Serum osteoprotegerin and its gene polymorphisms in patients with Takayasu's arteritis: a bicentric cross-sectional study.

INTRODUCTION: Takayasu's arteritis (TAK) patients are at an elevated risk of metabolic syndrome and cardiovascular diseases (CVD). Currently, there are no well-validated biomarkers to assess this risk in this population. Previous research in different cohorts has linked serum levels of osteoprotegerin (OPG) and its polymorphisms to accelerated atherosclerosis and a marker of poor prognosis in CVD. Thus, we assessed this protein as a potential biomarker of CVD in TAK patients. OBJECTIVES: To evaluate the serum levels of OPG and its SNPs (single nucleotide polymorphisms) in TAK patients and healthy controls, and to associate these parameters with clinical data. METHODS: This bicentric cross-sectional study included TAK patients who were compared with healthy individuals (control group). The serum levels of OPG and the frequency of OPG SNPs [1181G > C (rs2073618), 245 A > C (rs3134069), 163T > C (rs3102735), and 209 C > T (rs3134070)] were compared between the both groups and associated with clinical data. RESULTS: In total, 101 TAK patients and 93 controls were included in the study. The serum levels of OPG (3.8 ± 1.9 vs. 4.3 ± 1.8pmol/L, respectively; P = 0.059), and its four polymorphisms were comparable between both groups. In an additional analysis of only TAK patients, serum OPG levels and its four genes were not associated with any CVD parameters, except for higher OPG levels among patients without dyslipidemia. CONCLUSION: No significant differences were observed in serum OPG levels or in the genotype frequencies of OPG SNPs between the patient and control groups. Similarly, no correlation was found between laboratory parameters and clinical data on CVD risk in TAK patients.

The Current State of Knowledge on Baggio-Yoshinari Syndrome (Brazilian Lyme Disease-like Illness): Chronological Presentation of Historical and Scientific Events Observed over the Last 30 Years.

Baggio-Yoshinari Syndrome (BYS) is an emerging Brazilian tick-borne infectious disease that clinically mimics Lyme Disease (LD) present in the Northern Hemisphere. LD is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato complex and transmitted by Ixodid ticks of complex Ixodes rticinus. On the contrary, BYS is transmitted by hard Ixodid ticks of the genera Amblyomma, Rhipicephalus and Dermacentor. In 1992, the first cases of BYS were described in patients that developed EM rash, flu-like symptoms and arthritis after tick bite episodes. Since these findings, research in BYS has been developing for more than 30 years and shows that its epidemiological, clinical and laboratorial features are different from LD. Borrelia burgdorferi was never isolated in Brazil. In addition, specific serologic tests have shown little positivity. Furthermore, peripheral blood analysis of patients using electron microscopy exhibited structures resembling spirochete-like microorganisms or the latent forms of spirochetes (L form or cell wall deficient bacteria). For these reasons, Brazilian zoonosis was defined as an exotic and emerging Brazilian infectious disease, transmitted by ticks not belonging to the Ixodes ricinus complex, caused by latent spirochetes belonging to the B. burgdorferi sensu lato complex with atypical morphology. The Brazilian ecosystem, combined with its ticks and reservoir biodiversity, possibly contributed to the origin of this new zoonosis, which emerged as a result of the passage of B. burgdorferi through exotic vectors and reservoirs.

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases.

OBJECTIVE: To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. METHODS: Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. RESULTS: ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). CONCLUSIONS: We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX. Trial registration number NCT04754698.

Innate and Th1/Th17 adaptive immunity in acute and convalescent Brazilian borreliosis disease.

INTRODUCTION: Brazilian borreliosis (BB) disease is an infectious disease transmitted by ticks that mimics Lyme disease (LD) from the Northern Hemisphere. The BB clinical picture is characterized by a pathognomonic skin lesion (migratory erythema) and joint, neurological, cardiac and psychiatric symptoms. Innate and Th1/Th17 adaptive immunity seem to play an important role in the pathogenesis of Lyme disease. OBJECTIVE: The aim of this study was to characterize the role of innate and Th1/Th17 adaptive immunity in BB patients with acute (<3 months) and convalescent (>3 months) disease. METHODS: Fifty BB patients (28 with acute and 22 with convalescent disease) without treatment and 30 healthy subjects were evaluated. Levels of 20 cytokines or chemokines associated with innate and Th1/Th17 adaptive immunity were analyzed using Luminex (Millipore Corp., Billerica, MA). RESULTS: Overall, BB patients had increased levels of IL-8 (6.29 vs 2.12 p = 0.002) and MIP-1α/CCL3 (5.20 vs 2.06, p = 0.030), associated with innate immunity, and MIP3B/CCL19 (Th1; 297.86 vs 212.41, p = 0.031) and IL-17A (Th17; 3.11 vs 2.20, p = 0.037), associated with adaptive immunity, compared with the levels of healthy controls. When comparing acute BB vs. convalescent BB subjects vs. healthy controls, IL-1ß, IL-8 and MIP-1α/CCL3 (innate mediators) levels were highest in patients in the acute phase of disease (p < 0.05). TNF-α was associated with disseminated symptoms and with humoral reactivity against Borrelia burgdorferi. IL-10 was significantly correlated with IL-6 (r = 0.59, p = 0.003), IL-8 (r = 0.51, p < 0.001), MIP-1α/CCL3 (r = 0.42, p < 0.001) and MIP-3ß/CCL19 (r = 0.40, p = 0.002) in all BB patients. CONCLUSIONS: This is the first study describing that innate and Th1/Th17 adaptive immunity play a crucial role in BB disease. Furthermore, innate mediators are particularly important in acute BB disease, and TNF-α is associated with evolution of BB symptoms.

