Prevention of respiratory syncytial virus infections

Respiratory syncytial virus is the most important cause of viral lower respiratory illness in infants and children worldwide. By the age of 2 years, nearly every child has become infected with respiratory syncytial virus and re-infections are common throughout life. Most infections are mild and can be managed at home, but this virus causes serious diseases in preterm children, especially those with bronchopulmonary dysplasia. Respiratory syncytial virus has also been recognized as an important pathogen in people with immunossupressive and other underlying medical problems and institutionalizated elderly, causing thousands of hospitalizations and deaths every year. The burden of these infections makes the development of vaccines for respiratory syncytial virus highly desirable, but the insuccess of a respiratory syncytial virus formalin-inactivated vaccine hampered the progress in this field. To date, there is no vaccine available for preventing respiratory syncytial virus infections, however, in the last years, there has been much progress in the understanding of immunology and immunopathologic mechanisms of respiratory syncytial virus diseases, which has allowed the development of new strategies for passive and active prophylaxis. In this article, the author presents a review about novel approaches to the prevention of respiratory syncytial virus infections, such as: passive immunization with human polyclonal intravenous immune globulin and humanized monoclonal antibodies (both already licensed for use in premature infants and children with bronchopulmonary dysplasia), and many different vaccines that are potential candidates for active immunization against respiratory syncytial virus.

Alterações nucleares das cellulas do figado nas infecções de Macacus Rhesus e M. Cynomolgus pelo virus da febre amarella

No figado de um Macacus rhesus inoculado por BEAUREPAIRE ARAGÃO com sangue deum caso benigno de febre amarella e no qual elle descreveu symptomas e lesões typicas semelhantes ás obidas por STOKES, BAUER e HUDSON pela inoculação com o virus africano no mesmo animal, encontrámos alterações nucleares da mesma natureza das assignaladas, no herpes zoster, herpes symptomatico, varicella e virus III do coelho e descriptas ora sob o nome de "inclusões acidophilas intranucleares" (LIPSCHÜTZ, GOODPASTURE), ora sob o de "degeneração oxychromatica" (LAUDA e LUGER). Alterações nucleares semelhantes da cellula hepatica encontrámos, posteriormente em 13 M. rhesus e 2 M. cynomolgus inoculados com e virus brasileiro da febre amarella o qual fôra isolado independentemente por BEAUREPAIRE ARAGÂO e depois por A. MARQUES DA CUNHA e J. MUNIZ de dois casos benignos de febre amarella, tendo sido um dos macacos injectado directamente com o sangue do doente; dois macacos foram inoculados com Aedes aegypti infectados em homem e em macaco; os animais foram anímaes empregados em passagens em serie do virus pelo macaco, e talvez esse facto explique até certo ponto, as notaveis differenças por vezes encontradas nas alterações histopathologicas do figado, visto como, em condições naturaes, o virus nunca passa directamente de homem para homem. A intensidade com que se apresenta a degeneração oxychromatica de modo algum está na dependencia das alterações do conteúdo gorduroso, necrose e necrobiose encontradas; em um caso, ella era a unica alteração presente no figado, sendo então particularmente intensa. As inclusões acidophilas intranucleares (degeneração oxychromatica) não foram encontradas em diversos M. rhesus não inoculados e mortos por causas obscuras; no entanto, em taes figados eram presentes infiltração e degeneração gordurosas associadas a alterações de necrose e necrobiose. Alguns estadios (figuras intranucleares "em borboleta" e "em ameba", v. fig. g e h, Est. colorida) sendo abundantes, facilitam, em virtude de sua configuração especial, o reconhecimento da degeneração oxychromatica em córtes feitos segundo uma technica rapida (pequenos fragmentos de figado fixados em formol aquecido a 60°C.-trinta minutos, córtes em congelação, hematoxylina, eosina, alcool absoluto, phenol-xylol-creosoto, xylol, balsamo), não tendo, afóra isso, importancia especial. Ao passo que a degeneração e infiltração gordurosa, bem como a necrose e a necrobiose da cellula hepatica apresentam variações consideraveis em sua intensidade de um para outro animal em uma passagem em serie não interrompida do virus pelo M. rhesus, chegando mesmo a faltar interamente em dois animaes cujo figado, no entanto, mostrou-se capaz de reproduzir symptomas e lesões typicas na passagem seguinte, as inclusões acidophilas intranucleares (degeneração oxychromatica), de regra, se encontram com muito maior regularidade...

