General Medicine

AETIOLOGY & PATHOGENESIS

*Salmonella Typhi* (gram-negative bacillus; Enterobacteriaceae); faeco-oral transmission via contaminated water/food. Incubation: 7–14 days . Bacteria invade Peyer's patches (terminal ileum) → mesenteric lymph nodes → primary bacteraemia (1–3 weeks) → liver, spleen, bone marrow → secondary bacteraemia (symptomatic phase) → intestinal re-seeding via bile duct → ulceration of Peyer's patches (3rd week — risk of perforation/haemorrhage).

CLINICAL FEATURES — STEP-LADDER PATTERN

Relative bradycardia (Faget's sign) = pulse rate lower than expected for the degree of fever; characteristic of typhoid (and also seen in Legionella, Dengue, Yellow fever, Brucella).

DIAGNOSIS

• Blood culture (Gold Standard): Positive in 80–90% in week 1 (bacteraemia peak); sensitivity drops thereafter; inoculate aerobically + anaerobically
• Widal test (Widal reaction): Agglutination of O + H antigens by antibodies; O agglutinin (somatic) titre ≥ 1:160 in endemic areas = significant; H agglutinin (flagellar) titre ≥ 1:320; RISING TITRE on repeat testing (2 weeks apart) more significant than single titre
• Bone marrow culture — highest sensitivity (90%) even in antibiotic-treated patients; gold standard when blood cultures negative
• Stool culture (positive week 3); Urine culture; CBC — leucopenia + relative lymphocytosis (characteristic)

TREATMENT

▶ Ceftriaxone 2 g IV OD × 10–14 days — first-line for complicated/hospitalised typhoid; covers MDR strains; highly effective

▶ Azithromycin 1 g OD × 5–7 days — first-line for uncomplicated typhoid (outpatient); excellent intracellular penetration; DOC for children

▶ Ciprofloxacin 500 mg BD × 10–14 days — for fluoroquinolone-sensitive strains; decreasing efficacy due to nalidixic acid resistance (NARST)

▶ Dexamethasone 3 mg/kg loading, then 1 mg/kg q6h × 48 hrs — for severe typhoid with encephalopathy/shock (mortality benefit; not routinely used)

COMPLICATIONS

• Intestinal perforation (#1 cause of death) — week 3; ileal perforations at Peyer's patches; sudden worsening of pain → board-like rigidity → free air on X-ray; emergency surgical repair + IV antibiotics
• Intestinal haemorrhage — week 3; melaena/fresh PR bleed; blood transfusion; conservative management usually sufficient
• Typhoid encephalopathy (toxic state); myocarditis ; hepatitis ; osteomyelitis; meningitis
• Chronic carrier state — S. Typhi persists in gallbladder (60–70%) or urine; > 1 year; positive stool/urine culture; treat with high-dose fluoroquinolone + cholecystectomy if gallstones
• Vaccination: Vi polysaccharide vaccine (single dose IM; > 2 years; 70% efficacy; boosters q3 years); Ty21a oral live attenuated vaccine (4 doses alternate days; 60–70% efficacy; lasts 5 years)

COMPLICATIONS OF SEVERE FALCIPARUM MALARIA

• WHO criteria for severe malaria: impaired consciousness/coma, prostration, multiple convulsions, acidosis, hypoglycaemia, severe anaemia (Hb < 7 g/dL), acute kidney injury, jaundice, pulmonary oedema/ARDS, significant bleeding, shock, or hyperparasitaemia (> 10%).
• Management principles: IV artesunate (2.4 mg/kg at 0, 12 and 24 h then daily) is first-line for severe malaria and is superior to quinine; supportive care (treat hypoglycaemia, cautious fluids to avoid pulmonary oedema, control seizures, transfuse for severe anaemia); complete a full oral ACT course once improving.

AETIOLOGY

SARS-CoV-2 = beta-coronavirus (positive-sense ssRNA); uses ACE2 receptor (Angiotensin-Converting Enzyme 2) for cell entry (via spike protein — S protein); membrane priming by TMPRSS2 serine protease ; primarily infects respiratory epithelium but also heart, kidney, gut, CNS (ACE2 expressed widely). Zoonotic origin (bats via intermediate host); human-to-human transmission (respiratory droplets + aerosol + contact).

CLINICAL SPECTRUM

PATHOGENESIS

• SARS-CoV-2 infects Type II pneumocytes (ACE2 expression highest) → viral replication → cell death → inflammatory response
• Cytokine storm (IL-6, TNF-α, IL-1β) in severe disease → ARDS + multi-organ failure → hypercoagulability → venous thromboembolism (VTE) (PE, DVT)
• Endothelial dysfunction → widespread vascular damage → microvascular thrombosis → end-organ ischaemia

MANAGEMENT

▶ Dexamethasone 6 mg OD × 10 days (RECOVERY trial 2020) — reduces mortality in patients requiring O2/ventilation (NOT in mild disease without O2); 17% mortality reduction in ventilated patients

▶ Tocilizumab 8 mg/kg IV (IL-6 receptor antagonist) + dexamethasone — for severe/critical COVID requiring O2 or MV + ↑ CRP; reduces mortality (RECOVERY, REMAP-CAP)

▶ Remdesivir (nucleotide analogue — antiviral) 200 mg IV day 1 → 100 mg OD × 4 days — for moderate COVID requiring hospitalisation; reduces time to recovery

▶ Nirmatrelvir/Ritonavir (Paxlovid) — oral antiviral; within 5 days of symptom onset; for mild-moderate high-risk patients; protease inhibitor combination; dramatically reduces hospitalisation

• Anticoagulation: Prophylactic LMWH (enoxaparin 40 mg SC OD) in all hospitalised COVID; therapeutic if VTE confirmed
• Prone positioning (awake); O2 target SpO2 92–96%; HFNC before intubation; NIV

