The Spirochetes Gram-negative human pathogens Free living saprobes, or commensals of animals, not primary pathogens Treponema Leptospira Borrelia

Typical spirochete

Genus Treponema Thin, regular, coiled cells Live in the oral cavity, intestinal tract, and perigenital regions of humans and animals Pathogens are strict parasites with complex growth requirements Require live cells for cultivation

Treponema Pallidum: The Spirochete of Syphilis Humans are the natural host Extremely fastidious and sensitive; cannot survive long outside of the host Sexually transmitted and transplacental

Pathogenesis and Host Response Spirochete binds to epithelium (mucous membrane or abraded skin), multiplies, and penetrates capillaries Moves into circulation and multiplies Untreated syphilis marked by 3 clinical stages: Primary, secondary, tertiary Spirochete appears in lesions and blood during first 2 stages – communicable

Primary syphilis – appearance of hard chancre at site of inoculation; chancre heals spontaneously Secondary syphilis – fever, headache, sore throat, red or brown rash on skin, palms, and soles; rash disappears spontaneously Tertiary syphilis – about 30% of infections enter in tertiary stage; can last for 20 years or longer; numerous pathologic complications occur in susceptible tissues and organs Neural, cardiovascular symptoms, gummas develop Congenital syphilis – nasal discharge, skin eruptions, bone deformation, nervous system abnormalities

Primary syphilis lesion, chancre

Symptom of secondary syphilis

Manifestations of syphilis

Congenital syphilis

Diagnosis and Treatment Stages of syphilis mimic other diseases Consider symptoms, history, microscopic, and serological testing RPR, VDRL, FTA-ABS Treatment: penicillin G

Treponema pallidum

Nonsyphilitic Treponematoses Resemble syphilis; rarely transmitted sexually or congenitally; cutaneous and bone diseases endemic to specific regions Bejel – T. pallidum subspecies endemicum; deforming childhood infection of the mouth, nasal cavity, body, and hands Yaws – T. pallidum subspecies pertenue; invasion of skin cut, causing a primary ulcer that seeds a second crop of lesions Pinta – T. carateum; superficial skin lesion that depigments and scars the skin

Endemic treponematoses

Leptospira and Leptospirosis Tight, regular individual coils with a bend or hook at one or both ends L. biflexa – harmless, free-living saprobe L. interrogans – causes leptospirosis, a zoonosis Bacteria shed in urine; infection occurs by contact with contaminated urine; targets kidneys, liver, brain, eyes Sudden high fever, chills, headache, muscle aches, conjunctivitis, and vomiting Long-term infections may affect kidneys and liver 50-60 cases a year in U.S.

Borrelia: Arthropod-Borne Spirochetes Large, 3-10 coils irregularly spaced Borrelioses transmitted by arthropod vector B. hermsii – relapsing fever B. burgdorferi – Lyme disease

B. Hermsii – Relapsing Fever Mammalian reservoirs – squirrels, chipmunks, wild rodents Tick-borne After 2-15-day incubation, patients have high fever, shaking, chills, headache, and fatigue Nausea, vomiting, muscle aches, abdominal pain; extensive damage to liver, spleen, heart, kidneys, and cranial nerves Parasite changes and immune system tries to control it – Recurrent relapses Tetracycline

Pattern in relapsing fever

B. Burgdorferi – Lyme Disease Carried by white-footed mouse, transmitted by Ixodes ticks Complex 2-year cycle involving mice and deer Nonfatal, slowly progressive syndrome that mimics neuromuscular and rheumatoid conditions 50-70% get bull’s eye rash Fever, headache, stiff neck, and dizziness If untreated can progress to cardiac and neurological symptoms, polyarthritis Tetracycline, amoxicillin Vaccine for dogs, human vaccine discontinued Insect repellant containing DEET

Cycle of Lyme disease

Views of Lyme disease skin rash

Curviform Gram-Negative Bacteria and Enteric Diseases Three genera: Vibrio – comma-shaped rods, single polar flagellum Campylobacter – short spirals or curved rods; one flagellum Helicobacter – spirochete with tight spirals and several polar flagella

Vibrio Cholera Comma-shaped, possess unique O and H Ags El Tor biotype: survives longer, more infectious Infectious dose 108 Infects mucous barrier of small intestine, noninvasive Cholera toxin causes electrolyte and water loss through secretory diarrhea, “rice water stool”; resulting dehydration leads to muscle, circulatory, and neurological symptoms Treatment: oral rehydration, tetracycline Vaccine available

Alterations in intestinal function caused by cholera toxin

Alterations in intestinal function caused by cholera toxin

Pathogens Carried by Seafood Salt-tolerant inhabitants of coastal waters, associate with marine invertebrates Vibrio parahaemolyticus – gastroenteritis from raw seafood; symptoms similar to cholera Vibrio vulnificus – gastroenteritis from raw oysters; serious complications in persons with diabetes or liver disease Treatment – fluid and electrolyte replacement; occasionally antimicrobials

Diseases of the Campylobacter Vibrios Campylobacters – slender, curved, or spiral bacilli, often S-shaped or gull-winged pairs Polar flagella Common residents of the intestinal tract, genitourinary tract, the oral cavity of birds and mammals Most important: Campylobacter jejuni C. fetus

Campylobacter Jejuni Enteritis Important cause of bacterial gastroenteritis Transmitted by beverages and food Reach mucosa at the last segment of small intestine near colon; adhere, burrow through mucus and multiply Heat-labile enterotoxin CJT stimulates a secretory diarrhea like that of cholera Symptoms of headache, fever, abdominal pain, bloody or watery diarrhea Treatment with rehydration and electrolyte balance therapy

Campylobacter fetus – opportunistic pathogen that infects debilitated persons or women late in pregnancy Meningitis, pneumonia, arthritis, septicemia in the newborn

Helicobacter Pylori: Gastric Pathogen Curved cells discovered in 1979 in stomach biopsied specimens Causes 90% of stomach and duodenal ulcers; apparent cofactor in stomach cancer People with type O blood have a 1.5-2X higher rate of ulcers Produces urease which converts urea into ammonium and bicarbonate

The causative agent of stomach ulcers

Medically Important Bacteria of Unique Morphology and Biology

Family Rickettsiaceae Contains about 23 species of pathogens, mainly in the genus Rickettsia Cause diseases called rickettsioses All are intracellular parasites requiring live cells for cultivation Spend part of their life cycle in arthropod vectors Rickettsioses are important emerging diseases

Rickettsia Obligate intracellular parasites Gram-negative cell wall Among the smallest bacteria Nonmotile pleomorphic rods or coccobacilli Ticks, fleas, and lice are involved in their life cycle Bacteria enter endothelial cells and cause necrosis of the vascular lining – vasculitis, vascular leakage, and thrombosis

Specific Rickettsioses Epidemic typhus – R. prowazekii carried by lice; starts with a high fever, chills, headache, rash; Brill-Zinsser is a chronic, recurrent form Endemic typhus – R. typhi, harbored by mice and rats; occurs sporadically in areas of high flea infestation; milder symptoms Rocky Mountain spotted fever – R. rickettsii zoonosis carried by dog and wood ticks; most cases in Southeast and on eastern seaboard; distinct spotted rash; may damage heart and CNS Ehrlichia genus contains 2 species of rickettsias; tick-borne bacteria cause human monocytic and granulocytic ehrlichiosis

Trends in infection for Rocky Mountain spotted fever

Transmission cycle in Rocky Mountain spotted fever

Rash in RMSF

Related to the Rickettsioses Coxiella burnetti Bartonella sp.

Coxiella Burnetti Causes Q fever Intracellular parasite Produces an unusual resistant spore Harbored by a wide assortment of vertebrates and arthropods Infectious material includes urine, feces, milk, and airborne particles Usually inhaled causing pneumonitis, fever, hepatitis Tetracycline treatment Vaccine available

Bartonella Species Small gram-negative, fastidious, cultured on blood agar Cause: Trench fever, spread by lice Cat-scratch disease, a lymphatic infection associated with a clawing injury by cats Bacillary angiomatosus in AIDS patients Tetracycline, erythromycin, and rifampin

Cat-scratch disease

The Chlamydiaceae Obligate intracellular parasites Small, gram-negative cell wall Alternate between 2 stages: Elementary body – small metabolically inactive, extracellular, infectious form released by the infected host Reticulate body – noninfectious, actively dividing form, grows within host cell vacuoles

Life cycle of Chlamydia

Chlamydia Trachomatis Human reservoir 2 strains Trachoma – attacks the mucous membranes of the eyes, genitourinary tract, and lungs Ocular trachoma – severe infection, deforms eyelid and cornea, may cause blindness Inclusion conjunctivitis – occurs as baby passes through birth canal; prevented by prophylaxis STD – second most prevalent STD; urethritis, cervicitis, salpingitis (PID), infertility, scarring Lymphogranuloma venereum – disfiguring disease of the external genitalia and pelvic lymphatics

The pathology of primary ocular chlamydial infection

Diagnosis of chlamydial infection

Chlamydophila – A New Genus Contains members that used to be members of genus Chlamydia Chlamydophila pneumoniae – causes an atypical pneumonia that is serious in asthma patients C. psittaci – causes ornithosis, a zoonosis transmitted to humans from bird vectors; highly communicable among all birds; pneumonia or flulike infection with fever, lung congestion

Molliculites and Other Cell- Wall-Deficient Bacteria Called mycoplasmas Naturally lack cell walls, highly pleomorphic Require special lipids from host membranes Treated with tetracycline, erthyromycin M. pneumoniae – primary atypical pneumonia; pathogen slowly spreads over interior respiratory surfaces, causing fever, chest pain, and sore throat M. genitalium and Ureplasma urealyticum – weak sexually transmitted pathogens

The morphology of mycoplasmas

Bacteria That Have Lost Their Cell Walls Exposure to certain drugs or enzymes can result in cell wall-deficient bacteria called L forms or L-phase Induced or occur spontaneously May be involved in some chronic diseases L- phase variants of group A streptococci, Proteus, and Corynebacterium, Mycobacterium avium paratuberculosis