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Miscellaneous Bacterial Agents of Disease

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1 Miscellaneous Bacterial Agents of Disease
Chapter 21 Miscellaneous Bacterial Agents of Disease

2 Spirochetes Genus - Treponema Genus - Borrelia
T. pallidum ssp. pallidum (syphilis) T. pallidum ssp. pertenue (yaws) T. pallidum ssp. endemium (non-endemic syphilis) T. carateum (pinta) Genus - Borrelia B. recurrentis - relapsing fever B. burgdorferi - Lyme disease Genus - Leptospira interrogans

3 General characteristics of Spirochetes
Flexible, helically-shaped cylindrical body composed of peptidoglycan & cytoplasmic membrane enclosing cytoplasm Treponema - loosely coiled Borrelia - loosely coiled Leptospira - thin, tightly coiled with hooked ends

4 General characteristics of Spirochetes
Multi-layered outer envelope surrounding cell Flagella attached between outer membrane & cylindrical body at each end (internal) Have a flexous form of motility

5 Clinical Manifestations of Treponema
T. pallidum ssp. pallidum (syphilis) Goes through several stages over a period of years Primary syphilis - characterized by lesion at portal of entry into body = hard chancre; occurs about 3 weeks after infection; large numbers of organisms present in lesion; lesion heals spontaneously

6 T. pallidum ssp. pallidum (syphilis)
Secondary syphilis - may occur either before or after chancre has healed; lesions are widespread (organisms spread by lymphatics and blood) and contain many organisms; lesions most often found on mucous membranes and skin (including palms of hands & soles of feet); lesions disappear in 2-4 weeks; disease is either cured spontaneously after secondary stage or becomes latent

7 T. pallidum ssp. pallidum (syphilis)
Tertiary syphilis - may occur 3-20 years after initial infection; characterized by granulomatous lesions called gummas which may involved skin, mucous membranes, soft tissue, bone, eyes, CNS (may lead to paralysis and dementia) & cardiovascular system (may cause aortic aneurysm)

8 T. pallidum ssp. pertenue (yaws)
Largely restricted to rural areas of tropical countries Characterized by destruction of lesions of skin & bone

9 T. pallidum ssp. endemium (nonvenereal endemic syphilis)
Found solely in less-developed tropical & subtropical areas Milder form of syphilis occurring in childhood

10 T. carateum (pinta) Occurs in South & Central America
Characterized by dyschromic skin lesions that eventually become depigmented

11 Epidemiology of Treponema
Habitat Oral cavity, intestinal tract & genitals of humans & animals Routes of transmission Venereal (T. pallidum ssp. pallidum) and non-venereal (other treponemes) Prevention & Control As with other venereal disease Treatment Penicillin or tetracycline

12 Leptospira - leptospirosis
Zoonosis of worldwide distribution in rodents, bats fox, opossum and raccoon (usually asymptomatic) May be transmitted to domesticated animals including cattle, sheep, goats, pigs, horses & dogs Infection in humans not diagnostic - can manifest as meningitis, hepatic disease & kidney disease with symptoms such as headache, muscle tenderness, anorexia, nausea & vomiting; usually self-limiting Severe human infections characterized by icterus; often referred to as Weil’s disease; kidney failure may also occur

13 Epidemiology of Leptospira
Habitat Maintained in wild animals Routes of transmission Direct or indirect contact with infected urine Prevention & Control Drink only potable water; vaccines available for domestic animals, especially dogs Treatment Penicillin; appears to be effective only if given during early (2-4 days) of illness; supportive therapy may also be necessary

14 Borrelia: Arthropod-Borne Spirochetes
B. recurrentis - relapsing fever Louseborne (epidemic) or tickborne (endemic) Fever occurs 2-15 days after infection accompanied by headache & myalgia which lasts 4-10 days (spirochetemia) followed by afebrile period lasting a few days to several weeks during which new antigenic types develop Cycle repeats (usually once in louseborne & up to 10 times in tickborne) Myocarditis most common cause of death

