Cardiovascular Diseases: Lyme Disease, Toxoplasmosis, Schistosomiasis, and Gas Gangrene

Lyme Disease

• Causative Agent: Borrelia burgdorferi (gram-negative spirochete).
• Prevalence: Leading vector-borne disease in the U.S.
• Discovery: In 1975, an unusually high incidence of childhood arthritis was observed in Lyme, CT (100 times higher than expected).

Distribution and Incidence

• Most cases are found in the Northeast, upper Midwest, and Pacific West.
• Major Reservoirs: Field mice, squirrels, and white-tailed deer.
• Transmission: Direct contact via Ixodes ticks (deer tick saliva).
• High-risk groups: Farmers and landscapers.

Ixodes Ticks

• Blacklegged Tick (Ixodes scapularis).

Epidemiology

• The life cycle occurs over 2 years, requiring a blood meal at each stage.
• Tick larvae get infected from small animals.
• Adults feed on deer and mate.
• Lifecycle:
  • Uninfected six-legged larva hatches from egg and develops.
  • Larva feeds on small animal, becoming infected.
  • Larva develops into eight-legged nymph.
  • Nymph develops into adult tick.
  • Nymph feeds on animal or human, transmitting infection.

Signs and Symptoms

• Incubation Time: 3-30 days.
• Three Stages:
  • 1st Stage:
    • Erythema migrans: Bull’s-eye rash on skin at the site of the tick bite.
    • Flu-like symptoms.
  • 2nd Stage:
    • Heart irregularities.
    • CNS symptoms.
  • 3rd Stage:
    • Arthritis (likely caused by the immune response to the bacteria).
• Long-term complications (1/10 persons): Headaches, fatigue, depression.

Pathogenesis

• Early in infection involves penetration of vessels and dissemination, leading to Erythema migrans.
• Late in infection involves penetration of tissues and establishment of infections in the heart, joints, and skin, potentially causing carditis, arthritis, and facial palsy.
• Spirochetes evade the immune system in the blood due to proteins in their outer membrane.

Treatment and Prevention

• Treat early.
• Administer treatment within the first 6 weeks of infection to prevent arthritis.
• Drug of Choice: Doxycycline (generic).

Prevention

• LYMErix: Lyme Disease Vaccine (Recombinant OspA).
• DEET is effective because ticks 'taste' the surface of the skin with their legs and dislike the taste of DEET. The EPA reports that DEET is not a health threat to adults or children when applied topically.

Removal of Ticks

• Use fine-tipped tweezers.
• Grasp the tick close to the skin and quickly pull.
• Avoid using a hot match, nail polish, or petroleum jelly.

Toxoplasmosis

• Causative Agent: Toxoplasma gondii.

Epidemiology

• Definitive Host & Reservoir (sexual life cycle): Felidae family (wild or domesticated cats).
• Other reservoirs or intermediate hosts: Cattle, pigs, soil, rodents, and humans.

Oocysts

• Cyst form of T. gondii shed by cats.
• Cysts can survive in soil (up to 1 year) and salt water.

Transmission

• Direct:
  • Vertical transmission during pregnancy.
• Indirect:
  • Fecal/oral (kitty litter box).
  • Fecal/oral (contact with soil, i.e., gardening).
  • Eating undercooked pork or beef (contaminated food).

Epidemiology in Humans

• Human infection is common.
• High prevalence in Central America (stray cats), potentially as high as 95%.

Pathogenesis

• T. gondii is an obligate intracellular parasite.
• Humans ingest oocysts; free organisms are taken up by macrophages and delivered to various sites, lodging as cysts in the liver, heart, retina, brain/spinal cord.
• Organism capable of vertical transmission.
  • Effects on fetus: mental disabilities, blindness or vision abnormality, deafness, or stillbirth.
  • Effects on AIDS patients: development of encephalitis (25% of AIDS cases).
• Studies link infection to mental disorders like schizophrenia, but infection is a significant risk factor, not a cause.
• People with very high titers have high rates of suicide attempts.

Diagnosis, Treatment, and Prevention

• Diagnosis: Blood smear or CSF sample.
• No treatment for pets.
• Treatment (humans): Sulfonamide & Trimethoprim antibiotics & Macrolide Spiramycin (early in pregnancy).
• Best Prevention: Wash hands, limit “hunting” by cats, pregnant women should avoid eating raw meat and avoid flushing kitty litter down the toilet.

Schistosomiasis

• Epidemiology: Hundreds of millions infected per year (sub-Saharan Africa); 3rd leading endemic parasite after Malaria.
• Causative agents: Schistosoma species
  • S. mansoni (intestinal inflammation).
  • S. japonicum (intestinal inflammation).
  • S. hematobium (inflammation of the bladder wall); linked to female genital schistosomiasis.
• Reservoir: Wild animals (i.e., monkeys) and humans.

Signs and Symptoms

• Fever and rash.
• Blood in urine (haematuria) or stool.
• Enlarged liver or spleen (splenomegaly).
• Sometimes CNS can be affected.

Pathogenesis

• Cercariae penetrate skin and mature into adults in the blood; adult worms mate in the liver.
• Eggs are deposited in blood vessels (liver, bladder, small intestine)à Triggers inflammation à eggs shed in stools or urine.
• Complications: granulomas in bladder result in bladder cancer; colon cancer; liver damage; infertility.

Transmission

• Vector: Freshwater snail.
• Larvae (cercariae) in ponds or lakes penetrate skin (enter hair follicles).

Treatment and Prevention

• Treatment: Praziquantel.
• Prevention: Avoid snails in fresh water, proper disposal of human waste/sanitation, and control snail populations.
• No vaccine available, but several clinical trials are underway.

Praziquantel

• Mode of Action: Causes severe spasms of muscles in the worm, resulting in paralysis.
• Dead worms are passed through feces.

Vaccine

• Currently in clinical trials.
• Reinfection by schistosomes is common even after successful treatment because few individuals develop protective immunity.
• The high rate of reinfection underscores the urgent need for a preventive vaccine.

Gas Gangrene

• Causative agent: Clostridium perfringens
  • GRAM + rods; obligate anaerobes
  • Highly fermentive
• Reservoir: Human GI; soil; aquatic environments
• Responsible for 80-95% of wound-associated gangrene
• Transmission: Indirectly (open wound or trauma)

Signs and Symptoms

• Infection of deep tissue/trauma à swelling
• Loss of blood supply (ischemia) = creates oxygen-free zone
• Lots of pain & swelling at the site of infection
• Death of tissue (necrosis)
• Lots of gas within wounds

Epidemiology

• War & surgical wounds; miscarriage, intestinal injury, injuries in diabetics, frostbite

Pathogenesis

• Damage to blood supply in soft tissue leads to necrosis of tissue & growth of C. perfringens
• Alpha toxin: Breaks down cell membranes & triggers blood clots (thrombi)!
• Theta toxin (phospholipase): Forms pores in all cell membranes
• C. perfringens ferments sugars à fluids & gases cause swelling

Diagnosis, Treatment, and Prevention

• Diagnosis: Traumatic gas gangrene - fluid from wounds can be cultured
• Treatment: Surgery, hyperbaric O2 treatment, antibiotics
• Prevention: Wound care, precautionary antibiotics before surgeries