Module IV: Bacterial Diseases

Enteric Fever (Typhoid Fever)

  • Definition and Causative Agents:
        * Also known as Enteric Fever or Bilious Fever.
        * It is an acute illness characterized by fever, primarily caused by the bacterium Salmonella typhi.
        * A related, typically less severe form is caused by Salmonella paratyphi.

  • Epidemiology and Statistics:
        * The World Health Organization (WHO) estimates between 11imes10611 imes 10^{6} and 21imes10621 imes 10^{6} cases annually.
        * Typhoid-related deaths range from 128,000128,000 to 161,000161,000 per year worldwide.
        * The disease is highly endemic in India, where the annual incidence is 493.5/100,000493.5/100,000 persons per year.
        * Children aged 2−52-5 years are particularly vulnerable, with an incidence of 340.1/100,000340.1/100,000 cases per year.

  • Etiology and Microorganism Characteristics:
        * Agent: Salmonella Typhi.
        * Family: Enterobacteriaceae.
        * Classification: Gram-negative bacilli.
        * Growth Requirements: Optimal growth occurs at 37∘C37^\circ\text{C}.
        * Nature: Not zoonotic (human-restricted).

  • Transmission and Risk Factors:
        * Route: Faecal-oral route.
        * Vectors: Contaminated food and water, close contact with patients/carriers, and mechanical vectors like flies and cockroaches.
        * Incubation Period: Typically 7−147-14 days after ingestion.
        * Risk Groups: Children are most affected; the median age for cases is 6060 months, with 15%15\% of cases occurring in children < 24 months old.
        * Contagion: Highly contagious via faeces and (less commonly) urine. Bacteria can survive for weeks in water or dried sewage.

  • Virulence Factors of Salmonella:
        * Endotoxin: Located in the LPS layer; responsible for fever.
        * Enterotoxin: Causes diarrhea.
        * Vi capsule antigen: Inhibits complement binding; essential for full pathogenicity.
        * O antigen (Somatic): Inhibits phagocyte killing.
        * H antigen (Flagellar): Facilitates motility, adherence, and inhibits phagocyte killing.
        * Other Factors: Siderophores, Type 1 fimbriae (adherence), OxyR-induced anti-phagocytic proteins, virulence plasmids, and cytotoxins (inhibiting host cell protein synthesis).

  • Pathophysiology:
        1. Ingestion of contaminated food/water.
        2. Bacilli invade small intestinal mucosa.
        3. Taken up by macrophages and transported to regional lymph nodes.
        4. Multiplication in intestinal lymphoid tissue (interacts with enterocytes and ileal Peyer's patches during the 1−31-3 week incubation period).
        5. End of incubation marks the Bacteraemia phase (entry into bloodstream) and onset of fever.
        6. Invasion of the gallbladder, biliary system, and lymphatic tissue of the bowel with high-rate multiplication.
        7. Re-entry into the intestinal tract (excretion in stool).

  • Clinical Stages and Features:
        * Stage 1 (1st Week): Slowly rising "stepladder" fever for 4−54-5 days, abdominal pain, myalgia, malaise, headache, constipation, and relative bradycardia.
        * Stage 2 (2nd Week): Rose spots (slightly raised, rose-red spots that fade on pressure, visible mainly on white skin) on upper abdomen/back, cough, splenomegaly, abdominal distension, and diarrhea.
        * Stage 3 (3rd Week): Patient becomes toxic and anorexic; significant weight loss; "Typhoid state" (apathy, confusion, psychosis). High risk (5−10%5-10\%) of intestinal hemorrhage and perforation.
        * Stage 4 (4th Week): Recovery period. Fever and mental state improve; however, intestinal/neurological complications may persist. Some become chronic asymptomatic carriers.

