Viral respiratory tract infec6ons

Transcription

1 Viral respiratory tract infec6ons Leading Causes of Global Deaths from Infec8ous Diseases. Fauci AS, Morens DM. N Engl J Med 2012;366: Flint et al. Principles of Virology, 2:nd ed 1

2 Transmission Contact. Aerosol: droplets <10um. Airway secre6ons may contain virions/ml. Airways are a common portal of entry for viruses The airways is the most common entry point for viruses. The most common viral infec6ons are airway infec6ons. How common? /year for children /year for adults. Local respiratory tract infec6ons 1) Starts in the airways and stays there. Local infec6on. - Short incuba6on 6me (2-3days). - Short lived immune response (IgA) reinfec6ons are common. - High virus produc6on (even prior to symptoms). - Under symptoma6c phase, virions/ml secrete. - Examples: rhinovirus, coronavirus. 2) Starts in the airways followed by systemic infec6on. - Long incuba6on 6me. - Good immunity oven life long protec6on. - Examples: measles, chickenpox. RNA viruses causing respiratory tract infec6ons. RNA viruses dsrna ssrna(+) ssrna(- ) DNA viruses causing respiratory tract infec6ons. DNA viruses dsdna ssdna Reo Corona Flavi Calici Astro Retro Hepevirus (unclassified) Picorna Toga Papilloma Adeno Herpes Pox Polyoma Hepadna Anello Parvo Rhinovirus Deltavirus (unclassified) Rhabdo Filo Paramyxo Orthomyxo Arena Bunya 2

3 Viral respiratory tract infec6ons Upper respiratory tract infec6ons: Rhino Corona Adeno influensa parainfluensa RSV Faryngi6s: adeno, coxsackie, HSV, EBV. Lower respiratory tract infec6ons: - influensa - RSV - parainfluensa - adeno Rhinovirus RNA viruses causing respiratory tract infec6ons. dsrna ssrna(+) ssrna(- ) Reo Retro Hepevirus (unclassified) Corona Flavi Calici Astro RNA viruses Picorna Toga Rhinoviruses cause 50-80% of all common cold. Local infec6on in nasal mucosa. Runny nose, Sneezing, Sore throat, Low or no fever. Liale cell cytopathic effect in i nasal mucosa. Rhinovirus Rhabdo Filo Paramyxo Orthomyxo Arena Bunya Proinflammatory cytokines and vasoac6ve pep6des (kinin, bradykinin) cause many of the symptoms. Bradykinin given intranasally causes symptoms that resemble symptoms of rhinovirus infec6on. Deltavirus (unclassified) One virus par6cle is sufficient to start an infec6on. Rhinoviruses cause 50 80% of all common cold. Rhinoviruses belong to the family od Picornaviruses. Rhinoviruses have an +ssrna genome that translates into one polyprotein 3

4 Rhinovirus replica6on cycle Rhinovirus epidemiology Transmiaed via aerosol and contact. Common over the en6re world. OVen appear early autumn, probably related to school start, day care, etc. Rhinoviruses replicate at 33 C. Rhinoviruses replicate at 33 C. Rhinoviruses are sensi6ve to low ph and do not replicate in gastrointes6nal mucosa. Defense against rhinovirus infec6on Interferon produc6on is likely to limit virus replica6on*. IgA an6bodies disappear aver 18 months. Reinfec6ons are common as a result of the many subtypes >100 and the transient immune response. 4

5 RNA viruses causing respiratory tract infec6ons. RNA viruses Coronavirus dsrna ssrna(+) ssrna(- ) Reo Flavi Calici Astro Retro Hepevirus (unclassified) Corona Picorna Toga Rhinovirus Deltavirus (unclassified) Rhabdo Filo Paramyxo Orthomyxo Arena Bunya Coronaviruses Coronaviruses Coronaviruses Large RNA viruses nts Enveloped, around 100 nm. Humana coronaviruses Five human coronaviruses common cold. SARS MERS NEJM 2003;348:1948 Coronavirus Coronavirus infec6on is the second most common cause of common cold % of all upper respiratory tract infec6ons. Longer incuba6on 6me than rhinovirus infec6ons (3days). Replicates at C, BUT Coronavirus infec6ons Common during winter and spring. Serum an6bodies are common, but do not prevent re- infec6ons. Coronavirus has been found in pa6ents with diarrhea/ gastroenteri6s. 5

6 10/27/15 Coronavirus replica6on cycle SARS SARS epidemic in Atypical pneumonia: fever >38 C, chills, rigors, headache, dizziness, fa6gue, coughs and difficul6es to breathe. Virus is present in respiratory secre6ons, but also sweat, urine and faeces. 20% of the SARS infected get diarrhea. Viral glycoprotein corona protects the virus in the gastrointes6nal tract. Pathogenesis: virus + immune responses. No an6viral drugs, no vaccine. SARS HOTEL

