PATOLOGIA DO APARELHO RESPIRATÓRIO Pneumonias Carlos Robalo Cordeiro

sintomas de Infecção.R.aguda sinais focais no exame objectivo CASO CLÍNICO O termo pneumonia, do ponto de vista etimológico, deriva da noção de infecção pulmonar por pneumococo- Streptococcus pneumoniae. Pneumonia todo o processo infeccioso dos espaços alveolares ou do parênquima pulmonar, com substituição do seu conteudo aéreo por células inflamatórias e secreções Ambulatório sintomas de Infecção.R.aguda sinais focais no exame objectivo queixas sistémicas ausência de outra explicação 7 Jornadas

sintomas e sinais de Infecção.R.aguda + alterações radiológicas CASO CLÍNICO Pneumonia Hospitalar sintomas e sinais de Infecção.R.aguda + alterações radiológicas In THORAX 2001, 56, (suppl4)- BTS GUIDELINES 2001 7 Jornadas

Classificação Classificação radiológica epidemiológica segmentares CASO CLÍNICO Classificação radiológica segmentares lobares intersticiais broncopneumonia histológica alveolares etiológica bacteriana virusal fúngica tipo de evolução agudas subagudas crónicas Classificação epidemiológica PAC PN/PH P. Imunodeprimido 7 Jornadas

Epidemiologia Maioria tratada em ambulatório CASO CLÍNICO Epidemiologia Maioria tratada em ambulatório 0- 42 % requerem hospitalização 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Epidemiologia Incidência 5- 11/ 1000/ ano UK 4 Milhões de casos/ano 60.000 mortes/ ano PAC é uma importante causa de mortalidade 4-12 % D. internados In THORAX 2001, 56, (suppl4)- BTS GUIDELINES 2001

Etiologia 30- 60 % impossível identificar CASO CLÍNICO Etiologia 30- 60 % impossível identificar agente etiológico varia consoante: - área geográfica - idade - patologias associadas DPOC Patologia CV DM Lar Alcoolismo CT 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Etiologia Streptococcus pneumoniae 20- 60 % CASO CLÍNICO Etiologia Streptococcus pneumoniae 20- 60 % Haemophilus influenza 3- 10 Chlamydea pneumoniae 5- 17 Vírus 2- 15 anaeróbios 6- 10 gram - 3- 10 S. Aureus 3- 5 L. Pneumophila 2- 8 M. Catarrhalis 1- 3 2700 cc Queda 3 s emanas antes de ir a cir In CHEST/115/3/ MARCH, 1999 7 Jornadas

Factores que aumentam o risco de infecção por agentes específicos Penicillin-resistant and drug-resistant pneumococci   Age > 65 yr   B-Lactam therapy within the past 3 mo   Alcoholism   Immune-suppressive illness   Multiple medical comorbidities   Exposure to a child in a day care center Enteric gram-negatives   Residence in a nursing home   Underlying cardiopulmonary disease   Recent antibiotic therapy Pseudomonas aeruginosa   Structural lung disease (bronchiectasis)   Corticosteroid therapy (> 10 mg of prednisone per day)   Broad-spectrum antibiotic therapy for > 7 d in the past month   Malnutrition Factores que aumentam o risco de infecção por agentes específicos In AJCCRM- ATS Guidelines

expectoração purulenta dor torácica pleurítica dispneia CASO CLÍNICO Clínica febre tosse expectoração purulenta dor torácica pleurítica dispneia alteração estado geral odinofagia mialgias náuseas/ vómitos exame objectivo auscultação palpação percussão ECD H BQ GSA Radiologia 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Diagnóstico clínica radiologia exame objectivo p. alveolar radiologia CASO CLÍNICO Diagnóstico clínica exame objectivo radiologia confirmação DX localização extensão complicações radiologia p. alveolar p. broncopneumónico p. intersticial 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Diagnóstico- radiologia CASO CLÍNICO Diagnóstico- radiologia padrão alveolar Imagem de condensação homogénea de limites mal definidos Broncograma aéreo Distribuição segmentar ou lobar padrão intersticial Opacidades lineares, reticulo-micronodular 2700 cc Queda 3 s emanas antes de ir a cir padrão broncopneumónico Distribuição segmentar Aspecto algodonoso e multifocal, podendo coalescer 7 Jornadas

