Pertussis, Aspergillosis, Mucormycosis, and Other Infectious Diseases

Posted on Dec 24, 2024 in Biology

Laboratory Diagnosis of Pertussis

Causative Agent: Bordetella pertussis, a gram-negative coccobacillus.

Pathogenesis

The bacteria attach to the ciliated epithelial cells of the respiratory tract using adhesins (filamentous hemagglutinin, fimbriae).

B. pertussis produces toxins:

• Pertussis toxin: Increases cAMP levels, leading to mucus production and tissue damage.
• Tracheal cytotoxin: Paralyzes and damages ciliated epithelial cells.

This causes characteristic cough and mucus accumulation.

Clinical Stages:

1. Catarrhal Stage (1-2 weeks): Mild cold-like symptoms (rhinorrhea, sneezing, low fever).
2. Paroxysmal Stage (2-6 weeks): Severe coughing fits with the “whooping” sound.
3. Convalescent Stage: Gradual recovery phase lasting weeks to months.

Laboratory Diagnosis:

1. Specimen: Nasopharyngeal swab or aspirate (best in the catarrhal stage).
2. Culture:
   • Plated on Bordet-Gengou agar or Regan-Lowe charcoal agar.
   • Incubation for 3-7 days shows small, shiny colonies.
3. PCR: Detects B. pertussis DNA in nasopharyngeal samples (most sensitive and rapid method).
4. Serology: Detection of antibodies against pertussis toxin (useful in late stages).
5. Direct Fluorescent Antibody (DFA) Test: Detects bacteria directly on smears.

Treatment:

• Macrolides (e.g., azithromycin, clarithromycin).
• Supportive care (hydration, oxygen therapy).

Vaccination Against Pertussis

Vaccine: The DPT vaccine

Types of Vaccines:

1. Whole-cell Pertussis Vaccine (wP):
   • Contains killed Bordetella pertussis.
   • Highly effective but associated with mild side effects (fever, irritability).
2. Acellular Pertussis Vaccine (aP):
   • Contains purified pertussis components (pertussis toxin, filamentous hemagglutinin, fimbriae).
   • Fewer side effects but slightly less immunogenic than wP.

Immunization Schedule:

DPT vaccine is administered in a 5-dose series at:

• 6 weeks, 10 weeks, 14 weeks (primary doses).
• Booster doses at 18 months and 4-6 years.

Mechanism of Action:

Vaccination stimulates the immune system to produce antibodies against pertussis toxins and adhesins.

Adverse Effects:

• Mild: Fever, redness, swelling at the injection site.
• Rare: Severe allergic reactions.

Importance:

Reduces incidence of pertussis and prevents severe complications like pneumonia, encephalopathy, and death in infants.

Aspergillosis

Causative Agent: Fungi of the genus Aspergillus, primarily Aspergillus fumigatus.

Pathogenesis:

• Inhalation of fungal spores (conidia) from the environment.
• Spores settle in the lungs, where they germinate and form hyphae.
• In immunocompromised individuals (e.g., neutropenia, AIDS), the fungus invades tissues causing invasive aspergillosis.

Clinical Types:

1. Allergic Bronchopulmonary Aspergillosis (ABPA): Hypersensitivity reaction in asthma or cystic fibrosis patients.
2. Aspergilloma: Fungus ball formation in pre-existing lung cavities (e.g., tuberculosis cavities).
3. Invasive Pulmonary Aspergillosis: Severe infection in immunocompromised individuals, causing tissue necrosis and dissemination.

Laboratory Diagnosis:

1. Specimen: Sputum, bronchoalveolar lavage (BAL), or biopsy tissue.
2. Microscopy:
   • KOH Mount: Hyaline, septate hyphae with acute angle branching.
   • Stains: Lactophenol cotton blue, silver stain.
3. Culture: Grows on Sabouraud’s dextrose agar. Colonies appear fluffy with a greenish center.
4. Serology:
   • Detection of galactomannan antigen in serum (ELISA test for invasive aspergillosis).
5. Imaging:
   • Chest X-ray/CT: “Halo sign” in invasive aspergillosis or “fungus ball” in aspergilloma.

Treatment:

• ABPA: Oral corticosteroids and antifungals (itraconazole).
• Invasive Aspergillosis: Intravenous antifungals (voriconazole, amphotericin B).
• Surgical removal for aspergilloma if symptomatic.

Mucormycosis

Causative Agents: Fungi from the Mucorales order, including Rhizopus, Mucor, and Rhizomucor.

Risk Factors

• Immunocompromised states (e.g., diabetes, organ transplants, malignancies).
• Uncontrolled diabetes with ketoacidosis.
• Prolonged corticosteroid use.
• COVID-19-associated mucormycosis (post-COVID fungal infections).

Pathogenesis:

• Fungal spores are inhaled or ingested, and they germinate into hyphae.
• Hyphae invade blood vessels, causing thrombosis, tissue necrosis, and rapid dissemination.

