ABSTRACT
The recognition of hantavirus pulmonary syndrome (HPS) after the investigation of a cluster of unexplained respiratory deaths in the southwestern United States during the spring of 1993 showcased our ability to recognize new and emerging diseases, given the correct juxtaposition of a new clinical entity with circumscribed epidemiologic features that are analyzed with novel diagnostic methods. In less than a decade, HPS has become established as a pan-American zoonosis due to numerous viruses maintained by sigmodontine rodents with rodent- and virus-specific epidemiologic profiles. The classical features of the syndrome-acute febrile illness associated with prominent cardiorespiratory compromise after direct contact or inhalation of aerosolized rodent excreta-has been extended to include clinical variants, including disease with frank hemorrhage, that have confirmed that this syndrome is a viral hemorrhagic fever. Efforts are under way to refine prevention strategies, to understand the pathogenesis of the shock, and to identify therapeutic modalities.
Subject(s)
Hantavirus Pulmonary Syndrome/physiopathology , Hemorrhagic Fever, American/etiology , Orthohantavirus , Animals , Orthohantavirus/pathogenicity , Hantavirus Pulmonary Syndrome/virology , Hemorrhagic Fever, American/virology , Humans , Rats , Sin Nombre virus/pathogenicityABSTRACT
Zoonoses within wild reservoir host populations often occur focally obeying Pavlovskii's rules of "natural nidality". What appears to be a clear example is Bolivian hemorrhagic fever (BHF), a disease endemic to northeastern Bolivia. The etiological agent is Machupo virus (MACV, Arenaviridae). The vertebrate reservoir, identified 30 years ago, was Calomys callosus a wild rodent common to open biomes in the lowlands of southeastern South America. The lack of concordance between the occurrence of MACV and the range of its rodent host has puzzled cadres of researchers and could be used as an exemplar of natural nidality. Here, we show that the populations of rodents responsible for the maintenance and transmission of MACV are an independent monophyletic lineage, different from those in other areas of South America. Therefore a clearer understanding of the systematics of the host species explains the apparent natural nidality of BHF. Similar studies may prove to be informative in other zoonoses.
Subject(s)
Arenaviruses, New World/genetics , Hemorrhagic Fever, American/etiology , Sigmodontinae/virology , Animals , Arenaviruses, New World/classification , Disease Reservoirs , Hemorrhagic Fever, American/virology , Molecular Sequence Data , PhylogenyABSTRACT
Pichinde virus (PIC) is a reticuloendothelial arenavirus of the New World tropics. A guinea pig passage-adapted strain of this virus (adPIC) is uniformly lethal for inbred guinea pigs, while the related, prototype strain (PIC3739) has attenuated virulence. The abilities of adPIC and PIC3739 to induce tumor necrosis factor (TNF) in vivo and in cultured macrophages were compared. Infection with adPIC, but not PIC3739, was associated with detectable serum TNF that peaked in week 2 of infection. Tumor necrosis factor was found in the spleens of adPIC- and PIC3739-infected animals in week 1 of infection; TNF alpha mRNA levels in spleens and livers of adPIC infected animals increased and remained high throughout infection, whereas PIC3739-infected organs showed down regulation of TNF alpha mRNA late in infection. Peritoneal macrophages explanted from adPIC-infected animals showed enhanced lipopolysaccharide-inducible TNF production. Altered regulation of TNF production may play a role in the pathogenesis of guinea pig arenavirus disease.
