Upload
elmadana1988
View
37
Download
2
Tags:
Embed Size (px)
Citation preview
Whooping cough
Whooping cough is an acute highly contagious respiratory disease of only humans, which is caused by Gram– pathogenic Bordetella pertussis and is characterized by typical clinical presentation with coughing attacks with reprizes
Importance of whooping cough (Cherry D.J., 2005)
Annually about 40 million cases of pertussis are registered in the world
During the last 20 years the frequency increases among teenagers and adults
Atypical case frequency increasesEvery year about 300 thousand unvaccinated
children all over the world die, mostly before 6 months of age
About 70% of early age children with whooping cough are hospitalized
30% of hospitalized children develop severe complications
History of whooping cough1414
yearFirst mention about epidemics of whooping
cough in France
1540 year
The clinical presentation are first described in the book of Moultone “Mirror of health”
1578 year
The first medical description of whooping cough in Paris
1679 year
Sidenhem named the disease “whooping cough”. Pertussis (intensive cough), Tos ferina – in Spain and Tosse canina - in Italy (dog’s barking), Chincough – in England (suffocating cough), Coq luche – in France (cock’s cry)
1900 year
Bordetella pertussis was first found microscopically in mucus of a patient with whooping cough
1906 year
Borde and Geangou received culture of Bordetella pertussis
History of whooping cough
1908 year
The first experimental vaccine was created from killed culture of Bordetella pertussis
1926 year
Experimental vaccination of people against whooping cough is begun
1945-60 years
World-wide vaccination with whole cell vaccine is started
1965-1977 years
Development of acellular vaccine against whooping cough
1996 year
In USA, Europe and Japan the vaccination with acellular vaccine is started
2006 year
In USA scheduled revaccination of adult population is implemented
Epidemiology of whooping cough Whooping cough is a typical anthroponous disease, the nature reservoir of which is human
Epidemiological cycle of Bordetella pertussis before and after mass vaccination (Hewlett E.K. et al., NEMJ, 2005)
Epidemiology of whooping coughSpread All over the world
Way of transmission Air-born, droplets
Peak of frequency August - September
Epidemic cycles 3-4 years
Contagiousness 100% in non-vaccinated
Morbidity 1500 per 100 000
Sex (m/f) 0,85
Age structure of the disease
<1 year – 29,4%
1-4 years – 11,1%
5-9 years – 9,8%
10-19 years – 29,4%
≥20 years – 20,4%
Age structure of the mortality
≤6 months - 90%
5-9 years – 3,6%
>28 years – 3,6%
Etiology of whooping cough
Electronic microphotograph of Bordetella pertussis (х5000)
Bordetella pertussis – small, non-movable, Gram- , anaerobic coccobacillus
Bordetella toxin
Promotes adhesion to respiratory epithelium, sensitization to histamin, lymphocytosis, increased insulin secretion, provokes mitogenesis of T-lymphocytes, stimulates IL-4 and IgE production, block phagocyte activity of leucocytes, causes cytopathic effect
Filamentous hemagglutinin
Promotes adhesion to respiratory epithelium, agglutinates erythrocytes
Pertactin Promotes adhesion to respiratory epithelium
AgglutinogensPromote adhesion to respiratory epithelium
Main factors of virulence of Bordetella pertussis
Adenylate cyclase
Blocks phagocyte activity of leucocytes, induces apoptosis of macrophages, catalyses over-physiologic production of АМP, causes hemolysis
Tracheal toxin Stimulates IL-1 and NO production, causes ciliar stasis and necrosis of respiratory epithelium
Dermonecrotic toxin
Causes vasoconstriction and focal necrosis
Lipopolysaccharides
Acts as endotoxin
Fimbria (adhesin)Promote adhesion to respiratory epithelium
Main factors of virulence of Bordetella pertussis
Pathogenesis of whooping cough
Main key of pathogenesis believed to be local changes in bronchial epithelium (Mattoo S., Cherry D.J., Clin Microb Rew,
2005)
Scheme of local influence of Bordetella pertussis on ciliar respiratory epithelium (Kerr J.R., Eur J Clin Microbiol
Infect Dis ,2000)
Pathogenesis of whooping cough
Inoculation of В. pertussis into nasal mucous
Growth of ciliar epithelium with inflammation
Loss of ciliar epithelium
Epithelial metaplasia
Cough Vomiting
Increased intrathoracis pressure
Venous stasis
Encephalopathy
Recovery
Secretion of bronchial mucus
Bronchial obstruction
Secondary bacterial
pneumonia
Focal emphysema
Pneumothorax
Hypoxia
Schaechter M. (Ed.)
