Zika virus epidemic in Brazil. I. Fatal disease in adults: Clinical and laboratorial aspects

Abstract

Background Zika virus (ZIKV) was first detected in Brazil in May 2015 and the country experienced an explosive epidemic. However, recent studies indicate that the introduction of ZIKV occurred in late 2013. Cases of microcephaly and deaths associated with ZIKV infection were identified in Brazil in November, 2015. Objectives To determine the etiology of three fatal adult cases. Study design Here we report three fatal adult cases of ZIKV disease. ZIKV infection in these patients was confirmed by cells culture and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and by antigen detection using immunohistochemical assay. Samples of brain and other selected organs taken at autopsy from three patients were also analyzed by histopathological and immunohistological examination. Results The first patient, a 36-year-old man with lupus and receiving prednisone therapy, developed a fulminant ZIKV infection. At autopsy, RT-qPCR of blood and tissues was positive for ZIKV RNA, and the virus was cultured from an organ homogenate. The second patient, a previously healthy female, 16 years of age, presented classic symptoms of Zika fever, but later developed severe thrombocytopenia, anemia and hemorrhagic manifestations and died. A blood sample taken on the seventh day of her illness was positive RT-PCR for ZIKV RNA and research in the serum was positive for antinuclear factor fine speckled (1/640), suggesting Evans syndrome (hemolytic anemia an autoimmune disorder with immune thrombocytopenic purpura) secondary to ZIKV infection. The third patient was a 20-year-old woman hospitalized with fever, pneumonia and hemorrhages, who died on 13 days after admission. Histopathological changes were observed in all viscera examined. ZIKV antigens were detected by immunohistochemistry in viscera specimens of patients 1 and 3. These three cases demonstrate other potential complications of ZIKV infection, in addition to microcephaly and Guillain-Barre syndrome (GBS), and they suggest that individuals with immune suppression and/or autoimmune disorders may be at higher risk of developing severe disease, if infected with ZIKV.

Characterization of the Zika virus two-component NS2B-NS3 protease and structure-assisted identification of allosteric small-molecule antagonists

“…The risk of ZIKV infection has historically been restricted to tropical/subtropical regions, but the virus has now spread into the Southern US. Recent studies have demonstrated that ZIKV infects and is toxic to human neural precursors; however, the molecular mechanism is not precisely known (Azevedo et al, 2016; Cugola et al, 2016; Li et al, 2016; Mlakar et al, 2016). …”

Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques

“…A small number of severe human clinical cases have reported thrombocytopenia, anemia, and hemorrhagic manifestations detected by serum chemistry and complete blood count (CBC) tests (38). To investigate ZIKV-associated disease in the absence of outward clinical signs, serum chemistry panels, CBCs, body temperature, and body weight data were evaluated (S1 and S2 Figs) .…”

Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer?

“…What started as yet another tropical disease has ended up being a much more serious threat because of its association with neurologic complications. Based on our knowledge so far, an ideal ZIKV prophylactic or therapeutic agent will be required to satisfy various criteria such as,Prevent ADE for ZIKV infection in DENV-immune individuals and vice versa.Not increase the chances of developing/worsening GBS, which means that the use of live-attenuated vaccines may be ruled out until the cause of GBS is identified.Safe for use in pregnant population and immune-compromised individuals especially because persons with immunosuppression or autoimmune disorders are at a higher risk of developing severe disease (Azevedo et al 2016). …”