O virus do mixoma no coelho do mato (Sylvilagus minenses), sua transmissão pelos Aedes scapularis e aegypti

The brazilian wild rabbit (Sylvilagus minensis) is sensible to the virus of the mixomatosis but the desease takes on it a mild character, lasts for long time and generally do not kill the animal. The tumors are generally smaller and less numerous than those of the domestic rabbit, but sometimes there were noted large and flat lesions (fig. 3). The natural infection of the wild rabbit may be quite common not only because many rabbits caught in the country were found to be immune as also because it was found among the animals caught in the country near Rio, one that was infected with mixomatosis. The experimental infection of the Sylvilagus may be easily obtained by cutan, subcutan or conjuntival way and also when a health wild rabbit is placed in the same cage with a sick domestic animal. It is also possible to obtain the infection of the wild and domestic rabbits by the bite of infected blood sucking insects as fleas and mosquitoes. The infected mosquito can transmit the disease 2 or 3 times til 17 days after an infective meal on a sick rabbit. The transmission is a mecanical one and only the proboscis of the insect contains the virus as it was shown by the inoculation of emulsions of the proboscis, thorax and abdomen of the mosquito. Though mecanical this kind of transmission acts as an important epidemiological mean of dissemination of the deseasse and splains the suddendly outbreaks of mixomatosis in rabbits breedings where no new rabbits were introduced since very long time. The transmition of mixomatosis by fleas (Slenopsylla) was at first demonstrated by us, then S. Torres pointed out the capacity of Culex fatigans to transmit the desease and now we have proved that Aedes scapularis and Aedes aegypti were also able to transmit it (Foto 1 and 2). The virus of the mixomatosis (Chlamidozoon mixoma) is seen on the smeavs of the tumors of the wild reabbit with the same morphology, as in the material of the domestic animal.

Inoculação de virus amarílico em gatos jovens

1. Gatos jovens inoculados por via intracerebral com doses relativamente grandes de virus neurotrópico ou viscerotrópico, e por via intraperitoneal com virus viscerotrópico, não demonstram virus circulante até o 12º dia. 2. Tais gatos também não demonstraram sintomas ligados à infecção amarílica. 3. Foi impossivel isolar virus do cérebro dos gatos que morreram no decurso das observações e os exames anatomopatológicos não demonstraram ter havido processo de encefalite (apenas um caso de encefalite tóxica). 4. O desenvolvimetno de imunidade serológica, após a inoculação de virus neurotrópico por via intracerebral e intraperitoneal, foi observado na grande maioria dos casos; com virus Asibi, obtivemos apenas dois resultados positivos quando o virus foi inoculado por via intracerebral. CONCLUSÃO: Gatos jovens são relativamente insensiveis ao virus amarílico, sendo possivel apenas evidenciar reação de imunidade.

Suscetibilidade de camondongos ao virus amarílico administrado por vias extraneurais

1. Virus neurotrópico Francês, Asibi e de vacina (17D) infectaram camondongos jovens, quando instilados nas narinas, matando-os com encefalite ou desenvolvendo imunidade. 2. Virus neurotrópico Francês e Asibi (e talvez o virus de vacina) quando instilados no ouvido de camondongos jovens, podem infectá-los produzindo o desenvolvimento de imunidade. 3. Após instilação na córnea escarificada de camondongos jovens, virus neurotrópicos Francês, Asibi e, talvez de vacina, podem produzir infecção. Com a córnea íntegra, no entando, não foi possivel infectar camondongos. 4. virus neurotrópicos Francês, Asibi, de vacina, Asibi Egg I e Egg III introduzidos no estômago, podem infectar camondongos jovens, matando-os com encefalite ou imunizando-os. 5. É possivel infectar camondongos de 0-6 dias de idade por simples deposição de virus ou esfregando a suspensão na pele íntegra e escarificada.

