Molecular Epidemiology of Mayaro Virus among Febrile Patients, Roraima State, Brazil, 2018-2021.

We detected Mayaro virus (MAYV) in 3.4% (28/822) of febrile patients tested during 2018-2021 from Roraima State, Brazil. We also isolated MAYV strains and confirmed that these cases were caused by genotype D. Improved surveillance is needed to better determine the burden of MAYV in the Amazon Region.

Valor preditivo do national early warning SCORE 2 para admissão à unidade de terapia intensiva em pessoas com infecção por SARS-COV 2 / Predictive value of the national early warning SCORE 2 for admission to the intensive care unit in people with SARS-COV 2 infection

INTRODUÇÃO: Pacientes com infecção por SARS-CoV 2 podem apresentar rápida deterioração clínica, evoluindo para Síndrome do Desconforto Respiratório Agudo, sepse ou choque, bem como necessidade de ventilação mecânica ou de cuidados intensivos. É premente avaliar sinais de alerta de deterioração clínica, com vistas a intervir precocemente, aumentando as chances de sobrevida de pacientes com COVID-19. Tendo em vista que a alteração dos sinais vitais são frequentes na evolução da COVID-19, optou-se por utilizar a escala National Early Warning Score (NEWS2). O NEWS2 identifica o risco de deterioração clínica precoce e prediz os cuidados requeridos e sua frequência; sendo um indicador competente para intervenções precoces. No entanto, pouco se sabe sobre sua aplicação para pacientes com COVID-19. Este estudo visou analisar, de forma pioneira no Brasil, a performance prognóstica e o poder discriminatório do NEWS2 em unidades de internação adulto de um hospital universitário paulista quanto às admissões em unidades de terapia intensiva (UTI). MÉTODOS: Tratou-se de estudo de coorte retrospectivo que avaliou informações de 300 participantes hospitalizados por COVID-19 no período de março de 2020 a março de 2022. Foi utilizado o NEWS2 com vistas a obter um escore de risco de deterioração clínica precoce; e o Índice de Comorbidades de Charlson (ICC), para ajustar o risco estimado pelo NEWS2 de acordo com a prevalência de condições clínicas prévias. RESULTADOS: O escore médio do NEWS2 foi de 4,1 unidades, o que sugere moderada complexidade da atenção. O NEWS2 apresentou bom poder discriminatório, com sensibilidade de 71,1%, especificidade de 56,3%, Valor preditivo positivo de 22,4%, Valor preditivo negativo de 91,7%, Razão de verossimilhança positiva de 1,6 e Razão de verossimilhança negativa de 0,5. A análise da área sob a curva ROC (AUROC, 66%; IC95% = 0,57-0,54; p=0,0009) evidenciou que o índice foi modestamente capaz de predizer a deterioração clínica de pacientes com COVID-19 e a probabilidade de admissão na UTI. CONCLUSÕES: Conclui-se que o NEWS2 apresentou bom poder discriminatório para avaliar a gravidade de pacientes com COVID-19 e moderada capacidade de predição da admissão de pacientes com COVID-19 na UTI.

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.

Evidence for Human-to-Human Transmission of Hantavirus: A Systematic Review.

BACKGROUND: Hantavirus is known to be transmitted from rodents to humans. However, some reports from Argentina and Chile have claimed that the hantavirus strain Andes virus (ANDV) can cause human-to-human transmission of the disease. The aim of this systematic review was to assess the evidence for human-to-human transmission of hantavirus. METHODS: We searched PubMed (inception to 28 February 2021), Cochrane Central, Embase, LILACS and SciELO (inception to 3 July 2020), and other sources. We included studies that assessed whether interpersonal contact with a person with laboratory-confirmed hantavirus infection led to human-to-human transmission. Two reviewers conducted screening, selection, data extraction, and risk of bias assessment. RESULTS: Twenty-two studies met the inclusion criteria. Meta-analysis was not possible due to heterogeneity. With the exception of 1 prospective cohort study of ANDV in Chile with serious risk of bias, evidence from comparative studies (strongest level of evidence available) does not support human-to-human transmission of hantavirus infection. Noncomparative studies with a critical risk of bias suggest that human-to-human transmission of ANDV may be possible. CONCLUSIONS: The balance of the evidence does not support the claim of human-to-human transmission of ANDV. Well-designed cohort and case-control studies that control for co-exposure to rodents are needed to inform public health recommendations.

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

Neutralisation of SARS-CoV-2 lineage P.1 by antibodies elicited through natural SARS-CoV-2 infection or vaccination with an inactivated SARS-CoV-2 vaccine: an immunological study.

