3-5 July 2019 Round Table: Homage Ricardo Galler HISTORY OF YELLOW - PowerPoint PPT Presentation

REGIONAL MEETING RIIP-AMERICAS 3-5 July 2019 Round Table: Homage à Ricardo Galler HISTORY OF YELLOW FEVER 334 Years Yellow Fever in Brazil: and continues causing epidemic Akira Homma Assessor Científico Senior Bio-Manguinhos/Fundação Oswaldo Cruz 1 Ministério da Saúde

Flavivirus Genome Organization Chambers et al. , 1990 2

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MOLECULAR ANALYSIS OF YF VACCINE STRAIN 4

COMPLETE NUCLEOTIDE SEQUENCE OF 17D AND 17DD STRAINS 5

THE MOLECULAR BASIS OF VIRAL ATENUATION AND ITS USE AS EXPRESSION VECTOR 6

Yellow Fever - Origin • Yellow Fever vírus harbored in Monkeys - West Africa • First YF epidemic recorded in Yucatan in 1648, suggestion that mosquito vector and vírus introduced during the slave trade 371 years ago • The term “ yellow fever ” used first in 1750 – oubreak Barbados • 18th Century – YF became a major problem for colonial settlements is the Americas 7

Yellow Fever - Origin • 1793 – YF epidemic in Philadelphia, 10% of the populations died • 1878 – 13.000 deaths in Mississippi Valley • Throughout 18th and 19th centuries caused several epidemics/deaths in several regions in USA • USA, Spain, France, England, Italy, West Africa  Increase of navigation, slave trade, disseminated vector and vírus 8

Carlos Finlay and vector discovery • 1881, Carlos Finlay presented at the Cuban Royal Academy of Science the theory of mosquito transmission of Yellow Fever • 1900, Yellow Fever Commission – W. Reed, Carrol, Lazear & Agramonte, showed YF control through A. aegypti control • 1901, eradicated YF and vector from Cuba and lately from Panamá Canal • 1901, Reed & Carrol - experiments on human volunteers in Cuba, demonstrating the filterable agent transmited by A. aegypti – the 1st. demonstration of a virus causing disease 9

Yellow Fever – endemic regions Yellow Fever - 200,000 cases annualy and 30,000 deaths 10

YF in Americas and 334 years in Brazil, since 1685 Year/period Type of event Event Geographical location Probable origin of yellow fever in Africa, 3000 BP Africa according to modern sequence analysis of the viral genome. [11] Disease outbreaks similar in signs and symptoms to yellow fever are reported 1494 West Africa Epidemic from Canary islands and Cape Verde off the coast of Africa, and sometimes in coastal countries such as Gambia, and Sierra Leone. [2] The first definitive outbreak of yellow fever in 1647 Barbados Epidemic the Americas happens in the island of Barbados An outbreak is recorded by Spanish colonists in the Yucatán Peninsula, where the indigenous Mayan people call the 1648 Mexico Epidemic illness xekik ("blood vomit"). Yellow fever is found in Mayan manuscripts describing an outbreak of the disease in the Yucatan peninsula. [7][3] Yellow fever is brought in ships to and 1649 Gibraltar Epidemic from Africa and the West Indies, to Gibraltar. [2] The first yellow fever outbreak in English- 1668 United States Epidemic speaking North America occurs in New York City. [3] English colonists in Philadelphia and the 1669 major outbreaks of yellow fever. [ citation needed ] United States Epidemic French in the Mississippi River Valley record Bethell, Leslie. Colonial Brazil. Cambridge Brazil suffers its first yellow University Press 1987 1685 fever epidemic, Epidemic in Recife . [12] 11

Yellow Fever in Brazil – epidemiological and control 1850 1876 1942 1685 1907 1903 1958 1937 1849 1873 1903 - Oswaldo Cruz assigned by Rodrigues Alves as Director of Health Services 1849 – Introduction of YF in Rio de Janeiro - Adopt Carlos Finlay theory of Aedes aegypti vector transmission 1685 – Recife - ship from Green Cape, via Santo Domingo – 1907 - Eradication of the urban vector Aedes aegypti and 1942 – Sena Madureira, Acre – the last urban YF case in Brazil has erradicated Aedes aegypti in two 1876 - 3,476 death 1873 – 3,659 death 1850 – 266,000 inhabitants 1937, YF vaccination starts in Brazil Brasil – 69 years without urban YF cases occasions – 1958 and 1973 - Establish YF Prophylaxis Service (YFPS) : brought by USA Navarre ship, coming from dissemination of epidemic waves with thousand of deaths. Yellow Fever from the city of Rio de Janeiro – 90,658 sick & 15,000 death . Mosquito-kill Brigade; Sulphur and píretro; Bahia with sick people Spread-out to other geographic regions . Isolation of sick people in São Sebastião Hospital; . YFPS adopt the Fire Corps procedures;

