1999 Richard J. Duma/NFID Annual Press Conference and Symposium on Infectious Diseases
Please Choose a Presenter
» Gray Davis, Ph.D.
» Bruce Gellin, M.D., M.P.H.
» J. Thomas Grayston, M.D.
» Leslye D. Johnson, Ph.D.
» Ralph Nader
Whatever Happened to Herpes? The Forgotten Epidemic
By Gray Davis, Ph.D.
he number of new cases of all sexually transmitted diseases (STD) is estimated to be approximately 15 million a year. Even this may be a underestimate. The recent National Health and Nutrition Examination Surveys (NHANES III) found that in the United States, seroprevalence of herpes simplex virus-type 2 (HSV-2) increased from 16.4 to 21.9 percent in the decade of the 1980s. This suggests that there were 1.1 million new cases of herpes simplex virus type 2 (HSV-2) infections every year in the 1980s. When one considers that 25 percent of new cases of genital herpes are likely caused by HSV-1, the annual incidence of genital herpes increases to 1.3-1.4 million. With an epidemic such as this, how can it be forgotten?
How can an epidemic of this size be forgotten? One factor was the HIV epidemic. In the 1980s the medical community was responding to a national health crisis with the HIV. Herpes went from the "Scarlet Letter" to "Oh, it's only herpes." So much necessary focus was placed on the HIV crisis that non-life threatening infections were de-emphasized. However, given the link between HIV and HSV and the sharp rise in HSV seroprevalence in our teenage population, herpes cannot be forgotten any longer.
The good news about herpes is that major advances have been made in our ability to diagnose this disease. Until recently, accurate diagnosis in the primary care setting has been limited to viral culture, which requires the patient to have active lesions at the time of the office visit. Since recurrent episodes typically last only a few days and the active "shedding" cease one to two days after lesions appear, patients often present too late in the course of disease for a confirmatory culture. Therefore, the clinician is left with the dilemma of a diagnosis. Serologic tests to measure antibody to HSV have traditionally been unreliable in distinguishing between type 1 (the primary cause of fever blisters) and type 2 (the primary cause of genital herpes). Accurate serologic diagnosis was limited to a few research sites skilled in performing the Western blot assay. The hope on the horizon is the availability of point-of-care diagnostic tests which will allow the clinician to distinguish between type 1 and type 2 herpes. At least one of these tests should be available within the year.
The availability of a diagnostic test leads to new questions regarding how to most appropriately use it. Who do we screen? What do we tell them about the diagnosis? How do we manage the disease? These are all questions that are being evaluated by the Centers for Disease Control and Prevention, university scientists and pharmaceutical companies, as well as researchers in the private sector.
Once we know how to diagnose HSV and who to test, the next challenge is prevention of transmission. Traditional viral disease prevention measures, such as vaccines, have proven ineffective. While new vaccines are under development, it will be several years before they are available. The most immediate hope is that daily suppressive therapy with an antiviral can prevent transmission. The theory is that if viral replication can be stopped, transmission of infection will also stop. Clinical trials are underway to test this theory.
Though the challenge of stopping remains formidable, the recent technological breakthroughs in diagnostics have opened healthy new dialogues including both public and private sector about how we should curtail the rapid spread of this common STD.
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Maintaining the Public Trust in Vaccinations: A New IDSA Initiative
By Bruce Gellin, M.D., M.P.H.
Vaccines are the most powerful tools we have to prevent serious infectious diseases and their consequences. But, in some ways, immunization has become a victim of its own success. The diseases that threatened children just a generation ago have become abstract concepts or historical anecdotes. Concomitantly, a growing number of "controversies" about vaccine use--with no basis in fact--are being raised in the media, on the Internet and in the halls of government. In combination, these factors can erode public trust in immunizations, despite their demonstrated importance and nearly unanimous support among the medical and scientific communities. Moreover, it is clear that when immunization levels drop, disease returns.
The Vaccine Initiative is an independent resource to which parents, physicians, policy makers and journalists can turn for clear, balanced and scientific information about immunizations.
The Vaccine Initiative is designed to provide each of these audiences with the facts they need to be fully informed about immunization. While plans for specific materials are in development, at a minimum they will include educational materials for parents, and tools to help physicians effectively communicate with parents about the benefits and risks of vaccines.
The Vaccine Initiative has conducted qualitative research with parents, and research with legislators and physicians is underway or planned. The research suggests that parents largely trust and believe in the value of immunization. However, as patients increasingly take an active role in their health care decisions, they will assuredly continue to ask questions about immunization. Patients and parents will look to many sources of information, but most will seek--and trust and follow--their physicians' advice.
The Vaccine Initiative is a special education and communication project of the Infectious Diseases Society of America and the Pediatric Infectious Diseases Society. The Vaccine Initiative receives grant support from the Robert Wood Johnson Foundation.
