Download Tick-borne Diseases

4/15/2015
Tick-borne Diseases (TBDs)
TICK-BORNE DISEASES IN
USA: LYME AND BEYOND
GEORGE TURABELIDZE, MD, PHD
STATE EPIDEMIOLOGIST,
MISSOURI DEPARTMENT OF HEALTH AND SENIOR
SERVICES
TBDs are some of the world’s most rapidly
expanding arthropod-borne diseases
≈ 865 species of ticks known worldwide
Burden of TBDs in the US is of growing concern
Likely reasons for increasing TBDs:
- shifts in the prevalence and distribution of animal
reservoirs and tick vectors;
- movement of humans into areas where the animal
hosts and tick populations are abundant
Pediatric Grand Rounds, Buffalo, NY, April 17, 2015
TBDs and Climate
Emerging Infections Worldwide, 1940-2004
Climate change plays mixed and relatively minor
role in emergence of most TBDs
Climate change effects probably less than those of
changes in land use and social factors
The effects of climate on transmission are multiple,
non-linear, and act in opposing directions
In core transmission areas, warming may even
decrease transmission if decreases in vector survival
through heat and moisture stress overwhelm other
influences (Kilpatrick & Randolph, Lancet, 2012)
Tick-borne Diseases in USA
Lyme disease
STARI (Southern TickAssociated Rash Illness)
Anaplasmosis
Ehrlichiosis
Babesiosis
Powassan disease
Tick-borne relapsing fever
(TBRF)
Rocky Mountain Spotted
Fever (RMSF)
R. parkeri Rickettsiosis
364D Rickettsiosis
Colorado Tick Fever
Tularemia
Borrelia miyamotoi
Heartland virus
Bourbon virus
Lyme Disease
LD is the most commonly reported vector-borne
illness in the US
CDC estimates 300,000 cases annually in the USA
In 2013, 5th most common nationally notifiable
disease
95% of confirmed LD reported from 14 states:
Connecticut, Delaware, Maine, Maryland,
Massachusetts, Minnesota, New Hampshire, New
Jersey, New York, Pennsylvania, Rhode Island,
Vermont, Virginia, Wisconsin
Similar bacteria infected humans in Europe during
the ice age
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Approximate Distribution of the
Blacklegged Tick, CDC, 2010
Lyme Disease
In USA, Borrelia burgdorferi sensu stricto is only pathogen of LD
B. burgdorferi sensu lato complex comprises about 18 genospecies
In USA, transmitted Ixodes scapularis (black-legged tick, or deer tick)
in the East and Midwest and I. pacificus (western black-legged tick)
on the Pacific Coast
In highly endemic areas of New England, rates of infection of I.
scapularis are 20-30% for nymphs and 30-50% for adult ticks
To transmit, infected nymph must feed at least 36-48 hrs and adult
tick at least 72 hrs. In humans, risk of transmission about 25% for
nymph fed for at least 72 hrs
Low risk of LD (1-3%) after recognized tick bite in endemic areas
likely because in majority of cases tick fed for <48 hrs
LYME DISEASE INCIDENCE RATES BY STATE, 2004-2013
State
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
Connecticut
38.5
51.7
51.0
87.3
78.2
78.2
55.0
56.0
46.0
58.7
Delaware
40.8
76.7
56.5
82.7
88.4
111.2
73.1
84.6
55.3
43.2
Maine
17.1
18.7
25.6
40.2
59.2
60.0
42.1
60.3
66.6
84.8
Maryland
16.0
22.1
22.2
45.8
31.0
25.7
20.1
16.1
18.9
13.5
Massachusetts
23.9
36.3
22.2
46.3
60.9
61.0
36.3
27.3
51.1
57.0
Minnesota
20.1
17.9
17.7
23.8
20.0
20.2
24.4
22.2
16.9
26.4
New Hampshire
17.4
20.3
46.9
68.1
92.0
75.2
63.0
67.3
75.9
100.0
New Jersey
31.0
38.6
27.9
36.1
37.0
52.8
37.8
38.5
30.8
31.3
New York
26.5
28.8
23.1
21.6
29.5
21.2
12.3
16.0
10.4
17.9
Pennsylvania
32.1
34.6
26.1
32.1
30.7
39.3
26.0
37.2
32.5
39.0
Rhode Island
23.0
3.6
28.8
16.7
17.7
14.2
10.9
10.6
12.7
42.2
8.0
8.7
16.8
22.2
53.1
51.9
43.3
76.0
61.7
107.6
Wisconsin
20.8
26.4
26.4
32.4
26.5
34.5
44.0
42.2
23.9
25.2
U.S. Incidence
6.7
7.9
8.2
9.1
9.4
9.8
7.3
7.8
7.0
8.6
Vermont
Borrelia burgdorferi (darkfield microscopy)
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Reported Cases of Lyme Disease, USA,
1995-2013
Confirmed Lyme disease cases by
month of onset, USA, 2001-2010
Confirmed Lyme disease cases by age
and sex, USA, 2001-2010
Clinical Manifestations of Confirmed
Lyme Disease Cases, USA, 2001-2010
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Lyme Disease in Children
Similar to adults, except for meningopolyradiculoneuritis