COVID-19 VACCINATION

• Causative agent: Dengue virus (ssRNA Flavivirus); 4 serotypes; transmitted by *Aedes aegypti* (day-biting mosquito; breeds in clean stagnant water)
• Classic features: High fever + severe headache + retro-orbital pain + myalgia/arthralgia ('breakbone fever' ) + rash (day 3–4) + thrombocytopenia + positive Tourniquet test
• DHF criteria: Fever + haemorrhagic tendency + thrombocytopenia (≤ 100 × 10⁹/L) + plasma leakage (HCT ↑ ≥ 20%)
• DSS: DHF + narrow pulse pressure ≤ 20 mmHg or hypotension
• Diagnosis: NS1 antigen (days 1–5 ) + IgM antibody (from day 5 ) + CBC (thrombocytopenia + rising HCT)
• Management: Paracetamol ONLY (NO NSAIDs/aspirin ); oral/IV hydration; platelet transfusion if < 20 × 10⁹/L + bleeding; NO specific antiviral
• WHO 2009 warning signs: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation (ascites/effusion), mucosal bleeding, lethargy or restlessness, hepatomegaly > 2 cm, and a rising haematocrit with a rapid fall in platelets.
• Dengue haemorrhagic fever (DHF): plasma leakage (haematocrit rise >= 20%, pleural effusion, ascites) plus haemorrhagic tendency and thrombocytopenia; more common in secondary dengue infection (ADE - antibody-dependent enhancement) due to cross-reactive antibodies from a previous serotype.
• Fluid management: the critical principle is to avoid under-hydration (shock) and over-hydration (pulmonary oedema); monitor haematocrit 2-4 hourly; use isotonic crystalloid; reduce fluids during recovery phase to avoid fluid overload.
• Phases of illness: febrile phase (2-7 days) then critical phase around defervescence (days 4-6; plasma leakage with shock risk) then recovery phase (fluid reabsorption - watch for fluid overload).
• Vector control: Eliminate breeding sites; source reduction is single most effective intervention

VIROLOGY

HPV = non-enveloped double-stranded DNA virus (Papillomaviridae); > 200 genotypes; sexually transmitted (most common STI worldwide). Classified by oncogenic risk: High-risk (16, 18, 31, 33, 45 — most important: HPV 16 + 18 account for 70% of cervical cancers ); Low-risk (6, 11 — cause genital warts/condylomata acuminata ).

CLINICAL FEATURES

• Cervical cancer (#1 HPV-related malignancy) — 99% of cervical cancers caused by HPV; squamous cell carcinoma most common; presentation: abnormal vaginal bleeding + post-coital bleeding; PAP smear + colposcopy for screening
• Genital warts (Condylomata acuminata) — HPV 6 + 11; cauliflower-like, soft, flesh-coloured papillomatous growths; external genitalia, perianal region, vagina, cervix; treat with podophyllin/trichloroacetic acid/cryotherapy/surgical excision
• Other HPV-associated cancers: Oropharyngeal cancer (HPV 16 — rising incidence; tonsil/base of tongue); anal cancer; penile cancer; vulval/vaginal cancer; laryngeal papillomatosis (HPV 6, 11 — recurrent respiratory papillomatosis )

HPV ONCOGENESIS

• HPV infects basal keratinocytes (via micro-abrasion during sexual contact)
• Viral genome integrates into host DNA → E6 protein (binds + degrades p53 tumour suppressor via ubiquitin pathway) + E7 protein (binds Rb protein → releases E2F transcription factor → uncontrolled cell proliferation)
• Loss of p53 + Rb function → immortalisation → malignant transformation
• p16INK4a overexpression (surrogate marker for HPV oncogenesis) — used in histopathology to identify HPV-related cancers

HPV VACCINES

▶ Schedule: < 15 years: 2 doses (0 + 6 months); ≥ 15 years / immunocompromised: 3 doses (0, 1–2, 6 months). Best given before sexual debut. Recombinant L1 VLP (Virus-Like Particle) vaccine — contains no viral DNA; cannot cause HPV infection.

• Clinical approach: short incubation with predominant vomiting = preformed toxin (S. aureus, emetic B. cereus); longer incubation with diarrhoea = infective/in-vivo toxin; bloody diarrhoea = invasive organisms (Shigella, Salmonella, Campylobacter, EHEC); neurological features = botulism (descending paralysis) or scombroid/ciguatera.
• Investigations: largely clinical; stool culture and microscopy if severe, bloody, prolonged or part of an outbreak; U&E for dehydration; notify public health for outbreaks.
• Management: oral rehydration or IV fluids is the mainstay; antibiotics are usually unnecessary and are avoided in EHEC (HUS risk); avoid anti-motility agents in bloody/inflammatory diarrhoea; red flags - dehydration, bloody stools, high fever, neurological signs, immunocompromise.

DEFINITION (PETERSDORF & BEESON 1961)

PUO (FUO) = fever (> 38.3°C on multiple occasions) lasting > 3 weeks with no diagnosis after 1 week of inpatient investigation (or 3 outpatient visits).

CAUSES — FOUR CATEGORIES

DEFINITION

Neutropenic fever = ANC (Absolute Neutrophil Count) < 500/mm³ (or expected to fall below 500 within 48 hrs) with single oral temperature ≥ 38.3°C OR ≥ 38.0°C sustained for > 1 hour . A medical emergency — infection can be rapidly fatal without prompt empirical antibiotics.

