BACKGROUND/AIMS: Sera from patients from a single medical institution in New York State with human granulocytic anaplasmosis established by a positive polymerase chain reaction test (PCR) for Anaplasma phagocytophilum were used to assess the performance of serologic testing. All cases were also confirmed by culture in order to eliminate any false positive PCR samples. METHODS: A nested PCR was performed targeting the heat shock operon of A. phagocytophilum. Culture was done using the HL-60 promyelocytic cell line. Serologic testing was performed to detect IgG/A/M using an indirect immunofluorescence assay that incorporated a human isolate of A. phagocytophilum as the source of the antigen. RESULTS: From 1997 to 2009, 38 human granulocytic anaplasmosis patients were evaluated. On the baseline serum sample 21 (55.3%; 95% CI: 38.3%-71.4%) had a positive serologic test; 7 samples (33.1%) were positive at a titer of 80-320 and 14 samples (66.7%) at a titer of at least 640. Sixteen (94.1%) of the 17 with a negative baseline test had follow-up testing performed. All 16 tested positive on a convalescent phase serum sample obtained from 6 to 45 days later. CONCLUSION: PCR testing is the most commonly used direct diagnostic test to diagnose human granulocytic anaplasmosis. Our findings demonstrate that only approximately 55% of the PCR and culture positive cases were also seropositive on blood samples obtained at the same time point, indicating that serologic testing performed at the time of presentation has limited sensitivity. However, all of the 16 evaluable seronegative patients developed antibodies to A. phagocytophilum during convalescence. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies. center dot The American Journal of Medicine (2025) 138:669-672

Lyme disease, a bacterial zoonosis, is the most commonly reported vector-borne disease in the United States. Laboratory diagnosis has relied on a two-tier serologic approach, originally comprising an ELISA, or another first-tier assay, followed by separate IgG and IgM immunoblots to confirm a positive first-tier result. This standard two-tier testing (STTT) approach provides high specificity, but at the cost of low sensitivity in early Lyme disease. Recent studies have shown that a modified two-tier (MTTT) testing approach, in which a second ELISA replaces the immunoblot, can provide an increase in test sensitivity without a loss of specificity. Nevertheless, neither STTT nor MTTT is considered sensitive enough for diagnosing patients with erythema migrans, the most common clinical manifestation of early Lyme disease. We have developed a novel ELISA methodology termed "Hybrid Lyme ELISA" for single-tier Lyme antibody detection, which relies on the simultaneous binding of individual antibody molecules to the Borrelia burgdorferi surface protein VlsE and to the C6 peptide derived from it. This dual binding requirement builds exceptionally high specificity into the assay, eliminating the majority of non-specific antibody interactions. In this study, the single-tier Hybrid Lyme ELISA was shown to provide greater sensitivity, but with equivalent specificity, to both STTT and MTTT. In addition, given the >90% sensitivity of the Hybrid Lyme ELISA in patients with erythema migrans, this assay may not only transform serologic testing from two-step to single-step testing, but may also provide a means for the first time to diagnose patients with erythema migrans.IMPORTANCEThe diagnosis of Lyme disease, a tick-borne spirochetal infection caused by Borrelia burgdorferi sensu lato, is subject to two major limitations: the need for a two-tier serologic testing algorithm to provide adequate specificity, and the low sensitivity of this algorithm in practice for detection of early Lyme disease manifesting with the erythema migrans skin lesion, the most common clinical manifestation. This study presents the first description of a new assay, the Hybrid Lyme ELISA, which demonstrates sensitivity high enough to potentially diagnose over 90% of patients with erythema migrans, and specificity high enough to preclude the need for a second-tier test. These test characteristics suggest the potential for the Hybrid Lyme ELISA to be the first single-tier serologic test suitable for laboratory diagnosis of all stages of Lyme disease.

