12 café aula 01 - dr. vicente vaz - novagripe

Influenza A H1N1

Hospital Universitário Oswaldo CruzFaculdade de Ciências Médicas

Universidade de pernambucoVicente Vaz

abril/2010

Introdução 25 de abril – Emergência de Saúde Pública de

Importância Internacional (ESPII) Gabinete Permanente de Emergência em Saúde

Pública (GPESP) no CIEVS da SVS 11 de junho a OMS declarou estado pandêmico

(Fase 6)sem restrições ao comércio ou trânsito internacional

23 de junho o MS recomenda que a população de maior risco de complicações adiem viagem para os países de transmissão sustentada (México,EUA, Canadá, Chile, Argentina, Austrália e Reino Unido)

Influenza suína

Sobre a influenza:

• Agente etiológico: Vírus tipo A(H1N1), classificada como (A/CALIFORNIA/04/2009).

• Transmissão: pessoa a pessoa, principalmente por meio da tosse ou espirro e secreções respiratórias de pessoas infectadas. Segundo a OMS, não há registro de transmissão desse novo subtipo por ingestão de carne suína e produtos derivados.

• Período de incubação: 1 a 7 dias

Pandemias de Influenza no século 20

1957: “Gripe Asiática” A(H2N2)

1968: “Gripe de Hong Kong” A(H3N2)

25 a 100 milhões de

mortes

Credit: US National Museum of Health and Medicine

1-4 milhões de

mortes

1-4 milhões de

mortes

1918: “Gripe espanhola” A(H1N1)

2009:Gripe A

confirmados16.455 óbitos

Imprevisibilidade da atual pandemia

• O candidato mais provável era o da influenza aviária e o causador foi um rearranjo de vírus da influenza aviária + influenza suína + influenza humana

• A região inicialmente acometida seria a Ásia com seus grandes mercados de animais vivos e iniciou justamente na América do Norte

• A pandemia teve um início com vários óbitos em jovens previamente saudáveis e havia o prenúncio de um contágio mais fácil o que acabou por não se confirmar

Situação nos Estados Unidos desde abril 2009

• From the beginning of the pandemic in April 2009 until Feb. 13, 2010, the CDC estimates there were:

• * Between 42 million and 86 million H1N1 swine flu cases. Mid-range estimate: 59 million cases.

• * Between 188,000 and 389,000 H1N1 swine flu hospitalizations. Mid-range estimate: 265,000 hospitalizations.

• * Between 8,520 and 17,620 H1N1 swine flu deaths. Mid-range estimate: 12,000 deaths.

Situação atual nos Estados Unidosentre janeiro/fevereiro 2010

• 2.000.000 de casos

• 18.000 internamentos

• 310 óbitos

Hospitalizações em 2010

Óbitos em 2010

Isolamento de vírus influenza no Brasil (309.204 amostras)

• 71,4% Influenza pandemica A H1N1 2009

• 2,6% Influenza A sazonal H1N1

• 7,6% Influenza A sazonal H3N2

• 1,9% Influenza B

• 16,5% Influenza não subtipada

According to WHO, the majority of 2009 H1N1 influenza isolates tested worldwide remain sensitive to oseltamivir, an antiviral medicine used to treat influenza disease. Worldwide, 220 2009 H1N1 isolates tested have been found to be resistant to oseltamivir – 54 of these isolates were detected in the United States.

Resistência ao Oseltamivir

Vacina

Cronograma

Three Studies Demonstrate the Safety and Efficacy of Pandemic H1N1 Flu Vaccine

Summary and Comment by Bruce Soloway, MD

Published in Journal Watch General MedicineJanuary 21, 2010

Results are in from studies in the U.S., China, and Hungary.

Copyright © 2010. Massachusetts Medical Society. All rights reserved.

http://general-medicine.jwatch.org/

http://www.jwatch.org/misc/copyright.dtl

http://www.mms.org/

Covering

• Plennevaux E et al. Immune response after a single vaccination against 2009 influenza A H1N1 in USA: A preliminary report of two randomised controlled phase 2 trials. Lancet 2010 Jan 2; 375:41.

• Liang X-F et al. Safety and immunogenicity of 2009 pandemic influenza A H1N1 vaccines in China: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2010 Jan 2; 375:56.