MASCC RISK STRATIFICATION

MASCC score (Multinational Association for Supportive Care in Cancer) — identifies low-risk patients suitable for outpatient oral antibiotics:

MANAGEMENT

• Cultures BEFORE antibiotics: 2 sets blood cultures (peripheral + central line); urine culture; culture any accessible site

▶ High-risk: IV Piperacillin-tazobactam 4.5 g IV q6h OR Cefepime 2 g IV q8h OR Meropenem 1 g IV q8h — start within 1 hour of presentation

▶ Low-risk: Oral Ciprofloxacin 500 mg BD + Amoxicillin-clavulanate 625 mg TDS — outpatient management (MASCC ≥ 21)

• Add vancomycin if: MRSA risk, mucositis, skin/line infection, haemodynamic instability, blood culture positive for gram-positive
• Add antifungal (caspofungin ) if: fever persisting > 4–7 days on antibiotics (empirical antifungal for occult fungal infection)
• Duration: Continue until ANC ≥ 500/mm³ AND afebrile for 48 hours AND cultures negative

AETIOLOGY & TRANSMISSION

Varicella-zoster virus (VZV) = alpha-herpesvirus (HHV-3); primary infection = chickenpox ; reactivation = herpes zoster (shingles). Highly contagious — transmission by respiratory droplets + direct contact + aerosol; R0 = 10–12 (among most contagious of infectious diseases). Incubation: 10–21 days (average 14 days).

CLINICAL FEATURES

• Prodrome: 1–2 days before rash — fever, malaise, anorexia, headache (milder in children)
• Characteristic rash: Appears first on trunk/scalp → spreads centrifugally; all 4 stages simultaneously (pathognomonic — 'dewdrop on rose petal' ): macule → papule → vesicle (thin-walled, 1–4 mm, clear fluid — like a drop of water on skin) → pustule → crusting
• Intensely pruritic — scratching → secondary bacterial infection (most common complication in children )
• Enanthem — vesicles on mucous membranes (mouth, conjunctiva, vagina)
• Contagious from 2 days before rash until ALL lesions have crusted (usually 5–7 days after rash onset)

COMPLICATIONS

• Bacterial superinfection (#1 complication in children) — *S. aureus, S. pyogenes*; impetigo → cellulitis → necrotising fasciitis
• Varicella pneumonia — #1 complication in adults (especially pregnant women — high mortality); CXR: nodular infiltrates
• Cerebellar ataxia — post-infectious; 1–3 weeks after rash; complete recovery in children
• Encephalitis — rare but serious; altered sensorium; seizures; high mortality
• Reye's syndrome — aspirin use in children with viral illness (varicella/influenza) → mitochondrial dysfunction → hepatic failure + encephalopathy → NEVER give aspirin to children with febrile illness
• Congenital varicella syndrome (1st/2nd trimester); neonatal varicella (maternal varicella 5 days before – 2 days after delivery → VZIG + aciclovir)

TREATMENT

▶ Aciclovir — 800 mg 5×/day × 7 days (oral; adults); IV Aciclovir 10 mg/kg q8h (severe/immunocompromised); start within 72 hours of rash onset ; reduces severity and duration; NOT routinely needed in healthy children (self-limiting)

• Symptomatic: Calamine lotion + antihistamines (pruritus); paracetamol (fever); NO aspirin (Reye's)
• VZIG (Varicella-Zoster Immunoglobulin) — post-exposure prophylaxis within 96 hours for high-risk contacts (immunocompromised, pregnant, neonates, premature infants)
• Vaccine: Live attenuated; 2 doses (1–12 years); highly effective (> 95% prevention of severe disease); contraindicated in pregnancy + immunocompromised

• Clinical features: incubation 2-21 days; acute febrile illness with myalgia, headache, pharyngitis; haemorrhagic phase - petechiae, purpura, mucosal bleeding, internal haemorrhage; multiorgan failure in severe cases; mortality varies from 1% (dengue DHF) to 90% (Ebola).
• Infection control: barrier nursing in a negative-pressure room; PPE including gown, gloves, goggles and face shield; notify public health immediately; contacts traced and monitored for 21 days; no specific treatment for most VHFs (ribavirin for Lassa fever and CCHF).

DEFINITION

VHF = a diverse group of illnesses caused by RNA viruses from 4 families, characterised by fever + haemorrhagic manifestations (though bleeding is not universal). All are zoonotic (animal reservoir) except person-to-person transmitted forms. Category A bioterrorism agents (Ebola, Marburg).

General management of VHF: Strict isolation (PPE — N95, gloves, gown, face shield ); contact + droplet + airborne precautions; supportive care (fluids, electrolytes, blood products); avoid IM injections; notify public health authorities immediately.

AETIOLOGY

Scarlet fever = acute febrile illness caused by Group A beta-haemolytic Streptococcus (GAS, *S. pyogenes*) producing erythrogenic (pyrogenic) exotoxins (SPE A, B, C — also cause TSS-like syndrome). Most common in children 5–15 years. Spread by respiratory droplets/contact.

• Clinical features: follows GAS pharyngitis by 1-2 days; high fever, sore throat, strawberry tongue (initially white-coated with red papillae, then red papillae exposed - red strawberry tongue); characteristic sandpaper rash - diffuse, fine papular erythema starting on the trunk, sparing the perioral area (circumoral pallor), and accentuated in skin folds (Pastia lines in axillae and antecubital fossa).
• Diagnosis and treatment: throat swab for GAS culture; elevated ASO titre; treat with penicillin V 500 mg QDS x 10 days (or amoxicillin) to prevent complications; erythromycin if penicillin-allergic; complications include post-streptococcal GN and rheumatic fever.

