RESUMO
Argentine hemorrhagic fever (AHF) is a potentially lethal infection in Argentina. The case-fatality ratio is >15%, but treatment reduces the mortality rate to <1%. Diagnosis is based on clinical and laboratory criteria, but no case definition has been validated. A chart review was conducted for patients hospitalized with suspected AHF. Individuals with a fourfold rise in antibody titer were classified as cases. The combination of a platelet count of <100,000/mm3 and a white blood cell (WBC) count of <2,500/mm3 had a sensitivity and specificity of 87% and 88%, respectively, thus suggesting that the use of these criteria in a case definition would be helpful for epidemiological studies of AHF. The combination of a platelet count of <100,000/mm3 and a WBC count of <4,000/mm3 had a sensitivity of 100% and a specificity of 71%; the use of these criteria in a case definition should be helpful for screening patients for therapy with immune plasma in the region where AHF is endemic.
Assuntos
Infecções por Arenaviridae/diagnóstico , Febre Hemorrágica Americana/diagnóstico , Vírus Junin/isolamento & purificação , Adulto , Anticorpos Antivirais/sangue , Infecções por Arenaviridae/sangue , Argentina , Feminino , Febre Hemorrágica Americana/sangue , Humanos , Vírus Junin/imunologia , Contagem de Leucócitos , Masculino , Contagem de Plaquetas , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
Argentine hemorrhagic fever (AHF), caused by the arenavirus Junin, is a major public health problem among agricultural workers in Argentina. A prospective, randomized, double-blind, placebo-controlled, efficacy trial of Candid 1, a live attenuated Junin virus vaccine, was conducted over two consecutive epidemic seasons among 6500 male agricultural workers in the AHF-endemic region. Twenty-three men developed laboratory-confirmed AHF during the study; 22 received placebo and 1 received vaccine (vaccine efficacy 95%; 95% confidence interval [CI], 82%-99%). Three additional subjects in each group developed laboratory-confirmed Junin virus infection associated with mild illnesses that did not fulfill the clinical case definition for AHF, yielding a protective efficacy for prevention of any illness associated with Junin virus infection of 84% (95% CI, 60%-94%). No serious adverse events were attributed to vaccination. Candid 1, the first vaccine for the prevention of illness caused by an arenavirus, is safe and highly efficacious.
Assuntos
Arenavirus do Novo Mundo/imunologia , Febre Hemorrágica Americana/prevenção & controle , Febre Hemorrágica Americana/terapia , Vacinas Atenuadas/uso terapêutico , Vacinas Virais/uso terapêutico , Adolescente , Adulto , Doenças dos Trabalhadores Agrícolas/prevenção & controle , Doenças dos Trabalhadores Agrícolas/terapia , Doenças dos Trabalhadores Agrícolas/virologia , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/imunologia , Arenavirus do Novo Mundo/crescimento & desenvolvimento , Argentina , Células Cultivadas , Chlorocebus aethiops , Método Duplo-Cego , Febre Hemorrágica Americana/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estações do Ano , Vacinas Atenuadas/efeitos adversos , Células Vero , Vacinas Virais/efeitos adversosRESUMO
Oliveros virus is an agent isolated in cell culture from Bolomys obscurus (Rodentia, Muridae, Sigmodontinae) captured on the central Argentine pampa. Oliveros virus was shown to be related to members of the Tacaribe complex of the family Arenaviridae by immunofluorescent antibody (IFA) tests, electrophoretic pattern of viral proteins, and morphology as observed by electron microscopy. It was distinct from 12 other arenaviruses by a combination of plaque-reduction neutralization tests, comparison of endpoint titers among cross-IFA tests, and comparison of viral RNA sequence data. This agent is the third new arenavirus from South America described within the last three years.
