Transcript Duke in Darwin

Duke in Darwin
Eleni Boussios, MD, MSPH
Infectious Diseases Conference
April 21, 2009
Duke
History
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CC: 59-year-old, African-American man with fevers
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Symptoms x 7days
Generalized malaise
Subjective fevers
Nasal congestion with yellow discharge
Cough productive of white sputum
Decreased oral intake with nausea
Vomited (non-bloody, non-bilious) day prior to admission
“Dehydrated and weak”
Complained of moderate frontal headache
Seen by doctor 2 days after symptom onset & started on amoxicillin
for “sinusitis”
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Review of Symptoms
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No vision changes, neck pain, neck stiffness, sore throat, ear pain,
oral lesions, chest pain, shortness of breath, abdominal pain,
diarrhea, dysuria, urethral discharge, rash, or joint complaints
No recent change in medications aside from amoxicillin
No recent travel
No sick contacts
Past History
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Coronary artery disease with past MI
Hyperlipidemia
Cerebrovascular disease with past stroke
DVT LLE on warfarin anticoagulation
Cardiac arrhythmia on procainamide (has failed other treatments)
Medications
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HCTZ 25mg PO daily
Lisinopril 5mg PO daily
Metoprolol 25mg PO twice daily
Niacin 500mg PO TID
Nitroglycerin 0.4mg SL PRN
Procainamide 1500mg PO Q12H
Warfarin 9mg PO QHS
History
SHX:
 Married
 From Granville county
 Retired
 Occasional ETOH
 No tobacco
 No illicit drugs
 Turkey hunter as hobby
FHX:
 No known illnesses
Exam
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T: 39.9 initial SBP of 80  after 3L of NS 111/67
GEN: well-appearing male, alert, oriented, NAD
HEENT: dry mm, no JVD, no LAD, no oral lesions, no nuchal rigidity,
posterior OP clear, boggy nasal mucosa with mucous stranding
PULM: CTA bilaterally, no rhonchi, crackles, rales, or wheezes
CV: RRR without murmur
ABD: soft, + BS, NT/ND, no rebound or guarding, no organomegaly
EXT: no edema, no joint swelling
NEURO: CN 2-12 intact, good historian, no focal deficits
GU: negative for occult blood
SKIN: no rash!
Labs
15.1
6.1>---<96
47
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128/87/14
---------------<136
3.9/28/1.5
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1.2/212
---------249/184
Amylase 60
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D-dimer: 0.62
Fibrinogen: 460
CK: 493
INR: 3.03
PTT: 66
Ca: 8.8
Mg: 1.9
PO4: 2.4
UA: 13 RBC
Blood and urine cultures: NGTD
HIV: negative
Hepatitis A, B, C: negative
CXR: no infiltrate
Turkey Hunting
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Presentation was in late March
(spring in NC)
Found several ticks on his
body after turkey hunting in the
previous weeks
He was admitted to hospital to
the ICU
Commenced doxycycline
100mg twice daily empirically
He responded well to
treatment & was transferred to
the general medicine floor
couple days later & discharged
home shortly thereafter
Diagnosis
RMSF
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The presumptive diagnosis
was Rocky Mountain Spotted
Fever
Rapidly responded to
treatment
Diagnosis subsequently
confirmed by convalescent
antibody titers or IFA (indirect
fluorescent antibody test)
Rocky Mountain Spotted Fever
(RMSF)
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Caused by Rickettsia rickettsii,
a gram-negative, obligate
intracellular bacterium
Genus Rickettsia
Family Rickettsiaceae
Orientia is other genus in
family
Most common rickettsial
infection in the US
Presentation ranges from mild
to fulminant
History
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Originally recognized in 1896
in the Snake River Valley of
Idaho
Called “black Measles”
By 1900s the recognized
geographic distribution grew to