CLINICAL FEATURES

• Pharyngitis — exudative tonsillitis; tender cervical lymphadenopathy; sudden high fever + sore throat + odynophagia
• Strawberry tongue — initially white coating with red papillae protruding ('white strawberry tongue'); coating peels → 'red strawberry tongue' (raw, red, prominent papillae); seen days 4–5; highly characteristic
• Pastia's lines — linear petechial streaks in skin folds (antecubital fossa, axilla, groin); caused by capillary fragility + skin folds concentrating the rash
• Sandpaper rash — fine, diffuse, erythematous rash (feels like sandpaper on palpation ); appears within 1–2 days of fever; starts on neck/chest → spreads to trunk/extremities; spares face but circumoral pallor (white area around mouth)
• Skin desquamation — 1–2 weeks after rash; peeling of palms and soles (similar to TSS)

TREATMENT & COMPLICATIONS

▶ Phenoxymethylpenicillin (Penicillin V) 500 mg BD × 10 days — first-line; prevents rheumatic fever (reason for full 10 days ); OR Benzathine penicillin G 1.2 MIU IM single dose if compliance concern

▶ Amoxicillin 500 mg TDS × 10 days — alternative (but avoid in mononucleosis → rash )

▶ If penicillin allergy: Erythromycin/Azithromycin × 10 days

• Complications: Peritonsillar abscess; Acute Rheumatic Fever (2–3 weeks later — treat full 10 days penicillin to prevent); PSGN (3–6 weeks later — penicillin treatment does NOT prevent PSGN); Toxic Shock Syndrome

AETIOLOGY & TRANSMISSION

*Leptospira interrogans* — spirochaete; zoonosis (rats are main reservoir — *Leptospira icterohaemorrhagiae*); transmitted via contact of broken skin or mucous membranes with water/soil contaminated by infected animal urine ; common during flooding (India: post-monsoon ). Occupational risk: farmers, sewage workers, veterinarians, soldiers.

CLINICAL FEATURES — BIPHASIC ILLNESS

WEIL'S DISEASE

Weil's disease = severe icteric leptospirosis caused by *L. icterohaemorrhagiae*. Classic triad: Jaundice + Acute Kidney Injury + Haemorrhagic manifestations (thrombocytopenia → haemoptysis, haematuria, GI bleed). Mortality 5–40%.

• Liver: Direct hepatic invasion + cytokine-mediated → ↑ bilirubin + ↑ ALP (not AST/ALT — unlike viral hepatitis where transaminases much higher)
• Kidney: Tubulointerstitial nephritis → AKI; dialysis may be needed
• Lung: Leptospiral pulmonary haemorrhage syndrome (LPHS) — ARDS + massive haemoptysis; high mortality

LABORATORY DIAGNOSIS

• Phase 1 (leptospiraemia): Blood culture (EMJH medium — takes 2–6 weeks ); PCR on blood (most rapid ); dark-field microscopy (blood/CSF/urine)
• Phase 2 (immune): MAT (Microscopic Agglutination Test) — gold standard serological test; titre ≥ 1:100 (or 4× rise in paired samples); complex; reference lab only
• Rapid tests: IgM ELISA (Lepto Tek Dri Dot) — widely available; positive from day 5–8; good sensitivity
• Urine microscopy: Leptospires in urine from week 2 onwards (not early)

▶ Mild-moderate leptospirosis: Doxycycline 100 mg BD × 7 days OR Amoxicillin 500 mg TDS × 7 days

▶ Severe (Weil's disease): IV Penicillin G 1.5 MU q6h × 7 days OR IV Ceftriaxone 1 g OD × 7 days — equally effective; reduces duration; does NOT prevent renal/hepatic complications if started late

▶ Prophylaxis: Doxycycline 200 mg oral weekly — for short-term high-risk exposure (floods, soldiers)

OVERVIEW OF RICKETTSIAL DISEASES

SCRUB TYPHUS — CLINICAL FEATURES

• Eschar (tache noire) — painless, black necrotic ulcer with surrounding erythema at chigger bite site (axilla, groin, behind ear, neck — areas where chigger burrows into skin folds); highly characteristic; present in 50–70%
• High fever (39–41°C) + severe headache + myalgia + lymphadenopathy (regional + generalised)
• Maculopapular rash — appears day 5–7; trunk → extremities (spares face/palms/soles — unlike RMSF)
• Hepatosplenomegaly; conjunctival injection; relative bradycardia (Faget's sign)

NEUROLOGICAL MANIFESTATIONS

• Rickettsial meningoencephalitis — Rickettsia infects endothelial cells → vasculitis → CNS involvement
• Confusion + altered sensorium; aseptic meningitis ; encephalopathy; rarely focal deficits + seizures
• CSF: lymphocytic pleocytosis + mild protein elevation + normal/low glucose (aseptic meningitis pattern)
• Other serious complications: ARDS; AKI; myocarditis; hepatitis; DIC; multi-organ failure in severe cases

DIAGNOSIS & TREATMENT

• Weil-Felix reaction — agglutination of Proteus OX strains; OX-K positive in scrub typhus; OX-2 + OX-19 positive in epidemic/murine typhus; cheap, widely available but not specific
• IgM ELISA (SD Bioline Scrub Typhus kit) — rapid; sensitive; specific; widely used in India
• Immunofluorescence assay (IFA) — gold standard; PCR on eschar biopsy; Giemsa stain of buffy coat (Rickettsia visible in monocytes/neutrophils)

▶ Doxycycline 100 mg BD × 7–14 days — DOC for ALL rickettsial diseases including scrub typhus; start empirically when suspected (do NOT wait for confirmation ); dramatic response within 24–48 hrs (diagnostic + therapeutic)

▶ Azithromycin (500 mg OD × 5 days) — preferred in pregnancy and children < 8 years (doxycycline contraindicated in these groups)

AETIOLOGY

*Leishmania donovani* (in India/Africa) — intracellular protozoan; vector: female *Phlebotomus argentipes* sandfly (in India); sandfly bites → inoculates promastigotes → phagocytosed by macrophages → transform into amastigotes (Leishman-Donovan/LD bodies) → multiply in RES (spleen, liver, bone marrow, lymph nodes). India accounts for > 50% of global visceral leishmaniasis (VL) burden.

