Factors associated with the confirmation and death for Brazilian spotted fever in an important endemic area of the State of São Paulo, 2007-2021

ABSTRACT Background: We evaluated the predictive factors for case confirmation and death from Brazilian spotted fever in an endemic area of Southeastern Brazil. Methods: A cross-sectional study was conducted. All suspected cases reported between 2007 and 2021 were analyzed using two logistic regression models. Results: 60 cases were confirmed. Male sex, age group of 40-59 years, tick parasitism, presence of capybaras or horses, exanthema and hospitalization were positively associated with confirmation. Death was associated with a longer period between first symptom-hospitalization and shorter treatment. Conclusions: Complete clinical evaluation and information on risk exposure are key to early suspicion, diagnosis, treatment and prevention of deaths.

Lack of association of the KIR and HLA class I ligands with ZIKV infection in south and southeast of Brazil

BACKGROUND Zika virus (ZIKV) is an emerging arbovirus associated with foetal malformations and neurological complications. The infection is usually associated with mild symptoms. The comparison between the allelic frequency of polymorphic genes in symptomatic infected individuals in the population can clarify the pathogenic mechanisms of ZIKV. During ZIKV infection, cytokines are produced and natural killer (NK) cells are recruited, whose activation depends on signaling pathways activated by specific receptors, such as killer cell immunoglobulin-like receptors (KIR). These molecules interact with human leukocyte antigen (HLA) class I ligands and are encoded by polymorphic genes. OBJECTIVES This study aimed to evaluate the frequency of allelic variants of the genes encoding the KIR receptors and their HLA class I ligands in 139 symptomatic ZIKV-patients and 170 controls negative for the virus, and to evaluate the role of these variants for ZIKV susceptibility. METHODS KIR and HLA class I genes were genotyped using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique. FINDINGS No significant differences in the frequency distribution of KIRs and KIR-HLA in patients compared to controls were observed. MAIN CONCLUSIONS KIR and its HLA ligands might play a minor role in ZIKV infection in the south and southeast Brazilian individuals.

Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines.

A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8-3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.

Avaliação do sistema de vigilância epidemiológica da leptospirose em Campinas, São Paulo, 2007 a 2014 / Evaluation of the leptospirosis epidemiological surveillance system in Campinas, São Paulo

Resumo Introdução A leptospirose figura na lista de doenças de notificação compulsória no Brasil. Objetivo Avaliar o sistema de vigilância epidemiológica da leptospirose no município de Campinas, São Paulo, no período de 2007-2014. Método Foi realizado um estudo de prevalência dos casos de leptospirose no sistema de vigilância epidemiológica. Foram analisados 2.949 casos notificados, considerando-se os atributos do Updated Guidelines for Evaluating Public Health Surveillance Systems e os parâmetros propostos por Souza et al. (2010) ao Sistema Nacional de Vigilância Epidemiológica. Foram analisados os seguintes atributos: completude, aceitabilidade, sensibilidade, valor preditivo positivo, representatividade e oportunidade. Resultados A completude foi boa (94,1%); a aceitabilidade foi de 68,3%; o valor preditivo positivo foi de 10,7%; a representatividade foi de 98,4%; e a oportunidade ocorreu em 71,4% dos casos. Conclusão É possível concluir que o sistema de vigilância epidemiológica para a leptospirose em Campinas teve uma completude aceitável e bom percentual de suspeição da doença. Foram observados atraso na notificação e na investigação dos casos e precária integração entre os sistemas de informações. A avaliação do sistema de vigilância traz informações importantes para a organização dos serviços de saúde e deve fazer parte da rotina das ações previstas no sistema. Este trabalho pode ser usado como modelo para a avaliação de sistemas de informação de outras doenças de notificação compulsória.

