Diphtheria

Dr Arun Kumar
 Outline of the presentation
Epidemiology
Aetiopathogenesis
Transmission and communicability
Occurrence and reservoir
Clinical features and complications
Laboratory diagnosis
Case selection
Case management and public health
interventions

Diphtheria
WHO Position paper : Disease burden
In the period 20112015, India had the largest
total number of reported cases each year, with
a 5-year total of 18 350 cases,
followed by Indonesia and Madagascar with 3203
and 1633 reported cases respectively.
South-East Asia Region was source of 5599%
of all reported cases each year during this
period.
Analysis further showed a significant under-
reporting of cases to WHO
 Aetiopathogenesis
Bacterial disease caused by Corynebacterium
diphtheriae
Gram positive, club shaped, slender bacilli
Exotoxin producing bacteria
Four biotypes Gravis, Mitis, Intermedius, Belfanti
Pathogenesis
due to exotoxin and cell wall components
exotoxin causes local and systematic cell
destruction
High case fatality (> 10%) in endemic areas
Transmission and communicability
Person to person spread:
droplet (airborne)
direct contact with respiratory secretions
rarely through discharges from skin lesions

Incubation period: 1-5 days (range, 1-10 days)

Period of infectivity:
2 weeks from onset
antibiotic therapy promptly terminates shedding
Transient carriers may shed organisms for 6 months
or more
 Occurrence and reservoir
Disease has almost disappeared from developed
countries due to high immunisation coverage
Foci of epidemicity and endemicity exist in countries
with low immunisation coverage
Humans are the only known reservoir of C.
diphtheriae
Transmission to susceptible individuals mostly leads
to transient pharyngeal carriage rather than disease
Pre-school and school-age children most commonly
affected in endemic countries
Clinical features and complications..1
Mostly asymptomatic or mild clinical course
Respiratory diphtheria:
moderate fever
exudative pharyngitis:
sore throat and difficulty in swallowing
greyish white pseudomembrane:
tonsils, pharynx, larynx
bleeds on attempt to dislodge
laryngeal diphtheria is medical emergency; requires
tracheostomy
bull neck appearance:
inflammation of cervical lymph nodes and swelling of
surrounding soft tissue
Clinical features and complications..2
Other complications:
Cardiac complications: Myocarditis,
arrhythmias
Neuritis:
Bulbar dysfunctions: palatal, pharyngeal,
facial and oculomotor paralysis
Peripheral neuropathy
Pneumonias: occurs in >50% of fatal diphtheria
In infants: otitis media, respiratory insufficiency
 Laboratory diagnosis
Direct microscopy of smear not advisable due to
false positives and false negatives
Culture of organism on special media containing
Tellurite is gold standard test
Toxigenicity test: Elek test
Molecular test:
detection of regulatory gene for toxin production
Screening of primary isolates for presence of tox gene
Case selection for VPD
surveillance
 Considerations
For public health surveillance it is important to
define a disease by a set of criteria:
consistent reporting of cases by reporting network
improves specificity of reported cases
Reporting network should also be sensitised
about other less common features of the
disease
Relaxation in case definitions may be required
during investigations of outbreaks
 Case selection
Case definitions

Other associated signs and symptoms

Complications
 Case definition
A suspected case of diphtheria is defined as:
An illness of upper respiratory tract
characterized by the following:
Laryngitis or pharyngitis or tonsillitis
AND
Adherent membranes of tonsils, pharynx and/or
nose
 Case definition
Pharyngitis and tonsillitis:
fever with pain and redness of the throat and/or
tonsils
Laryngitis:
hoarseness of voice and cough
Adherent membrane:
 Adherent membrane
Pseudomembrane: confluent sharply demarcated
membrane, tightly adherent and dark grey in
color
Initially isolated spots of grey or white exudate in tonsillar
and pharyngeal area
Spots coalesce within a day to form pseudomembrane that
becomes progressively thicker
Extends beyond margins of tonsils into tonsillar
pillars, palate and uvula
Streptococcal infection: white membrane limited to tonsillar
area
Dislodging of membrane likely to cause bleeding
Other associated signs and symptoms
Dysphagia: difficulty in swallowing
Difficulty in breathing
Headache
Change of voice: hoarseness or thick speech
Nasal regurgitation
Serosanguineous nasal discharge
 Complications
Bull neck diphtheria:
massive cervical adenopathy with
oedematous swelling of
submandibular region and
surrounding areas
Systemic manifestations of toxin
Myocarditis
Polyneuritis
Bulbar dysfunction
Palatal, pharyngeal, facial, laryngeal,
oculomotor or ciliary paralysis
 Demonstration of diphtheritic membrane

