controversial positions on issues like gun control. It’s easy to envision them dashing from one outbreak to the next, using their time in transit to read up on anthrax, smallpox, or whatever other agent is suspected of sickening people in the places they’re heading. Reading Inside the Outbreaks is kind of like watching a season of a superhero TV show – there’s always a new villain threatening an innocent community (salmonella in cake mix one week, tapeworm from sheep the next), plus an old nemesis or two that can be weakened but not killed off (malaria, influenza). Not every episode ends in victory, but after reading the book I’m in awe of all the EIS has achieved.

As exciting as that is, though, it’s clear that there’s a lot of grunt work involved. Pendergrast uses the phrase “shoe-leather epidemiology” often – it’s a concept EIS founder Alexander Langmuir drummed into EIS officers’ heads. When EIS investigators arrive on the scene of an outbreak, they often start by taking lots of samples – of blood, stool, air, soil, and any other substances that might give them a clue. They survey people about what they’ve eaten, what activities they’ve been engaged in, and which parts of a building they walk through. Then they crunch the data – and if that doesn’t yield an answer, they have to go back and ask more questions. Here’s one description of an approach Langmuir taught to EIS recruits:

In tracing epidemics, Langmuir espoused what came to be called a cohort study of a carefully defined group of people (Who attended the church supper?), comparing their behavior (What did they eat? Where did they go? Who did they associate with?) and looking for key differences between those who had become ill and those who had not. Sometimes through such comparisons, the cause of an epidemic became obvious. It was the potato salad!

Langmuir stressed the importance of long division. To find the rate of a given disease in a particular population, you needed a numerator (number of ill over a defined period of time) and a denominator (the population at risk). “Stripped to its basics,” he said, “epidemiology is simply a process of obtaining the appropriate numerator and denominator, determining a rate, and interpreting that rate.” Thus, the three essential elements were time (when were people exposed and when did they become ill?), person (who was affected in what defined population?), and place (where did the epidemic take place?).

But how do you know that an epidemic is occurring? First, you establish the “normal” rate of disease for that area. Langmuir talked about the importance of routine disease surveillance to establish baseline data and to look for anomalous blips.

Traced on a time-line, tracking the number of accumulating daily cases, most epidemics form a classic epidemic curve, a bell-shaped hump. In the simplest version, an outbreak begins in a particular community with an index case, spreads to others, reaches a peak, and then gradually burns itself out, as susceptibles either survive and become immune or die. Looking at this epi-curve, the disease detective could deduce a fair amount. A common source epidemic, such as bad potato salad at a picnic, would have a sudden onset, sharp peak and rapid resolution among a limited population, whereas an ongoing problem such as a contaminated water supply might affect an entire community for a longer time. Once a likely moment of exposure was determined, i.e., the time of the picnic, the epi-curve also revealed the average incubation period, the time between infection and disease onset.

Classic examples like food poisoning at a church supper tend to be relatively straightforward for shoe-leather epidemiologists, but in many other cases it’s not clear what kind of agent is at work. Investigators may have to ask about potential agents that aren’t obvious, and initial data sets may be too small to show an effect. Persistence and creativity are often necessary, and there are plenty of examples of both throughout the book. One of the stories I found particularly interesting was that of Reye’s Syndrome, the often-fatal pediatric illness that an EIS officer first studied in 1962 in North Carolina (though it wasn’t named Reye’s Syndrome until the following year) and that continued to stump the medical community for decades. Here’s Pendergrast’s description of early EIS efforts to study the disease:

Reye’s syndrome, the childhood killer, had been investigated by several EIS officers who had established that most of the cases were preceded by influenza or chickenpox. EIS officer Tom Glick set up the first informal surveillance system for Reye’s syndrome. Over a 30-month period 1967-1969, he found 62 cases of Reye’s syndrome, with a median age of six. Only fifteen survived. Thirty-three children had been treated with aspirin. “Most, if not all, cases of Reye’s syndrome,” Glick concluded, “are etiologically unrelated to exogenous toxins or common medications.”

On November 3, 1971, EIS officer Larry Schonberger got a call from Duke Hospital where three infants with Reye’s syndrome had been admitted in the previous 11 days. Two had died, and the third was clinging to life on a respirator. Schonberger set up a surveillance system at Duke and three other North Carolina hospitals. By Christmas, he had found ten patients with Reye’s syndrome. Surprisingly, none had predisposing influenza B or chickenpox, though eight had some kind of cough, cold, sore throat, or congestion. Six survived. Schonberger conducted a study, as controls using children of similar ages admitted to the hospital for nonviral diseases. The results were inconclusive.