Abstract Background Leptospirosis is included in the list of diseases of compulsory notification in Brazil. Objective To evaluate the leptospirosis epidemiological surveillance system in the municipality of Campinas, state of São Paulo, Brazil, between 2007 and 2014. Method A study on the prevalence of leptospirosis cases was carried out in the epidemiological surveillance system. A total of 2949 reported cases were analyzed considering the attributes of the Updated Guidelines for Evaluating Public Health Surveillance Systems and the parameters proposed by Souza et al. (2010) for the National Epidemiological Surveillance System. The following attributes were assessed: completeness, acceptability, sensitivity, positive predictive value, representativeness, and timeliness. Results The following percentages were found for the respective attributes: completeness (94.1%), acceptability (68.3%), positive predictive value (10.7%), representativeness (98.4%) and timeliness (71.4%). Conclusion The leptospirosis epidemiological surveillance system in Campinas presented acceptable completeness and good positive predictive value of disease suspicion. Delays in the notification and investigation of cases and poor integration between the information systems were observed. The evaluation of the surveillance system provides important information for the organization of health services and should be part of the routine of actions provided for in the system. This study can be used as a model to evaluate information systems of other noticeable diseases.

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice.

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

Custo-efetividade da vacina contra influenza quadrivalente baseada em células comparada com a trivalente baseada em ovo do Programa Nacional de Imunizações brasileiro / Cost-effectiveness of cell-based quadrivalent versus egg-based trivalent influenza vaccination in the Brazilian National Immunization Program

Objetivos: Este estudo teve como objetivo avaliar desfechos clínico-econômicos associados à vacina contra influenza quadrivalente baseada em células (QIVc) versus a vacina trivalente atualmente utilizada (TIVe) para prevenção sazonal de influenza no Programa Nacional de Imunizações (PNI) brasileiro. Métodos: Um modelo estático de árvore de decisão foi usado. Considerou-se um total de 54.071.642 indivíduos vacinados em 2019; a circulação de influenza por subtipo foi baseada em dados de vigilância epidemiológica. A efetividade da vacina (EV) TIVe foi extraída de metanálises publicadas; já a EV relativa da QIVc foi retirada de um estudo observacional retrospectivo. A incompatibilidade antigênica da vacina com vírus circulantes foi baseada em fontes retrospectivas internacionais. O uso de recursos baseou-se em estudos do mundo real. Custos unitários foram retirados de tabelas-padrão publicados em 2019 em reais (BRL). Resultados: Substituir a TIVe pela QIVc pode evitar, anualmente, casos sintomáticos (452.065) e reduzir visitas ambulatoriais (118.735), hospitalizações (15.466), mortes (2.753), custos médicos (-BRL 46.677.357) e custos indiretos (-BRL 59.962.135). O número anual de anos de vida ajustados por qualidade de vida (QALYs) pode aumentar em 96.129. Resultados de base a partir da perspectiva do pagador mostram uma razão de custo-efetividade incremental (RCEI) de BRL 17.293/QALY e, da perspectiva da sociedade, o RCEI obtido foi de um ganho de BRL 16.669/QALY. Usando o Produto Interno Bruto (PIB) brasileiro como um limiar (BRL 34.533/QALY), trocar a TIVe pela QIVc no PNI pode ser uma estratégia altamente custo-efetiva. Conclusões: O uso da QIVc pelo PNI tem potencial para ser altamente custo-efetivo tanto da perspectiva do pagador quanto da sociedade