• Vajo Z et al. Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the 2009–10 influenza season: A multicentre, randomised controlled trial. Lancet 2010 Jan 2; 375:49.



http://www.mms.org/

Background

• An estimated 100 million doses of 2009 pandemic influenza A/H1N1 flu vaccines have been administered worldwide since September 2009.

• Three new reports, containing data previously available only to regulators, provide important information on the safety and efficacy of these vaccines.

• All vaccines used in these studies were inactivated injected vaccines, produced from a single H1N1 strain recommended by the World Health Organization.



http://www.mms.org/

The Research

• In a randomized U.S. study, 1300 healthy people received one of three formulations of H1N1 vaccine or placebo.

• At baseline, 20% to 30% of adults and relatively few children had protective levels of H1N1 antibody; 21 days after vaccination, seroprotection rates were 92% to 100% in adults and 45% to 69% in children.



http://www.mms.org/

The Research

• Chinese investigators randomized nearly 13,000 people to receive two doses (21 days apart) of one of eight H1N1 vaccine formulations or placebo.

• At baseline, few participants had protective H1N1 antibody levels; 21 days after first vaccination, seroprotection rates were 56% to 88% in children younger than 12 and 54% to 98% in older people.

• After second vaccination, seroprotection rates rose to 93% to 99% and 83% to 100%, respectively.



http://www.mms.org/

The Research

• In Hungary, researchers randomized 355 adults without detectable H1N1 antibodies to receive single injections of a low-dose H1N1 vaccine, with or without simultaneous trivalent seasonal flu vaccination.

• After 21 days, seropositivity rates were about 70% in both groups.



http://www.mms.org/

The Research

• In the two placebo-controlled studies, seroprotection rates essentially were unchanged in placebo recipients, and low-dose immunizations generally were as effective as higher doses in all but the oldest adults.

• In all three studies, adverse effects were mild and consisted primarily of injection-site tenderness and low-grade fevers.



http://www.mms.org/

Comment

• Taken together, these studies suggest that various H1N1 vaccines, given according to current recommendations (1 dose for adults and 2 for children), are safe and effective and that a low-dose immunization strategy can optimize vaccine distribution without compromising efficacy.

• Perhaps these reports will quell the skepticism and fear with which many patients have greeted the rapid deployment of these novel vaccines.



http://www.mms.org/

About Journal Watch

• Journal Watch helps physicians and allied heath professionals save time and stay informed by providing brief, clearly written, clinically focused perspectives on the medical developments that affect practice.

• Journal Watch is an independent, trustworthy source, from the publishers of the New England Journal of Medicine.

• These slides were derived from Journal Watch General Medicine.

• The best way to stay informed with Journal Watch, is through our alerts. To sign up, visit the My Alerts page.



https://secure.jwatch.org/ecom/common/my_alerts.aspx


http://www.mms.org/

Incidence and Case Fatality Rates of Novel 2009 Pandemic A/H1N1 Influenza in England

Summary and Comment by Paul S. Mueller, MD, MPH, FACP

Published in Journal Watch General MedicineJanuary 14, 2010

H1N1 influenza incidence was highest among children, but H1N1-associated mortality was highest among elders.




http://www.mms.org/

Covering

• Donaldson LJ et al. Mortality from pandemic A/H1N1 2009 influenza in England: Public health surveillance study. BMJ 2009 Dec 10; 339:b5213. (http://dx.doi.org/10.1136/bmj.b5213)



http://www.mms.org/

Background

• During April 2009, novel pandemic A/H1N1 influenza virus began causing illness in the U.K. In this study, investigators used data from a mandatory reporting system, primary care surveillance networks, and a national phone- and Internet-based pandemic influenza service to estimate H1N1 incidence and influenza-associated mortality in England.



http://www.mms.org/

The Research

• Between June 1 and November 8, 2009, an estimated 540,000 cases of H1N1 influenza occurred, and 138 confirmed deaths from H1N1 influenza were reported, for a case fatality rate of 26 per 100,000.

• Incidence and case fatality rates, however, varied by age.

• Children (age range, 5 to 14 years) had the highest estimated incidence rate and the lowest case fatality rate (11 per 100,000), whereas elders (age, ≥65) had the lowest estimated incidence rate and highest case fatality rate (980 per 100,000).

