Pennsylvania House Human Services Committee Hearing

House Bill #272

Robert C Bransfield, MD, DLFAPA

President ILADS

President New Jersey Psychiatric Association

Clinical Associate Professor RWJ-UMDNJ Med School

Board of Trustees Medical Society of NJ

August 30, 2011

Relevant Background

45 year interest in the causes of disease and studying the association between infections and chronic mental and somatic diseases

Organized and operate Microbes and Mental Illness Internet Discussion Group (400+ international membership)

American Psychiatric Association: Active in setting policy for insurance & pharmacy benefit management issues, access to care, mental health parity, media

Active with German Psychoimmunology Group Treated thousands of patients with mental symptoms

associated with Lyme/tick-borne diseases

ILADS Mission Statement

ILADS is a nonprofit, international, multidisciplinary medical society, dedicated to the diagnosis and appropriate treatment of Lyme and its associated diseases. ILADS promotes understanding of Lyme and its associated diseases through research and education and strongly supports physicians and other health care professionals dedicated to advancing the standard of care for Lyme and its associated diseases.

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In the 1600s Dr Thomas Wynne, William Penn’s physician and the first speaker for the Pennsylvania Assemblies who was also my ancestor treated a smallpox epidemic on the good ship Welcome threatening the early immigrants to Pennsylvania. Today we have a different epidemic—Lyme disease.

Lyme Disease: A Public Health Failure Causing a Public Health Crisis

Lyme disease draws critical attention to a number of problems in our healthcare system.

A critical issue in the Lyme disease controversy is how narrow or broad the disease is defined: CDC epidemiological definition (it keeps

changing) Narrow research definition Broad clinical definition

Patterns of Lyme disease diagnosis and treatment by family physicians in a southeastern state

This study examined how often physicians in Georgia diagnose and treat Lyme disease as well as the criteria they use to reach a diagnosis of Lyme disease

Of 710 responses, 167 physicians treated 316 cases of Lyme disease without a firm diagnosis. In addition, 125 physicians diagnosed 262 cases of Lyme disease, 130 without serologic testing and 132 with serologic testing. Family Physicians in Georgia diagnose Lyme disease at a rate 40 times greater than the surveillance case rate reported in Georgia

Boltri JM, Hash RB, Vogel RL. Mercer. J Community Health. 2002 Dec;27(6):395-402

As a psychiatrist I see the failures of our healthcare system

If a patient’s symptoms are “medically unexplained” by current beliefs, the patient is considered to need a psychiatrist.

In regard to Lyme disease, the late stage symptoms are mostly neuropsychiatric.

I have seen thousands of patients with a broad spectrum of neurological, cognitive and psychiatric symptoms, including cases of suicide, violence, homicide, autism, developmental disabilities and dementia.

Prevalence of Parent-Reported Diagnosis of Autism Spectrum Disorder Among Children in the US, 2007

The weighted current ASD point-prevalence was 11 per 1000. We estimate that 673,000 US children have ASD.[1]

According to background information in the study, the life-time healthcare costs for a person with autism are estimated to be more than $16 million.[1]

Chronic infections may be a contributor in well over 50% which would be trillions of dollars.

1. Kogan MD, Blumberg SJ, Schieve LA et al. Pediatrics. 2009 Oct 5.

Chronic Infections Provoke the Immune System & Cause Chronic Diseases

Infection orComplex

Interactive Infections

Pathophysiology Causing Symptoms

Immune EffectsTh1 & Th2

Poor Concentration

Social Withdrawal

Anorexia

Hypersomnia

Malaise

Anhedonia

Weakness

Cytokines Induce Sickness Behavior

Musselman DL, et al. N Engl J Med 2001;344:961-966.

Sickness Syndrome(Mediated by Proinflammatory Cytokines IL-1, IL-6, and TNF)

Persistent B burgdorferi Infections Cause Persistence of Sickness Syndrome

The IDSA guidelines categorize chronic mood and cognitive changes associated with tick-borne diseases as “subjective and nonspecific.”