Assuntos
Arenavirus do Novo Mundo/classificação , Reservatórios de Doenças , Febre Hemorrágica Americana/virologia , Doenças dos Roedores/virologia , Sigmodontinae/virologia , Animais , Animais Lactentes , Arenavirus do Novo Mundo/isolamento & purificação , Arenavirus do Novo Mundo/fisiologia , Argentina , Chlorocebus aethiops , Reações Cruzadas , Efeito Citopatogênico Viral , Eletroforese em Gel de Poliacrilamida , Imunofluorescência , Camundongos , Camundongos Endogâmicos ICR , Microscopia Eletrônica , Testes de Neutralização , Células Vero , Proteínas Virais/análise , Vírion/ultraestruturaRESUMO
We report the results of indirect fluorescent antibody screening for antibody to Junin virus in 1,101 sera from small mammals captured on two mark-recapture grids in the epidemic area of Argentine hemorrhagic fever. Twenty-six of 29 seropositive animals were the cricetid rodent Calomys musculinus, for a 30-month prevalence of 7.9% in that species. Combining these data with previously published data on antigen detection provided an estimated total prevalence of infection of 10.9% for this, the principal reservoir species. Other infected species included two cricetids, C. laucha and Bolomys obscurus, and a predatory carnivore, Galictis cuja. Approximately half of infected animals simultaneously carried serum antibody and antigen in blood and saliva, some for 29-61 days. Except for C. laucha, which was associated with crop habitats, seropositive animals were strongly associated with the relatively rare roadside and fence-line habitats. Seropositive C. musculinus were predominantly males in the oldest age and heaviest body mass classes, and seropositive males were twice as likely to have body scars as seronegative males. These observations suggest that most infections were acquired through horizontal transmission and that aggressive encounters among adult, male C. musculinus in relatively densely populated roadside and fence-line habitats are an important mechanism of transmission of Junin virus within reservoir populations.
Assuntos
Reservatórios de Doenças , Febre Hemorrágica Americana/veterinária , Vírus Junin/imunologia , Doenças dos Roedores/epidemiologia , Fatores Etários , Animais , Anticorpos Antivirais/sangue , Antígenos Virais/análise , Antígenos Virais/sangue , Argentina/epidemiologia , Arvicolinae , Carnívoros , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Febre Hemorrágica Americana/epidemiologia , Masculino , Muridae , Dinâmica Populacional , Prevalência , Roedores , Saliva/virologia , Estudos Soroepidemiológicos , Fatores SexuaisRESUMO
The safety and immunogenicity of Candid #1, a live-attenuated Junin virus vaccine, were evaluated in rhesus macaques. Candid #1 was inoculated subcutaneously in graded doses ranging from 16 to 127,200 plaque-forming units (PFU) into four groups of five animals each; four controls received saline. There was no significant effect of the immunization on any physical, hematologic, or biochemical parameter measured. Junin virus was recovered by cocultivation from peripheral blood mononuclear cells (PBMC) of 14 (70%) of 20 animals from 1 to 21 days after immunization; 27 (12%) of 223 PBMC samples that represented animals in all four dose groups were positive. In contrast, virus was recovered from the plasma of only two of 20 macaques (two of 225 samples [0.9%]), and only once (by amplification) from throat swabs. No evidence of reversion was detected in any blood isolate. All animals developed a detectable neutralizing antibody response following vaccination. These results indicate that Candid #1 is safe and immunogenic in nonhuman primates.
Assuntos
Arenavirus do Novo Mundo/imunologia , Febre Hemorrágica Americana/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Arenavirus do Novo Mundo/isolamento & purificação , Arenavirus do Novo Mundo/patogenicidade , Contagem de Células Sanguíneas/efeitos dos fármacos , Análise Química do Sangue , Feminino , Macaca mulatta , Masculino , Distribuição Aleatória , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Virais/efeitos adversos , Viremia/microbiologia , Virulência , Redução de PesoRESUMO
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.