Innate and Th1/Th17 adaptive immunity in acute and convalescent Brazilian borreliosis disease

Introduction: Brazilian borreliosis (BB) disease is an infectious disease transmitted by ticks that mimics Lyme disease (LD) from the Northern Hemisphere. The BB clinical picture is characterized by a pathognomonic skin lesion (migratory erythema) and joint, neurological, cardiac and psychiatric symptoms. Innate and Th1/Th17 adaptive immunity seem to play an important role in the pathogenesis of Lyme disease. Objective: The aim of this study was to characterize the role of innate and Th1/Th17 adaptive immunity in BB patients with acute (<3 months) and convalescent (>3 months) disease. Methods: Fifty BB patients (28 with acute and 22 with convalescent disease) without treatment and 30 healthy subjects were evaluated. Levels of 20 cytokines or chemokines associated with innate and Th1/Th17 adaptive immunity were analyzed using Luminex (Millipore Corp., Billerica, MA). Results: Overall, BB patients had increased levels of IL-8 (6.29 vs 2.12 p = 0.002) and MIP-1α/CCL3 (5.20 vs 2.06, p = 0.030), associated with innate immunity, and MIP3B/CCL19 (Th1; 297.86 vs 212.41, p = 0.031) and IL-17A (Th17; 3.11 vs 2.20, p = 0.037), associated with adaptive immunity, compared with the levels of healthy controls. When comparing acute BB vs. convalescent BB subjects vs. healthy controls, IL-1β, IL-8 and MIP-1α/CCL3 (innate mediators) levels were highest in patients in the acute phase of disease (p < 0.05). TNF-α was associated with disseminated symptoms and with humoral reactivity against Borrelia burgdorferi. IL-10 was significantly correlated with IL-6 (r = 0.59, p = 0.003), IL-8 (r = 0.51, p < 0.001), MIP-1α/CCL3 (r = 0.42, p < 0.001) and MIP-3β/CCL19 (r = 0.40, p = 0.002) in all BB patients. Conclusions: This is the first study describing that innate and Th1/Th17 adaptive immunity play a crucial role in BB disease. Furthermore, innate mediators are particularly important in acute BB disease, and TNF-α is associated with evolution of BB symptoms.

First report of mild Brazilian spotted fever associated to arthritis.

We describe the first Brazilian case of mild Rickettsiosis, complicated by knee monoarthritis, in young adult bitten by a tick on his left leg in Camburi zone, located in São Sebastião municipality, southern coastal region of the State of São Paulo, in the Atlantic rainforest region, Brazil. The patient developed inoculation eschar at the tick bite site associated with enlarged lymph nodes in the left groin, fever, polyarthralgia, headache and macular rash. Twenty days after tick bite episode, he displayed monoarthritis in his right knee. The diagnosis of mild Rickettsiosis was established by sequential immunological analysis in serum and synovial fluid, using the indirect immunofluorescence (IF) assay for antibodies reactive with Rickettsia parkeri and Rickettsia rickettsii. The mild Rickettsiosis is an emerging zoonosis, that must be investigated by physicians, including rheumatologists, in patients that present macular rash, fever and eventually arthritis, after visiting the southern coastal Atlantic rainforest region in Brazil.

Primeiro caso de febre maculosa brasileira branda associada à artrite / First report of mild Brazilian spotted fever associated to arthritis

Descrevemos o primeiro caso brasileiro de Riquetsiose branda, agravada por monoartrite em joelho, em adulto jovem picado por carrapato na perna esquerda na região de Camburi, localizada no município de São Sebastião, sul da região costeira do estado de São Paulo, Mata Atlântica, Brasil. O paciente apresentou uma escara de inoculação no local da picada do carrapato, associada ao aumento ganglionar em virilha esquerda, febre, poliartralgia, cefaleia e erupção macular. Vinte dias após o episódio da picada de carrapato, o paciente apresentou monoartrite em joelho direito. O diagnóstico de Riquetsiose branda foi estabelecido pela análise imunológica sequencial em amostras de soro e líquido sinovial, tendo sido empregada a técnica de imunofluorescência (IF) indireta para anticorpos reativos contra Rickettsia parkeri e Rickettsia rickettsii. A Riquetsiose branda é uma zoonose emergente, que deve ser investigada pelos médicos, incluindo reumatologistas, em pacientes que apresentem erupção macular, febre e, eventualmente, artrite, após visita ao sul da região costeira da Mata Atlântica no Brasil.

