30/06/2015
CHAPTER 25 INFECTIONS OF THE BLOOD
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
OVERVIEW
Infections of the Blood and Lymph
CIRCULATING PATHOGENS
BACTERIAL RICKETTSIAL VIRAL INFECTIONS PARASITIC INFECTIONS INFECTIONS OF OF THE BLOOD INFECTIONS OF THE BLOOD THE BLOOD OF THE BLOOD AND LYMPH AND LYMPH
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CIRCULATING PATHOGENS
¿ Depending on type of organism blood infections are classified as:
¿ Bacteremia
¿ Viremia
¿ Fungemia
¿ Parasitemia
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CIRCULATING PATHOGENS
¿ Bacteremia and fungemia can also be caused by pathogens growing inside or outside of intravenous devices
¿ Starts out as a minor problem
¿ Can quickly become serious:
¿ Particularly in patients debilitated from long hospital stays
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
BACTEREMIA
¿ Most cases of bacteremia result from an extravascular infection
¿ Organisms move from infected tissue into lymphatics
¿ From there they can get into the blood
¿ Most bacteria are caught by the lymph nodes
¿ If overwhelming numbers, some make it to the blood
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
BACTEREMIA
¿ Most common sources of bacteremia:
¿ Urinary tract infections
¿ Respiratory infections
¿ Skin infections
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INTRAVENOUS-LINE AND CATHETER BACTEREMIA
¿ Always large numbers of antibiotic-resistant bacteria in hospitals
¿ Makes the implantation of intravenous lines potentially serious ¿ In an infection from intravenous line or catheter, blood can become colonized by organisms normally found on the skin
¿ In a healthy host, this is quickly dealt with by host defense
¿ In debilitated hosts, the bacteremia can persist
¿ Increase the chances of infectious endocarditis and distal infections
¿ Commonly involves S. epidermis, S.aureus, and Cornyebacterium species ¿ Intravenous fluid can also become contaminated
¿ Commonly involves Gram-negative rods such as Pseudomonas species ¿ Removal and treatment with antibiotics will normally remedy catheter bacteremia
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
SEPSIS AND SEPTIC SHOCK
¿ Sepsis occurs when an infection causes massive immunological response
¿ Septic shock is characterized by sever hypotension
¿ Refractory septic shock in untreated cases
¿ Multiorgan failure, DIC, and death
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INTRAVASCULAR INFECTIONS
¿ Arise when pathogens enter the blood and damage the structures of cardiovascular system
¿ Endocarditis – infection of the heart
¿ Thrombophlebitis – infection in the veins
¿ Endoarteritis – infection of the arteries
¿ Most commonly caused by bacteria
¿ Fungi are sometimes involved
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INTRAVASCULAR INFECTIONS
¿ Infections of the cardiovascular are very dangerous
¿ Can be fatal
¿ Commonly produce shedding of organisms into the blood
¿ Cause persistent low-grade fever
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INFECTIOUS ENDOCARDITIS
¿ Once referred to as bacterial endocarditis
¿ Now known that organisms other than bacteria can cause it
¿ Infection affects the heart valves
¿ Can also develop on the septa of the heart and cardiac shunts
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INFECTIOUS ENDOCARDITIS
¿ Heart endothelium is altered by infecting pathogens
¿ Facilitates the colonization of area by pathogens
¿ Causes the deposition of platelets and fibrin
¿ Turbulence of blood flow leads to further irregularities and further deposition of fibrin and platelets
¿ Slows blood flow and causes more pathogen growth
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INFECTIOUS ENDOCARDITIS
¿ Circulating pathogens adhere to the fibrin and platelets
¿ Causes inflammatory response
¿ Causes activation of complement and further damage
¿ Process continues to form a thrombotic mesh
¿ Composed of platelets, fibrin, and inflammatory cells
¿ Known as mature vegetation
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INFECTIOUS ENDOCARDITIS
© CDC/Dr. Edwin P. Ewing, Jr.
