Chapare Hemorrhagic Fever and Virus Detection in Rodents in Bolivia in 2019.

BACKGROUND: In June 2019, the Bolivian Ministry of Health reported a cluster of cases of hemorrhagic fever that started in the municipality of Caranavi and expanded to La Paz. The cause of these cases was unknown. METHODS: We obtained samples for next-generation sequencing and virus isolation. Human and rodent specimens were tested by means of virus-specific real-time quantitative reverse-transcriptase-polymerase-chain-reaction assays, next-generation sequencing, and virus isolation. RESULTS: Nine cases of hemorrhagic fever were identified; four of the patients with this illness died. The etiologic agent was identified as Mammarenavirus Chapare mammarenavirus, or Chapare virus (CHAPV), which causes Chapare hemorrhagic fever (CHHF). Probable nosocomial transmission among health care workers was identified. Some patients with CHHF had neurologic manifestations, and those who survived had a prolonged recovery period. CHAPV RNA was detected in a variety of human body fluids (including blood; urine; nasopharyngeal, oropharyngeal, and bronchoalveolar-lavage fluid; conjunctiva; and semen) and in specimens obtained from captured small-eared pygmy rice rats (Oligoryzomys microtis). In survivors of CHHF, viral RNA was detected up to 170 days after symptom onset; CHAPV was isolated from a semen sample obtained 86 days after symptom onset. CONCLUSIONS: M. Chapare mammarenavirus was identified as the etiologic agent of CHHF. Both spillover from a zoonotic reservoir and possible person-to-person transmission were identified. This virus was detected in a rodent species, O. microtis. (Funded by the Bolivian Ministry of Health and others.).

Vigilancia de fiebre hemorrágica argentina: FHA / Argentine hemorrhagic fever surveillance

Características generales de la Fiebre Hemorrágica Argentina (FHA): Transmisión, presentación clínica, definición de caso sospechoso, tratamiento, medidas de prevención, y situación regional. Se describe el caso confirmado en la Ciudad de Buenos Aires.

[Spatial difference in the incidence of Argentine Hemorrhagic Fever and composition and abundance of rodents in the assemblage]. / Diferencia espacial de la incidencia de fiebre hemorrágica argentina y la composición y abundancia de roedores en el ensamble.

BACKGROUND: The Argentine Hemorrhagic Fever (AHF) is a zoonotic disease endemic in a wide area of the humid pampa of Argentina. The etiologic agent is the Junin virus that is maintained in the wild by the rodent Calomys musculinus and transmitted to humans, mainly, through aerosols generated from secretions and excretions. AIMS: To characterize and compare the assemblages of small rodent composition and diversity inside the epidemic, historic and non-endemic zone of AHF and to register C. musculinus abundance in each zone and in each area within each zone, registering the prevalence of infection in rodent populations. METHOD: One central and two peripheral areas were delimited to sample rodents in each zone with different incidence of AHF. Thus, 18 localities were selected to do the sampling in two years. Host abundance between zones and among areas inside each zone and among nearby areas between zones were compared applying nested ANOVA's. RESULTS: In each zone, the rodent assemblage showed differences in composition, diversity and numeric representation of C. musculinus. The epidemic zone was the richest of the three, registering also great host abundance; meanwhile in the historic zone, A. azarae was the dominant numeric species with less number of other species. Regarding the non-endemic zone, the assemblage composition and C. musculinus abundance varied respect the sampled year. Junin virus infection was only detected in C. musculinus individuals corresponding to the epidemic zone, with a prevalence of 2.7 and 1.1% for the years 2007 and 2008, respectively. CONCLUSION: In this system, the abundance of C. musculinus could be impacting over the pathogen dynamic, rather than the assemblage diversity or the A. azarae presence.

