Does Biological Sex Matter in Lyme Disease? The Need for Sex-Disaggregated Data in Persistent Illness.

Background: Biological sex should be included as an important variable in clinical research studies to identify outcome differences between men and women. Very few Lyme disease studies were designed to consider sex-based differences or gender bias as an important component of the research design. Methods: To assess sex-based differences in Lyme disease patients who were clinically diagnosed and reported remaining ill for six or more months after receiving antibiotic treatment, we analyzed self-reported clinical data from 2170 patients in the MyLymeData patient registry. We also reviewed previous Lyme disease studies for distribution of patients by biological sex according to stage of illness, data source, and definition of disease used as enrollment criteria. Results: In MyLymeData, women reported more tick-borne coinfections, worse symptoms, longer diagnostic delays, more misdiagnoses, and worse functional impairment than men. No differences were reported in antibiotic treatment response or side effects. In our review, of clinical research trials and data sources, we identified a smaller percentage of women in studies of acute Lyme disease and a larger percentage of women in studies of persistent illness. Samples and data sources that were more reflective of patients seen in clinical practice had a higher percentage of women than randomized controlled trials and post-treatment Lyme disease studies. Conclusion: Our results indicate that biological sex should be integrated into Lyme disease research as a distinct variable. Future Lyme disease studies should include sex-based disaggregated data to illuminate differences that may exist between men and women with persistent illness.

Role of hydroxychloroquine in multidrug treatment of COVID-19.

No abstract present.

Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Workers from India: A Meta-Analysis.

To date, the COVID-19 pandemic has resulted in more than 200 million cases of SARS-CoV-2 infection and more than four million deaths world-wide. 1 Although novel COVID-19 vaccines have become clinically available, the safety and efficacy of these vaccines remains open to question. 2 Alternate approaches to prevention of disease have received little attention, and one medication, hydroxychloroquine (HCQ), has been attacked and dismissed based on flawed studies and political controversy that obscured the value of this treatment as pre-exposure prophylaxis (PrEP) for SARS-CoV-2 infection.

Dermatological and Genital Manifestations of Lyme Disease Including Morgellons Disease.

Although the erythema migrans (EM) skin rash is traditionally considered a hallmark of Lyme disease, other dermatological manifestations of the tickborne disease are less well known. We describe a 49-year-old woman with erosive genital ulcerations, secondary EM rashes and jagged skin lesions associated with Lyme disease. The skin rashes exhibited fibers characteristic of Morgellons disease. Molecular testing confirmed the presence of Borrelia DNA in both vaginal culture and serum specimens. In further studies on a secondary EM lesion containing filaments, Gömöri trichrome staining revealed the presence of collagen in the filaments, while Dieterle and anti-Borrelia immunostaining revealed intracellular and extracellular Borrelia organisms. Intracellular staining for Borrelia was also observed in lymphocytic infiltrates. Lyme disease may present with a variety of genital lesions and dermatological manifestations including Morgellons disease. Careful evaluation is required to determine the presence of Borrelia organisms associated with these dermopathies.

Pre-Exposure Prophylaxis for COVID-19 in Pregnant Women.

Pregnant women are at higher risk for developing severe complications of COVID-19 including preterm delivery, respiratory failure, and death. Although vaccines to prevent COVID-19 are being developed, pregnant women are not included in the current COVID-19 vaccine trials and initially this population may not be eligible for COVID-19 vaccines due to lack of safety testing in pregnancy. As an alternate approach, we discuss the concept of pre-exposure prophylaxis (PrEP) using medications that are approved for use in pregnant women to prevent gestational problems and severe illness in this high-risk population. In particular, the use of hydroxychloroquine PrEP affords a safe and readily available means to avoid COVID-19 complications in pregnancy.

Antibiotic Treatment Response in Chronic Lyme Disease: Why Do Some Patients Improve While Others Do Not?

There is considerable uncertainty regarding treatment of Lyme disease patients who do not respond fully to initial short-term antibiotic therapy. Choosing the best treatment approach and duration remains challenging because treatment response among these patients varies: some patients improve with treatment while others do not. A previous study examined treatment response variation in a sample of over 3500 patients enrolled in the MyLymeData patient registry developed by LymeDisease.org (San Ramon, CA, USA). That study used a validated Global Rating of Change (GROC) scale to identify three treatment response subgroups among Lyme disease patients who remained ill: nonresponders, low responders, and high responders. The present study first characterizes the health status, symptom severity, and percentage of treatment response across these three patient subgroups together with a fourth subgroup, patients who identify as well. We then employed machine learning techniques across these subgroups to determine features most closely associated with improved patient outcomes, and we used traditional statistical techniques to examine how these features relate to treatment response of the four groups. High treatment response was most closely associated with (1) the use of antibiotics or a combination of antibiotics and alternative treatments, (2) longer duration of treatment, and (3) oversight by a clinician whose practice focused on the treatment of tick-borne diseases.