Objectives We sought to assess the performance of 3 laboratory tests on blood specimens for direct detection of Anaplasma phagocytophilum, the cause of human granulocytic anaplasmosis (HGA), in patients tested at a single medical institution in New York State.Methods Direct tests included microscopic blood smear examination for intragranulocytic inclusions, polymerase chain reaction (PCR), and culture using the HL-60 cell line. The HGA cases testing positive by only 1 direct test were not included, unless HGA was confirmed by acute or convalescent serology using an indirect immunofluorescent assay.Results From 1997 to 2009, 71 patients with HGA were diagnosed by at least 1 of the 3 direct test methods. For the subgroup of 55 patients who were tested using all 3 methods, culture was positive for 90.9% (50/55) vs 81.8% (45/55) for PCR vs 63.6% (35/55) for blood smear (P =.002). Most cultures (79.3%) were detected as positive within 1 week of incubation.Conclusions Although using culture to detect A phagocytophilum is likely not amenable for implementation in most hospital laboratories, in our experience, culture had the highest yield among the direct tests evaluated.

Alpha-gal syndrome (AGS) is an emerging allergic disease caused by an immunoglobulin E (IgE) response to galactose-α-1,3-galactose (alpha-gal), a sugar found in mammalian meat. The initial IgE sensitization follows a bite from the Amblyomma americanum (lone star) tick in the United States, although other tick species can also cause the disease. AGS presents with delayed symptoms, primarily gastrointestinal or allergic reactions like urticaria or anaphylaxis, hours after mammalian meat consumption. The nonspecificity of the symptoms can delay the diagnosis of AGS for years. Diagnosis relies on clinical evaluation and detection of alpha-gal-specific IgE in blood. As the lone star tick's range is expanding beyond the southern United States, AGS is gaining recognition in other regions. However, many healthcare providers remain unaware of the condition, leading to misdiagnosis. Infectious diseases physicians who frequently evaluate patients with tick exposure must be familiar with AGS, including tick identification, bite prevention, and knowledge of the alpha-gal-containing vaccines.

To determine the frequency of confirmed Lyme neuroborreliosis (LNB) cases in adult patients with three different clinical presentations consistent with early LNB. Data were obtained through routine health care at the UMC Ljubljana, Slovenia from 2005 to 2022, using clinical pathways. The patients were classified into three groups: (i) radicular pain of new onset (N = 332); or (ii) involvement of cranial nerve(s) but without radicular pain (N = 997); or (iii) erythema migrans (EM) skin lesion(s) in conjunction with symptoms suggestive of nervous system involvement but without either cranial nerve palsy or radicular pain (N = 240). The diagnosis of LNB considered the following variables: the presence of: (1) neurologic symptoms consistent with LNB (with no other obvious explanation); (2) cerebrospinal fluid (CSF) pleocytosis (> 5 × 106 leukocytes/L); and (3) demonstration of intrathecal synthesis of borrelial antibodies, and/or cultivation of borrelia from CSF, and/or the presence of EM. Patients fulfilling only the first two criteria were interpreted as having possible LNB, while those who satisfied all three criteria were regarded as having confirmed LNB. Of 1569 adult patients, 348 (22.2

The erythema migrans (EM) skin lesion is the most common clinical manifestation of Lyme borreliosis. Information about EM in Lyme borreliosis reinfection is limited. Of the 12,384 cases with diagnosed EM at an outpatient clinic during 1990-2014 in Slovenia, 1,962 (15.8%) cases occurred in patients who were treated previously for Lyme borreliosis, including 1,849 (94.2%) who had previously had EM. The percentage of reinfected patients who sought care with disseminated Lyme borreliosis at the time of reinfection, as manifested by multiple EM skin lesions, was significantly lower than for EM patients with no history of Lyme borreliosis (5.5% [108/1,962] vs. 7.4% [769/10,427]; p = 0.002). None of the clinical manifestations of Lyme borreliosis in Europe will completely protect against EM developing in patients in the future. The reoccurrence of Lyme borreliosis manifested by multiple EM lesions is significantly less likely than for patients with no history of Lyme borreliosis.

