The growing problem of viral respiratory infections 5th ESCMID School of Clinical Microbiology and Infectious Diseases Santander, Spain, 10 - 16 June 2006 Núria Rabella Respiratory tract Major portal of entry Most common afflictions in humans Wide range of clinical manifestations: from self-limited to devastating Children half a dozen each year, adults two or three. Most caused by viruses. Considerable impact on quality of life and productivity of society Respiratory tract Majority trivial colds and sore throats Serious lower respiratory tract infections tend to occur at the extremes of life Influenzavirus killing the elderly and respiratory syncytial virus killing the very young Altogether over 200 known viruses Respiratory tract infection High prevalence: large number of infectious agents and serotypes efficiency of transmission incomplete immunity Frequency: higher in children under 4 years Major reservoir it declines in teenagers schoolchildren rises again in parents lowest in the elderly Epidemiology (1) • Transmission: respiratory route • Shedding: sneezing, coughing or talking • sneeze: – 106 droplets < 10mm ê evaporation ê smaller- suspended in the air for several minutes – larger droplets fall to the ground • Spreading: • inhalation • direct contact Epidemiology (2) * Sneezing: 1.940.000 viral particles * To begin an infection: Adenovirus: 7 Influenza A virus: 3 Enterovirus: 6 * Some viruses remain infectious for prolonged periods Direct contact transmission Viral persistence Respiratory syncytial virus: porous surfaces for 30’ non-porous 6h Parainfluenzavirus: porous surfaces for 4h non-porous 10h Influenza A virus: porous surfaces for 8-12h non-porous 24-48h In the hands 5 minutes Nosocomial infection If health care workers do not wash hands between patients they can easily transmit the infection from one patient to another Epidemiology (3) 160 140 120 100 80 60 40 20 0 1 11 21 31 41 51 9 19 29 39 49 7 17 27 37 47 5 15 25 35 45 2 12 22 32 42 52 10 20 30 40 50 7 17 27 37 47 5 15 25 35 45 1997 1998 1999 2000 2001 2002 2003 2004 RSV FLUAV FLUBV CRV TOTAL Epidemiology (4) Winter incidence: • Not attributable to cold or wet “per se” • Predilection for shutting ourselves in ill- ventilated centrally-heated buildings • Ex: tropics, during the wet season people spend more time indoors in crowded conditions Respiratory viruses Influenza A, B, C virus Respiratory syncytial virus Parainfluenzavirus 1-4 Metapneumovirus Adenovirus Enterovirus Rhinovirus Coronavirus Characteristics of infection • Short incubation period (2-7 days) • Large number of virions, even before symptoms • Small number necessary to infect • Epidemic outbreaks When the proportion of uninfected susceptible persons in the community falls, the epidemic burns itself out. Viral entry •Inhaled droplets > 10 mm Ø are trapped in turbinates of the nose •Inhaled droplets 5 -10mm Ø often reach the trachea and bronchioles Clinical features •Above the epiglottis URTI Described according to the anatomical site of maximal involvement •Below the epiglottis LRTI Rhinitis Copious watery nasal discharge, congestion, sneezing, and a mild sore throat or cough. Little or no fever 50% last longer than 1 week and 25% last up two weeks LRTI in 60% in elderly persons common in young children Rhinitis Acute inflammation of the mucosa may contribute to the pathogenesis of otitis and sinusitis. Abnormalities observed in the sinus cavity in these patients appear to result from the entrapment of secretions and resolve 2 to 3 weeks later. Genus Rhinovirus Species More than 100 Responsible for about 50% of common colds • > 100 serotypes of Rhinovirus •re-infection can occur •infections year-round, most prevalent in fall and spring •incubation period about 2 days •symptoms peak on the 2nd and 3rd days Genus Coronavirus Species HCoV-229E HCoV-OC43 HCoV-NL63 HCoV-HKU1 SARS-CoV • Responsible for about 10-20% of common colds •re-infection is common •infections year-round, most prevalent in fall and spring •incubation period about 2 to 5 days SARS Coronavirus •SARS: Severe Acute Respiratory Syndrome Respiratory infection was caused by a coronavirus named SARS-CoV. •Disease extended to more than 24 countries in North-America, South-America, Europe and Asia. •8,098 persons presented the disease and 774 died. 21% health workers Pharyngitis • sore throat is the prominent symptom • erythema • swelling of the affected tissues • exudates: inflammatory cells overlaying mucous membranes • low-grade fever, mild general symptoms • difficult to differentiate from streptococcal infection Caused by the same viruses that cause common cold and adenovirus, enterovirus and influenza virus. Adenovirus 51 serotypes • Immunity correlates with the presence of