15 The Pattern in Relapsing Fever, based on symptoms (fever) over time

16 Borrelia: Arthropod-Borne Spirochetes
B. burgdorferi - Lyme Disease Zoonoses associated with rabbits transmitted to man via ticks that are maintained in environment in deer Begins as lesion at site of tick bite characterized by erythema that expands with time appearing as a bullseye; may be accompanied by malaise, fatigue, headache, fever, chills, stiff neck, arthralgias & myalgias May develop aseptic meningitis, encephalitis & carditis Untreated cases often develop arthritis Disease rarely fatal

17 The Cycle of Lyme Disease in the northeastern US

18 Epidemiology of Borrelia
Habitat Humans only reservoir of louseborne B. recurrentis; tickborne B. recurrentis primarily zoonoses in rodents with rabbits major source B. burgdorferi maintained in nature in rabbits & deer & transmitted to man via ticks Routes of transmission Insect borne Prevention & Control Avoid contact with lice & ticks Treatment Tetracycline

19 Curviform Gram-Negative Bacteria and Enteric Diseases
Vibrionaceae Vibrio Comma-shaped rods, with a single polar flagellum Campylobacteriaceae Camylobacter Short spirals or curved rods with one flagellum Helicobacteriaceae Helicobacter Tight spirals and curved rods with several polar flagella

20 V. cholerae O:1 and non-O:1 - cholera
Severity varies greatly - most severe characterized by massive loss of fluid (10-15 liters/day) and electrolytes through intestine; produce condition sometimes called “rice-water stools”; organisms do not spread beyond intestine; may be fatal in a few hours Acquired via contaminated food (esp. meat, fish and other seafood, milk & ice cream) & water - person to person transmission rare Fluid loss due to enterotoxin (choleragen) that acts similar to LT enterotoxin produced by E. coli

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22 V. parahemolyticus Causes acute illness characterized by severe cramping, abdominal pain and explosive watery diarrhea Organisms present in coastal waters throughout world including Louisiana; most cases in US traced to ingestion of incompletely cooked shellfish

23 V. vulnificus Causes both wound infections & gastroenteritis
Can also produce a life-threatening bacteremia which is most severe in persons with liver disease - acquired by ingestion of contaminated seafood or contamination of cuts with seawater

24 Epidemiology of Vibrio
Habitat Primarily of aquatic habitat; infections often acquired from water source Routes of transmission Ingestion - contaminated food (fish = vibrios) and water Prevention & Control Proper cooking of fish Vaccines - cholera vaccines give only limited protection; do not confer life-long immunity Treatment Antimicrobial therapy based on antibiogram Supportive therapy - fluid replacement

25 Campylobacter C. fetus ssp. fetus - septicemia of debilitated, immunosuppressed or elderly persons C. jejuni - one of leading causes of bacterial diarrhea world-wide; usually self-limiting with symptoms resolving in 3-6 days

26 Helicobacter H. pylori - associated with chronic active gastritis (peptic ulcer disease); may be associated with carcinoma of stomach

27 Epidemiology of Campylobacter and Helicobacter
Habitat Part of normal flora (intestinal tract) of humans or animals Routes of transmission Ingestion - contaminated food (chicken = campylobacters) and water (campylobacters) Prevention & Control Proper treatment & disposal of human waste Proper cooking of meat Treatment Antimicrobial therapy based on antibiogram Supportive therapy - fluid replacement, analgesics to lower fever

28 Family Rickettsiaceae
Rickettsia of clinical importance in the US Genus - Rickettsia R. prowazekii - epidemic typhus & Brill-Zinsser disease R. typhi - endemic typhus R. rickettsi - Rocky Mountain Spotted Fever R. akari - Rickettsial pox Genus - Coxiella ( C. burneti); insect vector not required Genus - Rochalimaea (R. quintana) - grow in cell-free media