Objectives: This study aimed to estimate health and economic outcomes associated to cell-based quadrivalent influenza vaccine (QIVc) versus current trivalent influenza vaccines (TIVe) for seasonal influenza prevention in the Brazilian National Immunization Program (NIP), from the societal and public payer perspectives. Methods: A 1-year static decision-tree model based on literature was used. 54,071,642 total vaccinated individuals in 2019 were considered; influenza subtype circulation was based on Brazilian epidemiologic data (2009-2019). TIVe vaccine effectiveness (VE) was extracted from a published meta-analysis and QIVc relative VE from an international retrospective observational study. A/H3N2 egg-adaptation and B mismatch to recommended strain were gathered from international retrospective sources. Resource use was obtained from real-world studies. Inputs were adjusted to influenza subtype and multiple age groups with Brazilian literature. Unit costs were retrieved from published standard tables in 2019 Brazilian Reais (BRL). Results: Replacing TIVe with QIVc, can annually avert symptomatic cases (452,065) and reduce outpatient visits (118,735); hospitalizations (15,466), deaths (2,753), overall medical direct costs (-BRL 46,677,357) and indirect costs (-BRL 59,962,135). The annual number of quality-adjusted life-years (QALYs) could be increased by 96,129. Base case results from the payer perspective show an incremental cost-effectiveness ratio (ICER) of BRL 17,293/QALY gained and from the societal perspective the ICER obtained was BRL 16,669/QALY gained. Using the Brazilian Gross Domestic Product (GDP) as a threshold (BRL 34,533/QALY) switching TIVe with QIVc in the NIP can be a highly cost-effective strategy, leading to a high QALY increment and preventing medical and indirect costs. Conclusions: The use of QIVc by the NIP has the potential to be highly cost-effective in the payer and society perspective

Bartonella henselae bacteremia diagnosed post-mortem in a myelodysplastic syndrome patient.

This study involves a 49-year-old male, who for three years suffered with a myelodysplastic syndrome and who needed frequent blood transfusions. One day following a transfusion, he presented fever and abdominal pain. The fever became persistent and only improved temporarily with two cycles of intravenous ciprofloxacin. Nearly 120 days after beginning the second cycle of treatment, he had experienced a weight loss of 16 kg and recurring fever. Screening for fever of unknown origin was conducted, including Bartonella infection. No etiology could be found. The patient improved with an antimicrobial regimen composed of oral doxycycline and intravenous ciprofloxacin. After 15 days afebrile, the patient was discharged with a four-month oral prescription of doxycycline and ciprofloxacin. Eight months following the antibiotic treatment, the patient received an allogeneic bone marrow transplant. Five days following the transplant, the patient initiated a febrile neutropenia and died. From a blood sample collected and stored at the time of hospitalization, a microbiological and molecular study was performed again. Blood- and liquid culture-PCRs from the same blood sample were all negative, but an isolate from solid subculture was found. The molecular reactions from this isolate were all positive and the sequence was 100% homologous to Bartonella henselae . The present report points to the limitations of laboratory techniques currently available for investigation of possible cases of bartonellosis in clinical practice, and the potential risk of Bartonella spp. transmission through blood transfusions.

A fatal case of Brazilian spotted fever in a non-endemic area in Brazil: the importance of having health professionals who understand the disease and its areas of transmission

Abstract Brazilian spotted fever (BSF) is caused by the bacterium Rickettsia rickettsii. Because of its high case-fatality rate and apparent increase in areas of transmission, it is considered to be the rickettsial illness of primary public health interest. Cases of this disease have historically occurred in Southeastern Brazil. This article reports the first fatal case of BSF in Southern Brazil. This case high lights the importance of BSF to be considered as a differential diagnosis for acute hemorrhagic fever in areas where cases of BSF may not be expected.

Antibodies for Rickettsia spp. in patients with negative serology for dengue virus, leptospirosis, and meningococcal disease in municipalities of São Paulo State, Brazil

Abstract INTRODUCTION Brazilian spotted fever is an infectious disease with a high mortality rate if not treated early. Differential diagnosis is difficult, as the first clinical signs are non-specific and can be confused with other diseases. The aim of the study was to investigate evidence of infection with Rickettsia rickettsii and Rickettsia parkeri in negative sera samples, collected in 2014, from patients with suspected leptospirosis, dengue fever, and meningococcal disease in Atibaia and Bragança Paulista municipalities of the State of São Paulo. METHODS The samples stored at the Institute Adolfo Lutz in Campinas were tested using an indirect immunofluorescence assay (IFA) with IgG and IgM against R. rickettsii and R. parkeri. Real-time polymerase chain reaction (PCR) testing was performed for the sera samples of patients who died (n = 3), those with initial suspicion of meningococcal disease (n = 6), and those with positive IFA results. RESULTS Of 258 samples from Bragança Paulista, 4 (1.6%) were positive, with IgG titers of 1:64 and 1:128 against R. rickettsii and R. parkeri, respectively. Of 155 samples from Atibaia, 2 (1.3%) were positive, with IgG titers of 1:64 and 1:128 against R. rickettsii and R. parkeri, respectively. No sample showed positive PCR results. CONCLUSIONS This serological investigation suggests there is evidence of exposure to Rickettsia spp. in residents of areas that have environmental conditions favorable to the spread of bacteria, in which Brazilian spotted fever incidence was not previously confirmed.