One of the surviving patients was a two-month-old girl. Schonberger gathered all of her medical records and questioned the mother intensely. “I left still puzzled,” he remembered, “but I kept those records.”

It wasn’t until several years later that another EIS officer was finally able to gather more data and make the connection that solved the puzzle:

In December 1978, a flu epidemic hit Phoenix. The day after Christmas, EIS officer Karen Starko, working at the Arizona Department of Health Services, got a call from EIS alum John Sullivan-Bolyai, who was doing his pediatric residency in Phoenix. He had learned of seven cases of Reye ‘s syndrome in children in three Phoenix hospitals and thought she might want to investigate this cluster.

Starko visited several of the children – five girls, two boys — in the hospital. They were in comas, on life support, holes drilled in their skulls to relieve the pressure. Within days, two were dead. She spoke to their parents. These had all been healthy, normal children who had had apparently routine bouts of influenza. After a day or two, the kids were out of bed, feeling better. Suddenly they began to vomit relentlessly, then became sleepy, delirious or combative, and finally fell into a coma.

Starko initiated a case-control study in January 1979, choosing as controls 16 of the victims’ elementary school classmates who had come down with flu and recovered uneventfully. Her questionnaire focused on the week prior to illness, asking about symptoms, medications, type of home heating, pets, and immunizations. In February, she began to analyze the results, but figuring out what was in the various medications proved to be a challenge. There were decongestants, gum, lozenges, and Pepto-Bismol, as well as aspirin (acetylsalicylic acid) and Tylenol (acetaminophen). After research and several visits to drug stores to study labels, Starko compiled her results.

Aspirin. All seven children who developed Reye’s syndrome had taken aspirin (salicylates) in one form or another, compared to half of the controls, and the cases took it in heavier doses.

Starko did some research. She found that EIS officer David Reynolds had investigated 11 fatal cases of Reye’s syndrome in Oklahoma from October 1968 through June 1970. EIS alum Calvin Linnemann had reported in 1974 on 24 Ohio children with Reye’s syndrome. All of the victims in both studies had taken aspirin. Starko brought her data to Larry Schonberger in Viral Diseases, but he said, “Gee, I think previous EIS officers looked at aspirin before in some studies and it was dismissed.” Stunned, she asked him to find the paper that ruled out aspirin.

A few weeks later, Schonberger called. He had reviewed studies by EIS officers Tom Glick (1967-1969) and Larry Corey (1973-1975). Over half of the victims in Glick’s study had taken aspirin, and he had not looked in brand-name medications. Corey had studied hundreds of cases during a nationwide influenza B epidemic, and 78 percent had taken aspirin. Schonberger had also looked at the medical records of the baby with Reye’s syndrome from his EIS days. She had been given aspirin.

Starko’s Arizona case-control study was compelling, but with only seven cases, it hardly constituted proof. Schonberger advised Gene Hurwitz, his EIS officer already working on a Reye’s case-control study in Ohio, to focus on aspirin use. Michigan-based EIS officer Ron Waldman, working on his own study, did the same.

One missing piece nagged at Starko – the unusual pathology findings of cerebral edema combined with tiny fat drops within liver cells. Perhaps salicylate poisoning produced something similar. Her supervisor Lyle Conrad suggested she write to the Armed Forces Institute of Pathology in Washington, DC. Within two weeks, on September 24, 1979, she received details of 11 cases of “acute salicylism in infants and children.” All had “small cytoplasmic fat vesicles.” Starko’s hands trembled as she read the letter. “I wanted to scream,” she recalls. “This was it!” Seven of those cases had antecedent upper respiratory infections. In other words, they were probably Reye’s syndrome cases.

Starko and her colleagues had more obstacles to surmount before it was possible to declare victory over Reye’s Syndrome, but this story of putting together different pieces – a case-control study with an extensive questionnaire, ingredient information gathered in drugstore aisles, pathology reports from another source – is a great example of the kind of persistence and creative thinking that have to come together to solve medical mysteries.

Inside the Outbreaks does a great job celebrating the combination of heroic and mundane work that goes into identifying and preventing disease. It’s also a great way to learn about epidemiology and why it’s so important. While the book is a fitting tribute to the EIS, it also reminded me how important it is to have strong state and local public health departments that can collect surveillance data year after year and spot outbreaks (like these) as they emerge.

So, go read Inside the Outbreaks and develop a new (or renewed) appreciation for epidemiology superheroes!