Flattening the Risk: Pre-Exposure Prophylaxis for COVID-19.

To date, more than 35 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), and more than one million have died in the COVID-19 pandemic. International economies are stalled and social isolation based on palpable fear of death remains the order of the day. The United States and other countries are moving toward resuming work activities and social interaction to boost economic recovery. While this makes financial sense, from a medical perspective our population has already suffered and will continue to suffer severe losses in the absence of a viable aggressive prophylaxis strategy for SARS-CoV-2. Herein, we present a plan to address this problem.

Lyme Disease: Diversity of Borrelia Species in California and Mexico Detected Using a Novel Immunoblot Assay.

BACKGROUND: With more than 300,000 new cases reported each year in the United States of America (USA), Lyme disease is a major public health concern. Borrelia burgdorferi sensu stricto (Bbss) is considered the primary agent of Lyme disease in North America. However, multiple genetically diverse Borrelia species encompassing the Borrelia burgdorferi sensu lato (Bbsl) complex and the Relapsing Fever Borrelia (RFB) group are capable of causing tickborne disease. We report preliminary results of a serological survey of previously undetected species of Bbsl and RFB in California and Mexico using a novel immunoblot technique. METHODS: Serum samples were tested for seroreactivity to specific species of Bbsl and RFB using an immunoblot method based on recombinant Borrelia membrane proteins, as previously described. A sample was recorded as seropositive if it showed immunoglobulin M (IgM) and/or IgG reactivity with at least two proteins from a specific Borrelia species. RESULTS: The patient cohort consisted of 90 patients residing in California or Mexico who met the clinical case definition of chronic Lyme disease. Immunoblot testing revealed that 42 patients were seropositive for Bbsl (Group 1), while 56 patients were seropositive for RFB (Group 2). Eight patients were seropositive for both Bbsl and RFB species. Group 1 included patients who were seropositive for Bbss (14), B. californiensis (eight), B. spielmanii (10), B. afzelii/B. garinii (10), and mixed infections that included B. mayonii (three). Group 2 included patients who were seropositive for B. hermsii (nine), B. miyamotoi (seven), B. turicatae (nine), and B. turcica (two). In the remaining Group 1 and Group 2 patients, the exact Borrelia species could not be identified using the immunoblot technique. CONCLUSIONS: Lyme disease is associated with a diverse group of Borrelia species in California and Mexico. Current testing for Lyme disease focuses on detection of Bbss, possibly resulting in missed diagnoses and failure to administer appropriate antibiotic therapy in a timely manner. The genetic diversity of Borrelia spirochetes must be considered in future Lyme disease test development.

Classification and Staging of Morgellons Disease: Lessons from Syphilis.

INTRODUCTION: Morgellons disease (MD) is a contested dermopathy that is associated with Borrelia spirochetal infection. A simple classification system was previously established to help validate the disease based on clinical features (classes I-IV). METHODS: Drawing on historical and pathological parallels with syphilis, we formulated a more detailed staging system based on clinical features as well as severity of skin lesions and corresponding histopathological infection patterns, as determined by anti-Borrelia immunohistochemical staining. RESULTS: Clinical classes I-IV of MD are further categorized as mild, moderate and severe, or stages A, B and C, respectively, based on histopathological findings. Stage A lesions demonstrated little or no immune infiltrates and little or no disorganization of cells; macrophages were not present, and hemorrhage was negligible. Extracellular isolated spirochetes and intracellular staining of keratinocytes in the lower epidermis was occasionally seen. Stage C lesions demonstrated positive staining of keratinocytes in the stratum basale and stratum spinosum and positive intracellular staining of macrophages for Borrelia. Aggregate Borrelia colonies were frequently encountered, hemorrhage was frequent, and intracellularly stained fibroblasts were occasionally seen. Stage B lesions demonstrated a pattern intermediate between Stages A and C. CONCLUSION: The enhanced staging system provides objective criteria to assess the severity of dermopathy in MD. Further studies are needed to determine the optimal treatment for MD based on this staging system related to Borrelia infection.

Line Immunoblot Assay for Tick-Borne Relapsing Fever and Findings in Patient Sera from Australia, Ukraine and the USA.

