Monday, February 25, 2013

Awareness Campaign On Diphtheria

Diphtheria is an acute toxic infection caused by toxigenic strains of Corynebacterium diphtheria, characterized by a local lesion consisting of a membrane. The constitutional symptoms are due to circulation exotoxin, which has a special affinity for nerve tissue, heart muscle and kidneys. 

Etiology:  Corynebacterium diphtheria
·        Corynebacterium species are aerobic, no encapsulated, non-sporeforming, mostly no motile, gram-positive bacilli.

·        Sensitive to high temperature and disinfection
·        Stabile to freezing and dryness
·        Three biotypes –
1.     mitis
2.     gravis
3.     intermedius

C.diphtheriae colonies

Transmission is from person-to-person (from a patient or carrier)
·       through direct contact
·       or airborne respiratory droplets
These materials include discharge from the nose, throat, and lesions on the skin, eyes and even the vagina.
Contagious index – 10-15%
Seasonality – autumn-winter
Immunity – instable

·       Entrance for the infection: throat, nose, larynx, sex organs, wound.
·       Dissemination of the Corynebacterium, production of exotoxin.
·       Local toxin effects with membranous inflammation.
·       Toxemia.
·       Diffuse toxic effects on kidneys, suprarenal glands, cardiovascular system, and peripheral nervous system.

Fibrinous inflammation
      Diphtheritic (on flat multilayer epithelium)
      Crupose (on cylindrical single layer epithelium)

Incubation period is short (from one to seven days)

Clinical features: diphtheria may be localized, spread, toxic (with edema of subcutaneous tissue), hypertoxic, hemorrhagic.

Classification of Diphtheria
Classification of Diphtheria by localization
1. Diphtheria of tonsills
      localized (catarrhal, islet-like, membranous)  
      spread form     
      toxic form:
1.     I grade  
2.     II grade
3.     III grade
4.     hypertoxic
      hemorrhagic   form
      gangrenous form

Diphtheria of the pharynxThe clinical onset is generally insidious with low-grade fever, cough, hoarseness, and mild sore throat. Intensity of the body temperature and intoxication increases proportionally to the square of damages (localized, spread, toxic forms). While examining the throat you could see a gray adherent membranous exudates on the tonsils (localized forms), extending to soft palate, cheeks, even tongue (spread form). The exudates bleed when removed. Hyperemia of throat has cyanotic color with edema of mucous membrane.  Regional lymph nodes are enlarged and tenderness appears. In case of toxic forms you could see “bull neck” due to the neck subcutaneous tissue edema which may extend even to the thorax. Hypertoxic form has sudden onset with hard intoxication (nausea, vomiting, seizures, unconsciousness, body temperature is more than 40oC) which exceeds local symptoms. Hemorrhagic form is characterized by hemorrhages, bleeding, membranous exudates consists blood.

Tonsillar diphtheria, localized (moderate)

Tonsillar diphtheria, spread (moderate)

Tonsillar diphtheria, toxic (severe)

Tonsillar diphtheria, toxic (“bull neck” sign)

2. Diphtheria of the larynx (laryngotracheitis, croup)
·       Localized croup   
·       Spread croup
1.     laryngotracheitis
2.     laryngotracheobronchitis
·       Stages of croup
1.     Catarrhal croup
2.     Stenosis
1.     Compensated 
2.     Subcompensated
3.     Decompensated
3.     Asphyxia

Diphtheria of the upper respiratory tract demonstrates clinical features of croup. It has slow development, intoxication usually is absent because between membranous exudates and mucous membrane of larynx, trachea and bronchi mucous is present. That’s why toxemia is absent. Croup has catarrhal, stenotic stages and asphyxia.
Catarrhal stage: - duration 2-3 days; intoxication is small or moderate; barking cough, voice becomes hoarse; slow development of signs and symptoms/
Stenotic stage: - duration 2 hours – 2-3 days; moderate intoxication; stenotic breathing appears; signs of hypoxia (peripheral, then general cyanosis, tachycardia, anxiety).
Asphyxia: - pallor or grayness of skin; sleepiness; superficial breathing; arrhythmia, hypotonia, hypothermia, other signs of coma, then – death of the patient.