Consolidação do lobo inferior direito

Diagnóstico Exmes laboratoriais Exame directo Cultura Hemograma CASO CLÍNICO Diagnóstico Exmes laboratoriais Exame directo Cultura Hemograma Bioquímica GSA Hemoculturas Serologia VIH Serologias específicas 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Pneumonia Típica // Atípica ??? CASO CLÍNICO Pneumonia Típica // Atípica ??? Apresentação clínico-radiológica diferente ? sobreposição de achados ? - AB b- lactâmicos ineficazes meios de diagnóstico específicos terapêutica diferente 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Mycoplasma pneumoniae Chlamydia pneumoniae Chlamydia psitacci CASO CLÍNICO Pneumonia Atípica etiologia: Mycoplasma pneumoniae Chlamydia pneumoniae Chlamydia psitacci Legionella pneumophila Coxiella burnetti 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

contexto epidémico/ epidemiológico manifestações extrapulmonares CASO CLÍNICO Pneumonia Atípica início mais gradual tosse irritativa contexto epidémico/ epidemiológico manifestações extrapulmonares mialgias conjuntivite exantema diarreia dor abdominal vómitos padrão radiológico intersticial dissociação clínico- radiológica 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Tratamento Estratificação de doentes Grupo 1 ambulatório sem factores modificadores Grupo 2 com doença cardio-pulmonar outros factores modificadores Grupo 3 D. Internados Grupo 4 D. Internados UCI In AJCCRM 2001, 163- ATS Guidelines

Grupo 1 Organisms Therapy Streptococcus pneumoniae CASO CLÍNICO Grupo 1 Organisms Therapy Streptococcus pneumoniae Advanced generation macrolide:    azithromycin or clarithromycin  or Doxycycline or  amoxicillin/clavulanate Mycoplasma pneumoniae Chlamydia pneumoniae Hemophilus influenzae Respiratory viruses Miscellaneous Legionella spp. Mycobacterium tuberculosis Endemic fungi 2700 cc Queda 3 s emanas antes de ir a cir Nova FQ In AJCCRM 2001, 163- ATS Guidelines 7 Jornadas

Grupo 2 Ambulatório Cardio pulmonar/ F. modificadores CASO CLÍNICO Grupo 2 Ambulatório Cardio pulmonar/ F. modificadores Organisms Therapy Streptococcus pneumoniae Mycoplasma pneumoniae Chlamydia pneumoniae Mixed infection (bacteria plus   atypical pathogen or virus) Hemophilus influenzae Enteric gram-negatives Respiratory viruses Miscellaneous Moraxella catarrhalis, Legionella spp.,   aspiration (anaerobes), Mycobacterium   tuberculosis, endemic fungi B-Lactam (oral cefpodoxime,   cefuroxime,   HD amoxicillin,   amoxicillin/clavulanate;or   parenteral ceftriaxone   followed by oral   cefpodoxime) plus Macrolide or doxycycline Or Antipneumococcal fluoroquinolone   (used alone) 2700 cc Queda 3 s emanas antes de ir a cir In AJCCRM 2001, 163- ATS Guidelines 7 Jornadas

a. Cardiopulmonary Disease and/or Modifying Factors CASO CLÍNICO Grupo 3 D. internados Organisms Therapy a. Cardiopulmonary Disease and/or Modifying Factors Streptococcus pneumoniae Hemophilus influenzae Mycoplasma pneumoniae Chlamdia pneumoniae Mixed infection (bacteria   plus atypical pathogen) Enteric gram-negatives Aspiration (anaerobes) Viruses Legionella spp. Miscellaneous   Mycobacterium tuberculosis, endemic     fungi, Pneumocystis carinii Intravenous B-lactam  (cefotaxime, cefuroxime,ceftriaxone,   ampicillin/sulbactam,   high-dose ampicillin) plus Intravenous or oral macrolide   or doxycycline or Iv antipneumococcal   fluoroquinolone alone 2700 cc Queda 3 s emanas antes de ir a cir In AJCCRM 2001, 163- ATS Guidelines 7 Jornadas

