late stage lyme disease kenny l. de meirleir, internal medicine emeritus gewoon hoogleraar v.u.b....

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LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine • Emeritus Gewoon Hoogleraar V.U.B. •Clinical Professor of Pathology, University of Nevada, Reno, U.S.A. •Medical Director Himmunitas VZW (Brussels) & WPI, University of Nevada, Reno, Nevada, U.S.A.

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Page 1: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

LATE STAGE LYME DISEASE

Kenny L. De Meirleir, internal medicine

• Emeritus Gewoon Hoogleraar V.U.B.•Clinical Professor of Pathology, University of Nevada, Reno, U.S.A.•Medical Director Himmunitas VZW (Brussels) & WPI, University of

Nevada, Reno, Nevada, U.S.A.

Page 2: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Chronic Fatigue Syndrome / M.E. (Fukuda & Canadian criteria)

+ 95 % Late Stage Lyme Disease

Lyme Stage III

+ 95 % Borrelia burgdorferi LTT

Page 3: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Lyme Stage III = Late Stage Lyme Disease• Multisystem disease with high morbidity• Incidence in Belgium: UNKNOWN

> 100.000 (up to 500.000) patients• Transmission:

1) Blood sucking arthropods (Ixodes Ricinus): ticks, insects, ...2) Sexual transmission between humans (new S.O.A.)3) Mother-fetus transmission4) Blood transfusion

• Co-infections:– Bartonella - Rickettsia– Babesia - Tularemia– Chlamydiae - Parvovirus B19– Mycoplasmae - Yersinia– Campylobacter

Page 4: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Borrelia species – gramnegative bacteria

• U.S.A.: Borrelia burgdorferi

• Europe:– Borrelia burgdorferi– Borrelia afzelii– Borrelia garinii– other

Page 5: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

DIAGNOSTIC TESTS• Borrelia burgdorferi antibody tests (Elisa, C6 peptide,

Western Blot→ mostly negative in LSLD

• Borrelia PCR tests:– Low sensitivity in blood– High specificity when combined and confirmed by sequencing

(U.L.)• Borrelia burgdorferi LTT*:

– Indirect test– Valuable in LSLD

• LTT accepted by FDA in 2011

• Borrelia culture→ not widely used; still investigational

• Microscopic detection of Borrelia spirochetes:– Semen– Vaginal swap

Page 6: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

• Early treatment (< 2 months): no chronic disease• Late treatment: outcome uncertain – many

develop “chronic diseases”: ME/CFS, ALS, MS, ...• Chronic microglial activation in LSLD – low grade

neuroinflammation• Markers blood:

– sCD14 (LPS)– PGE2– IL-8– Number of CD57+ lymphocytes in the blood– Other pro-inflammatory cytokines and chemokines

• No vaccine available

Page 7: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Bartonella – gramnegative bacteria• Bartonella henselae – cat scratch disease

Bartonella quintana – trench fever• 31 other species (8 subspecies are known to infect

humans)• Only commercial antibody tests for Bartonella henselae• PCR with sequencing (only in Belgium)• Culture of Bartonella – not approved by FDA yet for

clinical use• Infects endothelial cells in humans• Infect red blood cells – 3-4 Bartonella / millions red blood

cells• Cats = reservoir: 1.000.000 Bartonella / million red blood

cells

Page 8: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Symptoms Bartonella positive vs. Bartonella negative

SYMPTOMS Pearson Chi-Square

weight change 0,005

anxiety - which may include panic attacks 0,007

emotional labiality (mood swings) 0,005

frequent, unusual nightmares 0,002

difficulty moving your tongue to speak 0,024

alcohol intolerance 0,015

Rash of Herpes Simplex of Shingles 0,005

impotence 0,005

Page 9: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Bartonella & Borrelia 15/10/2011 - 15/10/2012

0%

10%

20%

30%

40%

50%

60%

70%

Belgium n=496

Netherlands n=159

Norway n=165

Denm ark Sweden

n=29

United Kingdom Ireland

n=21

Aus tralia n=15

Germ any Switzerland Luxem bourg

n=12

Spain Italy Portugal France

n=22

Bartonella positive

Borrelia positive

Bartonella positive& Borrelia positive

Page 10: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Box plots ( line in box is median and size box is interquartile range : 50 % of centrally located points)

Page 11: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,
Page 12: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,
Page 13: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Non-parametric Mann – Whitney test performed for two independent groups :

Conclusion : for all three variables : MW is significant with p-value < 0.0009,so all three increased medians for CFS group.

Page 14: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,
Page 15: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,
Page 16: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Regulation of T-cell immunity

Naïve T

cells

Naïve T

cells

TH1cellsTH1cells

TH2cellsTH2cells

TH17cellsTH17cells

Protection againstintracellular pathogens(viruses, bacteria)Excess: hypersensitivities

Protection againstextracellular pathogens(parasites, bacteria)Excess: allergies

Local immunity(mucosa, skin)Protection againstfungi, bacteriaExcess: autoimmunity, inflammation

IL-12

TGF- + IL-6

IL-4

IFN-

Page 17: LATE STAGE LYME DISEASE Kenny L. De Meirleir, internal medicine Emeritus Gewoon Hoogleraar V.U.B. Clinical Professor of Pathology, University of Nevada,

Borrelia: prevention

• Reservoir: Rodents / mammals mice / cats / deer ...new strategies to control tick-born diseases

• Early detection tick-born diseases – G.P. education

• Screening all pregnant women• Screening of blood – blood transfusion• Recognize Borrelia as a S.O.A.