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Chlamydia pneumoniae (TWAR) and Atherosclerosis
By J. Thomas Grayston, M.D.
Chlamydia pneumoniae is a newly described microorganism that is an important cause of pneumonia and other respiratory infections. It does not cause a sexually transmitted disease, like Chlamydia trachomatis, but is transmitted human-to-human via the respiratory tract. Seroepidemiological studies first suggested that C. pneumoniae and atherosclerosis might be related. They found that persons with atherosclerotic diseases, especially coronary heart disease, have specific antibody or immune complexes showing previous C. pneumoniae infection more frequently than persons without disease.
Compelling evidence for an association of C. pneumoniae and atherosclerosis comes from the repeated frequent demonstration of the organism in atherosclerotic plaques. The direct demonstration of the organism in atheroma has been accomplished by four techniques; electron microscopy (EM), immunocytochemistry (ICC), the polymerase chain reaction (PCR) and isolation of the organism in cell culture. In a series of nine studies carried out by our group at the University of Washington the organism was found in atherosclerotic lesions of coronary, carotid and popliteal/femoral arteries and the aorta. Specimens from 322 patients were examined and more than 50 percent were positive by ICC &/or PCR. The organism was not found in normal appearing arteries. These findings have now been confirmed by a number of investigators from different parts of the world. In addition, several investigators have grown C. pneumoniae in vitro in cells found in artery walls. Byrne at the University of Wisconsin studied human macrophages grown in cell culture with low density lipoprotein in the media. If they were infected with C. pneumoniae they showed an increased accumulation of cholesterol esters and some resembled foam cells.
These observational studies cannot prove an etiologic association of C. pneumoniae and atherosclerosis. Evidence from animal model studies and human treatment trials will allow more direct inference of causality. There are now a few reports of such studies, which, while far from definitive, are of interest. It has been shown in mice that following either intranasal or intraperiotoneal inoculation, macrophages quickly spread C. pneumoniae throughout the body. Two laboratories have reported aortic lesions following C. pneumoniae intranasal inoculation of New Zealand White Rabbits on a normal diet. Two studies, one in rabbits fed extra cholesterol and the other in Apo E deficient genetic knockout mice, showed that C. pneumoniae infection accelerated the atherosclerotic process seen in sham inoculated control animals. In the rabbit model the accelerating effect was eliminated by antibiotic treatment shortly after infection. These studies, if they can be repeated with larger numbers of animals observed over longer periods and extended to other species, will provide evidence that the organism can play a role in initiation and progress of the atherosclerotic process. In a different approach, Penninger showed that there is sequence homology between a mouse heart muscle protein that causes autoimmune heart disease and the Chlamydia outer membrane protein. The similar Chlamydia protein was capable of causing extensive heart damage in mice.
Initiation and acceleration of atherosclerosis can be studied in animals, but there are no animal models of late complications of atherosclerosis such as myocardial infarction. Inferences on the role of C. pneumoniae in complications of atherosclerosis can come from human antibiotic treatment studies. There are three recently reported retrospective studies of the effect of antibiotic usage on subsequent coronary artery disease events. The studies used large patient populations in the United States or Great Britain with computerized pharmacy records. In two studies, patients that had taken antibiotics effective against C. pneumoniae had a lower incidence of coronary events than controls. The third study failed to find this effect.
There have also been three pilot prospective human secondary prevention trials reported. Two found a reduction in coronary events and one did not. All were too small for reliable results. Now underway are at least two trials of adequate size and duration to determine if antibiotic treatment of persons with coronary artery disease can reduce the frequency of coronary events compared to placebo controls. If successful such trials would add a new treatment method for coronary artery disease and would suggest that C. pneumoniae plays a role in the process that leads to coronary heart disease events.
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Why You Should Know About Hepatitis C
By Leslye D. Johnson, Ph.D.
The Institute of Medicine includes hepatitis C virus (HCV) in its list of emerging infectious diseases. Scientists cloned and sequenced HCV 10 years ago and developed diagnostic tests. With them we've learned that about 4 million people in the United States (1.8 percent) are persistently infected. Those with the greatest risk of already being positive are individuals who have ever experimented with injection drugs (even once or twice in the distant past), had multiple sexual partners or received blood (e.g., a transfusion) prior to 1992.
HCV damages one of the body's most important organs, the liver. Symptoms of both acute and chronic infections are easily confused with less serious and shorter-term illnesses. In fact, most people's infection and disease is relatively free of physical symptoms and elevated liver enzymes for a couple of decades. Unfortunately, by the time there is concern, liver damage can be considerable and even irreversible.
