Testimony

Statement by

Phillip Baker, Ph.D.

Lyme Disease Program Officer

Division of Microbiology and Infectious Diseases,

National Institute of Allergy and Infectious Diseases,

National Institutes of Health

U.S. Department of Health and Human Services

on

Hearing: NIH Lyme Disease Research

before the

The Connecticut Department of Public Health and the Connecticut Attorney General's Office

January 29, 2004

Good afternoon. I am Dr. Phillip Baker, the Lyme Disease Program Officer and the Vector Borne/Zoonotic Bacterial Diseases Program Officer, with the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, U.S. Department of Health and Human Services.

Introduction

NIAID has a long-standing commitment to Lyme borreliosis research (Lyme disease) that began more than 20 years ago when the cause of the disease was not yet known. In 1981, NIAID-funded researchers identified Borrelia burgdorferi as the causative agent of Lyme disease, and since then, basic and clinical research efforts have been expanded in scope to address a variety of issues related to this illness. These activities include both intramural and extramural research on animal models, microbial physiology, molecular and cellular mechanisms of pathogenesis, mechanisms of protective immunity, vectors and disease transmission, efficacy of different modes of antibiotic therapy, and the development of more sensitive and reliable diagnostic tests for both early (acute) and late (chronic) Lyme disease.

Other NIH institutes and centers (ICs) that conduct Lyme disease research are the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Mental Health (NIMH), the National Institute of Neurological Disorders and Stroke (NINDS), the Fogarty International Center (FIC), and the National Center for Research Resources (NCRR).

Diagnostic Procedures

Approximately 20 percent of NIAID's extramural Lyme disease portfolio is devoted to the development of novel and more sensitive diagnostic procedures; the NIAID also regularly re-evaluates the effectiveness of currently-used diagnostic methods. In collaboration with the CDC, the Institute plays a major role in the development of new approaches for diagnosing Lyme borreliosis in the presence of co-infecting agents, as well as in individuals who have been immunized. In addition, there is a strong need to develop a procedure that will enable one to distinguish those who are actively infected with B. burgdorferi from those who either have recovered from a previous infection or have been immunized with the LYMErixTM vaccine. Since the genome of B. burgdorferi has now been completely sequenced, greater advances are anticipated as this information is used both to improve diagnosis and provide new insights on the pathogenesis of the disease through the application of micro-array technology and proteomics.

Co-Infection

Co-infection looms as a major potential problem, mainly because the Ixodes ticks that transmit B. burgdorferi often carry and simultaneously transmit other emerging pathogens such as Ehrlichia species, the causative agent of human granulocytic ehrlichiosis (HGE), and Babesia microti, which causes babesiosis. In Europe and Asia, Ixodes ticks also are known to transmit tick-borne encephalitis viruses; fortunately, this tick-borne viral infection has not yet been reported in the U.S., although co-infections with Powasan virus and deer tick virus have been reported. Co-infection by some or all of these other infectious agents may interfere with the clinical diagnosis of Lyme borreliosis and/or adversely influence host defense mechanisms, thereby altering landmark characteristics of the disease and the severity of infection. For example, studies conducted by NIAID extramural researchers have shown that co-infection with HGE increases the severity of Lyme borreliosis. The issue of co-infection and its potential implications also is being examined in all of NIAID's clinical studies on Lyme disease.

Antibiotic Therapy

A clinical study on the efficacy of antibiotic therapy for the treatment of chronic Lyme disease was completed in late 2000. It was funded through a contract awarded to the New England Medical Center (NEMC) in Boston and involved randomized, double-blind, placebo-controlled multi-center studies to examine the safety and efficacy of ceftriaxone and doxycycline for the treatment of patients with either seropositive or seronegative chronic Lyme disease. The clinical protocols for these studies, which have been posted on the NIAID Web site at http://www.niaid.nih.gov/dmid/lyme/#2a, were developed through collaboration and extensive discussions with Lyme disease research experts, as well as with an NIAID Lyme disease advisory panel composed of patients with Lyme disease, members of patient advocacy groups, practicing physicians who treat patients with Lyme disease, and basic research scientists with expertise in either infectious diseases or Lyme disease. This Panel provided input on the implementation of the protocols selected for use in this study, as well as on intramural clinical studies.

