The concept of an infectious disease, the patterns of development of the infectious process, its forms, periods. The main properties of microorganisms causing the infectious process, their variability. The main factors protecting the macroorganism from pathogenic infection. Classification of infectious diseases Principles of diagnostics of infectious diseases, main clinical syndromes, early diagnostics. The role of specific research methods in the diagnosis of infectious diseases. The role of serological and immunological research methods in the diagnosis of infectious diseases. The role of biochemical and instrumental research methods in the clinic of infectious diseases. The role of skin-allergic and biological tests in the diagnosis of infectious diseases. Principles of complex therapy of infectious patients. Methods of etiotropic therapy of infectious diseases. Serotherapy of infectious diseases and its possible complications. Methods of pathogenetic therapy of infectious diseases. Principles of infectious disease prevention, vaccination and immunoprophylaxis. Organizational structure of medical care for infectious patients. Structure and operating procedures of an infectious diseases hospital. Infectious diseases department. Early detection, rules for hospitalization and discharge of infectious patients, rehabilitation and medical examination of convalescents. Physician's tactics when identifying a patient with acute respiratory infections. Collecting specimens for laboratory testing from a patient (corpse) with acute respiratory infections. ITS, pathogenesis, stages, clinic. Treatment tactics for ITS. Therapy at the stages of medical care. DIC syndrome in infectious diseases, pathogenesis, clinical features, diagnostics. Treatment and prevention of DIC syndrome in patients with infectious pathology. Dehydration shock. Pathogenesis, stages, clinical features, and treatment strategies. Acute renal failure in infectious diseases. Pathogenesis, stages, clinical features, diagnosis, and indications for hemodialysis. Acute hepatic encephalopathy, mechanisms of development, clinical features, diagnostics, treatment. Viral hepatitis A and E. Etiology, epidemiology, pathogenesis, clinical features, diagnostics. Viral hepatitis B. Etiology, epidemiology, pathogenesis, clinical features, diagnostics. Viral hepatitis D. Etiology, epidemiology, pathogenesis, course variants, clinical features, diagnostics. Viral hepatitis C. Etiology, epidemiology, pathogenesis, stages of the infectious process, clinical features, diagnostics. Early diagnosis of viral hepatitis. Prehospital management. Laboratory diagnostics of viral hepatitis. Principles of treatment, clinical examination of convalescents of viral hepatitis and preventive measures. Typhoid fever. Etiology, pathogenesis, pathological anatomy, clinical presentation, diagnosis, treatment, discharge guidelines. Paratyphoid A and B. Typhoid fever. Specific complications of typhoid fever and their treatment. Clinical examination and prevention. Shigellosis. Etiology, epidemiology, pathogenesis, classification, clinical presentation, complications, diagnosis. Foodborne toxic infections. Etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. Cholera. Etiology, epidemiology, pathogenesis, early diagnosis, clinical features, laboratory diagnostics. Salmonellosis. Etiology, epidemiology, pathogenesis, classification, clinical presentation, complications, and diagnosis. Viral gastroenteritis. Etiology, epidemiology, pathogenesis, classification, clinical presentation, diagnosis, and treatment. Enterovirus infections. Etiology, epidemiology, pathogenesis, classification, clinical presentation, diagnosis, and treatment. Botulism. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, emergency care. Leptospirosis. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Brucellosis. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Pseudotuberculosis. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Intestinal yersiniosis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, and treatment. HFRS. Etiology, epidemiology, pathogenesis, classification, clinical presentation, diagnosis, treatment. HFRS. Early diagnosis and tactics at the prehospital stage. HFRS. Laboratory diagnostics, treatment, and medical examination Complications of HFRS: clinical presentation, diagnosis, treatment and prevention. Differential diagnosis of HFRS. Trichinellosis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Answer all the questions with the most important points but in short for infectious disease exam for medical students studying in russia.

Reading File

This is a very large exam review covering 50+ topics. Given budget constraints, I'll answer all questions comprehensively from my medical knowledge, as searching the library for each individual topic would exhaust the budget. Here is a complete, exam-focused review:

Infectious Diseases - Complete Exam Review

(For Russian Medical Students)

1. The Concept of an Infectious Disease; Patterns of the Infectious Process

An infectious disease is a set of pathological reactions arising from the interaction of a pathogenic microorganism with a macroorganism under specific environmental conditions, characterized by cyclical course, contagiousness, and the formation of post-infectious immunity.

Conditions required: pathogenic agent + susceptible host + transmission route.

Forms of the infectious process:

Manifest (clinical) - with clear symptoms
Subclinical (inapparent) - without symptoms, but with immune response
Latent - pathogen persists without replication/symptoms
Carrier state - pathogen present, no disease
Mixed infection - two pathogens simultaneously
Superinfection - new infection during existing one
Reinfection - same pathogen after recovery
Relapse - return of symptoms from same infection

Periods of infectious disease:

Incubation - from entry to first symptoms (pathogen multiplies, no symptoms)
Prodromal - nonspecific symptoms (malaise, fever, headache)
Height (acme) - full clinical picture, specific symptoms
Convalescence - symptoms subside, recovery
Outcomes: recovery, carrier state, chronicity, death

2. Main Properties of Pathogenic Microorganisms; Their Variability

Key properties:

Pathogenicity - genetic capacity to cause disease
Virulence - degree/measure of pathogenicity (quantifiable by LD50)
Infectivity - ability to penetrate and establish infection
Invasiveness - ability to spread in tissues
Toxigenicity - production of exo/endotoxins
Adhesiveness - ability to adhere to host cells
Antigenicity - ability to induce immune response

Variability mechanisms:

Mutations (spontaneous or induced)
Genetic recombination (conjugation, transduction, transformation)
Plasmid transfer - antibiotic resistance genes
Phase variation - switching surface antigens
Phenotypic adaptation - biofilm formation, antigenic drift (influenza), antigenic shift (influenza - new pandemic strains)
L-forms - bacteria without cell walls, resist antibiotics

3. Main Factors Protecting the Macroorganism

Non-specific (innate) defense:

Skin and mucous membranes (mechanical barrier)
Normal microflora (colonization resistance)
Secretory IgA, lysozyme, lactoferrin
Phagocytosis (neutrophils, macrophages)
Complement system
Natural killer (NK) cells
Interferons (antiviral)
Acute-phase proteins (CRP, fibrinogen)
Fever (unfavorable for pathogens)

Specific (adaptive) defense:

Humoral immunity: B-lymphocytes, antibodies (IgM - early, IgG - late/memory, IgA - mucosal)
Cellular immunity: T-lymphocytes (CD4 helpers, CD8 cytotoxic)
Immunological memory

Post-infectious immunity: can be lifelong (measles, typhoid) or short-lived (influenza, shigellosis).

4. Classification of Infectious Diseases

By etiological agent:

Bacterial, viral, fungal (mycoses), protozoal, helminthic, prion

By transmission mechanism (Gromashevsky):

Intestinal (fecal-oral): typhoid, cholera, shigellosis, hepatitis A/E
Respiratory (airborne): influenza, measles, meningitis
Blood (transmissible/parenteral): malaria, HIV, hepatitis B/C
Contact (outer integuments): rabies, tetanus, anthrax

By source of infection:

Anthroponoses (human source only)
Zoonoses (animal source): brucellosis, leptospirosis, HFRS
Sapronoses (environmental source): legionellosis, botulism

By organ system: intestinal, respiratory, nervous system, blood, skin/mucous membranes

By course: acute, subacute, chronic, recurrent

By severity: mild, moderate, severe, fulminant

5. Principles of Diagnostics; Main Clinical Syndromes; Early Diagnostics

Diagnostic principles:

Epidemiological history (contact, travel, food, occupation)
Clinical examination (syndrome identification)
Laboratory confirmation (specific + nonspecific)
Dynamic observation

Main clinical syndromes:

Febrile syndrome
Intoxication syndrome (headache, myalgia, weakness, anorexia)
Catarrhal syndrome (respiratory)
Diarrheal syndrome
Exanthema/enanthema (rash)
Hepatolienal syndrome (hepato-splenomegaly)
Meningeal syndrome
Hemorrhagic syndrome
Jaundice syndrome
Lymphadenopathy syndrome

Early diagnostics: based on epidemiological data + prodromal symptoms + first specific signs before full clinical picture develops.

6. Role of Specific Research Methods

Bacteriological: culture on media, colony identification, antibiogram
Virological: cell culture, embryonated eggs, PCR
Parasitological: microscopy (smear, thick drop)
Microscopy: Gram stain, Ziehl-Neelsen, dark-field
PCR/NAAT: highly sensitive and specific, detects nucleic acids, useful in early/latent stages
Molecular typing: RFLP, MLST for epidemiological tracing

Collection timing: before antibiotics, at peak fever, with correct specimen (blood, stool, urine, CSF, swab).

7. Role of Serological and Immunological Methods

ELISA (IFA): detects Ag or Ab; quantitative; widely used
RIF (Immunofluorescence): direct/indirect, rapid
RPHA, RA, RSK, RNGA: classic agglutination reactions
Western blot: confirmatory test (HIV, Lyme)
Widal reaction: typhoid (O and H antigens)
Complement fixation test (CFT): syphilis (Wassermann), many viruses
Immunoblot: protein-specific antibody detection
Seroconversion: 4-fold rise in titer between acute and convalescent sera (paired sera) - diagnostic gold standard

IgM = acute/early infection; IgG = past infection or immunity.

8. Role of Biochemical and Instrumental Methods

Biochemical:

ALT, AST - liver damage (hepatitis)
Bilirubin (total, direct, indirect) - jaundice type
Creatinine, urea - renal function (leptospirosis, HFRS)
Coagulogram (fibrinogen, PTI, aPTT) - DIC assessment
Blood glucose, lactate - sepsis severity
CRP, procalcitonin - bacterial infection markers
Electrolytes - cholera, dehydration
CPK - trichinellosis, myositis

Instrumental:

Ultrasound: hepato-splenomegaly, renal changes (HFRS), free fluid
Chest X-ray/CT: pneumonia, pleural effusion
ECG: myocarditis (brucellosis, diphtheria)
EEG: encephalitis
Sigmoidoscopy: shigellosis (mucosal changes)
Endoscopy: differential diagnosis of GI tract lesions

9. Skin-Allergic and Biological Tests

Skin-allergic tests (delayed hypersensitivity, type IV):

Mantoux (tuberculin) test - tuberculosis
Burnet test - brucellosis (brucellin)
Francisella test - tularemia
Leishmanin (Montenegro) test - leishmaniasis
Histoplasmin, coccidioidin tests - mycoses
Read at 24-72 hours; erythema/induration >5mm = positive

Biological tests:

Animal inoculation to confirm pathogenicity (mouse - botulism, plague)
Used when other methods fail or for identification
Antitoxin neutralization in mice - confirm botulinum toxin type

10. Principles of Complex Therapy of Infectious Patients

ETAM principle:

Etiotropic - eliminate the pathogen
Pathogenetic - correct pathological mechanisms
Symptomatic - relieve symptoms
Rehabilitation - restore function

General principles:

Strict bed rest in severe disease
Proper diet (table 4 - intestinal; table 5 - liver disease)
Monitoring of vital signs, fluid balance
Early treatment = better outcomes
Combination therapy for severe infections
Avoid poly-pharmacy; monitor side effects

11. Methods of Etiotropic Therapy

Antibacterials:

Beta-lactams (penicillins, cephalosporins, carbapenems): cell wall synthesis
Fluoroquinolones: DNA gyrase inhibition (typhoid, shigellosis)
Aminoglycosides: ribosome 30S (gram-negative sepsis, brucellosis)
Tetracyclines: ribosome 30S (brucellosis, rickettsias, leptospirosis)
Macrolides: ribosome 50S (respiratory infections)
Metronidazole: anaerobes, protozoa (amoeba, Giardia)

Antivirals:

Acyclovir (herpes), ganciclovir (CMV)
Oseltamivir/zanamivir (influenza)
Sofosbuvir/NS5A inhibitors (hepatitis C)
Tenofovir/entecavir (hepatitis B)
ARV therapy (HIV)
Ribavirin (hemorrhagic fevers)

Antiparasitics: mebendazole/albendazole (helminths), chloroquine (malaria), metronidazole (protozoa)

Antifungals: fluconazole (candida), amphotericin B (systemic mycoses)

12. Serotherapy of Infectious Diseases and Complications

Serum preparations:

Antitoxic sera: anti-botulinum (types A, B, E, F), anti-diphtheria, anti-tetanus, anti-gas gangrene
Antimicrobial sera: anti-plague, anti-anthrax (less used now)
Immunoglobulins: specific (anti-rabies, anti-hepatitis B, anti-tetanus) and non-specific

Before administration: Bezredka desensitization test (0.1 ml subcutaneous, observe 20-30 min)

Possible complications:

Anaphylactic shock (immediate, IgE-mediated) - administer adrenaline 0.1% 0.5 ml IM
Serum sickness (7-12 days after): fever, rash, arthralgia, lymphadenopathy - treat with antihistamines, corticosteroids
Local reactions: pain, induration at injection site

13. Methods of Pathogenetic Therapy

Detoxification:

Oral rehydration (mild-moderate): Regidron, glucose-saline solutions
IV infusions: 0.9% NaCl, Ringer's, 5% glucose, Hemodez
Forced diuresis with furosemide
Enterosorbents: activated charcoal, Enterosgel

Anti-inflammatory: NSAIDs, corticosteroids (ITS, severe infections)

Correction of homeostasis:

Electrolyte correction (K+, Na+)
Coagulation correction (fresh frozen plasma, heparin in DIC)
Colloids (albumin) for oncotic pressure

Immunocorrection: immunoglobulins IV (severe sepsis), interferons, immunostimulants

Supportive: O2 therapy, mechanical ventilation, renal replacement therapy, vasopressors (dopamine, norepinephrine in septic shock)

14. Principles of Prevention; Vaccination and Immunoprophylaxis

Three links of epidemic process:

Source (isolation/treatment)
Transmission routes (sanitary measures, disinfection)
Susceptible host (vaccination, chemoprophylaxis)

Active immunization (vaccines):

Live attenuated: measles, BCG, oral polio, yellow fever - strong, long-lasting immunity
Inactivated (killed): pertussis, hepatitis A, flu - safer, may need boosters
Toxoids: diphtheria, tetanus
Subunit/recombinant: hepatitis B, HPV, acellular pertussis
National Vaccination Schedule (Russia): BCG at birth, Hepatitis B (0-1-6 months), DTP+polio at 3-4.5-6-18 months, MMR at 12 months and 6 years

Passive immunization: specific immunoglobulins for post-exposure prophylaxis (rabies, hepatitis B, tetanus)

Emergency chemoprophylaxis: doxycycline for tick bites in endemic areas, amantadine for influenza contacts

15. Organizational Structure of Infectious Disease Care

Structure:

Infectious disease outpatient clinic (KIZ) at polyclinic
Infectious diseases hospital (ИКБ) - specialized inpatient facility
Epidemiological surveillance department

Infectious diseases hospital structure:

Admission/reception department: isolated examination rooms (by suspected diagnosis), full PPE, emergency sanitary treatment
Box-type wards (Meltzer boxes): individual room + anteroom + separate bathroom - for undiagnosed/mixed infections
Semi-box wards: separate entrance/exit for patients
Specialized departments: hepatitis, intestinal infections, neuroinfections, childhood infections
ICU/resuscitation department
Bacteriological lab, diagnostic lab
Separate air circulation, waste disposal, linen processing

Disinfection regimes: current (ongoing) and final (after discharge)

16. Early Detection, Hospitalization/Discharge Rules; Rehabilitation

Early detection:

At polyclinic, at home by GP, emergency services
Mandatory reporting: Form 058/y (emergency notification) within 12 hours

Indications for hospitalization:

All patients with severe/moderate disease
Epidemiological indications (workers in food service, children's institutions, communal living)
Inability to isolate at home
All cases of especially dangerous infections

Discharge criteria:

Clinical recovery
Laboratory cure (negative cultures for typhoid, cholera, shigellosis)
Specific terms after last symptom: hepatitis (clinical + biochemical normalization)

Rehabilitation and dispensary follow-up (dispenserization):

Hepatitis: 6-12 months observation
Typhoid: 3 months stool cultures
Brucellosis: 2 years
Meningitis: 2 years neurology follow-up
HFRS: nephrology follow-up until renal function normalization

17. Physician Tactics with Acute Respiratory Infections (Especially Dangerous)

Especially dangerous respiratory infections: plague (pneumonic), smallpox, SARS, COVID-19, MERS, Ebola, avian influenza (H5N1)

Tactics:

Do NOT leave the patient - contact supervisor by phone/intercom
Put on full PPE (anti-plague suit or equivalent): gown, mask (N95/FFP3), goggles, gloves, shoe covers
Isolate the patient in the room
Report to head physician, chief epidemiologist, SES (Rospotrebnadzor)
Quarantine of contact persons
Emergency prophylaxis for contacts

Specimen collection:

Nasopharyngeal swabs (NPS) + oropharyngeal swabs in viral transport media
BAL, sputum for lower respiratory tract
Blood for culture and serology
All samples in triple packaging (primary container + secondary + outer)
Label: name, date, time, suspected diagnosis
Transport at 4°C, within 24 hours, with accompanying documentation

18. Infectious-Toxic Shock (ITS): Pathogenesis, Stages, Clinic

ITS (septic/endotoxic shock) = acute circulatory failure due to massive release of bacterial toxins (LPS endotoxin in gram-negative, exotoxins in gram-positive).

Pathogenesis: Toxin → macrophage activation → TNF-α, IL-1, IL-6, IL-8 release → vasodilation, increased capillary permeability → distributive shock → tissue hypoperfusion → MOF.

Stages (Zilber):

Stage	BP	HR	Consciousness	Urine output
I (warm/hyperdynamic)	Normal or ↑	↑	Alert/anxious	Slightly ↓
II (cold/hypodynamic)	↓ (systolic <90)	↑↑	Confused	Oliguria (<30 ml/h)
III (irreversible)	Very low	↑↑↑	Stupor/coma	Anuria, MOF

Clinical features:

Sudden chill, high fever (39-40°C) then drop
Pale/mottled skin, cold extremities
Tachycardia, weak pulse, hypotension
Oliguria → anuria
Petechial rash (in meningococcemia), hemorrhages
DIC, MOF

19. Treatment of ITS

"Golden hour" principle - immediate intervention.

Prehospital: lay patient flat, IV access x2, 0.9% NaCl 500-1000 ml IV bolus, oxygen, call resuscitation team.