3. Diphtheria of the nasopharynx (nasopharyngitis, pharyngitis)
• difficulty of the nasal breathing;
• nasality of voice;
•throat pain with an irradiation in ears;
• nasal dyscharge is bloody-purulent;
• visible inflammation in the nasal cavity is absent;
• during posterior rhinoscopic examination edema and moderate hyperemia of  adenoid tonsill mucus and (or) fibrinous membranes on its surface;
• “spear-shaped” coat which slips down by the back pharyngeal wall;
• regional (posterior cervical) lymphadenitis;
• the signs of general intoxication are moderate or severe (fatigue, pallor, anorexia, increase of temperature).

4. Diphtheria of the anterior part of a nose
• Localized:
– Catarrhal,
– Islet-like,
– Membranous.
• Spread;
• Toxic.

Diphtheria of the anterior part of a nose also may be localized, spread and toxic. Signs of it: slow development; minimal toxic signs; it is hard to breathe by nose; purulent and bleed discharges from the nose; maceration of the perinasal area; rhinoscopy reveals gray adherent membranous exudates on the mucous membranes  or ulcers; in case of spread form they extend to additional cavities; in case of toxic form – perinasal edema appears, intoxication enlarges.

Diphtheria of the nose

5. Diphtheria of other localization: diphtheria of the eye, ear, sex organs,  umbilical, wounds, lip, and cheek.

diphtheria of the lip

In case of 2 or more localizations combined diphtheria is diagnosed.
• diphtheria of tonsills and diphtherial pharyngitis are the most frequent combination;
• diphtheria of tonsills and anterior part of nose;
• diphtheria of tonsills and laryngeal diphtheria;
• rapid growth of clinical symptoms and their dynamics;
• toxic syndrome is considerably severe;
• polymorphism of clinical symptoms.

Diphtheria severity
Tonsils (islet-form), nose
genital tract

Tonsils (membranous-form)
Localized croup

Tonsils, nose
genital tract

Toxic, hypertoxic
Spread croup

Tonsils , nose
genital tract

The course of disease
·       With complication
·       Without complication

-         early:
 toxic shock syndrome;
DIC syndrome
suprarenal glands insufficiency;
Kidneys insufficiency
Respiratory insufficiency
Plural organs insufficiency
 (in the end of 1st to 2nd week) nephritis; myocarditis; peripheral cranial nerves palsies;
Late (on the 3rd to 7th week): myocarditis; peripheral spinal nerves palsies.

Laboratory tests. Diphtheria can be confirmed with isolation of C.diphtheriae from the pharyngeal membrane, nose (bacterioscopic or bacteriologic method); serologic reactions, fluorescent antibody techniques are available.

Used to confirm infection combine isolation of C diphtheria on cultures with toxigenicity testing.

Bacteriologic culturing is essential to confirm the diagnosis of diphtheria.

Toxigenicity testing: Perform toxigenicity testing using the Elek test to determine if the C. diphtheriae isolate produces toxin.

Polymerase chain reaction

Serology: PHAR with erythrocyte diagnostic test before the DAT injection to measure the diphtheria toxin level in the blood; AR, PHAR, CBR with specific diagnostic test systems, growth of antibodies title in the dynamics.
Complete blood analysis: leucocytosis, neuthrophylosis with a shift to the left, the increased ESR.
Urinalysis: proteinuria, leucocyturia, erythrocyturia, casts, (infectiously-toxic damage of kidneys).
Biochemical blood test measure of the rest nitrogen, creatinine, urea
ECG in dynamics
Otolaryngologist, cardiologist, neurologist examination in dynamics, posterior rhioscopy in case of nasopharyngeal diphtheria, laryngoscopy in case of laryngeal diphtheria.