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INFECTIOUS ENDOCARDITIS
¿ Circulating pathogens adhere to the fibrin and platelets
¿ Mature vegetation protects the pathogens from host defense
¿ Also helps keep out antibiotics
¿ Also causes alterations in the cardiac endothelium
¿ Obstructs blood flow
¿ Increases turbulence
¿ Turbulence can cause part of the vegetation to fall off
¿ Forms an embolus
¿ Transport of emboli to brain or coronary arteries is a lethal event
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INFECTIOUS ENDOCARDITIS
¿ Immune complexes form as antibodies and infecting organisms form large aggregates
¿ These activate complement
¿ Causes peripheral problems:
¿ Nephritis
¿ Arthritis
¿ Cutaneous vascular lesions
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INFECTIOUS ENDOCARDITIS
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INFECTIOUS ENDOCARDITIS
¿ Complications from infectious endocarditis
¿ Risk of congestive heart failure
¿ Rupture of the chordae tendineae
¿ Perforation of the valves
¿ Kidney damage
¿ Blood is found in urine
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INFECTIOUS ENDOCARDITIS
¿ In addition to treatment, management is important ¿ The nature of the infection means:
¿ Response to therapy is slow
¿ A cure is difficult ¿ Antibiotic therapy must be aggressive
¿ Include bacteriocidal drugs given in high concentration but aren’t toxic
¿ Balancing act that can be difficult
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
INFECTIOUS ENDOCARDITIS
¿ Course of therapy can be prolonged
¿ More than four weeks
¿ Dental procedures are dangerous for people predisposed to infectious endocarditis
¿ Need to take high doses of antibiotics before dental procedures and for 6-12 hours after
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
BACTERIAL INFECTIONS OF THE BLOOD
¿ Circulatory-system infections caused by bacteria
¿ Plague
¿ Tularemia
¿ Brucellosis
¿ Lyme disease
¿ Relapsing fever
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PLAGUE
¿ Vector-transmitted to humans
¿ Most explosively virulent bacterial infection ever known
¿ Spreads from lymph nodes to blood
¿ From there can spread to the lungs
¿ Referred to as pneumonic plague
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
PLAGUE
¿ Pneumonic plague is easily spread from person to person
¿ Referred to as Black Death in Middle Ages
¿ All forms of plague lead to toxic shock and death in days
¿ No other bacterial infection kills this quickly
¿ Caused by the bacterium Yersinia pestis
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
PLAGUE
¿ Infection of rodents transferred to humans by bite of rat flea
¿ Exists in two forms:
¿ Sylvatic – seen in wild rodents
¿ Urban – seen in cities
¿ Urban form more infectious
¿ More potential hosts in the city
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PLAGUE
¿ Fleas become infected after feeding on infected rats
¿ Bacteria multiply in the intestine of the flea
¿ Regurgitated into a host as the flea bites ¿ Bite of the infected fleas causes bubonic plague
¿ Not normally contagious ¿ Bacteria can spread to the lungs
¿ Pneumonic form develops
¿ This form is highly contagious
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
PLAGUE: Pathogenesis
¿ Fleas and humans have a different temperature and ionic environment
¿ Change causes Y. pestis to produce virulence factors
¿ One of these is the F1 protein
¿ Forms gel-like capsule
¿ Prevents phagocytosis
¿ Allows bacteria to reach the lymph nodes
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PLAGUE: Pathogenesis
¿ Bacteria multiply very rapidly in lymph nodes
¿ Produces a bubo
¿ From bubo, bacteria spread rapidly into the blood
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PLAGUE: Pathogenesis
© CDC
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
PLAGUE: Pathogenesis
¿ Lipopolysaccharides and virulence enzymes are released into the blood
¿ Extensive systemic toxicity
¿ Bacteremia spreads to other organs
¿ In the lungs, causes necrotizing hemorrhagic pneumonia
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
PLAGUE: Pathogenesis
¿ Incubation period is 2-7 days
¿ Main signs are fever and painful buboes
¿ Without treatment, 50-75% develop bacteremia
¿ Septic shock causes death in several days
¿ If pathogen localizes in the lungs death occurs in 2-3 days
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PLAGUE: Treatment
¿ Treatment must be given within a day of onset of symptoms
¿ Any delay is almost always fatal
¿ Timely treatment cuts the mortality rate to less than 10%
¿ Streptomycin is the drug of choice
¿ Doxycycline, ciprofloxacin, gentamicin, and chloramphenicol are also used
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
TULAREMIA
¿ Infection of wild animals that can be transmitted to humans
¿ Infected animals may not show any signs
¿ Caused by Francisella tularensis
¿ Grows only on specialized medium
¿ Takes up to 10 days of incubation
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
TULAREMIA
¿ ID50 is small and there are many routes of infection:
¿ Inhalation
¿ Tick bite
¿ Ingestion of contaminated meat or water
¿ Direct contact with abrasion or cut ¿ Tularemia is seen throughout the Northern Hemisphere
¿ Distribution patterns vary widely
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TULAREMIA: Pathogenesis
¿ Incubation phase lasts 2-5 days
¿ An ulcerated lesion forms at the infection site
¿ Organisms move into organs of the mononuclear phagocytic system
