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Differentiation of Tetanus, Leprosy, Rabies, and AIDS

Overview Table

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1. TETANUS

Epidemiological Factors

• Global distribution: Worldwide; most cases in developing countries where immunisation coverage is low
• Reservoir: Soil and intestines of humans and animals; spores are ubiquitous
• High-risk populations: Unimmunised individuals, neonates (neonatal tetanus from umbilical cord contamination), elderly with waning immunity, IV drug users
• Incubation period: Median 7 days (range 4-14 days); shorter incubation = worse prognosis

Mode of Transmission

• Not transmitted person-to-person
• C. tetani spores enter the body through wounds - particularly soil-contaminated wounds, puncture wounds, burns, compound fractures, and devitalised tissue
• Anaerobic conditions in dead tissue allow spore germination and replication
• The bacterium produces tetanospasmin, an exotoxin that travels to the CNS via retrograde axonal transport and binds to neuromuscular junctions, blocking inhibitory neurotransmitter release (glycine, GABA)

Signs and Symptoms

• Trismus ("lockjaw") - painful spasm of masseter muscles; the first and most common sign
• Risus sardonicus - characteristic sardonic grin from facial muscle spasm
• Opisthotonus - arching of the whole body from paravertebral and extensor limb muscle spasm
• Dysphagia from pharyngeal muscle involvement
• Laryngospasm - leads to apnoea, asphyxia, and respiratory arrest
• Spasms triggered by any sensory stimulus (light, sound, touch)
• Autonomic instability: tachycardia, hypertension, profuse sweating
• Consciousness is preserved (unlike many other CNS infections)

Treatment

1. Human Anti-Tetanus Globulin (ATG): 250-500 IU IM for passive immunisation and neutralisation of circulating toxin; wound debridement should be done several hours after ATG
2. Wound care: Thorough debridement to eliminate the anaerobic environment
3. Antibiotics: Penicillin G 10-24 million units/day IV for 10-14 days; metronidazole is an alternative
4. Muscle spasm control: Diazepam (benzodiazepines) to suppress spasms; if sustained spasms, patient is paralysed, intubated, and ventilated
5. Supportive care: ICU with minimal sensory stimulation; gradual ventilator wean under anticonvulsants
6. Overall mortality ~45%; intrathecal antitoxin has been used in some centres

Prevention

• Active immunisation: Tetanus toxoid 0.5 mL IM; given as part of DTP/DPT schedule in childhood (3 doses primary + boosters)
• Passive immunisation: ATG 250-500 IU IM for heavily contaminated wounds in non-immune individuals
• Wound management: Prompt cleaning and debridement of all wounds
• Booster every 10 years in adults; immunisation during pregnancy prevents neonatal tetanus

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2. LEPROSY (Hansen's Disease)

Epidemiological Factors

• Global burden: ~200,000 new cases/year; endemic in Southeast Asia (India, Bangladesh), East Africa, Brazil
• Reservoir: Humans are the primary host; zoonotic transmission from armadillos (rare)
• Source of infection: Multibacillary cases (lepromatous and borderline lepromatous) are the most important source; all "active leprosy" patients considered infectious
• Age: Peaks at 20-30 years; presence in children indicates active spread in community
• Sex: Higher incidence and prevalence in males
• Incubation period: Very long - 2 to 10 years (average 3-5 years)
• Communicability: Highly infectious but low pathogenicity; 4.4-12% of household contacts of lepromatous cases develop signs within 5 years

Mode of Transmission

• Primarily via respiratory secretions (nasal droplets); lepromatous cases harbour millions of M. leprae in nasal mucosa discharged during sneezing/nose blowing
• Can also exit through ulcerated or broken skin of bacteriologically positive cases
• Prolonged close contact with an untreated case is required
• M. leprae is an obligate intracellular pathogen; proliferates in cool tissues (skin, extremities, superficial nerves) at 32-34°C
• Cannot be cultured in vitro

Signs and Symptoms

• Dry, scaly, flat, red skin lesions with indurated elevated margins and depressed pale (anaesthetic) centers
• Asymmetric involvement of large peripheral nerves
• Skin anaesthesia, muscle atrophy, susceptibility to trauma
• Few bacilli (paucibacillary)

