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HARRISON'S INFECTIOUS DISEASES - SECTION 1: BASIC CONSIDERATIONS

Complete Teaching Guide | Chapters 124-130

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CHAPTER 124 - APPROACH TO THE PATIENT WITH AN INFECTIOUS DISEASE

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1. HISTORIC PERSPECTIVE

• The miasma theory ("bad air") dominated thinking since the 16th century
• Pasteur and Koch in the late 19th century established the germ theory of disease - microorganisms directly cause infections
• The 20th century brought antibiotics and vaccines, leading Nobel laureate Sir Frank MacFarlane Burnet to declare in 1962 that infectious disease was "virtually eliminated"
• That optimism was premature. Infectious diseases struck back with HIV/AIDS, SARS-CoV-2, Ebola, mpox, and escalating antimicrobial resistance

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2. GLOBAL BURDEN

• Infectious diseases are the second leading cause of death worldwide
• 9.6 million deaths in 2019 despite dramatic reductions over the preceding 25 years
• Deaths disproportionately affect: children <1 year, adults >70 years, and persons in low/middle-income countries
• In sub-Saharan Africa, ~69% of deaths are infection-related

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3. THE CLINICAL APPROACH - HOW A MASTER DIAGNOSTICIAN THINKS

3a. The H&P is Everything

• Onset, duration, rate of progression
• Travel history (where, when, activities, water sources)
• Animal contacts / tick or mosquito exposure
• Sexual history, IV drug use
• Vaccination history
• Immunocompromising conditions (HIV, malignancy, transplant, steroids, diabetes, cirrhosis, asplenia)
• Recent antibiotics (predisposes to C. diff, resistant organisms)
• Dietary history, raw meat/unpasteurized dairy
• Contact with ill individuals
• Occupation
• Pregnancy (increases severity of influenza, COVID-19; risk to fetus from Listeria, Zika)

• Vital signs for hemodynamic compromise
• Skin: rash character (petechial, macular, vesicular), distribution
• Lymph nodes: generalized vs. regional
• Oropharynx: exudates, ulcers
• Fundoscopic exam (endocarditis emboli, CMV retinitis)
• Genital/rectal (often missed)
• Careful joint, bone, and soft-tissue assessment

3b. The Differential Diagnosis Framework

1. Host factors - immune status, age, comorbidities
2. Epidemiology - geography, season, exposure history
3. Syndrome - which organ system? Which pattern?
4. Microbiology - what organisms cause this syndrome in this host?

3c. The Microbiome Revolution

• Digestion and nutrition
• Training the immune system
• Resisting colonization by pathogens (colonization resistance)

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CHAPTER 125 - MOLECULAR MECHANISMS OF MICROBIAL PATHOGENESIS

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1. THE CONCEPT OF PATHOGENICITY AND VIRULENCE

• Pathogenicity = ability of a microbe to cause disease
• Virulence = the degree or severity of disease caused
• Virulence factors = specific molecular structures/secreted products that enhance the organism's ability to infect, evade defenses, and cause damage

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2. HOW PATHOGENS GET IN - BREACHING HOST BARRIERS

Skin

• Wounds, abrasions, insect bites
• Surgical incisions, IV lines, body piercings
• Some organisms penetrate intact skin (e.g., Schistosoma, hookworm larvae)

Mucosal Surfaces

• Mucus - traps organisms
• Ciliary beating - moves mucus upward (mucociliary escalator)
• Secretory IgA - prevents adherence
• Defensins - antimicrobial peptides
• Lysozyme - degrades bacterial cell walls
• Lactoferrin - sequesters iron

• Neisseria gonorrhoeae secretes IgA1 protease to cleave secretory IgA
• Bordetella pertussis disables ciliary function
• Influenza neuraminidase cleaves mucus

Gut-Associated Lymphoid Tissue (GALT)

• M cells in follicle-associated epithelia sample antigens by transcytosis and deliver them to dendritic cells, macrophages, and neutrophils below
• This initiates antigen presentation via MHC → stimulates adaptive immunity (B cells and T cells in lymph nodes)

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3. COMPLEMENT - THE FIRST LINE OF HUMORAL DEFENSE

• Classical pathway - antibody bound to pathogen recognized by C1 complex
• Lectin pathway - mannose-binding lectin recognizes carbohydrates on bacterial surfaces
• Alternative pathway - spontaneous C3 hydrolysis or amplification by plasma factors