Background:In the United States, Borrelia burgdorferi (Bb) is the principal etiologic agent of Lyme disease. The complex structure of Bb genomes has posed challenges for genomic studies because homology among the bacterium's many plasmids, which account for ~40% of the genome by length, has made them difficult to sequence and assemble. Results:We used long-read sequencing to generate near-complete assemblies of 62 isolates of human-derived Bb and collected public genomes with plasmid sequences. We characterized genetic diversity and population structure in the resulting set of 82 plasmid-complete Borrelia burgdorferi sensu stricto genomes. The Bb core genome is encoded by a chromosome and the conserved plasmids cp26, lp54, and lp17; the accessory genome is encoded by all other plasmids and the distal arm of the chromosome. Near-complete genomes reveal that the most granular Bb genotypes are clonal expansions of complex rearrangements among accessory genome elements. Ribosomal spacer types (RST) represent multiple collections of such genotypes, whereas OspC types are usually clonal. Structural rearrangements are non-randomly distributed throughout the genome, with cp32 plasmids undergoing dense exchanges and most linear plasmids, except lp54, sharing blocks among themselves and with the distal arm of the chromosome. OspC type A strains, known to possess greater virulence in humans, are distinguished by the presence of lp28-1 and lp56. Rearrangements among plasmids tended to preserve gene content, suggesting functional constraints among gene networks. Using k-partite graph decompositions, we identified gene sets with correlation patterns suggestive of conserved functional modules. Conclusions:Long-read assemblies reveal that Bb population genetic structure results from clonal expansion of lineages that have undergone complex rearrangements among plasmid-encoded accessory genome elements. Genetic structure is preserved among genes even when plasmid rearrangements occur, suggesting that selection among epistatic loci maintains functional genetic networks. The analysis of near-complete genomes assembled using long-read sequencing methods advances our understanding of Bb biology and Lyme disease pathogenesis by providing the first detailed view of population variation in previously inaccessible areas of the Bb genome.

Ixodes scapularis ticks are an important vector for at least seven tick-borne human pathogens, including a North American Lyme disease spirochete, Borrelia burgdorferi. The ability for these ticks to survive in nature is credited, in part, to their ability to feed on a variety of hosts without triggering an immune response capable of preventing tick feeding. While the ability of nymphal ticks to feed on a variety of hosts has been well documented, the host-parasite interactions between larval I. scapularis and different vertebrate hosts are relatively unexplored. Here we report on the changes in the vertebrate host transcriptome present at the larval tick bite site using the natural I. scapularis host Peromyscus leucopus, a non-natural rodent host, Mus musculus (BALB/c), and humans. We note substantially less evidence of activation of canonical proinflammatory pathways in P. leucopus compared to BALB/c mice and pronounced evidence of inflammation in humans. Pathway enrichment analyses revealed a particularly strong signature of interferon gamma, tumor necrosis factor, and interleukin 1 signaling at the BALB/c and human tick bite sites. We also note that bite sites on BALB/c mice and humans, but not deer mice, show activation of wound-healing pathways. These data provide molecular evidence of the coevolution between larval I. scapularis and P. leucopus and, in addition, expand our overall understanding of I. scapularis feeding.

Lyme disease (LD) is growing in incidence, with nearly 500,000 cases diagnosed annually in the United States. Despite treatment, some patients experience persistent symptoms. The immune mechanisms underlying LD remain poorly understood. We conducted a multiomic longitudinal analysis of 49 LD patients and matched controls, integrating plasma proteomics, metabolomics, PBMC immunophenotyping, and a meta-analysis of skin lesions. We identified compartmentalized immune responses in acute LD, with coordinated alterations in circulating plasma proteins and metabolites linked to endothelial barrier stability, metabolic reprogramming, and symptom severity, predominantly traced to tissue and vascular immune processes at the site of infection. In contrast, PBMCs remained largely quiescent, revealing a disconnect between localized tissue responses and systemic immunity. These findings provide novel insights into LD pathophysiology and highlight the potential for diagnostics leveraging tissue and vascular immune markers detectable in blood. They also provide a resource for biomarker discovery and predictive modeling to improve LD management. ### Competing Interest Statement CR, AB, HH, LP, MEB, DC, CL, ASA, BS, KS, PT, KW, NR, LH, and NS declare no competing financial interests. GPW reports receiving research grants from Biopeptides Corp., has served as an expert witness in malpractice cases involving Lyme disease, and is an unpaid board member of the non-profit American Lyme Disease Foundation. United States Department of Defense, https://ror.org/0447fe631, W81XWH2110664 Wilke Family Foundation Steven and Alexandra Cohen Foundation Global Lyme Alliance, https://ror.org/05tzrqq19

