Microbiology Exam 2
What are the symptoms of Lyme Disease?
*Erythema migrans (bull's eye)* begins as small papule and then enlarges over the next few weeks. Other early signs include: headache malaise severe fatigue fever chills myalgias lymphadenopathy
Streptolysin S and Streptolysin O
*Hemolysins* contained by S. pyogenes that lyse leukocytes, platelets & erythrocytes; Streptolysin is nonimmunogenic, but Streptolysin O is immunogenic and oxygen liable S. progenies are beta hemolytic
Describe the pathogenesis of Francisella Tularensis
*Lesion develops within 2-5 days of exposure* - becomes ulcerated Reticuloendothelial system involvement forming granulomas (Bacteremia rarely detected) Sometimes a chronic relapsing course Chronic facultative intracellular pathogen of macrophages, hepatocytes and endothelial cells - Inhibits phagosome-lysosome fusion - Inhibits phagosome acidification Disseminated sites characterized by abcesses, caseating granulomas, and necrosis
What is the key virulence factor of S. pyogenes?
*M protein* is a specific surface protein that acts as an adhesin Key functions: Mediates internalization by host cells Antiphagocytic to C3b-mediated phagocytosis Carboxyl terminus is highly conservative, but the *amino terminus is highly antigenic variable* (100 serotypes) *Cross-reacttive with human cardiac tissue*
Describe the symptoms of Rocky Mountain Spotted Fever (RMSF)
*Maculopapular rash* appears a few days later, often becoming petechial or purpuric. Rash is confusing in children.-- Affinity for vascular endothelium causing *vasculitis which presents as a rash on palms/soles of feet.* Fever, severe headache, myalgia and other respiratory symptoms. Splenomegaly and neurologic involvement is frequent with later onset of clotting defects (DIC), shock and death.
What is the vector and reservoir for Rocky Mountain Spotted Fever (RMSF)?
*Vector:* *Wood tick (Dermacentor andersoni)* or Dog tick (Dermacentor variabilis) *Reservoir:* Lower animals, rodents and birds
Rabbit Fever case study
A 12 yr old male is brought to his pediatrician because of an *ulcer on his right wrist* together with *swelling of the lymph nodes in the right axilla* with suppuration. He had just returned from summer camp and upon questioning, *admits to having played with rabbits* at the camp's breeding grounds. He has been suffering from *fever, headache, and muscle aches for almost one week*. Upon examination you also notice *mild splenomegaly and scattered rales in both lung bases.* He is diagnosed with a zoonosis by immunofluorescence of material directly taken from the ulcer.
Francisella Tularensis Case Study
A 27-year-old man was mowing his field when he ran over two young rabbits. When he stopped his mower, he realized that two other rabbits were dead in the unmowed part of the lawn. He removed all the rabbits and buried them. *Three days later he developed a fever, muscle aches,and a dry, nonproductive cough.* Over the next 12 hours he got progressively sicker and was transported by his wife to the area hospital. Results of a *chest x-ray showed infiltrates in both lung fields.* Blood cultures and respiratory secretions were collected, and antibiotics were initiated. *Blood cultures became positive with small gram-negative rods after 3 days of incubation, and the same organism grew from the respiratory specimen that was inoculated onto BCYE agar.* How is the tentative diagnosis of tularemia confirmed? How is it treated?
Bacillus anthracis Case study
A 53-year-old male *farmer* presents for evaluation of a growth on his arm. About a week previously, he noticed some *mildly itchy red bumps on his arm.* They started to *blister a day or two later* and then ruptured. During this time he had no ill contacts and had a low-grade fever, but otherwise felt well. Further questioning reveals that he has no ill contacts and never had anything like this before. He has *cows, horses, goats, sheep, and chickens on his farm.* On examination of his right upper arm, you find a 4.5-cm circular *black eschar surrounded by several vesicles (blisters) and edema*. He has *tender axillary lymph node enlargement (adenopathy).* A Gram stain of fluid drained from a vesicle and a biopsy from the eschar both show chains of *gram-positive bacilli* on microscopy. How is diagnosis of this infection confirmed?
Erysipelas
A bacterial infection of the skin's outer layers. Spreading infections of the skin or mucous membranes Sharp demarcating areas Caused by S. pyogenes
Malaise
A condition of general bodily weakness or discomfort, often marking the onset of a disease. A symptom observed a lot in Group A Streptococci infections
Maculopapular rash
A maculopapular rash looks like red bumps on a flat, red patch of skin. The reddish background area may not show up if your skin is dark. The rash is sometimes itchy, and it can last from two days to three weeks depending on the cause. Typically found on palms and soles of patients in Rocky Mountain Spotted Fever.