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4. LYSOSOMES AND PHAGOCYTOSIS

• Lysosomes contain hydrolytic enzymes in an acidic environment that kill and degrade microbes
• Lysozyme hydrolyzes peptidoglycan → kills gram-positive bacteria
• Gram-negative bacteria protect peptidoglycan between their two membranes, making it inaccessible
• Gram-positive bacteria evade lysozyme by acetylating sugars in the glycan strand
• The metabolite itaconate (mitochondria-derived) accumulates in lysosomes during Salmonella infection and limits bacterial growth
• Some pathogens (Mycobacteria, Legionella) actively block phagolysosome fusion to survive intracellularly

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5. INNATE IMMUNITY - PATTERN RECOGNITION

• NF-kB pathway → proinflammatory cytokines (TNF-α, IL-1, IL-6)
• Interferon pathway → antiviral state
• Inflammasome assembly → IL-1β and IL-18 secretion, pyroptosis

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6. KEY VIRULENCE MECHANISMS

Toxins

• Exotoxins (secreted proteins): highly potent; act at site distant from infection
  • A-B toxins: B subunit binds host cell, A subunit is the toxic enzyme
  • Examples: cholera toxin (activates adenylate cyclase → massive secretory diarrhea), diphtheria toxin (ADP-ribosylates EF-2 → blocks protein synthesis → cell death), botulinum toxin (blocks ACh release → flaccid paralysis)
• Endotoxin (LPS from gram-negative outer membrane): triggers TLR4 → massive cytokine release → septic shock, DIC

Adhesins

• Pili/fimbriae: E. coli type I and P fimbriae for UTI
• Non-pilus adhesins: Staphylococcal surface proteins, MSCRAMM family

Invasion

• Some bacteria invade epithelial cells and replicate intracellularly: Shigella, Listeria, Salmonella, Mycobacteria
• Actin rocket propulsion: Listeria and Shigella polymerize host actin to propel themselves cell-to-cell without exiting into extracellular space

Iron Acquisition

Biofilm Formation

• 100-1000x more resistant to antibiotics
• Protected from phagocytosis
• Classic in: Pseudomonas in cystic fibrosis lungs, prosthetic valve endocarditis, urinary catheter UTIs, orthopedic implants

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CHAPTER 126 - MICROBIOLOGY IN INFECTIOUS DISEASE (LABORATORY DIAGNOSTICS)

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1. THE DIAGNOSTIC REVOLUTION

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2. MICROSCOPY AND STAINING

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3. CULTURE - GOLD STANDARD (BUT SLOW)

• Blood cultures: Two sets (aerobic + anaerobic) drawn before antibiotics; sensitivity increases with volume
• Incubation time: Standard bacteria 24-72 h; Mycobacteria up to 6 weeks; fungi 2-4 weeks
• Key principle: Always collect cultures before starting antibiotics

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4. RAPID ANTIGEN TESTS

• Detect specific pathogen antigens in clinical specimens
• Examples: Strep throat (GAS), Flu A/B, COVID-19, RSV, Legionella urinary antigen, Pneumococcal urinary antigen, C. diff glutamate dehydrogenase
• Fast (15-30 min), point-of-care, but less sensitive than culture/PCR

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5. NUCLEIC ACID AMPLIFICATION TESTS (NAATs / PCR)

• PCR (Polymerase Chain Reaction): Amplifies specific DNA/RNA sequences; highly sensitive and specific
• Multiplex PCR panels: Detect 20+ pathogens simultaneously (e.g., respiratory panel: influenza, RSV, SARS-CoV-2, parainfluenza, adenovirus, Mycoplasma...)
• Real-time quantitative PCR (qPCR): Quantifies viral loads (HIV, HBV, HCV, CMV)
• NAAT for TB: Xpert MTB/RIF detects M. tuberculosis AND rifampin resistance in 2 hours

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6. NEXT-GENERATION SEQUENCING (NGS) / METAGENOMIC SEQUENCING

• Sequencing all DNA/RNA in a clinical specimen - no need to know what you're looking for
• Identifies novel pathogens, detects pathogens that cannot be cultured
• Detects co-infections and mixed infections
• Detects antimicrobial resistance genes directly from the specimen
• Identifies heterogeneous pathogen subpopulations within a single host (e.g., Pseudomonas diversification in CF lungs, minority HIV variants with resistance)
• Challenge: cost, turnaround time, distinguishing pathogen from normal flora/environmental contamination