7 SARS epidemic in 2003 SARS is a zoono6c virus became ill between Nov 1, July 11, deaths (9,6%). 29 countries affected MERS MERS- epidemic in 2013.?? MERS zoonosis? September 2013: MERS- RNA in bats and MERS- an6bodies in healthy camels. Disease Watch TRACKING DOWN MERS CORONAVIRUS Identifying the animal source of human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) is a priority. The detection of antibodies specific for the virus in dromedary camels and of identical viral sequences in tomb bats and in patients with MERS suggests that these two animals serve as MERS-CoV reservoirs. Epidemiological data indicate that currently circulating MERS-CoV strains are unlikely to cause an epidemic by spreading between humans, as their reproduction number (the number of new cases arising from a single infected person) is 0.69, which is too low to maintain continuous, widespread transmission; in comparison, the reproduction number of severe acute respiratory syndrome (SARS) CoV is Thus, by preventing viral transmission from animal reservoirs to humans, it is hoped that the spread of MERS-CoV can be stopped. BBC News/Lancet 7

8 Figure 1. Epidemic curve of MERS-CoV human cases as of 5 February 2015 (n=971) Figure 2. Countries reporting MERS-CoV infection as of 5 February 2015 Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June 2015 Tuesday 28 July BST South Korea: Mers virus outbreak is over Prime minister urges people to resume normal daily activities after 36 people died and panic left economy struggling South Korea has declared an end to a deadly outbreak of Middle East Respiratory Syndrome (Mers) that killed 36 people, triggered widespread panic and stymied growth in Asia s fourth-largest economy. Cowling, BJ. et al., Eurosurveilance. June 2015, vol 20, issue 25. DNA viruses causing respiratory tract infec6ons. DNA viruses Adenovirus dsdna ssdna Papilloma Adeno Herpes Pox Polyoma Hepadna Anello Parvo 8

9 Adenovirus Adenovirus Isolated in Now, approx. 50 human serotypes. Most common: serotypes 1 and 7. Six subgroups: A- F. Cause respiratory tract infec6ons, gastrointes6nal infec6ons, hemorrahgic cys66s and conjunc6vi6s. Adenovirus infec6ons Disease Respiratory tract infec6on: Tonsilli6s Upper resp. tract infec6on Pneumonia Eye infec6on Urinarytract infec6on Gastrointes6nal infec6on Sero type 1, 2, 5 4, 7 3, 4, 7 3, 4, 7, 8, , 41 Paramyxoviruses RNA viruses causing respiratory tract infec6ons. RNA viruses Paramyxoviruses dsrna ssrna(+) ssrna(- ) Reo Flavi Calici Astro Retro Hepevirus (unclassified) Corona Picorna Toga Rhinovirus Deltavirus (unclassified) Rhabdo Filo Paramyxo Orthomyxo Arena Bunya Flint et al. Principles of Virology, 2:nd ed 9

10 Paramyxoviruses - RS- virus (RSV) - Parainfluenzavirus Metapneumovirus Respiratory syncy8a virus (RSV). The most common cause of death due to respiratory tract infec6on sin small children and infants. The most common cause of hospitaliza6on of small children. Reinfec6ons in children and adults are common(milder symptoms). RS- virus can infect upper and lower respiratory tract (trachea, large and small bronchi, alveoli). RS- virus pathogenesis Symptoms: from common cold to pneumonia. Milder symptoms in adults. Complica6ons in small children: bronchioli6s, pneumonia. Cytoly6c virus that can cause syncy6a, but the immune system probably gives rise to most symptoms. Edema, and plugs in the bronchioli consis6ng of mucus, fibrin and necro6c cell material. RS- virus epidemiology Very contagious. Essen6ally all children <2år infected. Season variability RSV (every 2nd year) Common all over the world. Yearly epidemics during winther. Incuba6on 6me 4-5 days. Smiaskyddsins6tutet 10

11 n engl j med 371;8 nejm.org august 21, /27/15 Vaccine to RS virus lacking Vaccine development has failed. Passive immuniza6on with an6body to RSV (prematurely born). Ribavirin can be used (prematurely born or immunosuppressed). Progress in the Prevention and Treatment of RSV Infection Peter F. Wright, M.D. At long last, gratifying progress is evident on many fronts in combating respiratory syncytial virus (RSV) infection. RSV was discovered in 1956 as an agent causing coryza in chimpanzees. 1 Its clinical effects became evident shortly thereafter through a strong epidemiologic association of RSV infection with bronchiolitis and pneumonia in young infants. 2 In the almost 60 years since the virus was identified, the highlights of RSV research have been relatively few, in spite of dedicated groups working in this field. The reasons for this include the difficulty of working with RSV in the laboratory; the confinement of RSV replication in humans to the superficial epithelial cells lining the respiratory tract; the early recognition of the complex immune responses to RSV, in which efforts at prevention of illness led to enhancement of disease Human parainfluenza (HPIV). Upper (most common) and lower respiratory tract infec6ons of varying severity. From common cold to bronchi6s and croup*, but also pneumonia. Local infec6on in airways (no viremia). 2-6 days incuba6on 6me, recovery aver 48h. Cytoly6c virus. Cuases syncy6a. No an6viral drugs, no vaccines. Parainfluenza virus och croup Four serotypes: HPIV- 1, HPIV- 2, HPIV- 3 och HPIV- 4. HPIV 1-3 cons6tute second- most cause of serious, lower respiratory tract infec6ons in small children (aver RSV). Primary infec6on oven occurs in children <5 years of age. Children 6months- 6yeras: Can get laryngotracheobronchi6s (croup). Reinfec6ons of adults and children are common (milder symptoms). Short lived IgA response, but par6al immunity? 11