Necrotizing fasciitis
A progressive infection of subcutaneous tissue with destruction of fascia and fat due to S. pyogenes Organisms may rapidly spread from a localized lesion first involving the skin, then subcutaneous tissue to the deeper muscle tissue resulting in a highly destructive necrotizing cellulitis, fasciitis and myositis ("flesh eating bacteria") Deep infection of skin that involves destruction of muscle and fat layers Patients often die from shock and multisystem failure within 48 hours
Genus: *Rickettsia*
Any of a group of very small bacteria that includes the causative agents of typhus and various other febrile diseases in humans. Like viruses, many of them can only grow inside living cells, and they are frequently transmitted by mites, ticks, or lice.
Epidemiology of Anthrax
B. Anthracis is in sheep, cattle, and other herbivores so humans are exposed via inhalation of spores, breaks through the skin Human cases are rare in US-- Cutaneous anthrax accounts for 95% of cases in US;10-20% of cases can be fatal when untreated Hides, wool, bone meal from endemic countries are source of infection in the US Bioterrorism - present day threat - 2001 - envelope bioterrorism episode killed 22 people Weaponized spores: small size - remain suspended in air.
How is Lyme Disease diagnosed?
Borrelia can be cultured in NSK medium from early stage cutaneous tissues but rarely seen at later stages Culture takes several weeks, thus Lyme disease is primarily diagnosed on clinical presentation and known exposure Immunofluoresence assay (IFA) Western blots and ELISA assays used to detect antibody response (significant increase in antibody between acute and convalescent serum samples) False positive rxs. can occur in patients with syphilis
Genus: *Borelia*
Borrelia is a genus of bacteria of the spirochete phylum. It causes borreliosis, a zoonotic, vector-borne disease transmitted primarily by ticks and by lice, depending on the species. Members of the genus Borrelia cause two important human diseases: *Relapsing fever and Lyme disease* Weakly staining, gram-negative spirochetes; Stain well with Giemsa or Wright stain Can be easily seen by light microscopy in smears of patients with relapsing fever, but not those with Lyme disease (B. burgdorferi) From 7-20 periplasmic flagella Borreliae are microaerophilic and have complex nutritional needs Culture is generally unsuccessful, thus diagnosis of disease caused by borreliae is by microscopy (relapsing fever) or serology (Lyme disease).
Scarlet Fever
Can accompany pharyngitis or a streptococcal skin infection A generalized punctate erythematous rash sometimes described as *"sandpaper rash" and "strawberry tongue"*, accompanied by fever The rash is caused by the pyrogenic toxin released from S. pyogenes
Cutaneous anthrax
Characterized by *lesions (malignant pustule) on hands, forearms or head that may contain a dark, bluish black fluid* An erythematous papule develops *12-36 hrs* after entry of organism via breaks in the skin which quickly progresses to the formation of a pustule and then a necrotic ulcer from which the infection may disseminate (*eschar*)
What is the normal flora of the nose and throat?
Coagulase-negative staphylococci Diphtheroids Pneumococci S. aureus Moraxella Haemophilus *Sinuses, middle ear and larynx - are usually sterile*
What types of Anthrax can result from Bacillus anthracis?
Cutaneous anthrax Pulmonary anthrax
How does the immune system deal with rickettsia rickettsii?
Cytokine-mediated intracellular killing CD8 lymphocytes Antibodies directed to outer membrane proteins
Where is Francisella Tularensis distributed? (epidemiology)
Disease is primarily observed in Oklahoma, Missouri and Arkansas, but distributed throughout North America There are two types: A & B; Type A - most common in US
Lyme Disease: Stage 2
Disseminated (1-6 months) Secondary annular lesion Symptoms: meningitis, carditis musculoskeletal pain, eye pain
How is Lyme Disease treated?
Early therapy - Oral doxycycline, amoxicillin erythromycin Late stages - 3rd generation cephalosporins, ceftriaxone, cefotaxime (~ 50% effective)
Where is Borrelia burgdorferi distributed?
Eastern and midwestern US Ixodes pacificus in the western US Lyme disease has worldwide distribution
What is the main function of F proteins?
F protein is a virulence factor contained by S. pyogenes that mediates adherence to epithelial cells and internalization
What are the virulence factors of Francisella Tularensis?
Facultative intracellular pathogen LPS - appears to NOT be very toxic Lipid capsule - anti-phagocytic Factors that inhibit phagosome-lysosome fusion and prevent acidification
F protein
Fibronectin-binding proteins are adhesins which bind fibronectin and promotes adherence to fibronectin containing tissue, e. g. upper respiratory tract, female genital tract *Virulence factor of S. Pyogenes*
Genus: *Francisella*
Francisella is a genus of pathogenic, Gram-negative bacteria. They are small coccobacillary or rod-shaped, nonmotile organisms, which are also facultative intracellular parasites of macrophages.
How is Anthrax diagnosed?
