Flu in children


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Class presented at the University of Brasília for medical students - English version

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Flu in children

  1. 1. Acute diseases of the upper respiratory tract- 2010 English version of ‘doenças agudas de vias aéreas superiores Dario Palhares Pediatrician of the University Hospital of Brasília Email: dariompm@unb.br
  2. 2. Objectives of this class <ul><li>1) To know the most important virus that infect the upper respiratory tract </li></ul><ul><li>2) To clinically differentiate the viral diseases from the bacterial ones (accepting that there may be overlapping of signs and symptoms) </li></ul><ul><li>3) To rationally choose the antibiotics, based on the prevalent bacteria and on the profile of sensitivity </li></ul>
  3. 3. Roadmap of the class <ul><li>Brief review on anatomy and physiology of the upper respiratory tract </li></ul><ul><li>The virus of flu/cold </li></ul><ul><li>Clinical manifestations of flu/cold </li></ul><ul><li>Acute medium otitis </li></ul><ul><li>Microbes of bacterial otitis </li></ul><ul><li>Acute sinusitis </li></ul>
  4. 5. Specifities of the paranasal sinus in childhood <ul><li>At birth: maxillary sinus </li></ul><ul><li>some ethmoidal cells </li></ul><ul><li>Sphenoid sinus: after 3 years </li></ul><ul><li>Frontal sinus: after 6 years. </li></ul>
  5. 8. The mucosa <ul><li>The mucosa produces mucus </li></ul><ul><li>Ciliated cells, continous cilliar movement </li></ul><ul><li>Rhynopharynx: colonized by aerophilic bacteria </li></ul><ul><li>Physiologically, bacteria from pharynx and also from the gut (physiological episodes of reflux) reach the Eustachii tuba and the paranasal sinus </li></ul>
  6. 9. <ul><li>Mechanisms for maintenance of sterility on Eustachii tuba and paranasal sinus: </li></ul><ul><li>Mucocilliary clearance (load the secretions into the gut) </li></ul><ul><li>Sneezes </li></ul><ul><li>Blowing the nose (small children lack this mechanism) </li></ul>
  7. 10. <ul><li>Conclusion: the respiratory system is very vulnerable </li></ul><ul><li>From the Tao “Everything is born with its own germen of the self destruction” </li></ul>
  8. 11. Acute viral rhynopharingits: vulgarly, flu. <ul><li>Secretory otitis </li></ul><ul><li>Acute medium otitis </li></ul><ul><li>Asthmatic crisis Facial palsy </li></ul><ul><li>FLU Mastoiditis </li></ul><ul><li>Alleric rhinitis Pneumonia </li></ul><ul><li>Acute bacterial sinusitis Thrombosis of cavernous sinus </li></ul><ul><li>Periorbital cellulitis Cerebral abscess </li></ul>Discompensation of chronic diseases Febrile convulsions
  9. 12. Acute viral rhynopharingits <ul><li>Flu: caused by the influenza virus </li></ul><ul><li>Common cold: ohter virus: </li></ul><ul><li>Rhinovirus ( > 100 sorotypes) </li></ul><ul><li>Coronavirus </li></ul><ul><li>Parainfluenza </li></ul><ul><li>Respiratory syncytial virus (also causes bronchiolitis) </li></ul><ul><li>Adenovirus </li></ul><ul><li>All the aerial transmitted virus (exantematic diseases, rotavirus, etc). </li></ul>
  10. 13. <ul><li>Flu X common cold: clinically indistinguishable. </li></ul><ul><li>Epidemiologically, the influenza virus caused pandemics with a great mortality </li></ul>
  11. 14. Influenza Virus <ul><li>Etymology: influence, from Italian influenza. Word created in the epidemy of 1733, in allusion to divine punishments. </li></ul><ul><li>RNA – vírus </li></ul><ul><li>Family Orthomyxoviridae </li></ul><ul><li>Classified according to antigens from the surface proteins and matrix proteins: </li></ul><ul><li>Influenza A, B, C. </li></ul>
