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Purpose of Review: Because both incidence and awareness of tick-borne infections is increasing, review of major infections and recent advances related to their diagnosis and management is important., Recent Findings: A new algorithm, termed modified two-tier testing, for testing for antibodies to Borrelia burgdorferi , the cause of Lyme disease, has been approved and may replace traditional two-tier testing. In addition, doxycycline is now acceptable to use for treatment of and/or prophylaxis for Lyme disease for up to 21 days in children of any age. Borrelia miyamotoi , a bacterium in the relapsing fever type of Borrelia, is the first of this type of Borrelia that is transmitted by hard-bodied ticks such as Ixodes scapularis., Summary: Awareness of these infections and advances in their diagnosis and treatment is important to assure the best outcomes for affected patients. Table 1 contains a summary of infections discussed., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Lyme disease is an infection caused by Borrelia burgdorferi sensu lato, which is transmitted to humans through the bite of an infected Ixodes tick. The majority of patients recover without complications with antibiotic therapy. However, for a minority of patients, accompanying non-specific symptoms can persist for months following completion of therapy. The constellation of symptoms such as fatigue, cognitive dysfunction, and musculoskeletal pain that persist beyond 6 months and are associated with disability have been termed post-treatment Lyme disease syndrome (PTLDS), a subset of a broader term "chronic Lyme disease." Chronic Lyme disease is a broad, vaguely defined term that is used to describe patients with non-specific symptoms that are attributed to a presumed persistent Borrelia burgdorferi infection in patients who may or may not have evidence of either previous or current Lyme disease. The diagnoses of chronic Lyme disease and of PTLDS have become increasingly relevant to the practice of immunologists due to referrals for consultation or for intravenous immunoglobulin (IVIG) treatment. This review aims to explore the relationship between chronic Lyme disease, post-treatment Lyme disease syndrome, and the immune system. Here, we review the current literature on (1) issues in conventional and alternative diagnostic testing for Lyme disease, (2) the hypothesis that B. burgdorferi infection can persist despite appropriate use of recommended antibiotics, (3) current theories regarding B. burgdorferi's role in causing both immune dysregulation and protracted symptoms, and (4) the use of IVIG for the treatment of Lyme disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

A critical analysis was conducted of a doxycycline treatment trial of Indian rhesus macaques. In this treatment trial, the investigators attempted to infect the primates with Borrelia burgdorferi sensu stricto by at least 10 tick bites from artificially infected ticks. None of the primates became ill; nevertheless, 5 primates were treated with a 28-day course of oral doxycycline. In contrast to the conclusions of the authors, the data did not convincingly document the existence of viable B. burgdorferi in antibiotic-treated primates. The investigators were unable to cultivate the spirochete from any animal after treatment using highly sensitive in vitro methods. Like many prior animal studies, the current study also did not document that the doxycycline exposure in these animals was similar to that expected in humans. Numerous additional methodologic problems are discussed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Positive blood cultures for Lyme borrelia have been well documented in untreated patients with early Lyme disease. In this report we review the validity of three studies that reported the recovery of Borrelia burgdorferi sensu lato from the blood of a high proportion of patients for whom no evidence was presented, and no claim was made, that the patients had untreated early Lyme disease. In two of the studies the patients had been treated extensively with antibiotics for Lyme disease before the cultures were obtained. Critical evaluation of the three reports suggests that they are invalid. Indeed, two subsequently published studies could not reproduce the results of one of the reports. In a published analysis of another of the reports, investigators from the Centers for Disease Control and Prevention concluded that the cultures were likely to have been contaminated. When the biologic plausibility of recovering borrelia from blood is extremely low, the level of scientific rigor required of a study that claims a positive result should be particularly high., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose of Review: Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne illness in the United States. The pathogenesis, ecology, and epidemiology of Lyme disease have been well described, and antimicrobial treatment is very effective. There has been controversy about whether infection can persist and cause chronic symptoms despite treatment with antimicrobials. This review summarizes recent studies that have addressed this issue., Recent Findings: The pathogenesis of persistent nonspecific symptoms in patients who were treated for Lyme disease is poorly understood, and the validity of results of attempts to demonstrate persistent infection with B. burgdorferi has not been established. One study attempted to use xenodiagnosis to detect B. burgdorferi in patients who have been treated for Lyme disease. Another study assessed whether repeated episodes of erythema migrans were due to the same or different strains of B. burgdorferi. A possible cause of persistent arthritis in some treated patients is slow clearance of nonviable organisms that may lead to prolonged inflammation. The results of all of these studies continue to provide evidence that viable B. burgdorferi do not persist in patients who receive conventional antimicrobial treatment for Lyme disease., Summary: Patients with persistent symptoms possibly associated with Lyme disease often provide a challenge for clinicians. Recent studies have provided additional evidence that viable B. burgdorferi do not persist after conventional treatment with antimicrobials, indicating that ongoing symptoms in patients who received conventional treatment for Lyme disease should not be attributed to persistent active infection.