29 General characteristics of Rickettsia
All are obligate, intracellular parasites except Rochalimaea quintana Grow only in cytoplasm of eucaryotic cells (require living cells for growth) Obligate parasiticism stems from a leaky cell membrane - causes loss of essential metabolites; in particular ATP (possess both synthetic and energy-yielding enzymes)

30 General characteristics of Rickettsia
Require insect vectors for transmission except Coxiella Multiply by binary fission Contain both DNA and RNA Pleomorphic, but typically rod-like in form Cell wall composition similar to Gram negatives Stain poorly or not at all with usual bacterial stains

31 General characteristics of Rickettsia
Diseases of humans classified into 4 major groups Typhus fevers Spotted fevers Q fever Trench fever

32 General characteristics of Rickettsia
Pathogenesis of infections Infect vascular endothelium, usually after bite of an infected arthropod vector Organisms multiply in endothelial cells and become disseminated throughout vascular system Manifested as fever, headache and rash Virulence factors Endotoxin-like shock has been demonstrated in animals but role in human disease unknown

33 Clinical manifestations of Rickettsia Typhus fever group
Epidemic (louse-borne) typhus Acute infection caused by R. prowazekii Transmitted to man via body louse Appears during times when conditions are favorable for human body louse (war, famines, and social upheaval) Infected louse defecates while feeding; organism is rubbed into wound when host scratches Fatality increases with age of host from 10 to 60%

34 Clinical manifestations of Rickettsia Typhus fever group
Brill’s disease (Brill-Zinsser disease) Relapse or recrudescence of louse-borne typhus; occurs years after a primary attack Factors triggering relapse unknown - may involve fading immunity to organisms that have remained dormant in RE cells Milder, shorter and less debilitating than primary (partial immunity)

35 Clinical manifestations of Rickettsia Typhus fever group
Endemic (murine) typhus Caused by R. typhi Natural reservoir is urban rodent - transmitted to humans by rat flea 40-60 cases reported annually in US; predominantly in SE & Gulf states, especially Texas

36 Clinical manifestations of Rickettsia: Spotted fevers
Rocky Mountain Spotted Fever (RMSF) Caused by R. rickettsi - primarily a parasite of ticks Most likely encountered rickettsial disease in US; >1000 cases/year Mortality approximately 7%; most individuals recover spontaneously Highest attack rates occur in mid-Atlantic states, the Carolinas and Virginias between April & September when exposure to ticks most likely Symptoms include fever, headache, rash and mental confusion Rash begins on extremities & spreads to trunk - diagnostic if rash appears on palms of hands and soles of feet Complications occasionally encountered = DIC, thrombocytopenia, encephalitis, vascular collapse and renal and/or heart failure

37 Trends in infection for Rocky Mountain spotted fever

38 The transmission cycle in Rocky Mountain spotted fever
The transmission cycle in Rocky Mountain spotted fever. Dog ticks and wood ticks are the principal vectors

39 Clinical manifestations of Rickettsia Spotted fevers
Rickettsial pox Caused by R. akari Transmitted by rodent mite - primary reservoir is house mouse Distinguishing features is eschar at site of bite, vesicular rash and absence of Weil-Felix agglutination reaction Self limiting after 1 week - no deaths reported

40 Clinical manifestations of Rickettsia: Q fever
Only rickettsial disease transmitted from animals to humans by inhalation - does not require insect vector Caused by Coxiella burneti Primarily disease of cattle, sheep, goats, rodents and marsupials Occurs sporadically among people who work with infected animals or their products Manifested as systemic infection with or without pneumonia - fever, chills, mild dry, hacking cough, no rash*

41 Clinical manifestations of Rickettsia: Trench fever
Caused by Bartonella quintana Transmitted from human to human via body louse Only rickettsia to grow on cell-free media Disease characterized by abrupt onset with chills & fever which tend to subside and then recur in repeated cycles of 3-5 days duration Rash commonly present during febrile periods

42 Epidemiology of Rickettsia
Treatment - tetracycline and chloramphenicol Control - insect vector (insecticides); personal hygiene