Children have shorter-lasting symptoms and better outcomes
LD can be more difficult to identify because some of its signs and
symptoms are similar to other common diseases in this age group
Seroprevalence in children ranges from 2.6% to 15%
Likely that B. burgdorferi infections may have an asymptomatic
course in large number of children
Prophylactic antibiotics for I. scapularis tick bites in LD
hyperendemic regions can be effective in preventing
infection, especially given promptly after potentially
infectious ticks are removed from patients (within 72 hours)
Lyme Disease Testing
Testing in the first few weeks of illness is often negative
Patients sick for longer than 4-6 weeks, especially those in late
stage, will almost always test positive
Patient ill for months/years and has negative test, almost certainly
does not have LD as the cause of their symptoms
Because false (+) possible, consider underlying likelihood
If patient tested many times and rarely positive, it is likely that the
positive result is false (+)
EIA tests are very sensitive; false (+) due to other conditions
No PCR-based, FDA-approved assays available for LD
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Positive
Western blot
Lyme Disease Prognosis
Excellent when treated early with appropriate regimens
Recurrent infection is possible if bitten again (usually
different strain of Borrelia)
Those who receive late treatment or inappropriate
treatment may develop chronic musculoskeletal symptoms
and memory/concentration problems, and fatigue
Some develop chronic arthritis due to immunopathogenic
mechanisms and not active infection; eventually resolves
Cardiac involvement is rarely chronic
Rare neonatal death or stillbirth after pregnancies with
untreated or inadequately treated maternal borreliosis
Congenital infection with B burgdorferi is unlikely
Post-treatment Lyme disease syndrome
Lingering symptoms may persist for >6 months in
10-20% after recommended treatment: cognitive
disturbances, fatigue, joint or muscle pain,
headaches, hearing loss, vertigo, mood
disturbances, paresthesias, and difficulty sleeping.
Condition is often termed “Chronic Lyme “ disease,
but actually is a post-treatment Lyme disease
syndrome (PTLDS)
No evidence that prolonged antibiotics effective for
PTLDS; almost all patients recover with time
Ehrlichiosis and Anaplasmosis
In US, ehrlichiosisis caused by at least 3 species: Ehrlichia
chaffeensis, E. ewingii, and new Ehrlichia muris-like (EML)
Agent of anaplasmosis is Anaplasma phagocytophilum;
small mammals are the primary reservoir
E. ewingii and E. chaffeensis transmitted to humans by an
infected Lone Star tick, whereas A. phagocytophilum is
transmitted by the deer ticks
The Lone Star tick maintains the enzootic cycle of E.
chaffeensis primarily among white-tailed deer; deer and
domestic dogs likely reservoir species for E. ewingii
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Approximate Distribution of the Lone
Star Tick, CDC, 2011
Ehrlichiosis Case Fatality Rate by Age-group,
USA, 2008-2012
County level incidence
rates of
A , Ehrlichia chaffeensis
B , Anaplasma
phagocytophilum , and
C , undetermined,
unspecified, or other
agent,
United States, 2000–
2007.
Am J Trop Med, 2011
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Ehrlichiosis
Ehrlichiosis and Anaplasmosis
In 2002, in southwest Missouri, E. chaffeensis was
found in 9.8% of adult A. americanum ticks and
6.7% of D. variabilis ticks. E. ewingii DNA was
present at a rate of 5.4% in adult A. americanum
and 3.3% of D. variabilis ticks
In 2012 study of pets, E. chaffeensis seroreactivity
was 6.6% in the central region (AR, KS, MO, OK)
and 4.6% in the southeast region (GA, MD, NC, SC,
TN, VA). Seroreactivity to E. ewingii was also highest
in the central region (14.6%) followed by the
southeast region (5.9%)
Ehrlichiosis/Anaplasmosis Rash
Ehrlichiosis and Anaplasmosis
Skin rash is not a common feature of ehrlichiosis, and
should not be used to rule in/rule out infection; rash
less common in anaplasmosis (<5%)
Up to 60% of children may have rash compared with
< 30% of adults
Rash range: maculo-papular to petechial, not itchy.
