Presentatie de meirleir (1)

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.

Chronic Fatigue Syndrome / M.E. (Fukuda & Canadian criteria) ⇓ + 95 % Late Stage Lyme Disease Lyme Stage III + 95 %

Borrelia burgdorferi LTT ⊕

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) 2) 3) 4)

•

Blood sucking arthropods (Ixodes Ricinus): ticks, insects, ...

Sexual transmission between humans (new S.O.A.) Mother-fetus transmission Blood transfusion

Co-infections: – – – – –

Bartonella Babesia Chlamydiae Mycoplasmae Campylobacter

- Rickettsia - Tularemia - Parvovirus B19 - Yersinia

Borrelia species – gramnegative bacteria • U.S.A.: Borrelia burgdorferi • Europe: – Borrelia burgdorferi – Borrelia afzelii – Borrelia garinii – other

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

• 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

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

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

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

Bartonella positive

70%

Borrelia positive

60%

Bartonella positive & Borrelia positive

50% 40% 30% 20% 10% 0% Belgium n=496

Netherlands n=159

Norway n=165

Denmark Sweden n=29

United Kingdom Ireland n=21

Australia n=15

Germany Switzerland Luxembourg n=12

Spain Italy Portugal France n=22

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

Non-parametric Mann â&#x20AC;&#x201C; 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.

Regulation of T-cell immunity

TTHH1 1 cells cells

Protection against intracellular pathogens (viruses, bacteria) Excess: hypersensitivities

IL-12 IFN-γ

Naïve Naïve TT cells cells

IL-4

TTHH2 2 cells cells

Protection against extracellular pathogens (parasites, bacteria) Excess: allergies

TGF-β + IL-6

TTHH17 17 cells cells

Local immunity (mucosa, skin) Protection against fungi, bacteria Excess: autoimmunity, inflammation

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.