type- specific neutralizing antibodies • Endemic or epidemic, often during summer • Incubation period 4-7 days • Moderate to severe pharyngitis sometimes exudative • Fever and systemic symptoms • Rhinitis and follicular conjunctivitis are common Adenovirus 51 serotypes Pharyngo-conjunctival fever sporadical or epidemic outbreaks association with swimming pools Epidemic acute respiratory disease in military recruits pneumonia in 10-20% Pneumonia in immunocompromised pts BMT recipients: mortality 60% Nosocomial transmission: epidemic keratoconjunctivitis Genus Enterovirus • Great variety of clinical syndromes including respiratory manifestations • Numerous serotypes related to respiratory illness • Pharyngits is a common manifestation concomitant with other respiratory clinical findings that could be more prominent. Croup Laryngitis and croup : laryngeal obstruction • varying degrees of inspiratory stridor • cough, hoarseness • initially cold with fever •symptoms last 3 to 7 days •children < 4 years and boys > girls Important: must be differentiated from epiglottitis Laryngitis Croup In our experience: Parainfluenzavirus are responsible for about 46% of cases of laryngitis and 20% of cases of croup. Parainfluenzavirus The major cause of LRTI in young children and URTI in older children and adults There are 4 types named 1-4 Distinct seasonal pattern: type 1 and 2: fall, every other year type 3: endemic Parainfluenzavirus • More severe disease between 6 months and 3 years One third of children with primary infection during the first 2 years of age had involvement of the LRT • PIV 1, 2 - related to croup. PIV 3 - bronchiolitis or pneumonia PIV 4 - very mild illness • Re-infections are frequent at any age, usually mild Bronchitis Cough, severe or prolonged, fever, upper respiratory tract involvement Inflammatory disease of the larger air passages • Direct viral damage of the mucosa • Release of inflammatory mediators • Stimulation of airway irritant receptors Any of the respiratory viruses Influenzavirus • There are 3 influenza viruses: A, B, C • Depending on the internal protein • Winter . Sporadic and epidemic • Highly contagious •Period transmission: 7 days or throughout duration of symptoms Influenza A virus Neuraminidase (9) Hemagglutinin (16) • RNA fragmented genome: 8 • Drift: point mutation = variant could evade immunity • Shift: reassortment of two viruses = new virus Influenzavirus. Clinical features NO SYMPTOMS MILD DISEASE UPPER RESPIRATORY TRACT INVOLVEMENT INFLUENZA: abrupt onset, headache, chills, dry cough, high fever, myalgias, malaise, anorexia Influenzavirus Complications Benign: Sinusitis, otitis media, and bronchitis Severe: Viral or bacterial pneumonia Exacerbation of underlying illnesses Nosocomial infection Influenza A virus Brots epidèmics intrahospitalaris (Grip A). Nº 5 S. Microbiologia. Hospital de la Santa Creu i Sant Pau. 140 VRS VGA Mostres 120 100 80 41 patients 60 nombre de mostres 11 health workers 40 20 4 relatives 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 1999 2000 Clinical manifestations : light/moderate RD, URTI 10, LRTI 4, digestive symptoms 4, high fever 5, 2 died. Bronchiolitis Expiratory wheezing with tachypnea, air trapping, and costal retractions Narrowing of air passages: destruction of epithelium mononuclear infiltration necrosis + infiltrates accumulation mucus and debris Multiple atelectasis: image of pneumonitis Peak incidence: 2 to 10 months Respiratory syncytial virus • Major cause of RTI among children • From inapparent to severe (bronchiolitis) • 50% develop RSV infection by 12 months of age • Regularly produces epidemic outbreaks each winter Adults: URTI (previously healthy) to LRTI (elderly, immunocompromised) 40% children hospitalized for more than 7 days in winter 50% of health workers Metapneumovirus • Spectrum of diseases and epidemiology resembling that of RSV • Peak incidence between 4 and 6 months • Frequent coinfection with RSV •Assymptomatic or mild illness much more common HMPV infection in 22 patients (nº 251) 9 (41%) LRTI, 3 (33%) died Nosocomial infection RSV and HMPV * 432 hematological patients followed at HSCSP. October 1999 - May 2003 735 NPA, 170 BAL 304 episodes / 156 positive (51%). RSV infection: 38% (total 24) nosocomial HMPV infection: 45% (total 22) nosocomial Pneumonia Viruses are the most frequent cause in children in adults is not uncommon (FLUAV, RSV, PIV) Immunocompromised patients 44+ (26%) /170 BAL 432 p/7y 14% 17% 36% 18% 4% 1% 10% Influenza A virus Respiratory syncytial virus Enterovirus Adenovirus Parainfluenzavirus Influenza B virus Rhinovirus Respiratory viruses in bronchoalveolar lavages Community-acquired pneumonia and respiratory viruses Period 1999 2000 2001 Total: Nº of patients 27