  12. 15. Influenza <ul><li>Influenza B and C: antigenically stable </li></ul><ul><li>Influenza A: variations in the surface proteins (Hemagglutinin and Neuraminidase) with diverse recombinations. </li></ul><ul><li>Birds in general are naturally reservoirs of these virus </li></ul><ul><li>They were described with 16 antigenic groups of hemagglutinins and 9 of neuraminidases </li></ul>
  13. 16. Influenza <ul><li>In human populations, only three major groups of Hemagglutinin (H1, H2 and H3) and two of neuraminidases (N1 and N2) have been found. </li></ul><ul><li>Natural cycle of influenza in human populations: epidemics at each 3 years, pandemics at each 40 years in average </li></ul>
  14. 17. Influenza <ul><li>Historic Pandemics: </li></ul><ul><li>1918: virus type H1N1. Mortality of 2,5%. Inside the chaos of the First World War. </li></ul><ul><li>1958: virus type H2N2. Mortality of 0,03% </li></ul><ul><li>1968: virus type H3N2. Mortality of 0,03% </li></ul>
  15. 18. Influenza <ul><li>“ Asiatic chicken flu” of 2008: </li></ul><ul><li>373 confirmed cases, 236 deaths. </li></ul><ul><li>Virus type H5N1. </li></ul><ul><li>Which means, zoonosis with a reduced ability of human transmission. </li></ul><ul><li>Swine flu of 2009: virus H1N1 </li></ul>
  16. 19. Influenza <ul><li>Seasonal epidemics: USA estimative: 30 mil annual deaths, mainly in the winter and in sick population (elderly, chronic diseases). </li></ul><ul><li>Babies and children present with too many medical consults and internments, but with a low mortality. </li></ul>
  17. 20. Influenza <ul><li>Vaccin: does not protect against flu </li></ul><ul><li>It would protect against grave forms of flu and against post-flu pneumonia </li></ul><ul><li>Most recent studies have shown that the vaccination of the elderly does not alter the mortality rate of respiratory diseases: it is possible that the vaccine will be removed from the official vaccine calendar (but there are high economic interests involved) </li></ul>
  18. 21. Anti-influenza drugs <ul><li>Two classes: inhibitors of M2 protein (surface protein, less variable than hemagglutinins and neuraminidases): rimantadina and amantadina. </li></ul><ul><li>They were removed from the market because they quickly (three days in average) selected resistant virus, which preserved their infectivity and virulence </li></ul><ul><li>Amantadina: still present for the treatment of Parkinson´s disease </li></ul>
  19. 22. Influenza <ul><li>Antivirals: inhibitors of the neuraminidase: oseltamivir and zanamavir. </li></ul><ul><li>The pandemic of 2009 showed that they don´t alter the natural history of the infection, even in the grave forms </li></ul>
  20. 23. Influenza <ul><li>Serious denunciation: </li></ul><ul><li>“ The data over the effectivity of oseltamivir (...) come mainly from a single study (...) one metanalysis of 10 clinical essays that presented a mix of published and unpublished data (...) inaccessible to the free scrutiny” </li></ul><ul><li>Jefferson and cols, BMJ Brasil, fev/2010. </li></ul>
  21. 24. Adenovirus <ul><li>They cause rhynopharingitis and also: </li></ul><ul><li>Conjunctivitis </li></ul><ul><li>Parotiditis </li></ul><ul><li>Gastrenteritis </li></ul><ul><li>Hemorragic cystitis (uncommon) </li></ul><ul><li>Viral meningitis </li></ul>
  22. 25. Clinical features <ul><li>Fever: of any value (higher temperatures are not related to severity) </li></ul><ul><li>Cough </li></ul><ul><li>Rhinorrhea, nasal obstruction </li></ul><ul><li>Lachrymation </li></ul><ul><li>Otalgia </li></ul><ul><li>Pharingitis: it is common to present edema of tonsils with mild hyperemia (clinical subjectivity) </li></ul><ul><li>Cephalea: mild, related to fever, quick respond to the analgesic </li></ul><ul><li>Inappetence </li></ul><ul><li>Crisis of laryngospasm </li></ul>