Basic psychoimmunology demonstrates this symptom cluster is associated with cytokine mediated sickness syndrome as a result of persistent inflammation.

Persistent B burgdorferi infections cause persistent immune provocation and persistent inflammation.

Research & Clinical Observation:Microbes & TBD Cause Mental Illness Thousands of peer-reviewed journal articles

demonstrate the causal association between infections and mental illness.

250 peer reviewed scientific articles demonstrate the causal association between Lyme/tick-borne disease and mental illness.

Clinical observation by front line physicians also supports this view.

Some microbes associated with mental symptoms & mental illness I

Spirochetes: Borrelia afzelii (Lyme disease in UK,

Europe) Borrelia burgdorferi sensu stricto (Lyme

disease in USA,UK,Europe) Borrelia garinii (Lyme disease in UK,

Europe) Borrelia hermsii (Relapsing Fever) Borrelia turicatae (Relapsing Fever) Leptospira (Leptospirosis) Treponema pallidum pallidum (Syphilis) Bacteria: Anaplasmas phagocytophilum (Human

Granulocytic Ehrlichiosis) Bartonella henselae (cat scratch fever) Bartonella quintana (trench fever) Bartonella rochalimae (Bartonellosis) Brucella (Brucellosis) Chlamydophilia pneumoniae (Chlamydia) Chlamydophila psittaci (Chlamydia)

Coxiella burnetti (Q-Fever and "Post-Q Fever Fatigue Syndrome")

Ehrlichia chaffeensis (Human Monocytic Ehrlichiosis)

Francisella tularensis (Rabit Fever or Tularemia)

Haemophilus influenzae (Haemophilus) Helicobacter pylori Listeria Meningococcus (Meningococcal Meningitis) Mycoplasma fermentans Mycoplasma pneumoniae Mycobacterium tuberculosis (Tuberculosis) Rickettsia. akari (Rickettsialpox) Rickettsia rickettsii (Rocky Mountain

Spotted Fever) Rickettsia species (Eastern tick-borne

Rickettsiosis) Shigella (Shigellosis) Streptococcus pneumoniae or

Pneumococcus (Pneumonia) Streptococcus (PANDAS, Sydenham’s

Chorea, St Vitus Dance)

Bransfield RC. Pediatric Health. April 2009, Vol. 3, No. 2, Pages 125-140.

Some microbes associated with mental symptoms & mental illness II

Viruses: Borna virus Chikungunya virus Coltiviruse (Colorado Tick Fever) Coronaviruses Coxsackie virus Cytomegalovirus Enterovirus Flaviviridae virus (Japanese B encephalitis & Tick-

borne encephalitis virus) Hepatitis C virus Herpes virus family Human endogenous retroviruses Human herpesvirus 4 or Epstein-Barr virus Human immunodeficiency virus Human T-Cell Lymphotropic Virus Type 1 Influenza

A virus subtype H3N2 (Hong Kong Flu) Influenza virus Pandemic Influenza of 1918 Papopavirus Paramyxovirus (Measles virus) Parvo B19 Poliovirus Rabies virus Rubella Toga virus

Varicella zoster virus(Chicken Pox) Viral meningitis West Nile virus XMRV/HGRV Protozoa: Plasmodium (Malaria) Babesia microti (Babesiosis) Babesia duncani (Babesiosis) Other Babesia species (Babesiosis) Leishmania (Leishmmaniasis) Toxoplasma gondii (Toxoplasmosis) Parasites: Blastocystis (Blastocystosis) Strongyloides stercoralis (Strongyloidiasis) Taenia solium (Neurocysticercosis or Cysticercosis) Fungal: Cryptocococcus Coccidiomycosis Histomycosis Yeast: Candida albicans (Candidiasis) Candida dubliniensis Prion Variant Creutzfeldt-Jakob

Bransfield RC. Pediatric Health. April 2009, Vol. 3, No. 2, Pages 125-140.

CDC: Emerging Infectious Determinants of Chronic Diseases

Non-communicable chronic diseases can stem from infectious agents.