Source: https://www.youtube.com/watch?v=DsyO-f269fI Diphtheria

 Demonstration of laryngeal diphtheria

Source: https://www.youtube.com/watch?v=mbATsba5EuE
Case management and public
health interventions
 General principles
Morbidity and mortality still high in developing
countries
Early treatment reduces complications and
mortality
Prompt initiation of therapy on clinical suspicion
Dont wait for laboratory results for initiating specific
therapy
Collect specimen preferably prior to initiation of
treatment
Patient should be kept in strict isolation
 Management and Interventions

Case management:
Three main components:
Antibiotic therapy
Administration of diphtheria antitoxin
Supportive care

Public health interventions:

Two main components
Immunisation in community
Antimicrobial prophylaxis of contacts
 Antibiotic therapy
Drug of choice
Penicillin 0.6-1.2 g 6-hourly for 14 days
or erythromycin 0.5 g 6-hourly for 14 days
Advantages
Limit further bacterial growth
Limits carrier state
Limitation
No impact on already established toxin induced
lesions
Administration of diphtheria antitoxin
Reduces case fatality rates
Hyper-immune antiserum produced in horse
Administered
Intramuscular or intravenous
Early administration recommended as it neutralizes
free toxin
Recommended dose
Tonsillar diphtheria: 10 000 units
Pharyngeal diphtheria: 40 000 to 60 000 units
Extensive disease: 100 000 to 150 000 units
 Supportive care
Close monitoring including
Regular ECG to monitor cardiac manifestations
Attention to airway
Early interventions like
Pace maker for conduction disturbances
Drugs for arrhythmias
Tracheostomy or intubation to ensure continued
patency of airway
Mechanical removal of tracheobronchial
membrane
 Public health interventions
DPT to children less than 7 years of age
Persons aged more than 7 years can be given
DT/Td/Tdap depending on availability
DT full dose of Diphtheria and Tetanus Toxoid
Td low dose Diphtheria toxoid with full dose of
Tetanus Toxoid
Tdap - contains low dose of Diphtheria toxoid and
acellular pertussis along with Tetanus Toxoid
Post exposure microbial prophylaxis to all
contacts
 Public health interventions
Prophylaxis
Age Immunization
Antibiotic Dose Route Duration
Penicillin G 600 000 Single
IM
benzathine units dose
or
< 7 years
DPT
old Erythromycin (not 40 mg/kg
recommended for in 4 divided Per oral 7-10 days
age <1month) doses

Penicillin G
1.2 million IM Single
benzathine
units dose
> 7 years DT/Td/Tdap as
or
old per availability
1g/day in 4
Erythromycin divided Per oral 7-10 days
doses
 Post Exposure Prophylaxis
During outbreaks, vaccination records of all
contacts of each case should be reviewed.
Unvaccinated contacts should receive a full
course of diphtheria toxoid-containing vaccine
and
Under-vaccinated contacts should receive the
doses needed to complete their vaccination
series.
 Public health significance
Occurrence of diphtheria reflects inadequate coverage
under the routine immunization programme
Helps identify pockets of susceptible individuals
Aggressive efforts should be made to improve
immunization coverage
Epidemiological surveillance ensuring early detection
of diphtheria outbreaks, with laboratory facilities for
diagnosis essential
to guide control measures at local level
to assess progress and impact of vaccination programme
to generate data to formulate vaccination strategies

Diphtheria
 Surveillance for Vaccine Preventable Diseases
Disease Age Date of onset Sample collection WHO accredited
under group laboratory for
surveillance sample

Acute Flaccid Less Date of onset of Stool: 2 samples Sample can be KIPM Chennai
Paralysis than 15 Weakness within 14 days of collected till 2
years onset of weakness months of onset

Measles- Date of onset of Rash Serum: 4 to 28 Throat swab / Serum: PMCH Patna
Rubella days from onset of urine: Within 5 Throat swab/urine:
rash days of onset of KIPM Chennai
rash
Diphtheria Date of onset of sore Throat swab: 2nd day to 4 weeks KGMC Lucknow
All age throat with fever
group

Pertussis Date of onset of cough Naso-pharyngeal Serum: >4 week to NP Swab: NCDC
swab/Serum: 2 4 8 week of onset of Delhi
week from onset cough Serum: KGMC
of cough Lucknow

Neonatal Neonate Date of onset of No sample NA

Tetanus inability to suck

Note: AFP can be reported till 6 months from onset while MR/DPT till 3 months of their onset.
 Summary
Caused by exotoxin producing bacteria
Pseudomembrane over tonsil, pharynx, larynx is
pathognomonic
Myocarditis & neuritis are common complications
Bacterial culture is gold standard laboratory test
Case management involves antibiotics, antitoxin
serum and supportive care
Public health interventions involve appropriate
vaccination and prophylaxis for contacts
Diphtheria