Infectious Disease: Overview & Introduction

Harrison's Principles of Internal Medicine, 22nd Edition (2025)

Historic Perspective

• Identification of etiologic agents of countless diseases
• Discovery of antibiotics
• Development of vaccines against deadly infections
• Elimination of smallpox

Global Burden

• Infectious diseases remain the second leading cause of death worldwide
• 9.6 million deaths from infectious diseases in 2019
• Disproportionately affect:
  • Children < 1 year of age
  • Adults > 70 years
  • Persons in low- and middle-income countries
• ~17% of all global deaths in 2019 were infection-related; up to 69% in sub-Saharan Africa
• HIV-infected adults comprise 16–25%+ of the total population in some southern African countries

Infectious Agents & Their Diseases

Key Bacteria and Their Tropisms

Pathogenesis: How Microbes Cause Disease

1. Colonization vs. Infection

• Most microbes that encounter the human body are eliminated without causing disease
• Infection requires the pathogen to overcome host defenses, adhere to host cells, and proliferate

2. Mechanisms of Microbial Virulence

• Adhesins: Surface structures that allow attachment to host cells (e.g., fimbriae of E. coli)
• Invasion: Pathogens can invade host epithelial cells (e.g., Shigella, Salmonella)
• Toxins:
  • Preformed toxins (food poisoning): S. aureus enterotoxins, Bacillus cereus cereulide, botulinum toxin (blocks neurotransmitter release → botulism)
  • In vivo toxins: Produced during infection (e.g., C. diphtheriae exotoxin, C. difficile toxins A and B)
• Immune evasion: Capsules (e.g., Streptococcus pneumoniae), intracellular survival (e.g., Mycobacterium tuberculosis)
• Environmental modification: H. pylori converts urea → ammonia, raising gastric pH to survive in stomach acid

3. Infectious Diseases Linked to Malignancy

• ~16% of all malignancies are associated with infectious causes:
  • H. pylori → peptic ulcer disease & gastric carcinoma
  • HPV → cervical cancer
  • Hepatitis B & C → liver cancer

The Host Response

• The immune system is the primary defense against infection
• Innate immunity (first line): Physical barriers (skin, mucosa), phagocytes, complement, pattern recognition receptors (e.g., Toll-like receptors)
• Adaptive immunity (second line): T cells, B cells, antibodies — develops over days to weeks
• Immunocompromised patients (HIV, transplant recipients, those on biologics) are at markedly elevated risk for opportunistic infections

Emerging & Re-emerging Infectious Diseases

• New pathogens: HIV (1980s), SARS-CoV (2003), SARS-CoV-2 (2019), Ebola, mpox
• Antimicrobial resistance — a critical global threat:
  • Carbapenem-resistant Enterobacteriaceae and Acinetobacter spp.
  • Candida auris (multidrug-resistant fungus)
  • Drug-resistant M. tuberculosis (MDR-TB, XDR-TB)
  • Vancomycin-resistant enterococci (VRE)
• Bioterrorism potential of weaponized pathogens
• Climate change altering geographic distribution of vector-borne diseases

Approach to the Patient

Key Principles

1. Detailed history: Travel, exposures (animals, sick contacts), sexual history, immunization status, occupational risks
2. Physical examination: Fever patterns, rashes, lymphadenopathy, focal signs of infection
3. Epidemiologic context: Local disease prevalence is critically important — the same presentation has very different differentials in Boston vs. sub-Saharan Africa
4. Microbiologic confirmation: Cultures, PCR, serology, antigen tests — always attempt to identify the causative organism before or alongside treatment
5. Empirical therapy when needed: Use local antibiogram data and clinical syndrome to guide initial therapy (see Table 12-6 in Harrison's for empirical antibiotic regimens)
6. Antimicrobial stewardship: Use the narrowest effective agent; de-escalate based on culture results to limit resistance

When to Consult Infectious Disease

• Unusual or rare organisms
• Multidrug-resistant organisms
• Infections requiring prolonged or complex antibiotic courses (endocarditis, osteomyelitis, meningitis)
• Immunocompromised hosts with opportunistic infections
• Fever of unknown origin (FUO)

Microbial Genomics & Infectious Disease (Chapter 126, Harrison's)

• Whole-genome sequencing (WGS) enables outbreak investigation, drug-resistance genotyping, and pathogen identification
• Metagenomic sequencing can identify pathogens without prior culture
• The human microbiome — the trillions of commensal organisms living in and on the human body — plays a major role in health and disease susceptibility

Summary

"Infectious diseases continue to represent a formidable challenge for patients and physicians alike." — Harrison's Principles of Internal Medicine, 22nd Edition