# Infectious Disease Exam Answers — 5th Year Medical Faculty --- ## Q1. The concept of an infectious disease, patterns of development of the infectious process, its forms, periods. **Infectious disease** = a specific reaction of the macroorganism to invasion of a pathogenic microorganism, characterized by a complex of specific clinical and pathological manifestations and a contagious (epidemic) process. **Infectious process** = interaction of pathogen + macroorganism + environment. **Forms:** - Manifest (typical/atypical) - Inapparent (subclinical) - Latent (dormant) - Carrier state (acute, chronic, transient) **Periods of infectious disease:** 1. **Incubation** – from entry of pathogen to first symptoms; no clinical signs; patient may be infectious 2. **Prodromal (initial)** – non-specific symptoms (fever, malaise, headache) 3. **Peak (height)** – full clinical picture, specific syndromes appear 4. **Convalescence** – symptoms subside; may have relapse or complication 5. **Outcomes:** recovery, chronic form, carrier state, death --- ## Q2. Main properties of microorganisms causing the infectious process, their variability. **Key properties of pathogens:** - **Pathogenicity** – potential to cause disease (species-level trait) - **Virulence** – degree of pathogenicity of a specific strain - **Toxigenicity** – exotoxin (proteins, highly specific, neutralized by antitoxin) vs. endotoxin (LPS of gram-negative bacteria) - **Invasiveness** – ability to penetrate tissues - **Adhesins** – surface molecules for host attachment - **Aggressins** – enzymes (hyaluronidase, coagulase, neuraminidase) overcoming host defenses **Variability:** - Mutation (spontaneous/induced) - Recombination, transduction, transformation - R-plasmid transfer → antibiotic resistance - Antigenic variability (drift/shift in influenza) - L-form transformation → chronic infections --- ## Q3. Main factors protecting the macroorganism from pathogenic infection. **Non-specific (innate) defenses:** - Skin and mucous membrane barriers - Ciliary clearance (respiratory tract) - Normal microbiota (colonization resistance) - Phagocytosis (neutrophils, macrophages) - Complement system (classical, alternative, lectin pathways) - Natural killer cells - Acute-phase proteins (CRP, fibrinogen, ferritin) - Lysozyme, secretory IgA, defensins, lactoferrin - Fever (elevated temperature inhibits pathogen growth) - Inflammation **Specific (adaptive) defenses:** - Humoral immunity: B cells → plasma cells → antibodies (IgM, IgG, IgA, IgE) - Cellular immunity: T-helper (CD4), cytotoxic T (CD8) cells - Immunological memory --- ## Q4. Classification of infectious diseases. **By etiology:** - Bacterial, viral, fungal (mycoses), protozoal, helminthic, prion **By source of infection (reservoir):** - Anthroponoses (humans only) – typhoid, dysentery, HIV - Zoonoses (animals + humans) – brucellosis, rabies, plague - Sapronoses (environment) – legionellosis, tetanus **By transmission mechanism:** - Fecal-oral (enteric) – cholera, typhoid, hepatitis A - Airborne (respiratory) – influenza, measles, TB - Contact (wound) – tetanus, rabies - Blood (hemotransmissive) – HIV, hepatitis B/C - Vector-borne (transmissive) – malaria, typhus, tick-borne encephalitis - Vertical (transplacental) – rubella, CMV, toxoplasmosis **By organ system affected:** - Intestinal, respiratory, blood, tegumentary (skin/mucous membranes) --- ## Q5. Principles of diagnostics of infectious diseases, main clinical syndromes, early diagnostics. **Principles:** 1. Clinical (history, physical exam) 2. Epidemiological (contact, travel, occupation, vaccination history) 3. Laboratory and instrumental **Key clinical syndromes:** - Fever + intoxication (most infections) - Exanthema (rash) – measles, scarlet fever, typhus - Diarrhea/gastroenteritis – salmonellosis, cholera - Jaundice – viral hepatitis - Meningeal syndrome – meningitis, encephalitis - Lymphadenopathy – mononucleosis, HIV, tularemia - Catarrhal (respiratory) – influenza, ARI - Hemorrhagic syndrome – viral hemorrhagic fevers, meningococcemia **Early diagnosis:** - Epidemiological anamnesis is key - CBC: leukocytosis (bacterial), leukopenia + lymphocytosis (viral) - Immediate notification for quarantine diseases --- ## Q6. Role of specific research methods in diagnosis of infectious diseases. **Bacteriological (culture):** - Blood, stool, urine, CSF, swabs cultured on selective media - Gold standard for bacterial infections - Results in 24–72 hours **Virological:** - Cell culture, embryo inoculation - Isolation of virus from blood, secretions **Parasitological:** - Thick/thin blood smear (malaria) - Microscopy of stool (helminths, protozoa) **Molecular (PCR):** - Detects pathogen DNA/RNA - High sensitivity and specificity - Useful early, before antibodies develop (HIV, hepatitis C, herpes) - Real-time PCR for quantification (viral load) --- ## Q7. Role of serological and immunological methods in diagnosis. **Serological tests** detect antibodies (Abs) or antigens (Ags) in patient serum: - **ELISA** (enzyme-linked immunosorbent assay) – IgM (acute) vs. IgG (past/chronic) detection; most widely used - **RIA** (radioimmunoassay) - **Agglutination tests** (Widal for typhoid, Weil-Felix for rickettsia) - **Complement fixation** (CFT) - **Neutralization test** (virus-specific) - **Immunofluorescence** (IFA/RNIF/ELISA) – direct or indirect - **Western blot** – confirmatory for HIV **Immunological:** - T/B lymphocyte counts (CD4 in HIV) - Interferons, cytokines (IL-6, TNF for sepsis) - Immunoelectrophoresis **Principles:** 4-fold rise in antibody titer in