Tick-borne relapsing fever (TBRF) is caused by spirochete bacteria of the genus Borrelia termed relapsing fever Borreliae (RFB). TBRF shares symptoms with Lyme disease (LD) caused by related Lyme disease Borreliae (LDB). TBRF and LD are transmitted by ticks and occur in overlapping localities worldwide. Serological detection of antibodies used for laboratory confirmation of LD is not established for TBRF. A line immunoblot assay using recombinant proteins from different RFB species, termed TBRF IB, was developed and its diagnostic utility investigated. The TBRF IBs were able to differentiate between antibodies to RFB and LDB and had estimated sensitivity, specificity, and positive and negative predictive values of 70.5%, 99.5%, 97.3%, and 93.4%, respectively, based on results with reference sera from patients known to be positive and negative for TBRF. The use of TBRF IBs and analogous immunoblots for LD to test sera of patients from Australia, Ukraine, and the USA with LD symptoms revealed infection with TBRF alone, LD alone, and both TBRF and LD. Diagnosis by clinical criteria alone can, therefore, underestimate the incidence of TBRF. TBRF IBs will be useful for laboratory confirmation of TBRF and understanding its epidemiology worldwide.

Mixed Borrelia burgdorferi and Helicobacter pylori Biofilms in Morgellons Disease Dermatological Specimens.

BACKGROUND: Morgellons disease (MD) is a dermopathy that is associated with tick-borne illness. It is characterized by spontaneously developing skin lesions containing embedded or projecting filaments, and patients may also experience symptoms resembling those of Lyme disease (LD) including musculoskeletal, neurological and cardiovascular manifestations. Various species of Borrelia and co-infecting pathogens have been detected in body fluids and tissue specimens from MD patients. We sought to investigate the coexistence of Borrelia burgdorferi (Bb) and Helicobacter pylori (Hp) in skin specimens from MD subjects, and to characterize their association with mixed amyloid biofilm development. METHODS: Testing for Bb and Hp was performed on dermatological specimens from 14 MD patients using tissue culture, immunohistochemical (IHC) staining, polymerase chain reaction (PCR) testing, fluorescent in situ hybridization (FISH) and confocal microscopy. Markers for amyloid and biofilm formation were investigated using histochemical and IHC staining. RESULTS: Bb and Hp were detected in dermatological tissue taken from MD lesions. Bb and Hp tended to co-localize in foci within the epithelial tissue. Skin sections exhibiting foci of co-infecting Bb and Hp contained amyloid markers including ß-amyloid protein, thioflavin and phosphorylated tau. The biofilm marker alginate was also found in the sections. CONCLUSIONS: Mixed Bb and Hp biofilms containing ß-amyloid and phosphorylated tau may play a role in the evolution of MD.

Erosive Vulvovaginitis Associated With Borrelia burgdorferi Infection.

We describe a case of acute erosive vulvovaginitis accompanying Borrelia burgdorferi infection. The patient is a 57-year-old woman previously diagnosed with Lyme disease who presented with a painful erosive genital lesion. At the time of the outbreak, she was being treated with oral antibiotics, and she tested serologically positive for B burgdorferi and serologically negative for syphilis. Histological examination of biopsy tissue from the lesion was not characteristic of dermatopathological patterns typical of erosive vulvar conditions. Dieterle-stained biopsy sections revealed visible spirochetes throughout the stratum spinosum and stratum basale, and anti- B burgdorferi immunostaining was positive. Motile spirochetes were observed by darkfield microscopy and cultured in Barbour-Stoner-Kelly-complete medium inoculated with skin scrapings from the lesion. Cultured spirochetes were identified genetically as B burgdorferi sensu stricto by polymerase chain reaction, while polymerase chain reaction amplification of treponemal gene targets was negative. The condition resolved after treatment with additional systemic antibiotic therapy and topical antibiotics. In cases of genital ulceration that have no identifiable etiology, the possibility of B burgdorferi spirochetal infection should be considered.

Detection of tick-borne infection in Morgellons disease patients by serological and molecular techniques.

BACKGROUND: Morgellons disease (MD) is a skin condition associated with Lyme disease (LD) and tick-borne illness. Patients with this skin disorder experience ulcerative lesions that contain multicolored filamentous collagen and keratin inclusions. Infection with various species of Borrelia and other tick-borne pathogens has been detected in tissue and body fluid specimens from MD patients. We sought to explore this association further in a cohort of MD patients. PATIENTS AND METHODS: Sera from 30 patients with MD were tested for antibody reactivity to antigens from the Borrelia burgdorferi (Bb) group and the relapsing fever Borrelia (RFB) group of spirochetes. Tissue and/or body fluid specimens from these patients were also tested for the presence of Bb and RFB infection using PCR technology. In addition, tissue and body fluid specimens were tested for the presence of Bartonella henselae using PCR, and formalin-fixed skin sections from a subset of patients were tested using fluorescent in situ hybridization (FISH) with B. henselae-specific DNA probes. RESULTS: Seroreactivity to Bb, RFB or both was detected in 63% of the cohort, while positive PCR testing for Bb, RFB or both was detected in 53% of the cohort. Overall, 90% of patients tested positive for exposure and/or infection with Borrelia spirochetes. B. henselae infection was detected by PCR in skin sections or body fluids from 20% of the subjects, and B. henselae FISH testing was positive in 30% of the dermatological specimens submitted for study. CONCLUSION: The study demonstrates an association between MD and positive tests for both Bb and RFB spirochetes. In conjunction with previous studies, our study provides corroborative evidence linking MD to Borrelia infection and tick-borne illness.