43 Other Obligate Parasitic Bacteria: The Chlamydiaceae
Chlamydia of clinical significance Chlamydia psittaci (birds) Chlamydia trachomatis (humans) TWAR strains (Chlamydophila pneumoniae)

44 General characteristics of Chlamydia
Obligate intracellular parasites Once believed to be large viruses Are metabolically deficient - cannot synthesize ATP or reoxidize reduced NADP Possess both DNA and RNA Multiply in host cells by binary fission Are susceptible to several antibacterial agents Are small, generally rounded but show variation during replicative cycle Cell wall composition similar to Gram negatives

45 Unusual replication cycle having morphologically distinct forms
Elementary body - small, extracellular, infectious stage Enters host by endocytosis using specific cell receptors Remain within phagosomes Are metabolically active, reorganize within one hour into larger form called an initial or reticulate body

46 Unusual replication cycle having morphologically distinct forms
Initial or reticulate body - larger, intracellular, noninfectious stage Does not survive outside cell Uses ATP generating capacity of host cell to divide by binary fission elementary body Replicate within the cytoplasm of host cells forming characteristic intracellular inclusions which can be seen by light microscopy Between hours, cell ruptures and infective elementary bodies are released

47 Clinical manifestation: C. psittaci
Primarily disease of birds Human psittacosis = ornithosis Contracted through inhalation of respiratory secretions, or dust from droppings of infected birds Seen primarily in poultry workers and owners of psittacine birds Decreased incidence in US may be associated with use of antimicrobics in poultry feeds & quarantine of imported birds Symptoms in humans include those of lower respiratory infection with acute onset of fever, headache, malaise, dry (non-productive) cough and Xray evidence of bilateral pneumonia CNS involvement common - encephalitis, convulsions, coma, headache

48 Clinical manifestation: C. trachomatis
Eye infections - two distinct forms Trachoma - caused by serotypes A, B, Ba and C Inclusion conjunctivitis Genital infections - single most frequent cause of sexually transmitted disease in US (4 million cases/year in US)

49 Trachoma Chronic keratoconjunctivitis
Seen most often in underdeveloped countries (esp. Africa) - in US = American Indians Usually contracted in infancy or early childhood by close contact with another infected individual Transmitted by droplet, hands, contaminated clothing and eye-seeking flies Begins as acute conjunctivitis followed by severe corneal scarring - blindness often occurs in years if not treated Persistence and reinfections and associated inflammatory responses provide stimulus for major pathological effects Leading cause of preventable blindness in developing countries

50 Inclusion conjunctivitis
Acute inflammation of conjunctiva seen in adults and infants in population where chlamydial genital infections are common Neonatal form results from direct contact with infected cervical secretions of mother at delivery (use of tetracycline, erythromycin, or chloramphenicol eye drops at birth decreases incidence) - occurs 2-3 days after birth Presents as acute, copious, mucopurulent eye discharge Symptoms may resolve without medical treatment Adult form usually associated with concomitant (occurring at the same time) genital disease - autoinoculation believed to be route of transmission

51 Genital infections Cause a spectrum of sexually transmitted infections similar to N. gonorrhoeae including urethritis and epididymitis in men and cervicitis, salpingitis and urethral syndrome in women Shown to cause approximately 40% of non-gonococcal urethritis in men which may be indistinguishable from one the caused by N. gonorrhoeae (chlamydia will not be seen in Gram stained smears) Approximately one-half of all infants born to mothers excreting C. trachomatis during labor develop chlamydial diseases during the first year of life

52 Lymphogranuloma venereum (LGV) is a distinct venereal disease caused by C. trachomatis
One of five classic sexually transmitted diseases (gonorrhoeae, syphilis, herpes, chancroid and LGV) Occurs principally in S. America and Africa- uncommon in US - reservoir in US is mostly homosexual males Two stages with systemic manifestations occur; stage 1 = genital lesion - begins as a small genital ulcer which is usually painless and inconspicuous; stage 2 = lymph adenitis (marked swelling of inguinal lymph nodes; may suppurate) fever, headache and myalgia may accompany Systemic manifestations include hepatitis, pneumonitis & meningoencephalitis Diagnosis usually based on characteristic clinical appearance

