Experience of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017: advances and challenges. / Experiência do Comitê de Investigação de Óbitos por Arboviroses no Ceará em 2017: avanços e desafios.

OBJECTIVE: to describe the experience and preliminary results of the Arbovirus Death Investigation Committee in Ceará, Brazil, in 2017. METHODS: the Committee investigates and discusses all suspected cases of arbovirus deaths reported by the epidemiological surveillance service. RESULTS: a total of 443 suspected arbovirus deaths were reported, 220 (49.7%) of which were confirmed; of these, 88.2% were from chikungunya and 11.8% from dengue; the median age of chikungunya deaths was higher when compared to dengue (77 versus 56 years) and the time until death was also longer when compared to dengue (38 versus 12 days); median time for case closure was 54.5 days; in 2017, Ceará confirmed 80.4% of Brazilian chikungunya deaths. CONCLUSION: the investigation of deaths showed that CHIK viruses were responsible for the majority of arboviral deaths in the state of Ceará, in 2017.

Effect of Sindbis birus infection on survival of mice in the cold.

Mice infected with 10(9) plaque-forming units (PFU) of Sindbis virus 9 h prior to exposure to cold (5 degrees C) died more rapidly after entering the new environment than saline-injected control mice. The early deaths occurred in animals singly housed without bedding and only when food was withheld. Because deaths could be prevented by providing the infected animals with food, it was concluded that metabolic alteractions resulting from the virus infection were responsible for the deaths. As evidence, corticosteroid-inducible hepatic enzymes did not respond to hydrocortisone administration in virus-infected mice housed at 5 degrees C. Phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) was induced significantly in control mice held at 5 degrees C for 5 h, but failed to induce in infected mice in the cold. Tryptophan oxygenase (TO) (EC 1.13.11.11) activity was also induced in control mice at 5 degrees C, but was too low to be measured in livers of all infected mice including those exposed to cold. The conclusion that Sindbis virus-infected mice were unable to make the metabolic adjustments required for survival at 5 degrees C was further indicated by severe hypoglycemia and rapid drop in rectal temperature that occurred in infected mice after 5 h in the cold.

Emergence of a new arbovirus disease in Brazil. II. Epidemiologic studies on 1975 epidemic.

In April, 1975, an outbreak of human encephalitis caused by Rocio virus, a new flavivirus, occurred in the coastal region of southern São Paulo, Brazil. The epidemic started during the second half of March, 1975, and ended in June, 1975. A total of 465 cases with 61 deaths were recorded, and the overall attack rate was 15 per thousand population. The mortality rate was two per thousand inhabitants and the overall case-fatality rate was 13%. However, the case-fatality rate was markedly decreased when adequate hospital care was provided. The number of cases in the 15--30 years age group was higher than in the other age groups and the rate was higher in males than in females. Lack of evidence of person-to-person transmission, based on a study of families involved in the epidemic and on the antigenic relationship to other mosquito-borne flaviviruses, suggested that the virus was transmitted by a vector and that wild animals were involved in the virus cycle.

[2 aspects of immunity in experimental flavivirus infections]. / Dve storony immuniteta pri éksperimental'nykh flavivirusnykh infektsiiakh.

Experimentally, two aspects protective and damaging, of the immune response were demonstrated in the course of development of infection in mice inoculated with tickborne encephalitis (TBE) virus, Langat, yellow fever, dengue type 2 or West Nile viruses. The experiments were carried out in animals in which the functions of T- and B-lymphocytes, were temporarily inhibited with cyclophosphane (CP). It was demonstrated that the protective or damaging role of the immune response depended on the method of inoculation of the animals, the virus properties, and characteristics of the mouse strain. The conditions optimal for the development of immunopathological reactions in one infection (TBE) were not identical for those in another infection even when caused by an antigenically related virus (LANGAT). In mice of the AKR strain the possibility of producing a therapeutic effect upon treatment with CP of the animals inoculated with TBE virus was demonstrated.