Gram stain, culture and immunofluorescent assays of fluid or pus from local lesions, blood and sputum Can be cultured on normal blood agar Serological tests can demonstrate the presence of agglutinating antibodies; antibodies to toxin antigens
Genus: *Streptococcus*
Gram-positive cocci arranged in long or short (diplococci) chains All are catalase negative Streptococci bacteria are very important medically because they are important human pathogens: *Streptococcus pyogenes (Group A streptoocci)* Streptococcus agalactiae (Group B streptococci) Streptococcus bovis (Group D streptococci) *Streptococcus pneumoniae* *Enterococci (Enterococcus faecalis, E. faecium)* *Viridans streptococci (Streptococcus mutans, S. sanguis, S. salivarius, S. mitis)* Anaerobic streptococci (Peptostreptococcus)
Describe the morphology and general characteristics of *Streptococcus Pyogenes*
Gram-positive cocci arranged in pairs and long chains Lancefield Group A-- Most important species of group A streptococci Facultative anaerobe Catalase negative Beta hemolytic Bacitracin sensitive CAMP test negative Contains specific antigens: A, M, and F antigens Most common cause of bacterial pharyngitis Pus producing Causes a variety of suppurative and nonsuppurative diseases
What is the difference between Group A and Group B streptococci?
Group A are bacitracin sensitive and CAMP test negative Group B streptococci are bacitracin resistant and CAMP test positive
What is Antigen A of S. pyogenes?
Group-specific carbohydrate (A antigen) is a dimer of N-acetyl-glucosamine and rhamnose contained by Group A streptococci (S. pyogenes)
How is F. Tularensis diagnosed?
Growth on chocolate but not blood agar Oxidase negative, catalase-negative Reactivity of bacteria with specific antiserum (agglutination of organism with antibodies against Francisella) Microagglutination detects antibody titer in serum--- A single titer of 1:160 or greater in patients; Antibodies directed against Brucella can cross-react with Francisella Fluorescent Ab tests can detect the organism in tissue specimen
How is Bacillus anthracis infections treated/prevented?
Historically susceptible to penicillin - resistance genes to penicillin and doxycycline have been transferred to the organism-- *now recommend ciprofloxacin* Control measures include appropriate disposal of infected animal carcasses (incineration) Decontamination of animal products (autoclaving, gas sterilization) Use of protective clothing Immunization of domestic animals with live attenuated vaccine Vaccine consisting of purified protective antigen is available for humans at high risk
How does the immune system work to protect against S. pyogenes?
Host defense is dependent on complement opsonization, antibody opsonization and phagocytosis since streptococci are extracellular parasites Antibodies are directed to pili and the M and F proteins to prevent attachment and enhance phagocytosis Immunity is type specific-- Infection by S. pyogenes of one M type confers immunity to the same but not to other M types
How is Francisella Tularensis transmitted?
Human disease acquired from bite of infected "hard-shell" tick (Ixodes, Dermacentor) Disease is also contracted from ingestion of contaminated *meat or water, inhalation of infectious aerosol, skin abrasions, skinning animals*
Lyme Disease Case Study
In late August a twenty-three-year old Caucasian male presents at the Emergency Room with joint pain of his extremities. His pain is in both of his knees and his left elbow. He explains that the *pains have been jumping from one joint to another for the past week* despite his use of aspirin. Upon taking a detailed history of the patient you learn that the previous spring he worked as a *trail guide at a campground in Bath, Connecticut.* He ended his work there in June to start summer school at a local community college. He recalled having several of what he believed were insect bites below his right knee. Over the next week the irritation became worse, with the affected area spreading above and below the knee. *The rash was unusual in that the outer edges were raised, and of a deeper color than it's interior. It resembled a bull's eye.* Over a period of 3 weeks the rash slowly disappeared. Later, he began to *feel lethargic*, with little energy. He felt unusually warm and fatigued with frequent *headaches and nausea*. For a period of two days he had a swollen right eye and poor peripheral vision. Then all these symptoms disappeared. Towards the end of August after he had been feeling quite well over a month, he developed *pain in the right knee* which disappeared with the use of aspirin. Several days later he experienced pain and *swelling in both knees and his left elbow.* He had a new girlfriend with whom he had several sexual encounters. *He had not ever contracted syphilis or any other sexually transmitted diseases* that he knew of. His throat was not sore or inflamed and there were no sores visible on his penis. Nor was there a purulent discharge. You took blood samples, synovial or serous fluid and a urethral swab. What should be the results from these tests if the patient has Lyme Disease?