  23. 26. Fever <ul><li>Hours of peak: between 4 pm and 6 pm </li></ul><ul><li>It is common to appear at predawn </li></ul><ul><li>It can enhance intensity and frequence in the first three days, stabilizes until the 5th day and then starts to lower down. </li></ul>
  24. 27. Rhinorrhea <ul><li>Initially, aqueous </li></ul><ul><li>Becomes mucoid </li></ul><ul><li>Ends as mucopurulent </li></ul><ul><li>It is common to be more purulent at awakening than the rest of the day </li></ul><ul><li>Anterior rhinoscopy: hyperemic mucosa. Paleness, violet musoca: allergic rhinitis or use of vasoconstrictors </li></ul>
  25. 28. Otalgia <ul><li>Hiperemia of tympanum and/or auditory canal SUGGESTS VIRAL INFECTION </li></ul><ul><li>Sudden beginning, when exposure to cold: SUGGESTS VIRAL INFECTION </li></ul>
  26. 29. Inappetence <ul><li>Due to the greater ingestion of the nasal secretion (mucociliar clearance) </li></ul><ul><li>It is not a factor for prognosis, however, the recovery of the appetite indicates clinical ammelioration </li></ul>
  27. 30. Crisis of laryngospasm <ul><li>Often occurs during predawn </li></ul><ul><li>Rapid alleviation with inhalation of water vapour </li></ul><ul><li>Attention: high fever of sudden beggining + laryngospasm = malignant laringitis by Heamophilus (uncommon after the massive vaccination) </li></ul>
  28. 31. Seasonality <ul><li>Varies according the place </li></ul><ul><li>Related to unfavourable climatic periods. </li></ul><ul><li>Ex: temperate regions: winter </li></ul><ul><li>in Alaska: beginning of spring (the winter imposes complete isolation) </li></ul><ul><li>in Brasília: march/april (autumn): days too hot and cold nights </li></ul><ul><li>in Salvador (Bahia): september/october: rainy season </li></ul>
  29. 32. Exposition to cold weather <ul><li>Alone, it does not cause flu (obvious) </li></ul><ul><li>However, can start a crisis of allergic rhinitis (whose clinical features are very similar) </li></ul><ul><li>It may weaken the respiratory defenses (especially sudden changes of temperature) hence enhancing the chance of a sinusitis, otitis, pneumonia </li></ul>
  30. 33. Annual attacks <ul><li>In general, each child has 3 to 12 episodes per year </li></ul><ul><li>The entrance in nurseries and schools enhances the incidence </li></ul>
  31. 34. Laboratory <ul><li>Hemogram: first 2 days: inespecific response to aggression: leukicitosis (up to15.000 leukocytes/mL) with neutrophilia </li></ul><ul><li>After 2 days: normal leukometry or slight leukocitosis (up to 12.000 leukocytes/mL) with lymphocytosis or neutrophils and lymphocites in equal proportion </li></ul>
  32. 35. Radiography of thorax <ul><li>May present diffuse interstitial congestion (needs to correlate to the clinical manifestations) </li></ul>
  33. 36. Prophylaxis <ul><li>Delay the entrance in nurseries </li></ul><ul><li>The questionable vaccine against the influenza is indicated only to elders and to special groups </li></ul>
  34. 37. Treatment <ul><li>1) Measure axillary temperature and give analgesics: dipirone, ibuprofen, paracethamol. AAS is formally contraindicated due to the risk of Reye´s syndrome. </li></ul><ul><li>2) Frequent nasal cleaning with saline solution </li></ul><ul><li>3) Frequent oral hydration </li></ul><ul><li>4) Keep the normal and healthy diet and avoid junk food </li></ul><ul><li>5) Protect against cold weather </li></ul><ul><li>6) Keep attention to the signs of bacterial complication </li></ul>
  35. 38. The antigripal formulas <ul><li>READ the bula </li></ul><ul><li>Generally: analgesic + anti-histaminic + systemic nasal vasoconstrictor + caffeine </li></ul><ul><li>Which means: fight the fever, the allergic rhinitis and the sonolence induced by the anti-histaminic </li></ul><ul><li>Avoid in children, especially in babies. Pharmacon = poison! </li></ul>
