1
Q
Q fever tx
A
Treat with doxycycline +/- surgery for endocarditis
2
Q
Congo-Crimean Hemorrhagic Fever
sx
animals
location
A
– fever, hemorrhages
– tick, reservoir rodents
– Asia, Africa
3
Q
Leptospirosis: Management
A
Doxycycline or penicillin for 1 week
• Prophylactic doxycycline 200mg weeklyi s effective in data from military clinical trials
3
Q
Rickettsial infections
A
4
Q
Guillain-Barr’ is due to cross reaction between
A
capsular oligosccharides and glycosphingolipids on nerve surface (autoimmune disease)
5
Q
Yersinia pestis
• Vector
A
Xenophylla cheopis, the Rat Flea, is the main
vector; related fleas of rodents are secondary vectors
5
Q
Ixodes sp.: Life cycle
A
Eggs hatch to larvae (spring to summer)
Larvae require a vertebrate blood meal to develop into nymphs (early fall)
- Nymphs become dormant in winter; require another blood meal before they can become adults (spring to summer: most infectious stage)
- Adults mate and then lay eggs (summer to fall)
- Eggs remain dormant over the winter
6
Q
Lassa fever characteristics
A
Arenaviruses
most common febrile illness in Sierra Leone
– African bush rat ( Mastomys natalensis )
– Transmission from urine from rats and patient body fluids ( nosocomially)
6
Q
Flaviviruses
• Pathogenesis
A
– infect macrophages
– cell damage by cell mediators – tissue destruction by T- cell
– shock syndrome;
- virus-antibody complex enters monocytes via Fc rec
- antibody enhances infection
- generally increased production of cytokines
- severe illness, shock, hemorrhages
7
Q
Campylobater jejuni
• Diagnosis:
A
Presence of “S” shaped bacteria in stool
• Detection of Campylobacter antigens in stool is more sensitive and specific for diagnosis
8
Q
Campylobater jejuni
• sources
A
Worldwide round the year infections
• Poultry is the common source, ingestion of contaminated food, water and unpasteurized milk may cause diarrhea
9
Q
Anthrax in what animals
A
Native to hoofed domestic herbivorous animals: cattle, horses, etc.
9
Q
Brucellosis : pathogenesis
A
- Once skin or mucous membranes are penetrated by organisms they are carried to lymphatics by PMNs
- Cells multiply within macrophages
- Humoral response is ineffective; T-cell response required.
- Failure of T-cell control results in granulomatous inflammation with bacterial multiplication within the RES
- Waves of bacteria are released into the circulation from these sites resulting in recurrent bacteremia.
9
Q
Flaviviruses characteristics
A
- Genome:ss+ polarity, RNA
- Epidemiology:
– Arbovirus (except Hepatitis C )
– All flaviviruses serologically related- cross reacting antibodies
10
Q
Tularemia found in
A
Rabbits, beavers, deer (can be found in cats and dogs)
dog tick (Dermacentor variabilis), wood tick (Dermacentor andersoni), lone star tick (Amblyomma americanum), deer flies (Chrysops spp.)
10
Q
Anaplasmosis sx
A
>95%: fever, myalgia, headache; 75%: renal dysfunction;
• Rarely: pancarditis, myocarditis, abdominal pain, renal failure, ARDS….
10
Q
Filoviruses type of fever
A
MHF (Marburg Hemorrhagic Fever)
11
Q
Pasteurella multocida:Epidemiology
A
Normal respiratory biota of many lower animals,
including cats and dogs.
• Human is infected by bite ( dog commonly) or scratch
13
Q
Faliciparum zoonotic source
A
Birds (Chickens, Ducks)
14
Q
Yersinia pestis infection in flea vector
A
- Flea acquires Y. pestis when it takes a blood meal from an infected rodent host.
- Organism multiplies in proventriculus of the flea, eventually blocking the flea’s GI tract.
- Starving flea regurgitates infectious material when attempting to take another blood meal.
- Flea eventually dies of the infection
14
Q
Tularemia - Diagnosis
A
history
Direct fluorescent antibody on appropriate clinical material is sufficient
15
Q
Cat-scratch disease
A
_ Papule/pustule 3 - 10 days post cat-scratch, lick or bite.
