Flu in children
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Flu in children



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

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



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    Flu in children Flu in children Presentation Transcript

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