Identifying the relationships can affect health across populations, creating opportunities to reduce the impact of chronic disease by preventing or treating infection.

Infectious agents likely determine more cancers, immune-mediated syndromes, neurodevelopmental disorders, and other chronic conditions than currently appreciated.

To capitalize on these opportunities, clinicians, public health practitioners, and policymakers must recognize that many chronic diseases may indeed have infectious origins.

Siobh M. et al (CDC). Emerging Infectious Determinants of Chronic Diseases. Emerging Infectious Diseases. (2006)Vol. 12, No. 7

NIH Human Microbiome Project

A study researching all of the various microbes that live in people. The project has already established that the bacteria in the human microbiome collectively possess at least 100 times as many genes as the 20,000 or so in the human genome.

Bacterial cells outnumber human cells by 10 to 1 Humans depend on their microbiome for

essential functions, including digestion, leading microbiologists to conclude that a person should really be considered a superorganism.

With Emerging DiseasesThink Outside the Box

Always move forward

Medicine is undergoing a paradigm shift. High level researchers and some community

physicians recognize the importance of infections and immune reactions to them towards causing many previously unexplained chronic diseases.

Just as mathematics shifted from Newton to Einstein, we need to make a similar shift in medicine to use more complex models to understand complex disease.

Categories of disease causation

genetic (inherited alleles)

parasitic noninfectious environmental(diet, lifestyle, chemicals, radiation)

Paul W. Ewald

Disease Models

Bransfield RC. Pediatric Health. April 2009, Vol. 3, No. 2, Pages 125-140.

Persistent Infections & Lyme/Tick-borne Disease Cause…

Chronic Somatic Illnesses

Chronic Mental Illness

Theoretical Biology X X

Pathophysiology X X

Infectious Disease X X

Immunology X X

Psychoimmunology NA X

Psychiatry NA X

Animal Studies X X

Clinical Observations X X

International Studies X X

Epidemiology X X

Risk of Disease vs. Treatment

If Lyme disease is benign, the risk of the disease may not outweigh the risk of treatment.

If Lyme disease is serious, the risk of the disease may outweigh the risk of treatment.

Chronic Lyme Disease—The Standard of Careξ Two equally legitimate but divergent standards of care currently exist for

the diagnosis and treatment of Lyme disease: IDSA guidelines and ILADS guidelines

1) Johnson L, Stricker RB. Treatment of Lyme disease: a medicolegal assessment. Expert Rev Anti Infect Ther. 2004 Aug;2(4):533-57.

2) Evidence-based guidelines for the management of Lyme Disease.

Cameron, Horowitz, et al. Expert Review of Anti Infective Therapy 2(1)

2004ξ Many doctors in the United States do not follow IDSA guidelines. They

treat for seronegative disease, and treat for extended periods of time. “For chronic Lyme disease, 57% of responders treat 3 months or more.”

ξ Ziska MH, Donta ST, Demarest FC. Physician preferences in the diagnosis and treatment of Lyme disease in the United States. Infection 1996 Mar-Apr;24(2):182-6.

Horowitz R, Phillips S.

One Opinion

Lyme is difficult to catch, easy to treat, is never chronic and the current tests are very reliable

Analysis of Overall Level of Evidence Behind Infectious Diseases Society of America Practice Guidelines Conclusions More than half of the current

recommendations of the IDSA are based on level III evidence only. Until more data from well-designed controlled clinical trials become available, physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions.

Lee DH, Ole Vielemeyer O. Arch Intern Med. 2011;171(1):18-22

Guidelines vs. Clinical Judgment

Guidelines assist but never replace clinical judgment. We treat patients, not diseases and guidelines are based upon scientific studies that have different degrees of relevance to the unique clinical circumstances of any given patient.

Osler: History, Examination & Clinical Judgment

"There is no more difficult art to acquire than the art of observation."

"The good observer is not limited to the large hospital.“

"If you listen long enough, the patient will give you the diagnosis."