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7. TRANSCRIPTOMIC HOST-BASED DIAGNOSTICS

• Procalcitonin (PCT): Rises in bacterial infections more than viral; useful for guiding antibiotic de-escalation in pneumonia/sepsis, but limited specificity
• Transcriptomics: Identify RNA expression signatures in circulating white blood cells
  • Example: ~400 transcripts distinguish active from latent TB - driven by interferon-inducible myeloid genes. This signature tracks treatment response within 2 weeks
• Why it matters: Some infections are impossible to culture; host response is detectable even when the pathogen is not

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8. ANTIMICROBIAL SUSCEPTIBILITY TESTING

• MIC (Minimum Inhibitory Concentration): Lowest concentration of antibiotic that prevents visible bacterial growth
• Breakpoints: MIC values above which an organism is classified as Resistant, Intermediate, or Susceptible
• Disk diffusion (Kirby-Bauer): Zone of inhibition around antibiotic-impregnated disk
• MALDI-TOF: Identifies organism species in minutes by mass spectrometry of proteins; rapidly replacing conventional biochemical identification
• New rapid phenotypic AST: Transcriptional phenotype (bacteria respond differently to antibiotics at the gene expression level before growth differences appear) - can potentially identify resistance in minutes to hours vs days for traditional culture

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CHAPTER 127 - APPROACH TO THE ACUTELY ILL INFECTED FEBRILE PATIENT

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THE CORE PRINCIPLE

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1. FIRST LOOK - BEFORE YOU ASK A SINGLE QUESTION

• Anxious and agitated = possibly septic, meningitic
• Lethargic and apathetic = concerning for severe sepsis or CNS infection
• A subjective sense that the patient is "toxic" is often correct and should prompt urgent action

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2. HISTORY IN THE FEBRILE PATIENT

• Onset and rate of progression: Hours vs. days changes the differential dramatically
• Host risk factors: Asplenia, alcoholism/cirrhosis, IV drug use, HIV, diabetes, malignancy, obesity, transplant, chemotherapy → each predisposes to specific organisms AND more severe course
• Nidus for invasive infection: Recent URTI (sinusitis → meningitis), influenza (→ S. aureus pneumonia), varicella (→ group A Strep necrotizing fasciitis), skin breach, trauma, surgery, foreign body, prosthetic device
• Travel, animal contact, tick/mosquito exposure: Opens an entirely different differential
• Medication history: Recent antibiotics, immunosuppressants, NSAIDs (mask fever), steroids
• Pregnancy: Increased severity of influenza, COVID-19; fetal risk from Listeria, Zika
• Sexual contacts and menstrual history: Toxic shock syndrome link to tampon use; PID, gonococcemia

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3. PHYSICAL EXAMINATION - TARGETED FOR EMERGENCIES

• Elderly, uremic, cirrhotic patients, and those on steroids or NSAIDs may be afebrile despite serious infection
• Hypothermia in a sick patient = very high mortality risk (cold sepsis)
• Higher temperature at presentation actually correlates with lower 30-day mortality

• Petechiae/purpura → Meningococcemia, Rocky Mountain Spotted Fever (RMSF) - these are emergencies requiring immediate action
• Erythroderma → Toxic shock syndrome (TSS)
• Bullae, crepitus, dusky discoloration → Necrotizing fasciitis (surgical emergency)
• Erythema migrans → Lyme disease
• Maculopapular rash + fever + headache → Rocky Mountain Spotted Fever until proven otherwise
• Petechiae on palms/soles → RMSF (diagnostic clue - most rashes spare palms)

• Altered sensorium = suspect meningitis, encephalitis, septic emboli
• Neck stiffness, Kernig's sign, Brudzinski's sign
• Focal deficits → suggest brain abscess, epidural abscess, stroke from endocarditis

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4. INFECTIOUS DISEASE EMERGENCIES - KNOW THESE COLD

A. Meningococcemia / Bacterial Meningitis

• Fever + headache + neck stiffness + altered mental status
• Petechial/purpuric rash = meningococcemia until proven otherwise
• Act in minutes: LP (or CT first if papilledema/focal deficit), then immediate antibiotics (ceftriaxone + vancomycin + dexamethasone)
• Do not delay antibiotics to wait for CT or LP results in a deteriorating patient

