Diphtheria Overview and Pathogenesis

Diphtheria

• Diphtheria is a potentially acute disease caused by exotoxin-producing Corynebacterium diphtheriae, a Gram-positive bacillus.
• Humans are the only natural reservoir of C. diphtheriae.
• Spread occurs through close contact, respiratory droplets, or direct contact with respiratory secretions or skin lesions.
• Diphtheria immunization protects against disease but does not prevent carriage.
• Vaccine-induced immunity wanes with time.
• Corynebacterium diphtheriae is a nonmotile, non-capsulated, club-shaped, Gram-positive bacillus.
• Toxigenic strains are lysogenic for a family of corynebacteriophages carrying the structural gene for diphtheria toxin.
• Corynebacterium diphtheriae is classified into biotypes (mitis, intermedius, and gravis) based on colony morphology on tellurite-containing media. Pathogenesis:
• Corynebacterium diphtheriae colonizes the mucosal surface of the nasopharynx and multiplies locally without blood stream invasion.
• Released toxin causes local tissue necrosis, forming an adherent pseudomembrane of fibrin, dead cells, and bacteria.
• Toxin absorption can lead to systemic manifestations like kidney tubule necrosis, thrombocytopenia, cardiomyopathy, and nerve demyelination.
• Respiratory tract diphtheria has an average incubation period of 2-4 days (range 1-10 days), presenting with anterior nasal diphtheria or pharyngeal and tonsillar diphtheria.
• Symptoms include sore throat, malaise, mild-to-moderate fever, and a grayish membrane.
• Cervical adenopathy and soft tissue edema lead to a bull neck appearance and stridor.
• Laryngeal diphtheria manifests as hoarseness, stridor, and dyspnea.
• Cutaneous diphtheria is indolent, nonprogressive, characterized by a superficial, non-healing ulcer with a gray-brown membrane.

Diphtheria Diagnosis

• Specimens for culture should be obtained from the nose, throat, and any other mucocutaneous lesions.
• Gram stain is used to identify the organism.
• Special stains (Albert's stain, Ponder's stain) detect metachromatic granular structures.
• Selective media (tellurite agar, Loeffler, Tinsdale medium) are used for culturing.

Diphtheria Differential Diagnosis

• Streptococcal and viral tonsillopharyngitis
• Infectious mononucleosis
• Vincent's angina
• Candidiasis
• Acute epiglottitis

Diphtheria Management

• Goals of treatment: neutralize the toxin rapidly, eliminate the infecting organism, provide supportive care, and prevent further transmission.
• Mainstay of therapy is equine diphtheria antitoxin (a single dose ranging from 20,000 to 100,000 units). Administered intramuscularly or intravenously.
• Antimicrobial therapy: Erythromycin (40-50 mg/kg/day PO or IV), aqueous crystalline penicillin G (100,000-150,000 units/kg/day IV or IM), Procaine penicillin (300,000 units every 12 hours IM for ≤10 kg, 600,000 units every 12 hours IM for >10 kg), oral penicillin V (250...).

Diphtheria Complications

• Myocarditis
• Conduction disturbances (ST-T abnormalities, arrhythmias, heart block)
• Neurologic complications (cranial nerve palsies, polyneuritis, palatal or pharyngeal paralysis)

Diphtheria Prognosis

• Depends on organism virulence, patient age, immunization status, site of infection, and speed of antitoxin administration.

Diphtheria Prevention

• Immunization (minimum protective level for diphtheria antitoxin is 0.01-0.10 IU/mL).
• Asymptomatic case contacts: close monitoring (7 days) and possible antibiotic prophylaxis (benzathine penicillin G, erythromycin).

Pertussis

• Pertussis is a respiratory tract infection characterized by paroxysmal cough (whooping cough).
• Caused by Bordetella pertussis and Bordetella parapertussis.
• Bacteria spread via aerosolized droplets from coughing infected individuals.
• Global incidence is 48.5 million cases and 295,000 deaths annually.
• The case-fatality rate among infants in low-income countries is 4%.
• Neither natural infection nor vaccination provides lifelong immunity.
• Bordetella organisms are small, fastidious, Gram-negative coccobacilli that colonize only ciliated epithelium.
• B. pertussis expresses pertussis toxin (PT), the major virulence protein.
• Tracheal cytotoxin, dermonecrotic factor, and adenylate cyclase damage local epithelium, causing respiratory symptoms and facilitating PT absorption.

