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Etoricoxib orion 60mg b-Phenergan 40mg, methotrexate 20mg Trial Registration clinicaltrials.gov NCT01097840 Citation: Shoukhrat M, Khoddam H, Khan M (2016) A Comparison of Doxorubicin, Doxorubicin + Phenobarbital and Phenergan in Relapse Prevention of Chronic Lyme Disease. PLoS Med 13(3): e1001841. https://doi.org/10.1371/journal.pmed.1001841 Editor: Martin A. P. Visscher, University of Cologne, GERMANY Received: September 12, 2015; Accepted: March 30, 2016; Published: May 3, 2016 Copyright: © Shoukhrat et al. This is an open access article distributed under the terms of Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: This research was supported by The Lyme Disease Association Research Board, a member of The Lundbeck Foundation. funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: author has declared that no competing interests exist. Introduction Chronic Lyme disease (Chronic Lyme, Mycoplasma infection) is a relatively uncommon tick-borne illness characterized by widespread inflammation of the musculoskeletal-somatic system in its first 5 years of life [1, 2]. Symptoms consist of nonspecific muscle and Prescription drug trafficking canada joint pain, fever, malaise, swelling and cognitive disturbances, often preceded by other erythema migrans symptoms [3]. In this regard, the most common symptom pattern is ick and erythema migrans [3, 4]. Lyme disease is primarily self-limiting; the most notable side effects occur after the disease has progressed to disseminated viremia which leads neuroborreliosis (NTB). Chronic Lyme has become increasingly rare among adults as it is associated with increased mortality [5] and was nearly eliminated from the US by 1990. Today, however, there are few disease-specific reports in the literature, which suggests an increasing incidence in childhood and adults over the past few years. Most patients exhibit at least some erythema migrans symptoms; the more severe disease is likely to cause multiple symptoms, such as cognitive and muscle atrophy well as rashes [6]. Although the clinical spectrum is variable, a few reports have described treatment-resistant cases [7–10]. The cause and treatment of chronic Lyme disease have been examined in numerous case reports [11–15]. Chlamydia pneumoniae (CHL), a co-infection of Lyme disease and Chlamydia, is the most prominent bacteria [11]. Chancroid is a common complication resulting from the Chlamydia infection and usually progresses to relapsing–remitting (RR) or secondary (PRN) Lyme. Treatment options remain controversial despite the importance of CHL in Lyme disease [11–15]. the US, Chlamydia is most common vector-borne illness and CHL is rarely encountered [16] while a significant proportion of tick-borne illnesses is caused by Borrelia burgdorferi (B. burgdorferi) [17]. In fact, B. burgdorferi infection was recently designated as an emerging infection the current risk for is expected to grow over the next decade [18]. Several therapeutic strategies have been suggested in the recent last years for treating individuals with C. pneumoniae infection. However, none of the reported pharmacological strategies to treat C. pneumoniae or B. burgdorferi infections in animals have been studied as in vitro or animal studies have found no effect that can be attributed to the medications [16, 19]. It is widely believed that CHL was an inadvertent result of the initial antibiotic therapy used for Lyme disease in the 1970s. Consequently, antibiotic resistance is increasing due to CHL pathogenesis, which contributes further decline of clinical status in Lyme disease [20]. Moreover, this may be an overlooked source of clinical challenge for some patients as Lyme disease and CHL share a similar clinical picture, such as chronic and progressive inflammation, rashes, neuroborreliosis CNS involvement [19, 21–24]. Several recent clinical trials have been performed with the intention to assess efficacy and safety of the antibiotic therapies for CHL. It has been determined that several of these treatments are safe, have no systemic reactions, do not impair neuropsychological functioning, and have no significant systemic side effects [25–27]. For instance, in 2004 a randomized, double-blind, placebo-controlled trial investigated the use of cef.
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