¿ Form granulomas
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TULAREMIA: Pathogenesis
¿ Francisella multiplies in macrophages
¿ Disrupts the fusion of the phagosome and the lysosome
¿ Also multiplies in hepatocytes and endothelial cells ¿ Course of tularemia infection depends on:
¿ Inoculation site
¿ How far into the body the pathogens spread ¿ All outcomes start with acute onset of fever, chills, and malaise
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
TULAREMIA: Pathogenesis
¿ Ulceroglandular tularemia
¿ Causes localized papule at inoculation site
¿ Becomes ulcerated and necrotic
¿ Leads to swelling of the regional lymph nodes
¿ Very painful
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TULAREMIA: Pathogenesis
¿ Oculoglandular tularemia
¿ Infection acquired through the eyes
¿ Produces a painful purulent conjunctivitis
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
TULAREMIA: Pathogenesis
¿ Typhoidal tularemia
¿ Caused by ingesting a large number of Francisella bacilli
¿ Presents with symptoms similar to typhoid fever
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
TULAREMIA: Treatment
¿ Streptomycin is the drug of choice for all forms
¿ Gentamicin, doxycycline, and ciprofloxacin are also effective
¿ Important preventative measures
¿ Use of rubber gloves, masks, and eye protection
¿ Prompt removal of any ticks
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BRUCELLOSIS
¿ Zoonotic infection which involves infection of the reproductive tract ¿ Transmission to humans is by:
¿ Occupational contact
¿ Ingesting contaminated animal products ¿ Chronic illness in humans
¿ Can last for weeks or months
¿ Causes fever, night sweats, and weight loss
¿ Cyclic pattern of symptoms – undulant fever
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
BRUCELLOSIS: Pathogenesis
¿ Brucella enters the host through:
¿ Cuts in the skin
¿ Contact with mucous membranes
¿ Inhalation
¿ Ingestion
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
BRUCELLOSIS: Pathogenesis
¿ Organisms multiply in macrophages of the mononuclear phagocytic system
¿ Prevent host phagosomes and lysosomes from fusing
¿ Impair host’s ability to produce and release cytokines
¿ If not controlled locally small granulomas form throughout mononuclear phagocytic system
¿ Pathogens are released back into circulation
¿ Causes recurrent bouts of chills and fever
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BRUCELLOSIS: Pathogenesis
¿ Malaise, chills, and fever occur for 7-21 days after infection
¿ Drenching night sweats and fever reaching 40˚C are common ¿ Nocturnal fevers can last for weeks, months, or even years
¿ Other symptoms are headaches, body aches, and weight loss ¿ Mononuclear phagocytic system is affected in fewer than 25% of cases
¿ Causes splenomegaly, hepatomegaly, and lymphadenopathy
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
BRUCELLOSIS: Treatment
¿ Doxycycline and gentamicin are the primary antibiotics
¿ Streptomycin, gentamicin, or rifampin used as well for seriously ill patients
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE
¿ Transmitted to humans by Ixodes tick
¿ Caused by the spirochete Borrelia burgdorferi
¿ Gram-negative
¿ Properties similar to Treponema pallidum
¿ Requires specialized medium for growth
¿ Doubling time is between 8-24 hours
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LYME DISEASE
¿ B. burgdorferi has at least 10 subspecies
¿ All geographically localized
¿ B. burgdorferi is part of a complex life cycle
¿ Involves ticks, mice, and deer
¿ Humans are incidentally involved
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE
¿ Endemic in several areas worldwide
¿ US and Canada
¿ Temperate areas of Europe and Asia
¿ Mice are the primary reservoir for B. burgdorferi
¿ Also host early stages of the Ixodes life cycle
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LYME DISEASE
¿ Deer are host for the final stages
¿ Fertile adult female ticks gorge on blood
¿ Fall from deer and lay their eggs in the soil ¿ Eggs hatch and tick larvae seek out mice for blood meals
¿ Bacterium is picked up by the tick larvae feeding on the mice
¿ Remains with the tick throughout its development ¿ Larvae mature during the following spring or summer
¿ Parasitize deer
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE
¿ Complex life cycle – takes two years ¿ Humans contract Lyme disease through tick larvae ¿ Patients exhibit modulations in their immune response
¿ Inhibition of mononuclear and natural killer cell function
¿ Reduced production of cytokines ¿ Chronic Lyme disease has aspects very similar in autoimmune diseases
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE: Pathogenesis
¿ Acute Lyme disease characterized by:
¿ Fever
¿ Migratory bull’s-eye rash
¿ Muscular and joint pain
¿ Often meningeal irritation
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LYME DISEASE: Pathogenesis
¿ Chronic Lyme disease characterized by evolution of:
¿ Meningoencephalitis
¿ Myocarditis
¿ Disabling recurrent arthritis
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE: Pathogenesis
¿ Both the acute and chronic forms are highly variable
¿ Involve multiple body systems
¿ Signs and symptoms have overlapping patterns that come and go at different times
¿ Lyme disease is rarely fatal
¿ If untreated, source of chronic ill health
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE: Pathogenesis
¿ Primary lesions appear in the first month
¿ Expand to become annular lesions