Hospital treatment:

Volume resuscitation: crystalloids (NaCl, Ringer's) 20-30 ml/kg in 30 min, repeat to MAP >65 mmHg
Vasopressors (if MAP <65 after fluids): Norepinephrine first-line (0.1-0.3 mcg/kg/min), dopamine as alternative
Etiotropic: broad-spectrum antibiotics WITHIN 1 HOUR - cephalosporins III-IV gen + metronidazole, or carbapenems in severe cases
Corticosteroids: hydrocortisone 200 mg/day IV (refractory shock)
Correction of DIC: FFP, heparin
O2/mechanical ventilation as needed
Monitoring: CVP, diuresis, blood gases

20. DIC Syndrome in Infectious Diseases

Pathogenesis: Infection → tissue factor release, endothelial damage → coagulation cascade activation → microthrombi formation (consumption of coagulation factors + platelets) → then secondary fibrinolysis and hemorrhage.

Triggers: gram-negative sepsis, meningococcemia, leptospirosis, hemorrhagic fevers, plague.

Stages:

Hypercoagulation: fibrin microthrombi, organ ischemia
Consumption coagulopathy: ↓ platelets, ↓ fibrinogen
Hypocoagulation/fibrinolysis: diffuse bleeding, petechiae, ecchymoses

Diagnosis:

↑ PT, aPTT; ↓ fibrinogen (<1.5 g/l); ↓ platelets (<100×10⁹/l)
↑ D-dimer, fibrin degradation products (FDP)
Blood smear: schistocytes (fragmented RBCs)

Clinical: petechiae, bleeding from venipuncture sites, mucosal bleeding, hematuria, organ failure

21. Treatment and Prevention of DIC

Stage I (hypercoagulation):

Treat underlying cause (antibiotics)
Heparin 5000 U IV bolus then infusion (under aPTT control)
Fresh frozen plasma (FFP) 10-15 ml/kg

Stage II-III (hypocoagulation):

FFP 15-20 ml/kg (replace factors)
Cryoprecipitate (fibrinogen, factor VIII)
Platelet transfusion if <30×10⁹/l with bleeding
Heparin contraindicated in stage III
Antifibrinolytics (aminocaproic acid) in late stage

Prevention:

Early treatment of infectious trigger
Avoid prolonged shock
Prophylactic heparin in high-risk patients

22. Dehydration Shock (Hypovolemic Shock in Infectious Disease)

Cause: massive fluid loss in cholera, severe gastroenteritis, food poisoning.

Pathogenesis: Vomiting + diarrhea → fluid loss → hypovolemia → ↓ CO → tissue hypoperfusion → acidosis, electrolyte imbalance.

Stages (Pokrovsky, for cholera):

Stage	Fluid loss (% body weight)	Features
I (compensated)	1-3%	Thirst, slight tachycardia
II (subcompensated)	4-6%	Dry mucosa, oliguria, cramps
III (decompensated)	7-9%	Wrinkled skin, voice changes, anuria, cramps
IV (algid/hypovolemic shock)	>10%	Cyanosis, pulseless, anuria, hypothermia

Clinical: rice-water stools, vomiting (cholera), muscle cramps (electrolyte loss), skin turgor ↓, sunken eyes

Treatment:

Mild-moderate: oral rehydration - Regidron, WHO-ORS (glucose + Na + K + citrate)
Severe (III-IV): IV rehydration with Trisol/Quartasol/Ringer's - first 1-2 hours give volume = calculated deficit (weight loss in kg × 1000 ml), then maintenance
Correct K+ (not until urination established)
Monitor: weight, urine output, electrolytes

23. Acute Renal Failure (ARF) in Infectious Diseases

Causes: HFRS (direct viral damage to renal tubules), leptospirosis (interstitial nephritis), sepsis (renal hypoperfusion), hemolysis (malaria, toxins), DIC.

Pathogenesis: renal tubular necrosis (ATN) → ↓ GFR → oligo/anuria → uremia, hyperkalemia, acidosis, fluid overload.

Stages:

Oliguria (urine <500 ml/day): rapid rise of creatinine, K+, urea
Polyuria (diuresis recovery): large volumes, risk of hypovolemia and electrolyte loss
Recovery: normalization over weeks

Diagnosis: ↑ creatinine (>177 mcmol/l), ↑ urea, ↑ K+ (>6.5 mmol/l), metabolic acidosis, ↓ Na+; urinalysis: proteinuria, hematuria, granular casts

Indications for hemodialysis:

Urea >35 mmol/l
K+ >6.5 mmol/l (ECG changes)
Pulmonary edema due to fluid overload
Severe acidosis (pH <7.2)
Uremic encephalopathy, pericarditis

24. Acute Hepatic Encephalopathy (AHE)

Cause: fulminant hepatic failure (hepatitis B + D, toxic), or acute-on-chronic (hepatitis C cirrhosis).

Mechanisms:

Ammonia accumulation (↑ NH3 → brain edema, astrocyte swelling)
False neurotransmitters (aromatic amino acids)
GABA-ergic inhibition
Systemic inflammation

Stages:

Precoma I: inversion of sleep, behavioral changes, mild asterixis
Precoma II: confusion, asterixis (flapping tremor), writing deterioration
Coma I: stupor, responds to pain
Coma II: deep coma, no response

Diagnostics: ↓ prothrombin (PTI <40%), ↑ bilirubin, ↓ albumin, ↑ ALT/AST then drop (hepatocyte death), ↑ ammonia, EEG changes

Treatment:

Lactulose 30-50 ml x3/day (↓ ammonia absorption)
Rifaximin 400 mg x3/day (reduce gut bacteria)
Protein restriction (then gradual increase with BCAA)
↓ ammonia: ornithine-aspartate (Hepa-Merz)
Correct hypokalemia, alkalosis
Dextrose infusions (prevent hypoglycemia)
FFP, vitamin K (coagulopathy)
Avoid sedatives (↑ GABA)
ICU monitoring; liver transplantation in fulminant failure

25. Viral Hepatitis A and E

HAV (Hepatitis A):

Etiology: Hepatovirus A (RNA picornavirus)
Epidemiology: fecal-oral; contaminated water/food; endemic in developing countries; outbreaks
Incubation: 15-50 days (avg 28 days)
Pathogenesis: HAV → gut → portal → hepatocytes → direct cytopathic + immune-mediated damage → cholestasis, cytolysis
Clinical: preicteric (5-7 days: fever, nausea, dark urine, clay stools) → icteric (jaundice, pruritus, hepatomegaly) → convalescence; self-limiting, no chronicity
Diagnosis: anti-HAV IgM (acute); anti-HAV IgG (past/immune); ↑ ALT/AST, ↑ bilirubin

HEV (Hepatitis E):

Etiology: Hepevirus (RNA)
Epidemiology: fecal-oral; water-borne outbreaks (Asia, Africa, Central Asia); zoonosis (genotype 3/4 from pigs in Europe)
Incubation: 14-60 days
Special feature: VERY dangerous in pregnancy - fulminant hepatic failure, maternal mortality 20-25%
Diagnosis: anti-HEV IgM; HEV RNA (PCR)
Treatment: both HAV/HEV are self-limiting; supportive care; no specific antivirals routinely; ribavirin for severe HEV in immunosuppressed

26. Viral Hepatitis B

Etiology: HBV (DNA hepadnavirus); antigens: HBsAg (surface), HBcAg (core), HBeAg (active replication marker)
Epidemiology: parenteral (blood, needles), sexual, vertical (mother→child); risk groups: IV drug users, healthcare workers, sexual partners
Incubation: 45-180 days (avg 90 days)
Pathogenesis: HBV infects hepatocytes → immune response (CD8 T-cells destroy HBV-infected cells) → hepatocyte necrosis; NOT directly cytopathic; HBV DNA integrates → risk of HCC
Clinical:
- Acute: preicteric (arthralgia, urticaria, fever) → icteric phase; 1% fulminant
- Chronic (>6 months): in 5-10% of adults, 90% of neonates
- Chronic stages: immune tolerant → immune active → inactive carrier → reactivation
Diagnosis:
- HBsAg+ = infection
- HBeAg+ = high replication
- anti-HBs = recovery/immunity
- anti-HBc IgM = acute; anti-HBc IgG = past
- HBV DNA (PCR) = viral load
Treatment: tenofovir (TDF) or entecavir (ETV) for chronic HBV; peginterferon alfa-2a (48 weeks)

27. Viral Hepatitis D (Delta Hepatitis)

Etiology: HDV (RNA defective virus) - requires HBsAg as envelope - ONLY infects with HBV
Epidemiology: parenteral; IV drug users predominant; endemic in Mediterranean, Middle East, Central Asia
Co-infection: HBV + HDV simultaneously - acute, usually self-limiting, more severe
Superinfection: HDV in chronic HBV carrier - rapid progression, fulminant hepatitis (10x higher), cirrhosis (70% within 5-10 years)
Pathogenesis: HDV directly cytopathic + immune-mediated + accelerates HBV damage
Clinical: more severe jaundice, higher rates of fulminant hepatitis, rapid cirrhosis
Diagnosis: anti-HDV IgM/IgG; HDV RNA (PCR); HBsAg always positive
Treatment: peginterferon alfa (48-72 weeks); bulevirtide (new entry inhibitor); vaccination against HBV = prevention of HDV

28. Viral Hepatitis C

Etiology: HCV (RNA flavivirus); 6 genotypes (genotype 1 most common); high mutation rate → quasi-species → evades immunity
Epidemiology: parenteral; blood transfusions (pre-screening), IV drug use, tattoos, vertical
Incubation: 15-150 days (avg 50 days)
Pathogenesis: direct + immune-mediated damage; high rate of chronicity because HCV evades innate immunity (NS3/4A protease cleaves MAVS/TRIF)
Stages:
- Acute (6 months): often asymptomatic (80%), few cases icteric
- Chronic (75-85% of acute): persists >6 months
- Cirrhosis (20% at 20 years)
- HCC (1-5%/year in cirrhosis)
Clinical: fatigue, mild hepatomegaly; extra-hepatic: cryoglobulinemia, membranoproliferative GN, vasculitis, porphyria
Diagnosis: anti-HCV (screening); HCV RNA (PCR) - confirms active infection; genotype testing (for treatment); liver biopsy/Fibroscan (fibrosis stage)
Treatment: Direct-Acting Antivirals (DAAs) - sofosbuvir + NS5A inhibitor (ledipasvir, velpatasvir) - 8-12 weeks, SVR >95%

29. Early Diagnosis of Viral Hepatitis; Prehospital Management

Early diagnosis signs (preicteric phase):

Dyspeptic: nausea, vomiting, anorexia, right hypochondrium pain
Asthenic: weakness, fatigue
Flu-like: fever, malaise (HAV, HBV)
Dark urine (bilirubinuria) BEFORE jaundice appears - key early sign!
Clay/acholic stools
↑ ALT >10x (cytolytic syndrome)

Prehospital management:

Identify epidemiological risk factors
Check for dark urine, tender liver
Send for: ALT, total bilirubin, CBC, HBsAg, anti-HAV IgM
Bed rest, diet (table 5)
If HAV/HBE - oral rehydration, symptomatic
If moderate/severe or HBV/HCV suspected - refer for hospitalization
Mandatory reporting to epidemiological service
Isolation measures for HAV (fecal-oral)

30. Laboratory Diagnostics of Viral Hepatitis

Cytolytic syndrome: ↑ ALT, ↑ AST (ALT > AST in viral hepatitis; AST > ALT in alcoholic)

Cholestatic syndrome: ↑ direct bilirubin, ↑ ALP, ↑ GGT, ↑ cholesterol

Hepatocellular failure: ↓ albumin, ↓ PTI/INR, ↓ fibrinogen, ↑ ammonia

Markers:

Hepatitis	Acute marker	Chronic/past
A	anti-HAV IgM	anti-HAV IgG
B	HBsAg, anti-HBc IgM	anti-HBs (recovery), HBsAg >6m (chronic)
C	anti-HCV + HCV RNA PCR	HCV RNA >6m (chronic)
D	anti-HDV IgM, HDV RNA	anti-HDV IgG
E	anti-HEV IgM	anti-HEV IgG

Liver function panels: ALT, AST, GGT, ALP, bilirubin, albumin, PT/INR, CBС (thrombocytopenia in cirrhosis)

31. Principles of Treatment; Dispensary Follow-Up; Prevention of Viral Hepatitis

Treatment principles:

Diet: table 5 (low fat, no alcohol, no fried)
Rest: bed rest in acute phase, activity restriction
HAV/HEV: supportive only (IV glucose, enterosorbents, antispasmodics)
HBV acute: supportive; antivirals (TDF/ETV) if prolonged or severe
HBV chronic: TDF or ETV (long-term)
HCV: DAAs (sofosbuvir-based) 8-12 weeks
Cholestasis: ursodeoxycholic acid, antipruritic agents

Discharge criteria: clinical improvement, bilirubin near normal, ALT <3x ULN, no complications

Dispensary follow-up:

HAV: 1 month after discharge (LFTs)
HBV: 6-12 months; every 3 months (ALT, HBsAg, HBV DNA)
HCV: 6 months post-SVR (confirm cure)

Prevention:

HAV: hygiene, water/food safety; vaccine (2 doses)
HBV: vaccination (3 doses: 0-1-6); safe sex, sterile needles; specific immunoglobulin post-exposure
HCV: no vaccine; harm reduction (needle exchange)
HEV: water safety; vaccine available in China

32. Typhoid Fever: Etiology, Pathogenesis, Clinical Features, Diagnosis, Treatment; Paratyphoid A and B

Etiology: Salmonella typhi (gram-negative rod, Enterobacteriaceae); antigens: O (somatic), H (flagellar), Vi (capsular)

Epidemiology: fecal-oral; contaminated water/food; endemic in South Asia, Africa

Pathogenesis: ingestion → M-cell invasion → Peyer's patches → lymph nodes → bacteremia (1st week) → seeding of organs (liver, spleen, bone marrow, gallbladder) → re-entry into gut via bile → Peyer's patch necrosis (weeks 2-3) → ulceration/perforation risk

Pathological anatomy: Peyer's patch changes: 1-proliferation, 2-necrosis, 3-ulceration, 4-clean ulcers, 5-healing (5 weeks total)

Clinical:

Week 1: gradual fever increase (step-ladder), headache, bradycardia relative to fever, "typhoid tongue" (coated, red tip/edges)
Week 2: high constant fever, splenomegaly, rose spots (roseola - trunk, 8-10 mm, fade on pressure)
Week 3: complications peak - intestinal bleeding, perforation, hepatitis
Week 4: fever decreases

Diagnosis: blood culture (week 1-2, gold standard); Widal reaction (O+H agglutinins, 1:200 diagnostic, paired sera); bone marrow culture (most sensitive); stool culture (week 2-3); Vi-agglutination for carriers

Treatment:

Fluoroquinolones (ciprofloxacin 500 mg x2 for 10-14 days) - first line
Ceftriaxone 2 g/day x14 days (MDR strains)
Chloramphenicol (historical; still used in resource-limited settings)
Strict bed rest (weeks 2-3), diet 4a
Discharge after clinical cure + 3 negative stool cultures

Paratyphoid A (S. paratyphi A): similar but milder; rose spots earlier and more prominent; Widal H-A agglutinins Paratyphoid B (S. paratyphi B): often starts with gastroenteritis prodrome; milder

33. Typhoid Fever Complications; Clinical Examination; Prevention

Complications (weeks 2-3):

Intestinal bleeding: melena, drop in BP; manage conservatively (hemostatics, blood transfusion); surgery if massive
Intestinal perforation: sudden severe pain → peritonitis (Blumberg sign, board abdomen); EMERGENCY surgery
Infectious myocarditis: relative bradycardia becomes tachycardia, ECG changes
Typhoid pneumonia, hepatitis, cholecystitis, nephritis, meningitis: rarer

Clinical examination after discharge:

Monthly stool + urine cultures x3 months
Then 1 stool culture every 3 months for 2 years
Bi-annual stool cultures for life for food industry workers
Biliary carrier state: treat with antibiotics (ciprofloxacin 4 weeks) ± cholecystectomy

Prevention:

Water quality control, food safety, sewage
Vaccination: Vi capsular polysaccharide vaccine (1 dose IM, every 3 years); Ty21a (oral, 3 doses)
Case isolation, contact tracing

34. Shigellosis (Bacterial Dysentery)

Etiology: Shigella spp. (gram-negative, non-motile); S. dysenteriae (most severe - Shiga toxin), S. flexneri, S. sonnei (most common in Russia, mild), S. boydii

Epidemiology: fecal-oral; very low infectious dose (10-100 organisms); person-to-person, contaminated food/water; summer-autumn

Pathogenesis: Shigella → invades colonic epithelial cells → multiplies intracellularly → cell-to-cell spread → mucosal ulceration → bloody diarrhea; Shiga toxin (S. dysenteriae) inhibits protein synthesis + damages endothelium (HUS risk)

Classification:

Colitic form (typical): most common
Gastroenterocolitic form
Gastroenteritic form (atypical)
Mild, moderate, severe; acute/chronic (>3 months)

Clinical:

Acute onset: fever, cramps, tenesmus (painful defecation urge)
Stool: initially fecal → "rectal spit" (mucus + blood, small volume, frequent: 10-30x/day)
Left iliac fossa pain, sigmoid spasm (palpable)
Sigmoidoscopy: catarrhal → erosive → ulcerative mucosa

Complications: HUS (especially S. dysenteriae), toxic megacolon, reactive arthritis (Reiter syndrome with S. flexneri), intestinal perforation

Diagnosis: stool culture (bacteriological method - gold standard); RNGA with shigella antigens; sigmoidoscopy; CBC (leukocytosis, shift left)

35. Foodborne Toxic Infections (Пищевые Токсикоинфекции - PTI)

Etiology: Staphylococcus aureus (enterotoxin), Bacillus cereus, Cl. perfringens, Proteus, Klebsiella, Enterobacter - all produce preformed toxins or enterotoxins in food

Epidemiology: contaminated food (cream, mayonnaise, meat); group outbreaks; short incubation; food remains infective at room temperature; no person-to-person spread

Pathogenesis: Preformed toxin ingested → acts on small intestine → ↑ secretion → hypersecretory diarrhea + vomiting; no invasion, no fever (or mild)

Clinical:

Short incubation: 30 min - 6 hours (staph toxin); 6-24 hours (Cl. perfringens)
Sudden onset: nausea, vomiting, epigastric pain
Watery diarrhea (non-bloody)
Mild fever or afebrile
Self-limiting in 24-72 hours
Dehydration in severe cases

Diagnosis: clinical + epidemiological (group outbreak linked to specific food); bacteriological study of food remains, vomitus, stool

Treatment: gastric lavage (early), oral/IV rehydration, sorbents, symptomatic; antibiotics NOT indicated (toxin-mediated)

36. Cholera

Etiology: Vibrio cholerae O1 (El Tor biotype) and O139; gram-negative comma-shaped rod; produces cholera toxin (CT) - ADP-ribosylates Gs → ↑ cAMP → massive Cl- secretion (Na+ follows osmotically)

Epidemiology: fecal-oral; contaminated water (main route); pandemics (7th pandemic ongoing since 1961); endemic: South/Southeast Asia, Africa, Haiti; seasonal (summer)

Pathogenesis: V. cholerae → small intestine → CT → ↑ cAMP → massive isotonic fluid secretion (up to 20-30 L/day) → hypovolemia, electrolyte loss, acidosis; NO invasion, NO fever (toxin-mediated), NO blood in stool

Early diagnosis:

"Rice-water" diarrhea (watery, no fecal odor, white flakes of mucus)
Profuse vomiting (no nausea initially)
Rapid dehydration without fever
Epidemiological context (cholera region)

Clinical features (see dehydration stages above, Question 22)

Laboratory diagnostics:

Bacteriological (definitive): stool/rectal swab culture on TCBS agar; alkaline peptone water enrichment broth
Microscopy: characteristic "shooting stars" motility (dark-field)
Agglutination with O1/O139 antisera (rapid serotyping)
PCR for ctxA gene
Cholera is notifiable - WHO regulations (IHR 2005)

37. Salmonellosis

Etiology: S. enteritidis, S. typhimurium (non-typhoid Salmonella); gram-negative; >2500 serovars (Kauffmann-White scheme)

Epidemiology: zoonosis; contaminated eggs, poultry, meat, milk; person-to-person (nosocomial in infants); year-round

Pathogenesis: ingestion → invades small intestine epithelium → inflammatory response → diarrhea; may disseminate → bacteremia, focal infection

Classification:

Gastrointestinal (most common): gastroenteritis, gastroenterocolitis, enterocolitis
Typhoid-like (generalized): prolonged fever, rash, hepatosplenomegaly
Septic (septicemia/bacteremia): severe; focal metastatic infections
Subclinical/Carrier state

Clinical (gastrointestinal):

Incubation: 6-72 hours
Fever, nausea, vomiting, watery green stool ("swamp mud")
Abdominal cramping, dehydration
Self-limiting in 3-7 days in healthy adults

Complications: bacteremia → endocarditis, osteomyelitis, reactive arthritis; Reiter syndrome

Diagnosis: stool culture (blood culture for generalized forms); CBC (leukocytosis); serology (RNGA with Salmonella group antigens)

38. Viral Gastroenteritis

Etiology: Rotavirus (group A - main cause of diarrhea in children), Norovirus (most common in adults/all ages, outbreaks), Astrovirus, Adenovirus (serotypes 40/41), Sapovirus

Epidemiology:

Rotavirus: children <5 years; winter; fecal-oral + respiratory
Norovirus: all ages; year-round; very low infectious dose (10-100 particles); highly contagious; cruise ships, nursing homes
Fecal-oral transmission; food/water contamination

Pathogenesis: virus infects small intestine villous epithelium → enterocyte damage → ↓ brush border enzymes (lactase) → osmotic diarrhea + secretory diarrhea; no invasion/bacteremia

Clinical:

Incubation: 1-3 days
Watery diarrhea (non-bloody), vomiting (prominent in norovirus), fever (mild-moderate)
Duration: 3-7 days
Rotavirus in children: more severe dehydration risk

Diagnosis: clinical; ELISA for rotavirus Ag in stool; PCR (norovirus, rotavirus); electron microscopy

Treatment: Oral rehydration solution (ORS); no antibiotics; probiotics (some evidence); rotavirus vaccine (oral, live attenuated - Rotarix/RotaTeq) in national vaccination programs

39. Enterovirus Infections

Etiology: Enterovirus genus (Picornaviridae) - Poliovirus (3 serotypes), Coxsackievirus A (23 types) and B (6 types), Echovirus (31 types), Enterovirus 68-121 (newer)

Epidemiology: fecal-oral + respiratory; children predominantly; summer-autumn; person-to-person

Pathogenesis: gut → lymph nodes → primary viremia → target organs (CNS, heart, muscle, skin); tropism varies by serotype

Classification (clinical forms):

Herpangina (Coxsackie A): vesicles on soft palate/tonsils, fever
Hand-Foot-Mouth Disease (HFMD) (EV-A71, Coxsackie A16): vesicles on hands, feet, mouth; children
Epidemic myalgia (Bornholm disease) (Coxsackie B): pleurodynia - paroxysmal chest/abdominal pain
Aseptic meningitis (Echovirus, Coxsackie B): fever, meningeal signs, CSF: lymphocytic pleocytosis, normal glucose
Encephalitis: EV-A71 (brainstem)
Myocarditis/Pericarditis (Coxsackie B)
Epidemic conjunctivitis (EV-70, Coxsackie A24)
Exanthema ("Boston exanthem")
Poliomyelitis-like (flaccid paralysis)

Diagnosis: PCR (stool, CSF, throat swab); virus isolation; serology

Treatment: supportive; pleconaril (enterovirus specific, limited availability); no specific antivirals approved; IVIG in neonatal enteroviral sepsis

40. Botulism

Etiology: Clostridium botulinum (anaerobic gram-positive spore-forming rod); produces neurotoxin types A, B, E, F (cause human disease); heat-labile toxin (100°C for 10 min destroys it); spores heat-resistant (120°C required)

Epidemiology:

Foodborne: home-canned goods (vegetables, fish, mushrooms); anaerobic conditions
Wound botulism: C. botulinum in wound (especially black tar heroin injection)
Infant botulism: honey; gut colonization in <1 year olds
Iatrogenic: cosmetic/therapeutic botox overdose

Pathogenesis: toxin absorbed from gut → bloodstream → neuromuscular junction → binds irreversibly to presynaptic membrane → cleaves SNARE proteins → blocks ACh release → flaccid paralysis (descending, symmetric)

Clinical features:

Incubation: 2 hours - 10 days (avg 12-36 hours); shorter = more severe
No fever (unless wound botulism)
GI prodrome: nausea, vomiting, dry mouth (anticholinergic)
Ophthalmoplegia: diplopia, ptosis, mydriasis, loss of accommodation (FIRST cranial nerve signs)
Bulbar palsy: dysphonia, dysarthria, dysphagia
Descending flaccid paralysis: arms → trunk → legs → diaphragm → respiratory failure
No sensory impairment, consciousness preserved
Autonomic: dry mouth, constipation, urinary retention

Diagnosis: clinical; toxin detection in serum/food/stool (mouse bioassay - gold standard); ELISA; EMG (normal nerve conduction, absent NMJ transmission)

Emergency care:

Immediately: gastric lavage + siphon enema (remove unabsorbed toxin)
Anti-botulinum serum (polyvalent A+B+E): administer ASAP; after Bezredka test; 10,000-15,000 IU each serotype IM/IV
Guanidine hydrochloride (↑ ACh release, partial benefit)
Respiratory monitoring → mechanical ventilation if FVC <30%
ICU care; nasogastric feeding

41. Leptospirosis

Etiology: Leptospira interrogans (gram-negative spirochete); >25 serogroups; L. icterohaemorrhagiae (most severe), L. canicola, L. grippotyphosa, L. pomona

Epidemiology: zoonosis; reservoir: rats (main), dogs, pigs, cattle; humans via contact with contaminated water/soil (swimming, farming, occupational); summer-autumn; tropical/subtropical > temperate; NOT person-to-person

Pathogenesis: enters via skin abrasions/mucosa → leptospiremia (week 1: flu-like) → organ invasion (week 2: liver, kidneys, muscles, meninges, eyes) → toxin + immune complex damage; rhabdomyolysis → myoglobinuria → ARF

Clinical picture:

Incubation: 2-30 days (avg 10 days)
Anicteric leptospirosis (90%): sudden fever, severe myalgia (calves!), headache, conjunctival injection, maculopapular rash; self-limiting in 1-3 weeks
Icteric leptospirosis (Weil's disease) (10%): fever → jaundice (days 4-6) + ARF + hemorrhage (pulmonary, GI) → potentially fatal
Weil's triad: jaundice + ARF + hemorrhage
Aseptic meningitis (5-10%)
Myocarditis, uveitis (late complication)

Diagnosis: dark-field microscopy of blood/urine (early); culture (Ellinghausen-McCullough-Johnson-Harris - EMJH media); MAT (microscopic agglutination test) - gold standard serology; ELISA (IgM) early; PCR (acute phase)

Treatment: penicillin G 6-12 million IU/day IV or doxycycline 100 mg x2/day x7 days; severe: ceftriaxone 1 g/day; Jarisch-Herxheimer reaction possible; supportive: dialysis, transfusions

42. Brucellosis

Etiology: Brucella spp. (gram-negative, intracellular coccobacilli); B. melitensis (most virulent - goats/sheep), B. abortus (cattle), B. suis (pigs), B. canis (dogs)

Epidemiology: zoonosis; ingestion (raw milk, cheese, meat), contact (veterinarians, farmers, abattoir workers), inhalation; endemic in Central Asia, Caucasus, Mediterranean; no person-to-person

Pathogenesis: enters via mucosa → macrophages (intracellular survival, evades killing) → bacteremia → seeding of reticuloendothelial system + joints + genitals + CNS → granuloma formation; chronic inflammation

Clinical picture:

Incubation: 1-4 weeks
Acute: fever (undulant/remittent), profuse night sweats, arthralgia, lymphadenopathy, hepatosplenomegaly; characteristic: excessive sweating with low-grade fever
Subacute/Chronic: focal lesions predominate
Focal forms: osteoarticular (sacroiliitis! spondylitis, arthritis), neurobrucellosis, genital (orchitis, epididymitis), cardiovascular (endocarditis)

Diagnosis: blood culture (gold standard, prolonged incubation 4-6 weeks); Wright agglutination test (titer ≥1:200 diagnostic); Burnet skin test (intradermal brucellin, read 24-48h - allergic test); ELISA; PCR

Treatment:

Doxycycline 100 mg x2 + rifampicin 600-900 mg/day x6 weeks (standard)
Doxycycline + streptomycin (3 weeks streptomycin) - WHO preferred for complicated
Focal: longer courses (3-6 months)
Prevention: pasteurization of dairy, protective equipment for workers, vaccination of animals

43. Pseudotuberculosis (Far East Scarlatiniform Fever)

Etiology: Yersinia pseudotuberculosis (gram-negative rod, Enterobacteriaceae); psychrophilic (grows at 4°C in fridge!)

Epidemiology: zoonosis; reservoir: rodents; contaminated vegetables (especially stored in cellars/refrigerators), water; fecal-oral; winter-spring (cold storage)

Pathogenesis: similar to intestinal yersiniosis - invasion of Peyer's patches → mesenteric lymphadenitis → bacteremia → focal lesions; granuloma formation (pseudotuberculosis name)

Clinical picture:

Incubation: 3-18 days
Acute onset: fever, chills
Scarlatiniform rash: bright red, rough, distributed like scarlet fever (face, trunk, hands/"gloves and socks") - key feature
GI: nausea, vomiting, diarrhea
"Terminal ileitis" (Crohn's-like): right iliac fossa pain, tender mass
Arthralgia (reactive arthritis)
Hepatosplenomegaly
Lymphadenopathy
Relapsing course (20-40%)

Diagnosis: bacteriological (stool, blood); RPHA with Yersinia PS antigens (titer ≥1:200); agglutination test

Treatment: fluoroquinolones (ciprofloxacin) or doxycycline or co-trimoxazole x10-14 days; cephalosporins III gen for severe

44. Intestinal Yersiniosis

Etiology: Yersinia enterocolitica (gram-negative, serotypes O3, O9 most common); psychrophilic

Epidemiology: zoonosis (pigs main reservoir), contaminated pork, dairy, water; fecal-oral; more common in Europe; any season but more in cold months

Pathogenesis: invades terminal ileum → mesenteric lymph nodes → bacteremia in immunocompromised → focal lesions; autoimmune reactions (HLA-B27 linked reactive arthritis)

Clinical features:

Gastroenteritis form: most common; diarrhea (may be bloody), fever, vomiting; self-limiting 1-2 weeks
Pseudoappendicitis/mesenteric lymphadenitis form: right lower quadrant pain, simulates appendicitis (important differential!)
Generalized form: fever, hepatosplenomegaly, rash; septicemia in immunocompromised
Secondary forms (post-infectious): reactive arthritis (1-3 weeks after GI), erythema nodosum (ankles/legs), Reiter syndrome - especially in HLA-B27 positive

Diagnosis: stool culture (cold enrichment), serology (RPHA, agglutination), PCR; laparoscopy (enlarged mesenteric nodes with granulomas)

Treatment: fluoroquinolones or doxycycline or co-trimoxazole x10-14 days; severe/bacteremia: ceftriaxone + aminoglycoside; reactive arthritis: NSAIDs

45. HFRS (Hemorrhagic Fever with Renal Syndrome)

Etiology: Hantaviruses (Bunyaviridae family, RNA); in Russia: Puumala virus (Ural, Volga-Ural region - "European HFRS," milder), Hantaan, Seoul, Dobrava viruses (severe form)

Epidemiology: zoonosis; reservoir: rodents (bank vole for Puumala, field mouse for Hantaan); transmission: inhalation of infected rodent excreta (aerosol - main route), contact with rodent excreta, food contaminated; NO person-to-person; forest workers, agricultural workers, rural residents; spring-autumn (outdoor activity); Volga-Ural region most endemic in Russia

Pathogenesis: virus → respiratory tract → vascular endothelium (primary tropism) → capillary damage → ↑ permeability → plasma leak → hemoconcentration, thrombocytopenia, DIC → kidneys most affected: acute interstitial nephritis, tubular dysfunction, renal cortex/medulla hemorrhage → ARF; retroperitoneal edema; pituitary infarction possible

Classification by severity: mild, moderate, severe; based on degree of thrombocytopenia, creatinine level, hemorrhage

Clinical presentation (5 periods):

Febrile (1-4 days): acute fever 38-40°C, severe headache, myalgia, vision changes ("foggy vision" - retinal edema), flushing of face/neck ("burn face"), hemorrhagic enanthema on palate, petechiae (axillary folds - classic!)
Oliguric (4-11 days): fever drops → oliguria → ARF; flank/abdominal pain (retroperitoneal edema); hemorrhagic manifestations (petechiae, nosebleed, hematuria, melena); bradycardia
Polyuric (11-30 days): diuresis recovery (>2-3 L/day, up to 5-10 L); risk of dehydration
Convalescent (weeks-months): gradual normalization; tubular dysfunction persists; fatigue, nocturia

Diagnosis:

↓ platelets (thrombocytopenia 40-100×10⁹/l)
↑ creatinine, ↑ urea (ARF severity)
Urinalysis: massive proteinuria (Dunayev protein), hematuria, granular casts, isostenuria
↑ Hematocrit (hemoconcentration in febrile period)
ELISA for anti-Hantavirus IgM/IgG (serodiagnosis - key)
PCR (blood in early phase)

Treatment: see HFRS treatment question below

46. HFRS: Early Diagnosis and Prehospital Tactics

Early diagnosis:

Epidemiological: rural/forest area, rodent contact, endemic region (Volga-Ural), spring-autumn
Clinical triad of febrile period: fever + back/flank pain + oliguria
"Foggy vision" (vizmatch), facial flushing, axillary petechiae
Declining platelets + rising creatinine

Prehospital tactics:

Strict bed rest (risk of renal capsule rupture with physical activity!)
Do NOT give NSAIDs (worsen renal function) or diuretics without indication
No IM injections (bleeding risk with thrombocytopenia)
IV access with crystalloids if oliguria
Monitor urine output, BP
Mandatory hospitalization of ALL suspected cases
Transport in horizontal position (avoid jarring)

47. HFRS: Laboratory Diagnostics, Treatment, Medical Examination

Laboratory diagnostics (see Question 45 for full list):

Key: ELISA anti-Hantavirus IgM (appears from day 4-5, diagnostic)
CBC: thrombocytopenia, leukocytosis, hemoconcentration
Biochemistry: ↑ creatinine, ↑ urea, ↑ K+; metabolic acidosis
Urinalysis: Dunayev proteinuria (massive), casts, RBC
Coagulogram: DIC signs

Treatment:

Etiotropic: Ribavirin (early, within 5 days of onset): 2 g loading dose, then 1 g x4/day for 4 days, then 0.5 g x3/day for 5 days
Pathogenetic:
- Febrile period: crystalloids + antiplatelet agents (pentoxifylline) + ascorbic acid + antihistamines
- Oliguric period: fluid restriction (intake = urine output + 500-700 ml); NO diuretics in oliguria; dopamine at renal dose (2-5 mcg/kg/min); correct hyperkalemia and acidosis
- Hemodialysis indications (see Question 23)
- Polyuric period: oral rehydration, electrolyte correction
DIC treatment if present

Medical examination after discharge:

Observation by nephrologist
1, 3, 6, 12 months: creatinine, urinalysis, blood pressure
Until full renal function normalization
Restrictions: no physical labor, cold, alcohol for 1 year minimum

48. Complications of HFRS

Main complications:

ARF (main complication) - oliguria, uremia, hyperkalemia (see Question 23)
Infectious toxic shock (febrile/early oliguric period)
Pulmonary edema (fluid overload in oliguric period)
Spontaneous renal capsule rupture (from retroperitoneal edema + trauma/physical strain) - sudden worsening of flank pain, expanding hematoma; requires surgery
DIC with hemorrhage (petechiae, GI bleeding, pulmonary hemorrhage)
Neurological: encephalopathy, pituitary apoplexy (anterior pituitary infarction)
Cardiac: myocarditis, arrhythmias
Bacterial superinfection (pneumonia, UTI during oliguric phase)
Renal hypertension (long-term)

Clinical features, diagnosis, treatment: per the affected system; renal capsule rupture → CT/US → surgical consultation

Prevention: rodent control, PPE (masks, gloves when working in endemic areas), avoid rodent contact, disinfect rodent excreta

49. Differential Diagnosis of HFRS

Condition	Differentiating features
Leptospirosis	Animal contact (water), jaundice prominent, myalgia (calves), positive MAT
Acute pyelonephritis	Dysuria, bacteriuria, positive urine culture, no thrombocytopenia
Acute glomerulonephritis	Strep infection history, edema, hypertension, no fever course, no thrombocytopenia
Appendicitis/surgical abdomen	Different pain character, no febrile period pattern, no urinary changes
Influenza/ARVI	No renal involvement, no thrombocytopenia, no hemoconcentration
Typhoid fever	Stepladder fever, rose spots, hepatosplenomegaly, no ARF
Hemorrhagic fever (other): Ebola, Crimean-Congo	Travel history to endemic regions, different epidemiology, extreme hemorrhage
IgA nephropathy	Follows URTI, no epidemic pattern, biopsy diagnostic

Key HFRS diagnostic features: endemic region + rodent contact + febrile onset + axillary petechiae + thrombocytopenia + massive proteinuria + ARF progression = HFRS until proven otherwise.

50. Trichinellosis

Etiology: Trichinella spiralis (nematode); larvae encyst in striated muscle

Epidemiology: zoonosis; eaten raw/undercooked pork, wild boar, bear, walrus (in Russia!); humans are dead-end hosts; global distribution; trichinellosis is a notifiable disease in Russia

Pathogenesis: ingested larvae → small intestine → adult worms → release larvae → enter lymphatics/bloodstream → migrate to striated muscles → encyst (inflammatory reaction) → calcify over years; muscles most affected: diaphragm, intercostals, tongue, masseters, biceps (most active muscles)

Clinical features (by phase):

Intestinal phase (days 1-7): nausea, diarrhea, abdominal pain (adult worm invasion of mucosa)
Migration phase (days 7-21): cardinal triad: fever (39-40°C) + facial/periorbital edema + myalgia; urticaria, eosinophilia (KEY!), conjunctivitis, subungual/subconjunctival hemorrhages
Encystment phase (weeks 3-8): symptoms subside, residual myalgia, fatigue

Severe trichinellosis: myocarditis, pneumonitis, encephalitis (death possible)

Diagnosis:

Eosinophilia (key, up to 50-80% of WBC!)
Serology: ELISA/RPHA for Trichinella antibodies (appear week 3-4)
Muscle biopsy (deltoid, biceps): trichinella cysts under microscopy - gold standard
↑ CPK, LDH, aldolase (myositis)

Treatment:

Albendazole 400 mg x2/day or mebendazole 200-400 mg x3/day for 10-14 days (intestinal + migrating larvae; less effective once encysted)
Corticosteroids (prednisolone 1 mg/kg/day) for severe myositis, myocarditis, neurological involvement
Symptomatic: antipyretics, antihistamines, analgesics

Prevention: proper meat thermometry (>77°C for pork); trichinelloscopy of meat at slaughterhouses; no raw/salted/smoked pork; control of swine feeding practices

Quick Reference Summary Card

Disease	Key Pathogen	Key Diagnosis	Key Treatment
Typhoid	S. typhi	Blood culture + Widal	Fluoroquinolone/ceftriaxone
Shigellosis	Shigella spp.	Stool culture	Fluoroquinolone
Cholera	V. cholerae	TCBS culture	Rehydration + doxycycline
Salmonellosis	S. enteritidis	Stool culture	Supportive ± fluoroquinolone
Botulism	C. botulinum toxin	Mouse bioassay	Anti-toxin serum + ICU
Leptospirosis	L. interrogans	MAT + IgM ELISA	Penicillin/doxycycline
Brucellosis	Brucella spp.	Wright agglutination	Doxycycline + rifampicin
Pseudotuberculosis	Y. pseudotuberculosis	RPHA + culture	Fluoroquinolone
HFRS	Hantavirus	Anti-Hantavirus IgM	Ribavirin + supportive
Trichinellosis	T. spiralis	Eosinophilia + muscle biopsy	Albendazole ± prednisolone
Hepatitis A/E	HAV/HEV	IgM antibodies	Supportive
Hepatitis B	HBV	HBsAg, HBV DNA	Tenofovir/entecavir
Hepatitis C	HCV	anti-HCV + HCV RNA	DAAs (sofosbuvir)

This covers all 50 exam topics. Key themes to remember for your Russian infectious disease exam:

Epidemic triad: source → transmission → susceptible host
Gromashevsky classification by transmission mechanism
Periods of disease: incubation → prodrome → acme → convalescence
ITS stages and "golden hour" resuscitation
HFRS periods (5) and its unique features (Dunayev proteinuria, axillary petechiae, rodent contact)
Bezredka desensitization before any serum administration
Obligatory hospitalization for especially dangerous infections and food workers
Paired sera (4-fold titer rise) for serological diagnosis

Ascariasis. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Enterobiasis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Cestodoses (diphyllobothriasis, teniarinchiasis, taeniasis). Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Opisthorchiasis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Echinococcosis. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Toxocariasis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Diphtheria. Etiology, epidemiology, pathogenesis, classification, laboratory diagnostics. Oropharyngeal diphtheria. Clinical presentation, treatment, differential diagnosis with tonsillitis, and treatment. Laryngeal diphtheria. Clinical presentation, treatment, differential diagnosis with false croup, and treatment. Specific complications of diphtheria, clinical presentation, diagnosis, treatment. Influenza and other acute respiratory viral infections: etiology, epidemiology, pathogenesis, clinical presentation, diagnostic principles, and treatment Complications of influenza. Clinical presentation, treatment, and prevention. Parainfluenza. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Adenovirus infection. Etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. Coronavirus infection COVID -19. Etiology, epidemiology, pathogenesis, clinical features Coronavirus infection COVID -19. Clinical presentation, diagnosis, differential diagnosis, treatment, prevention. Hib infection. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Systemic tick-borne borreliosis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, and treatment. Herpes infections. Classification. Etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. Infectious mononucleosis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, and treatment. Cytomegalovirus infection. Etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. Strepcoccosis. Classification. Etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment. Erysipelas. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Meningococcal infection. Etiology, epidemiology, pathogenesis, classification, laboratory diagnostics, and treatment. Meningococcemia. Clinical features, diagnosis, treatment. Fulminant form. Meningococcal meningitis, meningoencephalitis. Clinical presentation, diagnosis, treatment. Complications of meningococcal infection: clinical presentation, emergency treatment. Malaria. Etiology, epidemiology, pathogenesis, classification, clinical picture, diagnosis. Tick-borne encephalitis. Etiology, epidemiology, pathogenesis, classification, clinical presentation, diagnosis, and treatment. Typhus. Etiology, epidemiology, pathogenesis, classification, clinical presentation, diagnosis, and treatment. Plague. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Tularemia. Etiology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment. Rabies. Etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. HIV infection. Etiology, epidemiology, pathogenesis, classification, clinical presentation. Epidemiology and prevention of HIV infection. Laboratory diagnostics of HIV infection and opportunistic diseases. HIV infection and opportunistic diseases, principles of therapy. Toxoplasmosis. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Anthrax. Etiology, epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. Erysipelas. Etiology, epidemiology, pathogenesis, clinical features, diagnosis, treatment. Sepsis. Etiology, epidemiology, pathogenesis, classification, clinical presentation, diagnosis, and treatment. Differential diagnosis of acute febrile illnesses. Pathogenesis of fever in infectious diseases. Types and types of fever. Differential diagnosis of exanthema and enanthema syndrome. Differential diagnostics of diseases occurring with gastroenteritis syndrome. Differential diagnostics of diseases occurring with colitis syndrome. Differential diagnosis of diarrhea. Differential diagnosis of viral hepatitis with jaundice of other etiologies. Differential diagnosis of lymphadenopathy syndrome. Differential diagnosis of serous and purulent meningitis. Meningeal syndrome, encephalitic syndrome in infectious diseases. Differential diagnostics of diseases involving the oropharynx. Differential diagnostics of catarrhal respiratory syndrome and atypical pneumonia. Answer all the questions with the most important points but in short for infectious disease exam for medical students studying in russia.

Infectious Diseases - Complete Exam Review Part 2

1. Ascariasis

Etiology: Ascaris lumbricoides (large intestinal roundworm, nematode); female up to 40 cm, male 25 cm; eggs very resistant in soil (years)

Epidemiology: fecal-oral; ingestion of embryonated eggs from contaminated soil, vegetables, water; geohelminthiasis (no intermediate host); endemic in tropics/subtropics; Russia: Caucasus, Central regions; children > adults

Pathogenesis:

Eggs ingested → larvae hatch in small intestine → penetrate mucosa → portal vein → liver → right heart → lungs (Löffler syndrome: eosinophilic infiltrates) → break into alveoli → ascend respiratory tract → swallowed → mature in small intestine → adult worms
Migration phase: allergic/toxic reactions, eosinophilia
Intestinal phase: mechanical obstruction, nutrient competition (B12, A), toxin secretion

Clinical picture:

Migration (larval) phase (2-4 weeks): urticaria, dry cough, dyspnea, low fever, eosinophilia, Löffler syndrome on X-ray ("volatile infiltrates")
Intestinal phase: nausea, abdominal pain (periumbilical), diarrhea/constipation alternating, poor appetite; worms may pass in stool/vomit/nose

Complications: intestinal obstruction (ascarid bolus), biliary obstruction, cholangitis, appendicitis, perforation, migration to liver/lungs/brain

Diagnosis: stool microscopy (Kato-Katz smear) - fertilized/unfertilized eggs; CBC: eosinophilia in migration; X-ray: volatile infiltrates (Löffler)

Treatment: Albendazole 400 mg single dose OR mebendazole 100 mg x2/day x3 days OR pyrantel pamoate 10 mg/kg single dose; repeat stool exam in 3 weeks

2. Enterobiasis (Pinworm Infection)

Etiology: Enterobius vermicularis (pinworm, nematode); small (female 10mm, male 3mm); lives in cecum/appendix region

Epidemiology: fecal-oral; most common helminthiasis worldwide; children 3-14 years predominantly; close contact/crowding; autoinfection and direct contact; eggs survive on surfaces 2-3 weeks

Pathogenesis: eggs ingested → hatch in small intestine → mature in large intestine → females migrate to perianal skin at night → lay eggs → intense pruritus → scratching → eggs under fingernails → autoinfection; minimal tissue damage (mechanical + toxic irritation)

Clinical features:

Perianal pruritus (especially nocturnal) - cardinal symptom
Sleep disturbance, irritability, grinding teeth (bruxism)
Girls: vulvovaginitis (worm migration)
Mild abdominal pain, nausea
CBC: mild eosinophilia or normal

Diagnosis: Graham scrape test (scotch tape applied to perianal area in morning before washing - eggs visible microscopically); repeat x3 on consecutive mornings; stool exam less sensitive (eggs not shed in stool)

Treatment: Mebendazole 100 mg single dose (children/adults) OR albendazole 400 mg single dose OR pyrantel 10 mg/kg single dose; repeat dose in 2 weeks (reinfection cycle); treat entire household; hygiene measures (nail cutting, underwear washing at 60°C)

3. Cestodoses

Diphyllobothriasis (Fish Tapeworm)

Etiology: Diphyllobothrium latum (broadfish tapeworm); up to 10-15 meters; two intermediate hosts: copepods + freshwater fish (pike, perch, burbot)

Epidemiology: ingestion of raw/undercooked freshwater fish (sushi, lightly salted fish); endemic in Siberia, Karelia, Finland, Great Lakes region

Pathogenesis: plerocercoid larvae in fish → ingested → attach to small intestine → adult tapeworm; competes for vitamin B12 (has high affinity for B12) → megaloblastic anemia

Clinical picture: often asymptomatic; abdominal pain, nausea, diarrhea; passage of strobila segments; B12-deficiency megaloblastic anemia (Hunter's glossitis, neurological symptoms) - distinctive feature vs other cestodoses

Diagnosis: stool microscopy - operculated eggs OR segments with characteristic uterine rosette pattern; CBC: megaloblastic anemia, ↓ B12

Treatment: Praziquantel 25 mg/kg single dose; or niclosamide 2 g single dose; B12 supplementation if anemia

Teniarinchiasis (Beef Tapeworm)

Etiology: Taenia saginata (unarmed tapeworm, no hooks); up to 10m; intermediate host: cattle

Epidemiology: raw/undercooked beef; worldwide; endemic in Africa, Central Asia, Russia (beef-eating regions)

Pathogenesis: cysticerci in beef → ingested → adult worm attaches by suckers (no hooks) to small intestine; toxic/allergic effect; nutritional competition (less B12 effect than D. latum)

Clinical: often only symptom = active migration of proglottids (segments crawl out perianally, seen in underwear/on stool); abdominal discomfort, nausea, weight loss; no cysticercosis (T. saginata larvae cannot develop in humans)

Diagnosis: stool - gravid segments (T. saginata: uterus has 15-30 lateral branches vs T. solium 7-13); perianal scrape for eggs

Treatment: Praziquantel 25 mg/kg single dose

Taeniasis (Pork Tapeworm) + Cysticercosis

Etiology: Taenia solium (armed tapeworm, has hooks + suckers); intermediate host: pigs; IMPORTANT: humans can also be intermediate host → cysticercosis

Epidemiology: raw/undercooked pork; Mexico, Latin America, Sub-Saharan Africa, India, Eastern Europe; fecal-oral for cysticercosis (person is also reservoir)

Clinical taeniasis: similar to T. saginata; segments less motile

Cysticercosis (larval migration in humans - ingestion of T. solium eggs):

Neurocysticercosis: epilepsy (most common cause of acquired epilepsy in endemic areas!), headache, hydrocephalus, focal neurological deficits; CT/MRI: ring-enhancing lesions, calcifications
Ocular, muscular, subcutaneous cysticercosis

Diagnosis: stool exam (eggs/segments); ELISA for cysticercosis; CT/MRI brain; X-ray (calcified cysts in muscle)

Treatment: taeniasis: praziquantel 25 mg/kg; neurocysticercosis: albendazole 15 mg/kg/day x8-30 days + corticosteroids (anti-inflammatory) + anti-epileptics; surgery for hydrocephalus

4. Opisthorchiasis

Etiology: Opisthorchis felineus (cat liver fluke, trematode); endemic in West Siberia (Ob-Irtysh river basin), Volga; Russia has highest prevalence worldwide

Epidemiology: two intermediate hosts: freshwater snails (Bithynia) + freshwater fish (carp family - roach, bream, carp, ide); humans infected via raw/lightly salted/frozen fish; zoonosis (cats, dogs, foxes)

Pathogenesis: metacercariae in fish → ingested → excyst in duodenum → migrate via bile duct → liver bile ducts + gallbladder + pancreatic duct → adults live 20-40 years; mechanical obstruction + toxic/allergic injury + epithelial hyperplasia → cholangitis, cholecystitis, pancreatitis → cholangiocarcinoma (long-term major complication)

Clinical features:

Acute (migration, 2-4 weeks): fever, urticaria, eosinophilia, hepatomegaly, right upper quadrant pain, Löffler syndrome
Chronic (years): biliary dyspepsia, right hypochondrium pain (post-fat meal), cholangitis, cholecystitis, cholelithiasis, pancreatitis; cholangiocarcinoma risk ↑ 25x

Diagnosis: stool/duodenal contents microscopy - small operculated eggs (key!); ELISA (IgG to opisthorchis); ultrasound (dilated bile ducts, thickened gallbladder wall); CBC: eosinophilia; liver enzymes ↑

Treatment: Praziquantel 75 mg/kg/day in 3 doses x1 day (25 mg/kg x3 doses with 4-hour intervals); choleretics (hepatoprotectors after); prevention: no raw fish in endemic areas; thorough cooking/freezing (-18°C for 5 days kills metacercariae)

5. Echinococcosis

Etiology:

Echinococcus granulosus → cystic echinococcosis (hydatid cyst)
Echinococcus multilocularis → alveolar echinococcosis (malignant-behaving, invasive)

Epidemiology: E. granulosus: definitive host = dogs (adult worm in intestine); intermediate hosts = sheep, cattle, humans; humans infected by ingesting eggs from dog feces (hands, water, vegetables); zoonosis; pastoral communities, Siberia, Central Asia, Mediterranean, Argentina; E. multilocularis: foxes → rodents → humans (berry/mushroom picking, hunters)

Pathogenesis: eggs ingested → larvae (oncospheres) hatch → penetrate intestinal wall → portal blood → liver (primary filter, 75%) or lungs (15%) or other organs; form hydatid cyst (slow growing over years): outer pericyst (host fibrous tissue), middle laminated membrane (parasite), inner germinal epithelium + daughter cysts + brood capsules with scolices + hydatid sand

Clinical picture:

Liver cyst: asymptomatic for years; then right upper quadrant dull pain, hepatomegaly, palpable mass; complications: rupture (anaphylaxis!), infection, biliary communication (jaundice, cholangitis), pressure on portal vein
Lung cyst: cough, hemoptysis, dyspnea; rupture → expectoration of salty fluid + "grape skins" + hydatid sand
Alveolar (E. multilocularis): infiltrative growth like cancer, liver failure, biliary obstruction; very severe

Diagnosis: ultrasound (Gharbi classification), CT/MRI - pathognomonic: daughter cysts, floating membranes ("water lily sign"), calcified rim; ELISA (IgG) + confirmatory Western blot; NEVER aspirate without treatment (anaphylaxis + seeding risk); chest X-ray for lung cysts

Treatment:

Surgery: cystectomy (PAIR procedure - Puncture-Aspiration-Injection-Reaspiration with hypertonic saline for small cysts)
Albendazole 400 mg x2/day in 28-day cycles (3+ cycles) - perioperative prophylaxis and unresectable cases
Alveolar: surgical resection + albendazole long-term (years)

6. Toxocariasis

Etiology: Toxocara canis (dog roundworm) or T. cati (cat); visceral larva migrans - larvae migrate but cannot complete lifecycle in humans (dead-end host)

Epidemiology: contact with dog/cat feces-contaminated soil (playgrounds, sandboxes); children 1-6 years most affected; geophagia increases risk; worldwide; underdiagnosed

Pathogenesis: embryonated T. canis eggs ingested → larvae hatch → penetrate gut wall → enter portal blood/lymphatics → migrate through liver, lungs, eyes, brain, other organs → CANNOT mature → die in granulomas → persistent eosinophilia and allergic reactions

Clinical features:

Visceral larva migrans (VLM): prolonged fever, hepatomegaly, hypereosinophilia (30-50%!), pulmonary infiltrates (cough, wheezing), urticaria, lymphadenopathy; young children
Ocular larva migrans (OLM): unilateral visual loss, strabismus, retinal granuloma/detachment; older children/adults; minimal systemic eosinophilia; may be misdiagnosed as retinoblastoma
Covert toxocariasis: subclinical, eosinophilia only

Diagnosis: ELISA (anti-Toxocara IgG, titer ≥1:400 significant); hypereosinophilia; elevated IgE; liver ultrasound (multiple hypoechoic foci); fundoscopy (OLM); stool exam USELESS (larvae in humans, no adult worms)

Treatment: Albendazole 10 mg/kg/day in 2 doses x10-14 days (preferred) OR mebendazole 100-200 mg x2/day x2-4 weeks; corticosteroids for severe allergic manifestations or ocular disease; ophthalmologist involvement for OLM

7. Diphtheria: Etiology, Epidemiology, Pathogenesis, Classification, Lab Diagnostics

Etiology: Corynebacterium diphtheriae (gram-positive, club-shaped, non-spore-forming, non-motile); toxin-producing strains (tox+ gene on phage) produce diphtheria exotoxin - most important virulence factor; three biotypes: gravis, mitis, intermedius

Diphtheria toxin mechanism: fragment B - cell entry; fragment A - inhibits EF-2 (elongation factor 2) via ADP-ribosylation → stops protein synthesis → cell death; affects heart, nervous system, kidneys, adrenals

Epidemiology: airborne (mainly); contact with patient/carrier; anthroponosis; source: patients + carriers (important!); incubation 2-10 days; low-vaccinated populations at risk; Russia: major epidemic 1990-1998 (vaccine decline)

Pathogenesis: C. diphtheriae colonizes oropharynx/larynx/etc. → toxin production → local (fibrinous membrane formation - grayish-white pseudomembrane that bleeds on removal, adheres firmly) + systemic (toxin absorption → myocarditis, polyneuritis, nephritis)

Classification by location:

Oropharyngeal (most common, 90-95%)
Laryngeal (croup)
Nasal
Rare: skin, ear, genital

Classification by severity: localized, widespread, toxic (I, II, III degrees)

Laboratory diagnostics:

Bacteriological (main): smear from oropharynx/nose on Löffler/Clauberg/Tinsdale media; identify morphology (Neisser stain: polar granules), biochemistry, toxigenicity
Toxigenicity test: Elek plate test (precipitation lines) or PCR for tox gene
ELISA for antibodies (low diagnostic value in acute)
CBC: leukocytosis, neutrophilia; ↑ fibrinogen
ECG (myocarditis monitoring), liver enzymes, creatinine

8. Oropharyngeal Diphtheria

Clinical presentation:

Localized (tonsil) diphtheria: low-grade fever, mild sore throat, white-grayish pseudomembrane on tonsils (extends BEYOND tonsil margin), submandibular lymphadenopathy; membrane: dense, pearlescent, bleeds on forced removal, does NOT dissolve in water (vs fibrinous exudate of tonsillitis)
Widespread: membrane spreads to uvula, soft palate, oropharynx
Toxic diphtheria (grade I-III): high fever, severe intoxication, bull neck (massive cervical lymphadenopathy + soft tissue edema - pathognomonic!), sweet-putrid odor, gray membrane covering all of oropharynx

Treatment:

Anti-diphtheria antitoxin serum (ADS) - main treatment, URGENTLY; doses: localized 20,000-40,000 IU; widespread 40,000-60,000 IU; toxic grade I 60,000-80,000 IU; toxic II-III 100,000-150,000 IU; give IM (Bezredka desensitization first)
Antibiotics (eliminate C. diphtheriae, NOT antitoxin effect): penicillin 6-12 million IU/day x14 days OR erythromycin/azithromycin
Detoxification, corticosteroids (toxic forms)

Differential diagnosis from bacterial tonsillitis:

Feature	Diphtheria	Bacterial tonsillitis (follicular/lacunar)
Membrane	Dense, gray, extends beyond tonsil	Yellow-white spots/exudate, within tonsil
Removal	Bleeds, adheres	Easily removed, no bleeding
Pain	Mild	Severe
Fever	Low-moderate	High
Lymph nodes	Enlarged + soft tissue edema	Enlarged, tender
Toxicity	Progressive, severe	Acute, responds to antipyretics
Spread	Spreads beyond tonsil	Stays on tonsil

9. Laryngeal Diphtheria (Diphtheric Croup)

Clinical presentation (3 stages):

Dysphonic (catarrhal) stage (1-3 days): hoarseness, rough "barking" cough, low fever
Stenotic stage: stridor (inspiratory noise from subglottic narrowing), voice progressively lost (aphonia), anxiety, retraction of suprasternal/intercostal spaces
Asphyxic stage: cyanosis, paradoxical breathing, seizures → death without intervention

Treatment: ADS immediately (20,000-40,000 IU); corticosteroids IV (dexamethasone); humidified oxygen; direct laryngoscopy (remove membranes if possible); intubation or tracheostomy if stage 2-3 stenosis; penicillin; ICU

Differential diagnosis from false croup (viral subglottic laryngitis):

Feature	Diphtheric croup	False croup (viral)
Onset	Gradual (days)	Sudden (often at night)
Voice	Progressive aphonia	Hoarse but present
Fever	Low-grade	Usually higher, ARVI symptoms
Membrane	Yes (laryngoscopy)	No membrane
Response to steam/epinephrine	No	Yes (false croup responds)
Progression	Worsens without treatment	Often improves spontaneously
Age	Any	Mostly 6 months - 3 years
Season	Any	Autumn-winter ARVI season

10. Specific Complications of Diphtheria

1. Myocarditis (most common cause of death):

Early (days 5-7): toxic; Late (days 10-14): immune
Clinical: tachycardia or bradycardia, muffled heart sounds, arrhythmias, cardiac dilation
ECG: ST changes, conduction blocks (complete AV block), bundle branch block
↑ Troponin, ↑ CK-MB
Treatment: strict bed rest (!), corticosteroids, antiarrhythmics, NO cardiac glycosides initially (fatal risk in toxic myocarditis)

2. Polyneuritis (neuropathy):

Early (week 1-2): palatal palsy → nasal voice, regurgitation through nose; oculomotor palsy → diplopia, ptosis, accommodation palsy
Late (week 4-6): peripheral polyneuropathy → glove-stocking hypesthesia, flaccid paresis/paralysis (limbs, diaphragm → respiratory failure)
Treatment: B vitamins, strychnine, physiotherapy; respiratory support if needed

3. Toxic nephropathy: proteinuria, cylindruria; usually transient; monitor creatinine

4. Toxic hepatitis: ↑ ALT/AST; usually mild

Treatment principles: strict isolation, absolute bed rest (especially myocarditis), ADS (if not already given), penicillin, symptomatic; duration of bed rest depends on complication severity

11. Influenza and Other ARVIs

Influenza:

Etiology: Influenza A (H-N subtypes, pandemic potential), B, C (mild); RNA orthomyxovirus; antigenic drift (annual epidemics) and shift (pandemics); H1N1, H3N2 currently circulating
Epidemiology: airborne; winter epidemics; rapid spread; attack rate 5-20%/year
Pathogenesis: virus binds sialic acid receptors on respiratory epithelium → hemagglutinin (HA) entry → neuraminidase (NA) facilitates release → epithelial destruction → viremia → toxemia (headache, myalgia, fever) → secondary bacterial complications
Clinical: sudden onset; high fever (39-40°C), severe headache, myalgia ("beaten"), photophobia, dry painful cough; minimal catarrhal symptoms initially - distinguishes from other ARVI; retrobulbar pain (eye movement); duration 5-7 days; recovery in 1-2 weeks

Other ARVIs (comparison table):

Disease	Pathogen	Key feature
Parainfluenza	Parainfluenza virus 1-4	Croup in children, moderate fever
Adenovirus	Adenovirus 1-51	Fever + conjunctivitis + pharyngitis (pharyngoconjunctival fever)
RSV	RSV	Bronchiolitis in infants
Rhinovirus	Rhinovirus	"Common cold," minimal fever
Coronavirus (seasonal)	HCoV-229E, OC43	Common cold, mild

Diagnosis: clinical; PCR (nasopharyngeal swab) - gold standard; rapid Ag test (lower sensitivity); serology (paired sera); CBC: leukopenia, lymphocytosis (viral)

Treatment:

Antivirals: oseltamivir (Tamiflu) 75 mg x2/day x5 days (within 48 hours!); zanamivir inhaled; baloxavir (newer); for influenza A/B
Symptomatic: antipyretics (paracetamol, ibuprofen; NOT aspirin in children - Reye syndrome), saline nasal irrigation, expectorants
Antibiotics ONLY for bacterial complications

12. Complications of Influenza

Viral pneumonia (primary): rapid onset day 1-2, bilateral interstitial infiltrates, ARDS; high mortality (H5N1, H1N1 pandemic); treatment: oseltamivir + mechanical ventilation if needed
Secondary bacterial pneumonia: days 5-7 after apparent improvement → new fever, productive cough, focal consolidation; pathogens: S. aureus (including MRSA), S. pneumoniae, H. influenzae; treatment: antibiotics (amoxicillin-clavulanate, cephalosporins, vancomycin for MRSA)
Toxic encephalopathy/encephalitis: seizures, altered consciousness; mainly in children; treatment: corticosteroids, oseltamivir
Myocarditis/pericarditis
Sinusitis, otitis media (especially children)
Exacerbation of chronic diseases: COPD, asthma, heart failure, diabetes
Reye syndrome (children, aspirin + influenza/varicella): encephalopathy + liver failure; NEVER give aspirin to children with viral infections

Treatment: treat underlying complication; antivirals; ICU as needed

Prevention: annual influenza vaccine (recommended for: >65 years, chronic disease, healthcare workers, pregnancy, children 6m-5y); neuraminidase inhibitors for post-exposure prophylaxis

13. Parainfluenza

Etiology: Parainfluenza virus types 1-4 (Paramyxoviridae, RNA); type 1,2 - croup; type 3 - bronchiolitis/pneumonia in infants; type 4 - mild

Epidemiology: airborne; children most affected; type 1,2 - autumn; type 3 - spring; worldwide

Pathogenesis: infects upper respiratory epithelium → local inflammation → laryngeal/subglottic edema (type 1,2) → "false croup"; type 3: lower respiratory tract → bronchiolitis

Clinical features:

False croup (acute laryngotracheobronchitis): sudden onset at night, barking cough ("seal bark"), inspiratory stridor, hoarse voice, low-moderate fever; children 6 months - 5 years; usually resolves with steam/cool air
Pharyngitis, rhinitis, tracheobronchitis (older children/adults)
Bronchiolitis (type 3, infants)

Diagnosis: clinical (typically); PCR; DIF with fluorescent antibodies; RTHA (paired sera)

Treatment: humidified air, cool mist; nebulized epinephrine (adrenaline) for moderate-severe croup; systemic dexamethasone (0.15-0.6 mg/kg) - reduces edema; hospitalization if severe; no specific antivirals

14. Adenovirus Infection

Etiology: Adenovirus (dsDNA), >50 serotypes; types 1-5 (endemic respiratory), 4,7 (military outbreaks), 8,19,37 (keratoconjunctivitis), 40,41 (gastroenteritis)

Epidemiology: airborne + fecal-oral + contact; children, military; year-round but winter peak; long-term latency in lymphoid tissue

Pathogenesis: infects respiratory epithelium, conjunctiva, gut epithelium, lymphoid tissue; direct cytopathic effect; persists in tonsils/adenoids; immune depression

Clinical presentation (syndrome classification):

Pharyngoconjunctival fever (PCF): fever + pharyngitis + acute conjunctivitis (often follicular) + lymphadenopathy; classical adenovirus syndrome
Epidemic keratoconjunctivitis (types 8,19): severe eye involvement, keratitis, photophobia; no fever
Acute respiratory disease (ARD): pharyngitis, tonsillitis, tracheobronchitis
Pneumonia: severe in immunocompromised, children
Gastroenteritis: types 40/41 in children
Acute hemorrhagic cystitis: types 11,21; hematuria + dysuria

Diagnosis: PCR (respiratory/stool/ocular specimens); DIF; cell culture; CBC: lymphocytosis

Treatment: supportive; ciprofloxacin eye drops for bacterial superinfection of conjunctiva; cidofovir for severe adenovirus in immunocompromised; adenovirus live oral vaccine for military (serotypes 4,7)

15. COVID-19: Etiology, Epidemiology, Pathogenesis, Clinical Features

Etiology: SARS-CoV-2 (betacoronavirus, RNA, enveloped); spike (S) protein binds ACE2 receptor; variants: Alpha, Delta, Omicron (dominant, less severe)

Epidemiology: airborne (aerosol main route), droplet, contact; pandemic 2019-2023; global spread; zoonotic origin (bats → intermediate host → humans); high R0 (Omicron: 8-15)

Pathogenesis: S protein + ACE2 (lung type II pneumocytes, intestine, kidney, heart, endothelium) → TMPRSS2 priming → cell entry → viral replication → innate immune suppression (delayed interferon response) → viral load peak day 3-5 → then adaptive immune response → cytokine storm in severe cases → ARDS, microvascular thrombosis, MOF; ACE2 downregulation → ↑ angiotensin II → vasoconstriction, inflammation

Clinical features:

Incubation: 1-14 days (Omicron 2-5 days)
Asymptomatic: 20-40%
Mild: fever, dry cough, anosmia/ageusia (pathognomonic for original strains), fatigue, myalgia, headache
Moderate: pneumonia without hypoxia; SpO2 >93%
Severe: pneumonia + SpO2 <93%, RR >30, bilateral infiltrates >50%
Critical: ARDS, septic shock, MOF

Severity risk factors: age >60, obesity, DM, CVD, chronic lung disease, immunosuppression

16. COVID-19: Clinical Presentation, Diagnosis, Differential Diagnosis, Treatment, Prevention

Clinical presentation (see above + complications):

Post-COVID syndrome: fatigue, brain fog, dyspnea, POTS persisting >12 weeks
Multisystem Inflammatory Syndrome in Children (MIS-C): 2-6 weeks post-infection, Kawasaki-like

Diagnosis:

PCR (NAAT): nasopharyngeal swab - gold standard; sensitivity 70-90%
Rapid antigen test: less sensitive but fast; high specificity
Serology (IgM/IgG): not for acute diagnosis; epidemiological/immunity assessment
CT chest: bilateral ground-glass opacities (GGO), peripheral/basal, "crazy paving" - highly suggestive; not primary diagnostic tool
CBC: lymphopenia (key!), thrombocytopenia; ↑ CRP, ↑ ferritin, ↑ D-dimer, ↑ IL-6 (severity markers); ↑ LDH, ↑ troponin

Differential diagnosis:

Influenza: clinically similar but no anosmia, different epidemiology; PCR differentiates
Other ARVI: milder, no pneumonia typically
Community-acquired pneumonia: bacterial - purulent sputum, focal consolidation, + culture
Pulmonary embolism: acute dyspnea, pleuritic pain, Wells score

Treatment (Russian clinical guidelines):

Mild (outpatient): symptomatic; consider antivirals (nirmatrelvir/ritonavir - Paxlovid if high risk, within 5 days); isolate
Moderate: hospitalization, oxygen; dexamethasone 6 mg/day x10 days; anticoagulation (prophylactic LMWH); antibiotics only if bacterial superinfection
Severe/Critical: ICU, O2/high-flow/mechanical ventilation; dexamethasone; therapeutic anticoagulation; baricitinib or tocilizumab (anti-IL-6) for cytokine storm; remdesivir (questionable benefit)

Prevention: vaccination (mRNA - Pfizer/Moderna; vector - Sputnik V in Russia; protein subunit - Novavax); masks (N95), hand hygiene, ventilation

17. Hib (Haemophilus influenzae type b) Infection

Etiology: Haemophilus influenzae type b (gram-negative coccobacillus); polysaccharide capsule (polyribose phosphate - PRP) determines pathogenicity; produces IgA protease, cytotoxins

Epidemiology: airborne; children 3 months - 5 years predominantly (maternal Ab wane after 3 months); before vaccine era: major cause of bacterial meningitis + epiglottitis in children; after Hib vaccine: dramatically reduced; adults: immunocompromised, asplenic

Pathogenesis: nasopharyngeal colonization → local infection OR bacteremia → meningitis, epiglottitis, pneumonia, septic arthritis, cellulitis, empyema

Clinical picture:

Meningitis: sudden fever, meningeal signs, bulging fontanelle in infants; can be rapid/fatal; sequelae: deafness, cognitive impairment
Epiglottitis: children 2-7 y; RAPID onset fever + drooling + dysphagia + tripod position (leaning forward, chin thrust) + stridor + muffled voice; LIFE-THREATENING airway emergency; "thumbprint sign" on lateral neck X-ray
Pneumonia: lobar/bronchopneumonia
Septic arthritis, cellulitis (orbital, buccal)

Diagnosis: blood/CSF culture; gram stain (gram-negative rods in CSF); latex agglutination for Hib capsular Ag; CBC: leukocytosis

Treatment: Ceftriaxone 100 mg/kg/day IV x10-14 days (or ampicillin if susceptible); for epiglottitis: secure airway FIRST (intubation in OR by skilled provider, never examine throat with tongue blade alone!), then antibiotics; dexamethasone pre-antibiotic for meningitis (reduces deafness)

Prevention: Hib conjugate vaccine (polysaccharide + protein carrier) - extremely effective; in Russian NIP: 3-4.5-6 months + booster at 18 months

18. Systemic Tick-Borne Borreliosis (Lyme Disease)

Etiology: Borrelia burgdorferi sensu lato (spirochete); Europe: B. afzelii (skin manifestations), B. garinii (neuro); North America: B. burgdorferi s.s.

Epidemiology: tick-borne; vector: Ixodes ricinus (Europe), I. scapularis (USA); reservoir: small rodents (mice), deer; spring-autumn; forested areas of European Russia, Siberia; tick must attach >24-36 hours to transmit

Pathogenesis: spirochete injected via tick saliva → skin (EM) → hematogenous spread → joints, nervous system, heart; evades immunity (antigen variation, complement evasion); chronic immune-mediated joint/neurological damage

Clinical features (stages):

Stage I (early localized, days-weeks): Erythema migrans (EM) - pathognomonic; expanding annular erythema with central clearing ≥5 cm at tick bite site; mild flu-like symptoms; may be absent in 30%
Stage II (early disseminated, weeks-months):
- Neuroborreliosis (Bannwarth): facial palsy (bilateral!), radicular pain, meningitis, cranial neuropathies
- Cardiac: AV block (up to complete), pericarditis
- Multiple EM lesions
Stage III (late, months-years):
- Lyme arthritis: oligoarthritis (knee most common!), remitting/relapsing
- Chronic neuroborreliosis: polyneuropathy, encephalopathy
- Acrodermatitis chronica atrophicans (ACA): B. afzelii; bluish skin atrophy on extremities

Diagnosis: clinical (EM diagnostic without serology); ELISA IgM/IgG (2-tier testing: ELISA → if positive/equivocal → Western blot); PCR (synovial fluid, CSF); serology negative in early stage (window period)

Treatment:

Stage I (EM): doxycycline 100 mg x2/day x14-21 days; or amoxicillin 500 mg x3/day x14 days
Neurological/cardiac (2nd/3rd degree AV block): ceftriaxone 2 g/day IV x14-28 days
Arthritis: doxycycline 100 mg x2 x28 days; if persistent: ceftriaxone IV
Post-exposure prophylaxis: doxycycline 200 mg single dose within 72 hours of tick removal

19. Herpes Infections: Classification, Etiology, Pathogenesis, Clinical Presentation, Diagnosis, Treatment

Classification (Herpesviridae, dsDNA):

HSV-1 (HHV-1): orolabial herpes, herpes encephalitis
HSV-2 (HHV-2): genital herpes, neonatal herpes
VZV (HHV-3): chickenpox (primary) + herpes zoster (reactivation)
EBV (HHV-4): infectious mononucleosis, EBV-associated lymphomas
CMV (HHV-5): CMV disease (immunocompromised, congenital)
HHV-6: roseola infantum (exanthema subitum)
HHV-7: similar to HHV-6
HHV-8: Kaposi's sarcoma (HIV patients)

Pathogenesis (common): primary infection → latency in ganglia (HSV: trigeminal/sacral; VZV: dorsal root; EBV: B-lymphocytes) → reactivation by stress, immunosuppression, UV

HSV-1 clinical: herpes labialis (cold sore - grouped vesicles on red base, lip/perioral); gingivostomatitis (primary, children); keratoconjunctivitis; encephalitis (temporal lobe, devastating)

HSV-2 clinical: genital ulcers (painful), recurrent; neonatal herpes (delivery); aseptic meningitis

VZV - Chickenpox: vesicular rash (different stages simultaneously - "starry sky"), centripetal distribution, fever, pruritus; complications: pneumonia (adults), encephalitis, secondary bacterial infection

VZV - Herpes Zoster (Shingles): reactivation after decades; unilateral dermatomal vesicular rash + severe pain; postherpetic neuralgia (main complication); Ramsay Hunt syndrome (facial nerve + ear); ophthalmicus (eye involvement)

Diagnosis: clinical; Tzanck smear (multinucleated giant cells); PCR (CSF for encephalitis, swab from lesions - gold standard); DIF; serology (VCA IgM for EBV)

Treatment:

Acyclovir: HSV mucocutaneous: 200 mg x5/day x5 days or 400 mg x3/day; herpes encephalitis: 10 mg/kg IV x3/day x14-21 days; VZV: 800 mg x5/day x7-10 days
Valacyclovir (prodrug, better bioavailability): 500-1000 mg x2/day
Famciclovir: similar spectrum
VZV zoster: start within 72 hours of rash; reduces severity, postherpetic neuralgia
Neonatal herpes: acyclovir IV high-dose
Vaccine: Varivax (live VZV, chickenpox prevention); Shingrix (recombinant subunit, zoster prevention, >50 years - highly effective)

20. Infectious Mononucleosis

Etiology: EBV (HHV-4); infects B-lymphocytes via CD21 (CR2); primary infection

Epidemiology: saliva contact ("kissing disease"); adolescents/young adults; ubiquitous; 90%+ of adults seropositive; most primary infections in children asymptomatic

Pathogenesis: EBV infects oropharyngeal epithelium + B-lymphocytes → B-cell proliferation → reactive T-cell (CD8) and NK-cell expansion → "atypical lymphocytes" → reactive lymphadenopathy, splenomegaly; heterophile antibodies (IgM reacting with sheep/horse RBCs)

Clinical features:

Incubation: 4-6 weeks
Classic triad: fever + exudative tonsillitis/pharyngitis (gray-white membrane, severe sore throat) + cervical lymphadenopathy (posterior > anterior; tender)
Splenomegaly (50-80%): risk of splenic rupture (avoid contact sports!)
Hepatomegaly + mild hepatitis (↑ ALT)
Maculopapular rash (5-10%); ampicillin rash: if amoxicillin/ampicillin given → 80-100% develop generalized maculopapular rash (diagnostic clue!)
Periorbital edema (Hoagland sign)
Palatal petechiae

Complications: splenic rupture, airway obstruction (massive tonsil enlargement), hemolytic anemia, thrombocytopenia, encephalitis, Guillain-Barré, myocarditis, chronic active EBV, EBV-associated lymphomas (immunocompromised)

Diagnosis:

CBC: lymphocytosis with atypical lymphocytes (>10%) - Downey cells (large, with vacuolated cytoplasm)
Heterophile antibody test (Paul-Bunnell-Davidsohn or monospot test): rapid, specific, positive in 85% of adolescents/adults
Specific EBV serology: VCA-IgM (acute), VCA-IgG, EA (early antigen, active infection), EBNA-IgG (past infection, appears late)
↑ ALT, ↑ AST (hepatitis)

Treatment: supportive; rest (avoid sports 3-4 weeks due to spleen rupture risk!); NO ampicillin/amoxicillin; corticosteroids (short course) if airway obstruction, severe thrombocytopenia; acyclovir (limited efficacy, not standard); tonsillectomy rare

21. Cytomegalovirus (CMV) Infection

Etiology: CMV (HHV-5); largest herpesvirus; dsDNA; latent in mononuclear cells

Epidemiology: worldwide; spread via saliva, sexual contact, blood transfusion, transplant, transplacental/perinatal (vertical); most adults seropositive (50-80%); disease mainly in immunocompromised and congenital

Pathogenesis: primary infection → latency in mononuclear cells/endothelium → reactivation in immunosuppression; "owl eye" intranuclear inclusions in infected cells

Clinical picture:

Immunocompetent: CMV mononucleosis (similar to EBV but heterophile-negative, less severe pharyngitis); often asymptomatic
Immunocompromised (AIDS, transplant):
- CMV retinitis: floaters, visual loss, "pizza pie" fundus (hemorrhages + exudates); leading cause of blindness in AIDS (<50 CD4)
- CMV esophagitis/colitis: odynophagia, diarrhea, GI bleeding; large shallow ulcers
- CMV pneumonitis: bilateral infiltrates, hypoxia; post-transplant
- CMV encephalitis/polyradiculopathy
Congenital CMV: "blueberry muffin" rash, microcephaly, periventricular calcifications, sensorineural hearing loss, chorioretinitis, hepatosplenomegaly; most common congenital viral infection

Diagnosis: PCR (blood, urine, CSF, BAL) - gold standard; pp65 antigenemia (WBC); ELISA IgM/IgG; biopsy with "owl eye" inclusions; culture (slow)

Treatment: Ganciclovir 5 mg/kg IV x2/day x14-21 days (induction); valganciclovir (oral, equivalent) for maintenance; Foscarnet (ganciclovir-resistant); Cidofovir (weekly, nephrotoxic); congenital: valganciclovir x6 months (improves hearing outcomes)

22. Streptococcosis: Classification, Etiology, Epidemiology, Pathogenesis

Etiology: Streptococcus pyogenes (Group A Streptococcus - GAS) - main pathogen; also Group B, C, G, viridans, S. pneumoniae, S. agalactiae

Classification of GAS diseases:

Suppurative (local): pharyngitis/tonsillitis, impetigo, cellulitis, erysipelas, wound infection
Invasive/severe: necrotizing fasciitis, streptococcal toxic shock syndrome (STSS), bacteremia
Toxin-mediated: scarlet fever
Post-streptococcal (non-suppurative): acute rheumatic fever (ARF), post-streptococcal GN

Epidemiology: airborne (throat infections), contact (skin infections); peak in children 5-15 years; winter/spring; pharyngitis leads to ARF; skin infections lead to GN

Pathogenesis:

Virulence factors: M protein (antiphagocytic, type-specific immunity), hyaluronidase, streptokinase, DNase, streptolysin O/S, pyrogenic exotoxins (SPE A,B,C - cause scarlet fever rash + STSS)
M protein cross-reacts with cardiac myosin (ARF mechanism - molecular mimicry)

Scarlet fever: SPE → systemic toxin effect → rash (punctate erythema, sandpaper skin), pharyngitis, strawberry tongue (red, prominent papillae), Pastia's lines (petechiae in skin folds), circumoral pallor; desquamation after rash

Diagnosis: rapid strep antigen test (throat swab); throat culture (gold standard); ASO titer (post-streptococcal complications); ASЛО >250 U in adults, >500 U in children = recent GAS infection

Treatment: Phenoxymethylpenicillin (penicillin V) 250-500 mg x4/day x10 days (10-day course is mandatory to prevent ARF!); or amoxicillin; azithromycin/cephalosporins if penicillin allergy; benzathine penicillin G 1.2 million IU IM single dose (excellent compliance)

23. Erysipelas

Etiology: Streptococcus pyogenes (GAS), group A; sometimes G; skin lymphatic infection

Epidemiology: contact; through skin micro-trauma (abrasions, cracks, fungal intertrigo); summer-autumn; recurrence common (same lymphatics affected); risk factors: lymphedema, chronic venous insufficiency, obesity, diabetes, athlete's foot (portal of entry)

Pathogenesis: GAS enters through skin break → infects dermis and superficial lymphatics → spreads along lymphatics → intense inflammatory reaction → edema, erythema, warmth; toxins → systemic intoxication; recurrences → lymphatic damage → lymphedema (elephantiasis)

Clinical features:

Prodrome: fever (39-40°C), chills, headache, malaise
Then (hours later): bright red, well-demarcated, raised border erythema on skin (lower legs most common, face); warm, tender, edematous; "advancing fire" (erysipelas = "red skin" in Greek)
Forms: erythematous (classic), erythematous-bullous (blistering), hemorrhagic, phlegmonous (deep), necrotizing (gangrene)
Recurrent erysipelas: in same location, leads to chronic lymphedema

Diagnosis: clinical; skin swab culture (rarely positive); blood culture (bacteremia, rare); CBC: leukocytosis, neutrophilia; ↑ ASO (streptococcal antibodies)

Treatment:

Benzylpenicillin 2 million IU IM x6/day x10-14 days (standard in Russia)
Amoxicillin-clavulanate or cephalosporins (broader spectrum for uncertain cases)
Clindamycin (toxin production inhibition in severe)
Local: NO wet compresses on bullous form; dry dressings; antiseptic
Physiotherapy (UVI after acute phase - promotes healing)
Recurrence prevention: benzathine penicillin 1.2 million IU IM every 3 weeks (prophylaxis for 1-3 years)

24. Meningococcal Infection: Etiology, Epidemiology, Pathogenesis, Classification, Lab Diagnostics, Treatment

Etiology: Neisseria meningitidis (gram-negative diplococcus, intracellular in CSF/blood); serogroups A, B, C, W, X, Y; polysaccharide capsule is main virulence factor; produces endotoxin (LPS - most potent, causes ITS) and IgA protease

Epidemiology: airborne; nasopharyngeal carriage (10-25% of population); invasive disease in <1%; children <5 years + teenagers 15-25 years; winter-spring; Africa meningitis belt (serogroup A); endemic disease + outbreaks

Pathogenesis: colonizes nasopharynx → invasive strains breach mucosal barrier → bacteremia → endotoxin release → cytokine storm → ITS + DIC → hemorrhagic necrosis of adrenals (Waterhouse-Friderichsen syndrome); meningitis from hematogenous seeding of meninges

Classification:

Localized: nasopharyngitis
Generalized: meningococcemia (without meningitis), meningitis, meningoencephalitis, combined (meningococcemia + meningitis)
Rare: endocarditis, arthritis, pneumonia, iridocyclitis
Severity: fulminant, typical

Lab diagnostics:

CSF (lumber puncture - KEY): turbid, ↑ pressure; pleocytosis (1000-10,000 cells, predominantly neutrophils); ↑ protein (1-10 g/l); ↓ glucose (<2.2 or <50% blood glucose); gram stain: gram-negative diplococci intracellularly
Blood culture: positive in 50-60%; gold standard
CSF culture: positive in 80%
PCR (blood, CSF): highly sensitive; positive even after antibiotics
Latex agglutination (CSF/blood): rapid detection of capsular antigen (A,B,C,W,Y)
CBC: leukocytosis 20-40×10⁹/l, shift left; ↑ CRP, ↑ procalcitonin
Coagulogram: DIC signs in meningococcemia

25. Meningococcemia: Clinical Features, Diagnosis, Treatment; Fulminant Form

Clinical features:

Prodrome (nasopharyngitis): 1-5 days sore throat
Sudden onset: high fever (40°C), chills, severe headache, prostration
Hemorrhagic rash - pathognomonic: starts as roseolae/papules → transforms into hemorrhagic petechiae → stellate (star-shaped) non-blanching hemorrhages → ecchymoses; first on buttocks, lower limbs, trunk
Hemodynamic deterioration: ITS

Fulminant meningococcemia (Waterhouse-Friderichsen):

Rapid development within hours: massive hemorrhagic rash with necrosis, ITS grade III
Bilateral adrenal hemorrhage → adrenal crisis (severe hypotension refractory to fluids)
DIC with diffuse bleeding
Mortality >80% if not treated immediately

Diagnosis: clinical picture + hemorrhagic rash = START TREATMENT IMMEDIATELY without waiting for confirmatory tests; blood PCR/culture; coagulogram

Treatment (emergency):

Penicillin G 300,000-500,000 IU/kg/day IV (adults: 24 million IU/day in 6 doses) - START PREHOSPITALLY
Ceftriaxone 4 g/day IV (if penicillin unavailable or uncertain diagnosis)
Volume resuscitation (crystalloids 20-30 ml/kg rapidly)
Norepinephrine (vasopressor)
Hydrocortisone 200-300 mg/day IV (adrenal insufficiency cover)
DIC correction (FFP, heparin)
ICU monitoring

26. Meningococcal Meningitis/Meningoencephalitis

Clinical presentation:

Sudden fever (39-40°C), severe bursting headache, photophobia, phonophobia
Meningeal signs: Kernig (inability to extend knee when hip flexed 90°), Brudzinski (neck flexion causes knee flexion; contralateral leg flexion when one leg tested), nuchal rigidity (neck stiffness)
Nausea, vomiting (projectile, no relief)
Altered consciousness (meningoencephalitis) → seizures, coma
In infants: bulging fontanelle, high-pitched cry, opisthotonos, refusal to feed
Cranial nerve palsies (VI, III, VII)

Diagnosis: CSF (see above - turbid, neutrophilic pleocytosis, ↑ protein, ↓ glucose); CT before LP if: focal neurological signs, papilledema, consciousness disorder, immunocompromised (to exclude herniation)

Treatment:

Penicillin G 24 million IU/day IV x7-10 days (or ceftriaxone 4 g/day)
Dexamethasone 0.15 mg/kg x4/day x4 days - start BEFORE or WITH first antibiotic dose → reduces neurological sequelae (deafness, brain damage)
Antipyretics, analgesics, sedation if agitation
Monitor ICP: head elevation 30°, restrict fluids if SIADH, mannitol if herniation signs
Contacts: rifampicin prophylaxis 600 mg x2/day x2 days (or ciprofloxacin 500 mg single dose)

27. Complications of Meningococcal Infection: Emergency Treatment

ITS/Septic shock: see Question 25 above (vasopressors, fluids, corticosteroids)
Intracranial hypertension/cerebral herniation: mannitol 1 g/kg IV; head elevation; hyperventilation (temporary); dexamethasone; neurosurgery consultation
DIC: FFP, cryoprecipitate, heparin (early stage)
Waterhouse-Friderichsen (adrenal crisis): hydrocortisone 100 mg IV bolus → 200 mg/day; fluid resuscitation
SIADH: fluid restriction to 2/3 maintenance; monitor Na+ (risk of hyponatremia → cerebral edema)
Septic arthritis, pericarditis: drainage if needed; continue antibiotics
Limb necrosis/gangrene: amputation may be necessary after stabilization
Sequelae: deafness (audiological assessment), neuropsychological sequelae, skin grafting for necrotic areas

28. Malaria: Etiology, Epidemiology, Pathogenesis, Classification, Clinical Picture, Diagnosis

Etiology: Plasmodium spp. (protozoa):

P. falciparum - most severe, cerebral malaria, Africa, drug resistance
P. vivax - most widespread, relapsing (liver hypnozoites)
P. ovale - similar to vivax, milder
P. malariae - quartan, nephritis, very long latency
P. knowlesi - zoonotic, Southeast Asia

Epidemiology: vector-borne; Anopheles mosquito (female, bites at dusk/dawn); tropics/subtropics; Africa (90% of deaths); imported in Russia (travel, migrants); vertical, transfusion, needle-sharing

Pathogenesis:

Sporozoites → liver → pre-erythrocytic schizogony (silent) → merozoites → erythrocytes → erythrocytic cycle: ring → trophozoite → schizont → merozoites released → RBC rupture = fever paroxysm (endotoxin release from RBC)
P. vivax/ovale: dormant hypnozoites in liver → relapses after months/years
P. falciparum: infected RBCs adhere to endothelium (cytoadherence, rosetting) → microvascular obstruction → cerebral malaria, severe anemia, renal failure, ARDS, hypoglycemia

Classification: uncomplicated malaria, severe malaria (P. falciparum criteria: coma, respiratory distress, severe anemia Hb<70, hyperparasitemia >5%, renal failure, hypoglycemia, shock)

Clinical picture (malarial paroxysm - classic):

Chills (30-60 min): intense shivering, teeth chattering
Heat (2-6 hours): 40-41°C fever, severe headache, myalgia, delirium
Sweating (1-2 hours): profuse diaphoresis, fever falls, exhaustion, sleep

Periodicity: P. vivax/ovale - tertian (every 48h); P. malariae - quartan (every 72h); P. falciparum - irregular (daily or tertian); INITIAL attacks may be daily

Diagnosis:

Thick blood smear (gold standard): stain with Giemsa; highest sensitivity; examine when febrile; 100-200 fields
Thin blood smear: species identification (morphology of parasite + RBC changes)
Rapid diagnostic test (RDT): HRP2 antigen (falciparum) or pan-malarial pLDH; point-of-care
PCR: highest sensitivity/specificity; speciation; research
CBC: anemia, thrombocytopenia, leukopenia; ↑ LDH, ↑ bilirubin (hemolysis)
Hypoglycemia (especially P. falciparum in pregnancy + quinine treatment)

29. Tick-Borne Encephalitis (TBE)

Etiology: TBE virus (Flavivirus, RNA); 3 subtypes: European (mild), Siberian (severe, chronic), Far Eastern (most severe, Russian Spring-Summer Encephalitis)

Epidemiology: tick-borne (Ixodes ricinus, I. persulcatus); endemic in forests of Siberia, Ural, European Russia; spring-summer (tick activity); also alimentary route (raw goat/cow milk); NOT person-to-person; tick removal within 4 hours significantly reduces transmission

Pathogenesis: virus inoculated via tick bite → skin replication → lymph nodes → viremia (febrile phase) → CNS invasion via blood-brain barrier → neuronal destruction; predilection for motor neurons of anterior horn (poliomyelitis-like), cerebellum, brainstem

Classification (clinical forms):

Febrile (abortive): just fever, no CNS involvement
Meningeal: aseptic meningitis
Meningoencephalitic: fever + meningitis + encephalitis
Poliomyelitis-like: flaccid paralysis of neck/arm muscles ("drooping head syndrome")
Polyradiculoneuritis
Chronic progressive: Siberian/Far Eastern subtypes

Clinical presentation (biphasic = classic for European type):

Phase 1 (viremia, 3-7 days): fever, myalgia, headache, then remission 1-2 weeks
Phase 2 (neurological, 30-50% of European): fever returns + meningitis/encephalitis signs; in Siberian/Far Eastern: often monophasic, worse

Characteristic: flaccid paralysis of shoulder girdle + neck muscles (anterior horn involvement) → drooping head, inability to raise arms

Diagnosis: serology (ELISA IgM in serum/CSF - appears early day 3-5 of neurological phase); PCR (early viremia phase); CSF: lymphocytic pleocytosis, ↑ protein

Treatment: no specific antivirals; TBE-specific immunoglobulin (within 4 days post-bite, prophylactic); supportive; corticosteroids (cerebral edema); anti-epileptics

Prevention: TBE vaccine (FSME-Immun, Encepur, Tick-E-Vac - in Russia); 3-dose primary series + boosters; tick repellents; protective clothing; avoid raw milk in endemic areas

30. Typhus (Epidemic Louse-Borne Typhus)

Etiology: Rickettsia prowazekii (obligate intracellular gram-negative coccobacillus); survives in human body louse (Pediculus humanus corporis) for life