  36. 39. Peculiar situations <ul><li>1) Recent fever, good general presentation (prodromic phase): </li></ul><ul><li>Since this situation can refer to any infectious disease, prescribe analgesics and give a WRITTEN ORDER to re-evaluate the child in 2-3 days. </li></ul>
  37. 40. Peculiar situations <ul><li>2) Referred fever, but not measured, good clinical presentation: </li></ul><ul><li>Teach to measure axillary temperature, re-evaluation in 2 days if fever is really happening </li></ul>
  38. 41. Peculiar situations <ul><li>3) Fever + aqueous nasal secretion IN NEONATES (less than 30 days of life), even if the general aspect is good : </li></ul><ul><li>INTERNMENT IS INDICATED </li></ul><ul><li>If it is the case, give a WRITTEN ORDER to re-evaluate the baby in 48 hours. </li></ul><ul><li>In general, the baby will spend just an overnight period in the hospital, but be careful with fevers in this period of life </li></ul>
  39. 42. Signs of bacterial complication <ul><li>Clinical worsening (enhancement of fever, of prostration, of coughing, of otalgia, of cephalea): a degree of subjectivity of the examinator will always be present </li></ul><ul><li>Appearance of tachypneia during resting </li></ul><ul><li>Recrudescence of fever </li></ul><ul><li>Delay in ammelioration (often with good general aspect, but with a ‘cold that doesn´t go away’) </li></ul>
  40. 43. Acute otitis media <ul><li>Definition: acute (less than 4 weeks) infection of the medium ear </li></ul><ul><li>Viral (most of the cases) or bacterial </li></ul>
  41. 44. Bacterial acute otitis media <ul><li>Tympanus arched </li></ul><ul><li>Liquid collection behind tympanus </li></ul><ul><li>Otorrhea </li></ul><ul><li>Tympanus with a yellow colour </li></ul><ul><li>Thickened tympanus: can be either viral or bacterial (correlate to the period of clinical evolution). </li></ul><ul><li>Hyperemia of tympanus inside an episode of flu is surely unlikely to be bacterial </li></ul>
  42. 45. Most common bacteria <ul><li>The commonest: </li></ul><ul><li>Streptococcus pneumoniae </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Others: </li></ul><ul><li>Moraxella catarrhalis </li></ul><ul><li>Staphylococcus aureus </li></ul><ul><li>-> from gut microbes: </li></ul><ul><li>Escherichia coli </li></ul><ul><li>Pseudomonas sp </li></ul><ul><li>Klebsiella sp </li></ul><ul><li>etc. </li></ul>
  43. 46. The pneumococcus <ul><li>It was sensitive to all antibiotics </li></ul><ul><li>Nowadays, there are a 50 to 70% of resistance to sulphas (emblematic example of inappopriate use of antibiotics) </li></ul><ul><li>Penicillins: in Brazil: </li></ul><ul><li>70 to 90% of the strains are sensitive </li></ul><ul><li>5 to 10% present an intermediary resistance </li></ul><ul><li>less than 5% with total resistance </li></ul>
  44. 47. The pneumococcusO pneumococo <ul><li>Sensible to penicillin: minimum inhibitory concentration inferior to 0,06 µg/mL (which means, the seric concentration obtained by benzathine penicillin) </li></ul><ul><li>Intermediary: MIC of up to 2 or even 4 µg/mL: value related to seric concentration of a dose of amoxicillin </li></ul><ul><li>Resistant: MIC above these values </li></ul><ul><li>Resistance is not due to betalactamase, but to changes in the penicillin binding proteins (PBP) </li></ul>
  45. 48. The pneumococcus strains resistant to penicillin <ul><li>65% resistant to sulphas </li></ul><ul><li>8% to eritromicin erythromycin </li></ul><ul><li>9% to clindamycin </li></ul><ul><li>2% to cephotaxime </li></ul><ul><li>0,8% to ofloxacin </li></ul><ul><li>No resistance was shown to chloramphenicol, riphampicine, vancomicine </li></ul>
