Lessons from a Multilaboratorial Task Force for Diagnosis of a Fatal Toxoplasmosis Outbreak in Captive Primates in Brazil.

Toxoplasmosis is an important zoonotic disease caused by the parasite Toxoplasma gondii and is especially fatal for neotropical primates. In Brazil, the Ministry of Health is responsible for national epizootic surveillance, but some diseases are still neglected. Here, we present an integrated investigation of an outbreak that occurred during the first year of the COVID-19 pandemic among eleven neotropical primates housed at a primatology center in Brazil. After presenting non-specific clinical signs, all animals died within four days. A wide range of pathogens were evaluated, and we successfully identified T. gondii as the causative agent within four days after necropsies. The liver was the most affected organ, presenting hemorrhage and hepatocellular necrosis. Tachyzoites and bradyzoite cysts were observed in histological examinations and immunohistochemistry in different organs; in addition, parasitic DNA was detected through PCR in blood samples from all specimens evaluated. A high prevalence of Escherichia coli was also observed, indicating sepsis. This case highlights some of the obstacles faced by the current Brazilian surveillance system. A diagnosis was obtained through the integrated action of researchers since investigation for toxoplasmosis is currently absent in national guidelines. An interdisciplinary investigation could be a possible model for future epizootic investigations in animals.

Seroprevalence of Hantavirus among Manual Cane Cutters and Epidemiological Aspects of HPS in Central Brazil.

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás-a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination.

Overview of Q fever in Brazil: an underestimated zoonosis.

This review aims to provide current information about Q fever, elucidating the etiological, epidemiological, pathogenic, clinical, diagnostic, therapeutic, and prophylactic aspects of the disease for the medical community. We discuss the main forms of presentation of the agent, its ability to persist in the body, the infinite possibilities of susceptible hosts, the main known forms of transmission, its importance in populations at occupational risk, and the role of arthropods in the natural history of the disease. Focusing on Brazil, we present the cases already described and studies developed since its first report, and how there is still much to unravel. We are aware of the possibilities of the persistence of the agent and the development of severe clinical pictures and the specific treatments currently instituted. We also wish to raise awareness about the future, the new genotypes that are emerging, the need to study the effects of vaccines, and the impact of Q fever on the population. Q fever is a poorly understood disease in Latin America, and recent studies, especially in Brazil, have revealed the importance of developing new studies.

Overview of Q fever in Brazil: an underestimated zoonosis

ABSTRACT This review aims to provide current information about Q fever, elucidating the etiological, epidemiological, pathogenic, clinical, diagnostic, therapeutic, and prophylactic aspects of the disease for the medical community. We discuss the main forms of presentation of the agent, its ability to persist in the body, the infinite possibilities of susceptible hosts, the main known forms of transmission, its importance in populations at occupational risk, and the role of arthropods in the natural history of the disease. Focusing on Brazil, we present the cases already described and studies developed since its first report, and how there is still much to unravel. We are aware of the possibilities of the persistence of the agent and the development of severe clinical pictures and the specific treatments currently instituted. We also wish to raise awareness about the future, the new genotypes that are emerging, the need to study the effects of vaccines, and the impact of Q fever on the population. Q fever is a poorly understood disease in Latin America, and recent studies, especially in Brazil, have revealed the importance of developing new studies.

Case Report: Hantavirus Cardiopulmonary Syndrome Diagnostic in the Face of the COVID-19 Pandemic.

Hantavirus cardiopulmonary syndrome (HCPS) is an emerging rodent-borne disease in the Americas. The most common initial symptoms of HCPS are similar to those of COVID-19 and other respiratory infections that evolve rapidly to respiratory failure, resulting from pulmonary edema and shock in about 40% of cases. We describe a fatal case of HCPS in a 24-year-old man who was hospitalized with fever, hemoconcentration, thrombocytopenia, leukocytosis, dry cough and a bilateral diffuse alveolar pulmonary infiltrate during the emergence of the COVID-19 pandemic in Brazil. HCPS needs to be ruled out in patients with clinical manifestations compatible with respiratory infections such as influenza and COVID-19.

Identification of Immunogenic Linear B-Cell Epitopes in C. burnetii Outer Membrane Proteins Using Immunoinformatics Approaches Reveals Potential Targets of Persistent Infections.