We describe the first Brazilian case of mild Rickettsiosis, complicated by knee monoarthritis, in young adult bitten by a tick on his left leg in Camburi zone, located in São Sebastião municipality, southern coastal region of the State of São Paulo, in the Atlantic rainforest region, Brazil. The patient developed inoculation eschar at the tick bite site associated with enlarged lymph nodes in the left groin, fever, polyarthralgia, headache and macular rash. Twenty days after tick bite episode, he displayed monoarthritis in his right knee. The diagnosis of mild Rickettsiosis was established by sequential immunological analysis in serum and synovial fluid, using the indirect immunofluorescence (IF) assay for antibodies reactive with Rickettsia parkeri and Rickettsia rickettsii. The mild Rickettsiosis is an emerging zoonosis, that must be investigated by physicians, including rheumatologists, in patients that present macular rash, fever and eventually arthritis, after visiting the southern coastal Atlantic rainforest region in Brazil.

Profile of patients with Baggio-Yoshinari Syndrome admitted at "Instituto de Infectologia Emilio Ribas" / Perfil dos pacientes com Síndrome Baggio-Yoshinari admitidos no "Instituto de Infectologia Emilio Ribas"

The aim of this study was to evaluate the epidemiological, clinical and laboratorial profile of patients with Baggio-Yoshinari Syndrome (BYS), who underwent internment at the Instituto de Infectologia Emilio Ribas in São Paulo, Brazil, during the period from July 1990 to July 2006. BYS is a new Brazilian tick-borne disease caused by Borrelia burgdorferi sensu lato microorganisms that resembles features of Lyme disease (LD), except for its epidemiological, clinical and laboratorial particularities. From 60 patients' records with positive serology to B. burgdorferi done by ELISA and Western-blotting methods, 19 cases were diagnosed as having BYS, according to criteria adopted at LIM-17 HCFMUSP, the Brazilian Reference Laboratory for the research of BYS. The other 41 remaining patients displayed miscellaneous infections or auto-immune processes. The beginning of symptoms in BYS group varied from one day to six years, from the onset of the disease. Four of 19 patients were included in acute disease stage, and 15 in latent. General unspecific symptoms were identified in almost all cases, with high frequencies of fever (78.9 percent) and lymphadenomegaly (36.8 percent). Six patients had skin lesions (31.5 percent); six arthralgia or arthritis (31.5 percent) and eight neurological symptoms (42 percent). Interestingly, two patients showed antibodies directed to B. burgdorferi exclusively in cerebrospinal fluid. Since BYS is a new emergent Brazilian zoonosis and its diagnosis is sometimes complex, all the new knowledge about BYS must be scattered to Brazilian Medical specialists, aiming to teach them how to diagnose this amazing tick-borne disease and to avoid its progression to chronic irreversible sequels.

O objetivo do estudo foi avaliar o perfil epidemiológico, clínico e laboratorial dos pacientes com Síndrome Baggio-Yoshinari (SBY), internados no Instituto de Infectologia Emilio Ribas, São Paulo, Brasil, no período de julho de 1990 a julho de 2006. SBY é uma nova doença transmitida por carrapatos, causada pela Borrelia burgdorferi sensu lato, que se assemelha a Doença de Lyme (DL), exceto pelas particularidades epidemiológicas, clínicas e laboratoriais. A partir dos registros de 60 pacientes com sorologia positiva para B. burgdorferi pelos métodos de ELISA e Western-blotting, 19 casos foram diagnosticados como SBY, de acordo com critérios adotados pelo LIM-17 HCFMUSP, laboratório de referência para a pesquisa de SBY no Brasil. Os outros 41 pacientes restantes foram classificados como tendo infecções diversas ou processos auto-imunes. O início dos sintomas no grupo SBY variou de um dia a seis anos. Quatro dos 19 pacientes foram incluídos na fase aguda da doença e 15 na fase latente. Os sintomas gerais inespecíficos foram identificados em quase todos os casos, com altas freqüências de febre (78,9 por cento) e linfoadenomegalia (36,8 por cento). Seis pacientes tiveram lesões de pele (31,5 por cento); seis artralgia ou artrite (31,5 por cento) e oito sintomas neurológicos (42 por cento). Curiosamente, dois pacientes apresentaram anticorpos para B. burgdorferi exclusivamente no líquido cefalorraquidiano. Uma vez que a SBY é uma zoonose emergente brasileira e seu diagnóstico é complexo, todo o conhecimento novo sobre SBY deve ser difundido para os médicos brasileiros, com o objetivo de ensiná-los a diagnosticar esta surpreendente doença transmitida por carrapatos, evitando-se a sua progressão para sequelas crônicas irreversíveis.

[Brazilian lyme-like disease or Baggio-Yoshinari syndrome: exotic and emerging Brazilian tick-borne zoonosis].

Lyme disease (LD) is a frequent zoonosis found in the Northern Hemisphere and is considered an infectious disease caused by spirochetes belonging sensu lato to the Borrelia burgdorferi complex transmitted by ticks of the Ixodes ricinus group. In 1992, first cases similar to LD were described in Brazil, when brothers, after a tick bite episode developed symptoms , as erythema migrans, general flu-like symptoms and arthritis. Careful analysis of Brazilian LD-like illness casuistry showed that epidemiological, clinical and laboratorial features in the country were very different from those exhibited by North American and Eurasian LD patients. Human blood-suckers Ixodes ricinus complex ticks were absent at risk areas; the disease is recurrent in the country; Borrelia burgdorferi was never isolated in Brazil and specific serologic tests have shown little positivity with inconsistent results. Furthermore, peripheral blood analysis of patients on electron microscopy exhibited structures resembling Mycoplasma spp, Chlamydia spp and spirochete-like microorganisms. In fact, they were assumed to be latent forms of spirochetes (L form or cell wall deficient bacteria) adapted to survive at inhospitable conditions in vertebrate and invertebrate hosts. For these reasons, the Brazilian zoonosis was named Baggio-Yoshinari Syndrome (BYS) and defined as: "Exotic and emerging Brazilian infectious disease, transmitted by ticks not belonging to the Ixodes ricinus complex, caused by latent spirochetes with atypical morphology, which originates LD-like symptoms, except for occurrence of relapsing episodes and auto-immune disorders".

Profile of patients with Baggio-Yoshinari Syndrome admitted at "Instituto de Infectologia Emilio Ribas".

The aim of this study was to evaluate the epidemiological, clinical and laboratorial profile of patients with Baggio-Yoshinari Syndrome (BYS), who underwent internment at the Instituto de Infectologia Emilio Ribas in São Paulo, Brazil, during the period from July 1990 to July 2006. BYS is a new Brazilian tick-borne disease caused by Borrelia burgdorferi sensu lato microorganisms that resembles features of Lyme disease (LD), except for its epidemiological, clinical and laboratorial particularities. From 60 patients' records with positive serology to B. burgdorferi done by ELISA and Western-blotting methods, 19 cases were diagnosed as having BYS, according to criteria adopted at LIM-17 HCFMUSP, the Brazilian Reference Laboratory for the research of BYS. The other 41 remaining patients displayed miscellaneous infections or auto-immune processes. The beginning of symptoms in BYS group varied from one day to six years, from the onset of the disease. Four of 19 patients were included in acute disease stage, and 15 in latent. General unspecific symptoms were identified in almost all cases, with high frequencies of fever (78.9%) and lymphadenomegaly (36.8%). Six patients had skin lesions (31.5%); six arthralgia or arthritis (31.5%) and eight neurological symptoms (42%). Interestingly, two patients showed antibodies directed to B. burgdorferi exclusively in cerebrospinal fluid. Since BYS is a new emergent Brazilian zoonosis and its diagnosis is sometimes complex, all the new knowledge about BYS must be scattered to Brazilian Medical specialists, aiming to teach them how to diagnose this amazing tick-borne disease and to avoid its progression to chronic irreversible sequels.

Doença de lyme-símile brasileira ou síndrome baggioyoshinari: zoonose exótica e emergente transmitida por carrapatos: [revisão] / Brazilian lyme-like disease or baggio-yoshinari syndrome: exotic and emerging brazilian tick-borne zoonosis: [review]

A Doença de Lyme (DL) é uma zoonose frequente no hemisfério Norte e considerada uma enfermidade infecciosa causada por espiroquetas do complexo Borrelia burgdorferi sensu lato e transmitida pela picada de carrapatos do grupo Ixodes ricinus. Os primeiros casos semelhantes à DL no Brasil foram descobertos, em 1992, em irmãos que após serem picados por carrapatos desenvolveram eritema migratório, sintomas gripais e artrite. Criteriosa análise da casuística brasileira, mostrou que os aspectos epidemiológicos, clínicos e laboratoriais no país, divergiam bastante dos exibidos pelos pacientes com DL nos Estados Unidos da América e Eurásia. Não foram encontrados carrapatos do complexo Ixodes ricinus hematófago ao homem nas áreas de risco; a enfermidade no país é recorrente; a Borrelia burgdorferi jamais foi isolada no Brasil e os ensaios sorológicos específicos exibem positividade baixa e oscilante. Além disso, o exame do sangue periférico dos pacientes quando analisados à microscopia eletrônica exibe estruturas sugestivas de Mycoplasma spp, Chlamydia spp e bacteroides. Na verdade, estas estruturas podem representar as formas latentes das espiroquetas (forma L ou bactérias desprovidas de parede), adaptadas a sobreviver em condições inóspitas em hospedeiros vertebrados e invertebrados. Assim, a zoonose presente no país recebeu a denominação de Síndrome Baggio-Yoshinari e definida como: "Enfermidade infecciosa nova e emergente brasileira, transmitida por carrapatos não pertencentes ao complexo Ixodes ricinus, causada por espiroquetas na sua morfologia atípica e latente, que origina manifestações clínicas semelhantes às observadas na DL, exceto pela ocorrência de recidivas clínicas e desordens autoimunes".

