RS

CORYNEBACTRIUM DIPTHERAE
Club-shaped gram-positive, non-capsulated, non-sporing, non-motile rods.

Chinese letter or cuneiform arrangement in smear-cells divide and daughter cells tend to lie at acute angles to each other.
Snapping type of division.
Metachromatic granules present at ends or poles of bacilli (also called polar bodies or
Babes Ernst bodies or volutin granules). Storage granules composed of polymetaphosphates. Special stains, such as
Albert’s, Neisser’s and Ponder’s stain.
Granules are well developed on enriched media, such as blood agar or Loeffler’s
serum slope.
○○ Volutin granules can also be possessed by:
▪▪ Corynebacterium xerosis
▪▪ Gardnerella vaginalis
▪▪ Spirillium
▪▪ Few Mycobacterium species
▪▪ Enterobacter aerogene
▪▪ Few yeasts.

Virulence Factor (Diphtheria Toxin)

Two fragments: Fragment A (active unit) and B (binding unit)
• Fragment B binds to the host cell receptors (such as epidermal growth factor) and helps
in entry of fragment A.
• Fragment A is internalized into the host cells and then causes→ ADP ribosylation of
elongation factor 2(EF2)→ inhibition of EF2→ irreversible inhibition of translation step
of protein synthesis→ cell death.
• Mechanism of DT is similar to exotoxin A of Pseudomonas.

Toxoid is used for Vaccination

• Diphtheria toxin is antigenic and antitoxins are protective in nature. However, as it is
virulent, cannot be given directly for vaccination.
• Toxin can be converted to toxoid which is used for vaccination.

Toxoid formation is promoted by formalin, acidic pH and prolonged storage.

Pathogenicity and Clinical Manifestations

Diphtheria is toxemia but never a bacteremia:

• Bacilli are noninvasive, present only at local site (pharynx), secrete the toxins which
spread by bloodstream to various organs.
• It is the toxin which is responsible for all types of manifestations including local
(respiratory) and systemic complications (except the skin lesions which may be caused
due to the organism).

Respiratory Diphtheria
This the most common form of diphtheria. Tonsil and pharynx (faucial diphtheria) are the
most common sites followed by nose and larynx and rarely non-respiratory mucosa, such as
conjunctiva or vagina. Incubation period is about 3–4 days:

Faucial diphtheria: Toxin elicits an inflammatory response that leads to necrosis of

the epithelium and exudate formation leading to formation of pseudomembrane
(tough leathery greyish white coat composed of an inner band of fibrin surrounded by
neutrophils, RBCs and bacteria).
Pseudomembrane is so named, as it is adherent to the mucosal base and bleeds on
removal in contrast to the true membrane which can be easily separated (e.g. as in
Candida).
Bull-neck appearance: Characterized by massive tonsillar swelling and neck edema.

Laboratory Diagnosis

™. Laboratory diagnosis is necessary only for:

„. Confirmation of clinical diagnosis
„. Initiating
the control measures
„. Epidemiological purposes.

Laboratory diagnosis consists of isolation of the bacilli

and toxin demonstration.

Elek’s gel precipitation test:

This is a type of immunodiffusion
in gel described by Elek (1949)
„. The strain isolated is streaked onto a media containing
a filter paper soaked with antitoxin
„. If the strain is toxigenic, it liberates the toxin which
diffuses in the agar and meets with the antitoxin to
produce an arrow-shaped precipitation band
„. This test can also be used to know the relatedness
between the strains isolated during an outbreak.
The precipitate bands of outbreak isolates (streaked
adjacent) when meet with each other, three patterns
may be observed (Fig. 60.5)
1. Cross-over with each other—indicates unrelated
Strain.
2. Spur formation—indicates partially related strain
3. Fused with each other—indicates identical strain.

DIPTHERIA VACCINE
Active immunization is done by diphtheria toxoid that induces antitoxin production in
the body.

Herd immunity of > 70% is required to prevent epidemic

Types of vaccine:
○○ Single vaccine: Diphtheria toxoid (alum or formal precipitated)
○○ Combined vaccine:
▪▪ DPT: Contains DT (diphtheria toxoid), Pertussis (whole cell) and TT (tetanus
toxoid)
▪▪ DaPT: Contains DT, TT and acellular pertussis (aP)
▪▪ DT: Contains DT and TT
▪▪ dT: Contains adult dose diphtheria toxoid (d) and TT.

DPT Vaccine

• DPT is the preparation of choice for vaccinating infants, because:

○○ Infants can be immunized simultaneously against three important childhood diseases:
diphtheria, tetanus and pertussis by single injection.
○○ Pertussis component acts as adjuvant and increases immunogenicity of DT and TT.
• There are two types of DPT:
○○ Plain formol toxoid (or fluid toxoid): Toxoid is prepared by incubating toxin with
formalin
○○ Adsorbed (alum adsorbed): Alum acts as adjuvant and increases the immunogenicity
of toxoid.
• Administration of DPT:
○○ Schedule: Under national immunisation schedule of India, total five doses are given;
three doses at 6, 10 and 14 weeks of birth followed by two booster doses at 16–24
months and 5 years.
○○ Site: DPT is given deep intramuscularly (IM) at anterolateral aspect of thigh, (gluteal
region is not preferred as fat may inhibit DPT absorption)
○○ Storage: DPT should be kept at 2–8°C, if accidentally frozen then it has to be discarded.
○○ Dose: 1 dose (0.5 ml)
○○ dT: It contains TT and adult dose (2Lf) of diphtheria toxoid. dT is given to adults
> 12 years (3 doses at 0, 1 month, and 1 year).

Reactions following DPT administration:

○○ Mild: Fever and local reaction (swelling and indurations)
○○ Severe: Whole cell killed Bordetella pertussis is encephalitogenic. It is associated
with neurological complications. DPT is not recommended after 6 yrs of age.
○○ Absolute contraindication to DPT:
▪▪ Hypersensitivity to previous dose
▪▪ Progressive neurological disorder
Acelluar pertussis component (aP) is devoid of neurological complication and is given safely
to older children.

SWINE FLU (H1N1)

™. Origin: H1N1 2009 flu originated by genetic reassortment
of four strains (1 human strain + 2 swine strains + 1 avian
strain) and the mixing had occurred in pigs
™. Though people commonly use the word ‘swine flu’
to describe H1N1 2009 flu, but this is not the correct
terminology as it is a reassortant of four strains
™. Transmission: It can be transmitted from human to
human, which has accounted for its rapid spread
™. However, it is less virulent.
™.Therefore in contrast to H5N1, the H1N1 2009 flu has
caused more morbidity but less mortality.

Clinical Features
™. Uncomplicated influenza:
mild upper respiratory tract illness and diarrhoea
™. Complicated/severe influenza very rarely
in high-risk groups, - secondary bacterial pneumonia, dehydration, CNS
involvement, and multiorgan failure.
Prevention

Strict hand hygiene

™. Isolation room:
™. Containment of coughs and sneezes
„. Respiratory hygiene and cough etiquette
„. Use of personal protective equipment (PPE) such as
gloves, 3-ply masks, gown and googles for a HCW.
Patient should wear a mask.
™. Work restriction:

Prophylaxis
• Vaccine: Both killed injectable and live nasal spray vaccines are available for A/H1N12009
flu.
• Chemoprophylaxis: Oseltamivir-75 mg once a day, duration depends on the clinical setting.