In late 2000, the Data and Safety Monitoring Board (DSMB) for the NEMC clinical trials reviewed a planned interim analysis of the data. After its review, the DSMB unanimously recommended that NIAID terminate the treatment component of these studies. The preliminary data analysis showed that, after 90 days of continuous antibiotic therapy, there were no significant differences in the percentage of patients who felt that their symptoms had improved, worsened, or stayed the same between the antibiotic treatment and placebo groups in either trial.

In addition, the DSMB further recommended that the investigators continue to follow the study patients to monitor their longer-term safety and to obtain additional information that might have value in determining the underlying basis of chronic Lyme disease and in suggesting more effective therapeutic approaches. These extensive follow-up studies are still in progress; no new therapeutic studies will be contemplated until these have been completed and the results analyzed. The results of the NEMC clinical trials were published in the New England Journal of Medicine (NEJM 345: 85-93, 2001).

Both the intramural and extramural studies mentioned above involved data collection as well as the maintenance of specimen repositories. Such specimens have been made available to other investigators working on Lyme disease and thus have contributed significantly to the development of improved and/or novel diagnostic procedures. Animal models also have provided considerable information on the transmission and pathogenesis of Lyme borreliosis, as well as on the mechanisms involved in the development of protective immunity. The NIAID, in collaboration with NINDS, has broadened these efforts to include comprehensive studies on non-human primate animal models for experimental research on the neuropathology associated with chronic Lyme borreliosis. These studies will expand knowledge of those factors that contribute to the pathology associated with persistent infection of the central nervous system by B. burgdorferi, and ultimately will enable researchers to devise more effective clinical approaches for the treatment of chronic Lyme borreliosis in humans. They also will supplement and enhance the results of current clinical studies on the efficacy of antibiotic therapies for the treatment of chronic Lyme disease, and provide precedents for use in the design of future clinical studies.

Vaccine Production

Two pharmaceutical companies have devoted considerable efforts towards the development of a vaccine for Lyme disease. Double-blind, randomized, placebo-controlled clinical trials involving more than 10,000 volunteers from regions in the U.S. where Lyme disease is highly endemic, have been completed for each of two B. burgdorferi recombinant outer-surface lipoprotein A (OspA) vaccines manufactured by GlaxoSmithKline (formerly SmithKline Beecham [SKB]) and Pasteur Merieux Connaught (PMC). These vaccines were found to be 49 to 68 percent effective in preventing Lyme disease after two injections, and 68 to 92 percent effective in preventing Lyme disease after three injections. The duration of the protective immunity generated in response to the SKB vaccine [LYMErixTM], which was licensed by the FDA in December of 1998, is not known.

Although LYMErixTM has been licensed for use in individuals from 15 to 70 years of age, the results of a recently-completed study involving about 250 children from 5 to 15 years of age indicate that LYMErixTM is well tolerated and highly immunogenic in children as well. A larger pediatric study involving more than 3,000 children from 4 to 14 years of age, showed that just two doses rather than the three usually given to adults, were enough to provide protection; only minor side effects were observed. The FDA is reviewing these findings to determine if LYMErixTM should be approved for use in children four years of age and older. The NIAID was not directly involved in the design and implementation of these particular vaccine trials. However, patents for cloning the genes used for the expression of recombinant OspA, as well as knowledge of the role of antibody(ies) against OspA in the development of protective immunity, were derived from basic research grants funded by the NIAID.

In April 2002, GlaxoSmithKline announced that, even with the incidence of Lyme disease on the increase, sales for the LYMErixTM declined from about 1.5 million doses in 1999 to a projected 10,000 doses in 2002. Although studies conducted by the FDA did not reveal that any reported adverse events were vaccine-associated (Vaccine 20: 1603, 2002), GlaxoSmithKline discontinued manufacturing the vaccine for economic reasons.

The NIAID also is funding pre-clinical studies on the development and testing of other candidate vaccines (e.g., decorin-binding protein A or DbpA) for Lyme disease. MedImmune, Inc. (a NIAID Small Business Innovation Research grantee) and Aventis Pharmaceuticals Inc., reported that a combination vaccine composed of the DbpA and OspA is more effective than either one being given alone in preventing the development of borreliosis in experimental animals. On the basis of these encouraging findings, both companies have entered into an agreement to develop a new, more effective, second-generation vaccine to prevent Lyme disease in humans.