• For infants and children (age, ≤14 years), adolescents (age range, 15–24), adults (age range, 25–64), and elders (age, ≥65), actual numbers of deaths were 29, 17, 66, and 26, respectively.



http://www.mms.org/

The Research

• Among those who died, 88 (64%) had severe underlying diseases before contracting H1N1 influenza; 108 (78%) had been prescribed antiviral drugs (but only 26 received such drugs within the recommended 48 hours of symptom onset).


Comment

• These data are entirely consistent with those reported from the U.S., including a higher incidence of H1N1 flu among children and a higher case fatality rate among elders (JW Gen Med Dec 31 2009).

• However, this study casts no new light on whether early treatment of H1N1 flu patients with neuraminidase inhibitors (i.e., oseltamivir [Tamiflu] or zanamivir [Relenza]) prevents serious morbidity or flu-related mortality.


Steroids Might Benefit Critically Ill Patients with Suspected H1N1 Influenza

Summary and Comment by Kristi L. Koenig, MD, FACEP

Published in Journal Watch Emergency MedicineJanuary 8, 2010

Combined treatment with antiviral agents and steroids led to significant improvements in organ function within 1 week.


Covering

• Quispe-Laime AM et al. H1N1 influenza A virus-associated acute lung injury: Response to combination oseltamivir and prolonged corticosteroid treatment. Intensive Care Med 2009 Nov 19; [e-pub ahead of print]. (http://dx.doi.org/10.1007/s00134-009-1727-6)


Background

• Patients with severe 2009 pandemic influenza A (H1N1) virus infections who present with pneumonia might develop acute respiratory distress syndrome (ARDS).

• In a case series of 13 consecutive patients (mean age, 39) with suspected H1N1 influenza, severe hypoxia requiring ventilator support, and clinical sepsis, researchers prospectively evaluated response to treatment with a combination of oseltamivir and corticosteroids in addition to empiric antibiotics administered on admission to an intensive care unit (ICU) in Buenos Aires, Argentina.

• Patients with severe ARDS received methylprednisolone (1 mg/kg/day), and other patients received hydrocortisone (300 mg/day) for an average of 21 days.

• Most patients (62%) had vasopressor-dependent shock.


The Research

• Twelve of the 13 patients had significant improvements in pulmonary and other organ function by the seventh day of treatment and were subsequently extubated and discharged from the ICU.

• Five nondiabetic patients developed hyperglycemia requiring insulin.

• No patient experienced either gastrointestinal (GI) bleeding requiring transfusion or neuromuscular weakness.

• The mortality rate at 60 days was 15%.


Comment

• Steroids mitigate the inflammatory response that might be responsible for the high mortality from H1N1 influenza in young, otherwise healthy patients with strong immune systems who experience a cytokine storm.

• The promising results of this small nonrandomized study suggest that adding low- to moderate-dose steroids to the treatment of critically ill patients with suspected H1N1 influenza might be beneficial.

• However, such patients should be carefully monitored for deleterious effects of steroid treatment (i.e., hyperglycemia, GI bleeding, weakness, psychosis, aspergillosis, and avascular necrosis).

• Other treatments for critically ill patients with H1N1 influenza include intravenous peramivir and extracorporeal membrane oxygenation (JW Infect Dis Nov 4 2009 and JW Emerg Med Nov 13 2009).


Vacinação de profissionais de saúde nos EUA

• 2005 a 2007 – 40% para influenza sazonal

• 2010 - 67% para influenza sazonal

• 2010 – 37% para influenza A H1N1 PANDÊMICA

• 81% consideram a vacina sazonal segura

• 67% consideram a vacina A H1N1 PANDÊMICA segura

Gestantes e a nova gripe

•Pandemic 2009 Influenza A(H1N1) Virus Illness Among Pregnant Women in the United States

Vol. 303 No. 15, April 21, 2010JAMA. 2010;303(15):1517-1525

• 788 pacientes entre abril e agosto

• 30 óbitos (5% de todos os óbitos)

• 509 hospitalizadas

• 22,6% em UTI

• Tratamento iniciado 4 dias após início dos sintomas = 56,9% foram para UTI

• Tratamento iniciado nas primeiras 48 horas = 9,4% foram para UTI

• Mortalidade no primeiro grupo 29

• Mortalidade no segundo grupo 1

Informações recentes sobre gestantes

• Pandemic 2009 Influenza A(H1N1) Virus Illness Among Pregnant Women in the United States

