Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes.

The annual incidence of Lyme disease, caused by tick-transmitted Borreliella burgdorferi, is estimated to be at least 476,000 cases in the United States and many more worldwide. Ten to 20% of antimicrobial-treated Lyme disease patients display posttreatment Lyme disease syndrome (PTLDS), a clinical complication whose etiology and pathogenesis remain uncertain. Autoimmunity, cross-reactivity, molecular mimicry, coinfections, and borrelial tolerance to antimicrobials/persistence have been hypothesized and studied as potential causes of PTLDS. Studies of borrelial tolerance/persistence in vitro in response to antimicrobials and experimental studies in mice and nonhuman primates, taken together with clinical reports, have revealed that B. burgdorferi becomes tolerant to antimicrobials and may sometimes persist in animals and humans after the currently recommended antimicrobial treatment. Moreover, B. burgdorferi is pleomorphic and can generate viable-but-nonculturable bacteria, states also involved in antimicrobial tolerance. The multiple regulatory pathways and structural genes involved in mediating this tolerance to antimicrobials and environmental stressors by persistence might include the stringent (rel and dksA) and host adaptation (rpoS) responses, sugar metabolism (glpD), and polypeptide transporters (opp). Application of this recently reported knowledge to clinical studies can be expected to clarify the potential role of bacterial antibacterial tolerance/persistence in Lyme disease and PTLDS.

Infarto agudo de miocardio en cuatro hospitales de atención secundaria en Cuba en la era COVID-19 / Acute myocardial infarction in four secondary care hospitals in Cuba in the COVID-19 era

RESUMEN Introducción: Las características clínico-epidemiológicas en el diagnóstico, evolución y tratamiento de los pacientes con infarto agudo de miocardio en la era COVID-19 dependen de varios factores. Objetivos: Precisar el comportamiento de algunas variables clínico-epidemiológicas en la atención y tratamiento de los pacientes con infarto agudo de miocardio en el curso de la COVID-19. Método: Se realizó un estudio observacional en cuatro hospitales de atención secundaria en Cuba. Se utilizaron las siguientes variables: número de ingresos por infartos, mortalidad hospitalaria, tiempo de demora mayor de 4 horas desde el inicio de los síntomas y la llegada a la primera asistencia médica y el porcentaje de trombólisis. Se definieron dos grupos, los ingresados entre el 1 de marzo al 30 de septiembre de 2019 (Grupo I) y los ingresados en igual período pero del 2020 (Grupo II). Las comparaciones entre ambos grupos se realizaron utilizando el test de Chi cuadrado. Resultados: Existió una disminución de 53 ingresos por infarto agudo de miocardio en Las Tunas (112 vs. 159, p<0.05), con un incremento del número de ingresos en el Hospital Enrique Cabrera en los pacientes del grupo II (98 vs. 68, p<0.05). Se incrementó el número de fallecidos y la mortalidad hospitalaria en el grupo II en todos los centros con relación al grupo I. En la mayoría de los centros se incrementó la demora desde el inicio de los síntomas y la llegada al lugar de la primera asistencia médica. El porciento de trombólisis fue superior al 50% en la mayoría de los centros en el grupo II. Conclusiones: Las características de la COVID-19 pueden modificar aspectos clínicos y epidemiológicos en la atención y tratamiento de los pacientes con infarto agudo de miocardio.

ABSTRACT Introduction: The clinico-epidemiological characteristics in the diagnosis, evolution and treatment of patients with acute myocardial infarction in the COVID-19 era depend on several factors. Objectives: To determine the behavior of some clinico-epidemiological variables in the management of patients with acute myocardial infarction during de COVID-19 pandemic. Methods: An observational study was carried out in four secondary care hospitals in Cuba. The following variables were used: number of admission due to acute myocardial infarction, hospital mortality, delay longer than four hours from the beginning of the symptoms to the arrival to the first medical assistance, and thrombolysis percentage. Two groups were defined, those admitted from March 1st to September 30th, 2019 (Group I) and those admitted in the same period, but from 2020 (Group II). Comparisons between both groups were made using the chi square test. Results: There was a decrease of 53 admissions due to acute myocardial infarction in Las Tunas (112 vs. 159; p<0.05), with an increase in the number of admissions in the Hospital Enrique Cabrera in patients from Group II (98 vs. 68; p<0.05). The number of deaths and hospital mortality in Group II increased in all the centers in relation to Group I. In most of the hospitals there was an increase of the time elapsed from the beginning of the symptoms to the arrival to the first medical assistance. Thrombolysis percentage in Group II was higher than 50% in most of the centers. Conclusions: The characteristics of COVID-19 may modify the clinical and epidemiological aspects in the management of patients with acute myocardial infarction.

