DIPHTHERIA%20The%20Past,%20Present%20

1
DIPHTHERIAThe Past, Present the Future
Dr Cummings
HenryConsultant PaediatricianDELSUTH
2
PRE TEST

1. Diphtheria has been eradicated
2. The is a resurgence of diphtheria
3. The mainstay of treatment is antibiotics
4. Vaccination remain the most effective control
   measure.

3
Outline

• The Past
• The Present
• The future

4
Diphtheria, The Past

• Introduction
• Epidemiology
• Aetio-pathogenesis
• Immunology
• Clinical Presentation
• Complications
• Differentials
• Investigations
• Treatment
• Prognosis
• Prevention

5
Introduction

• An ancient disease described by Hippocrates in
  the 5th century BC
• Plagued Europe the American colonies in the
  18th century
• Diphtheria is an acute toxic infectious disease
• A localized infection of mucous membrane /or
  skin
• May have systemic complications/manifestations

6
Epidemiology

• Reservoir
• - Exclusively in humans
• - Skin infection and skin carriage constitute
  silent reservoir
• Mode of spread
• primarily by airborne respiratory droplets
• direct contact with
• -respiratory secretions of infected
  individuals
• -exudates from infected skin lesions

7
Epidemiology contd.

• In the U.S
• - Pre-vaccination era(1920s) gt 115,000 cases
  and 10,000 deaths reported annually
• - Recently, lt 5 cases are reported annually
• In Nigeria
• - 5,039 cases reported in 1989
• - 3,995 cases in 2000
• - 2,468 cases in 2001
• - 312 cases in 2006 (7.8 of global report)

8
(No Transcript)
9
Epidemiology contd.

• Carriers are important in transmission -
  constitute 3-5 of healthy individuals in endemic
  region
• Estimated mortality rates?5-10
• (up to 20 in lt5yrs, gt 40yrs)

10
Epidemiology contd.

• Sex
• No significant difference in the incidence in
  males females of similar immunization status
• Age
• - Commoner in 6month-12yrs
• (esp. in the pre-vaccination era)

11
Risk factors

• Incomplete or absent immunization
• Low herd immunity
• Travel to endemic areas or regions with current
  epidemic
• Immunocompromised states e.g. HIV/AIDS
• Low socio-economic status
• Poor health care facilities
• Overcrowding

12
Aetio-pathogenesis

• Caused by toxigenic Corynebacterium diphtheriae
• Types
• - Corynebacterium diphtheriae
• mitis
• intermedius
• belfanti
• gravis
• - Corynebacterium ulcerans- causes cutaneous
  disease

13
Characteristics

• Gram positive
• Club-shaped bacillus
• Aerobic
• Non-motile
• Non-encapsulated
• About 2-4µm in length
• Assume L /or V configuration to each other
• Form a Chinese lettering pattern

14
Corynebacterium diphtheria
15
Corynebacterium diphtheria

• Gram stain

• Methylene blue stain

16
Virulence

• Depends on the ability to produce the diphtheria
  toxin-an exotoxin
• Toxigenicity depends on the presence of a
  lysogenic bacteriophage
• Non-toxigenic strain can become toxigenic by
  coming in contact with toxigenic strains

17
B-phage that carries the tox gene that encodes
the diphtheria toxin
18
The Exotoxin

• A 62,000 dalton polypeptide
• Composed of 2 joined major segments
• (A and B)

19
Actions of the Toxin

• Segment B bind receptors on susceptible cells and
  facilitate entrance of segment A
• Segment A mediates toxic actions
• - inactivates RNA translocase
• - inhibits protein synthesis
• - causing tissue necrosis

20
Actions of The Toxin contd.

• Formation of pseudomembrane
• a dense necrotic coagulum of organism,
  epithelial cells, fibrin, leucocytes RBCs
• grayish-white or brown in colour