Elaborated by Possas et al, Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation Mem. Inst. Oswaldo Cruz vol.113 no.10 13

Brazil – Evolution of Risk areas, 1997 to 2008 1997 2008 Endemic Transition Potential risk YF immunization recommended Indene YF immunization not recommended Yellow Fever Risk Areas with recommendation for vaccination, 1997 to 2008 Fonte: SVS/MS. 14

Yellow Fever in Brazil 1 01/01/2019 to 21/05/2019 Human cases Epizooties in notified: 1239 NHP: 82 confirmed – 1157 notified 14 deaths 48 confirmed 305 under 367 under investigation investigations 410 not 790 discardeds determined 394 discarded Fonte: Ministério da Saúde, Informe n o 17 de 3 junho de 2019. 1 por município do local provável de infecção e/ou de ocorrência, no Brasil, entre as semanas epidemiológicas 01 e 20/2019. 15

Risk areas and vaccination coverage Regions recommended for YF Vaccination Vaccination coverage Brazil, 2007 a 2016** Brazil, 2017. ASRV, Área sem Recomendação de Vacinação Fonte: SIAPI/CGPNI * ACRV = Área Com Recomendação De Vacinação (3.529 municípios) ** fevereiro de 2017, preliminar 2007 a 2016 Fonte: SVS/MS COES 32 16/03/2017 Slide cedido pro Carla Domingues 16

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Yellow Fever cases in Brazil in recent years • July 2016 up to 07 february 2017 – 509 cases - 159 deaths • July 2017 up to 30 june 2018 – 7.518 cases notified – 5. 364 cases discarded – 718 in investigation – 1.376 cases confirmed – 483 deaths 18

Confirmed YF cases in 2019 19

Source: Possas et al, Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation Mem. Inst. Oswaldo Cruz vol.113 no.10 20

Elaborated by Possas et al, Yellow fever outbreak in Brazil: the puzzle of rapid viral spread and challenges for immunisation Mem. Inst. Oswaldo Cruz vol.113 no.10 21

YF 17 D vaccine strain - attenuation of Asibi strain December 1933. Minced tissue were inoculated with monkey sera 0 infected with Asibi strain 18 18 passages in minced mouse embryo tissue 76 58 passages in minced whole chick embryo 130 designated 17D strain 30/06/1927 190 114 passages using chick embryo without nervous tissues 195 begin the 17DD strain ASIBI virus, 204 Mahaffi & Bauer passages using chick embryo tissues without 221 54 passages head and spinal cord and normal monkey or human serum 222 in rhesus monkeys 225 1936 - At 227th and 229th passages – experimental vaccination in Rockefeller Foundation employees. Acceptable 227 tolerability, development of neutralizing antibodies

Monath, T. In Vaccine, Plotkin S. Orenstein W & Offit Paul, 2008

Yellow Fever Vaccine in Brazil • 1937 March - H. Smith brought 17D strain and started the vaccine production in Brazil – Henrique de Azevedo Penna, the Brazilian partner  One year later > 60.000 people vaccinated  Smith, Penna e Paoliello, concluded “ there exists a safe method for production of YF vaccine in large scale ”. -Bica, Alfredo, Anais Simpósio 50 aniversário da introdução da cepa 17 D no Brasil, 1988 Vaccination at Fazenda Pedra Preta, on Três Pontas, MG, August 15, 1937

Production and use of YF vaccine in Brazil • From 1937 to 1986 – 154.383.814 vacinated – Rodopiano de Oliveira, A. In Anais Simpósio 50 aniversário da introdução da cepa 17 D no Brasil, 1988 • From 1987 to 2018 – 693.427.980 doses supplied to the National Immunization Program • 2019 – 40.183.000 doses – 19.176.500 doses already delivered • CMO Libbs - 22 million doses annually • Derem/Bio-Manguinhos, 2011 25

Vacina FA – Exportation after WHO Pre-Qualification Total: 72 países  2001-2018 > 154.668.250 million of doses Africa 26 countries Asia America Central, 10 paíse America do Norte e Caribe 23 países. Oceania America do Sul 1 país 11 paises Source: Derem/Bio-Manguinhos, 2011 26

Adverse events YF 17DD vaccine  International data  Rare severe adverse events:  Viscerotropic events (0,3/100.000 doses);  Neurologic events (0,4/100.000 doses);  Anafilaxis (0,8/100.000 doses) Fonte: Hayes EB, 2007 Not indicated: allergic to egg components; imunocompromised; children < 9 meses; eldery >59 anos 27

Muito obrigada pela atenção !! Sandra.deotti@saude.gov.br 28

In memorian Dr Reinaldo Martins Menezes  Clinical studies  Pharmacovigilance  Yellow Fever Vaccine  Dose-response study  Duration of immunity dose- response 29

Obrigado! akira@bio.fiocruz.br http://www.bio.fiocruz.br/