Mechanisms of bacterial diseases, 4th
еd, LWW, 2004
Typical clinical courseStage Clinical presentations Catarrhal (3-12 days)
Dry cough, persisting till 2 weeks; exudative rhinitis, subfebrile fever, lacrimation, conjunctive hyperemia
Paroxismal (1-6 weeks)
Classical pertussis cough: appears suddenly or after short symptoms (throat dryness, chest pressure, anxiety), presents with “attack of a seria of short coughs one after another, without interruption, after than a noisy whistling inspiration (reprises). These attacks follow each other. The attack finishes with expectoration of thick transparant mucus and/or vomiting, sleepiness. During the attack the appearance is very typical: face is reddish, or even cyanotic, cervical veins are bulging, eyes are hyperemic, lacrimation appears, the tongue is out of mouth, its tip flexes up.”Apnoe (reprises equivalent), signs of encephalopathy, weight loss, sclerae and chest hemorrhages, ulcer of tongue, umbilical and inguinal hernia, subcutaneous emphysema
Recovery (2-3 weeks)
Stepwise decrease of attacks frequency and severity
Severity criteria of whooping cough
Mild Attach frequency is 10-15/day, 3-5
reprises/day
Moderate Attach frequency is 15-25/day, up till
10 reprises/day
SevereAttach frequency is > 25/day, >
10reprises/day, apnea
Differential diagnosis of whooping cough
Factors for whooping coughFactors contra whooping cough
Contact with patient with whooping cough or with long-coughing person
Absent or incomplete vaccination
Preserved general condition between attacks
Presence of reprises Vomiting after cough Apnea, bradycardia (in early
age children)Shortness of breath, difficulty
of speaking Petechia over clavicles Lymphocytosis (normal cells)
FeverDiarrhea Exanthema Enanthema Tachypnea Wheezes Crepitating and rales in
lungsNeutropeniaLymphocitosis (atypical
cells)
Differential diagnosis of whooping cough
Whooping cough must be excluded / confirmed in all cases of cough longer than 2 weeks and/or with attacks
and vomiting
Diseases to differentiate with:
Parapertussis Parainfluenza Influenza Respiratory
mycoplasmosisRespiratory
chlamydiosis Adenoviral infection
Bronchiolitis Pneumonia Sinusitis Tuberculosis Respiratory foreign bodyCystic fibrosis Syndrome of post-
infectious cough
Methods of diagnosis Method Comments
Nasopharyngeal culture“Gold standard” – culture of Bordetella pertussis
PCRcyaA –fragment of Bordetella pertussis
DNADirect fluorescence Ag Bordetella pertussis
Serologic investigations: Not-informative in vaccinated
- IgA to pertussis toxin High titers testify infection
- IgG to pertussis toxinHigh titers testify infection , 4-fold titer increase in 2-4 weeks confirms infection
- IgA to pertactin High titers testify infection
- IgG to pertactinHigh titers testify infection , 4-fold titer increase in 2-4 weeks confirms infection
Methods of diagnosisMethod Comments
- IgA to filamentous hemagglutinin
High titers testify infection
- IgG to filamentous hemagglutinin
High titers testify infection , 4-fold titer increase in 2-4 weeks confirms infection
- IgA to fimbria High titers testify infection
- IgG to fimbriaHigh titers testify infection , 4-fold titer increase in 2-4 weeks confirms infection
CBC (leucocytosis, lymphocytosis, normal ESR)
Non-specific – in non-vaccinated children. WBC can be 20 - 70 thousands