What individuals are at high risk for Rocky Mountain Spotted Fever (RMSF)? (epidemiology)
Individuals camping, fishing, picnicking in wooded areas are highly susceptible Children playing in weeds or brush in Nashville area are highly susceptible Children are most commonly infected but their disease is milder Disease is most common April through October
Describe the pathogenesis of Bacillus anthracis
Infection is due to the entry of Bacillus anthracis spores through the skin and mucous membranes Spores germinate at the site of infection Bacilli spread to the lymphatics and in 10% of cases reach the blood to cause septicemia Continued multiplication and production of the toxin causes generalized toxic effects, edema and death Toxin - complex multi-component toxin with 3 components -Protective antigen (PA) - binds to host cell -EF -Edema factor- adenyl cyclase activity increased (increase in cAMP) resulting in tissue edema -LF - lethal factor - a protease that targets cell signaling proteins; cleaves MAP kinase leading to cell death
Acute otitis media
Inflammation of the middle ear mostly occurs in children Typically caused by *S. pneumonia, non-typable strains of Haemophilus influenzae and Moraxella catarrhalis* Symptoms: Bulging ear drum - Fever/pain, purulent fluid accumulates behind red tympanic membrane Treatment can be problematic due to increased antibiotic resistance
What individuals are at high risk for Lyme Disease? (epidemiology)
Ixodes scapularis in eastern and midwestern US Ixodes pacificus in the western US Individuals at risk for Lyme disease include people exposed to ticks in areas of high endemicity Seasonal incidence corresponds to feeding patterns of vectors Most cases in the US occur in late spring and early summer (feeding pattern of nymph stage of tick)
Describe the morphology and general characteristics of * Bacillus anthracis*
Large, aerobic, non-motile gram- positive rods Produce *lecithinase* (phospholipase) *Spore-formers* Animal products such as hides, bristles, hairs, wool and bone can become contaminated with spores Polypeptide capsule composed of D-glutamic acid interferes with phagocytosis (plasmid-encoded) *Causes Anthrax*
Lyme Disease: Stage 3
Latent, persistent infection (1-30 years) Acrodermatitis chronica atrophicans Symptoms: arthritic, chronic progressive neurologic/ cardiac disorders
Lyme Disease: Stage 1
Localized (1-4 weeks) Erythema Migrans is the key symptom Blood infection Fatigue, headache, fever, and malaise
Describe the pathogenesis of Lyme disease
Lyme Disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi. There are three stages associated with the disorder that resemble the progression of syphilis-- a localized stage, disseminated stage, and a latent stage. Characteristic skin lesion is erythema migrans
What disorder does Borrelia burgdorferi cause?
Lyme disease
How does the immune system deal with Bacillus Anthracis?
Mechanisms of immunity have not been identified but likely rely on antibody-mediated mechanisms
How is Rocky Mountain Spotted Fever diagnosed?
Microimmunofluorescence methods detect antibody production of outer membrane proteins of the bacteria (antibody titers of 1:160 or greater) Weil-Felix test is positive for Proteus OX2 or OX19a (infected patients make antibody to the rickettsiae that cross-react with the O antigen polysaccharide of Proteus vulgaris).
Pharyngitis or Tonsilitis
Most common bacterial cause is *S. pyogenes* Symptoms: Malaise, fever, headache and sore throat *with white exudate in the pharynx * Tonsils are enlarged and erythematous, anterior cervical nodes may be swollen
Describe the epidemiology of Streptococcus Pyogenes
Most group A streptococcal infections and sequelae are most frequently seen in children *10 years of age or younger* S. pyogenes is maintained in nature in human asymptomatic nasal and pharyngeal carriers Impetigo transmission involves *close contact* or the sharing of contaminated items Pharyngitis and scarlet fever are transmitted primarily by *droplet infection* (respiratory secretions)
What types of tularemia can result from F. Tularensis?
Multiple courses following 2-5 day incubation period; *all are characterized by acute onset of fever, chills, malaise* *Ulceroglandular* (cutaneous ulcer/swollen lymph node) - most common following skin abrasion or tick/fly bite (2-5 days) *Oculoglandular* - direct inoculation by contaminated hands, fingers, aerosol; painful, purulent conjunctivitis; cervical and preauricular lymphadenopathy *Glandular* - usually vector borne exposure, enlarged regional lymph nodes with no skin involvement *Typhoidal* - ingestion or inhalation; bacteremic spread and seeding to lung, liver, spleen; fever, weight loss, pneumonia--mimics typhoid fever, brucellosis, tuberculosis *Pneumonic* - results from inhalation of infectious aerosols-- Significant cause of fever of unknown origin (FUO); Mortality if untreated is 5-30% depending on the form
How does the immune system deal with Francisella Tularensis?
Natural infection confers long lasting and protective immunity Cell-Mediated Immunity plays a major role in resistance Vaccine is given to high risk individuals - provides partial protection - live attenuated form of bacteria provides one year protection
Define *M protein*
Pili contain a complex of M protein and lipoteichoic acid (LTA) M protein is an adhesin which promotes attachment to epithelial cells *containing keratin* but not to pharyngeal tissue Contains antiphagocytic and anticomplement properties More than 100 different antigenic types Immunologically cross-reactive with human cardiac tissue *Virulence factor of S. Pyogenes*
What nonsuppurative infections can result due to Streptococcus pyogenes?
