Preclinical assessment of the neutralizing capacity of antivenoms produced in six Latin American countries against medically-relevant Bothrops snake venoms.

Species of the genus Bothrops induce the vast majority of snakebite envenomings in Latin America. A preclinical study was performed in the context of a regional network of public laboratories involved in the production, quality control and development of antivenoms in Latin America. The ability of seven polyspecific antivenoms, produced in Argentina, Brazil, Peru, Bolivia, Colombia and Costa Rica, to neutralize lethal, hemorrhagic, coagulant, defibrinogenating and myotoxic activities of the venoms of Bothrops neuwiedi (diporus) (Argentina), Bothrops jararaca (Brazil), B. neuwiedi (mattogrossensis) (Bolivia), Bothrops atrox (Peru and Colombia) and Bothrops asper (Costa Rica) was assessed using standard laboratory tests. Despite differences in the venom mixtures used in the immunization of animals for the production of these antivenoms, a pattern of extensive cross-neutralization was observed between these antivenoms and all the venoms tested, with quantitative differences in the values of effective doses. This study reveals the capacity of these antivenoms to neutralize, in preclinical tests, homologous and heterologous Bothrops venoms in Central and South America, and also highlight quantitative differences in the values of Median Effective Doses (ED50s) between the various antivenoms.

Potency evaluation of antivenoms in Brazil: the national control laboratory experience between 2000 and 2006.

Envenoming from snakebites is an important public health issue in Brazil. In 2005, 28,597 cases were notified (15 cases/100,000 inhabitants), 87.5% due to Bothrops and 9.2% to Crotalus genus. Antivenoms available in Brazil are liquid preparations containing purified equine Fab'2. Since 1987, the National Institute for Quality Control in Health (INCQS/FIOCRUZ) has been testing all lots prior to batch release. Between 2000 and 2006, 619 lots of antivenoms were tested, comprising 2,513,690 ampoules. The potency assay was performed only for bothropic and crotalic antivenoms (485 lots corresponding to 1,866,726 ampoules) due to the unavailability of the other reference venoms. This paper aims to report the last 7-year activities of INCQS on the quality control, batch release and potency evaluation of antivenoms.

[Immunogenicity of the avirulent strain RV194-2 of the rabies virus in mice]. / Imunogenicidade da cepa avirulenta RV194-2 do vírus rábico em camundongos.

RV194-2 rabies virus, an avirulent mutant of CVS strain, induces an inapparent infection limited to the central nervous system (CNS) in adult mice inoculated intracerebrally. This fact suggest that immune response of the host is able to eliminate the virus in CNS. For this reason, we have studied the induction of interferon and the humoral immune responses in BALB/c mice after RV194-2 inoculation. These mice presented high levels of interferon in the plasma and in the brain, with elevated levels of neutralizing antirabies antibodies. The 2-5A synthetase, an enzyme marker of interferon action, was analyzed in the brain of inoculated animals. Its enhancement in parallel to the interferon production in the brain, showed biochemical evidence that this interferon is active. Forty five days after RV194-2 virus inoculation, mice were protected against a challenge with the CVS virulent strain. The results presented herein show that RV194-2 strain has a high level of immunogenicity.

Murine experimental infection with rotavirus SA-11: clinical and immunohistological characteristics.

Six- to eight-day old (lactent) mice were inoculated orally with simian SA-11 rotavirus. During the first hours after infection, the virus was already detected in villous apical enterocytes by immunohistologic reaction of paraffin sections of the duodenum and jejunum but not in the ileum. Late on the first day, some animals developed already diarrhoea and pathologic lesions were observed in the duodenum and jejunum. During the second day most mice developed diarrhoea; tissue lesions were intense and maximal from duodenum to ileum when compared to other days and some colon sections had mild pathological characteristics. At this point, the virus in the ileum was only detected by immunohistologic reaction. During the third day some animals still had diarrhoea but tissue histology was regenerated and no virus could be detected. We conclude that the SA-11 model follows an infection pattern similar to Epizootic Diarrhoea of Infant Mice (EDIM) and propose to study immunological parameters as young susceptible animals mature into adult resistant ones.

Serological evidence of rotavirus infection in guinea pig colony

Evidência sorológica de infecçäo por rotavírus em uma colônia de cobaios - Anticorpos reagindo com rotavírus símio SA11 foram demonstrados por ensaio imuno-enzimático (EIE) e por "Western blot assay" (WBA) em soros de cobaios mantidos para fins experimentais na Fundaçäo Oswaldo Cruz, Rio de Janeiro, Brasil. A proporçäo de animais soro-positivos e os níveis de anticorpos subiram rapidametne em 1985, mantiveram-se altos em 1986 e baixaram em 1987. Näo foram observados sinais de doença coincidente com a elevaçäo de anticorpos. Resultados de WBA sugerem que o rotavírus responsável pela resposta sorológica pertence ao subgrupo do grupo A

Serological evidence of rotavirus infection in a guinea pig colony.

Antibodies reacting with simian rotavirus SA11 were detected by enzyme immunoassay (EIA) and Western blot assay (WBA) in sera from guinea pigs bred for experimental use at the Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. The proportion of antibody-positive animals and the antibody titres rose sharply in 1985, were maintained at a high levels in 1986 and declined in 1987. There were no obvious signs of disease coinciding with serological evidence of infection. Results of WBA suggest that the virus involved belongs to subgroup 1 of group A rotaviruses.

Diarrhoea in mice infected with a human rotavirus.

Oral inoculation of newborn mice with the MET strain of human rotavirus produced transient diarrhoeal disease. Light and scanning electron microscopy showed typical rotavirus-induced morphological lesions in the villous epithelium of the small intestine consisting of extensive cytoplasmic vacuolation, villous necrosis and atrophy. Virus recovered from intestinal suspensions of infected mice showed the typical electrophoretic profile of the genome of the inoculated strain. Rotavirus antibody appeared in infected mice 10 to 20 days after inoculation but not in controls or nursing dams. The availability of a small animal model for experimental infection with human rotaviruses should prove useful for virulence and protection studies.