  • Diagnosis and Investigation:
        * Blood Culture: 90%90\% positive in the 1st week; 75%75\% in the 2nd week.
        * Widal Test: Serologic tube agglutination test detecting O (Felix tubes) and H (Dryers tubes) antibodies.
        * Stool/Urine Culture: Most effective in 2nd and 3rd weeks (50−80%50-80\% positivity).
        * Marrow Culture: Highest sensitivity (90%90\%).
        * Rose Spot Punch Biopsy: 63%63\% sensitive.

  • Treatment:
        * Antibiotics: Fluoroquinolones (e.g., Ciprofloxacin at 500 mg500\,\text{mg} bds) are the Drug of Choice. Resistance is common in India to Chloramphenicol (500 mg500\,\text{mg} qid), Ampicillin (750 mg750\,\text{mg} qid), and Co-trimoxazole.
        * Alternatives: 3rd generation cephalosporins (Ceftriaxone) or Azithromycin (500 mg500\,\text{mg} daily).
        * Supportive Care: Fluids, electrolytes, and corticosteroids for severe cases.

Cholera

  • Definition: Acute diarrheal illness caused by infection of the intestine with Vibrio cholerae.

  • Etiology:
        * Characteristics: Gram-negative, oxidase-positive, motile via a polar flagellum.
        * Metabolism: Both respiratory and fermentative; can multiply freely in water.

  • Epidemiology:
        * Rare in developed countries due to water treatment.
        * Global burden: 1.4×1061.4\times 10^{6} to 4.0×1064.0\times 10^{6} cases; 21,00021,000 to 143,000143,000 deaths annually.
        * India: Less than 100,000100,000 cases per year.

  • Pathophysiology Mechanism:
        1. V. cholerae accumulates in the stomach and produces toxins.
        2. Toxins bind to G-protein coupled receptors.
        3. Inactivation of GTPase causes the G-protein to be stuck in the "on" position.
        4. Increased cyclic AMP (cAMP) activates ion channels.
        5. NaClNaCl influx into the intestinal lumen drags water with it, leading to profuse watery diarrhea.

  • Clinical Presentation:
        * Profuse, watery diarrhea and vomiting.
        * Physical signs: Sunken eyes/cheeks, dry mucous membranes, leg cramps, and decreased urinary output.
        * Complications: Severe dehydration, shock, renal failure. Untreated mortality is 50−60%50-60\%, reducible to 1%1\% with treatment.

  • Diagnosis and Treatment:
        * Microscopy: Dark field/phase contrast shows motile organisms appearing like "shooting stars."
        * Culture: Yellow colonies on sucrose dishes.
        * Management: Oral Rehydration Salts (ORS) treats 80%80\% of cases. IV fluids (Ringer's Lactate) for severe cases. Antimicrobials to reduce duration.

  • Vaccines:
        * Parenteral: 50%50\% efficacy, short duration (66 months).
        * Oral (Killed WC/rBS): Whole-cell with recombinant Beta-subunit of toxin.
        * Oral (Live CVD 103-HgR): >90\% protection after 1 week.

Tuberculosis (TB)

  • Etymology and Definition: From Neo-Latin "Tubercle" (round nodule) and "Osis" (condition). It is a potentially fatal contagious infection primarily affecting the lungs.

  • Causative Organisms:
        * Mycobacterium tuberculosis: Human host.
        * Mycobacterium bovis: Animals (used for BCG vaccine).
        * M. tuberculosis complex: Includes M. africanum, M. microti, and M. canetti.

  • Bacterial Characteristics:
        * Gram-positive (though usually identified via acid-fast staining), obligate aerobe, non-motile rod.
        * Cell Wall: Lipid-rich, contains mycolic acid (50%50\% of cell wall dry weight). Confers resistance to detergents and antibacterials.
        * Growth: Slow generation time of 15−2015-20 hours.

  • Pathogenesis Steps:
        1. Inhalation of aerosolized droplet nuclei.
        2. Bacteria reach lungs and enter alveolar macrophages.
        3. Granulomatous lesion (tubercle) forms with caseous necrosis.
        4. Lesion may calcify and become dormant (95%95\%).
        5. Immune suppression can lead to reactivation and liquefaction of the lesion, leading to spread via blood/organs or coughing in sputum.