Assuntos
Arenavirus do Novo Mundo/isolamento & purificação , Reservatórios de Doenças , Febre Hemorrágica Americana/veterinária , Doenças dos Roedores/epidemiologia , Sigmodontinae/microbiologia , Fatores Etários , Animais , Antígenos Virais/análise , Antígenos Virais/sangue , Arenavirus do Novo Mundo/imunologia , Argentina/epidemiologia , Feminino , Febre Hemorrágica Americana/epidemiologia , Febre Hemorrágica Americana/transmissão , Incidência , Estudos Longitudinais , Masculino , Boca/microbiologia , Dinâmica Populacional , Prevalência , Doenças dos Roedores/transmissão , Estações do Ano , Fatores Sexuais , Tempo (Meteorologia)RESUMO
The protective efficacy of Candid No. 1, a live-attenuated vaccine against Argentine hemorrhagic fever (AHF), was evaluated in non-human primates. Twenty rhesus macaques immunized 3 months previously with graded doses of Candid No. 1 (16-127, 000 PFU), as well as 4 placebo-inoculated controls, were challenged with 4.41 log10 PFU of virulent P3790 strain Junin virus. All controls developed severe clinical disease; 3 of 4 died. In contrast, all vaccinated animals were fully protected; none developed any signs of AHF during a 105-day follow-up period. Viremia and virus shedding were readily detected in all placebo-vaccinated controls, while virus could be recovered only once (by amplification) from throat swabs of 2 Candid No. 1 vaccinees on day 21. Vigorous secondary-type neutralizing and immunofluorescent antibody responses were seen in most vaccinees that had received 3 log10 PFU Candid No. 1 or fewer; all others, including those receiving 127,200 PFU, maintained relatively stable titers during follow-up. Candid No. 1 was highly immunogenic and fully protective against lethal Junin virus challenge in rhesus macaques, even at extremely low (16 PFU) vaccine doses.
Assuntos
Arenavirus do Novo Mundo/patogenicidade , Febre Hemorrágica Americana/prevenção & controle , Vacinação , Vacinas Atenuadas/uso terapêutico , Animais , Anticorpos Antivirais/sangue , Arenavirus do Novo Mundo/imunologia , Arenavirus do Novo Mundo/isolamento & purificação , Febre Hemorrágica Americana/imunologia , Esquemas de Imunização , Macaca mulatta , Testes de Neutralização , Resultado do Tratamento , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Viremia , Eliminação de Partículas ViraisRESUMO
Small mammals were trapped during a 21-month period at 27 farm sites in 15 localities within and beyond the known endemic area for Argentine hemorrhagic fever (AHF). Prevalence of Junin virus (JV) was assessed by antigen-capture enzyme immunoassay (ELISA) on samples of body fluids and/or organs from 3, 282 captured rodents. Infection in rodent populations was variable (0-3.7%) among localities but, in all cases, was lower than previously reported rates. Overall prevalence was 1.4% in the AHF epidemic area, 0.6% in the historic (currently low incidence of AHF) area, and 0.4% in two localities beyond the previously defined endemic area. These low values underestimate the actual prevalence of JV, as ELISA validation by virus isolation indicated a sensitivity of 30% and a specificity of 99%. Of 37 positive rodents, 28 (76%) were of two species: Calomys musculinus (23 animals) and C. laucha (5 animals). Antigen also was found in three Akodon azarae, four Bolomys obscurus, one Mus musculus, and one Oxymycterus rufus, and JV was isolated from two Oligoryzomys flavescens. Three of these rodent species (B. obscurus, O. flavescens, and O. rufus) have heretofore not been implicated in JV maintenance in the field. Evidence suggests that the AHF endemic area may continue to expand northward.
Assuntos
Arenavirus do Novo Mundo/isolamento & purificação , Reservatórios de Doenças , Febre Hemorrágica Americana/epidemiologia , Doenças dos Roedores/epidemiologia , Animais , Antígenos Virais/análise , Arenavirus do Novo Mundo/imunologia , Argentina , Encéfalo/imunologia , Encéfalo/microbiologia , Ensaio de Imunoadsorção Enzimática , Febre Hemorrágica Americana/veterinária , Humanos , Prevalência , Roedores , Estações do Ano , Baço/imunologia , Baço/microbiologiaRESUMO
A vaccine against Argentine hemorrhagic fever, the "mal de los rastrojos" of the pampas, has been a dream of physicians and scientists involved with the disease since its recognition in the 1950s. Several killed and live immunogens have been produced and tested in pursuit of this goal, none of which has proved suitable for widespread human use. Recently, a new live-attenuated Junin virus vaccine, Candid #1, was developed through a cooperative international effort. Testing conducted to date indicates that this vaccine holds considerable promise.