BACKGROUND: Mutations accrued by SARS-CoV-2 lineage P.1-first detected in Brazil in early January, 2021-include amino acid changes in the receptor-binding domain of the viral spike protein that also are reported in other variants of concern, including B.1.1.7 and B.1.351. We aimed to investigate whether isolates of wild-type P.1 lineage SARS-CoV-2 can escape from neutralising antibodies generated by a polyclonal immune response. METHODS: We did an immunological study to assess the neutralising effects of antibodies on lineage P.1 and lineage B isolates of SARS-CoV-2, using plasma samples from patients previously infected with or vaccinated against SARS-CoV-2. Two specimens (P.1/28 and P.1/30) containing SARS-CoV-2 lineage P.1 (as confirmed by viral genome sequencing) were obtained from nasopharyngeal and bronchoalveolar lavage samples collected from patients in Manaus, Brazil, and compared against an isolate of SARS-CoV-2 lineage B (SARS.CoV2/SP02.2020) recovered from a patient in Brazil in February, 2020. Isolates were incubated with plasma samples from 21 blood donors who had previously had COVID-19 and from a total of 53 recipients of the chemically inactivated SARS-CoV-2 vaccine CoronaVac: 18 individuals after receipt of a single dose and an additional 20 individuals (38 in total) after receipt of two doses (collected 17-38 days after the most recent dose); and 15 individuals who received two doses during the phase 3 trial of the vaccine (collected 134-230 days after the second dose). Antibody neutralisation of P.1/28, P.1/30, and B isolates by plasma samples were compared in terms of median virus neutralisation titre (VNT50, defined as the reciprocal value of the sample dilution that showed 50% protection against cytopathic effects). FINDINGS: In terms of VNT50, plasma from individuals previously infected with SARS-CoV-2 had an 8·6 times lower neutralising capacity against the P.1 isolates (median VNT50 30 [IQR <20-45] for P.1/28 and 30 [<20-40] for P.1/30) than against the lineage B isolate (260 [160-400]), with a binominal model showing significant reductions in lineage P.1 isolates compared with the lineage B isolate (p≤0·0001). Efficient neutralisation of P.1 isolates was not seen with plasma samples collected from individuals vaccinated with a first dose of CoronaVac 20-23 days earlier (VNT50s below the limit of detection [<20] for most plasma samples), a second dose 17-38 days earlier (median VNT50 24 [IQR <20-25] for P.1/28 and 28 [<20-25] for P.1/30), or a second dose 134-260 days earlier (all VNT50s below limit of detection). Median VNT50s against the lineage B isolate were 20 (IQR 20-30) after a first dose of CoronaVac 20-23 days earlier, 75 (<20-263) after a second dose 17-38 days earlier, and 20 (<20-30) after a second dose 134-260 days earlier. In plasma collected 17-38 days after a second dose of CoronaVac, neutralising capacity against both P.1 isolates was significantly decreased (p=0·0051 for P.1/28 and p=0·0336 for P.1/30) compared with that against the lineage B isolate. All data were corroborated by results obtained through plaque reduction neutralisation tests. INTERPRETATION: SARS-CoV-2 lineage P.1 might escape neutralisation by antibodies generated in response to polyclonal stimulation against previously circulating variants of SARS-CoV-2. Continuous genomic surveillance of SARS-CoV-2 combined with antibody neutralisation assays could help to guide national immunisation programmes. FUNDING: São Paulo Research Foundation, Brazilian Ministry of Science, Technology and Innovation and Funding Authority for Studies, Medical Research Council, National Council for Scientific and Technological Development, National Institutes of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Respiratory Viral Shedding in Healthcare Workers Reinfected with SARS-CoV-2, Brazil, 2020.

We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.

Mapping Brazilian spotted fever: Linking etiological agent, vectors, and hosts.

Brazilian spotted fever (BSF) is a highly lethal disease in southeastern Brazil. BSF is caused by the bacterium Rickettsia rickettsii and is transmitted by the bites of the tick of the genus Amblyomma. The spatial distribution of BSF risk areas is not well known in the country given the complexity of the transmission cycle. This study used the ecological niche modeling (ENM) approach to anticipate the potential distribution of the etiological agent (Rickettsia rickettsii), vectors (Amblyomma sculptum and A. dubitatum), and hosts (Hydrochoerus hydrochaeris, Didelphis aurita, and D. marsupialis) of BSF in Brazil. We compiled occurrence records for all vectors, hosts, and BSF from our own field surveillance, online repositories, and literature. ENM identified BSF risk areas in southeastern and southern Brazil, and anticipated other dispersed suitable areas in the western, central, and northeastern coast regions of Brazil. Tick vectors and mammalian hosts were confined to these same areas; however, host species showed broader suitability in northern Brazil. All species ENMs performed significantly better than random expectations. We also tested the BSF prediction based on 253 additional independent cases identified in our surveillance; the model anticipated 251 out of 253 of these independent cases. Background similarity tests comparing the ENMs of R. rickettsii, tick vectors, and mammalian hosts were unable to reject null hypotheses of niche similarity. Finally, we observed close coincidence between independent BSF cases, and areas suitable for combinations of vectors and hosts, reflecting the ability of these model pairs to anticipate the distribution of BSF cases across Brazil.

A human case of spotted fever caused by Rickettsia parkeri strain Atlantic rainforest and its association to the tick Amblyomma ovale.

BACKGROUND: Rickettsia parkeri strain Atlantic rainforest has emerged in Brazil during the last 10 years, with three laboratory-confirmed human cases. While these cases were epidemiologically associated with the tick Amblyomma ovale, in none of them the tick specimens that bit the patients could be identified. RESULTS: We report a clinical case of spotted fever rickettsiosis that was acquired in an Atlantic forest area in Bahia state, northeast Brazil. The case was determined to be caused by R. parkeri strain Atlantic rainforest, based on molecular analysis of the crust removed from the tick bite site (inoculation eschar) of the patients' skin. DNA extracted from the crust yielded partial sequences of three rickettsial genes (gltA, ompA and ompB), which were 99-100% identical to R. parkeri strain Atlantic rainforest. The tick specimen that was attached to patient skin was identified as a female of A. ovale. CONCLUSIONS: We report the fourth confirmed case of spotted fever rickettsiosis caused by R. parkeri strain Atlantic rainforest, providing to our knowledge for the first time, direct evidence of R. parkeri strain Atlantic rainforest transmission by A. ovale.

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.

False Negative Results in Bartonellosis Diagnosis.

We report a fatal case of Bartonella henselae bacteremic patient. He had negative serology and PCRs from whole blood and liquid culture; only ftsZ nested PCR was positive from the blood liquid culture. The isolate had positive PCRs. When considered, bartonellosis diagnosis can be still challenging because of technical limitations.