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.