• Symmetric skin thickening and nodules; "leonine facies"
• Widespread invasion of Schwann cells - significant peripheral neuropathy
• Loss of eyebrows (madarosis), nasal septal perforation, saddle-nose deformity
• In advanced cases, bacilli present in sputum and blood (multibacillary)
• Immune complex deposition can cause erythema nodosum, vasculitis, glomerulonephritis

Treatment

• Rifampicin 600 mg once monthly (supervised)
• Dapsone 100 mg daily (self-administered)
• Clofazimine 300 mg once monthly + 50 mg daily
• Duration: 12 months

• Rifampicin 600 mg once monthly (supervised)
• Dapsone 100 mg daily (self-administered)
• Duration: 6 months

Prevention

• Early detection and complete MDT treatment - the fundamental principle
• BCG vaccination confers some protection against M. leprae (cross-immunity with M. tuberculosis)
• Contact tracing and examination of household contacts
• WHO Global Leprosy Strategy targets zero Grade-2 disability in children
• Health education and reduction of stigma
• No specific chemoprophylaxis widely recommended

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3. RABIES

Epidemiological Factors

• Global burden: ~55,000 deaths per year; nearly 100% fatal once clinical disease develops
• Reservoir: Bats, wild carnivores (skunks, foxes, raccoons, coyotes, wolves), and unimmunised dogs
• Geographic distribution: Worldwide; dogs are the main vector in developing countries; bats are the main source in North America and Europe
• Incubation period: Usually 1-3 months; range from 1 week to several years (depending on bite location - closer to CNS = shorter incubation)
• Organ transplant transmission has been documented (kidneys, liver, cornea, arterial segment from infected donors)

Mode of Transmission

• Animal bite (most common) - transdermal bites or scratches from infected animals
• Mucous membrane contact with saliva from reservoir species
• Aerosol exposure - documented in bat caves and laboratory accidents (rare)
• Organ transplantation from infected donors
• Superficial bat bites carry high risk as bat rabies variants can infect epithelial cells and fibroblasts
• Any bat exposure - with or without a recognised bite - should be treated as significant

Signs and Symptoms

• Fever, headache, malaise
• Paresthesias, pain, or pruritus at the site of inoculation (highly specific early sign)

• Hydrophobia (fear of water) - characteristic pharyngeal spasms triggered by attempts to swallow
• Aerophobia - spasms triggered by air currents
• Agitation, hallucinations, autonomic hyperactivity (hypersalivation, excessive sweating)
• Seizures
• Temperature may reach 105-107°F
• Spasms of pharyngeal and nuchal muscles lasting 1-5 minutes

• Progressive ascending paralysis similar to Guillain-Barré
• Less agitation, longer survival

Treatment

• No effective treatment once clinical symptoms appear - virtually 100% fatal
• Supportive ICU care (palliative)
• The "Milwaukee Protocol" (induced coma) has extremely limited success

1. Wound care: Thorough washing with soap and water, followed by povidone-iodine
2. Human Rabies Immunoglobulin (HRIG): 20 IU/kg - as much as possible infiltrated around the wound, remainder IM at a distant site; given once as soon as possible (up to 7 days after first vaccine dose)
3. Rabies vaccine (HDCV or PCEC): IM on days 0, 3, 7, and 14 into deltoid/anterolateral thigh
4. Previously immunised individuals: booster doses on days 0 and 3 only (no HRIG needed)

Prevention

• Pre-exposure vaccination for high-risk groups (veterinarians, wildlife workers, travellers to endemic areas)
• Animal vaccination programs - immunisation of dogs is the most effective public health measure
• Post-exposure prophylaxis (see above) - essentially 100% effective if given promptly
• Animal control: Confine and observe dogs/cats for 10 days after biting; euthanise and test if wild animal
• Avoid contact with wild animals and stray dogs
• Consult local public health officials before starting PEP

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4. AIDS (Acquired Immunodeficiency Syndrome)