paired sera (acute + convalescent, 2–3 wks apart) = diagnostic --- ## Q8. Role of biochemical and instrumental methods in infectious disease clinic. **Biochemical:** - LFTs (ALT, AST, bilirubin, ALP, GGT) → hepatitis, liver failure - Urea, creatinine → AKI in leptospirosis, HFRS - Electrolytes (K+, Na+) → dehydration, cholera - Coagulation (PT, APTT, fibrinogen, D-dimers) → DIC - CRP, procalcitonin → bacterial vs. viral infection, sepsis - Blood glucose → altered consciousness, sepsis - Lactate → tissue hypoperfusion in sepsis/shock **Instrumental:** - Chest X-ray → pneumonia, TB, plague - Abdominal ultrasound → hepatosplenomegaly, abscess - CT/MRI brain → encephalitis, cerebral malaria, tuberculoma - ECG → myocarditis (diphtheria, viral) - FGDS → colitis, esophageal candidiasis (HIV) - Lumbar puncture (CSF analysis) → meningitis --- ## Q9. Role of skin-allergic and biological tests in diagnosis. **Skin-allergic tests** (type IV hypersensitivity – delayed): - **Mantoux test (tuberculin test)** – PPD intradermal; induration ≥10 mm positive → TB sensitization (not disease) - **IGRA (QuantiFERON)** – in vitro alternative - **Tularin test** – tularemia - **Leishmanin (Montenegro)** – leishmaniasis - **Brucellin test (Burne)** – brucellosis - **Toxoplasmin test** – toxoplasmosis - **Histoplasmin, coccidioidin** – endemic mycoses **Biological tests:** - Inoculation of laboratory animals with patient material - Confirm pathogenicity; used for plague, anthrax, tularemia - Largely replaced by PCR and culture today --- ## Q10. Principles of complex therapy of infectious patients. **4 pillars:** 1. **Etiotropic** – targeting the causative agent (antibiotics, antivirals, antiparasitics) 2. **Pathogenetic** – correcting pathological processes (rehydration, detoxification, anti-DIC) 3. **Symptomatic** – alleviating symptoms (antipyretics, analgesics, antiemetics) 4. **Immunocorrective** – immunoglobulins, interferons, immunostimulants **General principles:** - Hospitalization for severe/quarantine cases - Bed rest during acute phase - Diet (table №4 for diarrhea, №5 for hepatitis) - Adequate fluid intake - Monitoring of vital signs and organ function - Prevent nosocomial spread (isolation, PPE) --- ## Q11. Methods of etiotropic therapy of infectious diseases. **Antibacterials:** - Beta-lactams (penicillins, cephalosporins, carbapenems) - Aminoglycosides (gentamicin, amikacin) - Fluoroquinolones (ciprofloxacin, levofloxacin) - Tetracyclines (doxycycline) – rickettsiae, brucella, chlamydia - Macrolides (azithromycin) – atypical pneumonia - Glycopeptides (vancomycin) – MRSA, C. difficile **Antivirals:** - Acyclovir/valacyclovir – herpes simplex, VZV - Ganciclovir – CMV - Oseltamivir (Tamiflu) – influenza - DAAs (sofosbuvir, NS5A inhibitors) – Hepatitis C (>95% SVR) - Tenofovir/emtricitabine + PI or INSTI – HIV (ART) - Entecavir, tenofovir – Hepatitis B **Antiparasitics:** - Chloroquine, artemisinin-based – malaria - Metronidazole – amebiasis, giardia, anaerobes - Pyrimethamine + sulfadiazine – toxoplasmosis - Albendazole – helminths **Antifungals:** - Fluconazole – candidiasis - Amphotericin B – severe systemic mycoses **Key principle:** Start empirically based on likely pathogen; narrow spectrum once culture/sensitivity known. --- ## Q12. Serotherapy of infectious diseases and its possible complications. **Serotherapy** = passive immunization using ready-made antibodies from animals or humans. **Types:** - **Antitoxic sera** – diphtheria antitoxin (horse), botulinum antitoxin (horse), tetanus antitoxin (TAT) - **Antimicrobial sera** – anti-plague, anti-anthrax (less used now) - **Immunoglobulins (human)** – anti-rabies, anti-hepatitis B, anti-tetanus (TIG), anti-varicella (VZIG), intravenous immunoglobulin (IVIG) - **Monoclonal antibodies** – newer agents **Complications:** - **Anaphylactic shock** – immediate (IgE-mediated); treat with epinephrine 0.1% 0.5 mL IM - **Serum sickness** – 7–14 days after horse serum; immune complex disease; urticaria, arthralgia, fever, lymphadenopathy; treat with antihistamines, corticosteroids - Local reactions: pain, induration at injection site **Precautions:** - Sensitivity test (Bezredka method) before horse serum: 0.1 mL of diluted serum SC → observe 30 min → if negative, give full dose - Always have resuscitation ready --- ## Q13. Methods of pathogenetic therapy of infectious diseases. **Rehydration and detoxification (most important):** - Oral rehydration: ORS (glucose-salt solution) – mild/moderate dehydration - IV rehydration: Ringer's lactate, 0.9% NaCl, trisol – severe dehydration (cholera, gastroenteritis) - Volume: replace deficit + ongoing losses + maintenance **Detoxification:** - IV colloids/crystalloids (saline, glucose) - Hemodez, reopoliglyukin (dextran) - Forced diuresis (furosemide after hydration) - Plasmapheresis, hemosorption – severe toxemia **Anti-DIC therapy:** - Early: anticoagulants (heparin), fresh frozen plasma (FFP) - Late (fibrinolytic stage): FFP, tranexamic acid, fibrinogen **Corticosteroids:** - Cerebral edema, septic shock, meningococcemia, severe toxicity - Dexamethasone 0.4 mg/kg in bacterial meningitis (reduces hearing loss) **Immunotherapy:** - Interferons (IFN-alpha, IFN-beta) - IVIG for severe bacterial infections **Symptomatic:** - Antipyretics (paracetamol; avoid aspirin in viral infections due to Reye syndrome risk) - Antiemetics, antispasmodics - O2 therapy, mechanical ventilation if needed --- ## Q14. Principles of infectious disease prevention, vaccination, immunoprophylaxis. **Prevention levels:** - **Primary** – preventing disease (vaccination, hygiene, safe sex, vector control) - **Secondary** – early detection and treatment - **Tertiary** – preventing complications **Types of immunoprophylaxis:** - **Active immunization (vaccines):** - Live attenuated: BCG, OPV, MMR, yellow fever, varicella → long-lasting immunity - Killed/inactivated: IPV, influenza (injectable), hepatitis A → safe in immunocompromised - Toxoids: diphtheria (DT), tetanus → against exotoxins - Subunit/recombinant: hepatitis B, HPV, acellular pertussis - mRNA: COVID-19 - **Passive immunization:** - Immunoglobulins (human): rapid protection, short-lived (3–4 weeks) - Used for post-exposure prophylaxis: rabies, hepatitis B, tetanus, varicella **Russian national vaccination calendar:** - BCG (day 3–7), HBV (birth, 1, 6 months), DPT (3, 4.5, 6 months), MMR (12 months), etc. **Non-specific prevention:** - Sanitation, vector control, quarantine, food safety, disinfection --- ## Q15. Organizational structure of medical care for infectious patients. **Outpatient level:** - Polyclinic: initial diagnosis, mild cases managed at home - Mandatory reporting (Form 058/u) to sanitary-epidemiological service (Rospotrebnadzor) within 12 hours **Inpatient level – Infectious Disease Hospital (Инфекционная больница):** - Box wards (Melzer boxes) – individual rooms with separate entrance/exit, laminar flow; for highly contagious patients - Semi-box/ward system for less contagious - Separate departments by pathogen type (intestinal, respiratory, etc.) - ICU for severe cases - Disinfection zone, sanitary checkpoint at entry **Structure:** - Reception/admissions (sanitary filter) – history, examination, preliminary diagnosis, disinfection - Clinical departments - Bacteriology/Virology laboratory - Disinfection department - Emergency department **Discharge criteria:** - Clinical recovery + bacteriological clearance (culture-negative for typhoid, cholera, dysentery) - Following epidemiological regulations --- ## Q16. Early detection, hospitalization and discharge rules, rehabilitation of convalescents. **Early detection:** - Active: screening (blood donors, pregnant women, food workers) - Passive: patient presentation to clinic - Emergency notification within 12 h for Group I (plague, cholera, VHFs) or 24 h for Group II diseases **Hospitalization indications:** - Clinical: severe course, complications, need for parenteral therapy - Epidemiological: quarantine diseases, food workers, children's institution staff, housing conditions **Isolation periods (examples):** - Typhoid: until 2 negative stool cultures (not before day 21 from onset) - Dysentery: 3 days after clinical recovery + negative stool culture - Diphtheria: 2 negative cultures - Hepatitis A: until clinical/biochemical recovery (minimum 28 days) **Discharge:** - Certificate of recovery - Referral to polyclinic for follow-up (dispensarization) **Rehabilitation/dispensarization:** - Typhoid: observation 3 months, monthly stool cultures - Hepatitis B/C: 12 months in hepatology - Brucellosis: 2 years - Meningococcal infection: 2 years (neurologist) --- ## Q17. Physician's tactics with acute respiratory infections (ARI). Specimen collection. **Physician's tactics:** - Epidemiological history (contact, travel – especially for influenza, COVID-19, SARS) - If "unusual" ARI (severe, unusual epidemiology, atypical course) → suspect dangerous infection - For highly pathogenic (H5N1, SARS, COVID-19): immediately contact chief physician, call Rospotrebnadzor, isolate patient, use PPE (FFP3 mask, gown, gloves, goggles) **Specimen collection:** - **Nasopharyngeal swab** – for influenza, COVID-19, adenovirus (PCR) - **Nasopharyngeal washings** – flu rapid antigen test - **Sputum** – bacteriological culture, AFB smear for TB - **Blood** – culture (sepsis), CBC, paired serology - **Broncho-alveolar lavage** – atypical pneumonia, PCP (in HIV) - From corpse: lung tissue, tracheal contents → must inform Rospotrebnadzor **Transport:** Cold chain (2–8°C), special containers, labeled with clinical data, sent to virological reference lab --- ## Q18. Infectious-toxic shock (ITS) – pathogenesis, stages, clinic. **Pathogenesis:** Massive release of bacterial toxins (endotoxin/exotoxin) → activation of macrophages, cytokine storm (TNF-α, IL-1, IL-6) → vasodilation, increased vascular permeability → distributive shock → organ hypoperfusion → MODS **Stages (Bone classification):** | Stage | BP | Features | |-------|-----|---------| | Stage I (warm shock) | Normal or ↑ | Hyperdynamic; skin warm, flushed; tachycardia; fever; urine output decreased | | Stage II (cold shock) | ↓ (90–60 mmHg) | Hypodynamic; skin cold, pale, clammy; oliguria; mental changes | | Stage III (irreversible) | <60 mmHg | Anuria, coma, DIC, MODS; often fatal | **Clinic:** High fever → sudden chills → skin flushing/pallor → tachycardia → hypotension → confusion → oliguria/anuria → hemorrhagic manifestations (DIC) Most commonly: meningococcemia, salmonellosis, typhoid, gram-negative sepsis, leptospirosis --- ## Q19. Treatment of ITS (stages of care). **Pre-hospital:** - IV access (2 large-bore lines) - Bolus crystalloids (0.9% NaCl or Ringer's lactate) 10–20 mL/kg over 15–30 min - Oxygen - Antibiotics ASAP (do not delay for cultures >45 min) - Corticosteroids: prednisolone 60–120 mg IV or dexamethasone 8–16 mg IV **Hospital (ICU):** - Aggressive fluid resuscitation: 30 mL/kg crystalloids in first 3 hours (Surviving Sepsis Campaign) - Vasopressors: norepinephrine (first choice) if MAP <65 mmHg despite fluids; target MAP ≥65 - Broad-spectrum antibiotics (within 1 hour): e.g., ceftriaxone 