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

Epidemiology:

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

Pathogenesis: 

·       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 pharynx: The 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 40^oC) 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

mild	localized	Tonsils (islet-form), nose eye ear skin genital tract
moderate	localized spread	Tonsils (membranous-form) Nasopharyngeal Localized croup Tonsils, nose eye ear skin genital tract
severe	Spread Toxic, hypertoxic	Spread croup Tonsils , nose eye ear skin genital tract

The course of disease

·       With complication

·       Without complication

Complications

-         early:

 toxic shock syndrome;

DIC syndrome

suprarenal glands insufficiency;

Kidneys insufficiency

Respiratory insufficiency

Plural organs insufficiency

 (in the end of 1^st to 2^nd week) nephritis; myocarditis; peripheral cranial nerves palsies;

Late (on the 3^rd to 7^th 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 1^st 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

Signs	Diphtheria of the pharynx	Scarlet fever	Infectious mononucleosis	Streptococcus (staphylococcus) tonsillitis
Beginning	acute	acute	acute	acute
Leading symptoms	fibrinous inflammation in a throat, toxic syndrome	tonsillitis,exanthema from1-2 day, Filalov’s sign,  toxic syndrome	Lymphoproliferative syndrome, tonsillitis 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
Lymphadenitis	Regional	Regional	General	Regional
Hepatosplenomegaly	Absent	Absent	Typical	Absent
Rashes	Absent	Pin-point, red	Maculous-papulous may be erythematic in 70-80% of patients, who take semisyntetic penicillins	Absent
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	Absent	Upon the regional lymph nodes in severe cases	Absent
Changes on the tongue	Coated	Coated, strawberry from the 4-5th day	Coated	Coated

 

Bacterial follicular tonsillitis

Bacterial lacunar tonsillitis

 

Necrotizing tonsillitis

 

Bacterial membranous tonsillitis

  

Candidiasis

 

Peritonsillitis, peritonsillar abscess

 

Mumps

Differential Diagnosis of the Respiratory Tract Diphtheria

Signs	Parainfluenza	Diphtheria	Chicken pox	Measles
Beginning	acute	gradual	acute	acute
Main signs	Catarrhal symptoms from the upper respiratory tract, laryngitis	Laryngitis, slowly development of airways obstruction, low intoxication	rashes	Catarrhal symptoms from the upper respiratory tract, conjunctivitis, rashes
Catarrhal symptoms (cough, corryza)	Expressed, moderate	absent	mild	expressed
Character of the cough	dry, rough, barking	“ barking”, then soundless	is rare	dry, or moist
Voice	Hoarse	Hoarse, then soundless	Is not changed	May be hoarse
Oropharyngeal changes	Moderate hyperemia	Absent or may be combined with oropharyngeal diphtheria	absent	Enanthema, light hyperemia
Lymphadenitis	absent	regional	absent	May be plural
Pathomorphology	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

Myocarditis:

• needs bed regimen on 35-50 days;

• cardiomonitoring;

• prednisone 2 mg/kg/ day per os;

• rhiboxin or ATPh,

• per oral potassium (panangin);

• diuretics.

Neuritis:

• 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.

Prophylaxis

Specific:

• 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

Nonspecific:

• 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.