Epidemiological Factors

• Global burden: ~38 million people living with HIV globally; one of the leading causes of death in sub-Saharan Africa
• Causative agent: HIV-1 (more common, more virulent) and HIV-2
• Mechanism: HIV attaches to CD4 (T-helper lymphocyte) receptors; progressive depletion of CD4+ T cells leads to profound cell-mediated immunodeficiency
• Case definition: AIDS = HIV infection + CD4 count <200 cells/mm³, OR presence of an AIDS-defining illness
• Incubation: 2-18 months to seroconversion; average 10 years from HIV infection to AIDS without treatment
• High-risk groups: Men who have sex with men (MSM), IV drug users, sex workers, recipients of unscreened blood/blood products, infants of HIV-positive mothers

Mode of Transmission

• Sexual intercourse (most common worldwide) - vaginal and anal; HIV is present in semen, vaginal secretions
• Blood/blood products: Transfusion of infected blood, sharing needles/syringes
• Perinatal (vertical): Mother-to-child transmission during pregnancy, childbirth, or breastfeeding (1-in-3 risk without intervention)
• HIV is found in semen, saliva, tears, and breast milk; blood becomes HIV-positive 2-18 months after infection
• No airborne transmission
• HIV remains viable in blood for up to 2 months
• HIV is present primarily in brain, colon, lungs, and lymphoid tissue

Signs and Symptoms

• Flu-like illness: fever, lymphadenopathy, pharyngitis, rash (maculopapular, 5-10 mm lesions)
• Myalgia/arthralgia, diarrhoea, anorexia, weight loss
• Headache (retroorbital pain), painful mucocutaneous ulceration
• 10-40% of acute infections are asymptomatic

• Constitutional: persistent fever, night sweats, weight loss (>10%) - "AIDS wasting"
• Opportunistic infections: Oral/esophageal candidiasis (most common), Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, CMV retinitis/colitis, cryptococcal meningitis, Mycobacterium avium complex
• AIDS-defining malignancies: Kaposi's sarcoma, non-Hodgkin's lymphoma, invasive cervical carcinoma
• Neurological: AIDS dementia complex, aseptic meningitis, progressive multifocal leukoencephalopathy

Treatment

• Highly Active ART (HAART): Combination of ≥3 drugs from at least 2 drug classes
• Main drug classes: NRTIs (e.g. tenofovir, emtricitabine), NNRTIs (e.g. efavirenz), Protease Inhibitors (e.g. ritonavir), Integrase Inhibitors (e.g. dolutegravir)
• ART reduces viral load to undetectable levels, preserves CD4 count, prevents opportunistic infections
• Current guidelines recommend treatment for all HIV-positive individuals regardless of CD4 count
• Treatment of opportunistic infections as they arise (fluconazole for candidiasis, co-trimoxazole for PCP prophylaxis, etc.)

Prevention

• Safe sex: Consistent and correct use of condoms
• Pre-Exposure Prophylaxis (PrEP): Daily tenofovir/emtricitabine for high-risk HIV-negative individuals
• Post-Exposure Prophylaxis (PEP): ART started within 72 hours of potential exposure
• Harm reduction for IV drug users: Needle exchange programs, opioid substitution therapy
• Blood safety: Screening of all blood donations; HIV+ blood must be discarded
• Prevention of Mother-to-Child Transmission (PMTCT): ART during pregnancy and labour; elective caesarean; avoidance of breastfeeding (or exclusive breastfeeding with maternal ART)
• HIV testing and counselling - requires pre- and post-test counselling; result disclosed face-to-face
• Mandatory testing (without consent) only for blood/organ/tissue donors

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Summary Comparison Table

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• Bailey and Love's Short Practice of Surgery 28th Edition (Tetanus)
• Park's Textbook of Preventive and Social Medicine (Leprosy, AIDS)
• Robbins, Cotran & Kumar Pathologic Basis of Disease (Leprosy)
• Bradley and Daroff's Neurology in Clinical Practice (Rabies)
• Goldman-Cecil Medicine International Edition (AIDS, Rabies)
• Essentials of Forensic Medicine and Toxicology 36th Edition (AIDS)