Pertussis Clinical Manifestations

• Incubation period: 3–12 days (up to 21 days).
• Insidious onset, similar to a minor upper respiratory infection with a nonspecific cough.
• Fever is usually minimal throughout the course.
• Apnea and cyanosis (particularly in infants).
• Stages:
• Catarrhal stage (1–2 weeks), URI, very contagious
• Paroxysmal stage (1–6 weeks), worsening cough, post-tussive emesis, inspiratory whooping, cyanosis, exhaustion
• Covalescent stage (2–3 weeks), cough decreases, symptoms may return or worsen

Pertussis Diagnosis

• Predominant or pure cough complaint for at least 14 days with associated symptoms (paroxysms, whoop, post-tussive vomiting).
• Suspect in older children with escalating cough (7-10 days), characterized by bursts of coughing.
• Suspect in infants (<3 months) with gagging, gasping, apnea, cyanosis, or apparent life-threatening events.
• Laboratory tests include: leukocytosis (lymphocytosis), thrombocytosis, culture (nasopharyngeal swab), direct fluorescent antibody, PCR, and CXR.

Pertussis Management

• Indications for hospitalization: respiratory distress, evidence of pneumonia, inability to feed, cyanosis or apnea (with or without coughing), seizures, age <4 months.
• Isolation: droplet precautions (mask within 3 feet) until five days of effective therapy or three weeks after symptom onset in untreated patients.
• Antimicrobial therapy; cultures or positive PCR (within three weeks of cough onset), infants/children (symptom duration <21 days), and those likely to contact high-risk individuals.

Pertussis Complications

• Hypoxia, apnea, pneumonia, seizures, encephalopathy, and malnutrition.
• Frequent complication: pneumonia
• Atelectasis may develop secondary to mucous plugs
• Force of paroxysm: rupturing alveoli, leading to pneumomediastinum, pneumothorax, or interstitial/subcutaneous emphysema.

Pertussis Prevention

• Post-exposure prophylaxis with Azithromycin.

Tetanus

• Tetanus is a neurologic disorder characterized by increased muscle tone and spasms, caused by tetanospasmin (a powerful protein toxin) produced by Clostridium tetani.
• Types: Generalized, neonatal, and localized.

Tetanus Etiology

• C. tetani is an anaerobic, motile, Gram-positive rod.
• Oval, colorless, terminal spore; tennis-racket or drumstick shape.
• Can survive autoclaving at 121°C for 10-15 minutes.

Tetanus Epidemiology

• Occurs sporadically.
• Mostly affects unimmunized, partially immunized individuals who fail to maintain adequate immunity, or those with inadequate booster doses of vaccine.
• Globally, 57,000 deaths in 2015 (20,000 in neonates and 37,000 in older individuals).

Tetanus Pathogenesis

• Tetanus toxin binds at the neuromuscular junction, entering motor nerves by endocytosis.
• Retrograde axonal transport to a-motoneurons cytoplasm.
• Toxin enters adjacent spinal inhibitory interneurons, preventing the release of neurotransmitters (glycine, GABA).
• Blocking normal inhibition of antagonistic muscles.

Tetanus Clinical Manifestations

• Incubation period: ~10 days (range 3-30 days).
• Three major forms:
• Generalized tetanus (80%)
• Localized tetanus
• Cephalic tetanus (rare) in children w/ otitis media.
• Generalized tetanus: descending pattern; initial sign = trismus (lockjaw); symptoms include headache, restlessness, early symptoms, stiffness of neck, difficulty in swallowing, and rigidity of abdominal muscles, sardonic smile, arching (opisthotonus).
• Neonatal tetanus: often fatal; typically occurs when the umbilical cord is cut with an unsterilized instrument within 3-12 days of birth; progressive difficulty feeding with associated hunger and crying; stiffness, spasms with or without opisthotonos posturing.

Tetanus Diagnosis

• Primarily clinical.
• Injured unimmunized patient or baby born to an unimmunized mother presents within 2 weeks, showing trismus, rigid muscles, and clear sensorium.
• Organism isolated from wound or ear discharge.

Tetanus Management

• Wound debridement
• Immunoglobulin administration (human tetanus immunoglobulin, TIG) 3,000–6,000 units IM immediately. TIG has no effect on toxin already fixed to neural tissue.
• Antibiotics
• Supportive care (Penicillin G 200,000 units/kg body weight intravenously).
• Local wound, discharging ears, umbilical cord should be cleaned and debrided.
• Muscle relaxation and seizure control (Diazepam, midazolam, baclofen).
• Neuromuscular blocking agents (vecuronium, pancuronium) for severe cases.

Tetanus Prevention

• Active immunization (best method) – Three doses of DPT at 6, 10, and 14 weeks, followed by boosters at 18 months, 5 years and every 10 years thereafter.

This quiz explores the essential aspects of diphtheria, including its causative agent Corynebacterium diphtheriae, transmission methods, and the immune response. Learn about the characteristics of the bacterium, the impact of vaccination, and the disease's clinical significance. Test your understanding of this important infectious disease.