– Fever and with regional lymphadenopathy (head, neck, axilla)
– Most cases recover completely & spontaneously
15
Q
Q fever ( “Q” for “Query”) caused by
A
Caused by Coxiella burnetti
16
Q
Rocky Mountain Spotted Fever carried by
A
– Dermacentor andersonii Wood Tick Western States
– Dermacentor variabilis Dog Tick Eastern States
– Ambylomma americanum Lone Star Tick Southwest
17
Diagnosis Anthrax
PCR
bx
culture
stain
17
Tularemia: Pathogenesis entry
through inhalation, ingestion, or injection
Bacteremic spread
– seeds RES \> granulomatous inflammation\>Ulcerated lesion develops at injection site
18
Leptospirosis: pathogenesis
Can get through intact skin/mucous membranes
• Prolonged immersion in contaminated waters e.g. from falling into river waters
18
Lyme Disease organism
(B. burgdorferi) has same range as
Ixodes sp. ticks
18
Rickettsial infections features
* Primary infection in human vascular epithelium with capillary leak syndromes; adrenal glands also affected
* Common Clinical Manifestations
– sustained high fever
– severe retro-orbital headache
– Rash (distribution and extent differs with different species)
19
Bunyaviruses
General characteristics
Genome:ss-RNA,3segments;S,M,L
20
Leptospirosis hosts
Rodent hosts esp. Rattus norvegicus
• L. ictero-haemorrhagiae is a classical parasite of rats, L. canicola of dogs, L. hebdomadis of cattle, L. pomona of pigs
21
what inhibits certain Gram-positive bacteria in maconkey agar
crystal violet
23
Anthrax: Clinical manifestations
Cutaneous: most common in humans- non lethal
## Footnote
Septicemic- high mortality
Pulmonary: highest mortality in humans; rare under natural circumstances: “Wool- Sorter’s Disease.”
24
Yersinia pestis animals
rodents
24
Filoviruses sx reservoir, location
– fever, rash, hemorrhage, probably disseminated intravascular coagulation
– no known reservoirs or vector
– first appeared in Marburg, Germany, 1967; lab infection from Ugandan monkeys
25
Virulence Factors: B. anthracis
• Lethal Factor
– tissue necrosis
• Edema Factor
– Causes infiltration and tissue swelling: enhance distribution of Lethal Factor
• Protective Antigen
– Probably the same substance as the Edema Factor with additional effect
26
Summary of Hemorrhagic Fever Viruses
27
Congo crimean fever characteristics
28
Diseases from the most common
human Bartonella spp.
29
Arenaviruses characteristics
Genome: ss - RNA, 2 segments( smaller is
ambisense )
– host ribosomes in the virus particle, no function
• Epidemiology:
– reservoir in rats of many species
– spreads through rat feces and urine – mortality ranges from 10 - 50%
30
Bacillary Angiomatosis seen in who
HIV
31
P. multocida: clinical Manifestations
infection at site of inoculation e.g. bite
* Associated cellulitis
* Systemic infection is uncommon but can be quite severe
31
Leptospirosis: Clinical Features
Initial blood stream invasion with localization in kidneys, liver, meninges and brain
• Incubation period is 1-2 weeks with 4 syndromes:
Bacteremic: flu-like, diarrhoea and vomiting; conjunctival congestion
Meningitic: like viral meningitis
Icteric: fever, hemorrhage, hepatic and renal impairment
Pulmonary:Adult Respiratory Distress Syndro
32
Tularemia: Francisella tularensis characteristics
Gram negative short rods
– Facultative, not spore forming
– Nutritionally fastidious: will not grow on blood or other common media; requires supplemental compounds
– Grown with Cysteine-Glucose Blood Agar (Aerobic)
– Slow growing: Requires 2 to 10 days for visible growth
32
Viral Hemorrhagic Fevers (VHFs)
viruses
Arena-, Bunya-, Flavi-, and Filoviridae
33
Smallpox zoonotic source
cattle
33
Bunyaviruses reservoirs
reservoir in mice, rats and ticks
34
Leptospirosis shed in
urine but infection is asymptomatic in animal host
34
VHF-Lassa Fever tx
Ribavirin
35
Brucellosis which one is the most infectious
B.melitensis
36
C. burnetti shows phase variation
Infected source isolates – phase I, highly infectious; phase II within in-vitro culture; not infectious
38
Pasteurella multocida animal
cats, dogs, horses
40
Plague: Diagnosis/CDC
pre-treatment
Lymph node aspirate: An affected bubo should contain numerous organisms that can be evaluated microscopically and by culture.