¿ Raised red border
¿ Central clear area
¿ Called bull’s-eye rash
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LYME DISEASE: Pathogenesis
© CDC/James Gathany
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE: Pathogenesis
¿ Ring of the bull’s-eye expands
¿ Forms an erythema migrans lesion
¿ Accompanied by fever, myalgia, headache, and joint pain
¿ If untreated, skin lesions disappear
¿ Other symptoms can persist for months
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE: Pathogenesis
¿ Secondary infection stage begins days, weeks, or months later
¿ Central nervous system and cardiovascular system may be involved
¿ Neurologic abnormalities include:
¿ Meningitis, facial nerve palsy, and peripheral nerve destruction
¿ Cardiovascular involvement can lead to:
¿ Myocarditis and enlargement of the heart
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LYME DISEASE: Pathogenesis
¿ Neurologic and cardiovascular symptoms usually resolve spontaneously in matter of weeks ¿ Arthritis can begin weeks to years after the initial onset of the infection
¿ Marks continuing stage of Lyme disease
¿ Occurs in two-thirds of untreated patients
¿ Involves large joints in particular the knee
¿ Serious cases cause erosion of bone
¿ Can be chronic involvement of central nervous system affecting memory, mood, and sleep
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
LYME DISEASE: Treatment
¿ Early stage treatment
¿ Doxycycline and amoxicillin preferred antibiotics
¿ Treatment after neurologic and cardiovascular involvement
¿ Intravenous penicillin G
¿ Response to therapy is very slow
¿ Requires continuous use of antibiotics for 30-60 days
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RELAPSING FEVER
¿ Caused by Borrelia species other than B. burgdorferi
¿ Transmitted to humans by either ticks or body lice
¿ Two forms, which develops depends on:
¿ Whether the vector was a tick or a louse
¿ Borrelia species involved
¿ Louse-borne form seen in epidemics
¿ Tick-borne form is not
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
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RELAPSING FEVER
¿ Occurrence and distribution of the tick-borne form determined by:
¿ Biology of the tick
¿ Relationship between the tick and the Borrelia reservoir
¿ Rodents, rabbits, birds, or lizards
¿ Ticks can remain infectious for several years
¿ Infected tick able to transfer the spirochete to its progeny
¿ Offspring are carriers even if they do not feed on infected animals
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RELAPSING FEVER
¿ Cycle is different for the louse-borne form
¿ Only human hosts
¿ Live for only about two months
¿ Do not pass the pathogenic spirochete to progeny ¿ Louse-borne form caused by Borrelia recurrentis
¿ Lice infected after biting an infected human ¿ B. recurrentis multiplies in endolymph of the louse ¿ Never moves to salivary glands or the feces
¿ To infect, louse must be crushed and scratched into the bite wound
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RELAPSING FEVER: Pathogenesis
¿ Presents with fever, headache, muscle pain, and weakness
¿ Symptoms disappear in about one week
¿ Return a few days later ¿ During the relapse, spirochetes can be found in the patient’s blood ¿ During periods between relapses, circulating organisms disappear
¿ May sequester in the organs
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RELAPSING FEVER: Pathogenesis
¿ At each relapse, spirochetes appear with new antigenic markers
¿ Periods of relapse correspond to development of new antibodies
¿ Incubation period approximately 7 days
¿ Huge number of spirochetes in the blood (spirochetemia)
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RELAPSING FEVER: Pathogenesis
¿ Tick-borne relapsing fever has only two relapses
¿ Fatalities are rare
¿ Louse-borne form can have as many as 10 relapses
¿ Fatalities can reach 40% if untreated
¿ Death is usually due to myocarditis, cerebral hemorrhage, or liver failure
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RELAPSING FEVER: Treatment
¿ A single dose of doxycycline or erythromycin is sufficient
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RICKETTSIAL INFECTIONS OF THE BLOOD ¿ Rickettsia are coccobacilli that have characteristics of both bacteria and viruses
¿ Divide by binary fission
¿ Very small
¿ Gram-negative but stain very poorly
¿ Better resolved with Giemsa stain
¿ Have a peptidoglycan cell wall with a Gram- negative outer layer
¿ Are obligate intracellular parasites
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RICKETTSIAL INFECTIONS OF THE BLOOD
¿ Cause spotted fevers and typhus-related illnesses
¿ Fevers are typically accompanied by vasculitis.
¿ Most have animal reservoirs
¿ Transmitted by arthropod vectors
¿ Spread through the vector’s life cycle
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RICKETTSIAL INFECTIONS OF THE BLOOD
¿ Most common infection is Rocky Mountain Spotted Fever (RMSF)
¿ Seen throughout the world ¿ Rickettsia grows in the cytoplasm of infected eukaryotic cells
¿ Can only be cultured in cell cultures and fertile eggs ¿ Pathogens start growing in cytoplasmic vacuoles
¿ Escape the vacuole
¿ Grow in cytoplasm ¿ Use directional actin polymerization to move through the cell and from cell to cell
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RICKETTSIAL INFECTIONS OF THE BLOOD
¿ Multiply until large numbers cause host cell to rupture
¿ Rickettsia cannot survive outside host cells.