CLINICAL FEATURES

• Prolonged undulant fever (weeks to months; twice-daily pattern); insidious onset; malaise
• MASSIVE SPLENOMEGALY — hallmark; Organ can reach the right iliac fossa; firm, non-tender; #1 cause of massive splenomegaly in India
• Hepatomegaly — less dramatic than splenomegaly; usually soft
• Hyperpigmentation — progressive darkening of skin (especially face + extremities); explains name 'Kala-Azar' = 'Black fever' in Hindi
• Cachexia — progressive weight loss and muscle wasting; pot-belly appearance (spleen + liver) with wasted limbs
• Pancytopenia — anaemia + leucopenia + thrombocytopenia from hypersplenism + marrow invasion
• Pedal oedema from hypoalbuminaemia; epistaxis; bleeding tendency; secondary infections (TB, pneumonia)

DIAGNOSIS

• Demonstration of LD bodies (amastigotes) in:

• Bone marrow aspirate (Gold Standard) — sensitivity 60–85%; Giemsa stain; LD bodies in macrophages
• Splenic aspirate — sensitivity 93–99% (highest) but risk of haemorrhage (do NOT do if platelets < 40 × 10⁹/L)

• rK39 strip test — rapid diagnostic test; IgG against *L. donovani* antigen; sensitivity 97%, specificity 98% in India; first-line rapid test
• Aldehyde (Napier's formol-gel) test — high globulins cause clotting with formaldehyde; non-specific but historically used; + means proteins > 10 g/dL
• CBC: Pancytopenia; very high ESR; ↑ IgG; albumin:globulin ratio reversed (hypoalbuminaemia + hyperglobulinaemia )

TREATMENT

▶ Liposomal Amphotericin B (L-AmB) 10 mg/kg single dose IV (India NVBDCP preferred regimen) — drug of choice for VL in South Asia; very high efficacy (> 95%); minimal side effects; encapsulated in liposomes → preferentially taken up by macrophages; rapidly fungicidal

▶ Miltefosine 2.5 mg/kg/day × 28 days (oral) — first oral drug for VL; MOA: inhibits phospholipid synthesis; side effects: GI (nausea/vomiting), teratogenic (AVOID in pregnancy + ensure contraception for 3 months post-treatment)

▶ Conventional Amphotericin B 1 mg/kg IV alternate days × 30 doses — if L-AmB unavailable; nephrotoxic + hypokalaemia

• Post-Kala-Azar Dermal Leishmaniasis (PKDL) — skin rash (hypopigmented macules → nodules) appearing months–years after VL cure; infectious reservoir; treat with miltefosine × 12 weeks

AETIOLOGY & TRANSMISSION

*Brucella* spp. — gram-negative coccobacillus; intracellular pathogen; zoonosis . Species: B. melitensis (#1 human pathogen; goats/sheep), B. abortus (cattle), B. suis (pigs), B. canis (dogs). Transmission: ingestion of unpasteurised milk/cheese , direct contact with infected animal products (slaughterhouse workers, farmers, veterinarians), inhalation of aerosols; rare person-to-person. Incubation: 1–8 weeks.

CLINICAL FEATURES — UNDULANT FEVER

• Undulant (brucellosis) fever — waves of fever (38–40°C) that rise and fall over days to weeks; classic feature gives it the name 'undulant fever'; can last months if untreated
• Profuse night sweats — drenching; characteristic; may smell of 'wet hay' (mouldy)
• Arthralgia/Arthritis — most common complication; large joints (sacroiliac joint — most specific); hip, knee; sacroiliitis on CT
• Hepatosplenomegaly ; lymphadenopathy; Faget's sign (relative bradycardia)
• Orchitis/Epididymo-orchitis — unilateral scrotal swelling + pain; important complication in adult males; can be first presentation
• Neurobrucellosis — meningoencephalitis; papilloedema; psychiatric symptoms; peripheral neuropathy
• Infective endocarditis — rare but highest mortality complication; aortic valve most common; *Brucella* HACEK group culture negative

DIAGNOSIS

• Blood culture (Gold Standard) — *Brucella* slow-growing; incubate for 4–6 weeks; BACTEC automated systems improve detection
• Brucella Agglutination Test (Rose Bengal Test/Wright's serology) — simple rapid screening test; titre ≥ 1:160 (endemic areas); Standard Agglutination Test (SAT) — definitive serology; single titre ≥ 1:160 significant; rising titres confirm active infection
• 2-ME (2-Mercaptoethanol) test — differentiates IgG (remains after 2-ME treatment) from IgM (destroyed); IgG persistence = active/chronic brucellosis
• Bone marrow culture (highest yield); PCR on blood/bone marrow; CBC: leucopenia + relative lymphocytosis

▶ Doxycycline 100 mg BD × 6 weeks + Rifampicin 600–900 mg OD × 6 weeks — most commonly used combination; oral; effective for uncomplicated disease

▶ Doxycycline 100 mg BD × 6 weeks + Streptomycin 1 g IM/day × 2–3 weeks — gold standard (WHO); lower relapse rate than doxy + rifampicin; parenteral streptomycin limits use

• Neurobrucellosis: Add rifampicin + use doxycycline + ceftriaxone; treat for 3–6 months
• Endocarditis: Triple therapy (doxycycline + rifampicin + aminoglycoside) × 3–6 months + surgery (valve replacement usually required)

AETIOLOGY & TRANSMISSION

Rabies virus = bullet-shaped, single-stranded negative-sense RNA virus (Rhabdoviridae, Lyssavirus genus); ALWAYS fatal once clinical symptoms develop (rare exceptions documented). Transmitted via bite of infected animal (dog — #1 in India; also bats, foxes, racoons) → virus enters muscle → travels along peripheral nerves (retrograde axonal transport ) → CNS → encephalitis → spreads to salivary glands.