Diagnosis example:
Diphtheria of the pharynx, local membranous form, moderate degree.
Diphtheria, combined form: pharyngeal, toxic 1st grade and laryngeal, local: severe degree


Differential diagnose

Diphtheria of the pharynx must be differentiated from scarlet fever, acute bacterial tonsillitis, infectious mononucleosis; diphtheria of the upper respiratory tract – with viral croup caused by parainfluenza, measles, chickenpox, and influenza viruses.

Differential diagnostic of tonsillitis different etiology

Diphtheria of the pharynx
Scarlet fever
Infectious mononucleosis
Streptococcus (staphylococcus) tonsillitis
Leading symptoms
fibrinous inflammation in a throat, toxic syndrome
tonsillitis,exanthema from1-2 dayFilalov’s sign, 
toxic syndrome
Lymphoproliferative syndrometonsillitis is not obvious (secondary)
Tonsillitis (follicle,lacunas, necrotizing, toxic syndrome
Throat changes
Cyanotic hyperemia, edema
Bright "blazing" hyperemia marked off from the hard palate
Absent or bright hyperemia
Bright hyperemia
Character of tonsilar exudates
Grey-white, or yellow membranes, can spread outside the tonsils, are dense, hardly removed, mucus membranes bleeds under them, after the removal arise up again, are not separated
purulent in follicles or in lacunas, keep only on the tonsils, is easily taken off, mucus membranes does not bleed, are separated
purulent in follicles or in lacunas, white-yellowish, keep only on the tonsils, is easily taken off, mucus membranes does not bleed, are separated
purulent in follicles or in lacunas, white-yellowish, keep only on the tonsils, is easily taken off, mucus membranes does not bleed, are separated


Pin-point, red
Maculous-papulous may be erythematic in 70-80% of patients, who take semisyntetic penicillins
Toxic sign
Proportional to the surface of the inflammatory process (mild, moderate or severe
Severe in the first days
Prolong with gradual development (moderate or severe)
moderate or severe in the first days
Subcutaneous fat edema

Typical for toxic forms
Upon the regional lymph nodes in severe cases
Changes on the tongue
Coated, strawberry from the 4-5th day

Bacterial follicular tonsillitis

Bacterial lacunar tonsillitis

Necrotizing tonsillitis

Bacterial membranous tonsillitis


Peritonsillitis, peritonsillar abscess


Differential Diagnosis of the Respiratory Tract Diphtheria

Chicken pox


Main signs
Catarrhal symptoms from the upper respiratory tract, laryngitis

Laryngitis, slowly development of airways obstruction, low intoxication
Catarrhal symptoms from the upper respiratory tract, conjunctivitis, rashes
Catarrhal symptoms (cough, corryza)
Expressed, moderate
Character of the cough
dry, rough, barking
“ barking”, then soundless

is rare
dry, or moist
Hoarse, then soundless
Is not changed
May be hoarse
Oropharyngeal changes

Moderate hyperemia
Absent or may be combined with oropharyngeal diphtheria
Enanthema, light hyperemia

May be plural
Edema of the larynx
Obstruction by fibrinous membranes
Edema of the larynx

Edema of the larynx

Normal larynx
 Viral laryngitis, treated viral laryngitis

 Fungal laryngitis

Death may occur from
Toxemia toward the end of the firth week
Cardiac failure from toxic myocarditis (second week of illness)
Respiratory failure due to peripheral neuritis affecting the vagus nerve (third to seventh week)

Treatment: all the patients are hospitalized into infectious or resuscitative department (for severe forms and in case of laryngeal diphtheria).
• Absolute bed regime (2-3 wks);
• Diphtheritic antitoxin therapy (etiological) (Doses see in table);
• Antibacterial therapy for 10-14 days
– In moderate or severe cases:
n Semisynthetic penicillines 50-100 mg/kg/day
n or cefalosporins 100 mg/kg/day
– In mild cases:
n Erythromycin 40-50 mg/kg/day or
n Rifampicin 10-15 mg/kg/day
• Antiseptic fluids locally (in spray or for gurgling);
• Disintoxication therapy (50-100 ml/kg/day) with glucose, crystalloid and colloid fluids IV in moderate or severe cases;
• Corticosteroids therapy by prednisolone 2-3 mg/kg/day in moderate form, 10-20 mg/kg/day in severe form.