"Medicine is learned by the bedside and not in the class room. Let not your conception of manifestations of disease come from work heard in the lecture room or read from the book: see and then research, compare and control. But see first.“

Lyme Disease (Borrelia burgdorferi) CDC 2011 Case Definition CSTE Position Statement Number: 10-ID-06

“This surveillance case definition was developed for national reporting of Lyme disease; it is not intended to be used in clinical diagnosis.”

CDC http://www.cdc.gov/osels/ph_surveillance/nndss/casedef/lyme_disease_current.htm

Sensitivity/Specificity of Commercial Two-Tier Testing for Lyme Disease

Study/Year Sensitivity Specificity •Schmitz et al, 1993 66% 100% Engstrom et al, 1995 55% 96%•Ledue et al, 1996 50% 100%•Trevejo et al, 1999 29% 100%• Nowakowski, 2001 66% 99% •Bacon et al, 2003 68% 99% •MEAN TOTAL 56% 99%

Stricker and Johnson BMJ 2007; 335:1008

AIDS testing has a sensitivity of 99.5% Would an AIDS test with a sensitivity of 56% be satisfactory?

Sensitivity/Specificity of Commercial Two-Tier Testing for Lyme Disease*

Stricker & Johnson, Minerva Med. 2010;101:419-25.

Study/Year Location Patients/Controls Sensitivity Specificity

Schmitz et al 1993

USA 25/28 66% 100%

Engstrom et al 1995

USA 55/159† 55% 96%

Ledue et al 1996

USA 41/53 44% 100%

Tilton et al 1997

USA 23/23 45% 100%

Trevejo et al 1999

USA 74/38 29% 100%

Bacon et al 2003

USA 106/559 67% 99%

Binnicker et al 2008

USA 35/5 49% 100%

Steere et al 2008

USA 76/86†† 18% 99%

TOTALS

USA: 8

435/951

46%

99%

* Limited to studies from USA that included negative controls † Non-commercial ELISA and Western blot †† Non-commercial ELISA

Evidence Based Medicine

The best evidence available Clinical judgment Patient considerations

What obstructs forward progress?

Dr Willie Burgdorfer, who discovered Borrelia burgdorferi, the spirochete causing Lyme, stated—“The controversy in the Lyme disease research is a shameful affair and I say this because the whole thing is politically tainted. Money goes to the same people who have for the last 30 years produced the same thing—nothing.”*

*Under Our Skin

This raises critical questions

How much NIH and CDC Lyme disease research has help patients in the past 30 years?

Could this disease have been improperly defined by a group of researchers to maintain the flow of research grant money to themselves, their institutions and their collaborators?

Total allocation of funding for tick-borne disease studies by agency/organization, 2006-2010

Total allocation of funding for tick-borne disease studies by study type, 2006-2010

The IDSA Lyme disease guidelines authors had:

$92,000,000 in NIH & CDC Lyme grants $130,000,000 in NIH & CDC Lyme grants to their

institutions & more to other collaborators 200 Lyme related patents

[The IDSA Lyme disease guidelines review panel considered income of $10,000 from treating Lyme patients to be a conflict of interests.]

Finding Answers

Religion is based upon faith Governments are based upon authority or

majority Science is based upon evidence Medicine is based upon a combination of the

best evidence available, clinical judgment, patient preferences and ethics

Freedom in Medicine

Dr. Benjamin Rush, signer of the Declaration of Independence and personal physician to George Washington stated—“Unless we put medical freedom into the Constitution, the time will come when medicine will organize into an undercover dictatorship to restrict the art of healing to one class of men and deny equal privileges to others: The Constitution of this Republic should make a special privilege for medical freedom as well as religious freedom.”

The Solution

Improve accurate epidemiological capability Identifying and dealing with the imbedded

interests that resist forward progress A shift towards more clinically based and more

credible research Public education, physician education Vote YES for House Bill #272

Thanks for your attention, commitment to preserve the integrity of our healthcare system and your help to our patients with Lyme & associated diseases.