21
The Pseudomembrane

• Histological

• Gross

22
Other effects of the toxin

• Paralysis of palate hypopharynx
• Systemic absorption
• - renal tubules necrosis
• - thrombocytopenia
• - cardiomyopathy
• - demyelination of nerves
• - paralysis of the diaphragm
• The toxin is converted to toxoid (for
  vaccination) when treated with formalin

23
Immunology

• Organisms invasion usually remain localized
• The main immune response is to the exotoxin
• Immune response is antibody-mediated
• The antibody is of the IgG type Antitoxin
• Immunity does not prevent colonization rather it
  protects against the effects of the toxin

24
Immunology Contd.

• Active antibodies production may be induced by
• - active disease
• - carrier state
• - vaccination with the toxoid
• Passive immunity transplacentally transferred
• Immunity was previously thought to be life long

25
Assessment of immunity

• The Schick test
• - Intradermal injection of 0.1ml 150 dilution
  of toxin
• - positive result inflammation appearing after
  24-36hrs persisting for 4days no antitoxin
  no immunity
• - negative result has antitoxin - immune

26
Immunity assessment contd.

• Assay of serum level of antitoxin
• - full protection 0.1IU/mL
• - basic protection 0.01- lt0.1IU/mL
• - no protection lt 0.01IU/mL
• N.B Epidemic outbreak is likely when gt 90 of
  the population has lt 0.01IU/mL of antitoxin

27
Clinical Presentation

• Incubation usually 2-4days with a range of
  1-7days
• Classified into
• - Respiratory Tract Diphtheria
• - Non-Respiratory Tract disease
• - Complicated disease

28
Respiratory tract diphtheria

• Nasal Diphtheria
• - commoner in infants
• - little or no constitutional symptoms
• - serosanguineous nasal discharge
• - epistaxis

29
Nasal Diphtheria contd.

• - purulent foul smelling discharge
• - shallow ulcers /- pseudomembrane
• - unilateral or bilateral
• - may persist for several weeks
• - major source of transmission

30
Tonsilo-Pharyngeal

• Most common (90 of cases)
• Malaise
• Fever mild to moderate
• Sore throat drooling, odynophagia /- dysphagia
• Bull-neck appearance
• Pseudomembrane of variable extent

31
Bull-Neck appearance
32
Pseudomenbrane
33
Laryngeal Diphtheria

• Usually an extension of pharyngeal disease
• Hoarseness of voice
• Cough
• Inspiratory stridor

34
Laryngeal Diphtheria contd.

• Suprasternal, substernal subcostal recessions
• Symptoms signs of sudden airway obstruction
• Sudden death
• May require intubation/tracheotomy

35
Tracheo-bronchial diphtheria

• Usually an extension from pharynx larynx
• Diphtheria pneumonia hemorrhagic
• Bronchiolar pseudomembrane
• Airway obstruction/sudden death

36
Diphtheria Pneumonia
37
Non-Respiratory disease

38
Cutaneous diphtheria
39
Cutaneous diphtheria

• superficial, non-healing ulcers
• well defined margins
• pseudomembrane on floor of ulcer
• erythema tenderness of surrounding skin
• important in transmission in the community

40
Cutaneous diphtheria contd.

• Predisposing factors
• - pre-existing dermatoses
• - laceration
• - burns
• - bites
• - impetigo

41
Other non-respiratory disease

• Ear- otitis externa
• Eye purulent and ulcerative conjunctivitis
• Genital tract purulent and ulcerative
  vulvo-vaginitis
• Rarely septicaemia

42
Complications

• Toxic Cardiomyopathy
• - commonly myocarditis, rarely endocarditis
• - usually occurs at the end of 2nd wk of
  illness
• - tachycardia out of proportion to fever
• - arrhythmias
• - symptoms signs of CCF
• - occurs in 10-25 of patients
• - accounts for 50-60 of deaths