Coxiella burnetii is a global, highly infectious intracellular bacterium, able to infect a wide range of hosts and to persist for months in the environment. It is the etiological agent of Q fever-a zoonosis of global priority. Currently, there are no national surveillance data on C. burnetii's seroprevalence for any South American country, reinforcing the necessity of developing novel and inexpensive serological tools to monitor the prevalence of infections among humans and animals-especially cattle, goats, and sheep. In this study, we used immunoinformatics and computational biology tools to predict specific linear B-cell epitopes in three C. burnetii outer membrane proteins: OMP-H (CBU_0612), Com-1 (CBU_1910), and OMP-P1 (CBU_0311). Furthermore, predicted epitopes were tested by ELISA, as synthetic peptides, against samples of patients reactive to C. burnetii in indirect immunofluorescence assay, in order to evaluate their natural immunogenicity. In this way, two linear B-cell epitopes were identified in each studied protein (OMP-H(51-59), OMP-H(91-106), Com-1(57-76), Com-1(191-206), OMP-P1(197-209), and OMP-P1(215-227)); all of them were confirmed as naturally immunogenic by the presence of specific antibodies in 77% of studied patients against at least one of the identified epitopes. Remarkably, a higher frequency of endocarditis cases was observed among patients who presented an intense humoral response to OMP-H and Com-1 epitopes. These data confirm that immunoinformatics applied to the identification of specific B-cell epitopes can be an effective strategy to improve and accelerate the development of surveillance tools against neglected diseases.

Orthohantavirus Survey in Indigenous Lands in a Savannah-Like Biome, Brazil.

In Brazil, the first confirmed cases of hantavirus cardiopulmonary syndrome in Indigenous populations occurred in 2001. The purpose of this study was to determine the seroprevalence of orthohantavirus infections in the Utiariti Indigenous land located in the southeastern region of the Brazilian Amazon. In December 2014 and 2015, a survey was conducted using an enzyme-linked immunosorbent assay in nine villages belonging to the Haliti-Paresí Indigenous communities. A total of 301 participants were enrolled in the study. Of the two study cohorts, the one from 2014 showed a prevalence of 12.4%, whereas the one from 2015 had a serum prevalence of 13.4%. Analysis of the paired samples of 110 Indigenous people who participated in both stages of the study enabled identification of four individuals who had seroconverted during the study period. Identifying the circulation of orthohantaviruses in the Utiariti Indigenous land highlights a serious public health problem in viral expansion and highlights the need to implement preventive measures appropriate to the sociocultural reality of these communities.

The Serological Cross-Detection of Bat-Borne Hantaviruses: A Valid Strategy or Taking Chances?

Bats are hosts of a range of viruses, and their great diversity and unique characteristics that distinguish them from all other mammals have been related to the maintenance, evolution, and dissemination of these pathogens. Recently, very divergent hantaviruses have been discovered in distinct species of bats worldwide, but their association with human disease remains unclear. Considering the low success rates of detecting hantavirus RNA in bat tissues and that to date no hantaviruses have been isolated from bat samples, immunodiagnostic tools could be very helpful to understand pathogenesis, epidemiology, and geographic range of bat-borne hantaviruses. In this sense, we aimed to identify in silico immunogenic B-cell epitopes present on bat-borne hantaviruses nucleoprotein (NP) and verify if they are conserved among them and other selected members of Mammantavirinae, using a combination of (the three most used) different prediction algorithms, ELLIPRO, Discotope 2.0, and PEPITO server. To support our data, we in silico modeled 3D structures of NPs from representative members of bat-borne hantaviruses, using comparative and ab initio methods due to the absence of crystallographic structures of studied proteins or similar models in the Protein Data Bank. Our analysis demonstrated the antigenic complexity of the bat-borne hantaviruses group, showing a low sequence conservation of epitopes among members of its own group and a minor conservation degree in comparison to Orthohantavirus, with a recognized importance to public health. Our data suggest that the use of recombinant rodent-borne hantavirus NPs to cross-detect antibodies against bat- or shrew-borne viruses could underestimate the real impact of this virus in nature.

Human Q Fever on the Guiana Shield and Brazil: Recent Findings and Remaining Questions.

PURPOSE OF REVIEW: In this review, we report on the state of knowledge about human Q fever in Brazil and on the Guiana Shield, an Amazonian region located in northeastern South America. There is a contrast between French Guiana, where the incidence of this disease is the highest in the world, and other countries where this disease is practically non-existent. RECENT FINDINGS: Recent findings are essentially in French Guiana where a unique strain MST17 has been identified; it is probably more virulent than those usually found with a particularly marked pulmonary tropism, a mysterious animal reservoir, a geographical distribution that raises questions. SUMMARY: Q fever is a bacterial zoonosis due to Coxiella burnetii that has been reported worldwide. On the Guiana Shield, a region mostly covered by Amazonian forest, which encompasses the Venezuelan State of Bolivar, Guyana, Suriname, French Guiana, and the Brazilian State of Amapá, the situation is very heterogeneous. While French Guiana is the region reporting the highest incidence of this disease in the world, with a single infecting clone (MST 117) and a unique epidemiological cycle, it has hardly ever been reported in other countries in the region. This absence of cases raises many questions and is probably due to massive under-diagnosis. Studies should estimate comprehensively the true burden of this disease in the region.

Vacinas / Vaccines

Apresenta breve histórico sobre o desenvolvimento de vacinas, o que são as vacinas e porque vacinamos. Comenta sobre a vanguarda do Brasil nos programas de vacinação no século XXI

MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism.

Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.

A Retrospective Survey of Rodent-borne Viruses in Rural Populations of Brazilian Amazon.