Subject(s)
Disease Models, Animal , Hemorrhagic Fever, American/etiology , Pichinde virus/pathogenicity , Tumor Necrosis Factor-alpha/analysis , Animals , Blotting, Northern , Cells, Cultured , Guinea Pigs , Hemorrhagic Fever, American/virology , Liver/metabolism , Macrophages/metabolism , Macrophages, Peritoneal/metabolism , Male , RNA, Messenger/analysis , Spleen/cytology , Spleen/metabolism , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Necrosis Factor-alpha/geneticsABSTRACT
The pathomorphological patterns and the activity of serum interferon, interleukin-1, tumor necrosis factor, natural killers, and proliferative activity of lymphocytes were studied in BALB/c and C57B1/6 mice intracerebrally infected with Machupo virus. The BALB/c mice showed 100% lethality at 8-9 days after inoculation while C57B1/6 mice were found nonsusceptible to Machupo virus inoculation by this route. The pathomorphological findings at the peak of clinical manifestations in BALB/c mice revealed no organ whose functional deficiency could lead to the death of the animals. Investigations of nonspecific immunity parameters revealed a direct dependence between their high activity and susceptibility of the animals to Machupo virus infection. It is assumed that the endogenous shock due to the high activity of immune response mediators is the cause of death in Machupo virus infection.
Subject(s)
Arenaviruses, New World , Hemorrhagic Fever, American/immunology , Animals , Cell Division , Haplotypes , Hemorrhagic Fever, American/etiology , Hemorrhagic Fever, American/pathology , Immunity, Cellular , Immunity, Innate , Mice , Mice, Inbred Strains , Spleen/immunology , Spleen/pathology , Time FactorsABSTRACT
The purpose of our work was to determine if aerosols of Junin virus can infect rhesus macaques and if the disease is the same as that produced by virus inoculated parenterally. The 6 macaques exposed to the virus by aerosol became acutely ill during the 3rd week after exposure, and all died. Three died by day 21, while the remainder died after 1 month. Junin virus was found primarily in visceral organs of those animals dying before 21 days after infection and in the central nervous system tissues from animals dying later. Histological changes were similar to those reported in rhesus monkeys after parenteral Junin viral infection. Gastrointestinal necrosis, however, was less severe in aerosol-infected animals and the associated septicemia was not seen. High levels of alpha interferon were detected by the 3rd day in all infected macaques. Experimental Argentine hemorrhagic fever induced by aerosol infection in rhesus macaques was similar to that seen after parenteral challenge and mimicked closely the clinical syndrome observed in humans.
Subject(s)
Arenaviruses, New World , Hemorrhagic Fever, American/etiology , Aerosols , Animals , Antibodies, Viral/blood , Arenaviruses, New World/immunology , Arenaviruses, New World/isolation & purification , Disease Models, Animal , Hemorrhagic Fever, American/blood , Hemorrhagic Fever, American/immunology , Interferons/blood , Macaca mulatta , Time FactorsABSTRACT
Las fiebres hemorrágicas constituyen síndromes de alta prevalencia actualmente en nuestro medio, razón por la cual es importante revisar su etiología, patogénesis y posibilidades terapáuticas. La reciente descripción de un virus hemorrágico en Venezuela hace este tópico de mayor interés
Subject(s)
Dengue/etiology , Hemorrhagic Fever, American/etiology , Lassa Fever/etiologyABSTRACT
En los últimos cuatro meses de 1989, comienzan a consultar al Hospital Universitario "Dr. Miguel Oráa", en Guanare, Estado Portuguesa, Venezuela, pacientes agricultores en su mayoría procedentes del Municipio Guanarito, con cuadro clínico caracterizado por fiebre, postración deshidratación, malestar general, cefalea, odinofagia, manifestaciones hemorrágicas (gingivorragias, hematemesis, epistaxis), alteraciones de laboratorio compatibles con leucopenia y trombocitopenia, los cuales fallecieron a los pocos días de ingresados en estado de shock sépticos o a consecuencia de severas manifestaciones neurológicas. A lo largo de 1990 se continuaron observando nuevos casos y en septiembre de 1990 fue aislado el virus de un caso fatal, en el Departamento de Virología del Instituto Nacional de Higiene "Rafael Rangel" de Caracas-Venezuela y posteriormente identificado por la Unidad de Investigación de Arbovirus de Yale y el Instituto de Investigación de Enfermedades Infecciosas de las Fuerzas Armadas de los