53 TWAR strains - proposed name = Chlamydophila pneumoniae
An acronym -TW (first isolated in Taiwan) and AR (acute respiratory) WW in distribution Most infections seen in persons between 7-30 years of age Associated with pneumonia, bronchitis, pharyngitis, sinusitis and flu-like illness Infections may be severe in elderly - otherwise are mild to moderate in severity

54 Epidemiology of Chlamydia
Treatment - antimicrobics; most commonly use tetracycline, erythromycin, sulfonamides and rifampin Control - treatment of known cases and prevention of exposure

55 Mycoplasmataceae Mycoplasma - require cholesterol for growth
Genital organisms M. hominis M. fermentans M. gentalium Respiratory organisms M. pneumoniae M. salivarium M. orale Ureaplasma - require urea for growth; hydrolyzes urea - U. urealyticum

56 General characteristics of Mycoplasma
Smallest free living organism; pleomorphic (coccoid, filamentous and large multinucleoid form found) Lack cell walls Bounded only by a cell membrane with no evidence of a cell wall Do not Gram stain but can be stained with Giemsa

57 General characteristics of Mycoplasma
Cell membrane unlike those of bacteria - contain sterols – sterols are not synthesized by the organism but are acquired as essential components from media or tissue in which it is growing Highly fastidious in growth requirements Require enriched media containing peptones, yeast extract (contain preformed nucleic acid precursors) and cholesterol (usually supplied by animal serum - 10 to 20%) to maintain proper osmotic conditions Urea needed for Ureaplasma Grow slowly - produce minute colonies on agar after several days; center of colony grows into agar; appears denser (inverted “fried egg” appearance) M. pneumoniae is aerobe but most other species are facultative

58 Clinical manifestations of Mycoplasma pneumoniae
Atypical pneumonia or walking pneumonia Associated with several syndromes including pharyngitis, tracheobronchitis, otitis media and pneumonitis; occasionally with arthritis, meningitis, hemolytic anemia and a rash Accounts for approximately 20% of pneumonias Usually less severe than common bacterial pneumonias May be called primary atypical pneumonia (PAP) or walking pneumonia

59 Clinical manifestations of Mycoplasma pneumoniae
Insidious onset with fever, headache, and malaise followed by a nonproductive cough Organisms interfere with ciliary action; leads to desquamation of mucosa & subsequent inflammatory reaction and exudate Organisms shed in URT for 2-8 days before onset of symptoms; continues for as long as 14 weeks after infection

60 Epidemiology of Mycoplasma pneumoniae
Natural habitat - human respiratory tract; more common in summer; especially prominent in temperate climates Most common age is between 5-15 years (accounts for more than one-third of all cases of pneumonia in teenagers); uncommon in children less than 6 months Modes of transmission - droplet Prevention and control - no method known; vaccines have been disappointing Treatment - erythromycin and tetracycline

61 Clinical manifestations of Mycoplasma hominis
Genital Major clinical condition is postabortal or post-partum fever - isolated from the blood of about 10% of women with this condition Disease appears to be self-limiting but antimicrobial therapy may decrease duration of fever and hospitalization PID may be associated with M. hominis infection of fallopian tubes

62 Epidemiology of Mycoplasma hominis
Natural habitat - genital tract of sexually active men and women; rarely found before puberty Transmission - endogenous; sexual Prevention and control - none known Treatment - tetracycline

63 Ureaplasma urealyticum
Clinical manifestations Approximately one-half of cases of nongonococcal, nonchlamydial urethritis in men caused by Ureaplasma Chorioamnionitis and postpartum fever in women Epidemiology - same as M. hominis


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