B. Rocky Mountain Spotted Fever (RMSF)

• Fever, headache, myalgias → rash appears Day 2-5 (starts wrists/ankles, spreads centripetally, involves palms/soles)
• Treat empirically with doxycycline - do not wait for confirmatory serology
• Delay in treatment = high mortality

C. Necrotizing Fasciitis / Myonecrosis

• Fever + pain "out of proportion" to skin findings + rapid progression
• Dusky skin, bullae, crepitus, skin necrosis = late findings
• Two types: Type I (mixed flora, diabetics/elderly) and Type II (Group A Strep, toxic shock)
• Emergent surgical debridement + antibiotics (penicillin + clindamycin for GAS; broad-spectrum for Type I)
• Clindamycin added because it inhibits toxin production (protein synthesis inhibitor)

D. Toxic Shock Syndrome (TSS)

• Staphylococcal TSS: fever + erythroderma + hypotension + multiorgan dysfunction; associated with tampon use, post-surgical wounds
• Streptococcal TSS: similar but often associated with necrotizing soft tissue infection; more severe
• Superantigens stimulate massive T-cell activation and cytokine release
• Treatment: source control + antibiotics + IVIG (for streptococcal)

E. Overwhelming Post-Splenectomy Infection (OPSI)

• Asplenic patients (surgical or functional) are exquisitely susceptible to encapsulated organisms: S. pneumoniae, H. influenzae, N. meningitidis
• Can deteriorate within hours from apparent wellness to death (Waterhouse-Friderichsen syndrome)
• Empiric antibiotics at first sign of fever, even before workup
• Prevention: vaccinate against pneumococcus, H. influenzae type b, and meningococcus + daily prophylactic penicillin for some

F. Malaria

• Any febrile patient with recent travel to malaria-endemic region = malaria until proven otherwise
• Periodic fever (every 48-72 h), headache, myalgias, GI symptoms
• Thick and thin blood smears (gold standard); also rapid antigen tests
• Falciparum malaria = medical emergency: cerebral malaria, acute lung injury, severe hemolysis, renal failure, hypoglycemia
• IV artesunate is now first-line for severe malaria

G. Dengue

• "Break-bone fever" - intense myalgias/arthralgias + fever + retro-orbital pain
• Leukopenia, thrombocytopenia
• Dengue hemorrhagic fever/dengue shock syndrome = life-threatening
• No specific antiviral; supportive care; avoid aspirin/NSAIDs (bleeding risk)

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5. APPROACH TO FEVER OF UNKNOWN ORIGIN (FUO)

• Infections (~30%): TB, brucellosis, endocarditis, abscess, CMV, EBV, HIV
• Non-infectious inflammatory conditions (~30%): adult Still's disease, SLE, vasculitis, inflammatory bowel disease
• Malignancy (~20%): lymphoma, renal cell carcinoma, hepatocellular carcinoma
• Miscellaneous/undiagnosed (~20%)

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CHAPTER 128 - PRINCIPLES OF IMMUNIZATION

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1. THE POWER OF VACCINES

Vaccines have averted more than 37 million deaths globally between 2000 and 2019 - a 45% reduction compared to a no-vaccination scenario.

• Vaccine: Inactivated or attenuated pathogen, or component (nucleic acid, protein), that when administered stimulates a protective immune response
• Adjuvant: Added to vaccines to nonspecifically boost immune response (aluminum salts, AS01B in shingles vaccine, MF59 in some flu vaccines)
• Vaccination: The act of administering a vaccine
• Immunization: The process of becoming resistant to disease (usually by vaccination, but may be passive)

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2. IMMUNE RESPONSE TO VACCINES

Primary vs Secondary Response

• Primary response: First exposure to an antigen → antibody peaks several weeks later; requires multiple doses for inactivated vaccines to prime the response
• Secondary (booster) response: Re-exposure → rapid antibody rise within days to a week; memory cells mobilized
• Live attenuated vaccines produce more robust responses, typically need only 1-2 doses
• Inactivated vaccines and toxoids often need multiple doses for adequate priming