Blood cultures: Organisms may be seen in blood smears if the patient is septicemic.
* Sputum: Culture is possible from sputum of very ill pneumonic patients; however, blood is usually culture-positive at this time as well.
* Bronchial/tracheal washing may be taken from suspected pneumonic plague patients
* In cases where live organisms are unculturable, lymphoid, spleen, lung, liver tissue, bone marrow samples useful for direct detection methods such as direct fluorescent antibody (DFA) or PCR.
41
B. burgdorferi within the tick vector
Borellia sp. cells adhere to epithelial cells of tick’s midgut and remain there indefinitely in a quasi- dormant state
41
Lyme Stages: analogous to Syphilis
• Primary stage:
– ECM (Erythema Chronicum Migrans/ the target
lesion occurs in 40 - 50% of cases
• Secondary stage:
– Secondary annular skin lesions (Exanthem)
– CNS, cardiovascular, ophthalmic and musculoskeletal manifestations
• Tertiary stage:
– ACA (Acrodermatitis Chronicum Atrophicans)
– Diverse CNS symptoms, Arthritis, Cardiomyopathy
41
Bunyaviruses pathogenesis
plasma and RBCs leak through vascular epithelium
43
CCR-5 Mutation
Persons having one copy (heterozygous) of the gene have increased resistance to HIV
* Persons having two copies (Homozygous) of the gene may be immune to HIV
* This mutation has been traced back to Western Europe in the late 14th Century: The time and Place of the Black Death!
45
Brucella spp animals
goats, cattle, swine, dogs
46
Bartonella (formerly known as Rochalimaea) characteristics
* Gram-negative bacteria
* Facultative intracellular pathogens
47
B. melitensis animal and location
goats, sheep, camels [Europe, Asia, Middle East, South & Central America]
48
Lyme Disease: tx
* Doxycycline or Amoxicillin for early disease
* Ceftriaxone or Cefotaxime for late disease with
prolonged therapy.
50
Brucella characteristics
Gram negative short rods
* Non-motile
* Nutritionally fastidious
– Facultative Intracellular Parasites
– Require complex artificial media in-vitro
– Slow growing (up to 10 days on Blood agar)
51
Leptospirosis: Diagnosis
PMNs rise, liver enzymes rise, CK rise ; platelets fall
* CSF shows a “viral pattern”
* Isolation from blood/ urine- special media & prolonged incubation
* Serology
* PCR
52
Scrub Typhus sx
Onset is sudden headache, fever, malaise, weakness and cough
* Maculo-papular rash about 5th – 7th day trunk, face, limbs including palms and soles with generalised painless lymphadenopathy
* Severe cases are prostrate with pneumonia, confusion ; cardiac, renal failure; hemorrhage and death
53
Rocky Mountain Spotted Fever (R. rickettsii)
* Incubationperiodcirca7days
* Rash on 3rd or 4th day looking like measles
* Skinhemorrhages
* Hepato-splenomegaly
Rash: appears on 2nd or 3rd days on wrists or ankles and spreads inward to the trunk within hours. (Centripetal Spread); extends to cover palms of the hands and soles of the feet
55
Tularemia tx
aminoglycoside
57
Yersinia pestis: Reservoirs
Sylvatic Plague: Rural reservoirs of Y. pestis still exist
in several areas of the world
– Semi-arid regions of the Southwestern U.S.A.