Probable transfusion-transmitted Zika virus in Brazil.

BACKGROUND: Zika virus (ZIKV) is an emerging arthropod-borne flavivirus transmitted by Aedes mosquitoes. Recent commentaries regarding ZIKV routes of transmission describe a potential transmission by transfusion. Herein, we report a probable case of transfusion-transmitted ZIKV infection through a platelet transfusion that was detected from postdonation information. CASE REPORT: A blood donor made a voluntary telephone report to the blood donor facility 3 days after donation and informed the facility of a febrile illness (fever, malaise, and headaches). Due to the ongoing dengue epidemic, the initial clinical investigation included dengue among other possible diagnoses. The serology and molecular laboratory results excluded dengue infection. However, stored samples from the donation were positive for ZIKV on reverse transcription-polymerase chain reaction (RT-PCR) analysis. A retrospective investigation demonstrated that the platelet concentrate, which was part of a pool, had been transfused after a liver transplantation. A physician had evaluated the patient 4 days after surgery. Laboratory investigation showed enzyme-linked immunosorbent assay results that were negative for dengue immunoglobulin M antibodies; however, the results were positive for hemagglutination inhibition antibodies against flavivirus. ZIKV RT-PCR and virus isolation analyses in cell cultures from recipient serum were both positive. The sequencing confirmed ZIKV in the donor and patient samples. Ten partial nucleotide sequences from the ZIKV strain that were detected in the donor were aligned and compared with the ZIKV genome detected in the recipient, revealing a 99.8% homology between the two strains. CONCLUSIONS: This is a case of probable transmission of ZIKV through blood transfusion. The patient had been transfused with the blood product from an infected donor, most likely in the incubation period after ZIKV infection but prior to clinical disease onset. This report emphasizes the importance of postdonation information and recipient investigations during outbreaks of potentially blood-borne infections.

Bleeding complications in dengue are not associated with significant changes in the modulators of the endothelial barrier.

Bleeding complications in dengue may occur irrespective of the presence of plasma leakage. We compared plasma levels of modulators of the endothelial barrier among three dengue groups: bleedings without plasma leakage, dengue hemorrhagic fever, and non-complicated dengue. The aim was to evaluate whether the presence of subtle alterations in microvascular permeability could be detected in bleeding patients. Plasma levels of VEGF-A and its soluble receptors were not associated with the occurrence of bleeding in patients without plasma leakage. These results provide additional rationale for considering bleeding as a complication independent of endothelial barrier breakdown, as proposed by the 2009 WHO classification.

Dry eye disease caused by viral infection: review.

Dry eye disease and ocular surface disorders may be caused or worsened by viral agents. There are several known and suspected virus associated to ocular surface diseases. The possible pathogenic mechanisms for virus-related dry eye disease are presented herein. This review serves to reinforce the importance of ophthalmologists as one of the healthcare professional able to diagnose a potentially large number of infected patients with high prevalent viral agents.

Dry eye disease caused by viral infection: review / Olho seco causado por infecções virais: revisão

Dry eye disease and ocular surface disorders may be caused or worsened by viral agents. There are several known and suspected virus associated to ocular surface diseases. The possible pathogenic mechanisms for virus-related dry eye disease are presented herein. This review serves to reinforce the importance of ophthalmologists as one of the healthcare professional able to diagnose a potentially large number of infected patients with high prevalent viral agents.

