Poor Vaccination Rates, Waning Immunity Cause Its Resurgence
Cover Story -- June 2002
By Ken Ortolon
In the mid-1970s, it appeared that pertussis was down for the count. The disease, which got its popular name from the whooping sound its victims make as they try to breathe following coughing spasms, had been a major source of illness and death among American children for centuries. One of the earliest suspected outbreaks in America was in the Plymouth colony in 1648.
But the introduction of the first pertussis vaccine in the mid-1940s had a dramatic impact in reducing whooping cough in the United States. By the mid-1970s, the disease had been all but eradicated and deaths from pertussis were rare.
Now, however, it appears that pertussis has dragged itself off the canvas. Outbreaks of pertussis increased steadily over the past several years as physicians and public health officials became complacent about a disease they thought was well in check.
"We let our guard down," said Mark Shelton, MD, a pediatric infectious disease specialist at Cook Children's Hospital in Fort Worth, which reported treating 52 cases of pertussis in 2001. "Pertussis is a huge problem. And it's not just a North Texas problem or a Texas problem. It's a national problem."
The Comeback Kid
Pertussis is caused by the bacterium Bordatella pertussis . It is characterized by a runny nose, sore throat, coughing spasms, shortness of breath, a high-pitched whooping sound, and vomiting. While pertussis is commonly thought of as a childhood disease, adolescents and adults are not immune.
For older children and adults, it certainly can be unpleasant, causing a chronic cough that can last for weeks. But for young children -- particularly infants who are too young to be immunized -- it can be deadly. And public health officials say it is the only vaccine-preventable disease making a resurgence in America today.
Before World War II, more than 200,000 Americans contracted whooping cough each year. Total confirmed cases in Texas peaked at 21,558 in 1947, and a record 494 Texans died from pertussis in 1934.
Widespread use of the pertussis vaccine, however, produced a rapid decline in pertussis cases throughout the 1950s and 1960s. Confirmed cases hit an all-time low of only 1,010 cases in the United States in 1976.
The original vaccine used whole pertussis cells and was given in conjunction with diphtheria and tetanus vaccines, producing the so-called "DTP" vaccine. Since 1991, pharmaceutical companies have manufactured an acellular, or partial cell, vaccine commonly referred to as the "DTaP" vaccine.
Since the low of 1976, pertussis cases trended slowly upward throughout the 1980s. But in 1991, cases began to spike sharply higher. The U.S. Centers for Disease Control and Prevention (CDC) reported in the Feb. 1, 2002, issue of its Morbidity and Mortality Weekly Report that between 1996 and 2000 the United States saw an average of more than 7,000 confirmed cases annually.
"Texas is very much mirroring what's going on all across the country," said David Bastis, MPH, director of the Surveillance and Epidemiology Program in the Texas Department of Health (TDH) Immunization Division.
Since 1996, pertussis cases in Texas have jumped from 151 to 603 in 2001. Between 1993 and 1997, only one pertussis death occurred in Texas. Since 1999, there have been 11, including five in 2001 and three that were reported in the first three months of this year.
In mid-April, the Laredo Health Department announced a Whooping Cough Alert after the deaths of two infants this year.
Health department officials held a press conference to brief the news media on the importance of whooping cough vaccination and awareness.
The department asked physicians to be alert for pertussis and to consider it "in their initial diagnosis of children."
Of those 11 reported deaths statewide, 10 have been among Hispanics. Sharilyn Stanley, MD, associate commissioner for disease control and prevention at TDH, says the agency is still struggling to determine why the toll has been so high in the Hispanic community.
"That's an interesting finding that, unfortunately, we don't have an answer to yet," Dr. Stanley said. One possible theory is a high level of contact between Hispanics in the United States and relatives or friends from Mexico who have never been vaccinated.
While TDH still is investigating that issue, Mr. Bastis says the reasons for the resurgence of pertussis are multifold. First, there is some suspicion that the acellular vaccine may not be as effective as the old whole-cell vaccine. While the increase in cases does coincide with the introduction of the acellular vaccine, this is just a theory.