b. No cardiopulmonary Disease, No Modifying Factors CASO CLÍNICO Grupo 3 D. internados b. No cardiopulmonary Disease, No Modifying Factors S. Pneumoniae H. influenzae M. pneumoniae C. pneumoniae Mixed infection (bacteria  plus atypical pathogen) Viruses Legionella spp. Miscellaneous   M. tuberculosis, endemic fungi, P. carinii Intravenous azithromycin alone.  If macrolide allergic   or intolerant:    Doxycycline  and a B-lactam or Monotherapy with an    antipneumococcal   fluoroquinolone 2700 cc Queda 3 s emanas antes de ir a cir In AJCCRM 2001, 163- ATS Guidelines 7 Jornadas

aparecimento de fármacos com maior semivida tecidular considerar: Duração do tratamento variável 7-14 D aparecimento de fármacos com maior semivida tecidular considerar: doenças associadas gravidade da doença evolução da doença agente etiológico M. Pneumoniae 10-14 D C. Pneumoniae Legionella 14 D In AJCCRM 2001, 163- ATS Guidelines

Reports of respiratory infection, WHO global surveillance networks, 2002–2003 27 November Guangdong Province, China: Non-official report of outbreak of respiratory illness with government recommending isolation of anyone with symptoms (GPHIN) 11 February Guangdong Province, China: Non-official report of health worker outbreak of atypical pneumonia with high mortality (e-mail) 14 February Guangdong Province, China: Official confirmation of outbreak of atypical pneumonia with 305 cases and 5 deaths (China) 19 February Hong Kong, SAR China: Official report of 33-year male and 9 year old son in Hong Kong with Avian influenza (H5N1), source linked to Fujian Province, China (FluNet) Fonte: OMS D. Heymann

Intensified surveillance for pulmonary infections, WHO, 2003 26 February Hanoi, Viet Nam: Official report of 48-year-old business man with high fever (> 38 ºC), atypical pneumonia and respiratory failure with history of previous travel to China and Hong Kong (Viet Nam) 4 March Hong Kong, SAR China: Official report of 77 medical staff from Kwong Wah Hospital reported with atypical pneumonia (Hong Kong, SAR) 5 March Hanoi, Viet Nam: Official report of 7 medical staff from French Hospital reported with atypical pneumonia (Viet Nam) 8 March WHO teams arrive Hong Kong and Hanoi, and with governments begin investigation and containment activities Fonte: OMS D. Heymann

SARS Global Alert: 15 March 2003 Atypical pneumonia with rapid progression to respiratory failure Health workers appeared to be at greatest risk Unidentified cause, presumed to be an infectious agent Antibiotics and antivirals did not appear effective Spreading internationally within Asia and to Europe and North America Fonte: OMS D. Heymann D. Heymann

SARS Síndroma respiratória aguda CASO CLÍNICO SARS Síndroma respiratória aguda Casos iniciais: China Vietnam Indonésia Filipinas Singapura descohecimento do agente etiológico mortalidade 2700 cc Queda 3 s emanas antes de ir a cir Alerta global 7 Jornadas

SARS: chain of transmission among guests at Hotel Metropole, Hong Kong, 21 February Index case from Guangdong Hospital 2 Hong Kong 4 HCW + 2 Canada 12 HCW + 4 Ireland Hospital 3 Hong Kong 3 HCW F G 156 close contacts of HCW and patients A Hotel M. Hong Kong K USA H I Hospital 1 Hong Kong 99 HCW E J D C B Germany HCW + 2 Viet Nam 37 HCW + ? Hospital 4 Hong Kong Singapore 34 HCW + 37 New York Bangkok HCW 4 other Hong Kong hospitals 28 HCW Source: WHO/CDC D. Heymann

