Identification of animal hosts of Fort Sherman virus, a New World zoonotic orthobunyavirus

An orthobunyavirus termed Fort Sherman virus (FSV) was isolated in 1985 from a febrile US soldier in Panama, yet potential animal reservoirs remained unknown. We investigated sera from 192 clinically healthy peri-domestic animals sampled in northeastern Brazil during 2014–2018 by broadly reactive RT-PCR for orthobunyavirus RNA, including 50 cattle, 57 sheep, 35 goats and 50 horses. One horse sampled in 2018 was positive (0.5%; 95% CI, 0.01–3.2) at 6.2 × 103 viral RNA copies/mL. Genomic comparisons following virus isolation in Vero cells and deep sequencing revealed high identity of translated amino acid sequences between the new orthobunyavirus and the Panamanian FSV prototype (genes: L, 98.8%; M, 83.5%; S, 100%), suggesting these viruses are conspecific. Database comparisons revealed even higher genomic identity between the Brazilian FSV and taxonomically unassigned Argentinian mosquito- and horse-derived viruses sampled in 1965, 1982 and 2013 with only 1.1% maximum translated amino acid distances across viral genes, suggesting the Argentinian viruses were also distinct FSV strains. The Panamanian FSV strain was an M gene reassortant relative to all Southern American FSV strains, clustering phylogenetically with Cache Valley virus (CVV). Mean dN/dS ratios among FSV genes ranged from 0.03 to 0.07, compatible with strong purifying selection. FSV-specific neutralizing antibodies occurred at relatively high end-point titres in the range of 1:300 in 22.0% of horses (11 out of 50 animals), 8.0% of cattle (4/50 animals), 7.0% of sheep (4/57 animals) and 2.9% of goats (1/35 animals). High specificity of serologic testing was suggested by significantly higher overall FSV-specific compared to CVV- and Bunyamwera virus-specific end-point titres (p = .009), corroborating a broad vertebrate host range within peri-domestic animals. Growth kinetics using mosquito-, midge- and sandfly-derived cell lines suggested Aedes mosquitos as potential vectors. Our findings highlight the occurrence of FSV across a geographic range exceeding 7,000 km, surprising genomic conservation across a time span exceeding 50 years, M gene-based reassortment events, and the existence of multiple animal hosts of FSV

Impact of El Niño/Southern Oscillation on Visceral Leishmaniasis, Brazil

We used time-series analysis and linear regression to investigate the relationship between the annual Niño-3 index from 1980 to 1998 and the annual incidence of visceral leishmaniasis (VL) in the State of Bahia, Brazil, during 1985–1999. An increase in VL incidence was observed in the post-El Niño years 1989 (+38.7%) and 1995 (+33.5%). The regression model demonstrates that the previous year’s mean Niño-3 index and the temporal trend account for approximately 50% of the variance in the annual incidence of VL in Bahia. The model shows a robust agreement with the real data, as only the influence of El Niño on the cycle of VL was analyzed. The results suggest that this relationship could be used to predict high-risk years for VL and thus help reduce health impact in susceptible regions in Brazil

Prevalência da infecção por Ehrlichia em cães e carrapatos no Nordeste do Brasil

This study investigated the epidemiology of canine ehrlichiosis in Northeastern Brazil, focusing the identification of the Ehrlichia species and vectors involved. Samples were collected from 472 domestic dogs residing in the health districts of Cajazeiras and Itapuã of Salvador city. The average prevalence of antibodies reactive to E. canis by immunofluorescent antibody test (IFAT) (titer > 1:80) was 35.6% (168/472). Blood samples from the E. canis-seropositive animals were tested by nested PCR in order to identify the Ehrlichia species responsible for the infection. Among the seropositives, 58 (34.5%) were found to be PCR-positive for E. canis. Ticks were found in 32 dogs. Nested-PCR analysis showed that 21.9% (7/32) of the Rhipicephalus sanguineus were infected by E. canis. In both dogs and Rhipicephalus sanguineus, nested-PCR for E. ewingii and E. chaffeensis was negative, with no amplification of DNA fragment.Este estudo objetivou pesquisar a epidemiologia da erliquiose canina no Nordeste do Brasil, com especial atenção na identificação da espécie de Ehrlichia envolvida nas infecções caninas e vetoriais detectadas. Para isso foram coletadas amostras de 472 cães domiciliados nos distritos sanitários de Cajazeiras e Itapuã. A prevalência de anticorpos anti-E. canis, pela imunofluorescência indireta (título > 1:80), em cães foi de 35,6% (168/472). Os animais soropositivos foram analisados por uma nested-PCR para identificação da espécie de Ehrlichia responsável pela infecção. Dentre os positivos, 58 (34,5%) cães foram PCR-positivos para E. canis. Foram coletados e classificados os carrapatos em 32 cães. A nested-PCR de Rhipicephalus sanguineus resultou em 21,9% (7/32) de infecção por E. canis. A nested-PCR de amostras de sangue de cães e Rhipicephalus sanguineus para E. chaffeensis e E. ewingii foi negativa, não havendo amplificação de fragmento de DNA.Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB

Evidence against Zika virus infection of pets and peri-domestic animals in Latin America and Africa

Decades after its discovery in East Africa, Zika virus (ZIKV) emerged in Brazil in 2013 and infected millions of people during intense urban transmission. Whether vertebrates other than humans are involved in ZIKV transmission cycles remained unclear. Here, we investigate the role of different animals as ZIKV reservoirs by testing 1723 sera of pets, peri-domestic animals and African non-human primates (NHP) sampled during 2013–2018 in Brazil and 2006–2016 in Côte d'Ivoire. Exhaustive neutralization testing substantiated co-circulation of multiple flaviviruses and failed to confirm ZIKV infection in pets or peri-domestic animals in Côte d'Ivoire (n=259) and Brazil (n=1416). In contrast, ZIKV seroprevalence was 22.2% (2/9, 95% CI, 2.8–60.1) in West African chimpanzees (Pan troglodytes verus) and 11.1% (1/9, 95% CI, 0.3–48.3) in king colobus (Colobus polycomos). Our results indicate that while NHP may represent ZIKV reservoirs in Africa, pets or peri-domestic animals likely do not play a role in ZIKV transmission cycles.Peer Reviewe

Seroepidemiological survey of canine visceral leishmaniasis in a continental island of northeast Brazil

Introdução: Leishmaniose Visceral (LV) é uma doença endêmica em municípios vizinhos à Ilha de Maré, situada na plataforma continental do município de Salvador, Bahia, Brasil. Entretanto, casos de LV não tem sido notificados nesta Ilha. Objetivo: foi investigar a soroprevalência e sinais clínicos de Leishmaniose Visceral Canina (LVC) e identificar a população de flebótomos presentes no povoado de Botelho, Ilha de Maré. Metodologia: Soro de cães locais foram testados para IgG anti-Leishmania por imunoensaios (teste rápido TR DPP™ e Elisa Indireto) e uma investigação entomológica foi conduzida. Resultados: 106 amostras foram testadas, sendo que sete (6,6%) foram positivas usando o teste rápido. As amostras positivas foram encaminhadas ao Laboratório Central da Bahia para a confirmação, entretanto, essas amostras apresentaram resultado negativo no ELISA indireto. Foi identificada a presença de nove exemplares da espécie Pressatia choti, subfamília Phlebotominae, espécie frequentemente encontrada em áreas de transmissão de leishmaniose cutânea no Brasil. Conclusão: Apesar deste trabalho não ter identificado a presença de LVC na Ilha de Maré, novos inquéritos sorológicos e analises entomológicas em uma maior área da ilha de Maré serão necessários para a manutenção de uma vigilância epidemiológico na região insular em destaque

A UTILIZAÇÃO DA IMUNOFLUORESCÊNCIA INDIRETA NO DIAGNÓSTICO DE ROTINA DA LEISHMANIOSE VISCERAL CANINA E SUAS IMPLICAÇÕES NO CONTROLE DA DOENÇA

Neste trabalho foram analisados, por enzyme-linked immunosorbent assay (ELISA) e imunofluorescência indireta (IFI), 101 soros caninos provenientes da Região Metropolitana de Salvador, Bahia, sendo 30 soros de cães com resultado parasitológico positivo para Leishmania chagasi em cultura esplênica e 71 soros de cães clinicamente sadios. Dez soros de cães com cultivo positivo e com resultados sorológicos concordantes ou não entre os testes ELISA e IFI foram testados pela técnica de Western-Blotting (WB). Das 30 amostras de soro com resultado positivo em cultura, o ELISA detectou 27 amostras positivas e o IFI mostrou resultado positivo em 12. Das 71 amostras de soro de cães clinicamente sadios, todas apresentaram resultados negativos no ELISA e uma apresentou resultado positivo no IFI. A sensibilidade e a especificidade foram de 90% e 100% para o ELISA e 40% e 98,6% para IFI, respectivamente. O índice de concordância Kappa entre os testes foi considerado moderado (0,53), e os resultados do WB apresentaram maior concordância com o ELISA. Este estudo demonstra a possibilidade de falha no teste IFI na detecção de cães infectados e discute a sua implicação no controle da doença em áreas endêmicas. PALAVRAS-CHAVE: Cães, ELISA, IFI, Leishmania chagasi, Western-Blotting

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe