Person-to-Person Diseases: Pathogens, Symptoms, and Transmission

Principles of Epidemiology and Disease Transmission

The ability of a disease to spread within a human population is quantified using the basic reproduction number, denoted as $R_0$. This value determines the potential rate of spread and suggests the future behavior of an infectious agent in a community. The thresholds for $R_0$ are defined as follows:

• If R_0 < 1: The disease will not spread and will eventually die out.

• If $R_0 = 1$: The disease will remain stable in the community as an endemic presence but will not cause an epidemic.

• If R_0 > 1: The disease will spread and possesses the potential to cause an epidemic.

There is a direct relationship between the $R_0$ of a pathogen and the Herd Immunity Threshold (HIT), which is the percentage of the population that must be immune to prevent an epidemic. The following data points correlate specific diseases with their $R_0$ and HIT values:

• Influenza: $R_0$ ranges from approximately $1.25$ (HIT = $20\%\text{}$) to $1.6$ (HIT = $37.5\%\text{}$).

• SARS and COVID-19 Ancestral Strain: $R_0 = 2.5$ with an HIT of $60\%\text{}$.

• COVID-19 Alpha Variant: $R_0$ ranges from $4$ (HIT = $75\%\text{}$) to $5$ (HIT = $80\%\text{}$).

• COVID-19 Delta Variant: $R_0 = 8$ with an HIT of $87.5\%\text{}$.

• Polio: $R_0 = 5$ with an HIT of $80\%\text{}$.

• Chickenpox: $R_0$ ranges from $10$ (HIT = $90\%\text{}$) to $12.5$ (HIT = $92\%\text{}$).

• Measles: One of the most infectious diseases, with $R_0$ ranging from $16$ (HIT = $93.75\%\text{}$) to $20$ (HIT = $95\%\text{}$).

Modes of Pathogen Transmission

Disease transmission is categorized into direct and indirect modes. Direct transmission occurs through person-to-person contact (sexual intercourse, direct touch) or droplet spread. Indirect transmission involves intermediaries, classified as either vehicle-borne (contaminated water/soil, needles, eggs, poultry) or vector-borne (mechanical or biological transmission via bites, stings, or worms). Person-to-person transmission is further subdivided into three major categories: Contact Transmission, Airborne Transmission, and Sexual Transmission.

Airborne Pathogens and Respiratory Dynamics

Airborne transmission relies on aerosols, which are suspensions of particles or droplets in the air. These include airborne dusts, mists, fumes, smoke, and saliva droplets. Most pathogens survive poorly in the air and are therefore effectively transmitted only over short distances. Airborne pathogens typically cause respiratory infections, though they can progress to system-wide (systemic) infections. Pathogens colonize specific regions of the respiratory tract based on environmental factors like temperature, air flow, and $\text{pH}$.

The anatomy of the respiratory tract filters particles by size and air speed:

• Nasal cavity: Air speed $150\,\text{cm/s}$; captures particles over $60\,\mu\text{m}$. Common resident: Staphylococcus aureus.

• Oral cavity: Common resident: Neisseria meningitidis.

• Pharynx: Common resident: Streptococcus pyogenes.

• Larynx: Common resident: Corynebacterium diphtheriae.

• Trachea: Air speed $59\,\text{cm/s}$; captures particles of $20\,\mu\text{m}$. Primary site for Haemophilus influenzae, Common cold virus, and Mycoplasma pneumoniae.

• Bronchi: Primary/secondary bronchi capture particles of $10\,\mu\text{m}$ (speed $20\,\text{cm/s}$) and $2\,\mu\text{m}$ (speed $14\,\text{cm/s}$). Sites for Influenza virus, Mycobacterium tuberculosis, and Coccidioides immitis.

• Lower Respiratory Tract (Bronchioles and Alveoli): Air speed drops to $1\,\text{cm/s}$ or less for particles below $3\,\mu\text{m}$. Sites for Bordetella pertussis, Streptococcus pneumoniae, Pneumonia viruses, Coxiella burnetii, and Chlamydophila pneumoniae.

Airborne Bacterial Pathogens

Streptococcus pyogenes: Commonly found in low numbers in the respiratory tracts of healthy individuals. It causes Strep throat, and can also infect the inner ear, mammary glands, and skin (impetigo). Certain Group A strains carry a lysogenic bacteriophage that encodes exotoxins, resulting in Scarlet Fever and Streptococcal Toxic Shock Syndrome. It can cause severe systemic infections such as cellulitis and necrotizing fasciitis (flesh-eating bacteria).

Streptococcus pneumoniae: The primary cause of pneumonia. While treatable with antimicrobial agents, drug-resistant strains are increasingly common.

Corynebacterium diphtheriae: Pathogenic strains produce a powerful exotoxin causing a pseudomembrane in the throat. Death results from a combination of suffocation by this membrane and tissue destruction. Treatment includes diphtheria antitoxin (necessary because antibiotics act too slowly against the toxin).

Bordetella pertussis: Causes whooping cough, primarily in school-age children. There has been a consistent upward trend in infections since the 1980s due to decreased vaccination. The DTaP vaccine prevents diphtheria, tetanus, and pertussis.

Mycobacterium tuberculosis (TB): A worldwide infectious disease transmitted by airborne droplets. Treatment involves antimicrobial therapy, typically using Isoniazid for a 9-month regimen, though resistance is a major concern.

Mycobacterium leprae (Hansen’s Disease): Characterized by bulblike lesions caused by bacterial growth in skin Schwann cells that insulate nerves. It is transmitted via direct contact and respiratory routes. Incubation varies from weeks to years. In 2017, there were over $210,000$ new cases, mainly in Africa, India, and Brazil.

Neisseria meningitidis: Causes bacterial meningitis, an inflammation of the meninges (membranes lining the CNS, spinal cord, and brain). It can also cause Meningococcemia, characterized by intravascular coagulation, gangrene (tissue destruction), shock, and death in over $10\%\text{}$ of cases.

Airborne Viral Pathogens

MMR Vaccine-Preventable Diseases:

• Measles: Caused by a paramyxovirus; a highly infectious acute epidemic disease affecting children.

• Rubella: Caused by a togavirus; symptoms resemble measles but are milder.

• Mumps: Caused by a paramyxovirus; involves inflammation of the salivary glands. Infections for all three are rising in the US due to vaccine hesitancy.

Varicella-Zoster Virus (VZV): A herpesvirus transmitted via infectious droplets. It causes chickenpox (varicella) and establishes a lifelong latent infection in nerve cells. It can reactivate as shingles, causing painful skin eruptions.

The Common Cold: The most common infectious disease, usually mild and short-term. Primarily caused by rhinoviruses (more than $150$ strains). The high volume of strains prevents the development of a complete vaccine.

Influenza: Divided into types A, B, and C, with Type A being the most significant human pathogen. Strains are identified by surface glycoproteins. The genome's plasticity allows for annual outbreaks. Notable historical events include the 1918 Spanish Flu.

Direct Contact and Sexually Transmitted Diseases

Staphylococcus aureus: Causes acne, boils, impetigo, pneumonia, carditis, meningitis, and arthritis. Diseases often result from pyogenic (pus-forming) infections or staphylococcal superantigen exotoxins.

Helicobacter pylori: A Gram-negative, motile, spiral-shaped bacterium associated with gastritis, ulcers, and gastric cancers. It colonizes the mucosa of the stomach and upper intestinal tract. It is transmitted via person-to-person contact or contaminated food/water.

Sexually Transmitted Diseases (STDs/STIs): These pathogens are generally restricted to body fluids of the genitourinary tract exchanged during sexual activity.

• Chlamydia trachomatis: The most common STI globally; treatable with antibiotics.

• Neisseria gonorrhoeae: Prevalent and often asymptomatic in women; untreated cases lead to pelvic inflammatory disease.

• Treponema pallidum (Syphilis): Progresses through primary, secondary, and tertiary stages. Penicillin is effective for early stages. Syphilis was the subject of the Tuskegee Experiment, one of history's greatest medical ethics violations, where treatment was withheld from African American men to study the disease's progression.

• Herpes Simplex Viruses (HSV): HSV-1 causes cold sores; HSV-2 causes genital blisters. Both are incurable but manageable.

• Human Papillomavirus (HPV): Over $200$ strains. Some cause warts, while others lead to cervical neoplasia, cervical cancers, and oral/esophageal cancers. The 9-valent Gardasil vaccine is widely used for prevention.

• HIV/AIDS: HIV, recognized in 1981, causes AIDS by progressively weakening CD4 cells. Approximately $1.1\text{ million}$ people are infected in the US. Globally, $80\text{ million}$ have been infected and $34\text{ million}$ have died.

Eukaryotic Pathogens: Fungi and Protists

Fungi cause disease through inappropriate immune responses (allergens/asthma), mycotoxins (e.g., aflatoxins from Aspergillus which grow on corn/peanuts and cannot be cooked away), or infections (mycoses). Unicellular Candida yeasts cause common mucosal vaginal infections, often triggered by antibiotic use which disrupts normal microbiota.

Specific protist pathogens include:

• Naegleria fowleri: A brain-eating amoeba found in warm soil-contaminated water. It enters through the nose and burrows into the brain, causing hemorrhage and damage.

• Giardia intestinalis: A flagellated anaerobic parasite causing "Beaver Fever" (foul-smelling diarrhea and cramps) transmitted through contaminated water.

• Cryptosporidium parvum: Produces thick-walled oocysts shed in feces. It was responsible for the largest single waterborne disease outbreak in US history (Milwaukee, WI, 1993).

• Toxoplasma gondii: Transmitted by cats and undercooked meat. It is often asymptomatic but can damage the eyes and brain in immunocompromised hosts.

• Plasmodium (Malaria): Transmitted by Anopheles mosquito vectors. It infects $250\text{ million}$ and kills $600,000$ annually. Malaria was historically common in the southern US, which is why the CDC is located in Atlanta. Sickle cell trait provides a degree of protection against Malaria. A vaccine was introduced in 2021.