  46. 49. Haemophilus <ul><li>Many species: the commonest is Haemophilus influenzae </li></ul><ul><li>Some strains present a glycopeptidic capsule that confers a greater ability of invasion </li></ul><ul><li>Serogroup b: causes100% of the meningitis and the laringites : that´s why the vaccine is against Haemophilus influenza b. </li></ul><ul><li>30% produce betalactamases. They can produce cephalosporinases as well </li></ul>
  47. 50. Treatment of bacterial acute otitis media <ul><li>1) Try to isolate the bacteria: swab of the otorrhea, tympanocentesis, hemoculture </li></ul><ul><li>2) Nasal desobstruction (frequent use of saline solution, anti-histaminics if the patient is allergic) </li></ul><ul><li>3) Degree of antibiotics </li></ul><ul><li>Choose: </li></ul><ul><li>a)amoxacillin (usual dosage) </li></ul><ul><li>b) amoxacillin in doubled dose or macrolids </li></ul><ul><li>c) First generation cephalosporins or betalactamase inhibitors </li></ul><ul><li>d) Other classes </li></ul><ul><li>In case of interment: </li></ul><ul><li>a)oxacillin </li></ul><ul><li>b) Association with third generation cephalosporin </li></ul><ul><li>c) Other classes </li></ul>
  48. 51. Duration of the treatment with antibiotics <ul><li>Most of the cases: after the third day, no more bacteria are found with PCR technique </li></ul><ul><li>Recomendation of CDC: 7 days -> Physiologically, this is the time for the immune system creates a complete response against the agent </li></ul><ul><li>Cases associated with obstruction of the Eustachii tuba: at least 10 days (shorter treatments are related to early recrudescence) </li></ul><ul><li>Secretory otitis: minimum of 15 days </li></ul>
  49. 52. Practical discussions about prescription of antibiotics <ul><li>1) Using amoxicillin in doubled dose twice a day is equally efficient as using the usual dose three times a day? </li></ul>
  50. 53. Amoxicillin BID <ul><li>a) The peak of a standard dose of 500 mg of amoxicillin is the reference for defining the pneumococci of intermediary resistance </li></ul><ul><li>b) Even a 4-fold dose is excreted from the blood in 8 hours </li></ul>
  51. 54. Amoxicillina BID: So... <ul><li>The administration of doubled dose twice a day: </li></ul><ul><li>Let the patient with no serum antibiotic for 1/3 of the day </li></ul><ul><li>Will quickly select fully resistant bacteria, as they will be exposed to higher concentrations of the antibiotics </li></ul><ul><li>Can only be indicated in ‘mild’ cases </li></ul>
  52. 55. Practical discussions about prescription of antibiotics <ul><li>2) Which is better: cephalexin or clavulanate (betalactamse inhibitor)? </li></ul>
  53. 56. Cephalexin x clavulanate <ul><li>Cephalexin: betalactamic resistant to betalactamases. Kills also several gram-negative bacteria </li></ul><ul><li>Clavulanate: inhibitor of the betalactamase of Heamophilus: limited experience in the treatment of staphylococcus </li></ul>
  54. 57. Cephalexin x clavulanate <ul><li>Pharmakocinetics: </li></ul><ul><li>Both present tissue concentrations similar to the blood (except in liquor, due to brain hematic barrier) </li></ul>
  55. 58. Cephalexin x clavulanate <ul><li>Some strains of haemophilus produce both betalactamases and cephalosporinases </li></ul><ul><li>These strains would be killed by clavulanate, but not by cephalexin </li></ul><ul><li>Costs: clavulanate: triple of cephalexin </li></ul>
  56. 59. Cephalexina x clavulanate: So... <ul><li>The prohibitive cost of clavulanate and its specificity to haemophilus makes the cost/benefit ration to be more favourable to cephalexin </li></ul>
  57. 60. Bacterial acute sinusitis <ul><li>Definition: infection of paranasal sinus less than 30 days. </li></ul><ul><li>Up to 10% of the patients with viral rhinopharingitis present bacterial sinusitis </li></ul>