43
Toxic Cardiomyopathy contd.

• ECG findings
• - prolonged PR interval
• - ST segment elevation
• - 1st, 2nd, or 3rd degree heart block
• Echocardiogram
• - dilated cardiomyopathy
• - hypertrophic cardiomyopathy
• - vegetations

44
Toxic Neuropathy

• Usually occurs at 3-4wks
• Affects mainly motor functions
• Paralysis of soft palate pharyngeal wall
• - nasal voice
• - difficulty in swallowing (esp. fluids)

45
Toxic Neuropathy contd.

• Occulomotor N. cillary paralysis
• - strabismus /or blurred vision
• Peripheral neuritis diminished DTR paralysis
• - occasionally glove stockings neuropathy
  ( like GBS)
• Paralysis of the diaphragm

46
Airway obstruction

• Commoner in laryngeal disease
• May be sudden
• Usually due to dislodgement of Pseudomembrane
• May require intubation/tracheotomy mechanical
  ventilation

47
Differentials

• Tonsillo-Pharyngitis
• Viral Croup
• Epiglottitis
• Peritonsilar abscess
• Angioedema
• Myocarditis (other causes)
• Peripheral neuropathy 2o GBS

48
Laboratory Studies

• Methylene blue /or gram staining
• Culture using tellurite-Loeffler media
• Toxigenicity test
• - Elek test
• - PCR

49
Laboratory studies contd.

• FBC moderate leucocytosis
• Urinalysis transient proteinuria
• Serum assay of antibodies immunity
• Serum assay of troponin 1 myocarditis

50
Radiological studies

• Echocardiogram ECG findings
• Neck soft tissue X-ray prevertebral soft tissue
  swelling

51
Treatment

• Diphtheria Antitoxin
• - mainstay of treatment
• - give at clinical diagnosis
• - can only neutralize free toxins
• - efficacy diminishes with delay
• - only available from CDC/WHO
• - preferably given IV
• - dosage depends on site involved duration of
  illness

52
Dosage of Antitoxin (units)

• Site and extent of lesion illnesslt72hrs
  illness gt72hrs
• Nasal
  10,000-20,000 10,000-20,000
• One tonsil 20,000
  20,000-40,000
• Both tonsils/-
• Pharyngeal
  20,000-40,000 40,000-60,000
• Laryngeal or
• Combined types 40,000-80,000
  60,000-80,000
• Very extensive
• Disease
  60,000-80,000 80,000-100,000
• N.B. Test for sensitivity before administration
  and desensitized if necessary

53
Testing for Sensitivity

• Skin test
• - Intradermal injection of 0.1mL of 110
  dilution of antiserum in saline
• - read in 20mins
• - a wheal 1cm positive sensitive
• Conjunctiva test
• - conjunctivitis lacrimation positive
• Caution! Ensure adrenalin is available

54
Desensitizing

• 0.1ml of a 120 dilution subcut. - wait 20mins
• 0.1ml of a 110 dilution subcut. - wait 20mins
• 0.1 ml undiluted subcut. - wait
  20mins
• 0.3ml undiluted IM - wait
  20mins
• 0.5ml undiluted IM - wait
  20mins
• If no reaction has occurred the rest of the dose
  can be given IM

55
Antimicrobial therapy

• Role
• - halt toxin production
• - treat localized infection
• - prevent transmission
• Drugs/dosage
• - IV/IM penicillin
• iv xtapen 100,000/kg/day in 6hrly dosing
• im procaine pen. 25,000iu/kg/day, 12hrly
• - Oral erythromycin, 40mg/kg/day 6hrly

56
Antimicrobial contd.

• Other drugs that can be used
• - Clindamycin
• - Tetracycline
• Give for 10 14 days
• Elimination of organism should be confirmed by at
  least 2 successive negative culture obtained
  24hrs apart.

57
Treatment contd.

• Isolation
• - respiratory isolation for respiratory disease
• - contact isolation for cutaneous disease
• Bed rest
• Secure airway if necessary
• NG tube feeding palatal/pharyngeal paralysis

58
Treatment contd.

• IV fluid administration if needed
• Vaccinate 10 series /or boosters
• Disease notification
• Contact tracing

59
Contact tracing Care

• The risk of developing the disease after
  household exposure to a case is 2
• The risk of disease after exposure to a carrier
• is 0.3
• Types of contacts
• - asymptomatic case contact
• - carrier

60
Asymptomatic case contact

• monitor for illness
• culture
• Antimicrobial prophylaxis
• Vaccinate
• primary schedule.
• booster dose

61
Carrier

• The reported rate of carriage in household
  contacts of case patients is 0-25
• Antimicrobial prophylaxis x 7days
• Isolation
• Monitor
• Vaccination

62
Prognosis

• Depends on
• Virulence of the organism. Gravis has the highest
  fatality followed by intermedius and the least is
  mitis.
• Age higher mortality rates in individuals lt 5yrs
  and those gt 40yrs.
• Immunization status worse in the unimmunized

63
Prognosis (contd.)

• Site of infection/involvement mortality occur
  in
• lt 1 of cutaneous disease
• 10 of uncomplicated respiratory disease
• 30 40 of bacteremic disease
• 60 - 90 of those with cardiac involvement.
• Speed of administration of antitoxin worse with
  delay

64
Prevention

• Immunization is the mainstay of prevention
• Given as DPT
• Immunization schedule (NPI)
• - DPT1 6wks
• - DPT2 10wks
• - DPT3 14wks

65
The Present
66
Emerging Issues

• Changing epidemiology
• - recent re-emergence in some developed and
  developing countries
• - Shifting of the disease into the older
  population

67
(No Transcript)
68

• Immunity wanes over time

69
(No Transcript)
70
Other Epidemiological issues

• Questionable Notification from Nigeria
• Erratic values
• - In 1996 reported 2016 cases
• - In 1997 ,, 31cases
• DPT3 coverage in 1996 30

71
Inconsistent figures

• In 2003 2004 no case reported
• In 2003 Nigeria had the worst immunization
  coverage in the world
• DPT1 coverage 43.2
• DPT3 coverage 24.8
• Only 12.8 were fully immunized

72
Latest Immunization Coverage

• Global 79 estimated DPT3 coverage
• Current coverage in Nigeria
• - DPT1 is 65
• - DPT3 is 77
• WHO proposed coverage is 90

73
(No Transcript)
74
(No Transcript)
75
Changes In Immunization strategies

• Effect of passive immunity on 10 series
• Commencing 1O series later e.g.
• - In the US
• DPT1 2mth
• DPT2 4mth
• DPT2 6mth

76
New Immunization Strategies contd.

• Boosters
• - Given at
• 18mths
• 5yrs
• adolescence
• every 10yrs thereafter

77
(No Transcript)
78
New Formulations of the Toxoid

• Td
• - tetanus toxoid with lower dose of diphtheria
  toxoid
• - adult type
• for adolescence beyond
• - less side effects
• Tdap
• - tetanus toxoid smaller dose diphtheria
  acellular pertusis vaccine
• - may be used for pregnant women

79
Other Emerging Issues

• Antitoxin for Carriers
• To give or not to give ?
• The need for vaccination of pregnant women

80
The Future
81
Recommendations

• Improve coverage of 10 schedule to 90 at least
• 4th 5th DPT doses at 18mths 5yrs respectively
• Improve disease Surveillance and notification

82
Recommendations contd.

• Research to evaluate the need to
• - delay commencement of the primary series
• - give booster doses at adolescence
  thereafter every 10yrs, using Td
• - give Td or Tdap to pregnant women

83
Conclusion

• The global goal is to eradicate diphtheria. This
  may only be achieved by not only making the right
  policies but also ensuring that these policies
  are completely and effectively implemented.

84
THANK YOU