Dengue Chikungunya Zika e Febre Amarela no...
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Dengue, Chikungunya, Zika e Febre Amarela no TMO
Marcia Garnica
Professora Adjunta
Faculdade de Medicina, Universidade Federal do Rio de Janeiro
Complexo Hospitalar de Niterói
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Pontos principais
• Brasil – Epidemia tripla desde 2015 – quadrupla desde 2016
• Dengue (DENV)–
• Chikungunya (CHKV)–
• Zika (ZIKV) –
• Febre Amarela (YFV) _
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Pontos principais
• Brasil – Epidemia tripla desde 2015 – quadrupla desde 2016
• Dengue (DENV)–
• Chikungunya (CHKV)–
• Zika (ZIKV) –
• Febre Amarela (YFV) _
No Transplante de medula...
Epidemiologia atualManifestações da infecção em receptores
de TMORisco de Transmissão pelo enxerto /
transfusao
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Introdução
• Brasil• Alta incidência de doenças veiculadas por mosquitos
• Áreas endêmicas e epidêmicas
• Grande parte da população em risco de aquisição de doença
• TMO – grande numero de transplantados em situação epidemiológica de risco
Machado et al. Blood Advances, 2017
Metsky et al. Nature 2017
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Vetor> DENV, CHKV, ZIKV, Mayaro, YFV
BRA desde 2015 –epidemia tripla*
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Dengue (DENV) e TMO
• OMS – 5 a 100 milhões de casos de DENV/ano
• Brasil: maior numero de casos nas Américas
• 95% dos casos por aquisição via vetor
• 3 casos assintomáticos : 1 sintomático
• Caso de transmissão via produto SCT (2 casos – Porto Rico, outro infecSri Lanka)
Sabino EC et al. J Infect Dis 2016; 213:694–702Bush et al. JID 2016
Darrigo et al. Curr Infect Dis Rep 2018
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Notificacao pelo doador após a coleta de HSCT!!!
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Manifestação clinica DENV
• Assintomaticos (~70%)
• 3 fases: febril, critica e convalescência
• Febre, mialgia, trombocitopenia, rash
• TMO ~ imunocompetente• Viremia mais longa
• Resposta imune T suprimida – poucos casos que evoluem para formas graves?
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Guideline, WHO
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DENV e TMO – Serie Brasileira
• Mortalidade series internacionais ~ 40%
• Serie Brasileira:• Sintomas prolongados - > 15 dias
• Menor frequência de artralgia (Corticoesteroides?)
• 40% casos mais graves – necessidade de hemoderivados (80%)
• Viremia por 30 dias vs. 4 – 7 dias no imunocompetente
Pereira et al. TID, 2017
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Fonte principal de infecção por DENV em TMO – via mosquito em região com circulação viral
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ZIKV
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ZIKV vs. DENV and CHKV
• 80% asymptomatic diseases
• Blood or organ donors may not know they have been infected.
• Sexual transmissible infection
• Cases of Zika virus transmission through platelet transfusions have been documented in Brazil.
• Viremia vs. Persistence of virus in tissues
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ZIKV
• Viremia in plasma 1 – 2 weeks (95% clearance in 19 days)
• Whole blood – 5 – 58 days
• Zika RNA persist in semen > 188 days
• Blood vs. Transplantation and tissues
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Guillain-Barré syndrome (GBS) after matched unrelated HSCT in a pediatric patient.
Serological assays strongly suggested a recent ZIKV infection, although infection by DENV or
co-infection with both viruses cannot be ruled out.
Provavel exposicao no Maranháo:
13 – 3 dias após GBS
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Chikungunya
• African language meaning "that which bends up" or "stooped walk"
• Transmission of chikungunya via blood products (France): nurse exposed to blood a patient infected in Réunion
• Blood products ~ organ transplantation —
• In theory, the virus could be spread through a blood transfusion: there are no known reports until now.
• Transmission via organ transplantation could also occur since chikungunya viremia (may exceed 109 RNA copies/mLplasma) is likely prior to onset of symptoms
• Chikungunya virus infects the human cornea and might be transmitted via corneal grafts – alredy docummented
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Chikungunya
• Majority are symptomatic.
• Incubation period 3–7 days (range, 1–12 days).
• Viremia is likely prior to onset of symptoms
• Acute onset of fever and polyarthralgia - typically resolve within 7–10 days.