  58. 61. Bacterial acute sinusitis <ul><li>Main element of the clinical features: enhanced production of nasal secretion: either mucoid or purulent </li></ul><ul><li>Two major clinical classes of acute sinusitis: </li></ul><ul><li>-> Grave sinusitis: persistently high fever, intense production of mucus, intense cephalea, facial hyperemia, facial edema </li></ul><ul><li>-> Persistent sinusitis: good general aspect, slight or no fever, persistent production of mucus, persistent of cough or nasal obstruction, inappetence, mild cephalea, maintenance of an asthmatic crisis </li></ul>
  59. 62. Sinusitis: temporal evolution (from Wald E: see references)
  60. 63. Bacterial acute sinusitis <ul><li>Golden pattern for diagnosis: culture of aspirated mucus: not a simple procedure, requires specialization </li></ul><ul><li>Radiography: can show inespecific sinusal signs. Does not show all the facial sinus. </li></ul><ul><li>Signs: thickening of mucosa </li></ul><ul><li>blurring of sinus </li></ul><ul><li>hydroaerial levels </li></ul><ul><li>Tomography: presents a nice accuracy, but can not differentiate between simple virus sinusitis and bacterial ones. </li></ul>
  61. 67. <ul><li>X-Ray with a complete blurring of the left sinuses </li></ul>
  62. 68. Etiology of acute bacterial sinusitis <ul><li>Basically, the aerophilic microbes from the rhinopharynx: </li></ul><ul><li>Pneumococcus </li></ul><ul><li>Haemophilus </li></ul><ul><li>Moraxella </li></ul>
  63. 69. Treatment <ul><li>1) Essential: nasal desobstruction: frequent washing with saline solution, control of the allergic rhinitis </li></ul><ul><li>2) Antibiotics </li></ul><ul><li>Principle: most of the persistent sinusitis will solve within 10 days. In these patients, the antibiotics reduce such time to 3-4 days </li></ul><ul><li>So, for mild sinusitis, 7 days is the standard </li></ul><ul><li>Severe forms: antibiotics in higher doses and for more time (10, 15 days) </li></ul><ul><li>3) Corticoids: a short usage of corticoids (3-4 days) is indicated in the severe cases. The action is to quickly reduce the edema of the mucosa and hence the ammelioration in the clearance of the sinus </li></ul>
  64. 70. Conclusion <ul><li>Very common </li></ul><ul><li>Use antibiotics rationally and reasonably </li></ul><ul><li>Re-evaluate your patients </li></ul><ul><li>Give written information to your patiens. </li></ul>
  65. 71. References <ul><li>Cecil Tratado de Medicina Interna </li></ul><ul><li>Penildon Silva Farmacologia </li></ul><ul><li>Brasil. Ministério da Saúde. Normas para o controle e assistência das infecções respiratórias agudas. 3ª edição, 1993. </li></ul><ul><li>Wald E. Sinusite bacteriana aguda-protocolo da Academia Americana de Pediatria. IV Manual de Otorrinolaringologia da IAPO. São Paulo: 2005. </li></ul><ul><li>Almeida e cols. Consenso para o tratamento e profilaxia da influenza no Brasil. Sociedade Brasileira de Pediatria. http://www.sbp.com.br </li></ul><ul><li>Jefferson e cols. Inibidores da neuraminidase para prevenção e tratamento da influenza em adultos saudáveis: revisão sistemática e metanálise. BMJ Brasil 3(21): 24-37, 2010 </li></ul><ul><li>Lopes e cols. Perfil farmacocinético de três diferentes doses diárias de amoxicilina. Revista Brasileira de Medicina 57(1/2): 70-74, 2000. </li></ul><ul><li>Mantese e cols. Prevalência de sorotipos e resistência antimicrobiana de cepas invasivas de Streptococcus pneumoniae . Jornal de Pediatria 79(6): 537-542, 2003. </li></ul><ul><li>Pereira e cols. Prevalência de bactérias em crianças com otite média com efusão. Jornal de Pediatria 80(1):41-48, 2004 </li></ul><ul><li>http://oradiologista.blogspot.com </li></ul><ul><li>http://www.combustao.org/2009/02/as-10-partes-mais-inuteis-no-seu-corpo/ </li></ul>