Conclusion

As demonstrated above, NIAID has a comprehensive Lyme disease research portfolio with the goal of advancing the understanding of the disease and developing ways to improve its diagnosis, treatment, and prevention. These efforts highlight several specific avenues of investigation: 1) improving the ability to diagnose Lyme disease in the presence of co-infecting agents; 2) evaluating the efficacy of antibiotic treatment for Lyme disease; 3) researching candidate replacement vaccines for the discontinued LYMErixTM vaccine.

The NIAID is fully committed to continuing to explore these and other, yet-undiscovered areas of research, in the hope that future research findings will provide important clues to better understanding this painful disease.

Lyme disease research will continue to be a priority for the NIAID for the foreseeable future.

Testimony

Statement by

Paul Mead, M.D., M.P.H.

Medical Epidemiologist

Division of Vector-Borne Infectious Diseases

National Center for Infectious Diseases,

Center for Disease Control and Prevention,

U.S. Department of Health and Human Services

on

Hearing: CDC's Lyme Disease Prevention and Control Activities

before the

Connecticut Department of Public Health and the Connecticut Attorney General's Office

January 29, 2004

Good afternoon. I am Dr. Paul Mead, Medical Epidemiologist with the Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases at the Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services. I will concentrate, as requested, on two main issues within my testimony: CDC funding for states to report Lyme disease and the surveillance case definition of Lyme disease.

Overview

Lyme disease is the most prevalent vector-borne infectious disease in the United States. It is one of the nationally notifiable diseases, with more than 23,000 cases reported to the CDC in 2002. If not diagnosed and treated in its early stages, Lyme disease can result in serious complications. Laboratory testing for Lyme disease has improved, but greater understanding is needed of its performance in clinical practice.

CDC Accomplishments

CDC's Lyme disease prevention and control activity is a science-based program of education, research, and service, which partners with the National Institutes of Health and other federal agencies, state and local health departments, and other non-federal organizations. CDC supports national surveillance, epidemiologic response, field and laboratory research, consultation, and educational activities through intramural initiatives. CDC also funds collaborative studies on community-based prevention methods, improved diagnosis and understanding of pathogenesis, tick ecology, and development and testing of new tools and methods for tick control.

CDC's budget for Lyme disease is allocated each year by Congress. CDC received $7.1 million for Lyme disease in FY 2003 and $7.4 million in 2002. CDC distributes the majority of these funds to states and universities in the form of cooperative agreements.

CDC has mapped the national distribution and risk for Lyme disease and has defined environments, activities, and behaviors that place people at high risk of infection. CDC has developed new and effective devices and methods for preventing infection and safely reducing vector ticks in the environment, such as insecticide-treated rodent bait boxes. CDC developed improved and standardized diagnostic tests for Lyme disease and provided physician standards for use of these tests. CDC's research programs have provided an understanding of the pathogenesis of infection with the Lyme disease bacterium, and of the transmission of the bacterium by ticks.

CDC Next Steps

Lyme disease and other emerging tick-borne infectious diseases are cause for increasing concern with regard to public health and safety in the outdoor environment. CDC's program for 2004 and beyond emphasizes the goal of working with Lyme disease endemic communities to develop an Integrated Pest Management (IPM) approach which includes a wide assortment of practical tick control strategies. IPM employs environmental management, biological and chemical control of ticks, and enhanced personal protection through tick avoidance and other measures to prevent Lyme disease.

Other areas of research include the development of natural forest products for use as environmentally acceptable alternatives in pest control, deer- and rodent-targeted methods of insecticide application, further efforts to predict Lyme disease risk on a national scale, and further understanding of host immune responses to infection with the Lyme disease bacterium. Continued education and implementation of improved laboratory tests for early and correct diagnosis and treatment will further the trend of reduced complications from Lyme disease. As mentioned by Dr. Baker, CDC works closely with the NIH on fundamental research related to immune responses and diagnostic development.