• Alicia M. Siston, PhD; Sonja A. Rasmussen, MD; Margaret A. Honein, PhD; Alicia M. Fry, MD; Katherine Seib, BS; William M. Callaghan, MD; Janice Louie, MD; Timothy J. Doyle, MPH; Molly Crockett, MPH; Ruth Lynfield, MD; Zack Moore, MD; Caleb Wiedeman, MPH; Madhu Anand, MPH; Laura Tabony, MPH; Carrie F. Nielsen, PhD; Kirsten Waller, MD; Shannon Page, BS; Jeannie M. Thompson, MPH; Catherine Avery, CFNP; Chasisity Brown Springs, MSPH; Timothy Jones, MD; Jennifer L. Williams, MSN; Kim Newsome, MPH; Lyn Finelli, DrPH; Denise J. Jamieson, MD; for the Pandemic H1N1 Influenza in Pregnancy Working Group

• JAMA. 2010;303(15):1517-1525.

Vol. 303 No. 15, April 21, 2010

Continuação

• De agosto a dezembro houve 280 casos novos em gestantes com 165 internamentos em UTI e 56 óbitos

• Gestantes são 1% da população americana e representaram 5% dos óbitos por H1N1

• Imunização e uso precoce do oseltamivir são essenciais para minimizar os riscos

Obstet Gynecol. 2010 Apr;115(4):711-6.Maternal and neonatal outcomes after antepartum treatment of influenza with antiviral medications.

Greer LG, Sheffield JS, Rogers VL, Roberts SW, McIntire DD, Wendel GD Jr.

University of Texas Southwestern Medical Center, Department of Obstetrics and Gynecology, Parkland Health and Hospital System, Dallas, Texas 75235-9032, USA. [email protected]

OBJECTIVE: To review the maternal and neonatal outcomes after antepartum exposure to M2 ion channel inhibitors or oseltamivir to provide some guidance on the risk, if any, of antiviral medication during pregnancy. METHODS: This was a retrospective cohort study examining maternal and neonatal outcomes after antepartum exposure to antiviral therapy for influenza. We evaluated maternal characteristics, pregnancy outcomes, and fetal outcomes and compared them with our overall obstetric population.

RESULTS: Exposure to antiviral therapies (M2 ion channel inhibitors [n=104] compared with oseltamivir [n=135] compared with the control group [n=82,097]) during pregnancy was not associated with increased rates of preterm birth (7% compared with 10% compared with 6%, P=.190), premature rupture of membranes (23% compared with 16% compared with 22%, P=.154), gestational diabetes (4% compared with 8% compared with 6%, P=.388), or preeclampsia (6% compared with 1% compared with 4%, P=.209). Exposure was not associated with increased duration of hospital stay for mother or neonate. There were no differences in the incidence of minor malformations (19% compared with 15% compared with 22%, P=.101). Liveborn singletons without major malformations did not have differences in fetal weight (3,238+/-586 g compared with 3,281+/-642 g compared with 3,336+/-571 g, P=.186), need for intubation (2% compared with 0.8% compared with 1%, P=.552), intensive care nursery admission (3% compared with 3% compared with 2%, P=.418), or hyperbilirubinemia (12% compared with 9% compared with 8%, P=.282). Liveborn singletons had no grade 3 or 4 intraventricular hemorrhages, seizures, or neonatal deaths. Two preterm neonates exposed to different classes of medications had necrotizing enterocolitis (1.0% compared with 0.8% compared with 0.02%, P<.001). CONCLUSION: We found no evidence of an association between antepartum antiviral exposure and adverse outcomes. LEVEL OF EVIDENCE: II.

PMID: 20308829 [PubMed - in process]

Obstet Gynecol. 2010 Apr;115(4):711-6.Maternal and neonatal outcomes after antepartum treatment of influenza

with antiviral medications.

O que aprendemos?• Vírus influenza são imprevisíveis

• Máscaras cirúrgicas foram eficazes

• Planos de contingência são essenciais

• Condutas terapêuticas muito agressivas devem ser evitadas

• Conflitos de interesses com grupos econômicos devem ser monitorados

• Gripes são comuns mas não são infecções essencialmente benignas

• Gestantes são um importante grupo de risco

Obrigado

[email protected]

12 café aula 01 - dr. vicente vaz - novagripe

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