Diferencia espacial de la incidencia de fiebre hemorrágica argentina y la composición y abundancia de roedores en el ensamble / Spatial difference in the incidence of Argentine Hemorrhagic Fever and composition and abundance of rodents in the assemblage

Resumen La fiebre hemorrágica argentina (FHA) es una enfermedad zoonótica endémica en una amplia zona de la pampa húmeda de Argentina. El agente etiológico es el virus Junin que es mantenido en la naturaleza por el roedor Calomys musculinus y transmitido, principalmente, al humano a través de aerosoles generados de las secreciones y excreciones. Objetivos: Caracterizar la composición y diversidad de los ensambles de pequeños roedores, determinar la abundancia del hospedador C. musculinus y la prevalencia del virus de la FHA en las zonas epidémica, histórica y no endémica de dicha enfermedad en Argentina. Métodos: Para el muestreo de roedores en cada una de las zonas se demarcaron un área central y dos periféricas para 18 localidades de la región central de Argentina (incluyendo las provincias de Córdoba, Buenos Aires y Santa Fe) muestreadas en dos años. Se comparó la abundancia de C. musculinus entre zonas y entre las áreas dentro de cada zona y áreas cercanas entre zonas, utilizando modelos de análisis de varianza anidados. Resultados. Dentro de cada zona, el ensamble de roedores mostró diferencia espacial en la composición específica, diversidad y abundancia de C. musculinus. La zona epidémica registró mayor número de especies y mayor abundancia del hospedador. En zona histórica se capturó el menor número de especies (de roedores) y Akodon azarae fue la más abundante. En zona no endémica la composición del ensamble y la abundancia de C. musculinus variaron entre los dos años. Sólo se detectó infección por virus Junin en C. musculinus correspondientes a la zona epidémica con una prevalencia de 2,7 y 1,1% para los años 2007 y 2008, respectivamente. Conclusión: En este sistema, la abundancia del hospedador estaría afectando la dinámica espacial de este virus, más que la diversidad del ensamble o la presencia de A. azarae.

Background. The Argentine Hemorrhagic Fever (AHF) is a zoonotic disease endemic in a wide area of the humid pampa of Argentina. The etiologic agent is the Junin virus that is maintained in the wild by the rodent Calomys musculinus and transmitted to humans, mainly, through aerosols generated from secretions and excretions. Aims: To characterize and compare the assemblages of small rodent composition and diversity inside the epidemic, historic and non-endemic zone of AHF and to register C. musculinus abundance in each zone and in each area within each zone, registering the prevalence of infection in rodent populations. Method: One central and two peripheral areas were delimited to sample rodents in each zone with different incidence of AHF. Thus, 18 localities were selected to do the sampling in two years. Host abundance between zones and among areas inside each zone and among nearby areas between zones were compared applying nested ANOVA's. Results: In each zone, the rodent assemblage showed differences in composition, diversity and numeric representation of C. musculinus. The epidemic zone was the richest of the three, registering also great host abundance; meanwhile in the historic zone, A. azarae was the dominant numeric species with less number of other species. Regarding the non-endemic zone, the assemblage composition and C. musculinus abundance varied respect the sampled year. Junin virus infection was only detected in C. musculinus individuals corresponding to the epidemic zone, with a prevalence of 2.7 and 1.1% for the years 2007 and 2008, respectively. Conclusion: In this system, the abundance of C. musculinus could be impacting over the pathogen dynamic, rather than the assemblage diversity or the A. azarae presence.

[New transmission scenarios of the Argentine hemorrhagic fever since the introduction of the live attenuated junin virus vaccine (Candid #1): an experience in migrant workers]. / Los nuevos escenarios de transmisión de la fiebre hemorrágica Argentina desde la introducción de la vacuna a virus junín vivo atenuado (Candid#1): una experiencia en trabajadores golondrinas.