¿ If they do not find a host cell:
¿ Metabolic activity declines
¿ Begin to leak proteins, nucleic acids, and other essential molecules
¿ Leads to a rapid loss of potential infectivity
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
RICKETTSIAL INFECTIONS OF THE BLOOD
¿ Epidemic typhus is a classic example of a rickettsial infection
¿ Most prevalent in US is RMSF
¿ Both characterized by fever, rash, and muscle aches
¿ Both may be fatal as a result of vascular collapse
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ROCKY MOUNTAIN SPOTTED FEVER
¿ Etiologic agent is Rickettsia rickettsii
¿ Infection causes acute febrile illness
¿ Occurs in association with exposure to wooded areas infested with ticks
¿ Vectors are ticks
¿ Different vectors in different geographic locations
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ROCKY MOUNTAIN SPOTTED FEVER
¿ Rickettsia pathogens do not harm the tick
¿ Live in the endolymph
¿ Passed from one vector generation to the next
¿ More than two-thirds of RMSF cases occur in children younger than 15
¿ Usually seen between April and September
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ROCKY MOUNTAIN SPOTTED FEVER: Pathogenesis
¿ Incubation from bite to onset of symptoms is 2 - 6 days
¿ Fever, headache, muscle aches, and mental confusion
¿ Rash appears first on the soles, palms, wrists, and ankles
¿ Moves toward trunk ¿ Rash is the most characteristic feature
¿ Usually develops on the third day
¿ Appearance makes it easy to distinguish RMSF from viral infections
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ROCKY MOUNTAIN SPOTTED FEVER: Pathogenesis
¿ Muscle tenderness can become extreme, particularly in calf muscles
¿ If untreated complications can include:
¿ Disseminated vascular collapse
¿ Renal and heart failure
¿ Results in death
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ROCKY MOUNTAIN SPOTTED FEVER: Pathogenesis
¿ Infection usually causes vascular lesions
¿ Pathogens multiply in the endothelial cells of small blood vessels
¿ Leads to thrombocytosis and leakage of blood causing rash
¿ Vascular lesions occur throughout body
¿ Most apparent in skin
¿ Most serious in the adrenal glands
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ROCKY MOUNTAIN SPOTTED FEVER: Treatment
¿ Antibiotic therapy highly effective if given in the first week
¿ Delay makes treatment much less effective
¿ If untreated, mortality is 25%
¿ With treatment, mortality is only 5 – 7%
¿ Doxycycline is the antibiotic of choice
¿ Sulfonamides contribute to the infection and should not be given
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
TYPHUS
¿ Several forms of typhus, but the two most important are:
¿ Epidemic
¿ Endemic
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EPIDEMIC TYPHUS
¿ Caused by Rickettsia prowazekii
¿ Transmitted by human louse Pediculus humanus corporis
¿ Historically seen in times of war or famine
¿ Crowding and infrequent bathing are common
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPIDEMIC TYPHUS: Pathogenesis
¿ Rickettsia circulates during acute febrile illness
¿ Lice feed on the body of an infected human and become infected ¿ 5-10 days later, the number of Rickettsia increases
¿ Found in louse feces ¿ Louse defecates while feeding
¿ Rickettsia rubbed into the bite wounds when scratched ¿ Dried louse feces can also be infectious
¿ Enter through the eyes, respiratory tract, and mucous membranes
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPIDEMIC TYPHUS: Pathogenesis
¿ Within two weeks of being bitten:
¿ Fever and headache develop
¿ Rash begins on trunk and moves to the extremities
¿ Complications are myocarditis and central nervous system dysfunction
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EPIDEMIC TYPHUS: Pathogenesis
¿ As with RMSF, vascular lesions are produced
¿ Pathogens multiply in the endothelial cells lining small blood vessels
¿ Leads to thrombocytosis
¿ Leakage of blood causes the rash
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPIDEMIC TYPHUS: Treatment
¿ Doxycycline and chloramphenicol very effective
¿ If untreated, fatality rate can be as high as 60%
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ENDEMIC TYPHUS
¿ Endemic typhus is caused by Rickettsia typhi
¿ Primary infection rodent to rodent
¿ Human infection incidental
¿ Transmitted to humans by the rat flea
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ENDEMIC TYPHUS: Pathogenesis
¿ Pathogenesis is similar to that of epidemic typhus, except for the vector
¿ Symptoms appear 1-2 weeks after infection
¿ Headache, muscle aches, and fever
¿ Maculopapular rash forms
¿ Fever may last 12-14 days if untreated
¿ Mortality and clinical complications are rare
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ENDEMIC TYPHUS: Treatment
¿ Doxycycline or chloramphenicol can reduce fever from 2 weeks to 2-3 days
¿ Control of rats helps prevent the infection
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
VIRAL INFECTIONS OF THE BLOOD
¿ Viruses can be found in the blood – viremia
¿ Some viruses use blood cells as their hosts
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CYTOMEGALOVIRUS
¿ CMV causes formation of perinuclear cytoplasmic inclusions
¿ Enlargement of host cell
¿ In developed countries:
¿ More than half of the population has antibodies
¿ 10-15% children are infected in the first five years
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CYTOMEGALOVIRUS
¿ CMV can be isolated from saliva, cervical secretions, semen, urine, and white blood cells
¿ Can be found years after initial infection ¿ Rate of congenital infection (infection is in utero) is 1% worldwide