Assuntos
Arenavirus do Novo Mundo/imunologia , Febre Hemorrágica Americana/prevenção & controle , Vacinas Virais , Animais , Humanos , Vacinas Atenuadas , Vacinas de Produtos InativadosRESUMO
In conjunction with field trials for a vaccine against Argentine Hemorrhagic Fever (AHF), small mammals were trapped during a 28-month period (1 November 1987 to 13 March 1990) in 3 epidemiologically defined areas of the central Argentine pampas: northern and central Buenos Aires provinces were included in the AHF "historic" area, where the disease was common 15-20 years ago, but case rates are currently low; southern Santa Fe province is the current high-incidence area for AHF; the nonendemic area was represented by two localities 60-90 km beyond the northernmost extension of human disease. Animals were live-trapped for 3 days per month in permanent "mark-recapture" grids in each of the 3 areas. Samples of blood, sera, and oral swabs were taken from these animals before they were marked and released at the site of capture. In addition, "removal" traplines provided animals from 16 localities in these 3 areas which were sacrificed to obtain samples of organs in addition to the aforementioned samples. Samples were tested for the presence of Junin virus (JV) antigen by enzyme immunoassay (ELISA). In this assay, a pool of 13 mouse anti-JV glycoprotein and nucleocapsid monoclonal antibodies adsorbed to the surface of microtiter plates was used to capture JV antigen in sample suspensions. A polyclonal rabbit anti-JV antiserum was added as a detector antibody, and an anti-rabbit antibody conjugated to horseradish peroxidase applied with substrate to complete the sandwich.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Vetores de Doenças , Febre Hemorrágica Americana/veterinária , Vírus Junin/isolamento & purificação , Doenças dos Roedores/epidemiologia , Animais , Argentina/epidemiologia , Febre Hemorrágica Americana/epidemiologiaRESUMO
In conjunction with field trials for a vaccine against Argentine Hemorrhagic Fever (AHF), small mammals were trapped during a 28-month period (1 November 1987 to 13 March 1990) in 3 epidemiologically defined areas of the central Argentine pampas: northern and central Buenos Aires provinces were included in the AHF [quot ]historic[quot ] area, where the disease was common 15-20 years ago, but case rates are currently low; southern Santa Fe province is the current high-incidence area for AHF; the nonendemic area was represented by two localities 60-90 km beyond the northernmost extension of human disease. Animals were live-trapped for 3 days per month in permanent [quot ]mark-recapture[quot ] grids in each of the 3 areas. Samples of blood, sera, and oral swabs were taken from these animals before they were marked and released at the site of capture. In addition, [quot ]removal[quot ] traplines provided animals from 16 localities in these 3 areas which were sacrificed to obtain samples of organs in addition to the aforementioned samples. Samples were tested for the presence of Junin virus (JV) antigen by enzyme immunoassay (ELISA). In this assay, a pool of 13 mouse anti-JV glycoprotein and nucleocapsid monoclonal antibodies adsorbed to the surface of microtiter plates was used to capture JV antigen in sample suspensions. A polyclonal rabbit anti-JV antiserum was added as a detector antibody, and an anti-rabbit antibody conjugated to horseradish peroxidase applied with substrate to complete the sandwich.(ABSTRACT TRUNCATED AT 250 WORDS)
RESUMO
In conjunction with field trials for a vaccine against Argentine Hemorrhagic Fever (AHF), small mammals were trapped during a 28-month period (1 November 1987 to 13 March 1990) in 3 epidemiologically defined areas of the central Argentine pampas: northern and central Buenos Aires provinces were included in the AHF [quot ]historic[quot ] area, where the disease was common 15-20 years ago, but case rates are currently low; southern Santa Fe province is the current high-incidence area for AHF; the nonendemic area was represented by two localities 60-90 km beyond the northernmost extension of human disease. Animals were live-trapped for 3 days per month in permanent [quot ]mark-recapture[quot ] grids in each of the 3 areas. Samples of blood, sera, and oral swabs were taken from these animals before they were marked and released at the site of capture. In addition, [quot ]removal[quot ] traplines provided animals from 16 localities in these 3 areas which were sacrificed to obtain samples of organs in addition to the aforementioned samples. Samples were tested for the presence of Junin virus (JV) antigen by enzyme immunoassay (ELISA). In this assay, a pool of 13 mouse anti-JV glycoprotein and nucleocapsid monoclonal antibodies adsorbed to the surface of microtiter plates was used to capture JV antigen in sample suspensions. A polyclonal rabbit anti-JV antiserum was added as a detector antibody, and an anti-rabbit antibody conjugated to horseradish peroxidase applied with substrate to complete the sandwich.(ABSTRACT TRUNCATED AT 250 WORDS)