Purpose: To determine the impact of booster COVID-19 vaccination on SARS-CoV-2 symptoms. Background: The Omicron surge of infections provided an opportunity to evaluate symptoms in relation to booster receipt. Methods: At a US medical college, the number, type, and duration of symptoms were evaluated for 476 students or employees, factoring in days between last vaccination and SARS-CoV-2 diagnosis. Results: Compared with vaccinated non-boosted individuals, boosted individuals reported a significantly higher frequency of nasal congestion (57.9% vs. 44.4%, p = 0.018) and nasal congestion and/or sore throat (77.2% vs. 62.0%, p = 0.003); in contrast, the frequency of body/muscle aches was significantly less among boosted individuals (22.1% vs. 32.4%, p = 0.038). With each one week increase in time since booster receipt, the probability of fever increased significantly by 4.4% (OR 1.044, 95% CI 1.01, 1.07, p = 0.001), and the probability of cough increased significantly by 4.8% (OR 1.048, 95% CI 1.01, 10.8, p= 0.010). Conclusions: Within a medical college population, during the first 7 months of the Omicron surge of infections, compared with vaccinated non-boosted individuals, boosted individuals significantly more often reported the following: nasal congestion as well as nasal congestion and/or sore throat. In contrast, body/muscle aches were reported significantly less often. The rates of fever and cough each significantly increased as time since booster dose receipt increased. These data suggest that having had a booster vaccination, as well the timing of receiving it, impacts the clinical manifestations of breakthrough SARS-CoV-2 infections. Additional studies are needed to precisely define SARS-CoV-2 symptoms in relation to booster vaccinations.