  • Classification:
        * Pulmonary TB: Primary (initial infection/Ghon's complex) and Secondary (reactivation/reinfection).
        * Extrapulmonary TB (20%20\%): Includes Lymph node (Scrofula), Pleural, Upper Airway, Genitourinary (15%15\% of extrapulmonary), Skeletal (spine/hip), Gastrointestinal, Meningitis (5%5\% of extrapulmonary), and Miliary (disseminated) TB.

  • Diagnosis:
        * Bacteriological: Ziehl-Neelsen stain or Auramine stain (fluorescence microscopy).
        * Culture: Lowenstein-Jensen (LJ) solid medium (4−184-18 weeks).
        * Mantoux Test (PPD): Intradermal injection of 0.1 ml0.1\,\text{ml} (0.04 μg0.04\,\mu\text{g} Tuberculin). Reaction read at 48−7248-72 hours.
            * < 6\,\text{mm}: Negative.         * 6−15 mm6-15\,\text{mm}: Hypersensitive (previous infection or BCG).         * > 15\,\text{mm}: Strongly hypersensitive; suggestive of disease.

  • Treatment and DOTS:
        * DOTS (Directly Observed Treatment, Short-course): Health worker ensures patient swallows every dose.
        * First-line Drugs: Isoniazid (inhibits mycolic acid), Rifampin (blocks RNA synthesis), Pyrazinamide, Ethambutol (bacteriostatic; inhibits arabinosyl transferase), Streptomycin (inhibits protein synthesis).
        * MDR-TB: Resistant to at least Isoniazid and Rifampicin.
        * XDR-TB: MDR plus resistance to any fluoroquinolone and second-line injectables (Amikacin, Kanamycin, Capreomycin).

Tetanus

  • Definition: Illness characterized by acute hypertonia, painful muscle contractions (jaw/neck), and generalized spasms.

  • Agent: Clostridium tetani:
        * Gram-positive, spore-forming, anaerobic bacilli.
        * Found in soil (manured) and animal feces. Spores are highly resistant and can survive for 100100 years.

  • Pathogenicity and Mechanism:
        * Toxin-mediated; produces Tetanospasmin (a neurotoxin) and Tetanolysin.
        * Toxin binds to peripheral nerve terminals, travels to the CNS, and blocks the release of inhibitory neurotransmitters.
        * This leads to overstimulation of muscles and spastic paralysis.

  • Clinical Features:
        * Lockjaw (stiffness of jaw), Opisthotonus (backward arching of the spine), tetanic seizures, and fever.
        * Neonatal Tetanus: Occurs via unsterile cutting of the umbilical stump.

  • Management:
        * Prevention: Tetanus Toxoid (formal-inactivated) immunization; boosters needed every 1010 years.
        * Clinical Care: Antibiotics (Penicillin), neutralization with Tetanus Immune Globulin (TIG), and muscle relaxants.

Diphtheria

  • Definition: Acute infectious disease of the upper respiratory tract caused by Corynebacterium diphtheriae.

  • Characteristics and Toxin:
        * Gram-positive, motile organism. Multiplies on mucous membranes.
        * Produces a powerful exotoxin (A-B toxin).
        * Mechanism: The A subunit ADP-ribosylates host eEF-2, inhibiting protein synthesis and killing the cell.

  • Symptoms:
        * Formation of a grey/leathery false membrane over the tonsils/pharynx/larynx.
        * "Bull neck" enlargement of lymph nodes, sore throat, and hoarseness.

  • Complications:
        * Obstructed breathing.
        * Myocarditis: Heart muscle inflammation due to toxin spread.
        * Neuritis (nerve damage) and renal damage.

  • Treatment: Diphtheria antitoxin + Antibiotics (Penicillin or Erythromycin). Prevention is via the DTP vaccine.