– Southeast Asia & Grasslands of Central Asia (the
original homeland of Y. pestis)
• Not found (in significant numbers) in: Western Europe, Africa or Australia
58
Korean Hemorrhagic Fever
characteristics
– Hemorrhagic Fever with Renal Syndrome
– mice, rats
– far east, Scandinavia, E. Europe,
– severe pulmonary syndrome in SW US (Sin Nombre)
58
Filoviruses pathogeneis
– tissue necrosis in parenchymal cells of liver, spleen, lungs and lymph nodes
– edema and hypovolemic shock
– BCX4430, small mol. Nucleoside analogue protected monkeys from Marburg virus and MERS-Cov
59
Lyme Disease: Diagnosis
Diagnosis:
* B. burgdorferi in blood smear during early stage only
* Serology for later stage is unreliable: ELISA, IFA
60
How does isoxazole stop filoviruses
blocks protein NPC1 which is needed for replication
61
Rickettsia spp. characteristics
gram-negative short bacillary forms
• They do not stain well with Gram’s but can be seen with Giemsa staining
intracell organisms
63
Plague:
Incubation
- Bubonic form is 4 to 7 days
- Pneumonic form is 18 to 36 hours
64
Venezuelan hemorrhagic fever (Guanaritovirus)
Characteristics
– fever, headache, sore throat, pharyngitis, loss of appetite, nausea, vomiting, seizures and nose and gum bleeding.
– reservoir in cane rats ( Zygodontomys brevicauda ) and cotton rats ( Sigmodon alstoni )
– mortality 30 - 40%
– no vaccines
– rodent control
66
Yersinia pestis in what animals
Voles, Rats, Ground
Hogs, Rock Squirrels
68
Francisella tularensis animals
rabbits
69
Measles zoonotic source
Cattle (Rinderpest)
70
Yellow Fever characteristics location, animal
Yellow Fever virus is a Flavivirus
Reservoir – monkeys; transmission from mosquitoes
Africa, South and Central America
72
Anthrax is endemic in
sub-Saharan Africa, Asia, South and Central America, Southern and Eastern Europe
73
Dengue fever- 4(5?) location
– India, SE Asia, Pacific, South America, and the Caribbean
75
B.suis animal and location
pigs [South Asia]
76
Tuberculosis zoonotic source
cattle
77
Yersinia pestis: Prevention and Containment
* Rat control
* Avoid handling, skinning wild animals in endemic areas
* 48h isolation on Rx; gowns, gloves, masks...
* Post-exposureprophylaxiswithcaseofpneumonic infection is doxycycline 100mg or ciprofloxacin 500mg bd for 1 week
* Inactivated vaccine does not work against pneumonic plague
78
Filoviruses: Ebola disease( Ebolavirus ) characteristics
– sudden febrile illness, vascular collapse, internal
bleeding, death
– Incubation period: 2-21 days
– Sudan and Zaire (Democratic Republic of the Congo) ; no known vector or reservoir ? bats/primates
– 1976 first epidemic, many epidemics
– 90% mortality
79
Cutaneous Anthrax : Pathogenesis:
Begins at site of 1° infection as a papule; progresses through a vesicular stage to a depressed black necrotic ulcer (eschar)
Edema, redness, and/or necrosis without ulceration may occur
Form most commonly encountered in naturally occurring cases
Incubation period: 1–12 days
81
Pasteurella multocida characteristics
Gram negative short rods/short bacilli
* Facultative;fermentscarbohydrates
* Oxidasepositive
* Grows readily on enriched media like Blood Agar, but not on media selective for Gram negatives (MacConkeys)
83
Brucellosis: Acute Infection
Incubation time: 7-21 days
## Footnote
Onset with drenching sweat with high fever (up to 40°C.); then a swinging fever, rigors, lethargy, headache, musculo-skeletal pain; scrotal pain
Occasionally delirium, abdominal pain, constipation
• Lymphadenopathy & splenomegaly
84
Ehrlichiosis/Anaplasmosis sx
• Symptoms include fever and GI abnormalities; severe cases progress through cough, diarrhea and lymphadenopathy up to respiratory insufficiency, renal insufficiency and CNS abnormalities.
85
HEMORRHAGIC FEVERS flow
88
How is anthrax transmitted person to person
cutaneous anthrax
89
Acute phase of plague
- Bubonic plague: swollen, painful inguinal lymph nodes; increasing fever, pooling of blood and microhemorrhages in face and extremities.
- Pneumonic: violent and fulminating bacterial pneumonia; nearly always fatal.
90
Leptospira interrogans characteristics
* Tight spiral. 0.15 thick x 5 to 15 long
* Sensitive to heat, drying and most chemicals
* Survives well ( 1 to 2 weeks) in slightly alkaline ground water or soil, but does not multiply.