¿ Infants excrete CMV in urine or in nasopharyngeal secretions
¿ Most infections are asymptomatic
¿ 20% show neurological impairment:
¿ Sensory-nerve hearing or psychomotor retardation, or both
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CYTOMEGALOVIRUS
¿ Congenital infection can become systemic and cause:
¿ Hepatosplenomegaly, jaundice, anemia, low birth weight, microencephaly and chorioretinitis
¿ Neonatal infection (infection acquired during or shortly after birth) rarely causes any problems
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CYTOMEGALOVIRUS INFECTION: Pathogenesis
¿ Causes a latent infection in leukocytes and bone marrow cells
¿ Responsible for infections associated with blood transfusions and organ transplants
¿ Produces a visceral infection
¿ Affects the organs
¿ Triggers a mononucleosis syndrome
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CYTOMEGALOVIRUS INFECTION: Pathogenesis
¿ Virus infects both epithelial cells and leukocytes
¿ Can cause both tissue damage and immunological damage ¿ In healthy young adults, can cause a mononucleosis syndrome ¿ In the immunosuppressed, primary infections and reactivation of latent infections can be severe
¿ In bone marrow transplants CMV causes interstitial pneumonia
¿ Leading cause of death in these patients (50-90% mortality)
¿ CMV often disseminates to visceral organs in AIDS patients
¿ Causes gastroenteritis and chorioretinitis
¿ Can infect the central nervous system
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CYTOMEGALOVIRUS INFECTION: Treatment
¿ CMV does not respond well to any antiviral drugs ¿ Ganciclovir has been shown to inhibit CMV replication
¿ Prevents infections in AIDS and transplant patients
¿ Reduces retinitis ¿ Combinations of immunoglobulin and ganciclovir reduce high mortality rate seen with pneumonia infections
¿ Long-term survival of these patients is not good
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
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EPSTEIN-BARR VIRUS
¿ Major etiologic agent of infectious mononucleosis and Burkitt’s lymphoma ¿ A human herpesvirus
¿ Small genome – been completely mapped
¿ Can be grown in culture ¿ Has an affinity for human B lymphocytes and epithelial cells
¿ Infection is nonproductive in B cells
¿ Infection is productive in epithelial cells
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPSTEIN-BARR VIRUS
¿ EB virus can be cultured from the saliva of 20-25% of healthy adults
¿ 90-95% of adults worldwide are seropositive
¿ Not highly contagious
¿ Primary EB infection in the second decade of life is usually accompanied by signs and symptoms of infectious mononucleosis
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPSTEIN-BARR VIRUS INFECTION: Pathogenesis
¿ Not very contagious
¿ Transmitted only after repeated contact ¿ Involved in development of malignant infections
¿ Burkitt’s lymphoma, and nasopharyngeal carcinoma
¿ Lymphoproliferative infections in immunocompromised patients ¿ Does not produce cytopathic effects or inclusion bodies
¿ Transformation is the major consequence for infected B cells
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EPSTEIN-BARR VIRUS INFECTION: Pathogenesis
¿ Only small amount of the viral DNA integrates into the host DNA
¿ Most is in a separate circular episome form
¿ After infection, viral proteins and DNA appear in the nucleus ¿ Virus enters B lymphocyte by means of glycoproteins located on its envelope
¿ Glycoproteins bind to CD21 receptors
¿ Normally used by the B cells as a complement receptor
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPSTEIN-BARR VIRUS INFECTION: Pathogenesis
¿ After about 18 hours:
¿ Viral proteins are detectable in the nucleus
¿ Infected B cells begin to express these proteins
¿ These viral proteins mark cell as infected
¿ Targets for cell-mediated killing by host defense
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPSTEIN-BARR VIRUS INFECTION: Pathogenesis
¿ In the acute phase of mononucleosis, 20% of B lymphocytes express viral proteins ¿ Patients with infectious mononucleosis show symptoms
¿ Fever, malaise, pharyngitis, tender lymphadenitis, and splenomegaly
¿ Symptoms persist for days to weeks
¿ Resolve slowly but without treatment ¿ 1-5% of cases have complications
¿ Laryngeal obstruction, meningitis, encephalitis, hemolytic anemia, thrombocytopenia, and splenic rupture ¿ Burkitt’s lymphoma is common in children in sub-Saharan Africa
¿ Lymphomas seem to cluster in areas where malaria is prevalent
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EPSTEIN-BARR VIRUS INFECTION: Pathogenesis
© Dr. M. A. Ansary / Science Photo Library
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EPSTEIN-BARR VIRUS INFECTION: Treatment
¿ Treatment for infectious mononucleosis is mostly supportive
¿ More than 95% make full recovery
¿ EB virus sensitive to acyclovir in laboratory tests but systemic administration has little effect
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ARBOVIRUS INFECTIONS
¿ Variety of infections are seen with arboviruses
¿ Some affect the blood
¿ Arbovirus infections in blood are classified as fever infections
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ARBOVIRUS INFECTIONS
¿ Arbovirus infections usually transmitted by mosquitoes
¿ Virus can be transferred from one generation of mosquitoes to the next
¿ Vector suffers no ill effects ¿ Virus multiplies in the vector during extrinsic incubation period
¿ Increases its numbers
¿ Enhances the chance of causing infection ¿ Transient viremia is a feature of arbovirus infection
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ARBOVIRUS INFECTIONS: Pathogenesis