PATHOGENESIS

• Wound inoculation: Virus injected by bite → replicates locally in muscle at inoculation site
• Peripheral nerve transport: Virus binds nicotinic acetylcholine receptors + NCAM → enters PNS → retrograde axonal transport along peripheral nerves at 12–24 mm/day (explains incubation period variability — 10 days to > 1 year, depends on bite site distance from brain)
• CNS invasion: Reaches spinal cord + brainstem → massive neuronal infection → limbic system predilection (explains rage, fear of water)
• Centrifugal spread: Virus travels from CNS → salivary glands (infective saliva ) → cornea → skin → enables disease transmission
• Negri bodies — cytoplasmic inclusions in hippocampal Purkinje cells and hippocampus ; eosinophilic; bullet-shaped; pathognomonic on post-mortem histology

CLINICAL FEATURES

DIAGNOSIS

• Antemortem: Skin biopsy of nape of neck (hair follicles — antigen by FAT); Saliva (RT-PCR); CSF (RT-PCR/antibodies); Corneal impression (antigen)
• Postmortem: Brain tissue by DFA (Direct Fluorescent Antibody test) — gold standard; Negri bodies on H&E (Sellar's stain)

POST-EXPOSURE PROPHYLAXIS (PEP)

• Wound care (most important first step): Thorough washing with soap and water × 15 min + antiseptic (povidone-iodine)
• Category assessment:

• Category I: Touching/feeding animal — no prophylaxis needed
• Category II (bites): Wash + vaccine only
• Category III (transdermal bites, mucous membrane exposure): Wound care + RIG (Rabies Immunoglobulin) + vaccine

• RIG (Rabies Immunoglobulin): 20 IU/kg (HRIG) — infiltrate ALL around wound; remainder IM (deltoid); give day 0 ONLY (not after day 7 — interferes with active immunity)

▶ Rabies vaccine: Cell culture vaccine (Vero cell based — VERORAB ); 5 doses — days 0, 3, 7, 14, 28 (Essen schedule ) OR 4 doses — days 0, 3, 7, 28 (Zagreb schedule) OR 2-site ID (intradermal) updated WHO schedule — days 0, 3, 7 (WHO 2018 recommendation — 3 visit schedule)

• NO 'window' for PEP — give even late; as long as symptoms haven't started, PEP can work

DOTS CATEGORY I REGIMEN (NTEP 2022)

• Patient type: New smear positive/negative pulmonary TB + new extrapulmonary TB + serious forms of TB (TB meningitis, miliary, pericardial, vertebral with neurological complications)

▶ Intensive Phase (IP): 2 months HRZE (daily fixed-dose combination tablets, weight-based dosing)
H = Isoniazid (INH); R = Rifampicin; Z = Pyrazinamide; E = Ethambutol
All 4 drugs DAILY for 2 months (under DOT — directly observed therapy )

▶ Continuation Phase (CP): 4 months HR (daily)
Isoniazid + Rifampicin DAILY for 4 months
Total: 6 months

• Pyridoxine (Vitamin B6) 10 mg/day — given with INH to prevent peripheral neuropathy

ADVERSE REACTIONS TO 1ST-LINE ATT DRUGS

DRUG-INDUCED SLE (DILE)

Drug-induced lupus (DILE) = SLE-like syndrome caused by certain drugs; resolves on drug withdrawal.

• Features of DILE: Arthritis + arthralgias + serositis (pleuritis/pericarditis) + fever; anti-histone antibodies (positive in > 95% of DILE — more specific than ANA); renal and CNS involvement rare in DILE (unlike idiopathic SLE); anti-dsDNA antibodies NEGATIVE (positive in idiopathic SLE)
• Treatment: Stop offending drug → symptoms resolve in weeks to months; NSAIDs/hydroxychloroquine for persisting symptoms

MDR-TB DEFINITIONS

• When to suspect MDR-TB: Treatment failure (smear +ve after month 4) | Relapse | Previously treated patient | MDR-TB contact | HIV co-infection | Prior incomplete/irregular treatment
• Diagnosis: CBNAAT (GeneXpert MTB/RIF) detects RIF resistance in 2 hours → confirm with LPA (Line Probe Assay) for 1st + 2nd line drugs → phenotypic DST on culture for definitive DST

▶ BPaL Regimen (WHO 2022) × 6 months:
Bedaquiline 400 mg OD × 2 wks → 200 mg 3×/wk × 22 wks (inhibits ATP synthase; QTc monitoring )
Pretomanid 200 mg OD × 26 wks (nitroimidazole)
Linezolid 600 mg OD × 26 wks (protein synthesis inhibitor; monitor: optic neuropathy + CBC )

LATENT TB INFECTION (LTBI)

LTBI = M. tuberculosis infection without active disease — TST or IGRA positive but no symptoms/signs/CXR abnormality.

▶ LTBI Treatment: 3HP (Isoniazid 900 mg + Rifapentine 900 mg weekly × 12 doses — 3 months ) — preferred (shorter, better completion); OR 6H (Isoniazid 300 mg OD × 6 months); OR 3HR (INH + RIF × 3 months). Treatment reduces risk of active TB by 60–90%.

FILARIASIS

*Wuchereria bancrofti* (#1 in India, 99%) — lymphatic filariasis; vector: Culex mosquito (night-biting); larvae (microfilariae) show nocturnal periodicity (appear in peripheral blood only 10 PM–2 AM — blood should be taken at night for diagnosis ).