broadly encompass the US
Dr. Howard T. Ricketts
identified the organism &
epidemiology of the disease in
1908
Research done at the Rocky
Mountain Laboratory
Dr. Ricketts ironically died of
typhus in 1910
Rocky Mountains—a Misnomer
Epidemiology
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Occurs throughout the US,
Canada, Mexico, Central
America, & parts of South
America
Most prevalent in SE &
south central US
NC accounts for >41% of
the cases in 2005
Most occur in the spring &
early summer
Average annual incidence
is 2.2 cases per million
persons in the US each
year
Cases Per Year
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Reportable disease
since 1920s
Incidence varies
greatly from year to
year
Incidence anywhere
from 250 to 1200
cases a year
E.g. only 395 cases
reported in 1997 yet
1843 reported in 2005
Etiology of variations
unclear
Disease Transmission
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The main vector the American
dog tick (Dermacentor
variabilis)
Dermacentor andersoni (the
Rocky Mountain wood tick)
primary vector west of the
Mississippi River
Transmitted via a tick bite
Adult feeds for about 2 weeks
R rickettsii is in the salivary
glands & is reactivated &
transmitted during blood meal
1/3 of patients do not recall tick
bite or tick contact
American Dog Tick Life Cycle
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R rickettsii maintain in the
wild by a lifecycle of
transmission between ticks
& small mammals that are
not adversely affected by
the disease
Ticks both vectors & natural
hosts/reservoirs
Maintained throughout all 4
lifecycles
Humans accidental “deadend” hosts
Dogs also play role in
transmission
Disease Transmission
Clinical Manifestations
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Symptoms 2 to 14 days after being bitten by an infected tick
(incubation period from 2-14 days)
Most between 5 & 7 days after exposure
Onset often sudden
Early symptoms: fever, headache, malaise, myalgias, arthralgias,
& nausea, +/- vomiting
Abdominal pain that can be severe
Other symptoms: cough, bleeding, edema, confusion, focal
neurologic deficits, & seizures
Rash
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Most develop rash within 3-5
days of symptoms
Only 14% have rash on the 1st
day
< 50% develop rash in 1st 72
hours
Rash never occurs in up to
10% of patients ("spotless"
RMSF)
Typical rash begins on the
ankles and wrists & spreads
both centrally & to the palms
and soles
Begins as a macular or
maculopapular & becomes
petechial
Urticaria & pruritus are not
present
Decision to Treat & Deadly
Outcomes
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Must not delay treatment!
Decision to treat Is based on the occurrence of typical symptoms in
patients from endemic areas
Duke retrospective study of 94 patients with RMSF, those treated
within 5 days of symptom onset were much less likely to die vs.
those treated after 5 days (6.5% vs. 22.9%)
Over 90% of patients saw a Dr. within the 1st 5 days of illness but
less than ½ received anti-rickettsial treatment
3 independent predictors of failure to treat: 1) no rash 2)
presentation within the 1st 3 days of illness & 3) presentation
between Aug 1st & April 30th
Case Fatality
Treatment
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Doxycycline 200mg/day in 2 divided doses for adults & children
>45kg
2.2mg/kg/dose Q12H for children <45kg
Some places (Duke) give a single loading dose of 200mg to critically
ill patients
Pregnant women should be treated with chloramphenicol
50/mg/kg/day in 4 divided doses
Treat at least 3 days after the patient becomes afebrile
Most patients are cured within 5-7 days of treatment
Diagnosis
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NO completely reliable diagnostic test in the early phases of illness
when therapy should be commenced
Therefore, if RMSF is suspected given the clinical presentation, one
should treat!