HCV is not related to either the hepatitis A or B viruses and diagnostic tests readily distinguish them. The major diagnostic tool is an antibody test. Unlike with many other infections, the presence of antibodies does not mean recovery. Although rare, recovery does occur; it can be detected using highly sensitive diagnostic tests for the viral genome (RNA). Unfortunately, such tests are not yet licensed, and there is laboratory variability.
Roughly 50 percent of chronic carriers do not even know they have hepatitis C, a disease that moves through specific stages of liver damage. Currently diagnosis of the stage requires a liver biopsy, i.e., removal of a very small piece of the liver, and evaluation of an even smaller piece using a microscope. The rate of progression is highly individual and can be characterized as slow, medium or fast. For most it is slow, i.e., after 20 years of chronic infection, only ~20 percent of individuals progress to cirrhosis. Two important factors that hasten progression are alcohol and other hepatitis viruses. Thus, if they know they are infected, individuals can help themselves by not using alcohol and by getting vaccinated to prevent hepatitis A and B.
The Food and Drug Administration has approved therapies that get rid of the virus and make the liver more normal. Three are interferons and the fourth combines interferon and ribavirin. Unfortunately, none are very effective and all have significant side effects. Currently, there is no way to know who will or won't respond. However, the best responses are seen in those who have viral genotypes 2 and 3, less severe fibrosis, females and those under the age of 40 years. It is important to note that genotype 1 predominates in this country.
The lack of symptoms, distant transmission and ability to intervene make it important for individuals to report accurate personal histories and for physicians to test for antibodies in order to detect hepatitis C as early as possible.
Hepatitis C virus infection and disease is an increasing public health concern. Without more effective therapies that produce recovery, the Centers for Disease Control and Prevention predicts that deaths due to HCV will double or triple in the next 15 to 20 years due simply to the length of time most people in the United States have been infected.
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The Global TB Emergency: Pay Now or Pay Much More Later
By Ralph Nader
Judging from U.S. public and private funding, or lack thereof, for tuberculosis, the federal government and the American public have dismissed tuberculosis (TB) disease of the past. Nothing can be farther from the truth about the world's biggest single infectious killer. More people died from TB worldwide last year than any other year in history, and the prevalence of multi-drug resistance continues to increase. In all reality, less is spent to apply known, inexpensive drug cures to those afflicted with TB than Westerners spend on anti-balding nostrums. While standard antibiotics that can cure one patient cost around $50 per patient in the developing world, only 16 percent of all TB patients receive this cost-effective, life-saving treatment according to the World Health Organization (WHO).
Of grave concern is the growing number of cases stemming from multi-drug resistant strains of TB (MDR-TB) worldwide. With bad quality drugs, inadequate drug supplies, lack of trained health workers and overall poor treatment programs, this entirely man-made phenomenon threatens to return the world to an era in which TB is incurable. Already 50 million people are believed to be infected by MDR-TB, with treatment for an infectious patient costing up to 100 times as much as a regular TB case. Even with treatment that costs about $250,000 in the U.S. per patient, individuals that fall ill with MDR-TB are not guaranteed survival.
While the Pentagon fumbles around without knowing what to do with their stealth bombers that cost $2 billion apiece, the WHO estimates that $1 billion per year will help control the global TB epidemic. The contrast is a pertinent one, given the fact that TB, especially MDR-TB, is a serious national security issue. The airborne disease has been deemed "Ebola with wings" by officials at WHO given its deadly nature and ease of transmission. Millions of Americans travel abroad to endemic countries each year, and the TB bacilli stops for no international borders. While the world spends $4 billion on military weapons each day worldwide, 8,000 people die needlessly from TB in the same time span. That's one human being dead from TB every 10 seconds.
The inaction of the western world concerning the TB epidemic is shameful given the fact that it touches on relatively every issue possible. TB is the number one killer of women, taking more lives than any other cause of maternal mortality. TB is a leading cause of orphanage in the developing world. TB is the number one killer of HIV-positive patients. Yet, research for an effective TB vaccine at the National Institutes of Health was a mere $5 million last year compared to billions for diseases comparable in destruction. Furthermore, not one single major U.S. foundation has stepped up to give significant resources to TB control programs abroad.
The United States spent $12 million on international TB control for each of the past two years through the United States Agency for International Development thanks to the efforts of Senator Leahy and the U.S. Congress. But just three years ago, the United States gave two to three times less to the WHO than countries like the Netherlands and Switzerland that are much smaller in size and wealth. Advocacy organizations including Princeton Project 55 TB Initiative, ALA/ATS and Results are working with Congress to appropriate $60 million in foreign assistance specifically for TB, a small but important contribution to the global war. It is in our best interest in terms of both national security and humanitarianism to take the lead in fighting this scourge.
The United States will never reach domestic goals of TB elimination without appeasing the TB "hot-spots" around the globe. And in today's global community where international travel for business and pleasure is commonplace, MDR-TB in the form of a cough or sneeze will continue to be a plane ride away.