Criteria of diagnosis
Criteria Comments
Clinical
Presence of cough for longer than 2 weeks and one or more of following: cough paroxysms, reprises or post-cough vomiting, with exclusion of other causes
Laboratory
Culture of Bordetella pertussisPositive PCR for Bordetella pertussis DNAPresence and/or increase of specific
antibodies (in non-vaccinated)
Criteria of diagnosisProved cases :
Disease with any duration of cough and positive culture of Bordetella pertussis
orDisease with above-mentioned clinics and positive PCR
or Disease with above-mentioned clinics, not confirmed by culture or PCR (or by serology in non-vaccinated) and with proved epidemiologic contact
Probable cases : Disease with above-mentioned clinics, not confirmed by culture or PCR (or by serology in non-vaccinated) and without proved epidemiologic contact
Risk factors of complication and death
Age under 1 years (especially under 6 months)
Absent or incomplete vaccinationParoxysms with reprises frequency > 10 / day
Vomiting > 4 / day Presence of apnea Hypotrophy Prematurity Anemia (Hb<90g/l)
Risk factors of complication and death
Hypovitaminosis АChronic pulmonary insufficiency (lung defects)
Chronic cardiac insufficiency (heart defects)
Chronic adrenal insufficiency Bronchial asthmaCNS diseases Major immunodeficiencies
Complications of whooping cough
PneumoniaRetinal hemorrhages
and ruptures
Encephalopathy Umbilical and inguinal
hernias
Seizures Esophageal rupture
Apnea Pneumothorax
Atelectasis Lung function damage in adults
Acute otitis media
Complications of whooping cough
SepsisRespiratory distress
syndrome
CNS hemorrhages Psychological and motor
development deficit
Weight loss Subcutaneous
emphysema
Dehydratation Rectal prolapse
Hyponatremia Death
Alkalosis
Medical management
Adequate follow-up (all children with risk factors must be hospitalized)
Prophylaxis and treatment of encephalopathy (oxygenation, brain edema treatment, anti-convulsive therapy, etc.)
Provision of adequate feeding (from enteral to complete parenteral)
Prophylaxis and treatment of dehydratation, electrolyte and metabolic disturbances
Early diagnosis and treatment of complications Etiotropic therapy Not to use mucolytics, anti-tussive, broncholytic,
sedative drugs (can be used only under strict control), corticosteroids, herbal and homeopathic drugs (no efficacy)
Etiotropic therapy and chemo prophylaxis
Drug Regime and dosage
Erythromycin 40-50 mg/kg qid - 14 days
Azithromycin 1st day – 10 mg/kg 2-5th days – 5 mg/kg
Clarythromycin
20 mg/kg - 7 days
SMT/TMP 8 (40) mg/kg bid - 7 days
Prophylaxis
In Ukraine there are 2 vaccines – whole-cell and acellular
“Thanks to vaccination, annually 85,5 millions of pertussis cases and 760 of deaths from that infection are prevented ” (Tatochenko V.K., 2001]
Vaccine Immunogenic component
DPT [acellular)
Pertussis toxin, filamentous hemagglutinin, pertactin
DPT [cellular) Killed bacteria Bordetella pertussis
ProphylaxisPrimary vaccination includes tree doses at age 3, 4 & 5 months. Revaccination in 18 months
(Наказ МОЗ України №48 від 03.02.2006р.)
Index / Vaccine DPT [acellular)
DPT [cellular)
Disease prevention 77-90% 64-83%
Severe forms and complications prevention 84-91% 85-92%
Mortality prevention 100% > 99%
Pertussis vaccine efficacy (Cherry D.J., 2005)