Infectious Diseases: Detailed Clinical Notes

1. Hydatid Disease (Cystic Echinococcosis)

Etiology & Epidemiology

• Caused by Echinococcus granulosus (the dog tapeworm); a variant caused by E. multilocularis occurs in colder climates and spreads by invasion rather than expansion
• The dog is the definitive host; intermediate hosts are humans, sheep, and cattle
• Eggs are passed in dog feces, are highly resistant to environmental extremes, and enter humans via the oral-fecal route
• Endemic globally; common in sheep-farming communities, the Middle East, Central Asia, and Africa
• In the UK, a sheep farmer from a rural community is the classic patient profile

Pathology

• Outer pericyst - derived from compressed host tissue
• Middle ectocyst (hyaline laminated membrane) - non-infective
• Inner endocyst (germinal layer) - contains viable protoscolices; can form daughter cysts

WHO Classification (2003, based on ultrasound activity)

Clinical Features

• Most common site: liver (~70%); lung is second most common; virtually any organ can be affected
• Often asymptomatic - discovered incidentally on imaging
• Symptomatic disease: dull pain/RUQ mass from liver capsule stretching; dyspnoea if pulmonary
• Daughter cysts may communicate with the biliary tree → obstructive jaundice
• Emergency presentation: rupture causing anaphylactic shock (medical emergency)
• Urticaria/eosinophilia may accompany cyst leak

Diagnosis

• CT scan is the best modality - shows a space-occupying lesion with smooth outline and internal septa (daughter cysts)
• Ultrasound useful for surveillance
• Serology (ELISA, indirect hemagglutination, Casoni skin test)
• Eosinophilia present in ~25%
• Do NOT perform needle aspiration without anti-parasitic cover - risk of anaphylaxis and seeding

Treatment

• Managed in a tertiary center with hepatobiliary surgery, interventional radiology, and infectious disease expertise
• PAIR (Puncture, Aspiration, Injection of scolicidal agent, Re-aspiration) - minimally invasive procedure after drug cover
• Drug therapy: Albendazole (pre- and post-operatively); praziquantel is sometimes added
• Open surgery for complicated cysts (communication with biliary tree, ruptured cysts)
• Inactive/calcified cysts may be managed conservatively

Complications

• Rupture → anaphylaxis, peritoneal seeding (secondary echinococcosis)
• Biliary obstruction / cholangitis
• Infection of cyst → abscess
• Pulmonary cysts: haemoptysis, pneumothorax

2. Brucellosis

Etiology & Epidemiology

• Gram-negative aerobic coccobacillus; 4 species infect humans:
  • B. melitensis (sheep/goats/camels) - most common & virulent
  • B. abortus (cattle, bison)
  • B. suis (pigs, feral swine)
  • B. canis (dogs)

• 500,000 cases/year reported to WHO; true incidence estimated 10-25x higher

• Endemic in Mediterranean region, Arabian Gulf, Latin America, China, Indian subcontinent
• Transmission: ingestion of unpasteurized dairy products or undercooked meat (most common); inhalation (occupational - slaughterhouse workers, farmers, vets, lab personnel); direct contact via skin wounds or mucous membranes; rarely human-to-human (sexual, breastfeeding, blood transfusion, vertical)

Pathogenesis

• Brucella is a facultative intracellular pathogen - survives within macrophages and dendritic cells by suppressing innate immune responses
• Forms granulomas in the reticuloendothelial system
• Can persist in mononuclear cells for months to years if untreated

Clinical Features

• Incubation: 1-4 weeks (up to months)
• Fever (>39.4°C) in 95% - classically undulant (waves of fever) or intermittent
• Relative bradycardia (pulse-temperature deficit) may occur
• Malaise, sweats, arthralgias, myalgias, headache, fatigue ("it feels like being hit by a bus")
• Splenomegaly (10-15%), lymphadenopathy (~14%), hepatomegaly (less common)
• Lab: mild anemia, leukopenia, lymphocytosis, thrombocytopenia

• Osteoarticular (most common): sacroiliitis (most common acute form), spondylitis/spondylodiscitis (lumbar), paravertebral/psoas abscess, peripheral arthritis
• Neurobrucellosis: meningitis, encephalitis, radiculopathy
• Endocarditis: rare but most serious, high mortality
• Hepatitis, splenic abscess
• Epididymo-orchitis (most common urogenital manifestation in males)
• Pregnancy: spontaneous abortion, congenital abnormalities, neonatal infection