Lyme disease (LD) is a frequent zoonosis found in the Northern Hemisphere and is considered an infectious disease caused by spirochetes belonging sensu lato to the Borrelia burgdorferi complex transmitted by ticks of the Ixodes ricinus group. In 1992, first cases similar to LD were described in Brazil, when brothers, after a tick bite episode developed symptoms , as erythema migrans, general flu-like symptoms and arthritis. Careful analysis of Brazilian LD-like illness casuistry showed that epidemiological, clinical and laboratorial features in the country were very different from those exhibited by North American and Eurasian LD patients. Human blood-suckers Ixodes ricinus complex ticks were absent at risk areas; the disease is recurrent in the country; Borrelia burgdorferi was never isolated in Brazil and specific serologic tests have shown little positivity with inconsistent results. Furthermore, peripheral blood analysis of patients on electron microscopy exhibited structures resembling Mycoplasma spp, Chlamydia spp and spirochete-like microorganisms. In fact, they were assumed to be latent forms of spirochetes (L form or cell wall deficient bacteria) adapted to survive at inhospitable conditions in vertebrate and invertebrate hosts. For these reasons, the Brazilian zoonosis was named Baggio-Yoshinari Syndrome (BYS) and defined as: "Exotic and emerging Brazilian infectious disease, transmitted by ticks not belonging to the Ixodes ricinus complex, caused by latent spirochetes with atypical morphology, which originates LD-like symptoms, except for occurrence of relapsing episodes and auto-immune disorders".

Neurological manifestations in Baggio-Yoshinari Syndrome (Brazilian Lyme disease-like syndrome) / Manifestação neurológica na síndrome de Baggio-Yoshinari (síndrome brasileira semelhante à doença de Lyme)

INTRODUÇÃO: A doença de Lyme (DL) é uma doença de picada de carrapato, causado pela espiroqueta Borrelia burgdorferi sensu lato, transmitida por carrapatos do complexo Ixodes ricinus, que promove múltiplas manifestações clínicas sistêmicas. No Brasil, uma síndrome diferente é descrita e mimetiza sintomas de DL, mas também se manifesta com alta frequência de episódios recorrentes e manifestações alérgicas e imunológicas. É transmitida pelo carrapato Amblyomma cajennense e o agente etiológico é uma espiroqueta não cultivável de forma atípica. Devido a essas particularidades, esta zoonose emergente tem sido denominada síndrome brasileira semelhante à doença de Lyme ou síndrome de Baggio-Yoshinari (SBY). OBJETIVO: Descrever o espectro da manifestação neurológica da SBY. PACIENTES: Foram analisados 30 pacientes com SBY e sintomas neurológicos. RESULTADOS: A média de idade dos pacientes foi de 34,2 ± 13,3 anos (6 a 63 anos); 20 eram mulheres e 10 homens. Um alto número de episódios recorrentes (73,6 por cento) e distúrbios psiquiátricos e psicossociais graves (20 por cento) foram características típicas. Eritema migrans similar ao visto em hemisfério norte foi identificado em 43,3 por cento dos pacientes no início da doença. A recorrência das lesões cutâneas diminuiu com a progressão da doença. Sintomas articulares (artrite) aconteceram em aproximadamente metade dos pacientes com SBY no início e durante o episódio de recidiva. CONCLUSÕES: A SBY é considerada uma nova doença transmitida por carrapato no Brasil que difere da clássica DL observada no hemisfério norte. A SBY reproduz sintomas neurológicos observados na DL, exceto pela presença adicional de recorrência de episódios e uma tendência de causar manifestações neurológicas crônicas e articulares.

INTRODUCTION: Lyme disease (LD) is a tick-borne disease, caused by Borrelia burgdorferi sensu lato spirochetes, transmitted by Ixodes ricinus complex ticks, which leads to multiple systemic clinical manifestations. In Brazil, a different syndrome is described that mimics LD symptoms, but that also manifests high frequencies of recurrent episodes and immune-allergic manifestations. It is transmitted by the Amblyomma cajennense tick and the etiological agent is an uncultivable spirochete with atypical morphology. Due to its particularities, this emerging zoonosis has been called Brazilian LD-like syndrome or Baggio-Yoshinari Syndrome (BYS). OBJECTIVE: To describe the neurological spectrum of BYS. PATIENTS: Thirty patients with neurological symptoms of BYS were analyzed. RESULTS: Mean age of patients was 34.2 ± 13.3 years old (6 to 63 years); 20 were females and 10 males. A high number of recurrent episodes (73.6 percent) and severe psychiatric or psycho-social disturbances (20 percent) were distinguishing features. Erythema migrans similar to those seen in the Northern hemisphere was identified in 43.3 percent of patients at disease onset. The recurrence of skin lesions diminished as the disease progressed. Articular symptoms (arthritis) happened in nearly half of patients at BYS onset and during relapsing episodes. CONCLUSIONS: The BYS is considered a new tick borne disease in Brazil that differs from classical LD observed in the Northern hemisphere. BYS replicates most of the neurological symptoms observed in LD, except for the additional presence of relapsing episodes and the tendency to cause chronic neurological and articular manifestations.