The authors of 4 National Institutes of Health-sponsored antibiotic treatment trials of patients with persistent unexplained symptoms despite previous antibiotic treatment of Lyme disease determined that retreatment provides little if any benefit and carries significant risk. Two groups recently provided an independent reassessment of these trials and concluded that prolonged courses of antibiotics are likely to be helpful. We have carefully considered the points raised by these groups, along with our own critical review of the treatment trials. On the basis of this analysis, the conclusion that there is a meaningful clinical benefit to be gained from retreatment of such patients with parenteral antibiotic therapy cannot be justified., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A critical analysis of two treatment trials of Chinese rhesus macaques infected with Borrelia burgdorferi indicates that insufficient attention was placed on documenting the blood levels, pharmacokinetics, and pharmacodynamic parameters of the antibiotics used in this host. Consequently, it is impossible to conclude that the findings have validity in judging the efficacy of doxycycline or ceftriaxone for the treatment of Borrelia burgdorferi in this animal model.

Advocacy for Lyme disease has become an increasingly important part of an antiscience movement that denies both the viral cause of AIDS and the benefits of vaccines and that supports unproven (sometimes dangerous) alternative medical treatments. Some activists portray Lyme disease, a geographically limited tick-borne infection, as a disease that is insidious, ubiquitous, difficult to diagnose, and almost incurable; they also propose that the disease causes mainly non-specific symptoms that can be treated only with long-term antibiotics and other unorthodox and unvalidated treatments. Similar to other antiscience groups, these advocates have created a pseudoscientific and alternative selection of practitioners, research, and publications and have coordinated public protests, accused opponents of both corruption and conspiracy, and spurred legislative efforts to subvert evidence-based medicine and peer-reviewed science. The relations and actions of some activists, medical practitioners, and commercial bodies involved in Lyme disease advocacy pose a threat to public health., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed?, Methods: The authors analyzed published studies (1983-2003) using a structured review process to classify the evidence related to the questions posed., Results: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis., Conclusions: There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (> or =8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A).

Background: There is little information about the long-term outcomes of children with facial nerve palsy attributable to Lyme disease, a group putatively at high risk for poor neurologic outcomes., Objective: The purpose of this study is to assess the long-term neuropsychologic and health outcomes of children with facial nerve palsy attributable to Lyme disease., Methods: We conducted a matched cross-sectional study of children with facial nerve palsy in Connecticut who met the Centers for Disease Control and Prevention national surveillance case definition for Lyme disease. We identified children with facial nerve palsy attributable to Lyme disease from population-based data for the state of Connecticut from 1984 to 1991 as well as from selected clinical practices from 1984 to 1998. For each case, 2 controls without Lyme disease, matched by age, were selected by sequential digit dialing technique. Both patients and controls (or their parents) were interviewed using structured questionnaires. Outcomes included self/parents' reports both of symptoms and of abilities to perform normal daily activities since the diagnosis was made (or for an equivalent period of time for controls). In addition, the patients with facial nerve palsy attributable to Lyme disease were evaluated with a battery of neuropsychologic tests., Results: Of the 43 patients, 30% were female and 93% were white. Median age at diagnosis was 8 years (range: 2-18 years). Mean time to follow-up was 49 months (range: 7-161 months). Of the patients, 16% had been treated parenterally with ceftriaxone and 84% had been treated orally with either doxycycline or amoxicillin. Overall, 79% believed they were cured of Lyme disease, 9% believed they were not cured, and 12% did not know. The proportions of patients and of matched controls that reported increased problems with normal daily activities (eg, exercise, academic performance, word recall, sleeping) were similar. Patients with facial nerve palsy attributable to Lyme disease were more likely than matched controls to report symptoms of neck pain, changes in behavior, pains in joints or muscles, numbness or funny sensations in nerves, and problems with memory, but three quarters of them did not attribute these problems to Lyme disease. Twenty patients agreed to undergo neuropsychologic testing; all had average to above average scores on tests of IQ (eg, mean IQ was 110.2), memory, learning, attention, concentration, math, reading and spelling performance, executive functioning, abstract thinking, sequential processing, visuospatial scanning, and motor speed. There were no apparent differences in outcomes between children who received oral versus parenteral treatment., Conclusions: The neuropsychologic and health outcomes of children with facial nerve palsy attributable to Lyme disease 7 to 161 months earlier are comparable to those who did not have Lyme disease.