An Unusual Case of Serologically Confirmed Post-Partum Lyme Disease Following an Asymptomatic Borrelia burgdorferi Infection Acquired during Pregnancy and Lacking Vertical Transmission in Utero.

In this report, we describe a 23-year-old female who, while pregnant, was exposed to Borrelia burgdorferi but did not develop significant signs or symptoms (joint pain, arthritis) of Lyme disease until shortly after delivering a healthy child at term. Serologic testing confirmed infection with B. burgdorferi. A 3-week course of treatment with doxycycline was completely curative. There was no evidence for congenital or perinatal transmission of this pathogen at any point pre-term or postnatally. The key reasons that could account for this unique clinical scenario are discussed in the context of previously published related reports.

Lessons learned from the successful polio vaccine experience not learned or applied with the development and implementation of the COVID-19 vaccines.

The eradication of polio during the latter half of the 20th century can be considered one of the greatest medical triumphs in history. This achievement can be attributed to the development of vaccines that received the public's almost unwavering acceptance of them, especially by parents who had been waiting/hoping for a medical breakthrough that would ensure that their children would not succumb to the devastating effects of infantile paralysis. Sixty years later, the worldwide population was now confronted with an equally devastating disease - Covid-19 - which by the 2020-2021 time period had reached pandemic levels not seen since the flu outbreak of 1918. Unlike polio, however, several vaccines against Covid-19 were rapidly developed and deployed due to advances in microbiologic and immunologic technology. But also, unlike the polio vaccine experience, there was not universal acceptance of the Covid-19 vaccines and this has led to continuation of the pandemic into 2023 (albeit at a reduced level). In addition, acceptance of the Covid-19 vaccines has been confronted with the uncertainty that they do not apparently prevent transmission in asymptomatic people, and the mutation rate of the virus requires periodic re-evaluation and possible upgrading of the vaccines. This review will focus on the various factors that have led to these contrasting attitudes toward these two different vaccines and how resistance and hesitancy to vaccine use can be overcome by implementing various measures, after introducing the key roles that the sciences of microbiology and immunology have played in vaccine development over the past 250+ years.

Use of the Western blot technique to identify the immunogenic proteins of Borrelia burgdorferi for developing a Lyme disease vaccine.

BACKGROUND: Lyme disease is a serious infectious disease having a restricted worldwide distribution for which there is no vaccine available for human use. OBJECTIVE: This study was designed to determine common reactive antigens involved in Borrelia burgdorferi (Bb) infection that are recognized in mammalian sera that may be useful for vaccine development. METHODS: Blood samples were collected from patients with documented Lyme disease, and from rabbits and mice experimentally infected with either tick-transmitted or culture-grown Borrelia burgdorferi. All samples were then processed for sera. For performing the Western blots, sonicated Bb organisms (whole cell lysates) and protein ladders were separated by protein gel electrophoresis. Immune reactivities of the electrophoresed proteins with the serum samples were then probed with anti-HRP IgG reagent. RESULTS: Rabbit, mouse and human sera consistently reacted with the 41 kDa band of Bb which corresponded to the flagellin protein - the major protein component of this organism's periplasmic flagella, also known as axial filaments or fibrils. Various other Bb antigens of wide molecular weight ranges were also recognized by rabbit and human sera, and less frequently with mouse sera. CONCLUSION: The strong immune response to the 41 kDa flagellin protein by the different mammalian species suggests the utility of a possible vaccine targeting this protein, although other proteins may also be appropriate, for preventing Lyme disease following a bite from an infected tick.

The major epidemiologic, microbiologic, immunologic, and clinical aspects of Lyme disease that form the basis for a newly developed vaccine that may become available soon for human use.