Prompt treatment with diphtheria antitoxin (DAT) from horse serum is mandatory following tests for hypersensitivity.

Diphtheria severity
First dose of serum (in thousands of IU)
Mild form of diphtheria
20 000 – 40 000
Moderate form of diphtheria
50 000 – 80 000
Severe form of diphtheria
90 000 – 120 000
Very severe form of diphtheria
(TSH syndrom, DIC syndrome)
120 000 – 150 000

In the mild case all the dose is given for one time IM.
In case of prolongation of intoxication and exudates or their increasing repeated dose should be given in 24 hours.
In the mild case when diagnosis is disputable serum may be given in 8-24 hours in case of positive bacteriological culture.
In the moderate case the repeated dose in 24 hours is used (as in table).
In the severe case the first dose is 2/3 of the total one. The repeated dose in 12 hours is used, or in 8 hours if all the serum was given IV.
In case of toxic and hypertoxic forms I dose of DAT must be put intravenously with physiologic saline.

In case of toxic shock syndrome:
- Immediately intravenous infusion of DAT with prednisone intravenously 30-50 mg before DAT;
- Prednisone 10-20 mg/kg/day in equal doses 2-4 times per day;
- Detoxication, correction of acid-base balance and electrolytes;
- Dopamine, trental, corglicon.
In case of diphtheria of the larynx (except DAT):
- Inhalation of antiedematous drugs (2 % NaHCO3, hydrocortisone, euphyllin, and mucolithics);
- suctioning of membranes and mucus;
inhalation of oxygen;
in the III stage of stenosis – intubation;
- In case of spread croup, combined with diphtheria of pharynx – tracheotomy.

Treatment of complications
• needs bed regimen on 35-50 days;
• cardiomonitoring;
• prednisone 2 mg/kg/ day per os;
• rhiboxin or ATPh,
• per oral potassium (panangin);
• diuretics.
• proserin;
• galanthamin;
• strychnine nitric;
• vitamins group B (B1, B6, B12), C;
• diuretics.
Discharge of the patient:
• Clinically healthy;
– Mild and moderate in 14-21 days;
– Severe – in 30-60 days.
• With two documented negative pharyngeal and nasal cultures taken 48 hrs apart in 3 days after stopping antibacterial treatment;
• Dispensarization not less than 6 months (in uncomplicated cases).

Treatment of healthy infected by C. diphtheria person:
– Erythromycin 40-50 mg/kg/day, or
– Roxitromycinum 5-8 mg/kg, or
– Rifampicin 10-15 mg/kg/day;
• Antiseptic fluids locally;
• Vitamins B-group, C;
• Immune modulators in case of chronic site of infection;
• Tonsillectomy, adenotomy in case of chronic carrying.

• by DTP vaccine from 3 months age 3 times with 30 days interval (3, 4, 5 months), revaccination in 18 months (DTaP), 6, 14, 18 years (DT), later – every 10 years.

Combined vaccines

• Close contacts who were previously immunized longer than 5 years before should receive booster dose of diphtheria toxicoid;
• Antibiotic (erythromycin, rifampin) orally for 7 days;
• Revealing, sanation of healthy infected persons;
• Looking after contacts for 10 days;
• Disinfection of epidemic focus.

Key words and phrases: diphtheria, localization, gray adherent membranous exudates, hyperemia with cyanotic color, regional lymph nodes enlargement, “bull neck”, croup,catarrhal, stenotic stage, asphyxia, fluorescent antibody technique, ultraviolet radiation.

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