Second, at least as far as Texas is concerned, is the fact that Texas has not done a good job in making sure its children are fully vaccinated. The state ranks 50th in the nation in the percentage of children 19 to35 months of age completing the recommended doses of several vaccines, including DTaP. By 19 months, children are supposed to have received four doses of the DTaP vaccine. They needa fifth dose by the time they start school or before age 7. Texas ranks last in the percentage of kids getting the fourthdose of DTaP by 19 to 35 months, Mr. Bastis says. "That fourth dose is not routinely given when it should be in Texas. Many children are getting the fourth dose when they start school."
But the major problem may be the vaccine itself.
"The vaccine for pertussis is less than ideal," Dr. Stanley said. "We know that immunity wanes over time. So, by the time you get to your teenage years, you're not likely to be very immune."
That's not necessarily a huge problem for teenagers or adults, who aren't at risk of life-threatening illness from pertussis. But pertussis is highly contagious and can quickly spread from an adolescent or adult with a chronic cough and put the life of an infant child or sibling at risk.
"So teenagers or adults get infected, they walk around with a cough for three or four weeks, and they end up infecting young infants or others," Dr. Stanley said.
A case highlighted in the July 31, 2001, issue of TDH's Disease Prevention News involved a 28-day-old Hispanic female who died after exposure to pertussis from her 15-year-old sister and 17-year-old brother.
Making the Right Diagnosis
Part of the problem is that physicians aren't thinking about pertussis when patients present with chronic coughs. "Many physicians just haven't seen pertussis," Mr. Bastis said.
Dr. Shelton, of Cook Children's Hospital, adds that pertussis is a difficult diagnosis. "There are all sorts of chronic cough syndromes," he said, adding that pertussis easily could be mistaken for the common cold, allergies, or even asthma.
"As pediatricians, we're very much aware of pertussis because it is thought of as a childhood disease," he said. "But I'm not sure internists or family practice doctors are geared to think of pertussis in their older patients."
But adolescents and adults are making up an increasing percentage of pertussis cases. Of the more than 28,000 cases reported in the United States since 1997, roughly half have involved patients 10 years old or older and nearly 6,000 have involved patients aged 20 or older.
Plus, CDC officials estimate that the number of confirmed cases of pertussis could be just the tip of the iceberg. In a report published on ABCNEWS.com on March 10, CDC epidemiologists estimated that as many as 90 percent of pertussis cases in America go undetected, meaning that as many as 500,000 Americans could have whooping cough and think it's merely a bad cold or allergy.
"We've had stories of moms taking their middle schoolers or high schoolers to the emergency room or doctor's office and the doctors saying, 'It can't be pertussis because he was vaccinated as a kid,'" Dr. Stanley said. "We haven't done a good job educating the physician community that this continues to be a problem."
Finding the Solutions
Public health officials across the country are working diligently to bring this whooping cough resurgence under control, but the fact that adolescents and adults seem to be the major source of the disease is a complicating factor. Currently, there is no adult vaccine for pertussis. Neither the DTP vaccine nor the DTaP vaccine is licensed for use in anyone older than age 7.
"It's a gap in our ability to respond to the disease," Dr. Stanley said.
But that gap may soon narrow. Dr. Stanley says the National Institute of Allergy and Infectious Diseases at the National Institutes of Health has made developing an effective adult pertussis vaccine a "high priority" and is funding research in that area. Also, Len Lavenda, a spokesman for pharmaceutical maker Aventis-Pasteur, says an adult pertussis vaccine is in Phase 3 clinical studies at several sites across the country, including the University of Missouri.
Meanwhile, TDH is acting aggressively to attempt to slow the spread of pertussis in Texas. Because the incidence rates have gone up more for Hispanic infants than in any other age or race/ethnic group, Mr. Bastis says TDH is in the process of developing a radio campaign targeted at the Hispanic community and Spanish-language radio. Also, TDH is preparing a pertussis outbreak kit for distribution through regional health departments and local health authorities. The kit will include sample letters to physicians alerting them to local outbreaks, sample materials in both English and Spanish for schools to send to parents, a pertussis fact sheet, and more. (See "What Your Patients Need to Know.")