91
Coxiella burnetti characteristics
* Obligate intracellular parasite
* Can survive in extracellular environment
* Cattle, sheep, goats are important reservoirs
* Transmission by inhalation of aerosolized particles
NO VECTOR!!
93
transmission of Bartonella (formerly known as Rochalimaea)
• Transmission vectors include ticks, fleas, sandflies, mosquitoes
94
Campylobater jejuni characteristics
Thin, curved gram negative rods
• Culturing requires Low Oxygen tension and higher incubation temperature ( 42oC)
95
Brucellosis carried to lymphatics by
PMNs
96
Tularemia: Clinical Presentation
Syndromes depend on site of infection:
– Ulcero-glandular (from injection: lowest mortality) – Typhoidal (resulting from ingestion)
– Pneumonia (from inhalation: highest mortality)
97
CSF in Neuro-leptospirosis.
Slightlyormoderatelyincreasedprotein levels in CSF in 50% of cases.
•
Moderately increased numbers of leucocytes with prevalence of neutrophils in 50% of cases (initially) but in following days monocytes prevalent.
Glucose levels normal in 80%..
So can look like listeria or viral meningitis
98
Pertussis zoonotic source
pigs, dogs
99
Inhilation Anthrax: clinical features
“Flu-like” illness
Meningitis in 50% of patients
100
Rocky Mountain Spotted Fever reservoir
– Dogs
– Wild Rodents
– The tick itself (Trans-ovarial maintenance)
101
Anaplasmosis transmitted by
tick
102
Scrub Typhus transmitted by
mites
103
Zoonoses due to Campylobacter
105
Yersinia pestis : Pathogenesis
Organism reaches lymph node where:
* Higher temperature induces formation of virulence factors.
* Rapid multiplication.
* Infected lymph node swells and becomes painful: a Bubo
* Progresses to bacteremia which seeds liver, spleen lungs and sometimes meninges
106
Brucella transmission
Direct occupational contact: Butchers, Veterinarians. Access through skin breaks, mucus membranes, aerosols, splashes. Ingestion of infectious dairy products. Organism is killed by pasteurization.
107
B. abortus- animal and location
cattle [Africa, Asia, South America]
108
Ehrlichiosis/Anaplasmosis
• E. canis & E. chafeensis: Human Monocytic Ehrlichiosis; transmitted by
Disease seems to be transmitted by the Brown Dog Tick in the US (?reservoir ?vector) ; often first misdiagnosed as Rocky Mountain Spotted Fever.
109
Brucellosis: Diagnosis
• Isolation from blood cultures; positive in 75% of
cases with B. melitensis and 50% with B. abortus
* Bonemarrowmaybeusefulinmorechronicstate
* CSF in neuro-infection : 30% culture positive
* Risk to laboratory staff from culture
* Serology
110
Q fever: clinical features
* Fever, headache, chills; 20% rash; pneumonia, hepatitis
* Osteomyelitis,encephalitis,endocarditisin chronic cases
* Diagnosis is serological; phase I and II, IgM peak at 4-6 weeks
111
Brucellosis which one forms abscess
B. suis
112
Brucellosis: Chronic infection signs
Prolonged cases show marked weight loss
* Few other physical findings or signs: sometimes glandular or hepatic symptoms
* Sacro-ileitis
* Depression
113
Scrub Typhus
• Caused by
Rickettsia –like organism; Orientia
tsutsugamushi
114
Brucella reservoir
Infected animals excrete organisms for prolonged periods in milk, animal urine, feces, vaginal discharge and uterine products.
115
Influenza zoonotic source
Pigs, Ducks
116
Bacillus anthracis characteristics
Anthrax
## Footnote
large, box-car, gram-positive rod; aerobic and spore forming
117
Filoviruses characteristics
* Genome: ss - RNA, long filamentous virus
* Epidemiology:
– no known reservoir
– mortality ranges from 20 - 90% – confined to Africa (?)
118
Zoonotic Gram-negative bacteria
Brucella
Yersinia pestis
Francisella tularensis
Pasteurella multocida
119
Plague: Yersinia pestis characteristics
* Gram negative short rods/bacilli
* Member of the Enterobacteriaceae:
– Gram negative non-spore forming rod
– Oxidase negative
– Facultative
– Glucose fermenter
* Grows readily in standard media
* Rich polysaccharide capsule present in virulent strains
Micro
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