Relapsing fever Borrelia in California: a pilot serological study.

BACKGROUND: Borrelia spirochetes are tick-borne Gram-negative bacteria that cause disease in humans and animals. Although many studies have focused on Borrelia burgdorferi (Bb), the agent of Lyme disease, recent studies have examined the role of Relapsing Fever Borrelia (RFB) in human disease. In this pilot study, we have evaluated serological reactivity against Bb and RFB in patients residing in California. METHODS: Serological testing for reactivity to Bb and RFB antigens was performed in 543 patients with suspected tick-borne illness using a Western blot technique. Further evaluation of a subset of 321 patients residing in California was obtained. Serum samples were tested for IgM and IgG antibodies reactive with Bb and RFB, and samples were classified by county of residence according to Bb reactivity alone, RFB reactivity alone, and dual reactivity against Bb and RFB. Seroreactivity was ranked in counties with the highest absolute number and the highest prevalence of positive samples. RESULTS: Of the 543 total serum samples, 32% were positive for Bb, 22% were positive for RFB, and 7% were positive for both Bb and RFB. Of the 321 serum samples from patients residing in California, 33% were positive for Bb, 27% were positive for RFB, and 11% were positive for both Bb and RFB. In the California cohort, the highest rates of positive serological testing for Bb were found in Santa Clara, Alameda, and Contra Costa counties, while the highest rates of positive serological testing for RFB were found in Santa Clara, Alameda, Marin, and San Francisco counties. The highest rates of dual reactivity against Bb and RFB were found in Contra Costa, Alameda, and San Francisco counties. Among the 24 counties with patients who were tested, Bb seropositivity alone was found in four counties, RFB seropositivity alone was found in two counties, and seropositivity for both Bb and RFB was found in 14 counties. CONCLUSION: Results of this pilot study suggest that seroreactivity against Bb and RFB is widespread in California, and dual exposure to Bb and RFB may complicate the diagnosis of tick-borne disease. Greater awareness of RFB and broader screening for this tick-borne infection is warranted.

Better drugs for Lyme disease: focus on the spirochete.

Twenty-five years ago, the AIDS epidemic was wreaking havoc around the world. Although "HIV denialists" threatened to undermine research efforts to combat the epidemic, development of targeted antiviral therapy eventually provided effective treatment for the disease. Now the Lyme disease epidemic is wreaking havoc around the world, and "Lyme denialists" are undermining efforts to combat the epidemic. Drawing on our experience with the AIDS epidemic, there is a significant need to develop targeted therapy to control the Lyme disease epidemic.

Clinical evaluation of Morgellons disease in a cohort of North American patients.

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi, the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study.

Persistent Borrelia Infection in Patients with Ongoing Symptoms of Lyme Disease.

INTRODUCTION: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borreliaburgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. METHODS: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of ten control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. RESULTS: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borreliaburgdorferi by three distinct polymerase chain reaction (PCR)-based approaches. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. CONCLUSIONS: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

History of Morgellons disease: from delusion to definition.

Morgellons disease (MD) is a skin condition characterized by the presence of multicolored filaments that lie under, are embedded in, or project from skin. Although the condition may have a longer history, disease matching the above description was first reported in the US in 2002. Since that time, the condition that we know as MD has become a polemic topic. Because individuals afflicted with the disease may have crawling or stinging sensations and sometimes believe they have an insect or parasite infestation, most medical practitioners consider MD a purely delusional disorder. Clinical studies supporting the hypothesis that MD is exclusively delusional in origin have considerable methodological flaws and often neglect the fact that mental disorders can result from underlying somatic illness. In contrast, rigorous experimental investigations show that this skin affliction results from a physiological response to the presence of an infectious agent. Recent studies from that point of view show an association between MD and spirochetal infection in humans, cattle, and dogs. These investigations have determined that the cutaneous filaments are not implanted textile fibers, but are composed of the cellular proteins keratin and collagen and result from overproduction of these filaments in response to spirochetal infection. Further studies of the genetics, pathogenesis, and treatment of MD are warranted.