INTRODUCTION: The Amazon tropical rainforest has the most dense and diverse ecosystem worldwide. A few studies have addressed rodent-borne diseases as potential hazards to humans in this region. METHODS: A retrospective survey was conducted using enzyme-linked immunosorbent assay for detecting mammarenavirus and orthohantavirus antibodies in 206 samples collected from rural settlers of the Brazilian Western Amazonian region. RESULTS: Six (2.91%) individuals in the age group of 16 to 36 years were found to possess antibodies against mammarenavirus. CONCLUSION: Evidence of previous exposure to mammarenavirus in the rural population points to its silent circulation in this region.

A Retrospective Survey of Rodent-borne Viruses in Rural Populations of Brazilian Amazon

Abstract INTRODUCTION: The Amazon tropical rainforest has the most dense and diverse ecosystem worldwide. A few studies have addressed rodent-borne diseases as potential hazards to humans in this region. METHODS: A retrospective survey was conducted using enzyme-linked immunosorbent assay for detecting mammarenavirus and orthohantavirus antibodies in 206 samples collected from rural settlers of the Brazilian Western Amazonian region. RESULTS: Six (2.91%) individuals in the age group of 16 to 36 years were found to possess antibodies against mammarenavirus. CONCLUSION: Evidence of previous exposure to mammarenavirus in the rural population points to its silent circulation in this region.

Hantavirus pulmonary syndrome in children: case report and case series from an endemic area of Brazil.

Hantavirus Cardiopulmonary Syndrome (HCPS) is an important emergent zoonosis associated with wild rodents in Brazil, where this viral infection in children is generally rare. We present HCPS in a child from the Pantanal Biome and a review of all reported pediatric cases in Mato Grosso State, an endemic area for HCPS in Brazil. The investigation used the Information System for Notifiable Diseases database (SINAN). A 12-year-old boy was hospitalized with fever and respiratory failure and hantavirus IgM and IgG antibodies were detected by ELISA in serum samples. During the period of 1999 to 2016, 32 HCPS pediatric cases confirmed by serology were reported to SINAN with a mortality rate of 34.4%. The possibility of hantavirus infection in children with acute febrile illness associated with respiratory failure should be considered mainly in recognized endemic areas as Mato Grosso State, contradicting a hypothesis that children are more protected from lung involvement.

Seroprevalence of rodent-borne viruses in Afro-descendent communities in Brazil.

During the Brazilian slavery period, many African migrants were brought to the American continent. Historically, some of these migrants escaped from the Brazilian gold mines and farms to which they had been brought and settled in remote valleys and this was the main mode of resistance to the slavery system. These runaway-slave descendant communities are called quilombos, a group with distinct ethnic identity, specific behavioral habits, including geographic isolation and conservative practices. The objective of this study was to investigate the prevalence of rodent-borne viruses in two Afro-descendent communities from Mato Grosso do Sul State, Midwestern Brazil. A total of 319 individuals from rural and urban quilombola communities were enrolled. Twelve (3.76%) had anti-rodent-borne virus IgG antibodies. Seven (2.19%) were anti-mammarenavirus reactive and nine (2.82%) had anti-orthohantavirus antibodies. The literature includes limited data on the health status of quilombola communities, but all the studies emphasize the disparity of attention of local healthcare personnel to these communities compared to the general population. The findings of this study highlight the vulnerability and the precarious health conditions of quilombola groups, especially those living in rural areas and thus, point to the need of preventive measures to improve access to healthcare for this ethnic group.

Malaria and Hantavirus Pulmonary Syndrome in Gold Mining in the Amazon Region, Brazil.

People living in mining regions are exposed to numerous biological agents by several specific types of transmission mechanisms. This study is designed to describe fatal hantavirus pulmonary syndrome (HPS) cases confirmed by serology and molecular analysis, where a seroprevalence survey was conducted in the gold mining regions of the state of Mato Grosso, in the official Amazon region, Brazil. Two fatal cases of HPS were confirmed in a mining area in the Legal Amazon, where malaria is one of the most important public health problems. A molecular analysis detected the presence of the genome of the Castelo dos Sonhos virus. Out of the 112 blood samples analyzed, five were positive for Plasmodium infection (four P. falciparum and one P. vivax), and four were seropositive for hantavirus, showing a seroprevalence of 3.57%. One of the four miners who was seroreactive for hantavirus concomitantly had P. falciparum infection, which was confirmed by thick blood smear. This manuscript highlights the importance of considering hantavirus pulmonary syndrome as a diagnostic possibility in febrile infection associated with pulmonary manifestations in mining areas where malaria cases are often identified.

Aporé virus, a novel mammarenavirus (Bunyavirales: Arenaviridae) related to highly pathogenic virus from South America.

Here, we report the complete genome sequence of the Aporé virus (Bunyavirales: Arenaviridae), obtained from a wild rodent Oligoryzomys mattogrossae captured in Mato Grosso do Sul state, Brazil. The genome of this virus showed strong similarity to highly pathogenic mammarenavirus from South America.