Working together, two major pharmaceutical companies have developed a Lyme disease vaccine consisting of recombinant-derived outer surface protein A (OspA) of the etiologic agent Borrelia burgdorferi. Multiple clinical trials have shown the vaccine to have good safety and efficacy results, and it is hoped that it would become available for human use at least by the year 2025 after receiving approval from the U.S. Food and Drug Administration. There are still challenges left to ensure that the vaccine has, at most, minimal side effects. Also, because the previously developed Lyme disease vaccine was discontinued in 2002 after four years of distribution, due in part, for frivolous reasons having little or no scientific basis, that even led to legal entanglements involving the vaccine manufacturer and some of the medical personnel overseeing the clinical trials, there will be concerns that this newly developed one could be subject again to some of the same unnecessary scrutiny rendering its implementation suboptimal. Initially this review will focus on the key epidemiological, microbiologic, immunologic and clinical aspects of Lyme disease that provide the foundation for developing this type of vaccine that could have a serious impact on the prevalence of this and even certain other tick-transmitted infections.

Pasteur, Vaccines, and the Refusal to Become Fully Vaccinated in the Midst of the COVID-19 Pandemic.

Vaccines are one of the most effective public health measures that are designed to prevent serious illness caused by a wide variety of infectious agents, which have become especially important in light of the coronavirus disease 2019 (COVID-19) pandemic. Despite the favorable outcomes associated with vaccine development and use, a new wave of hesitancy to get vaccinated has emerged that threatens the control or quick elimination of the highly contagious and life-threatening infection caused by SARS-CoV-2. At the forefront of the current anti-vaccine movement is the dissemination of false and misleading information. This essay explores the primary reasons, which also includes an historical connection, behind this anti-vaccine sentiment, and proposes several possible and realistic interventions that could be implemented to counter this notion and significantly improve vaccine acceptance, especially among young people.

Lack of Convincing Evidence That Borrelia burgdorferi Infection Causes Either Alzheimer Disease or Lewy Body Dementia.

The role that microorganisms might have in the development of Alzheimer disease is a topic of considerable interest. In this article, we discuss whether there is credible evidence that Lyme disease is a cause of Alzheimer disease and critically review a recent publication that claimed that Borrelia burgdorferi sensu stricto infection, the primary cause of Lyme disease in the United States, may cause Lewy body dementia. We conclude that no convincing evidence exists that Lyme disease is a cause of either Alzheimer disease or Lewy body dementia.

COVID-19 vaccines for high risk and immunocompromised patients.

The availability of multiple versions of vaccines designed to help prevent COVID-19 has offered an opportunity to at least control the current pandemic, and possibly to quickly eradicate this disease fully, along with the implementation of other preventive measures. In order to accomplish this feat more effectively, as many people as possible need to be vaccinated, especially for high-risk groups having co-morbid conditions such as diabetes, obesity and old age, and possibly those with various forms of immunodeficiencies, such as HIV/AIDS. This chapter focuses primarily on some of the basic biomedical aspects on vaccine design and use, and any possible concerns that need to be considered in getting people in the high-risk category vaccinated and monitored thereafter for their continuous health and well-being.

Hesitancy to get vaccinated against COVID-19 and how it might be overcome.

The hesitancy and resistance to get vaccinated against COVID-19, by a relatively small but significant part of the general population, has become a serious worldwide problem, and particularly in the United States, despite a vigorous and highly organized governmental advertising campaign promoting vaccination. The unwillingness to get vaccinated has its roots in mostly the spreading of non-scientific, unproven or misleading information. This chapter explains many of the reasons, including an historical connection, behind this anti-vaccine movement, and proposes several possible and feasible remedies to counter this sentiment.

COVID-19 Vaccines for HIV-Infected Patients.

Nearly 40 years have passed since the initial cases of infection with the human mmunodeficiency virus (HIV) were identified as a new disease entity and the cause of acquired immunodeficiency disease (AIDS). This virus, unlike any other, is capable of causing severe suppression of our adaptive immune defense mechanisms by directly infecting and destroying helper T cells leading to increased susceptibility to a wide variety of microbial pathogens, especially those considered to be intracellular or opportunistic. After T cells are infected, HIV reproduces itself via a somewhat unique mechanism involving various metabolic steps, which includes the use of a reverse transcriptase enzyme that enables the viral RNA to produce copies of its complementary DNA. Subsequent physiologic steps lead to the production of new virus progeny and the eventual death of the invaded T cell. Fortunately, both serologic and molecular tests (such as PCR) can be used to confirm the diagnosis of an HIV infection. In the wake of the current COVID-19 pandemic, it appears that people living with HIV/AIDS are equally or slightly more susceptible to the etiologic agent, SARS-CoV-2, than the general population having intact immune systems, but they may have more serious outcomes. Limited clinical trials have also shown that the currently available COVID-19 vaccines are both safe and effective in affording protection to HIV/AIDS patients. In this review, we further explore the unique dynamic of HIV/AIDS in the context of the worldwide COVID-19 pandemic and the implementation of vaccines as a protective measure against COVID-19, as well as what immune parameters and safeguards should be monitored in this immunocompromised group following vaccination.

The evolution of rapid antigen detection systems and their application for COVID-19 and other serious respiratory infectious diseases.

Making the correct diagnosis of a patient seeking medical attention is the ultimate goal of a practicing physician, irrespective of whether the cause of the patient's condition is infectious or non-infectious. Antigen detection tests can be used to aid in the diagnosis of various infectious-related disorders including COVID-19 where it has become especially important due to the serious nature of this disease and its worldwide prevalence. These tests closely mimic one of the earliest prototypes - the urine pregnancy test - and as a result they have gained wide acceptance based on their overall simplicity, low cost and relative accuracy. In some situations, especially as a screening test, they can be used instead of the more technically demanding and complex molecular and serologic assays that are still useful and helpful under many different circumstances. Antigen detection systems are based on finding a particular immunogenic component, typically a protein or polysaccharide molecule, that is both unique and an integral part of the pathogen or other biological entity. Because these tests generally provide only qualitative results, they often need to be supplemented with other and sometimes more sophisticated laboratory-based diagnostic procedures to corroborate the initial test result. In this review, we first describe general background information on antigen-detection methods, including any unique aspects of their overall design, and then follow with an extensive description on the merits and limitations of these tests for detecting COVID-19 and, to a lesser extent, for other serious respiratory diseases caused by three common bacterial pathogens - Streptococcus pyogenes, Streptococcus pneumoniae and Legionella pneumophila.

Passive immunization and its rebirth in the era of the COVID-19 pandemic.

The COVID-19 pandemic, caused by SARS-CoV-2, has led to a rapid search for therapeutic and preventive measures because of the potentially severe course of infection. The antiviral drug, remdesivir, and the anti-inflammatory agent, dexamethasone, have shown beneficial effects. As the current COVID-19 vaccines are not yet fully available to everyone, or they may not be readily and universally accepted, various treatment options are being evaluated and will still be needed under these conditions. One of these treatment options, passive immunization, has shown promise in some studies. Further research is needed to determine the utility of immunotherapy with convalescent plasma or artificially produced monoclonal antibodies for the treatment of symptomatic patients, and potentially for use as post-exposure prophylaxis, at least until more effective drugs are available or safe and effective vaccines are distributed and administered to everyone.

COVID-19: Is there a role for Western blots and skin testing for determining immunity and development of a vaccine?

Infection with the virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) stimulates an immune response which can serve as a marker for current or past exposure to this pathogen, and possibly for resistance to re-infection. This response to COVID-19 can be monitored based on the production of antibodies, and thus, serologic tests have become available for diagnostic purposes. Despite progress in this area, concerns have been raised that too many of the commercially available serologic detection systems are not completely reliable. To address this issue, Western blots should be considered for confirming a positive or borderline-positive result from a screening test, such as an ELISA. An additional benefit of Western blots would be to identify antigens that could form the basis for developing a vaccine. Little is known about the cell-mediated immune response against COVID-19. One way to address this would be to use skin testing to measure the delayed-type hypersensitivity response in patients recovering from COVID-19.

Clinical implications of nicotine as an antimicrobial agent and immune modulator.