SARS: number of probable cases by date of report worldwide SARS: number of probable cases by date of report worldwide*, 1 March–5 May 2003 (n = 5 393) Date of report 50 100 150 200 250 300 350 400 1-Mar-03 8-Mar-03 15-Mar-03 22-Mar-03 29-Mar-03 5-Apr-03 12-Apr-03 19-Apr-03 26-Apr-03 3-May-03 number of cases * Includes all cases from Hong Kong SAR, Macao SAR and Taiwan, China, but only those cases elsewhere in China reported after 3 April 2003 (1,190 cases between 16 November 2002 and 3 April 2003 not shown). The United States of America began reporting probable cases of SARS to WHO on 20 April 2003. Fonte: OMS D. Heymann

CASO CLÍNICO 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

World Health Organization Severe Acute Respiratory Syndrome (SARS): Global Alert, Global Response World Health Organization K. Stohr

SARS Epidemiology 1 Routes of transmission Mainly droplet; person-to-person Virus excreted through respiratory secretions, stool, urine, tears Fomites Incubation period Average: 2-7 d Case fatality rate Hong Kong: around 15%; Fonte:K. Stohr. WHO

SARS Epidemiology 2 Virus excretion Begins with onset of clinical signs (perhaps earlier) Respiratory tract Appears to peak around day 5; continues throughout the disease day 10: 95%; day 13: 90%, day 19: 75%; day 21: 47% Stool Begins as early as day 3; shedding up to 10log6; Day 10: 100%; day 16:95%; day 19: 80%; day 21: 67%) Fonte:K. Stohr. WHO

SARS Diagnosis Summary Virus and Ab detection tests available Test are reliable in scientific laboratories Invaluable in understanding the epidemiology of the disease Limited use for case management and infection control Virus detection useful for case-management but negative results can not exclude presence of SARS virus Ab detection comes too late in the course of the disease Negative test can not yet rule out earlier presence of disease Fonte:K. Stohr. WHO

SARS Síndroma respiratória aguda CASO CLÍNICO SARS Síndroma respiratória aguda Não é o primeiro caso de SARS, nem será o último Legionelose 1976 Hantanvírus 1993 EUA Hendra vírus 1994 H5 N1 influenza vírus 1997 Hong Kong Nipah vírus 1997 Metapneumovírus 2001 H7 N7 influenza vírus 2003 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

SARS Síndroma respiratória aguda CASO CLÍNICO SARS Síndroma respiratória aguda 50- 100 novos casos/DIA Definição de caso suspeito caso provável Critérios clínicos Critérios epidemiológicos Critérios laboratoriais - Acs SARS-CoV - RT- PCR - isolamento SARS- CoV T > 38 º C Tosse Polipneia Dispneia Hipoxémia Alt. Rx 2700 cc Queda 3 s emanas antes de ir a cir e Viagem ultimos 10 D início sintomas área SARS China, Hong Kong, Formosa, singapura, Toronto, Vietnam Contacto com pessoa sint resp. E viagem região SARS Com pessoa com SARS 7 Jornadas

Preliminary Clinical Description of Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome (SARS) is a disease of unknown etiology that has been described in patients in Asia, North America, and Europe. Most patients identified as of March 21, 2003 have been previously healthy adults aged 25-70 years. A few suspected cases of SARS have been reported among children (≤15 years). The incubation period of SARS is usually 2-7 days but may be as long as 10 days. The illness generally begins with a prodrome of fever (>38°C), which is often high, sometimes associated with chills and rigors and sometimes accompanied by other symptoms including headache, malaise, and myalgias. At the onset of illness, some cases have mild respiratory symptoms. Typically, rash and neurologic or gastrointestinal findings are absent, although a few patients have reported diarrhoea during the febrile prodrome. Fonte:CDC 16 MAIO

Preliminary Clinical Description of Severe Acute Respiratory Syndrome After 3-7 days, a lower respiratory phase begins with the onset of a dry, non-productive cough or dyspnea that may be accompanied by or progress to hypoxemia. In 10%-20% of cases, the respiratory illness is severe enough to require intubation and mechanical ventilation. The case fatality among persons with illness meeting the current WHO case definition for probable and suspected cases of SARS is around 3%. Chest radiographs may be normal during the febrile prodrome and throughout the course of illness. However, in a substantial proportion of patients, the respiratory phase is characterized by early focal infiltrates progressing to more generalized, patchy, interstitial infiltrates. Some chest radiographs from patients in the late stages of SARS have also shown areas of consolidation. Fonte:CDC 16 MAIO