The Argentine hemorrhagic fever (AHF) is a severe acute viral disease caused by the Junin virus of the Arenaviridae family. The AHF endemic area coincides geographically with the largest grain export agro-industrial complex of the country [Argentina]. Since the implementation of vaccination with the Candid #1 vaccine, a significant reduction in incidence was achieved and risk patterns were modified. A previous study allowed characterizing these changes and identifying three transmission scenarios: classic, emergent-reemergent, and traveler. The latter scenario includes seasonal migrant workers who move each year, mainly from the province of Santiago del Estero, the endemic area to work in the detasseling of maize. With the objective of protecting this group of workers, a prevention campaign was initiated which included: capacity building of health personnel in the province, health education, and immunization with the vaccine Candid #1. 3,021 workers were vaccinated. Prior to vaccination, serum samples were taken from a group of 104 volunteers. Tests for neutralizing antibodies specific to the Junin virus were performed and 6 (5.76%) tested positive. The unexpected finding of a high percentage of workers with antibodies suggests the need to evaluate several hypotheses: a) that the result is the product of non-probabilistic sampling; b) that it could be people who fell ill in previous travels, c) or who were vaccinated in previous travels; or d) consider this region as an emerging scenario.

Co-circulation of Clade C New World Arenaviruses: New geographic distribution and host species.

Clade C, of the New World Arenaviruses, is composed of only the Latino and Oliveros viruses and, besides the geographic range of their rodent reservoirs, the distribution of these viruses has been restricted to Bolivia and Argentina. In this study, the genetic detection and phylogenetic analysis of the complete S segment sequences of sympatric arenaviruses from Brazil revealed a new geographic distribution of clade C arenaviruses, as well as the association of Oliveros virus with a new rodent reservoir.

Isolation of Tacaribe virus, a Caribbean arenavirus, from host-seeking Amblyomma americanum ticks in Florida.

Arenaviridae are a family of single stranded RNA viruses of mammals and boid snakes. Twenty-nine distinct mammalian arenaviruses have been identified, many of which cause severe hemorrhagic disease in humans, particularly in parts of sub-Saharan Africa, and in Central and South America. Humans typically become infected with an arenavirus through contact with excreta from infected rodents. Tacaribe virus (TCRV) is an arenavirus that was first isolated from bats and mosquitoes during a rabies surveillance survey conducted in Trinidad from 1956 to 1958. Tacaribe virus is unusual because it has never been associated with a rodent host and since that one time isolation, the virus has not been isolated from any vertebrate or invertebrate hosts. We report the re-isolation of the virus from a pool of 100 host-seeking Amblyomma americanum (lone star ticks) collected in a Florida state park in 2012. TCRV was isolated in two cell lines and its complete genome was sequenced. The tick-derived isolate is nearly identical to the only remaining isolate from Trinidad (TRVL-11573), with 99.6% nucleotide identity across the genome. A quantitative RT-PCR assay was developed to test for viral RNA in host-seeking ticks collected from 3 Florida state parks. Virus RNA was detected in 56/500 (11.2%) of surveyed ticks. As this virus was isolated from ticks that parasitize humans, the ability of the tick to transmit the virus to people should be evaluated. Furthermore, reservoir hosts for the virus need to be identified in order to develop risk assessment models of human infection.

[Quali-quantitative study of the social variables defining transmission scenarios of Argentine Hemorrhagic Fever in the provinces of Buenos Aires and Santa Fe, 2001-2010]. / Estudio cualicuantitativo de las variables sociales que definen escenarios de transmisión de la fiebre hemorrágica argentina en las provincias de Buenos Aires y Santa Fe, 2001-2010.

The aim of this paper was to characterize transmission scenarios of Argentine Hemorrhagic Fever in the post-vaccination period (2001-2010). The study was made up of three phases. The first consisted of a quantitative analysis using the database of the Dr. Julio I. Maiztegui National Institute of Human Viral Diseases [Instituto Nacional de Enfermedades Virales Humanas] regarding the confirmed cases in the period of study (221 cases). Taking into account the transmission site and the known endemic area, cases were grouped into three hypothetical transmission scenarios, identified as: a) classical, b) emerging-reemerging, c) traveling. In the second phase, in order to test these hypotheses, in-depth interviews were carried out from August to September 2011 within an intentionally selected sample of patients distributed proportionally among the three hypotheses. Finally, in the third stage, the data obtained for each hypothetical scenario were grouped into three spatiotemporal scales: the microscale (subject), the mesoscale (locality) and macroscale (region). The results show that new transmission sites are associated with the social dynamics of cereal production and port-bound routes.