Additionally, TDH is adapting a monograph originally developed by the Washington State Department of Health that will be made available on the TDH Web site and will allow physicians to earn continuing medical education credit.
Finally, TDH is planning a pertussis seminar for June 22 in Austin. Details can be found on the TDH Web site at http://www.dshs.state.tx.us/ or by calling (800) 252-9152.
In the meantime, TDH is asking physicians to take several steps to reduce the spread of pertussis. First, make sure that all children under age 7 have received the recommended five doses of the DTaP vaccine.
"What we know is that the 15-to-18-month dose -- the fourth dose -- is frequently skipped," Dr. Stanley said. "So by the time children enter school, they've only had four doses. Now I can't tell you that children would maintain immunity longer if they got the five shots, but that is an area where doctors could perhaps increase immunity and make it last longer."
Second, Dr. Stanley asks that physicians maintain a high index of suspicion for pertussis. "Keep it on your list of differential diagnoses even in folks who have been vaccinated as children. And when the suspicion is high enough, go ahead and do the appropriate diagnostic tests."
The appropriate test is a nasopharyngeal swab. TDH says the preferred laboratory test for confirmation of pertussis is isolation of Bordatella pertussis by culture. Polymerase chain reaction (PCR) testing also is available in some laboratories.
Dr. Shelton says the PCR test has made diagnosing pertussis much easier. "Pertussis is relatively difficult to grow," he said. "You have to have a special medium, it takes a long time, and processing the specimen is critical. But the PCR test, if collected properly, has really made a difference."
Finally, start the patient and all close contacts on antibiotics immediately. That is a departure from recent pressure on physicians not to overuse antibiotics. But Dr. Stanley says it is critical to catch pertussis as early as possible.
"We feel like this is such a contagious disease we want to be aggressive," she said. "You'll get the results back fairly quickly, so go ahead and start the patient on antibiotics and stop it if it happens to not be pertussis."
Ken Ortolon can be reached at (800) 880-1300, ext. 1392, or (512) 370-1392; or by email at Ken Ortolon.
What Your Patients Need To Know
The Healthy Ending feature in this month's issue of Texas Medicine provides information for your patients on pertussis. The information is courtesy of the Texas Department of Health. Healthy Ending is printed in both English and Spanish. Please copy it and give it to your patients.
Pertussis usually starts with signs and symptoms of the common cold, but as the disease progresses in children, they have a choking cough that evolves into severe paroxysms of expiratory bursts often followed by a characteristic high-pitched whoop. Other symptoms include:
- Post-tussive vomiting,
- Cyanosis, and
Pertussis in adolescents and adults may appear as a mild upper respiratory tract infection with an unusually persistent cough.
The incubation period for pertussis is usually seven to 13 days, although it can range from four days to more than three weeks. The catarrhal stage usually lasts one to two weeks with symptoms including nasal congestion, tearing, mild conjunctival injection, malaise, and low-grade fever. An initial mild and nonproductive cough develops.
In the paroxysmal phase, the cough increases in severity. A series of short expiratory bursts is often followed by an inspiratory gasp against a partially closed glottis, producing the typical whoop. Severe coughing paroxysms may cause respiratory distress, cyanosis, or post-tussive vomiting. The cough is often worse at night. Between episodes of choking cough, the cough may be absent and the patient may feel well. The paroxysmal phase may last one to two months.
By the convalescent phase, the intensity and frequency of the paroxysms gradually decrease. Residual coughing may persist for as long as six months.
When pertussis is suspected, the Texas Department of Health recommends collection of nasal secretion specimens using a nasopharyngeal swab. While the procedure may be uncomfortable and difficult to perform on uncooperative children, it gives the highest yield of organisms. Nasal aspirates also are acceptable if collected early in the infection. Throat swabs are not acceptable. Laboratory confirmation of pertussis should be through culture or polymerase chain reaction tests.
Smallpox: Mass Vaccinations or Not?