Epidemiology: vector-borne; human louse (NOT tick!); feces of louse contaminate scratch wound (not bite); humans are reservoir; associated with poverty, war, crowding; Brill-Zinsser disease (recrudescence years later from persistent R. prowazekii in lymph nodes)

Pathogenesis: rickettsiae enter scratched skin → invade vascular endothelial cells → multiply → endothelial cell lysis → vasculitis (universal, all organs) → thrombi formation → "typhus nodules" (Popov-Davydovsky granulomas) in brain, heart, kidney, skin → clinical manifestations

Classification: classic (epidemic), Brill-Zinsser (recrudescent)

Clinical presentation:

Incubation: 10-14 days
Acute onset: high fever (39-40°C), severe headache, insomnia, agitation, photophobia
Day 4-5: roseolae-petechial exanthema - begins on trunk/lateral chest, spreads centrifugally (NOT to face, palms, soles - opposite of typhoid fever!); rose spots become petechial
Face hyperemic ("red"), conjunctival injection, "red eyes"; Chiari-Avtsyn sign (conjunctival hemorrhages)
"Cardboard tongue" (dry, brown-coated)
Hepatosplenomegaly
Neurological: encephalitis signs - agitation, delirium, "typhomania"; meningeal signs; status typhosus (extreme prostration, delirium, coma)
Bradycardia relative to fever (early), then myocarditis

Diagnosis: serology - Weil-Felix reaction (Proteus OX-19 agglutination, nonspecific but historic); ELISA (IgM/IgG to R. prowazekii) - specific; PCR; CBC: leukocytosis, thrombocytopenia

Treatment: Doxycycline 200 mg once then 100 mg/day x7-14 days (first choice); chloramphenicol; fever defervesces dramatically in 24-48 hours of doxycycline (diagnostic/therapeutic)

31. Plague

Etiology: Yersinia pestis (gram-negative coccobacillus, Enterobacteriaceae); bipolar staining ("safety pin"); produces F1 capsule, V/W antigens (anti-phagocytic), plasminogen activator, endotoxin, murine toxin; Category A bioterrorism agent

Epidemiology: zoonosis; natural foci (steppe, desert rodents - ground squirrels, gerbils, marmots); vector: Xenopsylla cheopsis (rat flea); bubonic plague (flea bite) → septicemic → pneumonic (airborne spread, most contagious); natural foci in Russia: Caspian steppes, Caucasus, Siberia, Central Asia

Pathogenesis: Y. pestis injected by flea → skin → regional lymph node → rapid multiplication → bubo (hemorrhagic necrosis of lymph node) → bacteremia → septicemia → secondary pneumonia (from bacteremia) → hematogenous seeding of all organs; endotoxin → ITS, DIC

Clinical picture:

Bubonic plague: bubo (acutely inflamed, exquisitely tender, fused lymph node mass, usually inguinal/axillary/cervical) + high fever + extreme intoxication; untreated mortality 50-90%
Septicemic plague: bacteremia without bubo; hemorrhagic rash, DIC, ITS; "black death" (skin gangrene from DIC)
Pneumonic plague (primary - inhalation; secondary - hematogenous): severe pneumonia, bloody sputum, ARDS; most lethal form (near 100% untreated); HIGHLY CONTAGIOUS person-to-person

Diagnosis: ESPECIALLY DANGEROUS INFECTION - full PPE immediately; bacteriological (blood, bubo aspirate, sputum): bipolar-staining rods; express diagnostics: DIF, RIF, PCR (results in 1-2 hours); biological test (animal); plague is IMMEDIATELY notifiable (WHO IHR)

Treatment: Streptomycin 30 mg/kg/day IM in 2 doses x10 days (traditional gold standard in Russia); gentamicin 5-7 mg/kg/day; doxycycline 200 mg/day x10 days; ciprofloxacin; chloramphenicol (meningeal/ocular); supportive (anti-shock); FULL ISOLATION

32. Tularemia

Etiology: Francisella tularensis (gram-negative coccobacillus); highly infectious - ID50 = 10-50 organisms; subspecies tularensis (type A, North America, most virulent) and holarctica (type B, Europe/Russia, less virulent); Category A bioterrorism agent

Epidemiology: zoonosis; reservoir: hares, rabbits, rodents; multiple transmission routes: contact (skinning/handling animals), bites (ticks - Ixodes, Dermacentor; mosquitoes; deerflies), inhalation (hay, grain dust), ingestion (water, food); summer months; Siberia, Central Russia, Volga region; NOT person-to-person

Pathogenesis: F. tularensis → skin/mucosa/lungs → facultative intracellular pathogen (survives in macrophages) → regional lymph nodes → granuloma formation → necrosis/suppuration (bubo) → bacteremia → systemic infection; strong cellular immunity develops

Clinical picture (forms):

Ulceroglandular (most common, 50-80%): primary ulcer at inoculation site + regional lymphadenopathy (bubo); fever, intoxication
Glandular (no ulcer): lymphadenopathy only
Oculoglandular: conjunctivitis (Parinaud) + preauricular lymphadenopathy
Oropharyngeal: tonsillitis + cervical lymphadenopathy
Abdominal: mesenteric lymphadenitis, intestinal tularemia
Pulmonary (most severe, inhalation): atypical pneumonia, pleuritis; high mortality untreated

Diagnosis: Francisella skin test (0.1 ml antigen ID, read 24-48h, ≥5mm induration = positive; appears from day 3-5); agglutination/RPHA (titer ≥1:100 diagnostic); ELISA (IgM/IgG); PCR; blood culture (hazardous - BSL-3!)

Treatment: Streptomycin 1 g x2/day IM x10-14 days (drug of choice); gentamicin; doxycycline 100 mg x2 x14-21 days (higher relapse rate); ciprofloxacin; bubo fluctuation → aspiration (not incision)

33. Rabies

Etiology: Rabies lyssavirus (Rhabdoviridae, RNA, bullet-shaped); invariably fatal once symptomatic

Epidemiology: zoonosis; transmitted via bite/scratch of infected animal (dog main reservoir globally; foxes/wolves in Russia; bats in Americas); virus in saliva; incubation inversely proportional to distance from CNS and inoculum size; no person-to-person (except transplantation)

Pathogenesis: virus enters peripheral nerve endings at bite → travels centripetally via axonal transport (3-4 mm/hour) → spinal cord → brain → replicates in neurons → Negri bodies (cytoplasmic inclusions in hippocampal neurons, Purkinje cells) → encephalitis → death; then travels centrifugally to salivary glands → virus in saliva before symptoms

Clinical presentation (4 stages):

Prodromal (2-4 days): paresthesias/pain at wound site (pathognomonic!), fever, anxiety, insomnia
Excitation (furious rabies, 80%): hydrophobia (painful laryngeal spasms on seeing/hearing water), aerophobia (breeze on face triggers spasm), agitation, hallucinations, autonomic instability, hypersalivation
Paralytic rabies (dumb rabies, 20%): ascending flaccid paralysis (Guillain-Barré-like), no hydrophobia
Coma → death: respiratory/cardiac failure; universal outcome without ICU

Diagnosis: clinical (post-exposure); DIF on corneal smear/skin biopsy (nuchal skin with nerve endings); brain biopsy post-mortem (Negri bodies, DIF); PCR (CSF, saliva, skin biopsy); serology (late)

Treatment:

Pre-exposure prophylaxis: vaccine x3 doses (day 0, 7, 21-28) for high-risk individuals; booster every 2-5 years
Post-exposure prophylaxis (PEP) (after bite):
1. Wound cleansing (soap + water 15 min, then antiseptic) - IMMEDIATELY
2. Rabies vaccine (KOKAV in Russia) - 1 ml IM on days 0, 3, 7, 14, 28, 90
3. Rabies immunoglobulin (RIG) - for WHO category III bites: infiltrate wound + remaining IM (20 IU/kg)
4. PEP has NO contraindications (pregnancy, immunosuppression)
No effective treatment once symptomatic; palliative care (Milwaukee Protocol - rare survivors, uncertain benefit)

34. HIV Infection: Etiology, Epidemiology, Pathogenesis, Classification, Clinical Presentation

Etiology: HIV-1 (global) and HIV-2 (West Africa); Lentivirus (Retroviridae); RNA virus with reverse transcriptase; envelope glycoproteins: gp120 (CD4 binding) + gp41 (membrane fusion); targets CD4+ T-lymphocytes (and monocytes, dendritic cells)

Epidemiology: parenteral (blood, IV drug use, transfusion, needlestick), sexual (unprotected, MSM highest risk), vertical (mother→child: pregnancy, labor, breastfeeding); >38 million living with HIV globally; Russia: IV drug use + heterosexual transmission predominate; NOT transmitted by casual contact

Pathogenesis:

gp120 binds CD4 + CCR5/CXCR4 (co-receptors) → membrane fusion (gp41) → viral RNA enters cell → reverse transcriptase makes DNA → integrase inserts proviral DNA into host genome (PERMANENT) → transcription → new virions → CD4 cell death
CD4 count progressively falls → immunodeficiency → opportunistic infections (OI) when CD4 <200/μl
Viral reservoir in resting CD4 cells, CNS, lymph nodes

Classification (WHO + Russian Pokrovsky):

WHO Stages:

Stage 1: asymptomatic or acute retroviral syndrome
Stage 2: minor conditions (seborrheic dermatitis, oral ulcers, herpes zoster, etc.)
Stage 3: moderate (oral candidiasis, pulmonary TB, bacterial pneumonia x2/year, etc.)
Stage 4 (AIDS): CD4 <200 or AIDS-defining illness (PCP, CMV, MAC, Kaposi, cerebral toxoplasmosis, PML, etc.)

Russian Pokrovsky Classification:

Stage 1: Incubation
Stage 2: Early (2A - acute retroviral syndrome; 2B - asymptomatic; 2C - PGL)
Stage 3: Subclinical
Stage 4: Secondary diseases (4A, 4B, 4C - by severity of OI)
Stage 5: Terminal (AIDS)

Clinical presentations:

Acute retroviral syndrome (ARS) (2-4 weeks after infection): "mono-like" - fever, pharyngitis, lymphadenopathy, rash (maculopapular), myalgia, arthralgia, night sweats; self-limiting in 2-4 weeks; high viral load, temporary CD4 drop
Persistent Generalized Lymphadenopathy (PGL): ≥2 extrainguinal sites, >1 cm, >3 months; no other explanation
Symptomatic HIV (pre-AIDS): oral candidiasis, recurrent herpes, weight loss, chronic diarrhea, hairy leukoplakia, pulmonary TB
AIDS-defining illnesses (CD4 <200): see next section

35. Epidemiology and Prevention of HIV

Epidemiology (see Question 34 for routes):

High-risk groups: IV drug users (sharing needles), MSM (men who sex with men), sex workers, multiple partners, STI history
Transmission rates per exposure: needle sharing ~1%; blood transfusion ~95%; receptive anal sex ~0.5-3%; mother-to-child (untreated) ~25-40%
Viral load is key determinant of transmission (undetectable = untransmittable - U=U principle)
Window period (infection → detectable antibodies): 3-12 weeks (4th gen tests: 2-4 weeks)

Prevention:

Behavioral: safe sex (condoms), sterile needles/harm reduction programs, testing of blood/organs
Pre-exposure prophylaxis (PrEP): tenofovir/emtricitabine (Truvada) daily for high-risk HIV-negative individuals; >90% effective
Post-exposure prophylaxis (PEP): 3-drug ART for 28 days; start within 72 hours of exposure; healthcare workers after needlestick
PMTCT (Prevention of mother-to-child transmission): ART during pregnancy + labor; elective C-section if viral load >1000; avoid breastfeeding; neonatal prophylaxis (AZT or nevirapine)
No vaccine available yet
HIV testing: routine screening in pregnancy, blood donors; voluntary counseling & testing (VCT) for high-risk

36. Laboratory Diagnostics of HIV and Opportunistic Diseases

HIV diagnostics:

4th generation ELISA (Ag/Ab combo): detects both HIV Ag (p24) and antibodies → shortens window period; screening test
Confirmatory Western blot (immunoblot): detects antibodies to specific HIV proteins (gp160, gp120, p24, etc.); positive = ≥2 of gp160/120/41 bands
HIV RNA PCR (viral load): quantitative; used for monitoring treatment; also for acute infection (window period); expressed as copies/ml
CD4 count: absolute number/μl; determines staging and OI prophylaxis thresholds

CD4 thresholds:

<500: start ART (in most guidelines, START at any CD4)
<200: PCP prophylaxis (cotrimoxazole); AIDS diagnosis
<100: MAC prophylaxis (azithromycin); risk of CMV, toxoplasmosis
<50: CMV retinitis, MAC, disseminated fungal infections

Opportunistic disease diagnostics:

PCP (Pneumocystis jirovecii): chest X-ray (bilateral interstitial "ground glass"), LDH ↑; bronchoalveolar lavage (BAL) with DIF/PCR; β-1,3-glucan ↑
Toxoplasmosis (cerebral): MRI brain (multiple ring-enhancing lesions, basal ganglia); Toxoplasma IgG+; response to empirical treatment (diagnostic and therapeutic)
CMV retinitis: fundoscopy; CMV PCR blood/aqueous humor
Cryptococcal meningitis: India ink stain CSF; cryptococcal antigen (CrAg) in CSF/blood; CSF culture
MAC (Mycobacterium avium complex): blood cultures; bone marrow biopsy
TB: Mantoux/IGRA; AFB smear; culture; molecular (Xpert MTB/RIF)
Kaposi sarcoma: clinical (violaceous skin/mucosal lesions) + biopsy; HHV-8 serology

37. HIV and Opportunistic Diseases: Principles of Therapy

Antiretroviral therapy (ART) principles:

Goal: viral suppression to undetectable (<50 copies/ml), CD4 restoration, prevent OI, prevent transmission
Start ART in ALL HIV+ patients regardless of CD4 (since 2015 guidelines)
First-line regimen (Russia/WHO): 2 NRTIs + 1 INSTI:
- Tenofovir (TDF) + Emtricitabine (FTC) + Dolutegravir (DTG) - preferred
- Alternative: TDF/FTC + Efavirenz (NNRTI)
Drug classes: NRTI (nucleoside RT inhibitors), NNRTI, PI (protease inhibitors), INSTI (integrase strand transfer inhibitors), CCR5 antagonists, fusion inhibitors
Adherence is critical (>95% required to prevent resistance)
Immune reconstitution inflammatory syndrome (IRIS): worsening of OI paradoxically when starting ART; treat underlying OI, consider corticosteroids

OI treatment:

PCP: cotrimoxazole (TMP-SMX) high dose x21 days + prednisolone (if PaO2 <70 mmHg)
Toxoplasmosis: pyrimethamine + sulfadiazine + folinic acid x6 weeks; then secondary prophylaxis until CD4 >200 x3 months
CMV retinitis: ganciclovir/valganciclovir induction x21 days → maintenance
Cryptococcal meningitis: amphotericin B + flucytosine x2 weeks → fluconazole consolidation/maintenance
MAC: azithromycin + ethambutol ± rifabutin
TB/HIV: treat TB (rifampicin-based) + start ART 2-8 weeks after TB treatment initiation

38. Toxoplasmosis

Etiology: Toxoplasma gondii (obligate intracellular protozoan); definitive host: cat family; forms: tachyzoites (acute), bradyzoites in tissue cysts (chronic), oocysts (shed in cat feces)

Epidemiology: worldwide; prevalence 10-80% seropositive (Russia: 30-40%); routes: ingestion of oocysts (cat feces-contaminated soil, unwashed vegetables), ingestion of tissue cysts (undercooked meat - pork, lamb), congenital (transplacental); blood transfusion, organ transplant (less common); NOT person-to-person

Pathogenesis: tachyzoites disseminate hematogenously → invade any nucleated cell → multiply → cell lysis → form bradyzoite cysts (brain, eye, muscle) → lifelong latency; in immunocompromised: cysts rupture → disseminated toxoplasmosis; congenital: maternal primary infection → transplacental passage → fetal damage

Clinical features:

Immunocompetent (acquired): usually asymptomatic; lymphadenopathy (posterior cervical, painless - like mono); mild fever, fatigue; self-limiting
Immunocompromised (reactivation, CD4 <100): cerebral toxoplasmosis (encephalitis) - headache, focal neurological deficits, seizures, ring-enhancing lesions on MRI (basal ganglia, corticomedullary junction), fever; chorioretinitis; pneumonitis; myocarditis
Congenital: classic triad: hydrocephalus + chorioretinitis + intracranial calcifications (periventricular); also: microcephaly, seizures, psychomotor delay; or subclinical at birth → late manifestations

Diagnosis: serology (Sabin-Feldman dye test, ELISA IgM/IgG); IgM = recent; IgG avidity test (high avidity = infection >3 months ago, excludes acute in pregnancy); MRI brain (cerebral toxoplasmosis); PCR (CSF, amniotic fluid, blood); clinical response to treatment (for cerebral toxo)

Treatment: Pyrimethamine (loading 200 mg, then 50-75 mg/day) + sulfadiazine (4-6 g/day) + folinic acid (25 mg/day to prevent bone marrow suppression) x6 weeks; or pyrimethamine + clindamycin; secondary prophylaxis until CD4 >200 for 3-6 months; congenital: pyrimethamine + sulfadiazine x12 months; prevention in pregnancy: spiramycin (reduces transmission)

39. Anthrax

Etiology: Bacillus anthracis (gram-positive, spore-forming rod); spores extremely resistant (decades in soil); produces anthrax toxin complex (PA + LF = lethal toxin; PA + EF = edema toxin) and polypeptide capsule (anti-phagocytic); Category A bioterrorism agent

Epidemiology: zoonosis; soil-based natural foci; herbivores (cattle, sheep, goats) die and contaminate soil; human routes: cutaneous (contact with infected animals/hides/wool), inhalation (spores in dust - woolsorters disease), gastrointestinal (undercooked infected meat), injection (contaminated heroin); endemic foci in Russia (Caucasus, Siberia, Volga); NOT person-to-person (cutaneous)

Pathogenesis: spores germinate → vegetative bacteria → toxin production → PA binds cell receptors → LF (metalloprotease) cleaves MAPKK → kills macrophages/neutrophils → LF enters blood → massive cytokine storm + hemorrhagic necrosis; EF (adenylate cyclase) → ↑ cAMP → edema, impaired phagocytosis; capsule prevents phagocytosis; inhalational: spores phagocytosed by alveolar macrophages → transported to mediastinal LN → hemorrhagic mediastinitis

Clinical picture:

Cutaneous (98% of cases): painless papule → vesicle → black necrotic eschar (malignant pustule) with characteristic non-pitting gelatinous edema; usually benign with treatment; "coal" (anthrax = coal in Greek) appearance
Inhalational: initial flu-like → sudden deterioration: mediastinal widening (X-ray) + hemorrhagic pleural effusions + ARDS + septicemia; 80-90% mortality even with treatment; widened mediastinum on CXR = key sign
Gastrointestinal: abdominal pain, bloody diarrhea, ascites, septicemia; high mortality
Meningeal: hemorrhagic meningitis; rapid death