Diagnosis

• Blood culture: gold standard; sensitivity 10-90% (up to 85% in B. melitensis)
• Bone marrow culture: more sensitive than blood culture in B. melitensis
• Standard Agglutination Test (SAT): 1:160 titer in endemic areas; 1:80 in non-endemic = presumptive diagnosis; fourfold rise in paired samples
• PCR / NAAT: highly accurate; cannot confirm cure as nucleic acid persists
• CSF culture positive in 45% of meningitis cases

Treatment

• Minimum 2 drugs for at least 6 weeks (focal disease: ≥3 months)
• Gold standard: IM streptomycin (0.75-1 g/day × 14-21 days) + doxycycline (100 mg BID × 6 weeks)
• WHO-favored alternative: Rifampin (600-900 mg/day) + doxycycline (100 mg BID) × 6 weeks - higher relapse rate (~10-20%)
• Children/pregnant women (cannot use tetracyclines): high-dose TMP-SMX
• Focal neurologic disease: standard regimen + ceftriaxone for 3-6 months
• Endocarditis: 3-drug regimen (aminoglycoside + tetracycline + rifampin ± ceftriaxone) × ≥4-6 months; often requires valve surgery
• Monotherapy is never adequate - resistance is rare but relapse from inadequate treatment is common

3. Leptospirosis (Weil's Disease)

Etiology & Epidemiology

• Caused by the spirochete Leptospira interrogans (>200 serovars); L. biflexa is non-pathogenic
• Worldwide distribution but highest burden in tropical/subtropical developing countries
• Reservoir hosts: rodents (key), dogs, pigs, cattle, horses - shed via urine into environment
• Humans are incidental hosts - infection occurs through contact with contaminated water/soil/mud via abraded skin, mucous membranes, or conjunctiva; rarely by ingestion
• Classic settings: flooding, agricultural work (rice paddy, sugarcane), occupational (farmers, sewer workers, military), urban slums, adventure sports/triathlons

Clinical Features

• Abrupt onset after incubation period of 2-26 days (mean 10 days)
• High fever, rigors, severe headache, myalgias (especially calves), malaise
• Conjunctival suffusion (redness without discharge) - highly characteristic
• Splenomegaly, lymphadenopathy, pharyngitis, hepatomegaly, rash, muscle tenderness

• Brief remission, then return of fever with immune-mediated manifestations
• Weil's disease (severe form, 5-15% of cases): jaundice + AKI + hemorrhage (the classic triad)
• Aseptic meningitis (common immune-phase manifestation)
• Uveitis (can occur weeks later and become chronic)
• Pulmonary hemorrhage syndrome (ARDS) - severe, high mortality

Organ Involvement

• Kidneys (AKI): 44-67% of patients; characteristically non-oliguric with hypokalemia; pathology = acute interstitial nephritis
• Liver: conjugated hyperbilirubinemia in 85%; elevated ALP; transaminases relatively mild
• Lungs: pulmonary hemorrhage → ARDS (serious; may require mechanical ventilation)
• CNS: aseptic meningitis

Diagnosis

• Microscopic Agglutination Test (MAT): gold standard; paired samples 2 weeks apart; fourfold rise = positive; performed against live Leptospira serovars
• PCR: best in first week (leptospiremic phase); earlier diagnosis
• Culture: definitive but slow (weeks); not practical for acute management
• Urinalysis: proteinuria, hematuria, casts
• Lab: elevated creatinine, bilirubin; leukocytosis; thrombocytopenia; raised CK

Treatment

• Mild-moderate disease: oral doxycycline 100 mg BID × 7 days (also prophylaxis in high-risk exposure: 200 mg weekly)
• Severe disease (Weil's): IV penicillin G or ceftriaxone × 7-14 days; ampicillin is an alternative
• Antibiotic therapy is most effective when started in the leptospiremic phase
• Supportive care: dialysis for severe AKI (often required), ventilatory support for ARDS

Complications

• AKI (may require dialysis)
• Pulmonary hemorrhage / ARDS
• Hepatic failure
• Uveitis (weeks-months later)
• DIC, thrombocytopenia
• Myocarditis, arrhythmias
• Mortality from Weil's disease: 5-15%; from pulmonary hemorrhage: up to 50%

4. Typhus Fever

Classification and Organisms

Epidemiology

• Epidemic typhus: historically caused catastrophic outbreaks during wars and famines; still occurs in poverty-stricken areas (Andes, Africa, disrupted social conditions); Brill-Zinsser disease = recrudescence years after primary infection
• Murine typhus: most important typhus in the USA today; tropical/subtropical coastal areas; Texas, California, Hawaii
• Scrub typhus: Asia-Pacific region; most prevalent rickettsial disease globally

Pathogenesis

• All rickettsiae are obligate intracellular organisms that infect vascular endothelial cells
• Vasculitis is the fundamental pathological process - leads to microvascular leakage, tissue injury in multiple organs
• Entry: infected flea feces scratched into skin (murine typhus); louse feces on skin/mucous membranes (epidemic); mite bite (scrub typhus)