Preliminary Clinical Description of Severe Acute Respiratory Syndrome Early in the course of disease, the absolute lymphocyte count is often decreased. Overall white cell counts have generally been normal or decreased. At the peak of the respiratory illness, up to half of patients have leukopenia and thrombocytopenia or low-normal platelet counts (50,000 – 150,000 / μl). Early in the respiratory phase, elevated creatine phosphokinase levels (up to 3000 IU / L) and hepatic transaminases (2- to 6-times the upper limits of normal) have been noted. Renal function has remained normal in the majority of patients. Fonte:CDC 16 MAIO

Preliminary Clinical Description of Severe Acute Respiratory Syndrome Treatment regimens have included a variety of antibiotics to presumptively treat known bacterial agents of atypical pneumonia. In several locations, therapy has also included antiviral agents such as oseltamivir or ribavirin. Steroids have also been given orally or intravenously to patients in combination with ribavirin and other antimicrobials. At present, the most efficacious treatment regime, if any is unknown. Fonte:CDC 16 MAIO

WHO multi-center collaborative network on SARS diagnosis First data on stability and resistance of SARS coronavirus compiled by members of WHO laboratory network The below table provides the first compilation of data on resistance of the SARS Coronavirus against environmental factors and disinfectants. WHO multi-center collaborative network on SARS diagnosis The major conclusions from these studies are: Virus survival in stool and urine Virus is stable in faeces(and urine) at room temperature for at least 1-2 days. Virus is more stable (up to 4 days) in stool from diarrhea patients (which has higher pH than normal stool). Fonte:CDC 16 MAIO

Virus survival in cell-culture supernatant Disinfectants Virus loses infectivity after exposure to different commonly used disinfectants and fixatives. Virus survival in cell-culture supernatant Only minimal reduction in virus concentration after 21 days at 4°C and -80°C. Reduction in virus concentration by one log only at stable room temperature for 2 days. This would indicate that the virus is more stable than the known human coronaviruses under these conditions. Heat at 56°C kills the SARS coronavirus at around 10000 units per 15 min (quick reduction). Fixatives (for use in laboratories only) SARS virus fixation (killing) on glass slides for immunofluorescence assays in room temperature does not kill virus efficiently unless the acetone is cooled down to -20oC. Fonte:CDC 16 MAIO

Worldwide 6727 cases 478 deaths Europe 36 cases 0 deaths 0.5% of total SARS- 6 MAIO Worldwide 6727 cases 478 deaths Europe 36 cases 0 deaths 0.5% of total Fonte: OMS

SARS- 6 MAIO Total countries 29 Europe 11 Fonte: OMS

Italy 9 Germany 7 UK 6 France 5 Sweden 3 Bulgaria 1 Poland 1 SARS- 6 MAIO Italy 9 Germany 7 UK 6 France 5 Sweden 3 Bulgaria 1 Poland 1 Rep of Ireland 1 Romania 1 Spain 1 Switzerland 1 Fonte: OMS

SARS- 6 MAIO SARS- 16 MAIO Worldwide 6727 cases 478 deaths Europe 36 cases 0 deaths 0.5% of total SARS- 16 MAIO Worldwide 7739 cases 611 deaths Fonte: OMS

SARS Síndroma respiratória aguda CASO CLÍNICO SARS Síndroma respiratória aguda este caso é importante para lembrar constante ameaça das D. Infecciosas possibilidade de aparecimento novos agentes infecciosos 2700 cc Queda 3 s emanas antes de ir a cir 7 Jornadas

Novos Fármacos Apesar dos avanços terapêuticos CASO CLÍNICO Novos Fármacos Apesar dos avanços terapêuticos “ Os esforços para controlar as infecções respiratórias não podem ser estáticos, dada a emergência de novos patogéneos e o aparecimento de resistências aos antibióticos comuns nos patogéneos antigos” Michael Niederman Iniciou oct a 26 dia 1 já não drenava 7 Jornadas