Report on the unusual presence of latent microorganisms in animals: a risk to research and health of employees / Relato inusitado de micro-organismos latentes em animais: riscos à pesquisa e à saúde dos funcionários

Relata-se inusitado achado de micro-organismos, semelhantes às espiroquetas, móveis e de diferentes morfologias e tamanhos, identificados pela microscopia de campo escuro, no sangue de animais do Centro de Bioterismo da Faculdade de Medicina da USP. As bactérias não crescem em meios habituais de cultivo, são pouco coradas pelo Giemsa e derivados da prata, e as provas sorológicas e moleculares foram negativas para Borrelia e Leptospira. A microscopia eletrônica revelou presença de micro-organismos com morfologia de Mycoplasma e, devido à sua mobilidade, sugeriu-se a presença de Mollicutes do gênero Spiroplasma. Visualizaram-se micro-organismos com mesmas características em 15 dos 26 funcionários (57,6 por cento) do Centro de Bioterismo da FMUSP; contudo, exames clínicos e laboratoriais indicaram que os indivíduos estavam saudáveis. Estudos adicionais desenvolvidos na Disciplina de Reumatologia da FMUSP mostraram que, aproximadamente, 94 por cento dos pacientes com Síndrome Baggio-Yoshinari (SBY) e 20 por cento dos indivíduos normais também exibiam as mesmas estruturas identificadas no Centro de Bioterismo. A microscopia eletrônica realizada com amostras de pacientes com SBY mostrou bactérias que apresentam semelhanças com Mycoplasma, Chlamydia e Bacteroides. Visto que as sorologias e os testes moleculares foram negativos para estes contaminantes e com base em publicações da literatura médica, sugeriu-se que estes agentes infecciosos latentes fossem bactérias na sua apresentação L, que são definidas como bactérias despojadas de parede celular, assumindo, assim, morfologia de Mycoplasma, sendo, na maioria dos casos, inofensivas aos hospedeiros. Concluímos que os "espiroquetídeos" visualizados em animais e funcionários do Centro de Bioterismo seriam bactérias na forma L, não patogênicas, provenientes de contaminantes do meio ambiente, infecções regulares habituais ou oriundos de micro-organismos endógenos da flora saprofítica normal. Ao contrário, os...

We report the unusual finding of mobile spirochetal microorganisms with different morphologies and sizes, on dark-field microscopy of the blood of animals from the Vivarium of the Medical School of USP. The bacteria did not grow in common culture media, shows faint staining to Giemsa and silver-derived stains, and serologies and molecular tests were negative for Borrelia and Leptospira. Electron microscopy revealed the presence of microorganisms with Mycoplasma-like morphology and, due to its mobility, it was suggested that they represented Mollicutes of the genus Spiroplasma. Microorganisms with the same morphology were also observed in 15 out of 26 employees (57.6 percent) of the Vivarium of FMUSP; however, clinical and laboratorial exams indicated that those individuals were healthy. Additional studies undertaken at the Rheumatology Department of FMUSP demonstrated the presence of the same structures identified at the Vivarium in approximately 94 percent of the patients with Baggio-Yoshinary syndrome (BYS) and 20 percent of healthy individuals. Electron microscopy of the blood of BYS patients showed bacteria that shared similarities with Mycoplasma, Chlamydia, and Bacteroides. Since serologies and molecular tests were negative for those contaminants, and based on publications in the medical literature, it was suggested that those latent infectious agents were L-form bacteria, defined as cell wall deficient bacteria, assuming, therefore, Mycoplasma morphology and they are, for the most part, harmless to the host. We concluded that spirochetal microorganisms visualized in animals and employees of the Vivarium were non-pathogenic L-form bacteria from contaminants in the environment, regular infections, or endogenous microorganism from the normal saprophytic flora. On the other hand, spirochetal organisms identified in BYS, by preserving the capacity to invade cells in vitro, are potentially pathogenic and related to the etiology of BYS. We consider BYS as a ...