Acquired Immune Deficiency Syndrome (AIDS) is caused by human immunodeficiency virus (HIV). In the United States (US) the most common viral cause is HIV type 1 (HIV 1), but some cases are caused by HIV type 2 (HIV 2). Identification of HIV 1 and 2 (HIV 1/2) infected patients is important to potentially reduce viral spread and to begin highly effective antiretroviral drug therapies. Of course, antiretroviral drug therapy will not cure HIV infection and needs to be administered life-long. US Food and Drug Administration (FDA) approved screening tests to detect HIV 1/2 infection have changed over time with the current recommendation for use of a fourth generation test1U.S. Preventive Services Task ForceScreening for HIV infection: recommendations statement.Am Fam Phys. 2019; 100 (636A-636E)Google Scholar. Fourth generation tests detect both the p24 antigen of HIV 1 and the presence of IgG and IgM antibodies to HIV 1 and to HIV 22-5. Testing at least once is recommended for all persons ages 15 to 65 years, irrespective of risk factors1U.S. Preventive Services Task ForceScreening for HIV infection: recommendations statement.Am Fam Phys. 2019; 100 (636A-636E)Google Scholar. To diagnose primary human immunodeficiency virus (HIV) infection (i.e., newly acquired HIV infection), use of a fourth generation HIV 1/2 antigen/antibody assay has better sensitivity than antibody testing alone, due to the time delay for developing detectable antibodies to HIV2Liu P Jackson P Shaw N Heysell S. Spectrum of false positivity for the fourth generation human immunodeficiency virus diagnostic tests.AIDS Res Ther. 2016; 13: 1https://doi.org/10.1186/s12981-015-0086-3Crossref PubMed Scopus (24) Google Scholar, 3Weber B Gurtler L Thorstensson R Michl U Muhlbacher A Burgisser P et al.Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity.J Clin Microbiol. 2002; 40: 1938-1946Crossref PubMed Scopus (73) Google Scholar, 4Chavez P Wesolowski L Patel P Delaney K Michael Owen S Evaluation of the performance of the Abbott ARCHITECT HIV AG/Ab Combo Assay.J Clin Virol. 2011; 52S: S51-S55Crossref Scopus (72) Google Scholar, 5Delaney KP Hanson DL Masciotra S Ethridge SF Wesolowski L Michele Owen S Time until emergence of HIV test reactivity following infection with HIV-1: Implications for interpreting test results and retesting after exposure.Clin Infect Dis. 2017; 64: 53-59Crossref PubMed Scopus (69) Google Scholar. Multiple FDA-approved fourth generation assays exist and directly detect the p24 antigen of HIV, in addition to detecting antibodies to HIV 1/22-5. Freely circulating p24 antigen in the absence of antibody to HIV is detectable for only up to approximately 10-14 days in primary infection. In addition, because p24 antigen becomes undetectable over time when assessed using fourth generation assays, a method to detect antibody to HIV is necessary to be included in HIV screening tests, as has been done for the fourth generation tests4Chavez P Wesolowski L Patel P Delaney K Michael Owen S Evaluation of the performance of the Abbott ARCHITECT HIV AG/Ab Combo Assay.J Clin Virol. 2011; 52S: S51-S55Crossref Scopus (72) Google Scholar, 5Delaney KP Hanson DL Masciotra S Ethridge SF Wesolowski L Michele Owen S Time until emergence of HIV test reactivity following infection with HIV-1: Implications for interpreting test results and retesting after exposure.Clin Infect Dis. 2017; 64: 53-59Crossref PubMed Scopus (69) Google Scholar. If simultaneous or subsequent HIV RNA testing is negative in an individual who was never treated for HIV, however, this usually indicates that a positive fourth generation screening assay was likely to have been a false positive result. False positive results on fourth generation screening assays for HIV, although generally infrequent, definitely do occur and at a rate slightly higher than was found for third generation HIV enzyme immunoassays3Weber B Gurtler L Thorstensson R Michl U Muhlbacher A Burgisser P et al.Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity.J Clin Microbiol. 2002; 40: 1938-1946Crossref PubMed Scopus (73) Google Scholar. False positivity due to cross reactive antibodies to HIV 1/2 has been reported for patients with numerous other infections and inflammatory conditions2Liu P Jackson P Shaw N Heysell S. Spectrum of false positivity for the fourth generation human immunodeficiency virus diagnostic tests.AIDS Res Ther. 2016; 13: 1https://doi.org/10.1186/s12981-015-0086-3Crossref PubMed Scopus (24) Google Scholar, 3Weber B Gurtler L Thorstensson R Michl U Muhlbacher A Burgisser P et al.Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity.J Clin Microbiol. 2002; 40: 1938-1946Crossref PubMed Scopus (73) Google Scholar, 4Chavez P Wesolowski L Patel P Delaney K Michael Owen S Evaluation of the performance of the Abbott ARCHITECT HIV AG/Ab Combo Assay.J Clin Virol. 2011; 52S: S51-S55Crossref Scopus (72) Google Scholar, 5Delaney KP Hanson DL Masciotra S Ethridge SF Wesolowski L Michele Owen S Time until emergence of HIV test reactivity following infection with HIV-1: Implications for interpreting test results and retesting after exposure.Clin Infect Dis. 2017; 64: 53-59Crossref PubMed Scopus (69) Google Scholar, 6Smotrys M, Magge T, Alkhuja S, Dilbagh Gandotra S. Babesiosis as a cause of a false-positive HIV serology. BMJ Case Rep doi:10.1136/bcr-2017-223738.Google Scholar. Polyclonal B-cell stimulation may be one potential explanation for some of these associations7Klarkowski D O'Brien DP Shanks L Singh KP. Causes of false-positive HIV rapid diagnostic test results.Expert Rev Anti Infect Ther. 2014; 12: 49-62Crossref PubMed Scopus (0) Google Scholar. Of course, another potential cause of false positivity is assay dysfunction/malfunction4,7. Arguably, false positivity due to detection of the p24 antigen of HIV occurs less commonly than false positive antibody testing, or at least has been less well documented to date. Irrespective of the mechanism involved, false positive HIV tests are highly undesirable and can lead to substantive psychologic distress for the person being tested and receipt of unneeded antiretroviral drug therapy8Hakobyan N Yadav R Abaza K Friedman A. False-positive Human Immunodeficiency Virus results in COVID-19 patients.Cureus. 