Estudio cualicuantitativo de las variables sociales que definen escenarios de transmisión de la fiebre hemorrágica argentina en las provincias de Buenos Aires y Santa Fe, 2001-2010 / Quali-quantitative study of the social variables defining transmission scenarios of Argentine Hemorrhagic Fever in the provinces of Buenos Aires and Santa Fe, 2001-2010

El objetivo de este artículo es caracterizar los escenarios de transmisión de fiebre hemorrágica argentina (FHA) en el período de vacunación (2001-2010). El estudio constó de tres etapas. En la primera, se realizó un análisis cuantitativo de la base de datos del Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui" (INEVH) de casos de FHA confirmados en el período (221 casos) que, sobre la base del lugar de transmisión y la zona endémica conocida, se agruparon según tres hipótesis de escenario: clásico, emergente-reemergente, y viajero. En la segunda etapa, para poner a prueba las hipótesis, se realizaron entrevistas en campo, entre agosto y octubre de 2011, a una muestra de selección intencional de pacientes distribuida proporcionalmente entre las tres hipótesis. Finalmente, en una tercera etapa, los datos generados para cada hipótesis de escenario se agruparon en tres escalas espacio-temporales: microescala (sujeto), mesoescala (localidad) y macroescala (región). Los resultados muestran que los nuevos lugares de transmisión estarían asociados a las dinámicas socioproductivas del cereal y las rutas al puerto.

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Scientist tests the public trust.

An unreported accident in a virus laboratory at Yale is but one of many factors that challenge society's trust in scientists' promises to do hazardous research.

Field studies on the epidemiology of Venezuelan hemorrhagic fever: implication of the cotton rat Sigmodon alstoni as the probable rodent reservoir.

During February 1992, field studies on the epidemiology of Venezuelan hemorrhagic fever (VHF) were carried out in a rural area of Portuguesa State in central Venezuela. The objective of this work was to determine the prevalence of infection with Guanarito virus, the etiologic agent of VHF, among wild rodents and humans living within an endemic focus of the disease. A total of 234 rodents, representing nine different species, were collected and their spleens were cultured for virus. Thirty-one Guanarito virus isolates were made from two rodent species: 19 from 40 Sigmodon alstoni and 12 from 106 Zygodontomys brevicauda. Guanarito virus antibody rates among these two species were 5.1% and 15.0%, respectively. Nine of the 12 Z. brevicauda that yielded virus from their spleens also had Guanarito virus antibodies in their sera. In contrast, none of the 19 Guanarito virus-positive S. alstoni had antibodies to the virus. These data suggest that S. alstoni usually develops a persistent nonimmunizing infection with Guanarito virus, while Z. brevicauda develops an immunizing infection. Based on knowledge of the behavior of other human pathogenic arenaviruses, these results imply that S. alstoni is the principal rodent reservoir of Guanarito virus in nature. To determine the prevalence of Guanarito virus infection among humans in the same region, 195 people living near one of the rodent collecting sites were bled and their sera were tested for antibodies to the virus. Five individuals (2.6%) had Guanarito virus antibodies; all were adults, and two had been diagnosed previously as having VHF.(ABSTRACT TRUNCATED AT 250 WORDS)

[Present status of zoonotic hemorrhagic fevers of South America]. / Actualité des fièvres hémorragiques zoonotiques d'Amérique du sud.