Diagnosis: skin swab/blister fluid/blood culture (BSL-3!); gram stain (large gram-positive rods in chains); DIF with fluorescent antibodies (rapid); PCR; serology (Ascoli's precipitation test on hides/animal materials); CXR (mediastinal widening in inhalational)

Treatment: Ciprofloxacin 400 mg IV x2/day (or 500 mg PO x2/day) x60 days (long course - spores may remain dormant); doxycycline as alternative; penicillin G (if susceptible); anthrax antitoxin (raxibacumab, obiltoxaximab) for inhalational/systemic; post-exposure prophylaxis: ciprofloxacin + anthrax vaccine x60 days

40. Sepsis (already covered in ITS - key points specific to sepsis)

Definition (Sepsis-3, 2016): life-threatening organ dysfunction caused by dysregulated host response to infection; SOFA score ≥2 increase

Etiology: any pathogen; gram-negative (E. coli, Klebsiella, Pseudomonas) most common; gram-positive (S. aureus, Streptococcus); fungal (Candida) in immunocompromised; no pathogen identified in 30-50%

Epidemiology: nosocomial and community-acquired; ICU-associated; immunocompromised, elderly, post-surgery, burns, IV catheters

Pathogenesis: infection → PAMP recognition (TLR) → massive cytokine release (TNF-α, IL-1, IL-6) → endothelial activation → vasodilation, capillary leak → distributive shock → microvascular thrombosis → organ ischemia → MOF

Classification:

Sepsis: organ dysfunction from infection
Septic shock: sepsis + vasopressor-requiring hypotension (MAP <65) + lactate >2 mmol/l despite adequate fluids; mortality ~40%

Clinical: fever (or hypothermia <36°C), tachycardia (>90), tachypnea (>20), altered consciousness; organ dysfunction markers: ↑ creatinine, ↑ bilirubin, ↓ platelets, ↑ lactate, ↓ GCS

Diagnosis: SOFA score; blood cultures x2 (before antibiotics); procalcitonin (>2 ng/ml bacterial); lactate; CBC, metabolic panel, coagulogram; source imaging

Treatment ("Hour-1 Bundle"):

Blood cultures BEFORE antibiotics
Broad-spectrum antibiotics WITHIN 1 HOUR (early = best outcome)
30 ml/kg crystalloid bolus for hypotension/lactate ≥4
Vasopressors (norepinephrine, MAP ≥65)
Re-measure lactate after fluids
Source control (drain abscess, remove catheter)
Corticosteroids (hydrocortisone 200 mg/day) for refractory shock

DIFFERENTIAL DIAGNOSIS SECTION

41. Differential Diagnosis of Acute Febrile Illnesses; Pathogenesis of Fever; Types of Fever

Pathogenesis of fever: Infection/PAMP → macrophage activation → pyrogens (IL-1, IL-6, TNF-α, PGE2) → hypothalamus set-point ↑ → heat conservation (vasoconstriction, shivering) + heat production → fever

Types of fever by temperature: subfebrile (37-38°C), febrile (38-39°C), high (39-40°C), hyperpyrexia (>40°C)

Fever curve types:

Type	Pattern	Disease
Continuous (febris continua)	Variation <1°C/day	Typhoid, lobar pneumonia
Remittent (remittens)	Variation >1°C, never normal	Most infections
Intermittent (intermittens)	Normal periods + fever	Malaria (tertian/quartan), sepsis
Hectic (septic)	>2°C swings, chills/sweats	Sepsis, abscess
Undulant	Waves of fever	Brucellosis, lymphoma
Recurrent (recurrens)	Fever-free periods (days) then return	Relapsing fever (Borrelia recurrentis)
Inverse	AM temp > PM temp	Miliary TB

DD of acute febrile illness:

Fever + rash → see exanthema section
Fever + meningism → bacterial/viral meningitis
Fever + jaundice → viral hepatitis, leptospirosis, malaria
Fever + lymphadenopathy → mononucleosis, toxoplasmosis, tularemia, HIV
Fever + diarrhea → intestinal infections
Fever + respiratory symptoms → ARVI, influenza, pneumonia
Fever returning from tropics → malaria (first!), typhoid, dengue, viral hemorrhagic fever

42. Differential Diagnosis of Exanthema and Enanthema

Exanthema (skin rash):

Disease	Rash type	Location	Timing	Features
Measles	Maculopapular	Hairline → face → trunk → extremities (centrifugal)	Day 3-4 of fever	Koplik spots (enanthema) before rash
Rubella	Fine maculopapular	Face → trunk (faster than measles)	Day 1-2	Postauricular/suboccipital LN; mild
Scarlet fever	Punctate erythema (sandpaper)	Trunk, spares perioral (circumoral pallor)	Day 1-2	Pastia lines, strawberry tongue
Chickenpox	Polymorphic vesicular (all stages)	Centripetal (trunk > extremities), scalp	Day 1-2	"Starry sky", pruritic
Typhus	Roseolae-petechial	Trunk (NOT face/palms/soles)	Day 4-5
Typhoid	Rose spots	Trunk	Day 8-10	Few (5-20), fades on pressure
Meningococcemia	Petechial/stellate hemorrhagic	Buttocks/legs, any	Hours	NON-blanching, expanding
Secondary syphilis	Roseolae-papular	Palms + soles involved!	Weeks later	Painless
Enterovirus	Maculopapular	Variable	Early	HFMD (hands/feet/mouth)

Enanthema (mucous membrane):

Koplik spots: pathognomonic for measles; white/bluish spots on buccal mucosa opposite lower molars; appear 1-2 days BEFORE rash
Forscheimer spots: soft palate petechiae - rubella
Palatal petechiae: EBV mononucleosis
Strawberry tongue: scarlet fever, Kawasaki
Aphthous ulcers: enterovirus (herpangina, HFMD)

43. DD of Diseases with Gastroenteritis Syndrome

Disease	Onset	Vomiting	Diarrhea	Fever	Key features
PTI (Staph)	1-6 hours	Prominent, early	Watery	Low/absent	Group outbreak, specific food, rapid onset
Salmonellosis	6-72 hours	Yes	Green "swamp mud"	Yes	Contaminated eggs/poultry
Cholera	Hours	Yes, late	Rice-water, massive	No	Rapid dehydration, no pain
Rotavirus	1-3 days	Prominent	Watery, yellow	Moderate	Children, winter
Norovirus	1-2 days	Prominent	Watery	Low	All ages, outbreaks
ETEC	1-3 days	Yes	Watery (traveler's diarrhea)	Low	Travel history

44. DD of Diseases with Colitis Syndrome

Disease	Diarrhea	Blood	Tenesmus	Fever	Diagnosis
Shigellosis	Small volume, frequent	Mucus + blood	Yes (severe)	High	Stool culture, sigmoidoscopy
Salmonellosis (colitic)	Moderate	Sometimes	Mild	Yes	Stool culture
Campylobacteriosis	Bloody	Yes	Mild	Yes	Stool culture
Amoebiasis	Intermittent, "raspberry jelly"	Yes	Mild-moderate	Low/absent	Trophozoites in stool, serology
Nonspecific ulcerative colitis (NUC)	Bloody	Yes	Yes	Low	Colonoscopy, biopsy, chronic
Crohn's disease	Variable	Variable	Variable	Low	Colonoscopy, terminal ileum
Antibiotic-associated (C. difficile)	Watery/bloody	Sometimes	Variable	Yes	CDT/PCR, hospital/antibiotic history

45. Differential Diagnosis of Diarrhea

Secretory: watery, large volume, osmotic gap <50, persists with fasting (cholera, ETEC, V. cholerae)

Inflammatory/invasive: small volume, blood/mucus, fever, tenesmus (shigellosis, salmonellosis, amoebiasis, C. difficile)

Osmotic: stops with fasting (lactase deficiency, sorbitol, Mg)

Acute bloody diarrhea: shigellosis, EHEC (O157:H7) → HUS risk, salmonellosis, campylobacter, amoebiasis, ischemic colitis

Key differentials: antibiotic history → C. difficile; travel → traveler's diarrhea, amoebiasis, cholera; immunocompromised → CMV colitis, Cryptosporidium, MAC

46. DD of Viral Hepatitis with Jaundice of Other Etiology

Types of jaundice:

Hepatocellular: ↑ ALT/AST >10x, ↑ both direct + indirect bilirubin; urine dark (bilirubinuria); stools pale
Obstructive (cholestatic): ↑ ALP >3x, ↑ GGT, ↑ direct bilirubin; bile duct dilation on ultrasound
Hemolytic (prehepatic): ↑ indirect bilirubin; ↑ reticulocytes; ↓ haptoglobin; dark urine (hemoglobinuria in intravascular hemolysis)

Condition	Key differentiators
Viral hepatitis A	Anti-HAV IgM, epidemic/contact history, prodromal symptoms, ↑ ALT
Viral hepatitis B	HBsAg+, risk factors (sexual, parenteral), anti-HBc IgM
Viral hepatitis C	anti-HCV+, HCV RNA, parenteral risk factors, mild acute illness
Leptospirosis	Jaundice + ARF + hemorrhage (Weil's); MAT; myalgia, zoonotic history
Infectious mononucleosis	EBV markers, atypical lymphocytes, lymphadenopathy
Drug-induced hepatitis	Drug history (paracetamol, TB drugs, statins); negative serology
Alcoholic hepatitis	AST:ALT >2:1; GGT ↑↑; alcohol history
Obstructive (gallstones, pancreatic cancer)	ALP ↑↑, US shows duct dilation, no fever/ALT elevation initially
Hemolytic anemia	↑ indirect bilirubin, ↑ reticulocytes, anemia, ↑ LDH
Autoimmune hepatitis	ANA, anti-SMA, SPEP (↑ IgG), F: typically female, young/middle

47. Differential Diagnosis of Lymphadenopathy Syndrome

Condition	Node characteristics	Associated features	Diagnosis
Infectious mononucleosis (EBV)	Posterior cervical, bilateral, tender	Pharyngitis, splenomegaly, atypical lymphocytes, rash on ampicillin	Monospot, EBV serology
CMV mononucleosis	Less prominent	Mild pharyngitis, hepatitis	CMV IgM, PCR
HIV (acute/PGL)	Multiple sites, bilateral	Risk factors, constitutional symptoms	HIV Ab/Ag, viral load
Toxoplasmosis	Posterior cervical, isolated, painless	Mild fever, no pharyngitis	Toxoplasma IgM
Tularemia	Regional, suppurative bubo	Ulcer at entry site, systemic	Serology, Francisella skin test
Bubonic plague	Massive, exquisitely tender bubo (inguinal/axillary)	Extreme intoxication	Culture, PCR (BSL-3!)
Brucellosis	Generalized, moderate	Undulant fever, sweats, sacroiliitis	Wright agglutination
TB lymphadenitis	Cervical (scrofula), firm, may drain	Contact with TB	Mantoux, culture, biopsy
Lymphoma (Hodgkin's)	Rubbery, painless, non-tender, progressively enlarging	Night sweats, weight loss, fever (B-symptoms)	Biopsy
Reactive (bacterial infection)	Regional, tender, warm	Local infection	Antibiotics response

48. DD of Serous and Purulent Meningitis

Feature	Serous (viral) meningitis	Purulent (bacterial) meningitis
Onset	Subacute (days)	Acute/sudden (hours)
Fever	Moderate (38-39°C)	High (39-40°C)
Meningeal signs	Moderate	Severe
Consciousness	Usually preserved	Often altered
CSF color	Clear/opalescent	Turbid/purulent
CSF pressure	Moderately ↑	↑↑
Pleocytosis	100-1000 cells (lymphocytes)	1000-100,000 (neutrophils >80%)
Protein	0.5-1.5 g/l	1-10 g/l
Glucose	Normal (>50% of blood)	Markedly ↓ (<50% blood)
Gram stain	Negative	Positive (50%)
Culture	Negative	Positive (80%)
Etiology	Enterovirus (most common), HSV-2, HIV, mumps	Meningococcus, pneumococcus, H. influenzae (children), Listeria (immunocompromised, elderly)
Treatment	Symptomatic (± acyclovir if HSV suspected)	Immediate IV antibiotics + dexamethasone

49. Meningeal Syndrome and Encephalitic Syndrome

Meningeal syndrome (meningeal irritation):

Symptoms: headache (diffuse, intense, "worst of life"), photophobia, phonophobia, nausea/vomiting
Signs:
- Nuchal rigidity: resistance to passive neck flexion
- Kernig: flex hip 90°, cannot extend knee (>135°)
- Brudzinski (upper): neck flexion → knee/hip flexion bilaterally
- Brudzinski (lower): press on one knee → contralateral leg flexes
- Lasegue (lower limbs)
- In infants: bulging fontanelle, opisthotonos, high-pitched cry

Encephalitic syndrome (brain parenchyma involvement):

Symptoms: altered consciousness (confusion → stupor → coma), personality/behavioral changes, disorientation
Signs: focal neurological deficits (hemiparesis, aphasia, cranial nerve palsies), seizures, movement disorders, pyramidal signs
Specific syndromes:
- Temporal lobe encephalitis (HSV): personality change, memory impairment, olfactory hallucinations, temporal focus on EEG/MRI
- Brainstem encephalitis: cranial nerve palsies, ataxia (TBE, EV-A71)
- Cerebellitis: ataxia (VZV)

CSF interpretation (mandatory in meningeal/encephalitic syndrome):

Normal: clear, 0-5 lymphocytes, protein 0.15-0.45 g/l, glucose 2.8-3.9 mmol/l
Contraindications to LP: papilledema, focal signs, low GCS (herniation risk) → CT first

50. DD of Diseases Involving the Oropharynx

Condition	Tonsillar/pharyngeal findings	Fever	Key features
Streptococcal tonsillitis	Yellow-white exudate on tonsils, within tonsil margin	High	Severe pain, submandibular LN, rapid strep test
Diphtheria	Gray-white membrane BEYOND tonsil, bleeds on removal	Low-moderate	Spreading membrane, bull neck (toxic), sweet odor
Infectious mononucleosis	Exudative tonsillitis, palatal petechiae	Moderate	Posterior LN > anterior, splenomegaly, ampicillin rash, monospot
Vincent's angina (fusobacterium)	Unilateral gray-green pseudomembrane + ulcer	Moderate	Poor oral hygiene, smokers, foul odor, gram stain shows fusiform + spirochetes
Herpangina (enterovirus)	Vesicles/ulcers on soft palate/anterior tonsillar pillars	High	Children, summer, painful
Aphthous stomatitis (HSV)	Multiple shallow ulcers, gingivostomatitis	High (primary)	Very painful, first episode
Candidal pharyngitis	White curd-like plaques (scrape off leaving red), not adherent	Variable	Immunocompromised, antibiotic use, diabetes
Peritonsillar abscess	Unilateral bulging of peritonsillar space, uvula displaced	High	Hot potato voice, trismus, requires drainage

51. DD of Catarrhal Respiratory Syndrome and Atypical Pneumonia

Catarrhal respiratory syndrome (upper respiratory tract):

Disease	Key differentiator
Rhinovirus (common cold)	Rhinorrhea >> fever, minimal systemic symptoms
Influenza	Sudden high fever, severe myalgia, minimal catarrh initially
Parainfluenza	Croup in children (barking cough, stridor)
Adenovirus	Pharyngoconjunctival fever (tonsillitis + conjunctivitis)
COVID-19	Anosmia/ageusia, potential pneumonia, PCR
RSV	Bronchiolitis in infants; COPD exacerbation in elderly

Atypical pneumonia (walking pneumonia, radiological > clinical severity):

Pathogen	Key features	Diagnosis	Treatment
Mycoplasma pneumoniae	Young adults, dry cough, headache, gradual onset, extrapulmonary (hemolytic anemia, rash)	Cold agglutinins ↑; PCR; serology	Azithromycin or doxycycline
Chlamydophila pneumoniae	Adults, pharyngitis + gradual pneumonia	PCR, serology	Doxycycline or azithromycin
Legionella pneumophila	Air conditioning/water cooling towers, hyponatremia (↓ Na+), GI symptoms, hepatitis, high fever; Pontiac fever (milder form)	Urinary Legionella antigen; PCR; serology (Pontiac: seroconversion)	Fluoroquinolones or azithromycin
Influenza pneumonia	Rapid ARDS progression, bilateral GGO, influenza season	Influenza PCR	Oseltamivir + supportive
COVID-19 pneumonia	SpO2 drop, bilateral GGO, lymphopenia, ↑ D-dimer	PCR, CT chest	Dexamethasone, O2, anticoagulation

Quick Reference Card - Part 2

Disease	Key Diagnostic	Key Treatment
Ascariasis	Kato-Katz stool smear	Albendazole 400 mg single dose
Enterobiasis	Graham scotch tape test (AM)	Mebendazole 100 mg × 2 doses (2 wks apart)
Diphyllobothriasis	Stool eggs + B12 level	Praziquantel 25 mg/kg; B12 supplement
Opisthorchiasis	Duodenal/stool eggs + ELISA	Praziquantel 75 mg/kg/day (3 doses)
Echinococcosis	Ultrasound + ELISA	Surgery + albendazole
Diphtheria	Culture + toxigenicity	ADS serum (URGENT) + penicillin
Influenza	PCR NPS	Oseltamivir within 48h
Lyme disease	ELISA → Western blot	Doxycycline (stage I); ceftriaxone IV (neuro)
TBE	IgM serology	Supportive; TBE-Ig prophylactic
Typhus	Weil-Felix + ELISA	Doxycycline
Plague	Culture + DIF (BSL-3!)	Streptomycin/ciprofloxacin
Tularemia	Francisella skin test + serology	Streptomycin
Rabies	Clinical + DIF	PEP (vaccine + RIG); preventable if treated before symptoms
Meningococcemia	Hemorrhagic rash + clinical	Penicillin G STAT + corticosteroids
Malaria	Thick/thin blood smear	P. falciparum: artemisinin-based; P. vivax: chloroquine + primaquine
HIV	4th gen ELISA → Western blot	TDF/FTC + DTG (ART)
Sepsis	Blood cultures + SOFA	Broad-spectrum antibiotics within 1 hour

Key Russian exam mnemonics and buzzwords to remember:

Bezredka desensitization before ANY serum administration
Gromashevsky classification: intestinal, respiratory, blood, integument
Pokrovsky HIV classification (Russian standard)
"Bull neck" = toxic diphtheria
"Axillary petechiae" = HFRS
"Rice-water stools" = cholera
"Raspberry jelly stools" = amoebiasis
"Starry sky" rash = varicella
Drooping head = TBE (poliomyelitis-like form)
Ampicillin rash = infectious mononucleosis
B12-deficiency anemia + tapeworm = D. latum
Eosinophilia >30% + muscle pain = trichinellosis

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