A síndrome do olho seco e as doenças de superfície ocular podem ser causadas ou agravadas por agentes virais. Diversos vírus são causadores ou tem associação suspeitada com as doenças de superfície ocular. Esta revisão apresenta os possíveis mecanismos patogênicos envolvidos no olho seco causado por infecões virais e reinforça a importância do oftalmologista como um dos profissionais de saúde capazes de diagnosticar um grande número de pacientes infectados por agentes virais altamente prevalentes.

Autoimmune features caused by dengue fever: a case report

Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.

Lessons from the epidemiological surveillance program, during the influenza A (H1N1) virus epidemic, in a reference university hospital of Southeastern Brazil / Lições aprendidas pelo programa de vigilância epidemiológica, durante a epidemia pelo vírus da influenza A (H1N1), em um hospital universitário na região sudeste do Brasil

INTRODUCTION: The case definition of influenza-like illness (ILI) is a powerful epidemiological tool during influenza epidemics. METHODS: A prospective cohort study was conducted to evaluate the impact of two definitions used as epidemiological tools, in adults and children, during the influenza A H1N1 epidemic. Patients were included if they had upper respiratory samples tested for influenza by real-time reverse transcriptase polymerase chain reaction during two periods, using the ILI definition (coughing + temperature ≤ 38ºC) in period 1, and the definition of severe acute respiratory infection (ARS) (coughing + temperature ≤ 38ºC and dyspnoea) in period 2. RESULTS: The study included 366 adults and 147 children, covering 243 cases of ILI and 270 cases of ARS. Laboratory confirmed cases of influenza were higher in adults (50%) than in children (21.6%) ( p < 0.0001) and influenza infection was more prevalent in the ILI definition (53%) than ARS (24.4%) (p < 0.0001). Adults reported more chills and myalgia than children (p = 0.0001). Oseltamivir was administered in 58% and 46% of adults and children with influenza A H1N1, respectively. The influenza A H1N1 case fatality rate was 7% in adults and 8.3% in children. The mean time from onset of illness until antiviral administration was 4 days. CONCLUSIONS: The modification of ILI to ARS definition resulted in less accuracy in influenza diagnosis and did not improve the appropriate time and use of antiviral medication.

INTRODUÇÃO: A definição de síndrome gripal é uma ferramenta epidemiológica importante durante epidemias de influenza. MÉTODOS: Foi conduzido estudo de coorte prospectivo para avaliar o impacto das definições de síndrome gripal (SG) e doença respiratória aguda grave (DRAG) como ferramenta de vigilância epidemiológica, em adultos e crianças, durante a epidemia de influenza A H1N1. Os pacientes foram incluídos se tivessem coleta de secreção respiratória alta testada por PCR real time para o vírus da influenza. Os dados clínicos e epidemiológicos foram estudados comparando-se dois períodos: período 1: SG (tosse + temperatura ≤ 38ºC), e período 2: DRAG (tosse + temperatura ≤ 38 e dispnéia). RESULTADOS: Foram incluídos 366 adultos e 147 crianças, em um total de 243 casos de SG e 270 DRAG. A confirmação laboratorial de influenza em adultos (50%) foi significativamente maior do que em crianças (21,6%) (p < 0,0001) e a definição de SG foi mais confirmatória de infecção por influenza (53%) do que DRAG (24,4%) (p < 0,0001). Adultos referiam mais calafrios e mialgias do que as crianças (p = 0,0001). Oseltamivir foi prescrito, respectivamente, em 58% e 46% dos adultos e crianças com influenza A H1N1. A letalidade por influenza A H1N1 foi de 7% em adultos e 8,3% em crianças. CONCLUSÕES: A mudança de definição do critério de vigilância epidemiologia de SG para DRAG resultou em redução significativa da acurácia do diagnóstico de influenza e não contribuiu para melhor indicação do antiviral como também para a sua prescrição no tempo apropriado.