By Patti Patterson, MD, MPH, and James A. Reinarz, MD
The last case of smallpox in the United States occurred in 1949, and the last naturally occurring case in the world was in Somalia in 1977. The disease was eradicated by a worldwide vaccination program. That public health triumph has now become a major problem.
Half a century ago, smallpox would have been much less of a bioterrorist threat because the majority of the world's population was immune to the disease. With the eradication of the disease and discontinuation of the vaccine program because it was no longer deemed necessary, the majority of the world's population is now susceptible to this infection. In the April 25, 2002, edition of the New England Journal of Medicine , Dr. Anthony S. Fauci calls for informed debate on the issue of universal vaccination for smallpox (1). This discussion among public health officials, homeland security experts, and medical professionals is occurring in a context that has never been encountered in health policy development.
Unfortunately, the discussion seems to be colored more by the unknown than by the known. We do not know the true risk of this virus being used as a biological weapon. Massive amounts have been produced and were "weaponized," and the virus remains viable in the lyophilized state. With the dissolution of the USSR, some of the virus may have fallen into unreliable or unstable circumstances. The potential is strong enough, however, that terrorism experts feel that the deliberate release of smallpox virus is a possibility.
While the threat is not fully known, the vulnerability of the United States and virtually the whole world's population is clear. Individuals born after the mass immunization program for smallpox was discontinued in 1972 are not immune. With the exception of certain populations (e.g., military), those who were born before 1972 and received the vaccine are likely to have waning immunity with uncertain protection. Case-fatality rates could exceed 25 percent if smallpox were released as a bioterrorism weapon (2). This brings us to the unfortunate position of making decisions about mass immunization of an unprotected population -- not for a naturally occurring pathogen but for a disease resulting from hatred.
Many other unknowns are involved in this policy odyssey. Never before have we had to consider the potential for the release of a pathogen previously declared eradicated from the planet. The well-documented natural spread of the disease may not be applicable when the majority of the population has no immunity to the pathogen, and those vaccinated in the remote past probably have waning immunity.
Although the incidence of adverse reactions in healthy individuals is low, the composition and demographics of the U.S. population have changed significantly since the universal vaccine programs of the mid-20th century. There are now many more immune-compromised patients in the general population. Our experience with universal vaccine programs took place before the AIDS epidemic, organ transplantation, chronic hemodialysis, extensive cancer chemotherapy, and other medical advances that have the significant side effects of immune suppression. These subpopulations are large and growing.
Further, does the United States have the right or moral imperative to immunize its own population without offering the same opportunity to other countries? Such decisions must be based on risk of disease exposure and risk of adverse effects of the vaccine in a particular population.
The current Centers for Disease Control and Prevention (CDC) smallpox plan does not recommend mass vaccination campaigns in anticipation of a potential release or in response to documented cases. For a variety of reasons, public health officials have taken the position of withholding vaccine that could effectively protect the public from a terrible disease until an outbreak is confirmed. The decision involves vaccine availability and safety, the potential benefits and risks of mass pre-exposure vaccination, and the likelihood of success of postexposure vaccination programs.
The primary benefit of a voluntary mass immunization would be to reduce the threat of smallpox as a weapon by reducing the number of susceptible persons. Therefore, an outbreak might be smaller, more localized, and easier to manage. This strategy allows vaccinations to be carefully planned and methodical.
One of the leading arguments against mass immunization is the incidence of adverse effects, some of which would be severe. An estimated 180 deaths could occur in a nationwide immunization effort. That estimate is based on adverse events of 1968 and extrapolated to the present population (3). This estimate does not take into account the increased numbers of individuals with AIDS or immune suppression from other causes who could be impacted or the secondary spread to non-intended populations. Also, the public perception of immunizations has changed since smallpox vaccination programs were widely employed. While vaccines have been continually improved to reduce adverse side effects, the public's demands for safety have become more stringent, and manufacturers' and health care professionals' liability has increased. While wide and diverse input should be sought, we must be prepared to support whatever decision is made at the highest level. It is reasonable to expect that a final decision will not be made unless it is forced upon us by events.