▶ Diethylcarbamazine (DEC) 6 mg/kg/day × 12 days (microfilaricidal + macrofilaricidal); Mass Drug Administration (MDA) — annual DEC + Albendazole for entire endemic population (India NVBDCP strategy ); albendazole + ivermectin in Africa

HERPES ZOSTER (SHINGLES)

VZV reactivation from dorsal root ganglia (or trigeminal) → dermatomal vesicular rash. Risk: advancing age + immunocompromised.

• Clinical features: Prodrome of dermatomal pain + hyperaesthesia (1–4 days) → unilateral dermatomal vesicular rash (does NOT cross midline ); thoracic dermatomes most common (T3–L3)
• Ramsay Hunt syndrome — VZV reactivation in geniculate ganglion (facial nerve ganglia) → triad: ipsilateral LMN facial palsy + zoster vesicles in external ear (auricle ) + ipsilateral loss of taste (anterior 2/3 tongue)
• Postherpetic neuralgia (PHN) — burning pain persisting > 3 months after rash; most common complication; elderly; treat with gabapentin /pregabalin/amitriptyline/capsaicin
• Herpes zoster ophthalmicus — V1 (ophthalmic) trigeminal branch; Hutchinson's sign (vesicle on tip of nose = nasociliary branch involvement = high risk of ocular complications); refer ophthalmology

▶ Aciclovir 800 mg 5×/day × 7 days (start within 72 hrs of rash onset); Valaciclovir 1 g TDS × 7 days (preferred — better bioavailability, simpler dosing); IV aciclovir for severe/immunocompromised

• Zoster vaccine (Shingrix — recombinant subunit): 2 doses 2–6 months apart; ≥ 50 years or immunocompromised ≥ 19 years; > 90% efficacy; prevents PHN

GONORRHOEA

*Neisseria gonorrhoeae* — gram-negative diplococcus (kidney-shaped, intracellular — found inside PMNs on smear); sexually transmitted; incubation 2–7 days ; pili + Opa proteins mediate attachment to columnar/transitional epithelium.

• Male: Acute purulent urethritis (profuse yellow-green discharge + dysuria); epididymitis; prostatitis; urethral stricture (chronic)
• Female: Often asymptomatic (80%); mucopurulent cervicitis; Pelvic Inflammatory Disease (PID) → salpingitis → infertility; Bartholin's abscess; Fitz-Hugh-Curtis syndrome (perihepatitis — RUQ pain + violin-string adhesions on laparoscopy)
• Disseminated gonococcal infection (DGI) — bacteraemia → septic arthritis (monoarthritis; knee > wrist > ankle) + dermatitis (pustular rash on extremities ) + tenosynovitis (DGI triad )
• Ophthalmia neonatorum (neonatal conjunctivitis from birth canal)

▶ Ceftriaxone 500 mg IM single dose — first-line (dual therapy: ceftriaxone + azithromycin if chlamydia not excluded); cefixime 400 mg oral (if IM not possible)

ANAEROBIC INFECTIONS

NEUROCYSTICERCOSIS (NCC)

NCC = invasion of CNS by larval stage (Cysticercus cellulosae) of *Taenia solium* (pork tapeworm ). Humans are accidental intermediate host (via ingestion of T. solium eggs from contaminated food/faeco-oral self-infection). #1 cause of acquired epilepsy in developing countries including India.

• Clinical features: New-onset seizures (#1 presenting symptom); headache; focal neurological deficits; hydrocephalus (ventricular/subarachnoid cysts obstructing CSF flow ); meningitis (racemose cysticercosis )
• Diagnosis: CT brain — ring-enhancing lesion (cyst + surrounding oedema ± scolex 'dot sign' — pathognomonic); calcified lesions (dead cysts); MRI superior; serology (ELISA) on blood + CSF

▶ Albendazole 15 mg/kg/day (max 800 mg) × 8 days + Dexamethasone (reduces oedema from dying cysts) + Antiepileptics (phenytoin/levetiracetam) for seizure control

• Surgery — for obstructive hydrocephalus (VP shunt); giant/ventricular cysts

ELEPHANTIASIS

Elephantiasis = end-stage chronic lymphoedema causing massive non-pitting oedema with thickened, hardened (fibrosed), rugose skin resembling elephant hide. In India: almost exclusively from lymphatic filariasis (*W. bancrofti* ).

• Pathogenesis: Repeated ADL episodes → lymphatic vessel inflammation → fibrosis → lymphatic obstruction → protein-rich fluid accumulation in interstitium → fibroblast proliferation → skin fibrosis → elephantiasis
• Sites: Legs (most common); scrotum (scrotal elephantiasis — very specific to filariasis); vulva; arms; breasts
• Management: No reversal of established elephantiasis; MDA with DEC + albendazole (prevent further damage); hygiene + physiotherapy; compression bandaging; surgery (debulking) for severe scrotal involvement
• Neurocysticercosis - imaging: CT shows ring-enhancing cystic lesion with perilesional oedema in active stage (viable cyst with scolex - "hole with a dot" sign on MRI); degenerating cyst with colloidal content; calcified nodule in inactive stage; MRI is superior for detecting posterior fossa and brainstem lesions.
• Treatment algorithm: single calcified lesion - anti-epileptics only; single enhancing lesion - albendazole + dexamethasone + anti-epileptics; multiple lesions - prolonged albendazole; ventricular cysts or hydrocephalus - neurosurgery (endoscopic removal or VP shunt).
• Filariasis prevention: annual mass drug administration (MDA) with DEC + albendazole in endemic areas; mosquito control; protective clothing; avoiding exposure during peak biting hours; surveillance for microfilaraemia.

AETIOLOGY & TRANSMISSION

Chikungunya virus = alpha-togavirus (ssRNA) ; transmitted by *Aedes aegypti* AND *Aedes albopictus* (both bite during daytime — shares vector with dengue). Name means 'that which bends up' in Makonde language (reflects stooped posture from arthralgia ). Incubation: 2–12 days. No animal reservoir — humans are primary amplifying host during epidemics.