CDC Funding for Connecticut Lyme Disease Prevention

As previously mentioned, CDC distributes most of its Lyme disease funds to the states and universities via cooperative agreements. In accordance with federal rules and regulations, cooperative agreements are awarded competitively based on objective review of proposals submitted by state health departments and other applicants. In general, Lyme disease cooperative agreements are re-competed every 3 years.

For over a decade, the Connecticut Department of Public Health has competed successfully for CDC Lyme disease funding, with the amount of funding increasing from approximately $140,000 per year in 1991, to approximately $845,000 per year in fiscal year 2003. Connecticut universities have also competed successfully, receiving just under $490,000 in CDC cooperative agreement funds in fiscal year 2003. Overall, CDC provided approximately $1.4 million to institutions in Connecticut for Lyme and tickborne diseases in fiscal year 2003.

As a partner in the cooperative agreement process, CDC is responsible for assuring that the overall objectives of cooperative agreements are modified over time to reflect new information and changing public health goals. In general, the overall objectives of Lyme disease cooperative agreements have shifted over the last decade from counting cases to devising and testing methods for preventing infection. The Connecticut Department of Public Health's decision to discontinue mandatory laboratory reporting reflects this increased emphasis on prevention. This particular form of surveillance for Lyme disease is costly and relatively inefficient. Money spent on mandatory laboratory reporting decreases the amount of funds available for prevention efforts.

In 2002, after five years of mandatory laboratory surveillance, Connecticut had the highest incidence of reported Lyme disease of any state. This is precisely where the state ranked in 1997, the year before implementing mandatory laboratory surveillance. There is no question that Lyme disease is an important public health concern in Connecticut; the question is how to prevent it. It is towards this question that CDC cooperative agreements are focused.

Lyme Disease Case Definition and Clinical Diagnoses

A clinical diagnosis is made for the purpose of treating an individual patient and should consider the many details associated with that patient's illness. Surveillance case definitions are created for the purpose of standardization, not patient care; they exist so that health officials can reasonably compare the number and distribution of "cases" over space and time. Whereas physicians appropriately err on the side of over-diagnosis, thereby assuring they don't miss a case, surveillance case definitions appropriately err on the side of specificity, thereby assuring that they do not inadvertently capture illnesses due to other conditions.

As adopted by the Council of State and Territorial Epidemiologists, a case of Lyme disease is defined for national surveillance purposes as physician diagnosed erythema migrans > 5 cm in diameter or at least one objective manifestation of late Lyme disease (musculoskeletal, cardiovascular, or neurological) with laboratory confirmation of B. burgdorferi infection using a 2-tiered assay. Laboratory confirmation is considered critical for late stage Lyme disease because the symptoms mimic many other common conditions. Without firm objective evidence of B. burgdorferi infection, persons with other diseases would be counted erroneously as having Lyme disease.

No surveillance case definition is 100% accurate. There will always be some patients with Lyme disease whose illness does not meet the national surveillance case definition. For this reason, CDC has stated repeatedly that the surveillance case definition is not a substitute for sound clinical judgment. Given other compelling evidence, a physician may choose to treat a patient for Lyme disease when their condition does not meet the case definition.

Conclusion

In conclusion, addressing public health issues such as Lyme disease depends on a strong public health system and sustained and coordinated efforts of many individuals and organizations. CDC will continue to work with its partners to develop and implement community-wide strategies to prevent Lyme disease, including educational efforts, tick control efforts, and the development of improved diagnostic methods.

The tick borne spirochete infection known as Lyme disease was named after Lyme, CT – a part of the country where the disease remains endemic. It is therefore especially poignant that the Connecticut state senate unanimously passed Public Act No. 09-128: AN ACT CONCERNING THE USE OF LONG-TERM ANTIBIOTICS FOR THE TREATMENT OF LYME DISEASE.The bill had previously passed the state House, also unanimously

Substitute House Bill No. 6200

Public Act No. 09-128

AN ACT CONCERNING THE USE OF LONG-TERM ANTIBIOTICS FOR THE TREATMENT OF LYME DISEASE.