Suscetibilidade de pintos ao virus amarílico neurotrópico

1. O virus neurotrópico Francês pode ser transferido em série de cérebro de pinto, sem modificações essenciais no comportamento do virus em camondongos e pintos. 2. Pintos são suscetiveis à inoculação de virus por via intracerebral, intraritoneal e intradérmica, evidenciando virus circulante e desenvolvimento de imunidade, em alta percentagem, para os inoculados nos primeiros dias de nascidos. A presença, porem, de virus no sangue varia na razão inversa da idade. Não parece ser possível infetar pintos por via gástrica. 3. O virus pode ser encontrado, ocasionalmente, no pulmão, fígado, baço e rim; alguns dias depois é apenas isolado do cérebro, onde pode ser evidenciado até o 10.° dia post-inoculação intraperitoneal e até o 15.° dia depois de inoculação intracerebral, e talvez em data posterior. Não conseguimos, porem, isolar virus das feses. 4. Não parece haver diferença na suscetibilidade ao virus amarílico, em pintos com avitaminose B. 5. Anticorpos são evidenciaveis no soro em media 10 a 11 dias após inoculação intraperitoneal e intracerebral, sendo possível isolar ao mesmo tempo, virus do cérebro. 6. A idade tem influencia nítida no desenvolvimento da imunidade, em pintos inoculados por via intraperitoneal. 7. A multiplicação e circulação de virus após inoculação intradérmica de 50 a 160 D. M. M., torna possível a hipótese de mosquitos infectados difundirem o virus entre pintos e talvez a outras aves, com poucos dias de idade.

Subsídio ao melhor conhecimento do tifo exantemático neotrópico no Brasil: presença do virus no leite

In articles, already published, we have proved that the strain V. B. of Brazilian virus, goes through the placenta (Macacus rhesus) (1) and the apparently normal gastro-intestinal tube (1934-1937) (Canis familiaris) (2). Today we present the idea that the Brazilian virus can reach the milk of an animal even when the latter has only the unapparent disease. In former articles (**), we have shown that the goat (Capra hircus) can be an excellent reservoir of Brazilian virus, having the strain V. B. in its blood and presenting a Weil Felix reaction high and in “group”, with the disease unapparent. When the goats are bred in the laboratory, and even in some foci of the disease, they give a negative Weil Felix, being zero for all the nine strains of Proteus. In the interior of Brazil, in many localities, goats substitute cows, in supplying milk for children and adults, and in some districts goat’s milk is considered superior to cow’s milk, possessing marvellous qualities for men, women an children. Having proved, now, that goat’s milk can contain the virus even when the animal presents nothing clinically, and having also shown that this virus goes through the digestive tube apparently sound, it is easy to understand how infants-in-arms, that is, only a few months old, living in strictly domestic surroundings, can contract the disease; we have many such cases on record. Protocol of the experiments: Goat nº 2, white, January 1948. This animal had been inoculated with the V. B. strain of the Brazilian virus in June 1947, via intra-peritoneal, presenting nothing then, not even a feverish reaction. On that occasion it was not possible to isolate the virus of the blood, although the Weil Felix reaction was positive, high and in “group”. Now January 17, 1948, seven months later, the same animal was reinoculated with a semple of virus V. B. in the same manner (intra-peritoneal) two days after bringing forth two sturdy kids. The virus V. B. was obtained from guinea-pig n. 7170 whose thermic graph was as follows: Temperatura – 38,8 – 39,1 – 39,5 – 39,4 –39,8 – 40,4 – 40,2 – 40,1 - + Necropsy – Typical lesions. The spleen weighed 5 grammes. With 3c.c. of emulsion from the nervous system of this guinea-pig, we inoculated not only the goat, as also two guineapigs, number 14 and number 5. The following is the thermic graph of one: - Guinea-pig n. 14 – 38,9 – 39,1 – 39,2 – 39.2 – 40,7 – 41,0 – 40,5 – 40,4 – 40,1 - + Typical lesions. Guinea-pig n. 2 presented the following thermic graph after the infective inoculation: - 39,5 – 39,7 – 39,7 – 39,7 – 39,5 – 39,3 – 39,5 – 39,5 – 39,5 – etc. Clinically, this animal presented nothing unusual, feeding well and suckling the kids normally. The Weil Felix reaction was positive, in “group” high very similar to the reaction obtained in June 1947, with the first infective inoculation. On the third, fourth, fifth, sixth and seventh day after the infective inoculation, we took milk from the goat and inoculated male guinea-pigs via intra-celular and via intra-peritoneal, giving 5 c.c. to each animal. Guinea-pig n. 4663, inoculated with 5 c.c. of milk, via intra-muscular, taken on the third day of the infectaive inoculation, presented the following thermic graph: - 38.8 (*) – 39,1 – 39,0 – 39,1 – 40,1 – 40,1 – 40,8 (**) – 40,8 – Killed – Typical deisions (***). The virus V. B. of this goat, circulated naturally in the blood up to the third day, having passed into the milk, producing nothing in the kids, on account of the natural resistance of these animals to the disease. The Weil Felix reaction and that of Widal for the Burcellas suis, abortus and militensis were negative for the goat and the kids. It is remarkable that, even with inoculation of the living virus after a period of seven months we cannot get a real and absolute immunity of sensitive animals. We shall return to this subject later. The hart Mazama simplicicornis may be a carrier of the virus in Brasil. The experimental serum against the virus of Exanthematic neotropical typhus has not protected guinea-pigs.