Active vs Passive Immunity

• Nirsevimab (Beyfortus): RSV monoclonal antibody now recommended for all infants <8 months entering their first RSV season and for high-risk infants up to 24 months
• SARS-CoV-2 monoclonal antibodies were beneficial during COVID-19 pandemic, especially for immunocompromised individuals

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3. TYPES OF VACCINES

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4. CORRELATES OF PROTECTION

• A correlate of protection is an immune marker (usually serum antibody level) that predicts protection against disease
• Examples: Anti-HBs antibody >10 mIU/mL = protected against Hepatitis B; anti-tetanus toxoid antibody; measles hemagglutination-inhibition titer
• Important because: enables licensure of new vaccines without requiring full efficacy trials; monitors vaccine-induced protection in population

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5. HERD IMMUNITY (COMMUNITY IMMUNITY)

• When a sufficient proportion of the population is immune, transmission chains are broken, protecting even the unvaccinated
• Herd immunity threshold varies by basic reproduction number (R0) of the pathogen:
  • Measles: R0 = 12-18 → requires ~95% immune population
  • Polio: R0 = 5-7 → requires ~80-85% immune population
  • COVID-19 Delta variant: R0 ~5-8 → requires ~80% immune population

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6. VACCINE SAFETY AND ADVERSE EVENTS

• Local reactions: Erythema, swelling, pain at injection site - common, self-limited
• Systemic reactions: Fever, malaise - especially with live vaccines
• Serious adverse events (rare but important):
  • Anaphylaxis: ~1.3 per million doses for most vaccines; requires epinephrine
  • Vaccine-strain viral disease: VAPP (vaccine-associated paralytic poliomyelitis) with OPV - reason US switched to IPV
  • Intussusception: First rotavirus vaccine (RotaShield) - withdrawn; current vaccines have much lower risk
  • Febrile seizures: MMR, MMRV
  • Guillain-Barré syndrome: Some influenza vaccines, very rare
  • Myocarditis: mRNA COVID-19 vaccines, especially in young males after second dose - rare but real; usually mild and self-limited

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CHAPTER 129 - IMMUNIZATION PRINCIPLES AND VACCINE USE

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1. IMPACT AND OVERVIEW

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2. COMPLETE TABLE OF VACCINE-PREVENTABLE DISEASES (US)

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3. DIRECT AND INDIRECT (HERD) EFFECTS

• Direct effect: Vaccine protects the vaccinated person (prevents infection or reduces severity)
• Indirect effect (herd immunity): High vaccination rates reduce community circulation, protecting the unvaccinated
• Disease reduction vs elimination vs eradication:
  • Reduction: fewer cases but disease still circulates
  • Elimination: no indigenous transmission in a region
  • Eradication: pathogen eliminated globally (only achieved for smallpox)
• Some vaccines reduce disease severity (rotavirus → less severe gastroenteritis) or complications (zoster vaccine → less postherpetic neuralgia)

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4. IMMUNIZATION SCHEDULE - KEY CONCEPTS

Childhood Vaccines (US):

• Birth: Hepatitis B
• 2, 4, 6 months: DTaP, IPV, PCV15/20, Rotavirus, Hib
• 6 months onwards: Influenza (annually)
• 12-15 months: MMR, Varicella, Hepatitis A (first dose), PCV booster
• 4-6 years: DTaP, IPV, MMR, Varicella boosters
• 11-12 years: Tdap, MenACWY, HPV series

Adult Vaccines:

• Influenza: Annually for all adults
• Tdap: Every 10 years (tetanus/diphtheria booster); plus Tdap once in adulthood + every pregnancy
• Pneumococcal: PCV20 for all adults ≥65; earlier for high-risk conditions
• Zoster (RZV - Shingrix): Two doses for adults ≥50; preferred over old live zoster vaccine
• RSV: RSVPreF (Abrysvo) or mResvia for adults ≥60; Abrysvo also licensed for use in late pregnancy to protect newborns
• COVID-19: Updated annually for all adults

Catch-Up Immunization:

• Adults who missed childhood vaccines can receive catch-up doses
• Ask vaccination history at every clinical encounter

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5. SPECIAL POPULATIONS

Immunocompromised Patients:

• Live vaccines are generally contraindicated (MMR, varicella, yellow fever, LAIV, BCG) - risk of vaccine-strain disease
• Inactivated vaccines are safe but may have reduced immunogenicity
• HIV patients with CD4 >200 cells/µL can generally receive MMR and varicella
• Extra doses or higher-dose formulations may be needed (e.g., high-dose or adjuvanted influenza for immunocompromised)

Pregnant Women:

• Safe in pregnancy: Influenza (IIV, not LAIV), Tdap (27-36 weeks - protects newborn via maternal antibody transfer), COVID-19, RSVPreF (Abrysvo at 32-36 weeks)
• Contraindicated in pregnancy: Live attenuated vaccines (MMR, varicella, yellow fever)
• Maternal vaccination protects the newborn before they can receive their own vaccines

Elderly:

• High-dose (Fluzone HD) or adjuvanted (Fluad) influenza vaccines recommended for ≥65 years - superior immunogenicity
• All adults ≥65 should receive PCV20 + pneumococcal vaccines
• Shingrix (RZV) is >90% effective against zoster in adults ≥70

Post-Splenectomy:

• Vaccinate before elective splenectomy (≥2 weeks before if possible)
• Pneumococcal, meningococcal (including MenB), and Hib vaccines required

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6. VACCINE HESITANCY - THE DOCTOR'S ROLE

• Vaccine hesitancy is a major public health threat; WHO lists it as one of the top 10 threats to global health
• Physicians are the most trusted source of vaccine information for most patients
• Use presumptive, not participatory approach: "Your child is due for these vaccines today" vs "What vaccines do you want today?"
• Acknowledge concerns empathetically; provide evidence-based responses
• Address specific myths (e.g., autism, "too many vaccines overwhelm the immune system")

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CHAPTER 130 - HEALTH RECOMMENDATIONS FOR INTERNATIONAL TRAVEL

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1. THE EPIDEMIOLOGY OF TRAVEL

• 1.4 billion international tourist arrivals in 2019
• Air travel means travelers can circumnavigate the globe in <24 hours - shorter than the incubation period of nearly all infections
• 43-79% of travelers develop a travel-related illness
• Most are minor; hospitalization in <1-3%
• Leading causes of death in travelers: Cardiovascular events (most common), then injuries (motor vehicle accidents, drowning, homicide, suicide) - NOT infections
• Most common illness: Traveler's diarrhea
• Most common vaccine-preventable illness: Influenza (and now COVID-19)

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2. THE PRE-TRAVEL CONSULTATION - 5 KEY ELEMENTS

Element 1: Risk Assessment

• Detailed itinerary: specific countries, cities, rural vs urban, activities, duration, transit stops
• Medical profile: age, comorbidities, medications, allergies, pregnancy status, immune status
• Type of traveler: tourist, business, VFR (visiting friends and relatives - highest risk!), student, mission worker, medical tourist
• VFR travelers (immigrants/their descendants visiting home countries) often underestimate their risk (loss of acquired childhood immunity), are less likely to seek pre-travel advice, and account for a disproportionate share of travel-associated typhoid, hepatitis A, and malaria

Element 2: Immunizations for Travel

• Influenza, COVID-19, Tdap, MMR, Varicella, Hepatitis B, Polio

• Live attenuated vaccine (17D strain); single dose provides lifetime immunity
• Required by many countries for entry if arriving from endemic country
• Contraindicated in: Infants <6 months, immunocompromised, severe egg allergy, thymus disease, adults ≥60 (increased risk of vaccine-associated viscerotropic disease)

Element 3: Malaria Prevention

Element 4: Traveler's Diarrhea

• Most common travel illness: affects up to 50% of travelers to developing countries
• Major pathogens: ETEC (enterotoxigenic E. coli) most common; also Campylobacter, Salmonella, Shigella, rotavirus, norovirus, Giardia, Cryptosporidium, entamoeba
• Food and water precautions ("boil it, cook it, peel it, or forget it"):
  • Drink bottled/boiled water, avoid ice
  • Avoid raw vegetables, salads, unpasteurized dairy, raw shellfish
  • Eat only fully cooked hot foods
  • Be careful with street food

• Mild (no fever, no blood): Oral rehydration + loperamide (slows motility; do NOT use if fever or blood)
• Moderate: Azithromycin 500mg x1 (preferred; covers Campylobacter, ETEC, Shigella) or fluoroquinolone (increasing resistance, especially in South/Southeast Asia)
• Severe (fever, blood, signs of dehydration): Azithromycin 500mg daily x 3 days; seek medical care
• Rifaximin (poorly absorbed): Effective for non-bloody traveler's diarrhea due to ETEC; not for Campylobacter or invasive pathogens