Clinical Features - Epidemic Typhus (R. prowazekii)

• Incubation: 10-14 days
• Abrupt onset of fever, severe headache, myalgias
• Rash: appears days 5-6 in ~80% of patients with fair skin; macular/maculopapular; starts on trunk, spreads centrifugally (note: face, palms, soles often spared initially)
• Neurologic manifestations: up to 80% of cases (confusion, stupor, meningism)
• Respiratory manifestations: 40-70%
• Eschar: NOT typically seen in epidemic typhus (present in scrub typhus)
• Without treatment: case fatality rate up to 60%

Clinical Features - Murine Typhus (R. typhi)

• Incubation: 1-2 weeks
• Fever, severe headache, chills, myalgias, nausea
• Rash (macular/maculopapular, trunk, day 5-6): visible in 80% of fair-skinned patients, only 20% of dark-skinned
• Generally less severe than epidemic typhus
• Pulmonary, hepatic, renal complications possible

Clinical Features - Scrub Typhus (O. tsutsugamushi)

• Eschar at the mite bite site (pathognomonic when present) with regional lymphadenopathy
• Fever, headache, myalgias, rash (maculopapular, trunk)
• Can cause meningoencephalitis, hepatitis, interstitial pneumonitis, myocarditis
• AKI is a known complication

Diagnosis

• Serology: Weil-Felix test (historical - cross-reactive antibodies against Proteus species); now replaced by Indirect Fluorescent Antibody (IFA) - gold standard
• Immunohistochemistry of skin biopsy (eschar in scrub typhus)
• PCR of blood or eschar tissue
• Clinical diagnosis is often presumptive while awaiting serology

Treatment

• Doxycycline is first-line for ALL forms of typhus (100 mg BID × 7-14 days)
• Start empirically when suspected - do not wait for confirmation
• Response to doxycycline is often dramatic and diagnostic
• Chloramphenicol is an alternative (used especially in children; concern about aplastic anemia)
• Azithromycin is used in scrub typhus (especially in pregnant patients and in areas with doxycycline-resistant scrub typhus)
• Prophylaxis: doxycycline 200 mg once weekly in highly endemic scrub typhus areas

5. Measles (Rubeola)

Etiology & Epidemiology

• Caused by measles virus (genus Morbillivirus, family Paramyxoviridae) - single-stranded negative-sense RNA virus
• Transmission: respiratory droplets and aerosols - extremely contagious (R0 ~12-18)
• Incubation: 9-12 days
• Affects predominantly unvaccinated children; but in current outbreaks, older children, adolescents, and adults can be affected
• Two-dose vaccine (MMR) achieving >95% coverage leads to measles elimination; Japan and some EU countries have struggled to reach this threshold
• Still causes ~100,000+ deaths/year globally, predominantly in under-5 children in developing nations

Clinical Features

• 3 Cs: Cough, Coryza (nasal congestion), Conjunctivitis
• High fever, malaise
• Koplik spots (pathognomonic): 1-mm white papules on an erythematous base on the buccal mucosa opposite the lower molars; appear during the prodrome, 1-2 days before the rash

• Rash appears on day 3-5 of illness
• Begins at hairline/forehead and behind ears → spreads centrifugally down the face, then trunk, then extremities (3-day progression)
• Maculopapular, coalescing - most confluent on face, more discrete on extremities
• Lesions blanch with pressure initially
• Fever peaks with rash and falls 6-7 days later as rash clears
• Purpura on extremities can be seen (especially "black measles" - severe form with DIC)

Differential Diagnosis

Complications

• Otitis media (most common complication, ~1-9% of cases)
• Pneumonia (most common cause of measles death; giant cell/Hecht pneumonia)
• Encephalitis (<1% but can be fatal; post-infectious demyelinating encephalomyelitis)
• Subacute sclerosing panencephalitis (SSPE): rare, progressive fatal encephalitis occurring 7-10 years after measles infection; due to persistent defective measles virus in CNS
• Thrombocytopenic purpura
• Keratitis → corneal blindness (especially in Vitamin A-deficient children)
• Worse in immunocompromised (T-cell deficiency, HIV) - rash may be absent; giant cell pneumonia without rash
• Infection in pregnancy: fetal death, premature birth

Diagnosis

• Primarily clinical (prodrome + Koplik spots + typical rash)
• Serology: measles-specific IgM (rises 3-4 days after rash onset); fourfold rise in IgG in paired sera
• Viral culture, RT-PCR of respiratory secretions or urine