2023; https://doi.org/10.7759/cureus.34096Crossref Google Scholar. One scenario apparently associated with a high frequency of false positive antibody testing for HIV was due to the direct incorporation of two fragments of a protein naturally found in HIV into an experimental SARS-CoV-2 vaccine preparation being developed in Australia9Ives M. Australia scraps Covid-19 vaccine that produced H.I.V. false positives. New York Times, 2020https://www.nytimes.com/2020/12/11/world/australia/uq-coronavirus-vaccine-false-positive.htmlGoogle Scholar,10Watterson D Wijesundara DK Modhiran N Mordant FL Li Z Avumegah MS et al.Preclinical development of a molecular clamp-stabilised subunit vaccine for severe acute respiratory syndrome coronavirus 2.Clinical & Translational Immunology. 2021; : e1269https://doi.org/10.1002/cti2.1269Crossref Scopus (33) Google Scholar. Indeed, research on this vaccine was discontinued because of the resulting false positive HIV testing9Ives M. Australia scraps Covid-19 vaccine that produced H.I.V. false positives. New York Times, 2020https://www.nytimes.com/2020/12/11/world/australia/uq-coronavirus-vaccine-false-positive.htmlGoogle Scholar,11McIntyre P Joo YJ Chiu C Flanagan K Macartney K. COVID-19 vaccines – are we there yet?.Aust Prescr. 2021; 44: 19-25Crossref PubMed Scopus (0) Google Scholar. Of note, however, evidence also exists that COVID-19 infection per se can at least transiently result in a false positive HIV 1/2 fourth generation assay in a very small proportion of infected individuals8Hakobyan N Yadav R Abaza K Friedman A. False-positive Human Immunodeficiency Virus results in COVID-19 patients.Cureus. 2023; https://doi.org/10.7759/cureus.34096Crossref Google Scholar,12Gudipati S Shallal A Peterson E Cook B Markowitz N. Increase in false-positive fourth-generation Human Immunodeficiency Virus tests in patients with Coronavirus disease 2019.Clin Infect Dis. 2023; 77: 615-619Crossref Scopus (0) Google Scholar,13Miller M Cevigney R Ayyash M Shaman M Kole M. False-positive human immunodeficiency virus screening results in pregnancy during the Coronavirus Disease 2019 (COVID-19) pandemic.Obstet Gynecol. 2023; 142: 381-383Crossref Scopus (0) Google Scholar. A recent retrospective study conducted in Michigan clearly demonstrated that COVID-19 patients, who tested positive by a SARS-CoV-2 polymerase chain reaction (PCR) test, were significantly more likely to have a false positive test result on a particular fourth generation HIV test, compared with individuals with a negative SARS-CoV-2 PCR test result12Gudipati S Shallal A Peterson E Cook B Markowitz N. Increase in false-positive fourth-generation Human Immunodeficiency Virus tests in patients with Coronavirus disease 2019.Clin Infect Dis. 2023; 77: 615-619Crossref Scopus (0) Google Scholar. The false positive test result on the fourth generation HIV 1/2 assay used in this study was 2.93 more likely to occur in patients with COVID-19 compared to those without COVID-1912. The false positivity rate was 0.47% among the active COVID cases in this study12Gudipati S Shallal A Peterson E Cook B Markowitz N. Increase in false-positive fourth-generation Human Immunodeficiency Virus tests in patients with Coronavirus disease 2019.Clin Infect Dis. 2023; 77: 615-619Crossref Scopus (0) Google Scholar. However, of note the false positive HIV test results were associated with detection of the p24 HIV antigen portion of the assay. Although false positive antibody testing was also found in 37.5% of the active COVID-19 patients with a false positive HIV 1/2 fourth generation assay, the reactive antibody test component was not the sole determinant of the HIV test positivity in any of these cases12Gudipati S Shallal A Peterson E Cook B Markowitz N. Increase in false-positive fourth-generation Human Immunodeficiency Virus tests in patients with Coronavirus disease 2019.Clin Infect Dis. 2023; 77: 615-619Crossref Scopus (0) Google Scholar. False positive testing for the p24 antigen had previously been reported for organ transplant recipients using prior testing methods, which although transient, could last for weeks to months14Agbalika F Ferchal F Garnier J-P Eugene M Bedrossian J Lagrange PH False-positive HIV antigens related to emergence of a 25-30 kD protein detected in organ recipients.AIDS. 1992; 6: 959-962Crossref PubMed Google Scholar. Some degree of antigenic similarity between HIV-1 and certain SARS-CoV-2 proteins has been noted, but not consistently across different studies15Kliger Y Levanon EY. Cloaked similarity between HIV-1 and SARS-CoV suggests an anti-SARS strategy. 3. BMC Microbiology, 2003: 20http://www.biomedcentral.com/1471-2180/3/20Google Scholar,16Zhang C Zheng W Huang X Bell EW Zhou X Zhang Y. Protein structure and sequence reanalysis of 2019-nCoV genome refutes snakes as its intermediate host and the unique similarity between its spike protein insertions and HIV-1.J Proteome Res. 2020; 19: 1351-1360Crossref PubMed Scopus (191) Google Scholar, and whether this would explain the HIV false positivity found in such a small proportion of active SARS-CoV-2 cases remains unclear. Certainly, one theory put forward, however, is that COVID-19 infection produces a SARS-CoV-2 peptide or protein that to some extent mimics the p24 antigen of HIV, at least in a small proportion of infected patients. Conversely, and of interest, a false positive SARS-CoV-2 rapid antigen test was observed anecdotally in a person with primary HIV-1 infection17Yamaniha K Kinjo T Akamine M Setoguchi M Tateyama M Fujita J. False-positive for SARS-CoV-2 antigen test in a man with acute HIV infection.J Infect Chemother. 2021; 27: 1112-1114Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar. Whether false positive testing for HIV might vary according to the particular circulating variant of SARS-CoV-2 is unknown. Also, although it is clear that false positive test results can occur in patients with active COVID-19 using several different fourth generation HIV 1/2 assays8Hakobyan N Yadav R Abaza K Friedman A. False-positive Human Immunodeficiency Virus results in COVID-19 patients.Cureus. 2023; https://doi.org/10.7759/cureus.34096Crossref Google Scholar,12Gudipati S Shallal A Peterson E Cook B Markowitz N. Increase in false-positive fourth-generation Human Immunodeficiency Virus tests in patients with Coronavirus disease 2019.Clin Infect Dis. 2023; 77: 615-619Crossref Scopus (0) Google Scholar,13Miller M Cevigney R Ayyash M Shaman M Kole M. False-positive human immunodeficiency virus screening results in pregnancy during the Coronavirus Disease 2019 (COVID-19) pandemic.Obstet Gynecol. 2023; 142: 381-383Crossref Scopus (0) Google Scholar, whether the rate of false positivity might differ according to which fourth generation HIV antibody-antigen test kit that is being used is also unknown. Dr. Wormser reports receiving research grants from Biopeptides, Corp. and Pfizer, Inc. He is an unpaid board member of the non-profit American Lyme Disease Foundation. Other authors: none. None