The current CDC policy decision is to rely upon ring vaccinations in the event of a proven case rather than implementing a universal vaccine program. Postexposure ring vaccination efficiency depends on rapid identification of disease, immediate and complete quarantine of exposed persons, and quick identification and immunization of numerous contacts of exposed persons and their secondary contacts. Given the mobility of the population and the frequent venues of large crowds and a susceptible population, this approach might be expected to have limited success in an intentional multiple-release scenario. A postexposure strategy could result in managing an outbreak in a crisis operation mode rather than in a carefully orchestrated preventive plan of action. It is also believed by some that this crisis implementation of a mass vaccination effort could lead to more adverse events because of vaccination of immune-compromised individuals or their exposure to newly immunized individuals.
This policy was driven in part by limited supplies of vaccine. Recent studies have shown that a diluted vaccine can produce an immune response, thus significantly extending impact of the available sources (4). In addition, production of second-generation smallpox vaccines will increase supplies to the point that broader programs could be implemented. Also, stocks of old smallpox vaccine have been recently discovered. Vaccine availability should soon become less of a factor in policy development. It is clear that once any decision is made, the information could be very valuable to a potential terrorist or adversary as the most efficient means to work his or her mischief.
All of that said, vaccination is only one component of an overall system needed to address these public health threats. Scholars, scientists, politicians, and ordinary people are well aware that our world has changed forever. "Old thinking" will not likely serve us well when presented with the daunting new problems.
The public health infrastructure has been "dwindling" over many years. Local expertise and resources are absolutely essential for the disease surveillance and outbreak investigation required to identify potential epidemics as early as possible. An effective response to an act of terror would require a highly coordinated effort that would draw upon a multitude of resources. Health departments, cities, counties, universities, health science centers, hospitals, and numerous other entities are engaged in bioterrorism preparedness. The use of biological agents as weapons could very quickly expand beyond being a local issue and could certainly have regional, state, and even national implications. Planning processes must involve systems approaches at regional and state levels that feed into national efforts. Each component of emergency response could function well on its own, but the overall response would not be effective if the various components did not function synchronously.
It is essential not to undermine other crucial public health issues as policymakers address these issues of bioterrorism. Texas remains last among the states in childhood immunization rates. Any effort to address these new problems should not undermine efforts to protect children from known health threats they face every day.
Perhaps a single policy is not the best policy. To restrict our thinking to "immunize everyone" or "epidemic containment" is too restrictive. Perhaps a program in which all health care professionals and primary responders are offered immunizations at screenings or a gradual immunization of selected groups (e.g., all first graders, all high school seniors, blood donors, postal workers, Peace Corps workers) in addition to the military would provide hard data on complication rates, direct logistic improvements, and over time lead to a substantial percentage of immunized individuals. Our challenge is to be proactive, to act with reason and commitment, to control our public health destiny, and to use this impetus to improve disease prevention at all levels .
Dr. Patterson is chair of the TMA Council on Public Health and vice president for rural and community health at Texas Tech University Health Sciences Center in Lubbock. Dr. Reinarz is on the teaching staff of the Department of Internal Medicine and Infectious Diseases at John Peter Smith Hospital in Fort Worth.
- Fauci, AS.Smallpox vaccination policy -- the need for dialogue . N Engl J Med. 2002;346:1319-1320.
- Breman JG, Henderson DA.Poxvirus dilemmas -- monkeypox, smallpox, and biologic terrorism. N Engl J Med. 1998;339:556-559.
- Bicknell WJ.The case for voluntary smallpox vaccination. N Engl J Med. 2002;346:1323-1325.
- Frey SE, Couch RB, Tacket CO, et al.Clinical responses to undiluted and diluted smallpox vaccine . N Engl J Med. 2002;346:1265-1274.
- Frey SE, Newman FK, Cruz Z, et al.Dose-related effects of smallpox vaccine. N Engl J Med. 2002;346:1275-1280.
Pertussis Deaths -- United States, 2000 ( MMWR . 2002;51:616-618)
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