Treatment

• No specific antiviral therapy for uncomplicated measles
• Supportive: antipyretics, fluids, nutrition
• Vitamin A supplementation: WHO recommends for all children with measles in developing countries (reduces mortality and severity of pneumonia and encephalitis); two doses of 200,000 IU (100,000 IU in infants <1 year)
• Ribavirin: used for severe measles in immunocompromised patients (evidence limited)
• Secondary bacterial complications (otitis media, pneumonia): antibiotics

Prevention

• MMR vaccine (live attenuated): 2 doses; 93-97% efficacy after 2 doses
• Post-exposure prophylaxis: MMR within 72 hours of exposure; IVIG within 6 days for immunocompromised and infants <12 months

6. Varicella (Chickenpox)

Etiology & Epidemiology

• Caused by Varicella-Zoster Virus (VZV) - alpha-herpesvirus; double-stranded DNA; single serotype but multiple genotypes
• Primary VZV infection = varicella (chickenpox); reactivation = herpes zoster (shingles)
• Transmission: airborne droplet nuclei and direct contact with vesicular fluid; highly contagious (attack rate in susceptible household contacts ~65-86%)
• Incubation: 10-21 days (average 14-16 days)
• Before vaccination era, most cases in children aged 5-9; now shifting toward adolescents/adults in vaccinated populations
• Live attenuated Oka-strain vaccine has virtually eliminated varicella in countries with routine immunization

Pathogenesis

• Entry via upper respiratory tract mucosa → infects tonsillar T cells → primary viremia (seeding reticuloendothelial system)
• Secondary viremia (day 10-14): larger viremia → systemic symptoms and skin lesions
• Lesions in crops reflect cyclic viremia terminated by VZV-specific T-cell immunity after 3-5 days
• Latency: VZV retreats to sensory ganglia (trigeminal, dorsal root T1-L2) → persists for life; reactivation causes herpes zoster

Clinical Features

• 2-3 days before rash: mild fever, malaise, headache, anorexia, backache, sore throat
• Children often have no prodrome - rash is the first sign

• Begins on face and scalp → spreads to trunk (dense distribution) → relative sparing of extremities; central distribution (denser on back between shoulder blades)
• Classic lesion: "dewdrop on a rose petal" - a 2-3 mm superficial thin-walled vesicle on erythematous base
• Rapid progression over 12-24 hours: macule → papule → vesicle → pustule → crust
• Lesions in all stages simultaneously (pathognomonic feature distinguishing from smallpox)
• 3-5 crops over several days; total ~250-500 lesions in uncomplicated cases
• Mucous membrane lesions (oropharynx, genital mucosa) common
• Lesions on palms and soles: uncommon but possible

Complications

• Bacterial superinfection (most common): Staphylococcus aureus and Streptococcus pyogenes (cellulitis, impetigo, necrotizing fasciitis, streptococcal toxic shock)
• Varicella pneumonia: most serious complication in adults; occurs 3-5 days after rash; dyspnoea, tachypnoea, cyanosis; higher mortality in pregnancy
• CNS complications: cerebellar ataxia (most common neurological complication, usually benign, self-limited); encephalitis; Reye's syndrome (associated with aspirin use)
• Haemorrhagic varicella: petechiae/purpura around lesions; can progress to DIC
• Neonatal varicella: maternal varicella within 5 days before to 2 days after delivery → severe neonatal varicella (up to 30% mortality if untreated; transplacental VZ-IG insufficient)
• Congenital varicella syndrome (maternal infection weeks 13-20): limb hypoplasia, skin scarring (cicatricial), neurological defects, eye abnormalities
• Herpes zoster in later life (reactivation)
• Immunocompromised patients: progressive disseminated varicella with visceral involvement (pneumonitis, hepatitis, encephalitis)

Diagnosis

• Clinical in typical cases
• Tzanck smear of vesicle base: multinucleated giant cells (not specific to VZV, also seen in HSV)
• Direct fluorescent antibody (DFA) on vesicle scraping: specific and rapid
• PCR of vesicle fluid or crusts: most sensitive and specific
• Serology (VZV IgM/IgG) for atypical cases

Treatment

• Avoid aspirin in children with varicella (risk of Reye's syndrome)
• Calamine lotion, antihistamines for pruritus; acetaminophen for fever

Prevention

• Varicella vaccine (live attenuated Oka/Merck): 2-dose series; >95% efficacy against severe disease
• Varicella-Zoster Immune Globulin (VZIG): post-exposure within 96 hours for high-risk susceptible individuals (immunocompromised, neonates, pregnant non-immune women)
• For herpes zoster prevention: Shingrix (recombinant adjuvanted glycoprotein E subunit, 2 doses) - superior efficacy to Zostavax; reduces zoster by >90% in older adults

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