RESUMO
In conjunction with field trials for a vaccine against Argentine Hemorrhagic Fever (AHF), small mammals were trapped during a 28-month period (1 November 1987 to 13 March 1990) in 3 epidemiologically defined areas of the central Argentine pampas: northern and central Buenos Aires provinces were included in the AHF [quot ]historic[quot ] area, where the disease was common 15-20 years ago, but case rates are currently low; southern Santa Fe province is the current high-incidence area for AHF; the nonendemic area was represented by two localities 60-90 km beyond the northernmost extension of human disease. Animals were live-trapped for 3 days per month in permanent [quot ]mark-recapture[quot ] grids in each of the 3 areas. Samples of blood, sera, and oral swabs were taken from these animals before they were marked and released at the site of capture. In addition, [quot ]removal[quot ] traplines provided animals from 16 localities in these 3 areas which were sacrificed to obtain samples of organs in addition to the aforementioned samples. Samples were tested for the presence of Junin virus (JV) antigen by enzyme immunoassay (ELISA). In this assay, a pool of 13 mouse anti-JV glycoprotein and nucleocapsid monoclonal antibodies adsorbed to the surface of microtiter plates was used to capture JV antigen in sample suspensions. A polyclonal rabbit anti-JV antiserum was added as a detector antibody, and an anti-rabbit antibody conjugated to horseradish peroxidase applied with substrate to complete the sandwich.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Animais , Doenças dos Roedores/epidemiologia , Vírus Junin/isolamento & purificação , Vetores de Doenças , Febre Hemorrágica Americana/veterinária , Argentina/epidemiologia , Febre Hemorrágica Americana/epidemiologiaRESUMO
Junin virus-infected rhesus macaques received prophylactic and therapeutic ribavirin to assess the potential of this drug for treating humans with Argentine hemorrhagic fever. When ribavirin was administered intramuscularly at the time of experimental infection with the lethal P3790 strain of Junin virus, all animals were protected from clinical disease. A delay in the initiation of therapy until after the onset of illness resulted in improvement and resolution of systemic signs of disease; however, survivors subsequently developed a late-onset central nervous system infection which was fatal in two of three animals. Side effects of ribavirin included thrombocytosis and severe anemia, both of which resolved promptly on withdrawal of drug therapy. Results of this study suggest that ribavirin may prove useful in treating humans with Argentine hemorrhagic fever.
Assuntos
Febre Hemorrágica Americana/tratamento farmacológico , Ribavirina/uso terapêutico , Ribonucleosídeos/uso terapêutico , Animais , Arenavirus do Novo Mundo/isolamento & purificação , Testes Hematológicos , Febre Hemorrágica Americana/prevenção & controle , Macaca mulattaRESUMO
Two isolates of Junin virus (Espindola and Ledesma) inoculated into rhesus macaques produced distinct lesions which were strain-constant and similar to reported human cases of Argentine hemorrhagic fever. The Espindola isolate was associated with hemorrhagia, necrosis of bone marrow, and mild hepatocellular necrosis. Ledesma isolate was associated with pronounced polioencephalomyelitis and autonomic ganglioneuritis, but very mild or absent hepatocellular necrosis, bone marrow necrosis, and hemorrhagia. Deaths of Espindola-infected macaques were usually attributed to hemorrhagia with severe secondary bacterial infections, while in Ledesma-infected macaques, death was associated either with early severe secondary bacterial infections or slowly progressive polioencephalomyelitis. These two Junin virus isolates demonstrated hemorrhagic viscerotropism or neurotropism in macaques, suggesting that the variety of Argentine hemorrhagic fever syndromes in man may be virus-isolate determined.