Element 5: Injury and Other Condition Prevention

• Road traffic accidents are the leading cause of death in travelers
• Advice: Wear seatbelts; avoid motorcycles/mopeds in unfamiliar areas; never drive after drinking; be aware of road conditions at night
• Drowning: respect local ocean conditions, riptides; no alcohol while swimming
• Sun protection: high-SPF sunscreen, protective clothing, avoid peak sun hours
• Altitude sickness: prophylaxis with acetazolamide for rapid ascent; gradual acclimatization
• Schistosomiasis: avoid freshwater swimming in sub-Saharan Africa
• Blood-borne infection: avoid tattoos, piercings, and unprotected sex during travel
• Psychiatric health: travel stressors can exacerbate depression, anxiety, and other conditions

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3. POST-TRAVEL ILLNESS

• Always: Malaria smears/RDT regardless of prophylaxis compliance
• Dengue: 1-2 week incubation; leukopenia + thrombocytopenia
• Typhoid: 1-3 week incubation; relative bradycardia, rose spots
• Rickettsial disease: eschar + fever + rash
• Viral hemorrhagic fever (rare but critical to consider after travel to Ebola-endemic regions)
• Hepatitis A/B/E
• Consider: HIV (if at-risk exposures)

• <1 week: Dengue, traveler's diarrhea, meningococcal, SARS-CoV-2
• 1-3 weeks: Malaria (falciparum), typhoid, hepatitis A

• 3 weeks: Malaria (vivax), viral hepatitis (B, E), TB, brucellosis, visceral leishmaniasis

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4. SPECIAL TRAVELER GROUPS

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MASTER REVIEW: HIGH-YIELD EXAM POINTS

Quick-Fire Summary

1. Germ theory: Pasteur + Koch (late 19th century); miasma theory before
2. Infection-associated cancers: H. pylori → gastric cancer; HPV → cervical cancer; HBV/HCV → liver cancer (~16% of all cancers)
3. Microbiome: Essential, not pathological; disruption → C. diff; FMT is proven therapy
4. Complement pathways: Classical (antibody), Lectin (mannose-binding lectin), Alternative (spontaneous). All converge at C3 → opsonization or MAC (lysis)
5. C5-C9 deficiency → recurrent Neisseria infections
6. Lysozyme: Kills gram-positive bacteria (degrades peptidoglycan); gram-negative are protected by outer membrane
7. A-B toxins: Cholera (activates adenylate cyclase), Diphtheria (blocks protein synthesis), Botulinum (blocks ACh)
8. Biofilm = dramatically increased antibiotic resistance + protection from phagocytosis
9. Petechiae + fever = meningococcemia or RMSF → emergent
10. RMSF treatment = doxycycline immediately, don't wait for serology
11. Hypothermia in infection = very high mortality
12. Asplenia → encapsulated organisms (pneumococcus, H. flu, meningococcus); vaccinate + prophylaxis
13. FUO: Infections 30%, inflammatory 30%, malignancy 20%
14. PET scan = most sensitive for occult infection/malignancy in FUO
15. Live vaccines contraindicated in pregnancy and immunocompromised
16. Herd immunity for measles requires ~95% vaccination (R0 12-18)
17. VFR travelers = highest risk group in travel medicine
18. Malaria: Always test in returning febrile traveler even if prophylaxis taken; P. falciparum = emergency; P. vivax/ovale need primaquine for hypnozoites (check G6PD first)
19. Traveler's diarrhea treatment: Azithromycin preferred (fluoroquinolone resistance rising)
20. Deaths in travelers: Cardiovascular > Injuries >> Infections
21. mRNA vaccines (COVID-19, RSV, flu): encode antigen; no replication; rapidly developed
22. Nirsevimab (Beyfortus): RSV monoclonal for all infants <8 months
23. Shingrix (RZV): >90% effective for zoster in elderly; preferred over old live vaccine
24. MALDI-TOF: Identifies organisms in minutes by protein mass spectrometry
25. NGS/Metagenomic sequencing: Identifies novel pathogens with no preconceived hypothesis required

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