Be it enacted by the Senate and House of Representatives in General Assembly convened:

Section 1. (NEW) (Effective July 1, 2009) (a) As used in this section, (1) "long-term antibiotic therapy" means the administration of oral, intramuscular or intravenous antibiotics, singly or in combination, for periods of time in excess of four weeks; and (2) "Lyme disease" means the clinical diagnosis by a physician, licensed in accordance with chapter 370 of the general statutes, of the presence in a patient of signs or symptoms compatible with acute infection with borrelia burgdorferi; or with late stage or persistent or chronic infection with borrelia burgdorferi, or with complications related to such an infection; or such other strains of borrelia that, on and after July 1, 2009, are recognized by the National Centers for Disease Control and Prevention as a cause of Lyme disease. Lyme disease includes an infection that meets the surveillance criteria set forth by the National Centers for Disease Control and Prevention, and other acute and chronic manifestations of such an infection as determined by a physician, licensed in accordance with the provisions of chapter 370 of the general statutes, pursuant to a clinical diagnosis that is based on knowledge obtained through medical history and physical examination alone, or in conjunction with testing that provides supportive data for such clinical diagnosis.

(b) On and after July 1, 2009, a licensed physician may prescribe, administer or dispense long-term antibiotic therapy to a patient for a therapeutic purpose that eliminates such infection or controls a patient's symptoms upon making a clinical diagnosis that such patient has Lyme disease or displays symptoms consistent with a clinical diagnosis of Lyme disease, provided such clinical diagnosis and treatment are documented in the patient's medical record by such licensed physician. Notwithstanding the provisions of sections 20-8a and 20-13e of the general statutes, on and after said date, the Department of Public Health shall not initiate a disciplinary action against a licensed physician and such physician shall not be subject to disciplinary action by the Connecticut Medical Examining Board solely for prescribing, administering or dispensing long-term antibiotic therapy to a patient clinically diagnosed with Lyme disease, provided such clinical diagnosis and treatment has been documented in the patient's medical record by such licensed physician.

(c) Nothing in this section shall prevent the Connecticut Medical Examining Board from taking disciplinary action for other reasons against a licensed physician, pursuant to section 19a-17 of the general statutes, or from entering into a consent order with such physician pursuant to subsection (c) of section 4-177 of the general statutes. Subject to the limitation set forth in subsection (b) of this section, for purposes of this section, the Connecticut Medical Examining Board may take disciplinary action against a licensed physician if there is any violation of the provisions of section 20-13c of the general statutes.

Approved June 18, 2009

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CT Mirror

Blumenthal takes Lyme disease fight to the Senate

H.B. No. 5104

Session Year 2013

Printer-Friendly

AN ACT ESTABLISHING A TASK FORCE TO STUDY LYME DISEASE TESTING.

To establish a task force to study Lyme disease testing.

Introduced by: Public Health Committee

Bill History (in reverse chronological order)

Co-sponsors of HB-5104

Rep. Prasad Srinivasan, 31st Dist.

Rep. Melissa H. Ziobron, 34th Dist.

Rep. Juan R. Candelaria, 95th Dist.

Rep. David Zoni, 81st Dist.

Rep. Patricia M. Widlitz, 98th Dist.

Rep. Elissa T. Wright, 41st Dist.

Rep. Noreen S. Kokoruda, 101st Dist.

Rep. Lonnie Reed, 102nd Dist.

Rep. Stephen D. Dargan, 115th Dist.

Rep. Cecilia Buck-Taylor, 67th Dist.

Rep. Jay M. Case, 63rd Dist.

Rep. Charlie L. Stallworth, 126th Dist.

Rep. Catherine F. Abercrombie, 83rd Dist.

Rep. Theresa W. Conroy, 105th Dist.

Rep. Vincent J. Candelora, 86th Dist.

Rep. Fred Camillo, 151st Dist.

Rep. Brenda L. Kupchick, 132nd Dist.

Rep. Al Adinolfi, 103rd Dist.

Rep. Michael L. Molgano, 144th Dist.

Rep. Mike Demicco, 21st Dist.

Rep. Christie M. Carpino, 32nd Dist.

Rep. David Arconti, 109th Dist.

Sen. Toni Boucher, 26th Dist.

Rep. John K. Hampton, 16th Dist.

Rep. Sandy H. Nafis, 27th Dist.

Rep. Auden Grogins, 129th Dist.

Sen. John A. Kissel, 7th Dist.

Click for Public Hearing Testimony

Please direct all inquiries regarding the status of bills to the House and Senate Clerks' Offices.

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