BACKGROUND:Early syphilitic lesions are typically painless; however, several recent case studies have included patients with tender lesions and no evidence of concurrent infections. Here we present the manifestations and serological and molecular findings of a patient from New York State with a painful tongue lesion. METHODS:The diagnosis of syphilis was based on a combination of physical examination, serologic, pathologic, and immunohistochemical findings. DNA obtained from a formalin-fixed, paraffin-embedded biopsy was used to characterize the infecting pathogen using polymerase chain reaction, multilocus sequence typing, and whole-genome sequencing methods. RESULTS:Polymerase chain reaction and multilocus sequence typing of the biopsy specimen confirmed infection with T. pallidum subspecies pallidum ( T. pallidum ) of the Nichols cluster. Whole-genome sequencing analysis of this strain (herein called NYMC01) showed that it contained 17 unique single nucleotide variations and 4 more complex genetic differences; this novel genotype matched only 2 specimens, both from a patient in Seattle, Washington. The presence of this rare genotype in 2 geographically distinct locations suggests the potential emergence and spread of a new subgroup of the Nichols cluster. CONCLUSIONS:To our knowledge, this is the first genomic sequence obtained from a T. pallidum strain linked to a painful lesion, and the third description of whole-genome sequencing of T. pallidum from formalin-fixed, paraffin-embedded tissue. Analysis of additional specimens may reveal that the NYMC01-related genotype represents an emerging T. pallidum subgroup and may also aid in determining whether the painful clinical presentation of primary syphilis is related to specific T. pallidum genotypes.

