RESUMO
The emergence of Hendra Virus (HeV) and Nipah Virus (NiV) which can cause fatal infections in both animals and humans has triggered a search for an effective vaccine. Here, we have explored the potential for generating an effective humoral immune response to these zoonotic pathogens using an alphavirus-based vaccine platform. Groups of mice were immunized with Venezuelan equine encephalitis virus replicon particles (VRPs) encoding the attachment or fusion glycoproteins of either HeV or NiV. We demonstrate the induction of highly potent cross-reactive neutralizing antibodies to both viruses using this approach. Preliminary study suggested early enhancement in the antibody response with use of a modified version of VRP. Overall, these data suggest that the use of an alphavirus-derived vaccine platform might serve as a viable approach for the development of an effective vaccine against the henipaviruses.
Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Vírus da Encefalite Equina Venezuelana/genética , Vírus Hendra/imunologia , Infecções por Henipavirus/prevenção & controle , Vírus Nipah/imunologia , Animais , Feminino , Expressão Gênica , Vetores Genéticos , Vírus Hendra/genética , Infecções por Henipavirus/imunologia , Camundongos , Camundongos Endogâmicos C3H , Vírus Nipah/genética , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologiaRESUMO
Over the past 2 decades, the Amazon region of Brazil has experienced reemergence of Plasmodium vivax malaria, with reported occurrence of severe disease. The frequency and manifestations of this severe disease are unlike previous clinical experience. The hypothesis has been raised that the occurrence of severe disease may relate to the emergence of a variant form of the parasite. To test this hypothesis, we conducted a retrospective cohort study of P. vivax strains in the State of Amazonas. We determined nucleic acid sequences of segments of three genes, the 18S SSUrRNA Type A gene, the circumsporozoite surface protein (CSP) gene and the MSP-1 gene. Sequences were determined for parasites infecting 11 hospitalized (Inpatients) and 21 non-hospitalized (Outpatients) patients. We observed two common polymorphisms in the 18S SSUrRNA Type A gene; a thymidine (T)/adenine (A) polymorphism at residue 117 was significantly more common in the Inpatient group (p<0.05). Types of variation in the CSP gene included the numbers of repeat nonapeptide segments, alanine/aspartic acid polymorphism at position 5 of the nonapeptide repeat, and sporadic mutations. Alanine was more common as the fifth residue of the nonapeptide repeat in Inpatients and in strains causing second infections (both, p<0.05). Synonymous substitutions of the common repeat sequence occurred frequently in codons 1, 2, and 7, while the mutations at codon 5 were always non-synonymous, indicating that variation at codon 5 reflected selective pressure. Among MSP-1 gene sequences, recombination among progenitor strains, related to the Salvador I and Belém strains, was the main source of diversity. Phylogenetic analyses that incorporated sequence data for all three genes tested did not reveal clustering of sequences from inpatients. Our data do not affirm that the hypothesis that severe P. vivax disease in Amazonas is related to emergence of a new variant, but do suggest that variation in the fifth position of the CSP gene nonapeptide repeat may relate to disease manifestations.
Assuntos
Variação Genética , Malária Vivax/epidemiologia , Epidemiologia Molecular , Plasmodium vivax/genética , Sequência de Aminoácidos , Animais , Brasil/epidemiologia , DNA de Protozoário/análise , DNA de Protozoário/isolamento & purificação , Humanos , Malária Vivax/parasitologia , Malária Vivax/fisiopatologia , Proteína 1 de Superfície de Merozoito/genética , Dados de Sequência Molecular , Filogenia , Plasmodium vivax/patogenicidade , Proteínas de Protozoários/genética , RNA Ribossômico 18S/genética , Análise de Sequência de DNARESUMO
We focused on rates of malaria in the state of Amazonas and city of Manaus, Brazil. Plasmodium vivax accounted for an increased number and rate of hospital admissions, while P. falciparum cases decreased. Our observations on malaria epidemiology suggest that the increased hospitalization rate could be due to increased severity of P. vivax infections.
Assuntos
Doenças Endêmicas , Hospitalização/estatística & dados numéricos , Malária Vivax/epidemiologia , Animais , Brasil/epidemiologia , Bases de Dados Factuais , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/epidemiologia , Malária Vivax/diagnóstico , PrevalênciaRESUMO
Human T-cell lymphotropic virus type 1(HTLV-1) is associated with adult T-cell leukemia, tropical spastic paraparesis, and other immune-mediated diseases. There are reports of groups with high prevalences of HTLV-1 infection in Peru, but there is limited knowledge of the epidemiology of infection or which routes of infection are most important. We studied 2,492 women presenting to a large maternity hospital in Lima for prenatal, delivery, or abortion services. HTLV-1 seropositivity was confirmed in 42 women (1.7%; 95% confidence interval, 1.2-2.2). Seroprevalence increased with age but did not vary by region of birth or recency of migration to Lima. Age greater than 30 years and sexual intercourse before 20 years of age were strongly and independently associated with infection. History of abortion and history of transfusion were of borderline significance. Women whose male partner had a characteristic that might be a marker for risk of sexually transmitted infections were also more likely to be infected. HTLV-1 is common among Peruvians throughout the country and is maintained by a low level of neonatally acquired infection that is amplified by sexual transmission. In addition to screening of the blood supply, instituted in 1997, programs designed to reduce neonatal and sexual transmission should be effective.