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: Blood sucking arthropods (Ixodes Ricinus): ticks, insects, ... Sexual transmission between humans (new S.O.A.) Mother-fetus transmission Blood transfusion Co-infections: Bartonella - Rickettsia Babesia - Tularemia Chlamydiae - Parvovirus B19 Mycoplasmae - Yersinia Campylobacter

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 Pearson Chi-Square weight change 0,005 anxiety - which may include panic attacks 0,007 emotional labiality (mood swings) frequent, unusual nightmares 0,002 difficulty moving your tongue to speak 0,024 alcohol intolerance 0,015 Rash of Herpes Simplex of Shingles impotence

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

so all three increased medians for CFS group. 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.

Regulation of T-cell immunity TH1 cells Protection against intracellular pathogens (viruses, bacteria) Excess: hypersensitivities IL-12 IFN-g Naïve T cells TH2 cells Protection against extracellular pathogens (parasites, bacteria) Excess: allergies IL-4 TGF-b + IL-6 TH17 cells Local immunity (mucosa, skin) Protection against fungi, bacteria Excess: autoimmunity, inflammation 16

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.