Potentiation of langat virus infection by lead intoxication--influence on host defenses.

Pathogenesis was studied in mice with moderate levels of lead intoxication after Langat virus infection. Both lead chloride and lead nitrate increased mortality by 40--50%. This increase was associated with decreased in vivo interferon and neutralizing antibody synthesis. The increased mortality was associated with enhancement of viral growth in peripheral tissues as evidenced by early appearing and long-lasting high titer viremia following lead intoxication. This resulted in early penetration of blood brain barrier and led to much higher virus titers in the brain. The data strongly suggest that lead increased mortality following infection by complex means, the most important being the enhacement of encephalitogenic potential of Langat virus.

Adaptation studies with Ross River virus: laboratory mice and cell cultures.

Ross River virus, an Australian group A arbovirus, was adapted by serial passage to cell cultures and to day old mice. The results of titrations in mice of different ages allowed the comparison of virulence between different stocks. Passage in cell cultures depressed the virulence of virus while passage in mice raised the level of virulence. Clones of original virus populations revealed heterogeneity with respect to virulence but none of the 41 clones was as highly virulent as virus passed 10 times in mice. Clones selected in sequence during serial passage in mice indicated that adaptation proceeded by the overgrowth of variants of increasingly higher virulence, and that clones from relatively hhighly passaged s strains were still heterogeneous in virulence.

Adaptation studies with Ross River virus: retention of field level virulence.

Two field strains of Ross River virus (RRV) which differed in virulence for laboratory mice were maintained without detectable change in virulence when passaged alternately in Aedes aegypti mosquitoes and newborn mice. No biological mechanism or selection pressure was identified to explain this suppression of the usual change to higher virulence observed when RRV is passed serially in infant mice. The maintenance of initial virulence by alternating passages appears to be related to the fact that A. aegypti can be infected only if fed on mice during the period of peak viraemia and that at this time a sub-population of higher virulence may not be present in high enough infectivity to be represented in the mosquito's blood meal.

Effects of Newcastle disease virus (NDV) on infection of adult mice with the Thogoto-like Ar-126 arbovirus.

Inoculation of mice with Newcastle disease virus (NDV) alters the course of infection with the Thogoto-like arbovirus Tho-Ar-126. The Tho-Ar-126 content of liver, spleen, and lymph nodes was approximately 10 times greater in mice treated with NDV 24 h before infection; the mortality was somewhat increased, but liver damage (as indicated by serum transaminase levels) did not seem to be potentiated. Lymphocytopenia was observed in NDV-inoculated mice, and in the spleen and lymph nodes the proportion of lymphocytes susceptible to lysis by anti-theta (a marker for thymus-derived lymphocytes) was markedly decreased in these animals. This suggests that NDV potentiates infection by Tho-Ar-126 through its action on thymus-derived lymphocytes.

Influence of certain immunodepressants on experimental flavivirus and enterovirus infections in mice.

The effects of cyclophosphamide and 1,3-(piperidinomethyl)-5-phenyl-5-ethylbarbituric acid on certain flavi- and enterovirus infections in mice were studied. Differential enhancement of mortality rates after extraneural and, less markedly, intracerebral virus inoculation was noted. While depression of humoral and/or cell-mediated immunity is considered to be responsible for the effects observed in flavivirus infections, impaired function of the reticuloendothelial system seems to contribute mainly to the potentiation of Mengo virus infection by the immunodepressants used.

The influence of hyperthermia and poly I:C on Semliki Forest virus infection in mice.

In mice infected intraperitoneally with 10(3) intracerebral suckling mice LD50 of Semliki Forest virus an additive reduction in mortality was found when the protective effect of hyperthermia and synthetic polyriboinosinic and polycytidylic aicds (Poly I:C) was combined. The effects of the two treatments seem to be independent of each other as Poly I:C was found to have no influence on the body temperature of mice, nor did hyperthermia increase the amount of interferon induced by Poly I:C.