Clinical Forms:

1. Rhinocerebral Mucormycosis:
   • Involves sinuses, orbits, and brain.
   • Symptoms: Facial pain, black necrotic eschar in the nasal cavity, headache, and cranial nerve palsies.
2. Pulmonary Mucormycosis:
   • Lung involvement with cough, hemoptysis, and chest pain.
3. Cutaneous Mucormycosis: Skin infection following trauma.
4. Gastrointestinal Mucormycosis:
   • Rare; abdominal pain, gastrointestinal bleeding.

Laboratory Diagnosis:

1. Specimen: Nasal discharge, tissue biopsy, sputum.
2. Microscopy:
   • KOH Mount: Broad, ribbon-like hyphae with right-angle branching.
3. Culture: Growth on Sabouraud’s dextrose agar at 25-37°C.
4. Histopathology: Hematoxylin and eosin (H&E) staining shows tissue necrosis and fungal invasion.
5. Imaging:
   • CT/MRI of the sinuses, chest, or brain shows invasive features.

Treatment:

• Immediate antifungal therapy: Liposomal amphotericin B (drug of choice).
• Surgical debridement of necrotic tissue.
• Control of underlying conditions (e.g., hyperglycemia, ketoacidosis).

Infectious Mononucleosis

Causative Agent: Epstein-Barr virus (EBV), a member of the Herpesviridae family.

Pathogenesis:

• EBV is transmitted through saliva (hence the name “kissing disease”).
• The virus infects the oropharyngeal epithelial cells and subsequently infects B lymphocytes via the CD21 receptor.
• Infected B cells proliferate, triggering a strong T-cell immune response.
• This leads to atypical lymphocytosis, lymphadenopathy, and the clinical symptoms of the disease.
• EBV can establish latency in B cells, persisting for life.

Clinical Features:

• High fever.
• Sore throat with tonsillar enlargement.
• Cervical lymphadenopathy.
• Splenomegaly.
• Fatigue and malaise.

Laboratory Diagnosis:

1. Complete Blood Count (CBC):
   • Presence of atypical lymphocytes (>10%).
2. Serology:
   • Monospot Test: Detects heterophile antibodies (screening).
   • EBV-specific antibodies:
     • Anti-VCA IgM (early infection).
     • Anti-VCA IgG (past infection).
     • Anti-EBNA IgG (late marker of infection).
3. PCR:
   • Detects EBV DNA in blood or saliva (useful for complicated cases).
4. Liver Function Tests (LFTs):
   • Elevated liver enzymes (mild hepatitis is common).

Treatment:

• Supportive care: Rest, hydration, and analgesics.
• Avoid contact sports (due to the risk of splenic rupture).

Mumps

Causative Agent: Mumps virus, a member of the Paramyxovirus family.

Mode of Transmission:

• Respiratory droplets from infected individuals.
• Contact with saliva.

Pathogenesis:

• Virus enters through the respiratory tract and infects the parotid glands via viremia (virus in the blood).
• It can spread to other organs like testes, ovaries, pancreas, and the CNS.

Symptoms:

• Fever, headache, malaise.
• Painful parotid gland swelling (unilateral or bilateral).
• Difficulty chewing or swallowing.
• Orchitis (testicular inflammation) in post-pubertal males.
• Oophoritis in females (ovarian inflammation).
• Aseptic meningitis (rare complication).

Diagnosis:

• Clinical features: Swelling of parotid glands.
• RT-PCR: Detects viral RNA in saliva or blood.
• Serology: IgM antibodies against mumps virus.

Treatment:

• Supportive care: Rest, hydration, analgesics.
• Orchitis: Scrotal support, ice packs, pain relief.

Prevention:

MMR Vaccine (Measles, Mumps, Rubella): Live attenuated vaccine given at 9-12 months and booster at 15-18 months.

H1N1 / Swine Flu

Cause: Influenza A virus subtype H1N1 (genetic reassortment between avian, swine, and human influenza viruses).

Mode of Transmission:

• Respiratory droplets (coughing/sneezing).
• Contact with contaminated surfaces.

Symptoms:

• Fever, chills, sore throat, cough.
• Fatigue, myalgia, headache.
• Vomiting and diarrhea (common in children).

Diagnosis:

• RT-PCR: Detects viral RNA in nasopharyngeal swabs.
• Rapid antigen tests.

Treatment:

• Antivirals: Oseltamivir (Tamiflu), Zanamivir.
• Supportive care: Fluids, rest, antipyretics.

Prevention:

• Influenza vaccination.
• Hand hygiene, respiratory etiquette (covering mouth/nose while coughing or sneezing).

BCG Vaccine

Full Form: Bacillus Calmette-Guérin Vaccine.

Purpose: Prevention of tuberculosis (TB) caused by Mycobacterium tuberculosis.

Type of Vaccine:

Live attenuated vaccine derived from Mycobacterium bovis.

Mechanism of Action:

• When administered, the vaccine stimulates the immune system to develop a T-cell mediated response against Mycobacterium tuberculosis.
• Induces delayed-type hypersensitivity (DTH) and formation of memory T-cells for long-term immunity.

Indications:

• Administered at birth in TB-endemic countries.
• Given intradermally over the deltoid region of the arm.