CLINICAL FEATURES

• Abrupt-onset high fever (> 39°C); sudden start; lasts 2–5 days
• Severe, debilitating joint pain — THE hallmark; polyarthralgia/arthritis predominantly affecting SMALL joints (wrists, fingers, ankles ); bilateral, symmetrical; patient adopts flexed posture (explains etymology)
• Rash — maculopapular; appears day 2–5; trunk + limbs; may involve face; occasionally bullous in children
• Myalgia; headache; conjunctival injection; retroorbital pain (like dengue — distinguishing from dengue: chikungunya has more severe joint pain but less thrombocytopenia)
• Chronic arthritis — most important distinguishing feature; joint pain can persist months to years (60% have persistent arthritis at 3 months; 12–15% at 3 years); leads to significant disability
• Atypical severe forms: Meningoencephalitis; Guillain-Barré-like syndrome; myocarditis; hepatitis (immunocompromised)

DIAGNOSIS & MANAGEMENT

• RT-PCR — days 1–7 (viraemic phase); gold standard for acute diagnosis
• Serology — IgM antibody ELISA (from day 5); IgG for past exposure; paired serology (4× rise in titres confirms diagnosis)
• Chikungunya vs Dengue: Similar presentation; chikungunya = severe arthralgia + less thrombocytopenia; dengue = DHF risk + severe thrombocytopenia + haemorrhagic features; both share same vector

Treatment: No specific antiviral. Supportive only:

▶ Paracetamol for fever and pain (NEVER aspirin or NSAIDs in first 5 days — cannot exclude dengue )

▶ NSAIDs (diclofenac/naproxen) or hydroxychloroquine — after dengue excluded (day 5+); for chronic arthritis

• Chikungunya vaccine (VLA1553 — Ixchiq): Live attenuated; single dose; FDA approved 2023 for ≥ 18 years travelling to endemic areas; > 98.9% immunogenicity

EBOLA VIRUS DISEASE (EVD)

Ebola virus — filovirus (ssRNA, filamentous); 5 species; most pathogenic: Ebola virus (Zaire ); natural reservoir: fruit bats ; transmitted human-to-human via direct contact with blood/body fluids/secretions of symptomatic patients (not airborne — contact + droplet); CFR 25–90% .

• Clinical features: Abrupt fever + severe headache + myalgia → nausea/vomiting/diarrhoea → haemorrhagic phase (bleeding from mucosal surfaces, IV sites; haematemesis; melaena; maculopapular rash ) → MODS → death or recovery (day 6–16)
• PCR (RT-PCR) — gold standard; blood sample; result within hours; positive from day 3 of illness; Antigen RDT for field use
• Treatment: Atoltivimab + Maftivimab + Odesivimab (Inmazeb) — triple mAb cocktail; FDA approved 2020 for Zaire Ebola; dramatically reduces mortality. Ansuvimab (Ebanga) single mAb — also approved
• Strict isolation + PPE (full face shield + gown + double gloves + N95 or higher ); contact + droplet precautions; environmental decontamination (bleach)

H1N1 (SWINE FLU)

H1N1 (2009 pandemic influenza A) — novel reassortant influenza A virus (H = haemagglutinin; N = neuraminidase); swine-origin (genes from human + swine + avian strains). WHO declared pandemic June 2009 — first influenza pandemic of 21st century.

• Clinical features: Fever (abrupt) + cough + sore throat + myalgia + headache; gastrointestinal symptoms (nausea/vomiting/diarrhoea) more common than seasonal flu ; severe disease: ARDS + viral pneumonia
• High-risk groups for severe disease: Pregnancy (3× mortality risk); extremes of age; BMI > 40; chronic illness (DM, CKD, CVD, respiratory, immunocompromised); healthcare workers

▶ Oseltamivir (Tamiflu) 75 mg BD × 5 days — neuraminidase inhibitor; treatment of choice; start within 48 hrs of symptom onset; also prophylaxis (75 mg OD × 10 days) for high-risk contacts

▶ Zanamivir (inhaled) — alternative; for oseltamivir-resistant strains

• Annual influenza vaccine — includes H1N1 component; updated annually; recommended for all high-risk groups
• Diagnosis: RT-PCR on nasopharyngeal swab — gold standard; RIDT (rapid antigen test) — quick but less sensitive

AETIOLOGY

*Mycobacterium leprae* — acid-fast bacillus; obligate intracellular pathogen ; grows in Schwann cells (peripheral nerves) and skin macrophages; cannot be cultured in vitro; slowest doubling time of any bacterium (12–14 days ); transmitted by respiratory droplets (Nasal secretions of untreated lepromatous patients); long incubation: 3–20 years. India has ~50% of global leprosy burden. Eliminated as a public health problem (< 1/10,000 prevalence) in India 2005.

CLASSIFICATION (RIDLEY-JOPLING)

CARDINAL SIGNS OF LEPROSY

• Hypopigmented/erythematous skin lesion with loss of sensation (anaesthesia) in the lesion
• Thickened peripheral nerve — most common nerves: Ulnar nerve (claw hand), Common peroneal (foot drop ), Posterior tibial (plantar anaesthesia), Lateral popliteal, Great auricular, Facial nerve
• Positive skin smear/biopsy for AFB — done from slit-skin smear from earlobes + active lesions

MDT (MULTI-DRUG THERAPY)

• Lepra reactions (immunological reactions during treatment):
  Type 1 (Reversal reaction) — improved immunity → inflammation in existing lesions; treat with prednisolone
  Type 2 (Erythema Nodosum Leprosum — ENL) — immune complex-mediated; tender red nodules on new sites; fever; iritis; orchitis; treat with thalidomide (most effective) or prednisolone