E.E.U.U., indicando que este Virus es un nuevo miembro de la familia Arenaviridae perteneciente al complejo Tacaribe. Con el interés de conocer aspectos epidemiológicos, clínicos, anatomopatológicos y de laboratorio de esta nueva entidad, analizamos todos aquellos casos que ingresaron al Hospital Universitario "Dr. Miguel Oráa" en el lapso comprendido entre el 1- de enero de 1989 al 31 de diembre de 1991, que cumplieran con los siguientes criterios: 1) manifestaciones clínicas de fiebre, cefalea, malestar general, odionofagia, manifestaciones hemorrágicas por mucosas u orificios naturales alteraciones neurológicas como temblor y convulsiones; 2) alteraciones de laboratorio como leucocitos menor de 4000 xmm3 y plaquetas menor de 140.000 xmm3.; 3) procedencia de la zona geográfica correspondiente al Municipio Guanarito; 4) presencia de cultivos de tejido o sangre o serología para Arenavirus. Se recopila una muestra de 188 casos, 62% del sexo masculino, dedicados en su gran mayoría a la actividad agricola 43.6%. el grupo etario más afectado estaba comprendido entre 15 y 44 años (67%). Hubo 41 muertos (21%), las cuales en su gran mayoría presentaron en la autopsia hemorrágica pulmonar, edema renal, hepatomegalia, hemorragia gastrointestinal, neumoní, esplenomegalia, y cardiomegalia. Hallazgos que semejan reportes de la literatura de la fiebre de Lassa, la Argentina y la Boliviana
Subject(s)
Infant, Newborn , Infant , Child, Preschool , Adolescent , Adult , Middle Aged , Humans , Male , Female , Arenaviridae/pathogenicity , Hemorrhagic Fever, American/diagnosis , Hemorrhagic Fever, American/etiologySubject(s)
Arenaviruses, New World/analysis , Hemorrhagic Fever, American/history , Antigens, Viral , Arenaviridae/classification , Arenaviruses, New World/isolation & purification , Arenaviruses, New World/ultrastructure , Cloning, Molecular , Culture Media , Hemorrhagic Fever, American/diagnosis , Hemorrhagic Fever, American/etiology , GenesSubject(s)
Hemorrhagic Fever, American/history , Arenaviruses, New World/analysis , Hemorrhagic Fever, American/etiology , Hemorrhagic Fever, American/diagnosis , Arenaviruses, New World/ultrastructure , Arenaviruses, New World/isolation & purification , Arenaviridae/classification , Culture Media , Antigens, Viral , Genes , Cloning, MolecularABSTRACT
In studying pathogenetic mechanisms of Pichinde virus-induced disease in strain 13 guinea pigs, a large decrease of body weight (approximately 28%) observed within 14 days postinoculation raises a question concerning the validity of standardizing body or organ functions in terms of body weight. This study was to examine changes in body weight and body surface area of Pichinde virus-infected strain 13 guinea pigs after various days postinoculation. Control guinea pigs were also subjected to the same experimental procedures and experimental days. While body weights and body surface areas increased progressively in controls, I observed only slight decreases in body surface areas (4-6%) in the infected guinea pigs, despite large decreases of body weights throughout the 14-day experimental period. In conclusion, Pichinde virus-infected strain 13 guinea pigs demonstrated a small reduction of body surface area within 14 days postinoculation, suggesting that body surface area, rather than body weight, should be used for standardizing body or organ functions for comparison with their own baseline values.
Subject(s)
Body Surface Area , Body Weight , Hemorrhagic Fever, American/etiology , Animals , Body Temperature , Guinea Pigs , MaleABSTRACT
The role that polymorphonuclear leukocytes (PMN) may play in Argentine hemorrhagic fever (AHF), an endemo-epidemic disease caused by Junín virus (JV), was investigated in experimentally infected guinea pigs depleted of PMN by means of specific antiserum. In leucopenic animals the evolution of the infection with a highly pathogenic strain of JV was more severe, with earlier mortality and higher virus yields in blood and viscera. The pathological study showed similar lesions in both the control and PMN-depleted animals with the exception of the lung, which showed the pathological picture of the human "pulmonary distress syndrome of the adult" in nontreated guinea pigs and appeared histologically unaltered in the PMN-depleted animals. On the basis of these results it is suggested that in AHF, PMN play a dual role. In the first stage of infection they display a defensive antiviral action, but later on they participate in the pathogenesis of tissue damage.