Laboratory Diagnosis of TB (if relevant):

• Sputum Examination: Acid-fast bacilli (AFB) staining using Ziehl-Neelsen stain.
• Culture: Lowenstein-Jensen medium for M. tuberculosis growth.
• Mantoux Test: Tuberculin skin test to detect latent TB infection.

MDR-TB (Multidrug-Resistant Tuberculosis)

Definition: Tuberculosis resistant to at least isoniazid (INH) and rifampicin (RIF), the two first-line TB drugs.

Pathogenesis:

• MDR-TB arises due to inadequate treatment, non-adherence to therapy, or misuse of antibiotics.
• Genetic mutations in M. tuberculosis lead to drug resistance (e.g., mutations in katG gene for INH resistance and rpoB gene for RIF resistance).

Laboratory Diagnosis:

1. Sputum Microscopy: Acid-fast staining.
2. Culture & Drug Susceptibility Testing:
   • Performed on Lowenstein-Jensen medium or liquid culture systems like MGIT (Mycobacteria Growth Indicator Tube).
3. GeneXpert (CBNAAT): Detects M. tuberculosis DNA and rifampicin resistance.
4. Line Probe Assay (LPA): Molecular test to detect mutations causing drug resistance.

Management:

• Second-line anti-TB drugs: Fluoroquinolones, aminoglycosides, and newer drugs like bedaquiline and linezolid.

Mycoplasma Pneumonia

Causative Agent: Mycoplasma pneumoniae – a small, atypical bacterium lacking a cell wall.

Pathogenesis:

• Transmission occurs via respiratory droplets.
• Bacteria attach to the respiratory epithelium using adhesins, damaging the cilia and epithelium.
• Causes mild atypical pneumonia (also called “walking pneumonia”) characterized by patchy inflammation.

Clinical Features:

• Gradual onset of low-grade fever, dry cough, and headache.
• Often occurs in young adults and school-aged children.

Laboratory Diagnosis:

1. Serology:
   • Detection of cold agglutinins (IgM antibodies).
2. PCR: Detects M. pneumoniae DNA in respiratory samples.
3. Culture: Growth on Eaton’s agar (slow and rarely done in practice).
4. Chest X-ray: Shows diffuse, patchy infiltrates (“ground-glass appearance”).

Treatment:

• Macrolides (azithromycin) or tetracyclines (doxycycline).

Pulmonary Anthrax

Causative Agent: Bacillus anthracis – a gram-positive, spore-forming rod.

Pathogenesis:

• Inhalation of anthrax spores (Woolsorter’s disease).
• Spores are phagocytosed by alveolar macrophages, germinate, and release toxins:
  1. Edema Toxin: Causes fluid accumulation.
  2. Lethal Toxin: Causes tissue necrosis.
• Leads to hemorrhagic mediastinitis and sepsis.

Clinical Features:

• Initial flu-like symptoms: Fever, cough, fatigue.
• Progresses to severe respiratory distress, shock, and death if untreated.

Laboratory Diagnosis:

1. Microscopy: Gram stain shows gram-positive rods in chains.
2. Culture: Grows on blood agar, showing non-hemolytic colonies with a “Medusa head” appearance.
3. PCR: Detects anthrax DNA.
4. Chest X-ray: Shows a widened mediastinum (hallmark of pulmonary anthrax).

Treatment:

• High-dose ciprofloxacin or doxycycline.
• Anthrax antitoxin for severe cases.

DPT Vaccine

Components:

• D: Diphtheria toxoid.
• P: Pertussis vaccine (whole-cell or acellular).
• T: Tetanus toxoid.

Indications:

• Protects against diphtheria, pertussis, and tetanus.
• Administered in 5 doses (6 weeks, 10 weeks, 14 weeks, 18 months, and 4-6 years).

Mechanism of Action:

• Stimulates the immune system to produce antibodies against diphtheria, pertussis toxins, and tetanus toxin.

Laboratory Diagnosis of DPT Diseases (Overview):

• Diphtheria: Throat swab cultured on Loeffler’s medium; Elek test for toxin detection.
• Pertussis: Culture on Bordet-Gengou agar; PCR.
• Tetanus: Clinical diagnosis; rarely cultured.

Adverse Effects:

• Pain, fever, and swelling at the injection site.

Streptococcal Pharyngitis

Causative Agent: Streptococcus pyogenes (Group A Streptococcus).

Pathogenesis:

• Infection occurs via respiratory droplets.
• S. pyogenes produces virulence factors:
  • Streptolysin O and S: Cause tissue damage.
  • M protein: Helps evade phagocytosis.
• Inflammatory response in the pharynx causes redness, pain, and swelling.

Clinical Features:

• Sore throat, fever, tonsillar exudates, and tender cervical lymphadenopathy.
• Complications: Rheumatic fever, glomerulonephritis, and scarlet fever.

Laboratory Diagnosis:

1. Throat Swab Culture: Grows on blood agar, showing beta-hemolytic colonies.
2. Rapid Antigen Detection Test (RADT): Detects Group A strep antigen.
3. ASO Titer: Measures antistreptolysin O antibodies (useful for post-infectious complications).

Treatment:

• Penicillin or amoxicillin (drug of choice).