Professor Christian Perrone

[Pages:5]Professor Christian PERRONNE, MD, PhD

3 May 2016

Chief of the Infectious and Tropical Diseases Department

H?pitaux Universitaires Paris-Ile de France-Ouest

Assistance Publique ? H?pitaux de Paris (Greater Paris University Hospitals)

University of Versailles ? St Quentin, Paris-Saclay

92380 Garches, France

c.perronne@aphp.fr

I have been head of the Infectious Diseases Unit in the H?pitaux Universitaires Paris-Ile de FranceOuest since 1994. My predecessor, the late Professor Eric Dournon was a pioneer in the management of Lyme disease in France when the disease was first described at the end of the seventies, and, although it has not been my main research topic, I have, over the past 20 years, acquired a very extensive experience in the clinical management of Lyme disease. I am also strongly involved in the area of public health policy and evidence-based guidelines. I was chairman at the AFSSAPS (the French Drug Agency, now called ANSM) of the working group which developed the official French guidelines for the use of systemic antibiotic treatment in upper and lower respiratory tract infections (Perronne C. Clin Microbiol Infect Dis 2003; 9: 1162-1178). I was chairman of the French National Immunization Technical Advisory Group of experts (Comit? technique des vaccinations, CTV) at the Ministry of Health (the equivalent of the American ACIP) from 2001 to 2007. Since 2007, I have been Chairman of the Communicable Diseases Commission at the French High Council for Public Health (Haut Conseil de la Sant? Publique), the main group of experts making official recommendations for the Health Minister, until March 2016. I am also vice-president of the European Technical Advisory Group of Experts on Immunization (ETAGE) at the World Health Organization. I am past-president of the French College of Professors of Infectious and Tropical diseases (CMIT) and co-founder and pastpresident of the French Federation for Infectious Diseases (F?d?ration Fran?aise d'Infectiologie). I am past-president of the National Council of Universities, sub-section Infectious and tropical diseases.

In a letter that I published in 2011 (Perronne C. Lyme disease antiscience. Lancet Infect Dis, 11, 713719, 2011), I wished to alert the medical community that evidence based data in the literature show that Borrelia burgdorferi serology remains a suboptimal diagnostic tool with poor sensitivity, with the risk of underdiagnosis and underestimation of the prevalence of the disease. I also wanted to emphasize that experts should consider the potential role of other borreliae (not detected by the current tests) and of other micro-organisms that could be involved in the pathophysiology of tick-borne diseases. Since that letter was written, new major developments have occurred that appear to support my views which are now shared by many colleagues:

1. From a historical perspective, the discovery of the Tyrolean iceman shows that the disease was already present in Europe during the ice age.

2. Regarding the diagnostic tests, the American CDC revised their case definition for Lyme disease at the end of 2011, and included a single-tier IgG immunoblot seropositivity as a diagnostic criterion for Lyme disease. However, this new definition has not been taken into account by the current national or international guidelines and is not followed by most of the physicians or health insurance decisionmakers.

3. After dramatically revising their estimates of 30,000 cases to 300,000 cases per year in the USA, the CDC are now concluding (August 2013) that "Lyme disease is a tremendous public health problem in the United States".

4. Several species of borreliae belonging to the Borrelia burgdorferi sensu lato complex (other than B. garinii and B. afzelii already known to be responsible for Lyme disease) are isolated from symptomatic patients increasingly often but, due to the lack of large field studies, their pathogenic role has not been established.

5. Borrelia miyamotoi, despite its close phylogenetic similarity to relapsing fever borreliae, is now recognized as a pathogen responsible for a Lymelike disease in Eurasia and North America. However this species is not currently considered by clinicians, and even if it were, it would not be detected since it does not cross react with B. burgdorferi tests.

6. A novel Borrelia sp. has been found in Boston in the post-treatment serum of a patient presenting with a suspect Lyme neuroborreliosis (Lee).

7. More recently, a novel species has been shown to be responsible for Lyme disease cases in the United States : Borrelia mayonii.

At present, doctors badly lack protocols that could guide them through the uncharted waters they are forced to tread when trying to help patients suffering from these unexplained chronic diseases. During years I made my own experience. Major publications have shown the efficacy of long term treatment for chronic Lyme disease, with a large proportion of patients improving [Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997;25:S52-6. Donta ST. Macrolide therapy of chronic Lyme disease. Med Sci Monit 2003;9:136-42. Clarissou J, Song A, Bernede C, Guillemot D, Dinh A, Ader F et al. Efficacy of a long-term antibiotic treatment in patients with a chronic tick associated poly-organic syndrome (TAPOS). Med Mal Infect 2009;39:108-15].

For their condition to improve, patients with a long history of the disease required longer antibiotic treatments. Several randomized studies tried to evaluate the efficacy of antibiotic treatment versus placebo in chronic Lyme disease. In one study, no difference was shown [Klempner et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001;345:85-92]. However, in the two following studies, a significant albeit limited beneficial effect of antibiotic therapy was demonstrated. In the study by Krupp et al., a four week course of treatment with ceftriaxone improved the fatigue syndrome as reassessed at 6 months, with a significant improvement of 64% in the ceftriaxone group versus 18.5% in the placebo group (p ................
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