Rheumatic fever Acute glomerulonephritis
Describe the morphology and general characteristics of *Rickettsia Rickettsii*
Rickettsia rickettsii is a small, rod-shaped bacterium known to cause Rocky Mountain spotted fever (RMSF). Related to gram-negative organisms Stains poorly with the gram strain (*Giemsa or Gimenez is better*)
Describe the pathogenesis of Rocky Mountain Spotted Fever (RMSF)
Rickettsiae multiply in the skin at site of wood tick bite and then spread to blood and infect vascular endothelium in lung, spleen, brain and skin. After an *incubation period of about 1 week*, there is onset of fever, severe headache, myalgia and other respiratory symptoms.
What disorder does Rickettsia rickettsii cause?
Rocky Mountain Spotted Fever
Where is Rocky Mountain Spotted Fever (RMSF) distributed?
Rocky Mountain region Eastern and Southeast United States Endemic in Tennessee
What are the common suppurative infections caused by Group A streptococci?
S. pyogenes may produce primary infections which are acute pyogenic (suppurative) infections of any tissue. 1. Pharyngitis or tonsillitis 2. Impetigo/pyoderma 3. Erysipelas 4. Cellulitis 5. Necrotizing fasciitis 6. Scarlet Fever 7. Streptococcal toxic shock syndrome Other: Puerperal sepsis, lymphangitis, *pneumonia*
What is the main functions of pyrogenic exotoxins?
S. pyrogenes' superantigens that interact with macrophages and helper T cells resulting in the hyper release of cytokines Cause Scarlet Fever
Describe the morphology and general characteristics of *Francisella Tularensis*
Small gram-negative coccobacillus Causes Tularemia-- "rabbit fever" or "deerfly fever" Intracellular obligate aerobe (macrophages) Inhibits phagosome- lysosome fusion Requires cysteine for growth; can grow on BCYE (buffered charcoal yeast extract) Oxidase negative, catalase-negative
General Properties: Rickettsia
Small, rod-shaped bacteria that are obligate intracellular parasites Related to gram-negative organisms Contain diaminopimelic acid (DAP) in cell wall Replicate by binary fission Stains poorly with the gram strain (*Giemsa or Gimenez is better*) Can persist in the body for a long time (latent)
Spirochetes
Spiral-shaped bacteria that have flexible walls and are capable of movement
What bacteria is the number one cause for *acute otitis media*?
Streptococcus Pneumoniae
How to determine *Streptococcus Pyogenes-Group A* bacteria in the lab?
Streptococcus Pyogenes (S. pyogenes)-Group A undergo the following test: 1. Catalase test- negative 2. *Beta* hemolysis 3. Bacitracin test- *Sensitive*
How is Streptococcus Pyogenes infections diagnosed?
Streptozyme Test-- Antibody to five Group A streptococcal antigens (streptolysin O, DNAse B, streptokinase, hyaluronidase, NADase) are used to identify the presence of S. pyogenes An Anti-Streptolysin O titer (ASO) is also used to diagnose presence of the bacteria Antigen Detection test-- based on the direct extraction of Group A antigen from a nasopharyngeal swab and can be performed in physician's office; specificity is high but sensitivity varies from 70-90%
How is Rocky Mountain Spotted Fever treated/prevented?
Tetracycline, doxycycline, fluoroquinolones, chloramphenicol, erythromycin No available vaccine
Pharyngitis
The acute inflammation of the throat that results in pain when swallowing and swollen pharyngeal mucosa 50-75% of cases are caused by viruses and *Group A streptococci* (25% adenoviruses, 20% rhinoviruses, and 15-30% Group A streptococci) Peak incidence of disease is between *3 to 18 years old*
What disorder does Francisella tularensis cause?
Tularemia "Rabbit Fever" "Deerfly Faver"
Acute Rheumatic Fever
Valvular murmurs/scarring Valvular stenosis Inability of heart valve to close properly back flow - regurgitation Inflammation of endocardium, connective tissue--patients are at risk of developing *infective endocarditis* *Only group A strep causes ARF following pharyngitis* No more than 10% of people are susceptible to ARF--cellular autoimmunity is the basis for ARF
What organisms can cause pharyngitis?