Nicotine is perhaps the most important and potent, pharmacologically active substance in tobacco products. This commentary examines the possible effects that nicotine has on microbial viability and also on the host's immune system as it responds to the indigenous microflora (the microbiome) due to nicotine-induced changes to the indigenous microbial environment and any associated antigenic stimulation / immunization that may occur. To our knowledge, the analysis of such profound microbiologic changes attributable to a tobacco-related product, such as nicotine, has not been fully explored in the context of its consequences on the viability of the microbiome/microbiota and on some of the host's basic physiologic processes, such as the immune response, and its possible association on the induction and persistence of certain immunologically related diseases. Future studies should be aimed at uncovering the molecular mechanisms involved in such interactions, especially in the context of manipulating them for therapeutic purposes.

Transfusion-Associated Lyme Disease - Although Unlikely, It Is Still a Concern Worth Considering.

Even though hematogenous spread of the Lyme disease spirochete, Borrelia burgdorferi, has been well documented, and there are more than 300,000 cases per year of Lyme disease in the United States, no evidence (anecdotal or published) of transfusion-associated Lyme disease has been reported. Such a possibility would seem to exist but various factors, as discussed in this perspective, make this less likely to occur. Nonetheless, if not done already, safeguards need to be put in place at blood collection and dispensing facilities, possibly with the assistance of diagnostic microbiology and immunology laboratories, to ensure that the potential for the transfer of the Lyme disease spirochete through a blood transfusion remains a theoretical consideration rather than a real possibility.

Ketamine intervention limits pathogen expansion in vitro.

Ketamine is one of several clinically important drugs whose therapeutic efficacy is due in part to their ability to act upon ion channels prevalent in nearly all biological systems. In studying eukaryotic and prokaryotic organisms in vitro, we show that ketamine short-circuits the growth and spatial expansion of three microorganisms, Stachybotrys chartarum, Staphylococcus epidermidis and Borrelia burgdorferi, at doses efficient at reducing depression-like behaviors in mouse models of clinical depression. Although our findings do not reveal the mechanism(s) by which ketamine mediates its antifungal and antibacterial effects, we hypothesize that a function of L-glutamate signal transduction is associated with the ability of ketamine to limit pathogen expansion. In general, our findings illustrate the functional similarities between fungal, bacterial and human ion channels, and suggest that ketamine or its metabolites not only act in neurons, as previously thought, but also in microbial communities colonizing human body surfaces.

Was it authentic Lyme disease or some other disorder?

We compared the evidence presented recently that challenges the long-standing belief that, in 1922, two French physicians reported the first case of neurological Lyme disease with a further analysis of the original findings that were translated and re-published in 1993. Alternative possibilities are offered that could explain these discrepant interpretations on what was considered to be a landmark clinical case of historical significance.

A Gram Stain Hands-On Workshop Enhances First Year Medical Students' Technique Competency in Comprehension and Memorization.

BACKGROUND: Laboratory diagnostic tests have an essential role in patient care, and the increasing number of medical and health professions schools focusing on teaching laboratory medicine to pre-clinical students reflects this importance. However, data validating the pedagogical methods that best influence students' comprehension and interpretation of diagnostic tests have not been well described. The Gram stain is a simple yet significant and frequently used diagnostic test in the clinical setting that helps classify bacteria into two major groups, Gram positive and negative, based on their cell wall structure. METHODS AND FINDINGS: We used this technique to assess which educational strategies may improve students' learning and competency in medical diagnostic techniques. Hence, in this randomized controlled study, we compared the effectiveness of several educational strategies (e.g. workshop, discussion, or lecture) in first year medical students' competency in comprehension and interpretation of the Gram stain procedure. We demonstrated that a hands-on practical workshop significantly enhances students' competency in memorization and overall comprehension of the technique. Interestingly, most students irrespective of their cohort showed difficulty in answering Gram stain-related analytical questions, suggesting that more emphasis should be allocated by the instructors to clearly explain the interpretation of the diagnostic test results to students in medical and health professional schools. CONCLUSION: This proof of principle study highlights the need of practical experiences on laboratory medical techniques during pre-clinical training to facilitate future medical doctors' and healthcare professionals' basic understanding and competency in diagnostic testing for better patient care.