Estudo laboratorial de agentes infecciosos transmitidos por carrapatos em pacientes com doença de Lyme-símile brasileira (síndrome Baggio-Yoshinari) / Laboratorial study of tick-borne infectious agents in patients with brazilian Lyme-like disease (Baggio-Yoshinari Syndrome)

Ehrlichiose Monocítica Humana, Anaplasmose Granulocítica Humana, Babesiose, Febre Maculosa das Montanhas Rochosas e Doença de Lyme são doenças transmitidas por carrapatos encontradas no Hemisfério Norte. No Brasil, a DL-símile chamada de Síndrome Baggio-Yoshinari (SBY) é descrita, mas as características epidemiológicas, clínicas e laboratoriais são diferentes da DL original. Nos Brasileiros, as outras doenças transmitidas por carrapatos são pouco estudadas. O objetivo desta pesquisa é estudar a possibilidade de co-infecção entre a SBY e outras doenças transmitidas por carrapatos, através de ensaios laboratoriais para Ehrlichia spp, Babesia spp and Rickettsia spp em um grupo de 70 pacientes com SBY. Dez pacientes estavam na fase inicial da doença e 60 no estágio latente. Eritema Migratório (EM) esteve presente em 27 (38,6%), artrite em 26 (37,1%), febre em 13 (18,5%), cefaléia em 29 (41,4%), artralgia em 36 (51,4%), mialgia em 51 (72,8%), fadiga em 38 (54,3%), meningite em 4 ((5,7%), neurite craniana em 8 (11,4%), radiculopatia periférica em 9 (12,8%), encefalomielite em 4 (5,7%), cardiopatia em 7 (10%), lesão de pele atípica em 10 (14,3%) e anemia em 10 (14,3%). O ELISA (Enzyme Linked Immunosorbent Assay) para Borrelia burgdorferi foi positivo em 21 (30%) pacientes do grupo da SBY e apenas em 3 dos 50 (6%) indivíduos do grupo controle (p = 0.01). Usando o método de Western blotting (WB) modificado para antígenos da B. burgdorferi, trinta e cinco (50%) dos pacientes com SBY foram positivos, e 2 (4%) indivíduos do grupo controle. (p0,001). A Reação de Imunofluorescência Indireta (RIFI) (IgG) apresentou resultados significativos para três das cinco espécies de Rickettsia spp analisadas: R. parkeri (8,6%) (p = 0,032), R. amblyommii (22.8%) ( p = 0,031) e para R. bellii (8.6%) ( p = 0,032). O Teste do Qui-quadrado foi usado para análise estatística. . Poucos pacientes apresentaram positividade para antígenos de B. bovis (RIFI e ELISA) e B. equi (RIFI)...

Human Monocytic Ehrlichiosis, Human Granulocytic Anaplasmosis, Babesiosis, Rocky Mountain Spotted Fever and Lyme Disease (LD) are tick-borne diseases commonly found in the North hemisphere. In Brazil, a LD-like illness called Baggio- Yoshinari Syndrome (BYS) is described, but epidemiological, clinical and laboratorial features are different from the original LD. In Brazilian humans, the other tick-borne diseases are less frequently studied. The aim of this survey was to verify the possibility of co-infections between BYS and other tick-borne diseases, using laboratorial assays to Ehrlichia spp, Babesia spp and Rickettsia spp in a group of 70 patients with BYS. Ten patients were at initial stage of the disease and 60 patients were in a latent stage. Erythema migrans (EM) was present in 27 patients (38.6%), arthritis in 26 (37,1%), fever in 13 (18.5%), headache in 29 (41.4%) arthralgia in 36 (51.4%), myalgia in 51 (72,8%), fatigue in 38 (54,3%), meningitis in 4 (5.7%), cranial neuritis in 8 (11.4%), peripheral radiculopathy in 9 (12.8%), encephalomyelitis in 4 (5.7%), cardiopathy in 7 (10%), atypical skin eruptions in 10 (14.3%) and anemia in 10 patients (14.3%). ELISA (Enzyme Linked Immunossorbent Assay) for Borrelia burgdorferi antigens was positive in 21 patients (30%) of BYS group, while only 3 (6%) from 50 normal individuals had positive reactions (p = 0.01). Using the modified Western Blotting (WB) method for B. burgdorferi antigens, 35 (50%) of the BYS patients were positive, and 2 normal individuals (4%) from the control group (p 0,001). Indirect Immunofluorescence Assay (IFA) (IgG) presented positive results for three of five species of Rickettsia tested: R. parkeri (8, 6%) (p = 0,032), R. amblyommii (22.8%) (p = 0,031) and for R. bellii (8.6%) (p = 0,032). Chi-square test was used for the statistic analysis. A few patients developed a positive reaction to B. bovis (IFA and ELISA) and B. equi antigens (IFA).IFA for Ehrlichia canis antigens was positive...

Coexistence of antibodies to tick-borne agents of babesiosis and Lyme borreliosis in patients from Cotia county, State of São Paulo, Brazil.