• Rare complications: neonates exposed intrapartum, older adults (e.g., > 65 years), and persons with underlying medical conditions (e.g., hypertension, diabetes, or cardiovascular disease).
• Some relapses of rheumatologic symptoms (e.g., polyarthralgia, polyarthritis, tenosynovitis) months following acute illness.
• Mortality is rare and occurs mostly in older adults.
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Febre Amarela
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Ciclo silvestre e urbano - YFV
MG e SP
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Manifestações clinicas - YFV
• Most people will not have symptoms.
• Some people will develop yellow fever illness with initial symptoms including:• Sudden onset of fever, Chills, Severe headache, Back pain• General body aches• Nausea, Vomiting• Fatigue (feeling tired)
• Most people with the initial symptoms improve within one week.
• A few people will develop a more severe form of the disease.• Severe symptoms include: High fever, Yellow skin (jaundice), Bleeding, Shock, Organ failure
• Among those who develop severe disease, 30-60% die.
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Febre + Rash; investigação de arbovirose(DENV; ZKV; CHKV; YFV*) vs. GVHD
Pereira et al. TID, 2017Machado et al. Infect Dis Clin N Am, 2012
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DENV vs. CHKV vs. ZIKV vs. YFV*
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• February - May 2016, 9 of the 26 patients (34.6%): DENV (3 cases), ZIKV (4 cases), and CHKV (2 cases)
• Thrombocytopenia (55%) was the most frequent complication.
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Guideline, WHO
Diagnostico: Fase aguda: - Deteccao de antígeno- PCR- NAT* – positivo mais de 1 semana
Após a fase aguda: sorologia
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Exemplo..
• Investigação em fase inicial em um Centro de TMO:• Zika: PCR sangue ou urina, LCR
• Chikungunya: PCR
• Dengue NS1, PCR
• Após a fase inicial:• Zika: IgG, IgM
• Chikungunya: IgG, IgM
• Dengue: IgG, IgM
• Febre Amarela: IgG, IgM
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Tratamento DENV, ZIKV, CHIKV, YFV
• Suporte
• Não há tratamento especifico até o momento
• Acompanhamento de complicações
• Guias de tratamento de suporte – orientação nos serviços de entrada (Emergência, UPA, etc) para náo haver atraso na identificação e inciodas medidas de suporte.
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DENV e Doação
• Historia de dengue não impede a doação se já houve resolução de sintomas • Sorologia – se positiva – fora do
período de viremia
Machado et al. Infect Dis Clin N Am, 2012
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• Samples from 16 241 donations
• Dengue IgM-positive/ IgG-positive: 6.2% incidence
• 0.5% viremic (DENV-4 RNA +)
• Viremia - 9.1-day period (95% CI, 4.4–13.9 days)
• 1 RNA-positive donation was identified per 800 DENV cases.
• Viremic donations will be rare relative to clinical disease cases
• 16 viremic units infused – 6 possible TTIs (clinically ~uninfectect controls)
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NAT – 3% positivo
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Notas técnicas Anvisa
• Critérios Triagem doadores de sangue - CHKV e ZIVK (19/08/2016)• CHKV – inaptos por 30 dias (viajantes para região endêmica, moradores, casos
confirmados)*
• ZIKV – inaptos por 30 dias se:• doença documentada
• relação sexual com parceiro homem teve documentação de ZIKV nos últimos 90 dias
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Febre Amarela (YF) e TMO
• Não há relatos de transmissão de YFV por Órgãos/tecidos até o momento• Infectados por YFV prévios – inaptos por 6 meses
• Residentes em área de risco não vacinados – inaptos
• Viajantes em área de risco – inaptos por 30 dias
• Relato de transmissão de vírus vacinal por hemocomponentes*
Atenção a janela de doação após a vacinação! – 4 semanas
Sabino EC et al.. 2015;1–10.CDC. MMWR 2010;59
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Pontos principais – Conclusões
• Brasil – Epidemia tripla desde 2015 + YFV em 2016
• Controle de vetores e medidas físicas contra exposicao (essencial)
• Alto índice de suspeição – RASH + Febre = investigação
• DENV e CHKV – provável baixo risco de TTI
• Zika (ZIKV) – potencial risco de TTI • Relatos de casos mais graves pós TMO
• Febre Amarela (YFV) _ • Risco de TTI do vírus vacinal; evitar exposição a zonas com casos
documentados e medidas físicas