Assuntos
Febre Hemorrágica Americana/patologia , Animais , Arenavirus do Novo Mundo/patogenicidade , Sistema Nervoso Autônomo/patologia , Medula Óssea/patologia , Sistema Nervoso Central/patologia , Sistema Digestório/patologia , Glândulas Endócrinas/patologia , Hemorragia/patologia , Febre Hemorrágica Americana/microbiologia , Fígado/patologia , Tecido Linfoide/patologia , Macaca mulatta , Mucosa/patologia , Nervos Periféricos/patologia , Sistema Respiratório/patologia , Bexiga Urinária/patologiaRESUMO
A nonhuman primate model for Argentine hemorrhagic fever has been developed that closely mimics the human clinical syndrome. Parenteral infection of adult Macaca mulatta with low-passage isolates of two Junin viral strains resulted in distinctive hemorrhagic or neurological disease in rhesus macaques that correlated with clinical illness patterns present in the humans from whom the viral strains were obtained. Transient leukopenia, together with thrombocytopenia and secondary bacterial septicemia, were documented among animals infected with both viral strains. In contrast, differing patterns of viremia, oropharyngeal viral shedding, and antibody response occurred in the two virus-infected groups. These results, together with postmortem virologic and histopathologic findings, suggest that viral-strain-specific factors are important determinants of clinical disease patterns in this model system.
Assuntos
Arenaviridae/fisiologia , Arenavirus do Novo Mundo/fisiologia , Febre Hemorrágica Americana/microbiologia , Animais , Anticorpos Antivirais/análise , Antígenos Virais/análise , Arenavirus do Novo Mundo/imunologia , Arenavirus do Novo Mundo/isolamento & purificação , Sistema Nervoso Central/microbiologia , Modelos Animais de Doenças , Hemorragia/etiologia , Febre Hemorrágica Americana/complicações , Contagem de Leucócitos , Macaca mulatta , Orofaringe/microbiologia , Contagem de Plaquetas , Sepse/complicações , ViremiaAssuntos
Arenaviridae/patogenicidade , Arenavirus do Novo Mundo/patogenicidade , Febre Hemorrágica Americana/microbiologia , Animais , Anticorpos Antivirais/análise , Arenavirus do Novo Mundo/crescimento & desenvolvimento , Arenavirus do Novo Mundo/imunologia , Arenavirus do Novo Mundo/isolamento & purificação , Modelos Animais de Doenças , Hemorragia/etiologia , Febre Hemorrágica Americana/complicações , Febre Hemorrágica Americana/imunologia , Macaca mulatta , Doenças do Sistema Nervoso/etiologia , Testes de Neutralização , Orofaringe/microbiologia , Púrpura/etiologia , Especificidade da Espécie , ViremiaAssuntos
Arenaviridae/patogenicidade , Arenavirus do Novo Mundo/patogenicidade , Cebidae/imunologia , Cebus/imunologia , Modelos Animais de Doenças , Febre Hemorrágica Americana/imunologia , Animais , Anticorpos Antivirais/análise , Arenavirus do Novo Mundo/imunologia , Vacinas Atenuadas , Vacinas Virais , VirulênciaRESUMO
Multiresistant Klebsiella pneumoniae has been endemic among adult patients at Vanderbilt University Medical Center since 1973. Multiresistant K. pneumoniae was absent from pediatric wards until 1979, when it produced an epidemic in the intensive care nursery followed a year later by a second epidemic involving K. pneumoniae of the same serotype. The 105 megadalton (Md) conjugative resistance (R) plasmid (pCER7999) transferring multiple antibiotic resistance in the adult, endemic strain was found also in isolates from the first epidemic in the intensive care nursery. The mother of a child in the nursery harbored E. coli containing the same 105 Md R plasmid. The second epidemic also involved a 105 Md conjugative R plasmid, which, however, by molecular analysis was different from the first epidemic plasmid and also pCER7999. Thus, the second epidemic resulted from the introduction of a new, unrelated multiresistant K. pneumoniae strain. Contemporary hospital epidemiology often requires the application of molecular techniques for an understanding of nosocomial infections.