Subject(s)
Hemorrhagic Fever, American/etiology , Lung/pathology , Neutrophils/physiology , Animals , Antilymphocyte Serum/pharmacology , Arenaviruses, New World/growth & development , Guinea Pigs , Hemorrhagic Fever, American/microbiology , Hemorrhagic Fever, American/pathology , Male , NeutropeniaABSTRACT
Balkan nephropathy is a chronic kidney disease of a completely unknown etiology. Most epidemiologists believe that the disease has been caused by viruses, though all attempts to prove such a relationship have been fruitless. A common feature of most of the clues offered for elucidating the role of the viruses, is that they interfere with the epidemiological evidence on BN. Therefore, a hypothesis is put forward that the disease has been caused by slow viruses transmitted by rodents which contaminate food and articles in the house. Such an explanation fits most of the existing epidemiological data.
Subject(s)
Balkan Nephropathy/etiology , Nephritis, Interstitial/etiology , Virus Diseases/complications , Animals , Disease Vectors , Food Contamination , Hemorrhagic Fever, American/etiology , HumansSubject(s)
Arenaviridae Infections/etiology , Hemorrhagic Fevers, Viral/etiology , Animals , Arenaviridae/pathogenicity , Cricetinae , Disease Models, Animal , Guinea Pigs , Haplorhini , Hemorrhagic Fever, American/etiology , Immune Tolerance , Lassa Fever/etiology , Lymphocytic Choriomeningitis/etiology , Mice , Ribavirin/therapeutic useABSTRACT
The 2-day-old rat is known to resist intracerebral infection with the XJ prototype strain of Junin virus, but 95-100% mortality results when infected with the attenuated XJC13 strain. When this animal was inoculated by intraperitoneal route, behaviour was diametrically opposite: the XJ strain proved lethal, while de XJC13 led to low mortality. Studies on mortality, virus titer in different organs, and anti-viral humoral response in 2-day-old rats infected with Junin virus strains were carried out in order to use this system as a new attenuation marker. Mortality rates recorded for rats inoculated with either strain, were markedly different, being 84% in the XJ-infected group and barely reaching 17% in the XJC13 group. Brain viral titers were higher in the former group than the latter (10(5.26) PFU/ml vs. 10(3) PFU/ml at day 17 pi). For this reason, viral replication may be used as a virulence marker in this experimental model. Antibody levels were also higher in the XJ group most likely due to greater viral replication. The above findings support the use of the 2-day-old rat as a biologic attenuation marker since susceptibility to infection is strain-dependent.
Subject(s)
Arenaviridae/classification , Arenaviruses, New World/classification , Animals , Animals, Newborn , Antibodies, Viral/biosynthesis , Arenaviruses, New World/immunology , Arenaviruses, New World/pathogenicity , Brain/microbiology , Disease Susceptibility , Hemorrhagic Fever, American/etiology , Hemorrhagic Fever, American/immunology , Hemorrhagic Fever, American/microbiology , Injections, Intraperitoneal , Liver/microbiology , Rats , Rats, Inbred Strains , Spleen/microbiology , VirulenceABSTRACT
Infection of guinea pigs with an attenuated strain of Junin virus (JV) produced 16% mortality between days 17 and 27 postinfection (p.i.). The morphological study showed a marked pancreatitis between days 6 and 23 p.i. and meningoencephalitis between days 17 and 20 p.i. in a large proportion of the animals. These lesions were coincident with the presence of JV antigenic determinants in the pancreatic acinar cells, neurons and blood vessels of the brain. Infectious virus could be isolated from lymph nodes, spleen, bone marrow, lungs, adrenal glands, and brain. The lesions appeared to be reversible, as they were absent in animals studied after day 64 p.i. Meningoencephalitis, present in all animals dying spontaneously, appeared to be the most important cause of death. Our observations indicate that more accurate markers of virulence must be investigated in the search for attenuated strains of JV as potential vaccine candidates for Argentine hemorrhagic fever.