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)