In their recent letter [1], Dow and Smith proposed a treatment trial of hospitalized babesiosis patients (presumably infected with Babesia microti specifically) comparing a 3-drug treatment regimen consisting of 800 mg of tafenoquine (TAF) administered as a daily 200 mg dose over the first 4 consecutive days of treatment in combination with a 10-day course of azithromycin plus atovaquone, also initiated on day 1 of treatment.Presumably, the subjects enrolled would be patients who were to receive their first treatment for babesiosis, rather than patients experiencing relapsing infection despite having been previously treated with one or more anti-babesia drug regimens.The two-drug regimen of azithromycin plus atovaquone alone is generally considered to be the preferred initial treatment regimen for B. microti infections [2], and this regimen will serve as the 10-day comparator in this trial, and which will be given in conjunction with an initial 4-day course of a matching TAF placebo.

Diagnosis of (European) Lyme neuroborreliosis has been based on clinical presentation, cerebrospinal fluid (CSF) pleocytosis and demonstration of intrathecal borrelial antibody synthesis (ITBAS) to document Borrelia burgdorferi s. l. infection. It is not known if other criteria to document Borrelia infection may contribute to the diagnosis. We compared the sensitivity of three individual criteria (ITBAS, CSF Borrelia culture, and the presence of erythema migrans [EM]) to confirm the diagnosis of early Lyme neuroborreliosis in 280 patients ≥ 15 years of age evaluated at a Lyme borreliosis outpatient clinic in Slovenia. The patients had either radicular pain of new onset or involvement of a cranial nerve but without radicular pain, each in conjunction with CSF pleocytosis. Evaluation was of patients who had each of the three confirmatory criteria assessed, and for whom at least one criterion was positive. Analysis of 280 patients, 120 women and 160 men, median age 57 (range 15–84) years, revealed that ITBAS was the most frequently observed positive criterion (85.4

From 2011-2020 the number of reported cases of Lyme disease in the USA was lower in each even-numbered year compared with the preceding odd-numbered year. This observation suggests that fewer nymphal stage Ixodes scapularis ticks infected with Borrelia burgdorferi were present during even-numbered years in locations where people spend time.

Information on asplenic Lyme borreliosis (LB) patients with erythema migrans (EM) is lacking. We compared the course and outcome of 26 EM episodes in 24 post-trauma splenectomized patients (median age 51 years) diagnosed at a single clinical center in Slovenia during 1994–2023 with those of 52 age- and sex-matched patients with EM but with no history of splenectomy. All patients were followed for one year. A comparison of pre-treatment characteristics revealed that EM in splenectomized patients was of shorter duration before diagnosis (4 vs. 8 days, p = 0.034) with a smaller EM diameter (10.5 vs. 14 cm, p = 0.046), and more frequently fulfilled criteria for disseminated LB (3/26, 11.5% vs. 0%, p = 0.034). Treatment failure occurred in 5/26 (19.2%) EM episodes in splenectomized patients versus 0/52 in non-splenectomized patients (p = 0.003). The five treatment failure cases were retreated with antibiotic regimens used to treat EM and had complete resolution of all symptoms/signs. In conclusion, our study showed that splenectomized adult patients with EM differ somewhat in presentation and more often have treatment failure compared with non-splenectomized patients with EM.

BackgroundAntibiotic therapy for patients with early Lyme disease is necessary to prevent later-stage Lyme disease complications. This systematic review and meta-analysis compares shorter versus longer antibiotic regimens in treating early Lyme disease.MethodsA systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted up to November 2023. We examined treatment failure, complete response, and photosensitivity. Short vs. long therapy was defined as ≤10 days vs. >10 days. Subgroup analyses included antibiotic type and varying treatment durations. Analysis utilized RStudio 4.1.2. PROSPERO registration: CRD42023423876.ResultsSeven studies, encompassing 1,462 patients, were analyzed. No significant differences in treatment failure, 12-month complete response, final visit complete response were found between short and long durations of antibiotic therapy. Subgroup and sensitivity analyses corroborated these findings.ConclusionShorter and longer antibiotic regimens for early Lyme disease show similar efficacy, highlighting the potential of ≤10-day courses, as effective treatment options.