This paper reports a case of coinfection caused by pathogens of Lyme disease and babesiosis in brothers. This was the first case of borreliosis in Brazil, acquired in Cotia County, State of S o Paulo, Brazil. Both children had tick bite history, presented erythema migrans, fever, arthralgia, mialgia, and developed positive serology (ELISA and Western-blotting) directed to Borrelia burgdorferi G 39/40 and Babesia bovis antigens, mainly of IgM class antibodies, suggestive of acute disease. Also, high frequencies of antibodies to B. bovis was observed in a group of 59 Brazilian patients with Lyme borreliosis (25.4%), when compared with that obtained in a normal control group (10.2%) (chi-square = 5.6; p < 0.05). Interestingly, both children presented the highest titers for IgM antibodies directed to both infective diseases, among all patients with Lyme borreliosis.

Coexistence of antibodies to tick-borne agents of babesiosis and Lyme borreliosis in patients from Cotia county, State of São Paulo, Brazil

This paper reports a case of coinfection caused by pathogens of Lyme disease and babesiosis in brothers. This was the first case of borreliosis in Brazil, acquired in Cotia County, State of São Paulo, Brazil. Both children had tick bite history, presented erythema migrans, fever, arthralgia, mialgia, and developed positive serology (ELISA and Western-blotting) directed to Borrelia burgdorferi G 39/40 and Babesia bovis antigens, mainly of IgM class antibodies, suggestive of acute disease. Also, high frequencies of antibodies to B. bovis was observed in a group of 59 Brazilian patients with Lyme borreliosis (25.4 percent), when compared with that obtained in a normal control group (10.2 percent) (chi-square = 5.6; p < 0.05). Interestingly, both children presented the highest titers for IgM antibodies directed to both infective diseases, among all patients with Lyme borreliosis

Perfil clínico e laboratorial da doença de Lyme-símile no Estado de Mato Grosso do Sul: análise de 16 pacientes / Clinical and laboratorial outline of lyme-like disease, in Mato Grosso do Sul State: analysis of 16 patients

Objetivo: Relatar o perfil epidemiológico, clínico e laboratorial da doença de Lyme-símile em Mato Grosso do Sul. Pacientes e métodos: Dezesseis pacientes preencheram o critério do Centro de Referência para Doença de Lyme no Brasil. Avaliaram-se dados epidemiológicos e manifestações clínicas; a reatividade sorológica e liquórica, pelas técnicas de ELISA e Western blot (WB), utilizando como substratos: Borrelia burgdorferi sensu strictu, B.garinii e B. afzelii; e a amplificação do DNA no soro e líquor pela técnica da reação em cadeia de polimerase (PCR). Resultados: Quinze pacientes moravam na zona urbana, 25 por cento foram picados por carrapatos e 18,7 por cento tiveram contato direto: entre a picada e o início dos sintomas o intervalo foi de 15 dias a dois meses. O eritema migratório crônico ocorreu em oito (50 por cento) pacientes e destes, cinco desenvolveram eritemas anulares secundários; 31,2 por cento dos pacientes apresentaram lesões com características incomuns, inclusive com aspecto esclerodérmico. Cinco pacientes (31,2 por cento) apresentaram mialgia, quatro (25 por cento), artralgia e, outros quatro (25 por cento), artrite. Seis (37,5 por cento) apresentaram comprometimento neurológico; pleocitose linfocítica foi a única alteração liquórica. As amostras negativas pelo ELISA foram positivas ao WB e aquelas positivas pelo primeiro método confirmaram-se pelo segundo. Comparativamente, WB foi o melhor método para o diagnóstico da doença (p = 0,0352). Não ocorreu a amplificação do DNA pelo PCR. Conclusão: A doença de Lyme no Brasil apresenta características epidemiológicas, clínicas e laboratoriais distintas das presentes em demais continentes, sugerindo tratar-se de doença Lyme-símile (doença de Yoshinari), sendo o próximo grande desafio o isolamento e identificação do seu agente etiológico

Oviposition and eclosion periods of Ixodes didelphidis Fonseca and Aragäo, 1951 (Acari: Ixodidae) under laboratory conditions

Oviposition and eclosion periods for Ixodes didelphidis were observed under two temperatures (25o.C and 27o.C) and 90-95 percent humidity. Although there was a significant increase in the eclosion period (p<0.05) and a tendency to increase the oviposition period at 25o.C, there was neither significant differences in the interval (days), until maximum peak of eclosion nor in the number of emerging larvae during the peak nor the total number of emerged larvae. These temperature values are not critical for embryological development of the species. Because at 27o.C and under high humidity the oviposition and eclosion periods are shorter, and the percentage of emerged larvae is higher, we consider this to be the ideal temperature for laboratory studies

Síndrome da doença de Lyme-símile e manifestações cutâneas / Lyme disease-like syndrome and skin manifestations

O artigo tem por objetivo apresentar as manifestações cutâneas da síndrome da doença de Lyme-símile no Brasil, que revela aspectos histopatológicos em comum com inúmeras doenças difusas do tecido conjuntivo. Os autores relatam o primeiro caso de paniculite lobular associado à borreliose no país e comentam a evolução sorológica sequencial e tratamento desta entidade clínica