The diagnosis can be later confirmed by skin biopsy or serological
testing
Lab Findings
Normal white count
 Thrombocytopenia
 Reduced fibrinogen concentration
 Elevated fibrin split products
 Hyponatremia
 Elevated aminotransferases & bilirubin
 Azotemia
 Prolonged PTT & INR
 Renal failure & elevated creatinine
CSF:
 WBC <100
 PM or lymphocytic predominance
 Moderately elevated protein
 normal glucose
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Diagnosis—Skin Biopsy & Serology
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Skin biopsy: using direct immunofluorescence is 70% sensitive &
100% specific
Indirect fluorescent antibody (IFA) test:
Antibodies appear 7-10 days after illness onset (95% sensitive)
Convalescent antibody titer 14 to 21 days after the onset of
symptoms (min 1:64)
False-negatives likely in the first 5 days of symptoms because
antibodies not yet detectable
False negative in patients treated within 48 hrs because they do not
develop detectable convalescent antibody titers
Positive IFA Reaction
Other Diagnostic Tests
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Blood cultures*
Enzyme immunoassay
Complement fixation
Latex agglutination
Indirect hemagglutination
Microagglutination
Whole blood PCR not useful but some labs can perform PCR
on skin biopsies
Other US Tick-Borne Infections
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Ehrlichiosis (Ehrlichia
chaffeensis)
Human granulocytic
anaplasmosis (Anaplasma
phagocytophilum)
Lyme disease (Borrelia
burgdoferi)
STARI/southern tickassociated rash illness
(Borrelia lonestari)
Babesiosis (Babesia microti)
Other Rickettsial SFG Diseases
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Rickettsia of the spotted fever group (SFG) cause human illness
throughout the world
Many have been newly identified in recent years 20 species
currently known
Their clinical & epidemiological characteristics vary but they all
share 3 common features:
All cause fever, headache, & abdominal pain
All are arthropod borne
Rash &/or eschar occur in most
Australia: Queensland tick typhus, Flinders Island spotted fever,
Australian spotted fever, Murine typhus, & Scrub typhus
Australian SFG Diseases
Queensland Tick Typhus
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Caused by R. australis
Occurs along the entire east
coast of Australia
Transmitted by the scrub tick
(Ixodes holocyclus)
Circulates between ticks,
rodents, & small marsupials &
incidental human infection
Eschar at the site of the tick
bite occurs in ½ to a third
Regional LAD
Maculopapular, petechial, or
vesicular rash
Flinders Island & Australian
Spotted Fever
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Recognized by an Australian GP
in the 1980s in patients living in
the Bass Straits between
Tasmania & the mainland
R. honei
Mild disease
A fourth develop a necrotic
inoculation lesion at the site of
bite
½ localized LAD
Almost all with fever, headache,
& myalgias
Skin rash maculopapular but
rarely petechial
Scrub Typhus
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Orientia tsutsugamushi
(previously R. tsutsugamushi)
Gram negative coccobacillus
Mite-borne (chiggers)
Endemic to Queensland
Has been found in the NT
Symptoms: headache, high
fever, & myalgias
½ with non-pruritic macular or
maculopapular rash that
begins in the abdomen &
spreads to the extremities
Petechiae rare
Some develop eschar at site of
tick bite
Scrub Typhus
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Other symptoms: LAD, nausea,
vomiting, diarrhea, cough,
meningitis, encephalitis,
pericardial effusion
Bloods: thrombocytopenia,
elevated LFTs, elevated
creatinine, & leukopenia
Diagnosis: serology/IFA, skin
biopsy, culture*, blood PCR*
Confirmed cases of scrub typhus
acquired in Litchfield Park since
1990
References
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Chen L, Sexton D. What’s new in Rocky Mountain Spotted Fever. Infect Dis Clin
North Am. 2008 Sep;22(3): 415-432.
Kirkland KB, Wlikinson WE, Sexton DJ. Therapeutic delay & mortality in cases of
Rocky Mountain Spotted Fever. Clin Infect Dis. 1995;20(5):1118-1121.
Currie B, O’Connor L, Dwyer B. A new focus of scrub typhus in tropical Australia. Am
J Trop Med Hyg. 1993 Oct;49(4):425-429.
Sexton DJ. Treatment of Rocky Mountain spotted fever. In: UpToDate, Basow, DS
(Ed), UpToDate,
Waltham, MA, 2008.
Sexton DJ. Clinical Manifestations & Diagnosis of Rocky Mountain spotted fever. In:
UpToDate, Basow, DS (Ed), UpToDate,
Waltham, MA, 2008.
Sexton DJ. Other spooted fever group rickettsial infections. In: UpToDate, Basow, DS
(Ed), UpToDate,
Waltham, MA, 2008.
http://www.cdc.gov