Viruses and Group A streptococci *Streptococcus pyogenes- mostly in 5-10 year old children* Nisseria gonorrhoeae- Often asymptomatic; usually via orogenital (oral sex) contact Corynebacterium diptheriae-Often mild; but toxic illness can be severe Haemophilus influenzae- epiglottitis Borrelia vincentii plus fusiform bacilli- Vincent's angina; commonest in adolescents and adults
Describe the morphology and general characteristics of *Borrelia burgdorferi*
Weakly staining, gram-negative spirochetes Stain well with Giemsa or Wright stain Causes Lyme Disease
Bacillus Anthracis Summary
*Organism:* Bacillus Anthracis *Disease*: Anthrax *Culture*: Gram-positive rod, best grown on a blood agar *Virulence Factors:* Anthrax toxin which consists of a protective antigen, an edema factor, and a lethal factor; poly D-glutamic acid capsule; spores *Epidemiology*: Primarily a disease of sheep, cattle, horses, and herbivores; rarely infects humans in the US *Pathogenesis:* The bacteria travel through the lymphatics and in 10% of the cases reach the blood and cause septicemia; There are three forms of the disease-- cutaneous, pulmonary, and ingestion anthrax *Onset of symptoms:* In the case of the cutaneous anthrax, 12-36 hours *Key symptoms:* Cutaneous- eschar, Pulmonary- malaise, mild fever, non-productive cough Ingestion- abdominal pain, nausea, vomiting, and bloody diarrhea *Transmission:* Spores; Contaminated animal products are a source of infection; micronized spores are used in bioterrorism *Diagnosis:* Gram-stain material from lesions; agglutinating antibody to toxin antigens; immune fluorescence assays of blood, local lesions, etc. *Treatment/prevention:* Penicillin resistance reported so now recommend ciprofloxacin; Antibody mediated mechanisms are important in immunity; Ab to anthrax toxin important in immunity *Msc:* Vaccine for humans at high risk is purified protective antigen; live attenuated vaccine is available for domestic animals
Borrelia Burgdoferi Summary
*Organism:* Borrelia Burgdoferi *Disease*: Lyme Disease *Culture*: Gram-negative spirochete, best stained with Giemsa/Wright stain; not easily cultured *Virulence Factors:* N/A *Epidemiology*: Prominent in the NE; most cases in US occur in late spring and early summer (feeding patterns of ticks) *Pathogenesis:* There are three stages associated with the disorder that resemble the progression of syphilis-- a localized stage, disseminated stage, and a latent stage. *Onset of symptoms:* 1 to 4 weeks *Key symptoms:* Erythema migrans, malaise, fever, severe fatigue, headache, myalgia, secondary annular lesion, acrodermatitis chronic atrophicans *Transmission:* Ixodes dammini, deer ticks, found on the body of mainly white-footed mice and deer *Diagnosis:* Western blot and ELISA assays to detect antibody response *Treatment/prevention:* Oral doxycycline, erythromycin, and 3rd generation cephalosporins in late stages *Msc:* Borrelia recurrent can cause relapsing fever
Francisella Tularensis Summary
*Organism:* Francisella Tularensis *Disease*: Rabbit Fever or tularemia (deerfly fever) *Culture*: Gram-negative coccobacillus, best grown on a BCYE (requires cysteine) *Virulence Factors:* Parasitizes macrophages and all phagocytic cells and inhibits phagosome- lysosome fusion; facultative intracellular pathogen; lipid capsule *Epidemiology*: Primarily observed in Oklahoma, Missouri and Arkansas *Pathogenesis:* Febrile illness, swollen, painful lymph nodes and formation of granulomatous lesions around cells of the Reticuloendothelial system *Onset of symptoms:* Lesions develop within 2-5 days of exposure *Key symptoms:* depends on the type of disease--- ulceroglandular, oculoglandular, glandular, typhoidal, and pneumonic *Transmission:* "Hard shell" infected ticks (Ixodes, Dermacentor) found on wild animals, especially rabbits and beavers. Ingestion of contaminated rabbit meat or water, inhalation of infectious aerosols, skin abrasions *Diagnosis:* Microagglutination detects antibody titer in serum; fluorescent Ab tests can detect the organism in tissue *Treatment/prevention:* Streptomycin, but is very toxic so gentamicin is a good alternative; cell mediated immunity is involved; vaccines are given to high risk patients *Msc:* To prevent infection, avoid rabbits, ticks, biting insects; Wear gloves when skinning and eviscerating animals; Protective clothing, insect repellents
*Rickettsia Rickettsii Summary*
*Organism:* Rickettsia Rickettsii *Disease*: Rocky Mountain Spotted Fever *Culture*: Gram-negative rods, best stained with Giemsa/Gimenez stain *Virulence Factors:* Obligate intracellular parasites *Epidemiology*: Wooded areas in the rocky mountain region, eastern and SE United States; endemic in Tennessee *Pathogenesis:* Affinity for vascular endothelium causing vasculitis which presents as a rash on palms/soles of feet *Onset of symptoms:* About one week *Key symptoms:* Maculopapular rash, fever, severe headache, myalgia and other respiratory symptoms. (Splenomegaly and neurological problems in late development) *Transmission:* Transovarian Transmission by wood ticks and dog ticks found on the body of lower animals, rodents and birds *Diagnosis:* Microimmunofluorescence methods detect antibody production of outer membrane proteins of the bacteria *Treatment/prevention:* Tetracycline and related drugs (*doxycycline*, fluoroquinolones, chloramphenicol, erythromycin); no vaccine is present; CD8 T cells are active in the immune system *Msc:* Weil-Felix test used to be the diagnosing test, but is no longer used
How is Streptococcus Pyogenes treated?