RS virus diagnosis: comparison of isolation, immunofluorescence and enzyme immunoassay

Two techniques for rapid diagnosis, immunofluorescence (IFAT) and enzyme immunoassay (EIA), have been compared with virus isolaion in tissue culture for the detection of respiratory syncytial virus (RSV) in specimens of nasopharyngeal secretions. The specimens were obtained from children under five years of age suffering from acute respiratory iliness, during a period of six months from January to June 1982. Of 471 specimens examined 54 (11.5%) were positive by virus isolation and 180 (38.2%) were positive by immunofluorescence. The bacterial contamination of inoculated tissue cultures unfortunately prevented the isolation of virus from many samples. Specimens from 216 children were tested to compare enzyme immunoassay and immunofluorescence. Of these 60 (27%) were positive by EIA and 121 (56%) were positive by IFAT. Our results suggest that the EIA technique although highly specific is rather insensitive. This may be because by the time these tests were done the originl nasopharyngeal secretions were considerably diluted and contained more mucus fragments than the call suspension used for IFAT. Of the three techniques, IFAT gives the best results although EIA may be useful where IFAT is not possible.

An outbreak of dengue virus at Rio de Janeiro - 1986

Dengue virus type 1 has been isolated in Aedes albopictus cell strain, from sera of patients living in the Nova Iguaçu county, by Rio de Janeiro. The clinical picture was characterized by fever, headache, retrobulbar pain, backache, pains in the muscles and the joints and prostration. Studies in paired sera confirmed the presence of recent infection by dengue virus type 1. The outbreak reached adjacent areas, including Rio de Janeiro city (May, 1986).

Isolation and antigenic characterization of human immunodeficiency virus (HIV) in Brazil

A retrovirus infecting a Brazilian AIDS patient was isolated and characterized in terms of its reactivity with sera from individuals infected with human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2). The Western blot analysis revealed that the Brazilian isolate is very similar to the well characterized HIV-1 strain. The serum of the patient from whom the virus was isolated did not react with the 140 kDa envelope glycoprotein specific for HIV-2.

Jatobal virus antigenic characterization by ELISA and neutralization test using EIA as indicator, on tissue culture

A virus antigenic characterization methodology using an indirect method of antibody detection ELISA with virus-infected cultured cells as antigen and a micro virus neutralisation test using EIA (NT-EIA) as an aid to reading were used for antigenic characterization of Jatobal (BeAn 423380). Jatobal virus was characterized as a Bunyaviridae, Bunyavirus genus, Simbu serogroup virus. ELISA using infected cultured cells as antigen is a sensitive and reliable method for identification of viruses and has many advantages over conventional antibody capture ELISA's and other tests: it eliminates solid phase coating with virus and laborious antigen preparation; it permits screening of large numbers of virus antisera faster and more easily than by CF, HAI, or plaque reduction NT. ELISA and NT using EIA as an aid to reading can be applicable to viruses which do not produce cytopathogenic effect. Both techniques are applicable to identification of viruses which grow in mosquito cells.

Prevalence of human T cell leukemia virus-I (HTLV-I) antibody among populations living in the Amazon region of Brazil (preliminary report)

Forty-tree (31.4%) out of 137 serum samples obtained from two Indian communities living in the Amazon region were found to be positive for HTLV-I antibody, as tested by enzyme-linked immunosorbent assay (Elisa). Eighty-two sera were collected from Mekranoiti Indians, yielding 39% of positivity, whereas 11 (20.0%) or the 55 Tiriyo serum samples had antibody to HTLV-I. In addition, positive results occurred in 10 (23.2%) out of 43 sera obtained from patients living in the Belem area, who were suffering from cancer affecting different organs. Five (16.7%) out of 30 Elisa positive specimens were also shown to be positive by either Western blot analysis (WB) or indirect immunogold electron microscopy (IIG-EM).