¿ Three major manifestations, depending on the arbovirus target:
¿ Central nervous system
¿ Major organs, particularly liver
¿ Small blood vessels, causing hemorrhagic fever ¿ All arboviruses produce a cellular necrosis
¿ Instigates inflammation
¿ Leads to fever
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
YELLOW FEVER
¿ Arbovirus attacks the liver
¿ Causes necrosis of hepatocytes ¿ Can also affect:
¿ Urinary system by destroying the renal tubules
¿ Brain
¿ Heart by destroying myocardium ¿ Major complication is hemorrhage ¿ Clinical symptoms associated with yellow fever:
¿ Abrupt onset of fever, chills, headache, and hemorrhaging
¿ Hemorrhaging may become severe
¿ Cause bradycardia and shock
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DENGUE FEVER
¿ Four related serotypes of the virus
¿ Spread throughout the world ¿ Vector for dengue fever same as for yellow fever
¿ Aedes aegypti mosquito ¿ Clinical infection in dengue different from yellow fever
¿ Fever, rash, severe pain in back, head, muscles, and joints
¿ Severe infections lead to shock, pleural effusion, hemorrhage, and death
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
ARBOVIRUS INFECTIONS: Treatment
¿ No specific treatment other than supportive care
¿ There is a vaccine for yellow fever
¿ Prevention is enhanced by control of the vector population
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILOVIRUS FEVERS
¿ Filamentous viruses
¿ Branched, fishhook, and circular configurations
¿ Negative single-stranded RNA genome
¿ Ebola and Marburg are the only two filoviruses that infect humans
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FILOVIRUS FEVERS
¿ Ebola is very contagious
¿ Transmission is person-to-person
¿ 10% of population in rural Central Africa carry Ebola antibodies
¿ Marburg virus has also been seen in nosocomial settings
¿ 25% mortality rate
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EBOLA & MARBURG INFECTION: Pathogenesis
¿ Both cause hemorrhaging in the skin, mucous membranes, and internal organs
¿ Liver cells, lymphoid tissue, kidneys, gonads are all destroyed
¿ Can also cause brain edema ¿ Reasons for such rapid hemorrhaging are still not clear
¿ Evidence that Marburg replicates in vascular endothelial cells
¿ Causes necrosis and bleeding ¿ Ebola causes symptoms in as little as 4-6 days
¿ Mortality rate is extremely high: 60-80%
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
EBOLA & MARBURG INFECTION: Treatment
¿ There is no treatment
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PARASITIC INFECTIONS OF THE BLOOD
¿ There are several important and dangerous parasitic infections of the blood:
¿ Malaria
¿ Trypanosomiasis
¿ Chagas’ disease and filariasis
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE
¿ American form of trypanosomiasis
¿ Caused by the flagellate protozoan Trypanosoma cruzi
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE
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CHAGAS’ DISEASE
¿ T. cruzi trypomastigotes are disseminated in fecal material of the transmitting vector
¿ Vector for T. cruzi is the reduviid
¿ Large winged insect that feeds on sleeping hosts in the evening hours
¿ Once bitten, trypomastigotes spread from the site by circulating in host’s blood
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE
¿ T. cruzi does not multiply extracellularly – must invade host tissue cells
¿ Trypomastigotes lose their flagella
¿ Assumes the amastigote form
¿ Amastigote form begins to multiply by binary fission
¿ Large numbers soon cause host cell to rupture
¿ Parasites are released back into the blood
¿ Revert to the trypomastigote form
¿ Trypomastigotes invade other host cells
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE
¿ If an uninfected reduviid bites an infected host:
¿ Some trypomastigotes are taken up by the reduviid
¿ Infected insect bites a new host
¿ Infection cycle continues
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CHAGAS’ DISEASE
¿ Trypomastigotes in the reduviid move to the hindgut
¿ Deposited in the feces of the insect
¿ Infected feces deposited on new host during a blood meal
¿ Process can recur with every bite for periods up to two years
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE: Pathogenesis
¿ Found from Central America to southern Argentina
¿ Affects between 16 million and 18 million people
¿ Causes approximately 50,000 deaths each year
¿ Leading cause of heart infection
¿ Accounts for 25% of all deaths between ages of 25 and 44 years
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE: Pathogenesis
¿ Reduviid called the kissing bug
¿ Preferentially bites near the lips and eyes ¿ Most infections in children
¿ Can also be acquired in utero and through breast feeding ¿ Also affects dogs, cats, rats, and opossums, which can become reservoirs ¿ Multiplication of the parasite at the site of the bite stimulates the accumulation of neutrophils, lymphocytes, and tissue fluids
¿ Results in the formation of a local chancre called a chagoma
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CHAGAS’ DISEASE: Pathogenesis
¿ Dissemination of parasite in the host causes febrile illness
¿ Persists for up to three months
¿ Causes widespread organ damage
¿ Any cells can be infected
¿ Heart, skeletal muscle, and glial nerve are the most susceptible
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE: Pathogenesis
¿ In the amastigote form the parasite multiplies freely to produce a pseudocyst
¿ An enlarged and distorted host cell
¿ When pseudocysts rupture, many parasites disintegrate
¿ Initiates a powerful inflammatory response