Management of patients presenting with generalized musculoskeletal pain and a suspicion of Lyme disease.

Lyme disease is caused by bacteria of the B. burgdorferi sensu lato complex, and can give polymorphic clinical manifestations that can affect several organs such as the skin, the central nervous system, or the joints. In recent years, patients' associations and physicians have been supporting the hypothesis that this infection would manifest as chronic generalized musculoskeletal pain symptoms, named "chronic Lyme disease". Fibromyalgia is a clinical presentation characterized by chronic generalized musculoskeletal pain with a major impact on quality of life and social and psychological functioning. We analyzed existing literature data on pain syndromes associated with Lyme disease (post-treatment Lyme disease syndrome) or tick bites (polymorphic symptoms after a tick bite). We also analyzed existing data on the diagnosis, pathophysiology, and treatment of fibromyalgia. Our review shows that post-treatment Lyme disease syndrome has characteristics very close to post-infectious fibromyalgia. On the other hand, patients presenting for Lyme disease screening because of chronic generalized musculoskeletal pain symptoms after a tick bite should also be screened for fibromyalgia to allow appropriate management. Antibiotics are not recommended here.

Functional neuroimaging in patients presenting with somatoform disorders: A model for investigating persisting symptoms after tick bites and post-treatment Lyme disease syndrome?

Approximately 10% of patients presenting with Lyme disease experience fatigue, musculoskeletal pain, concentration disorders, or short-term memory deficits in the six months following treatment. This entity has been defined as post-Lyme disease syndrome or post-treatment Lyme disease syndrome. The pathophysiology of this syndrome is unknown, but neither persistence of the bacterium nor effectiveness of antibiotics are currently reported in the literature. The French High Council for Public Health (French acronym HCSP) has recently defined a new entity called "persistent polymorphic symptoms after a tick bite" allowing for designing studies to better understand these subjective presentations, for which objective biomarkers are currently lacking. This entity encompasses patients experiencing fatigue and generalized pain in the months following a tick bite and can be associated with several subjective symptoms with major impact on the quality of life. In the field of somatoform disorders, this article reviews functional neuroimaging studies in patients presenting with subjective complaints and discusses potential clinical implications for persisting symptoms after tick bites and post-treatment Lyme disease syndrome.

Association of small fiber neuropathy and post treatment Lyme disease syndrome.

OBJECTIVES: To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction. METHODS: This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored. RESULTS: 10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv. CONCLUSIONS: SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS.

Post-bacterial infection chronic fatigue syndrome is not a latent infection.

Post-infectious chronic fatigue syndrome is a public health problem. Etiologies and physiopathological mechanisms are unknown. Some viruses are known to be involved in post-infectious chronic fatigue syndrome, but the role of bacterial infection is still questioned, especially in cases of post-treatment Lyme disease syndrome where subjective symptoms are regularly attributed to the presence of the dormant bacterium without scientific evidence. However, the medical experience of recalcitrant infections, relapses, and reactivations questions the role of "dormant bacteria" in asymptomatic latent infections as well as in subjective symptoms. We summarized scientific literature data on post-bacterial infection chronic fatigue syndrome, the role of dormant bacteria in latent infections, and bacterial asymptomatic carriage. Subjective symptoms described in post-infectious chronic fatigue syndromes are still misunderstood and there is no evidence suggesting that such symptoms could be related to dormant bacterial infection or carriage of viable bacteria. Psychological trauma may be part of these subjective symptoms. Post-infectious chronic fatigue syndrome could nonetheless be due to unknown microorganisms. Antibiotic treatment is not required for latent infections, except for latent syphilis and latent tuberculosis infections to prevent, after the primary infection, progression to the secondary or tertiary stage of the disease.