2 g + metronidazole ± vancomycin - Corticosteroids: hydrocortisone 200 mg/day IV if vasopressor-refractory shock - Correct metabolic acidosis, electrolytes - Heparin for DIC (early phase), FFP - Organ support: mechanical ventilation (ARDS), RRT (AKI) - Monitoring: hourly urine output, CVP, SpO2, lactate clearance --- ## Q20. DIC Syndrome in infectious diseases – pathogenesis, clinical features, diagnostics. **Pathogenesis:** Infection → endotoxin/exotoxin → activation of coagulation cascade (tissue factor pathway) → widespread microthrombi (thrombotic phase) → consumption of clotting factors (fibrinogen, platelets, factors V, VIII) → hemorrhagic phase → organ ischemia **Clinical features:** - **Phase I (hypercoagulation):** skin mottling, acrocyanosis, thrombosis, organ dysfunction - **Phase II (consumption coagulopathy):** bleeding from injection sites, mucous membranes, GI, hematuria; petechiae/ecchymoses - **Phase III (fibrinolysis):** massive hemorrhage, shock **Associated infections:** meningococcemia, sepsis, leptospirosis, typhus, viral hemorrhagic fevers, plague **Diagnostics:** - Platelet count ↓ (<100,000) - PT/APTT prolonged - Fibrinogen ↓ (<1 g/L in severe) - D-dimer ↑ (fibrin degradation products) - Schistocytes on blood smear (microangiopathy) - ISTH DIC score: platelets + PT + fibrinogen + D-dimer → score ≥5 = overt DIC --- ## Q21. Treatment and prevention of DIC in infectious patients. **Treatment by phase:** **Phase I (hypercoagulation):** - Treat underlying infection (antibiotics) - Unfractionated heparin 5000–10,000 U IV bolus → 500–1000 U/h infusion (monitor APTT ×1.5–2.5) - Fresh frozen plasma (FFP) 10–15 mL/kg – replaces all clotting factors - Antiplatelet agents if needed **Phase II (consumption):** - Discontinue/reduce heparin - FFP 15–20 mL/kg - Cryoprecipitate (fibrinogen + factor VIII) if fibrinogen <1 g/L - Platelet transfusion if <20,000 or active bleeding - Antithrombin III concentrate **Phase III (fibrinolysis/hemorrhage):** - Tranexamic acid (antifibrinolytic) 10–15 mg/kg IV - FFP, cryoprecipitate, platelets - Corticosteroids for vascular stabilization - No heparin in this phase **Prevention:** - Prompt treatment of infection - Avoid triggers (hypothermia, acidosis, hypoxia) - Monitoring of coagulation in high-risk patients (sepsis, meningococcemia) --- ## Q22. Dehydration shock – pathogenesis, stages, clinical features, treatment. **Pathogenesis:** Massive fluid and electrolyte loss (vomiting/diarrhea) → intravascular volume depletion → decreased cardiac output → compensatory vasoconstriction → tissue hypoperfusion → lactic acidosis → MODS Classic cause: Cholera (rice-water stools, up to 20 L/day) **Stages (Russian classification of dehydration):** | Degree | Fluid Loss (body weight) | Clinic | |--------|--------------------------|--------| | I | 1–3% | Thirst, slight dry mucosae, normal BP | | II | 4–6% | Dry skin, sunken eyes, tachycardia, BP normal or ↓, oliguria, muscle cramps | | III | 7–9% | Severe dehydration, hypotension, acrocyanosis, anuria, aphonia | | IV (algid) | >10% | Cold skin, anuria, asphyxia, hypotension, coma, DIC | **Treatment:** - Degree I–II: oral rehydration (ORS – WHO formula: NaCl 3.5g, KCl 1.5g, NaHCO3 2.5g, glucose 20g per 1L) - Degree III–IV: IV rehydration - **Trisol** (NaCl 5g + KCl 1g + NaHCO3 4g per 1L water) – standard Russian solution - **Quartasol, Acesol, Ringer's lactate** - Primary rehydration: replace calculated deficit in 1–2 hours; then compensatory rehydration matching ongoing losses - Monitor: BP, pulse, urine output, electrolytes, acid-base balance --- ## Q23. Acute Renal Failure (ARF) in infectious diseases. **Causes in infections:** - Direct renal involvement: leptospirosis (tubular), HFRS (hantavirus – hemorrhagic fever with renal syndrome), malaria - Indirect: shock (sepsis, dehydration, ITS), DIC, myoglobinuria (tetanus, diphtheria), nephrotoxic antibiotics (aminoglycosides) **Stages:** 1. **Oliguric** – urine output <400 mL/day; rising creatinine/urea; hyperkalemia; fluid overload 2. **Polyuric** – urine output increases (often >3 L/day); risk of hypokalemia, dehydration 3. **Recovery** – gradual return of concentrating ability (months) **Clinical features:** - Oliguria/anuria, edema, hypertension - Uremic symptoms: nausea, drowsiness, asterixis - Hyperkalemia → cardiac arrhythmias - Metabolic acidosis **Diagnosis:** - Creatinine ↑, urea ↑, GFR ↓ - Urine: low specific gravity, proteinuria, casts (granular in ATN) - Ultrasound: normal/enlarged kidneys (acute vs. chronic) **Indications for hemodialysis (AEIOU):** - **A**cidosis (pH <7.1) - **E**lectrolytes (K+ >6.5 mmol/L) - **I**ntoxication (uremic symptoms, toxic ingestion) - **O**verload (refractory pulmonary edema) - **U**remia (urea >30 mmol/L, symptoms) --- ## Q24. Acute hepatic encephalopathy – mechanisms, clinical features, diagnosis, treatment. **Mechanism:** Massive hepatocyte necrosis (fulminant viral hepatitis B, B+D, drug toxicity) → failure to detoxify ammonia → ammonia crosses BBB → glutamine accumulation in astrocytes → cerebral edema + neurotransmitter imbalance (false neurotransmitters, GABA agonists) **Clinical stages (West Haven criteria):** | Stage | Features | |-------|----------| | I | Mild confusion, sleep-wake reversal, euphoria/anxiety | | II | Drowsiness, disorientation, asterixis (liver flap) | | III | Stupor, responds to stimuli, marked asterixis | | IV | Coma, no response to stimuli | **Other signs:** Fetor hepaticus (sweet-musty breath), jaundice, bleeding tendency (PT ↑ ↑), shrinking liver **Diagnostics:** - Ammonia ↑ (arterial >200 μmol/L = severe) - Bilirubin ↑↑ (>200 μmol/L in severe) - ALT/AST ↑↑ initially, then ↓ (liver destruction) - PT/INR markedly prolonged - EEG: triphasic waves - CT/MRI: cerebral edema **Treatment:** - ICU, avoid sedatives - Lactulose 30–45 mL orally TID (reduces NH3 absorption) - Rifaximin 550 mg BD (reduces ammonia-producing gut bacteria) - Protein restriction (moderate, not severe) - Correct hypoglycemia (10% glucose) - FFP, vitamin K for coagulopathy - Manage cerebral edema: elevate head 30°, mannitol 20%, avoid fluid overload - Liver transplantation (definitive for fulminant hepatic failure) --- ## Q25. Viral Hepatitis A and E. **HAV:** - RNA picornavirus; fecal-oral transmission; water/food-borne outbreaks - Incubation: 15–50 days (avg 28 days) - **Self-limiting** – no chronic form; complete recovery in >99% - At-risk: children, travellers, poor sanitation areas **HEV:** - RNA hepevirus; fecal-oral; contaminated water (endemic in India, Central Asia, Africa) - Incubation: 15–60 days - **High mortality in pregnancy (20–25%)** in genotype 1/2 - Genotype 3/4: zoonotic (pigs); can cause chronic hepatitis in immunocompromised **Both: Clinical features (icteric form):** - Preicteric: 5–7 days; fever, malaise, nausea, right upper quadrant pain, dark urine - Icteric: jaundice appears; fever subsides; hepatomegaly; pruritus; pale stools - Recovery: 2–4 weeks **Atypical forms:** Anicteric (most common), cholestatic, fulminant (rare) **Diagnosis:** - Anti-HAV IgM (acute HAV), anti-HAV IgG (past/immune) - Anti-HEV IgM; HEV RNA by PCR - LFTs: ALT ↑↑ (>10× ULN in acute), bilirubin ↑↑ (conjugated dominant) **Treatment:** Supportive (rest, diet №5, no alcohol, avoid hepatotoxic drugs) **Vaccine:** HAV – inactivated vaccine (2 doses); HEV – recombinant vaccine (HEV 239, approved in China) --- ## Q26. Viral Hepatitis B. **Etiology:** HBV – partially double-stranded DNA hepadnavirus; highly infectious (100× more than HIV) **Antigens:** - HBsAg (surface) – marker of infection (acute + chronic) - HBeAg – marker of active replication/high infectivity - HBcAg – core antigen (not detectable in serum) - HBV DNA – best marker of replication **Epidemiology:** Blood, sexual contact, vertical (perinatal) transmission **Incubation:** 60–180 days **Outcomes:** - Acute: 90–95% adults recover; 5–10% → chronic - Neonates: 90% → chronic - Chronic → cirrhosis (20%) → HCC (hepatocellular carcinoma) **Serology interpretation:** | HBsAg | Anti-HBs | Anti-HBc IgM | Anti-HBc IgG | Interpretation | |-------|----------|--------------|--------------|----------------| | + | – | + | – | Acute HBV | | – | + | – | + | Past infection / immune | | – | + | – | – | Vaccinated | | + | – | – | + | Chronic HBV | **Treatment:** - Acute: supportive; no antivirals unless fulminant - Chronic: entecavir 0.5 mg/day or tenofovir (TDF/TAF) – lifelong; goal: suppress HBV DNA, prevent cirrhosis/HCC - Pegylated IFN-alpha (48 wks) – finite course option; less tolerated **Prevention:** HBV vaccine (3 doses, 0-1-6 months); HBIG for post-exposure prophylaxis (newborns + needlestick) --- ## Q27. Viral Hepatitis D. **Etiology:** HDV (delta agent) – defective RNA virus; requires HBsAg for assembly; can only infect those with HBV **Types of infection:** - **Coinfection** (HBV + HDV simultaneously): usually self-limiting; low risk of chronicity; higher risk of fulminant hepatitis - **Superinfection** (HDV in chronic HBV carrier): rapid progression to cirrhosis; >90% become chronically co-infected; worst prognosis **Epidemiology:** Blood and sexual transmission (same as HBV); endemic in Mediterranean, Eastern Europe, Central Asia, South America (Amazonia) **Clinical:** More severe than HBV alone; biphasic pattern in coinfection; rapid cirrhosis in superinfection **Diagnosis:** - Anti-HDV total/IgM antibodies - HDV RNA (PCR) – most sensitive - HBsAg must be positive **Treatment:** - Pegylated IFN-alpha (48–72 weeks) – only approved therapy; 25% SVR - Bulevirtide (Hepcludex) – new entry inhibitor (blocks NTCP receptor); approved in Europe 2020 - HBV suppression with nucleos(t)ide analogs (controls HBV but not HDV replication directly) **Prevention:** HBV vaccination prevents HDV (since HDV needs HBV) --- ## Q28. Viral Hepatitis C. **Etiology:** HCV – RNA flavivirus; 7 genotypes (1–7); genotype 1 most common globally, most prevalent in Russia **Epidemiology:** Blood-borne (IV drug use, transfusions pre-screening, medical procedures); sexual/vertical – less efficient than HBV **Incubation:** 15–180 days (avg 7 weeks) **Stages:** - Acute: 80% asymptomatic; 20% jaundice - Chronic (75–85% of acute cases): silent; decompensated cirrhosis in 20% after 20 years; HCC risk **Clinical:** Often discovered incidentally via elevated ALT or screening; "silent killer" **Diagnosis:** - Anti-HCV antibodies (ELISA) – screening; positive 8–12 weeks after exposure - HCV RNA (PCR) – confirms active infection; appears within 1–2 weeks - HCV genotype – guides treatment - Liver biopsy/elastography (FibroScan) – assess fibrosis **Treatment (DAAs – Direct-Acting Antivirals):** - Sofosbuvir/ledipasvir (Harvoni), Sofosbuvir/velpatasvir (Epclusa) – pangenotypic - 8–12 weeks course; SVR (sustained virological response = cure) >95–98% - SVR = HCV RNA undetectable 12 weeks after treatment end **Prevention:** No vaccine; needle exchange programs, blood screening --- ## Q29. Early diagnosis of viral hepatitis. Prehospital management. **Early (preicteric) signs to detect:** - Flu-like prodrome (fatigue, anorexia, nausea, RUQ discomfort) before jaundice - Dark urine (bilirubinuria) appears before clinical jaundice – key early sign - Pale stools (acholia) - ALT elevation precedes jaundice by 5–10 days **Early diagnostic markers:** - ALT/AST ↑ (often 10–100× ULN) – most sensitive early marker - Bilirubin ↑ (conjugated) - Thymol turbidity test (protein fraction changes) - Urinary bilirubin (dipstick) **Prehospital management:** - Bed rest - Diet №5 (restrict fats, fried food, alcohol, hepatotoxic drugs) - Oral rehydration - Symptomatic: antiemetics, hepatoprotectors (ursodeoxycholic acid – controversial) - Refer to hospital: fulminant course, pregnancy, elderly, immunocompromised, hepatitis B/C with complications - Epidemiological measures: identify contacts, notify Rospotrebnadzor (HAV/HEV = acute notification) --- ## Q30. Laboratory diagnostics of viral hepatitis. **Non-specific (functional liver tests):** - ALT, AST (cytolysis syndrome) – ↑↑ in acute hepatitis - Bilirubin (total, conjugated/unconjugated) - ALP, GGT (cholestasis) - Albumin, PT/INR (synthetic function – ↓ in severe) - Thymol turbidity ↑ **Specific markers:** | Hepatitis | Acute | Chronic/Past | Replication | |-----------|-------|-------------|------------| | HAV | Anti-HAV IgM | Anti-HAV IgG | – | | HBV | HBsAg + Anti-HBc IgM | HBsAg + Anti-HBc IgG | HBeAg, HBV DNA | | HCV | Anti-HCV IgM/IgG | Anti-HCV IgG | HCV RNA (PCR) | | HDV | Anti-HDV IgM | Anti-HDV IgG | HDV RNA | | HEV | Anti-HEV IgM | Anti-HEV IgG | HEV RNA | **Additional:** - Ultrasound: hepatomegaly, splenomegaly, altered echogenicity - Liver biopsy / FibroScan (FibroTest): fibrosis staging - AFP ↑ → HCC screening (HBV/HCV cirrhosis) --- ## Q31. Principles of treatment, clinical examination of viral hepatitis convalescents, preventive measures. **Treatment principles:** - Hepatitis A/E: supportive (bed rest, diet №5, no alcohol, no hepatotoxics) - Hepatitis B acute: supportive; if fulminant → antivirals (entecavir) - Hepatitis B chronic: entecavir or tenofovir (lifelong or until HBsAg seroconversion) - Hepatitis C: DAAs (sofosbuvir-based) 8–12 weeks; >95% cure - Hepatitis D: pegIFN-alpha; bulevirtide **Clinical examination (dispensarization):** - HAV convalescents: 3 months follow-up; LFTs at 1 and 3 months - HBV: 12 months observation; LFTs + HBsAg every 3 months; if HBsAg persists >6 months → chronic - HCV: SVR assessment at 12 weeks post-treatment; annual ultrasound if cirrhosis - HBV/HCV cirrhosis: 6-monthly AFP + ultrasound for HCC surveillance **Prevention:** - HAV: vaccine (2 doses), sanitation, hand hygiene - HBV: vaccine (universal infant immunization), HBIG for newborns of HBsAg+ mothers, safe sex, universal precautions - HCV: no vaccine; harm reduction (needle programs), blood screening, universal precautions - HEV: safe water, no vaccine widely available (except China) --- ## Q32. Typhoid Fever – etiology, pathogenesis, pathological anatomy, clinical presentation, diagnosis, treatment, discharge guidelines. **Etiology:** Salmonella enterica serovar Typhi (gram-negative, facultative anaerobe) **Pathogenesis:** Fecal-oral → colonizes Peyer's patches (ileum) → bacteremia (1st week) → seeding liver, spleen, gallbladder, bone marrow → lymph node hyperplasia → necrosis of Peyer's patches → ulceration (3rd week) → healing (4th week) **Pathological anatomy (Peyer's patches stages):** 1. Medullary swelling (week 1) 2. Necrosis (week 2) 3. Ulcer formation (week 3) – risk of bleeding/perforation 4. Clean ulcer (week 4) 5. Healing (week 5) **Clinical (4 weeks classic course):** - Fever: stepwise rise (Wunderlich curve) to 39–40°C by end of week 1 - Relative bradycardia (pulse-temperature dissociation) - Headache, adynamia, anorexia - Roseolar rash (rose spots) on abdomen/trunk – appears day 8–10; sparse (5–20 elements); blanches on pressure - "Typhoid tongue" – coated center, red edges/tip - Hepatosplenomegaly - Constipation typical (diarrhea "pea soup" stools later) **Complications:** Intestinal bleeding (week 3–4), intestinal perforation (peritonitis), hepatitis, myocarditis, pneumonia, nephritis **Diagnosis:** - Blood culture (bacteremia) – weeks 1–2 (most sensitive early) - Bone marrow culture – most sensitive overall - Stool culture – week 2 onward - Urine culture – week 2 onward - Widal test (agglutination): O-antibodies (active disease) + H-antibodies (past/vaccine); requires 4-fold rise in paired sera; less specific - PCR available - CBC: leukopenia, eosinopenia, relative lymphocytosis; ESR normal **Treatment:** - Fluoroquinolones (ciprofloxacin 500 mg BD × 10–14 days) – 1st choice - Ceftriaxone 2g IV OD × 14 days (for MDR strains) - Chloramphenicol, ampicillin (historical, resistance common) - Azithromycin (500 mg × 7 days) for uncomplicated **Discharge:** Not before day 21 of illness + 2 negative stool cultures (3–5 days apart) + negative urine culture --- ## Q33. Salmonellosis – etiology, epidemiology, pathogenesis, clinical forms, diagnosis, treatment. **Etiology:** Salmonella enteritidis, S. typhimurium, and 2500+ other serovars (not S. Typhi) **Epidemiology:** Zoonosis; contaminated poultry, eggs, dairy, meat; fecal-oral; outbreaks in food establishments **Pathogenesis:** Ingestion of large dose → colonize small intestine → produce enterotoxin + endotoxin → inflammation, secretory diarrhea → may invade and bacteremia **Clinical forms:** 1. **Gastrointestinal (most common – 96%):** - Gastritis, gastroenteritis, gastroenterocolitis - Onset 6–72 hours after exposure - Nausea, vomiting, fever (38–39°C), watery diarrhea (not bloody usually) - No tenesmus (vs. dysentery) 2. **Typhoid-like** – fever, headache, hepatosplenomegaly; no Peyer's patches changes 3. **Septic (bacteremic)** – high fever, chills, pyemic foci (osteomyelitis, meningitis); mainly immunocompromised 4. **Carrier** – asymptomatic, transient (>1 month = chronic) **Diagnosis:** - Stool culture (main method) – from early diarrhea - Blood culture – in septic/typhoid-like forms - Serology (RNGA) – diagnostic if >1:200, 4-fold rise - PCR **Treatment:** - Mild/moderate GI: rehydration (oral), no antibiotics needed - Severe GI/systemic: ciprofloxacin 500 mg BD × 5–7 days - Septic form: ceftriaxone IV × 14 days - Rehydration: oral (ORS) or IV (trisol, Ringer's) --- ## Q34. Cholera – etiology, epidemiology, pathogenesis, clinical, diagnosis, treatment. **Etiology:** Vibrio cholerae O1 (biotypes: classical, El Tor) and O139; comma-shaped gram-negative rod; highly acid-labile **Epidemiology:** Fecal-oral; contaminated water (main); 7 pandemics; endemic in South Asia; El Tor pandemic ongoing since 1961 **Pathogenesis:** Ingestion → colonize small intestine → produce CT (choleragen = cholera toxin, AB5 structure) → CT activates adenylate cyclase via Gs protein → ↑cAMP → hypersecretion of Cl⁻ and water; Na⁺ absorption blocked → massive watery secretory diarrhea (up to 20 L/day); no mucosal invasion; no fever initially **Clinical features:** - Sudden watery diarrhea ("rice-water stools") – no blood, no odor - Vomiting (no nausea) - No fever or low-grade - Rapid severe dehydration: muscle cramps (K+ loss), dry skin, sunken eyes/fontanelle, husky voice → aphonia → oliguria → algid stage (hypothermia, circulatory collapse, coma) **Diagnosis:** - Dark-field microscopy (motile vibrios in stool) – rapid - Stool culture on TCBS agar (selective) - Agglutination with specific antisera - PCR - Quarantine disease – immediate reporting **Treatment:** - **Rehydration = cornerstone:** - Degree I–II: oral (ORS) - Degree III–IV: IV Trisol, Quartasol; primary rehydration rapid (within 2 hours) - Antibiotics: doxycycline 300 mg single dose or tetracycline; ciprofloxacin 1g single dose – reduce duration/shedding - **No antidiarrheal agents (loperamide contraindicated)** - Strict isolation, contact tracing, chemoprophylaxis of contacts (doxycycline) --- ## Q35. Food poisoning (Bacterial toxicoses) – etiology, pathogenesis, clinical, diagnosis, treatment. **Etiology:** - **Staphylococcal toxicosis** (S. aureus enterotoxin A–F, heat-stable) - **Botulism** (Clostridium botulinum neurotoxin, types A–G) - **Bacillus cereus** toxin (emetic or diarrheal type) **Food Poisoning (non-toxicosis – PTI = Pищевая токсикоинфекция):** - Caused by: Salmonella, E. coli (ETEC), Proteus, Klebsiella, Enterobacter, Clostridium perfringens - Live bacteria ingested → multiply → produce toxins in gut **Staphylococcal toxicosis:** - Incubation: 1–6 hours (most rapid) - Violent nausea/vomiting, abdominal pain, ± diarrhea - No fever (toxin, not invasion) - Short duration (12–24 hours) **PTI in general:** - Incubation: 6–24 hours - Acute onset: nausea, vomiting, watery diarrhea, abdominal cramps, fever - May cause dehydration **Diagnosis:** Epidemiological (group outbreak + specific food); culture of food/stool/vomitus; toxin detection (ELISA) **Treatment:** - **Gastric lavage** if vomiting not complete (early, <6 hours) - **Rehydration** (oral or IV depending on severity) - Enterosobents (activated charcoal, smectite) - No antibiotics for mild PTI (self-limiting) - Antibiotics for severe/systemic: ciprofloxacin - Botulism: antitoxin (polyvalent A+B+E horse serum antitoxin) + ICU --- ## Q36. Botulism – etiology, epidemiology, pathogenesis, clinical, diagnosis, treatment. **Etiology:** Clostridium botulinum – spore-forming, anaerobic gram-positive rod; produces botulinum neurotoxin (types A, B, E most common in humans); most potent biological toxin known **Epidemiology:** Food-borne (home-canned foods, smoked fish, mushrooms); wound botulism (IV drug use); infant botulism (honey, spores); no person-to-person transmission **Pathogenesis:** Toxin absorbed in upper GI → bloodstream → peripheral cholinergic nerve terminals → irreversibly blocks ACh release at NMJ → flaccid paralysis (descending, bilateral, symmetric) **Clinical (triad):** 1. Descending flaccid paralysis (cranial nerves first → respiratory muscles) 2. Autonomic dysfunction (dry mouth, constipation, urinary retention, fixed dilated pupils) 3. No fever, consciousness preserved, no sensory loss **Cranial nerve signs first:** diplopia, ptosis, dysarthria, dysphagia → respiratory failure **Diagnosis:** - Clinical (descending paralysis + autonomic signs + food history) - Mouse bioassay (gold standard – detect toxin in serum/food/stool in mice) - ELISA for toxin - EMG: decremental response at high-frequency stimulation (vs. Eaton-Lambert: incremental) **Treatment:** - **Equine trivalent antitoxin (A+B+E) – earliest possible** (neutralizes unbound toxin) - ICU: respiratory support (mechanical ventilation if FVC <30%) - Enteric decontamination: activated charcoal, laxatives (if ingestion <12 hrs) - No antibiotics (unless wound botulism – penicillin) - Supportive care: NG feeding, catheterization, eye care --- ## Q37. Dysentery (Shigellosis) – etiology, epidemiology, pathogenesis, clinical, diagnosis, treatment. **Etiology:** Shigella dysenteriae (most severe), S. flexneri (most common globally), S. sonnei (mildest), S. boydii; gram-negative non-motile rods; very low infectious dose (10–100 organisms) **Epidemiology:** Fecal-oral; person-to-person (dirty hands), food, water; mainly affects children; no animal reservoir **Pathogenesis:** Shigella invades colonocytes of distal colon → intracellular multiplication → cell-to-cell spread → colonic mucosa inflammation, ulceration → bloody mucous diarrhea; Shiga toxin (S. dysenteriae) → HUS (hemolytic uremic syndrome) **Clinical:** - **Prodrome (1–2 days):** Fever, headache, abdominal pain - **Colitis syndrome:** Tenesmus (painful straining), frequent small stools (up to 20–30/day) with blood and mucus ("rectal spitting"), severe lower abdominal cramps, palpable sigmoid colon - Dehydration less common than cholera (colon, not small intestine) **Forms:** Mild, moderate, severe; toxic (ITS, convulsions in children) **Complications:** HUS (S. dysenteriae type 1), rectal prolapse, perforation (rare) **Diagnosis:** - Stool culture (main) – culture on Ploskirev's or MacConkey agar; positive in 50–70% - Colonoscopy: catarrhal → fibrinous → ulcerative colitis changes - CBC: leukocytosis, neutrophilia; ESR ↑ - Serology: RNGA ≥1:200 (diagnostic); 4-fold rise **Treatment:** - Mild: rehydration only - Moderate-severe: **ciprofloxacin** 500 mg BD × 5 days (1st choice); azithromycin for resistant strains - Children: azithromycin; avoid fluoroquinolones <18 yrs when possible - Ceftriaxone for severe/HUS-associated - **No antidiarrheal agents (loperamide contraindicated)** – worsens invasive colitis - Rehydration (mainly oral) --- ## Q38. Escherichia coli Intestinal Infections. **Classification of pathogenic E. coli:** | Type | Mechanism | Disease | |------|-----------|---------| | ETEC | Heat-labile/stable toxin (↑cAMP/cGMP) | Traveler's diarrhea, watery diarrhea | | EPEC | Attaches + effaces | Infant diarrhea | | EIEC | Invasive (like Shigella) | Dysentery-like | | EHEC (O157:H7) | Shiga toxin 1+2 | Bloody diarrhea + HUS | | EAEC | Aggregative adhesion | Persistent diarrhea | **ETEC** – most common cause of traveler's diarrhea; watery, profuse; self-limiting **EHEC O157:H7:** - Undercooked beef, unpasteurized dairy; outbreak source - Bloody diarrhea (colitis) → HUS in 5–10% (children, elderly): microangiopathic hemolytic anemia + thrombocytopenia + AKI - **Do NOT give antibiotics** (↑ toxin release → ↑ HUS risk) - **Do NOT give antidiarrheals** - Supportive care, dialysis for HUS **Diagnosis:** Stool culture; EHEC: sorbitol-MacConkey agar (O157 is sorbitol-negative); Shiga toxin ELISA; PCR **Treatment (general):** Rehydration; antibiotics only for ETEC/EIEC (ciprofloxacin 3–5 days); azithromycin for traveler's diarrhea --- ## Q39. Yersinioses – etiology, epidemiology, pathogenesis, clinical forms, diagnosis, treatment. **Two species:** 1. **Yersinia enterocolitica** – intestinal yersiniosis 2. **Yersinia pseudotuberculosis** – pseudotuberculosis (Far East scarlatina) **Epidemiology:** Zoonosis (pigs, rodents, cattle); contaminated food (pork, vegetables, milk); fecal-oral; no person-to-person; Y. pseudotuberculosis – vegetables, water **Pathogenesis:** Colonize ileum/cecum → invade Peyer's patches → mesenteric lymphadenitis → possible bacteremia and dissemination → immune complex complications **Y. enterocolitica clinical forms:** - Gastroenteritis (most common): fever, diarrhea (±blood), abdominal pain - Pseudoappendicitis: severe RIF pain (mimics appendicitis); mesenteric lymphadenitis - Terminal ileitis - Septicemia (immunocompromised, iron overload) - Post-infectious: reactive arthritis (HLA-B27), erythema nodosum, uveitis **Y. pseudotuberculosis (Far East scarlatina):** - Fever, scarlatiniform rash (palms/soles), "strawberry tongue," arthralgia - Mesenteric lymphadenitis, hepatosplenomegaly **Diagnosis:** - Stool/blood culture (cold enrichment helps: CIN agar) - RNGA serology: ≥1:200 diagnostic - CBC: leukocytosis, ↑ESR - PCR **Treatment:** - Mild GI: supportive - Moderate-severe: ciprofloxacin 500 mg BD × 7–10 days OR doxycycline × 10 days - Septicemia: ceftriaxone + doxycycline or ciprofloxacin × 14 days --- ## Q40. Amebiasis – etiology, epidemiology, pathogenesis, clinical forms, diagnosis, treatment. **Etiology:** Entamoeba histolytica; exists as trophozoite (invasive, large, hematophagous – "E. histolytica magna") and cyst (4-nucleate, infective form) **Epidemiology:** Fecal-oral; contaminated water/food; endemic in tropics (India, Africa, Mexico); 50 million infections/year; 100,000 deaths/year **Pathogenesis:** Cysts ingested → excyst in colon → trophozoites invade colonic mucosa → flask-shaped ulcers (undermined edges) → may invade portal vein → liver abscess (and rarely other organs) **Clinical forms:** 1. **Intestinal amebiasis (amebic colitis):** - Gradual onset; bloody mucous diarrhea with little fever - Tenesmus, abdominal pain (mainly RIF + right flank) - No systemic toxicity (unlike shigellosis) - Chronic form with alternating diarrhea/constipation 2. **Amebic liver abscess:** - Fever (hectic), RUQ pain (radiates to right shoulder), tender hepatomegaly - No diarrhea (50% have no gut symptoms) - Ultrasound: single abscess in right lobe - Risk of rupture into pleura/peritoneum 3. **Extraintestinal** (lung, brain, skin) – rare **Diagnosis:** - Stool microscopy: motile hematophagous trophozoites (gold standard for colitis) - Stool antigen test (ELISA for E. histolytica) - PCR (most sensitive) - Serology (anti-amebic IgG): positive in >94% of liver abscess - Colonoscopy: flask-shaped ulcers (ameboma) - Ultrasound/CT: liver abscess **Treatment:** - Intestinal/invasive: **metronidazole** 750 mg TID × 10 days (or tinidazole 2g/day × 3 days) - Then luminal agent (to eliminate cysts): **paromomycin** 500 mg TID × 7 days (or diloxanide furoate) - Liver abscess: metronidazole ± drainage (if large >5 cm, risk of rupture) - Asymptomatic cyst passer: paromomycin alone ---