¿ Destroys the surrounding tissue
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE: Pathogenesis
¿ Adaptive immune response eventually destroys T. cruzi
¿ Acute infection is terminated ¿ Only about one-third of newly infected individuals develop clinical symptoms
¿ Primarily children ¿ Onset of parasitemia causes:
¿ Sustained fever and enlargement of spleen and lymph nodes
¿ Can be a transient rash
¿ Heart can also be affected, leading to congestive heart failure
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CHAGAS’ DISEASE: Pathogenesis
¿ Symptoms can last for weeks to months
¿ 5-10% of untreated patients have heart or brain problems that are lethal
¿ Also chronic forms of Chagas’ disease
¿ Seen only in adults
¿ Usually result in coronary dysfunction
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
CHAGAS’ DISEASE: Treatment
¿ There is no effective treatment
¿ Nifurtimox and benznidazole reduce the severity of the acute form
¿ Ineffective in the chronic forms
¿ Have serious side effects
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS
¿ Umbrella term for a group of infections caused by the superfamily Filarioidea
¿ Inhabit the lymphatic systems causing:
¿ An acute inflammatory response
¿ Chronic lymphatic blockade
¿ Swelling of the extremities and genitalia – elephantiasis
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FILARIASIS
© CDC
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS
¿ Two parasites are most commonly involved:
¿ Wuchereria bancrofti
¿ Brugia malayi ¿ Both are threadlike worms that lie coiled up in the lymphatic vessels for decades ¿ Females produce large numbers of fertile eggs ¿ Once eggs are laid, embryos uncoil to their full length – microfilariae
¿ Shell of each egg elongates to become a flexible sheath
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS
¿ Microfilariae leave lymph and enter host’s blood
¿ Accumulate in the pulmonary vessels during the day
¿ At night, worms spill into the systemic circulation ¿ Movement between systemic and pulmonary circulation called periodicity
¿ Determines which type of mosquito will serve as the vector and intermediate host
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FILARIASIS
¿ Mosquito feeding on an infected human ingests microfilariae
¿ Microfilariae transform into the larval form in thoracic muscles of the mosquito ¿ When the mosquito bites, microfilariae penetrate the feeding site
¿ Microfilariae migrate to the lymphatic vessels through series of molts
¿ Reach adulthood in 6-12 months
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS: Pathogenesis
¿ About 120 million people infected with either W. bancrofti or B. malayi
¿ Mostly in Africa, Latin American, Pacific islands, and Asia
¿ Humans are the only known vertebrate hosts
¿ Pathology is confined primarily to the lymphatic system
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS: Pathogenesis
¿ Two types of infection:
¿ Acute
¿ Chronic
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FILARIASIS: Pathogenesis
¿ Acute form caused by presence of molting adolescent and dying adult worms, which stimulate:
¿ Dilatation of the lymphatics
¿ Hyperplastic changes to the vessel endothelium
¿ Cause infiltration of lymphocytes, plasma cells, and eosinophils
¿ Formation of a granuloma
¿ Fibrosis
¿ Permanent lymphatic blockade
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS: Pathogenesis
¿ Repeated acute infections cause massive lymphatic blockade
¿ Skin and subcutaneous tissues fill with edematous fluids
¿ Bacterial and fungal superinfections can now occur
¿ Contribute to further tissue damage
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS: Pathogenesis
¿ Chronic form develops 10-15 years after the onset of first acute attack
¿ Incidence and severity tend to increase with age
¿ Main characteristics are chronic lymphangitis, thickened lymphatic trunk, chronic lymphedema, and elephantiasis
¿ People indigenous to areas usually remain asymptomatic after infection
¿ Some experience filarial fevers and lymphadenitis for 8-12 months
¿ Fevers are usually low-grade and accompanied by chills and muscle aches
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FILARIASIS: Pathogenesis
¿ Lymphadenitis first noted in femoral areas as an enlarged, red, tender lump
¿ Inflammation spreads down the lymphatic channel of the leg
¿ Vessels become enlarged and tender
¿ Overlying skin becomes red and edematous ¿ Acute manifestations last a few days then resolve spontaneously
¿ Reoccur periodically for weeks or even months
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS: Pathogenesis
¿ Repeated infections can cause permanent lymphatic obstruction
¿ Edema, ascites, pleural, and joint effusion
¿ Persistent lymphadenopathy can cause lymphatic channels to rupture
¿ Causes formation of abscesses
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
FILARIASIS: Treatment
¿ Diethyl carbamazine eliminates microfilariae from blood
¿ Also kills or injures adult worms
¿ Suppresses the infection in the long-term
¿ Is a potential cure
¿ Dying worms can elicit an allergic reaction in host:
¿ Reaction is occasionally severe
¿ Requires the use of antihistamines and corticosteroids
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
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FILARIASIS: Treatment
¿ Tissue changes seen in elephantiasis are often irreversible
¿ Enlarging of the extremities may be ameliorated through the use of pressure bandages
¿ Control of the vector helps prevent infection
Microbiology: A Clinical Approach,Approach (2bynd TonyEdition) Srelkauskas © Garland © ScienceGarland Science ISBN: 978-0-8153-6514-3
47