Since 1958, the geographical distribution of Argentine hemorrhagic fever (AHF) has especially extended non only into the province of Buenos Aires but also towards the provinces of Santa Fe and Cordoba, leading to an estimated population at risk of about 1.2 M inhabitants. Recent epidemiological field studies has confirmed the major role of Calomys musculinus and C. laucha rodents in both transmission to man and conservation of Junin virus in nature. However, the human infection may result essentially from contacts with infected C. musculinus. Clinical condition of patients with AHF was greatly improved using AHF convalescent plasma and additional administration of vidarabin may still improve the results of treatment. A live attenuated vaccine, Candid No 1, is presently under evaluation in endemic foci of AHF. On the contrary Bolivian hemorrhagic fever (BHV) appears at present quite silent. A new disease resembling both AHF and BHF, the Venezuelan hemorrhagic fever, appeared in 1989 in the rural areas of central Llanos of Venezuela. The mortality was very high, reaching 23% or more among severely ill patients. The wild small rodents responsible for the disease were identified as Sigmodon alstoni and Zygotontomys brevicauda. Recent extension of agricultural practices and massive immigration may probably explain the recent emergence of this new viral zoonosis.

A longitudinal study of Junin virus activity in the rodent reservoir of Argentine hemorrhagic fever.

We monitored Junin virus (JV) activity in rodent populations for 30 months at seven mark-recapture grids located in agricultural fields and adjacent roadsides and fence lines in endemic and nonendemic areas of Argentine hemorrhagic fever. Blood and oral swabs taken from rodents captured at five-week intervals were analyzed by enzyme-linked immunosorbent assay for JV antigen (Ag). Calomys laucha and C. musculinus were the most frequently captured rodents, making up 47% and 22% of captures, respectively. Of 41 Ag-positive captures, 37 were C. musculinus and four were C. laucha; 34 were from two trapping grids in the same locality. Antigen-positive Calomys were more frequently male (76%), and were found significantly more frequently among the oldest animals and the largest body mass classes. These patterns, combined with the greater mobility and higher frequencies of wounds among males than females, implicated horizontal transmission as the primary route of JV transmission between rodents. Seasonal maximum levels in JV prevalence (up to 25% of captured Ag-positive C. musculinus) occurred during periods of maximal population densities of Calomys. Spatial distribution of Ag-positive rodents reflected habitat preferences; most Ag-positive C. musculinus were captured from border habitats (roadsides and fence lines), and all Ag-positive C. laucha were captured in crop fields. These distinct, but previously undocumented, habitat preferences suggest that the disease in humans may be related to exposures to the primary reservoir species, C. musculinus, in border habitats rather than in crop fields.

Venezuelan haemorrhagic fever.

An outbreak of severe haemorrhagic illness began in the municipality of Guanarito, Portuguesa State, Venezuela, in September, 1989. Subsequent detailed study of 15 cases confirmed the presence of a new viral disease, designated Venezuelan haemorrhagic fever. Characteristic features are fever, toxicity, headache, arthralgia, diarrhoea, conjunctivitis, pharyngitis, leucopenia, thrombocytopenia, and haemorrhagic manifestations. Other features include facial oedema, cervical lymphadenopathy, nausea/vomiting, cough, chest or abdominal pain, and convulsions. The patients ranged in age from 6 to 54 years; all were residents of rural areas in central Venezuela, and 9 died. Infection with Guanarito virus, a newly recognised arenavirus, was shown by direct culture or by serological confirmation in all cases. Epidemiological studies suggest that the disease is endemic in some rural areas of central Venezuela and that it is rodent-borne. Venezuelan haemorrhagic fever has many similarities to Lassa fever and to the arenavirus haemorrhagic fevers that occur in Argentina and Bolivia.

Vertical transmission of Junin virus in experimentally infected adult Calomys musculinus.

The response to infection with Junin virus, wild strain Cba An 9446, and the antenatal and postnatal transmission of the pathogen in its natural host, Calomys musculinus, were studied. Intranasal infection in adult animals (90-120 days) did not produce mortality or illness during the 150-day period of observation. From day 21 to 150 after infection, 50% of the animals showed viral persistence with shedding of virus in both urine and saliva. The remaining half became seropositive, and no infectious virus was recovered from them. Although the virus did not infect fetuses during gestation, 50% of weaned pups nursed by viremic mothers were infected. Neither persistence nor immunologic response altered the reproductive pattern of the animals. The absence of reproductive failure in the infected host and the efficiency of postnatal transfer of Junin virus indicate that vertical transmission could contribute to the viral maintenance over time.