*Penicillin is the antibiotic of choice* *Erythromycin* is used for patients allergic to penicillin Appropriate treatment with antibiotic will prevent an initial attack of rheumatic fever but not glomerulonephritis *There is no vaccine available against S. pyogenes*
Moraxella Catarrhalis
*Ranked third as causative agent of acute otitis media and sinusitis behind S. pneumoniae and H. influenzae* Most important species of Moraxella Normal flora of the upper respiratory tract (URT) of 40-50% school children Small gram-negative coccobacilli that is closely related to Neisseria because it is *oxidase positive* Unlike Neisseria - *does not ferment carbohydrate* and grows well on blood agar
How is Francisella Tularensis infections treated/prevented?
*Streptomycin* is the antibiotic of choice for treatment of all forms of tularemia, but has high level of toxicity. *Gentamicin* is a good alternative. Fluroquinolones (ciprofloxacin) have good bactericidal activity in vitro and mouse animal model To prevent infection, avoid rabbits, ticks, biting insects Wear gloves when skinning and eviscerating animals Protective clothing, insect repellents
What are the virulence factors of Streptococcus Pyogenes?
*Surface proteins:* M protein and Fibronectin-binding proteins Capsular polysaccharide--nonimmunogenic, antiphagocytic capsule made of hyaluronic acid *Toxins and superantigens:* pyrogenic toxin *Hemolysins:* Streptolysin O and Streptolysin S *Extracellular enzymes:* Streptodornase (DNAase), Streptokinase and Hyaluronidase---facilitates invasion of tissues and spreading
What is the vector and reservoir for Francisella Tularensis?
*Vector:* *"Hard-shell" ticks (Dermacentor, Ixodes) *Reservoir:* Found in variety of wild animals, birds, blood-sucking arthropods, *rabbits*, ticks, hares, voles, muskrats, beavers, etc. (zoonotic) Disease is also contracted from ingestion of contaminated *meat or water, inhalation of infectious aerosol, skin abrasions, skinning animals*
What is the vector and reservoir for Borrelia burgdorferi ?
*Vector:* *Deer tick (Ixodes scapularis)* *Reservoir:* mice, deer, ticks (especially *white-footed mouse*)
Case study: *Rocky Mountain Spotted Fever*
A ten year old African-American female is brought to the rural North Carolina Clinic where you are volunteering for the summer. She presents with a *severe headache and high fever.* Also, she appears to be in pain, and is squinting at the exam room's bright illumination. Since she is on summer vacation, his daughter often follows him into the nearby foothills to collect blackberries for pastries. Her mother ensured she has had all of her shots required for school attendance, and she has never had rheumatic fever, mononucleosis nor any other serious illness. She is also prepubescent. Physical exam reveals that she has a temperature of 103.2 F, and she is perspiring. When she is asked where the *pain* is, she points to her *forehead and her legs.* There is evidence of *myalgia* as you palpate the rear of her leg. You also notice her *inguinal lymph nodes are swollen*, as well as her *axillary nodes*. EENT exam reveals that her eyes are *photophobic*, her ears are normal; however, her nasal passages show evidence of *coryza*. Her throat is not inflamed and her tonsils appear normal. *The lymph nodes of her head and neck appear to be swollen also.* There is an obvious *rash on her palms and soles* that is less noticeable on her arms and legs and torso.
Streptokinase
A virulence factor contained by S. pyogenes that lyses blood clots, facilitates spread of bacteria in tissues
Define Cellulitis
Acute spreading infection of the skin that involves subcutaneous tissue Caused by S. pyogenes and C. perfringens
Glomerulonephritis
Also referred to as Post-streptococcal acute glomerulonephritis (PSAGN) Streptococcal antigen-antibody complexes are deposited at the basement membrane of the kidney glomeruli and injury to the glomerulus occurs as a result of an excessive inflammatory response an immune complex disease (Type III hypersensitivity) Clinical features include facial edema, dark urine (hematuria) and hypertension *Post-streptococcal sequelae-- May follow a cutaneous or respiratory infection*
Rheumatic Fever
Also referred to as Rheumatic Heart Disease An autoimmune Type II condition caused by cross- reactivity of streptococcal antigens and human heart, joint and nervous tissue Characterized by inflammation of the myocardium or endocardium, especially the mitral and aortic valves arthritis (inflammation of joints) and neurologic symptoms (uncontrolled involuntary movements) Carditis, arthritis, chorea *Post-streptococcal sequelae-- Follows respiratory but not skin infections*
Streptococcal Toxin Shock Syndrome
Also referred to as Toxic Shock-like Syndrome Caused by S. pyogenes, but presents with many of the symptoms similar to those seen in toxic shock syndrome due to S. aureus, i. e. high fever, disseminated vascular coagulation Symptoms are caused by the release of TNF, IL-1, IL-2 and possibly IL-6 due to the superantigen activity of pyrogenic toxins A and B (SPE A and B)
Pulmonary anthrax
Also referred to as Woolsorter's disease Acquired by inhalation of spores by handlers of raw wool, hides or horse hair *Spores germinate in the lungs* or the tracheobronchial lymph nodes Symptoms include non-specific *malaise, mild fever, and non-productive cough* Progressive *respiratory distress and cyanosis* will follow with *massive edema of the neck and chest*
Pyrogenic toxin
Also referred to as erythrogenic toxin 3 immunologically different forms called *pyrogenic toxins A, B and C (or SPE A, B and C)* Cause direct toxic damage to the skin, produce a delayed hypersensitivity response and are responsible for the rash seen in *scarlet fever* Act as superantigens to stimulate the production of excessive amounts of TNF alpha and beta, IL-1, IL-2, IL-6, and IFN-gamma *SPE A and C encoded by a gene on a temperate phage. Only phage containing cells produce toxin.* Tox- strains of S. pyogenes can be converted by phage infection to Tox+ by a process called phage conversion or lysogenic conversion.
What disorder does Bacillus anthracis cause?
Anthrax
Anthrax
Anthrax is primarily a disease of sheep, cattle, horses (herbivores) Humans are only occasionally infected Infection is due to the entry of Bacillus anthracis spores through the skin and mucous membranes Spores germinate at the site of infection Bacteria multiply and produce the anthrax toxin which consists of a *protective antigen, an edema factor (an adenylate cyclase) and a lethal factor, all are plasmid encoded* Toxic activity requires the protective antigen and at least one of the other two Host defenses are inhibited by the anti-phagocytic capsule
A 27-year-old woman at 19 weeks gestation developed fever to 38 degrees celsius (100.9 degrees Fahrenheit), headache, nausea, and abdominal pain one week after a camping trip with her husband. On the fourth day of this illness, she noticed an erythematous macular rash on the wrists and ankles, gradually progressing to the trunk of the face and becoming petechial. Laboratory studies including CBC and CSF analysis are normal. Routine blood cultures are negative. Which of the following is most appropriate therapy for this patient? A- Chloramphenicol B- Ciproflaxin C-Doxycycline D-Piperacillin/tazobactam E-Vancomycin
The best answer is chloramphenicol (option A). This patient has Rocky Mountain spotted fever (RMSF), which is caused by the bacterium Rickettsia rickettsii and transmitted by a tick vector. The illness begins 2-14 days following a tick bite, and may initially include fever, headache, myalgias, arthralgias, nausea, and abdominal pain. After 3-5 days, the macular rash develops on the wrists and ankles, eventually spreading to the trunk as described. Because R. rickettsii is an intracellular organism, it does not grow on routine blood cultures. The preferred treatment for RMSF is doxycycline (option C), but tetracycline antibiotics are teratogenic and should be avoided in pregnant patients. Chloramphenicol (option A) is the recommended therapy for treatment of RMSF during pregnancy. Concerns about so-called "gray baby syndrome" due to chloramphenicol are likely unwarranted in this patient. Gray baby syndrome may rarely be seen when chloramphenicol is given to premature infants and neonates, not when it is given to pregnant women. Chloramphenicol given during pregnancy has not been associated with an increased risk of teratogenesis. Caution is recommended when using chloramphenicol in a pregnant patient near term or during labor, but the CDC affirms that chloramphenicol may be used for the treatment of RMSF in pregnant women.
Why are SpeA, SpeB, SpeC, and SpeF clinically important?
These pyrogenic toxins are virulence factors released by S. pyogenes as *superantigens.* They stimulate the production of many cytokines including TNF-alpha, and they are responsible for the *rash observed in scarlet fever.* Encoded by temperate phages
Rheumatic Fever case study
This 6 year old female presented with a *1 week history of a febrile illness with a sore throat and headache.* She was given oral ampicillin by her local physician. One day prior to admission, the patient awakened with pain and swelling in the right ankle. She was evaluated on the day of admission, and in addition to a warm swollen right ankle, She was noted to have a new grade III/IV systolic murmur thought to be consistent with mitral regurgitation (insufficiency of the mitral valve). She was admitted to the hospital with a presumptive diagnosis of acute rheumatic fever.
How is Borrelia burgdorferi transmitted?
Transmitted by hard ticks from mice to humans Year 1 - adult ticks feed and mate on certain deer during late fall or winter and drop to the ground. Eggs deposited on bushes hatch into larvae in the spring. In summer larvae obtain blood meal from white-footed mouse which is main reservoir for B. burgdorferi. Larvae mature into nymphs. Year 2 - During following spring-summer, infected nymphs feed on vertebrate hosts including white footed mouse. Infected or non-infected nymphs fall off host and mature into adult males and females and then parasitize available deer to start cycle all over again. Human host is usually infected by infected nymphs.
How is Rocky Mountain Spotted Fever (RMSF) transmitted?
Transovarian Transmission Vertically from adult tick to egg