Erythroderma in some patients
Rash spares face, may spread to palms and soles;
may resemble RMSF rash
Unknown whether patients recovered from ehrlichiosis
are immune or susceptible to re-infection
Diagnosis: Blood Smear
Pancytopenia is a hallmark of ehrlichiosis. Anemia in ≈1/2
of cases within 2 weeks. Leukopenia (largely lymphopenia)
in ≈ 2/3 of cases. Marked thrombocytopenia is
pathognomonic (70-90%)
Some elevation in hepatic transaminases in ≈90%, with
increased ALP and bilirubin in some
Elevated CRP common in the first week of illness
Mild/moderate hyponatremia in ≈1/2 of adults, and more
often in children
Routine blood cultures cannot detect Ehrlichia or Anaplasma
Diagnosis of Ehrlichiosis/Anaplasmosis
Characteristic morulae in
leukocytes (peripheral
blood, bone marrow or
CSF). Morulae occur more
frequently in
anaplasmosis (up to 80%)
than in ehrlichiosis (20%)
in the first week of illness
Anaplasmosis tends to be less severe than ehrlichiosis
Both present with non-specific fever, HA, myalgia, arthralgia
GI symptoms more with ehrlichiosis. Altered mental status and severe
abdominal pain frequent in pregnant and children with ehrlichiosis
Severe disease may have GI, renal, respiratory, blood, and CNS
involvement, and death
Neurologic manifestation of ehrlichiosis (up to 20% of cases) could
be meningitis/encephalitis; ucommon in anaplasmosis
Long-term sequelae: footdrop, speech problems, diminished reading
and fine motor skills in children
Significant number ehrlichiosis /anaplasmosis cases could be
asymptomatic
PCR is test of choice for both at early stages when
antibody levels are low. Effectiveness of PCR much lower
after 1st week
IgM and IgG specific to E. chaffeensis or A. phagocytophilum
by IFA is the “gold standard”; predominantly used
EIA tests from commercial laboratories are qualitative. Some
EIA assays measure IgM antibody alone, which may have a
higher frequency of false (+)s
Up to 12% of healthy people in endemic areas (20% of
children) may have elevated antibody titers due to past
exposure to Ehrlichia species or similar organisms
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Ehrlichiosis/Anaplasmosis Treatment
Diagnosis of Ehrlichiosis/Anaplasmosis
IgG IFA test negative up to 80% of patients in 1st week;
IgM uninformative. IgM/IgG increase in most by 2-3d week
IgM less specific than IgG, more likely be false (+). Request
IgM titers concurrent with IgG titer
Test for both, E. chaffeensis and A. phagocytophilium,
because of high rate of cross-reactivity
Early treatment with a tetracycline antibiotics may reduce
or abrogates the antibody response to E. chaffeensis
Rare patients do not develop measurable antibodies
Rocky Mountain Spotted Fever (RMSF)
Doxycycline is treatment of choice including children
Response is best when given early (within 5 days)
Some untreated cases may result in death in 2-d week of
illness, or progress to febrile illness lasting 2-3 weeks
Response is typically rapid, and fever >72 hrs after
initiation of treatment strongly suggests an alternative
diagnosis
Preventive antibiotics after tick bite are not recommended
Common Tick Vectors in USA
RMSF caused by gram (-) bacterium Rickettsia rickettsii
Transmitted to humans by infected American dog tick,
Rocky Mountain wood tick, and recently identified
vector brown dog tick
Ticks serve as both the reservoir for infection and the
vector for transmission
RMSF is among the most virulent infectious diseases; preantibiotic case-fatality rates >25%
Children 5 times more likely than adults to die from RMSF
Reported incidence and case fatality of RMSF in the
United States, 1920–2010
RMSF cases reported to CDC, 1993–2010
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RMSF, Annual Incidence, USA, 2010
RMSF, Average annual incidence by age-group, 2000-2010
RMSF cases by month of onset, 1993-2010
SFGR Case fatality rate by age-group, USA,
2008-2012
RMSF
Symptoms 2-14 days post infected tick bite: fever,
rash, headache, nausea, and myalgia (calf and back
pain is common). Vomiting, abdominal pain (may mimic
acute abdomen), and conjunctival injection also possible
Thrombocytopenia and hyponatremia (50-60%),
anemia, hypoalbuminemia and elevated liver
enzymes may not be present in all patients
RMSF Rash
Increased band neutrophils often seen while WBC
could be normal; WBCs elevated in up to 30%
Children more likely to develop early rash, but less
likely to report headache; some may develop
symptoms of cough, sore throat, and diarrhea leading
to misdiagnosis
Most (90%) have some type of rash during illness
Typical rash 2-5 days after fever onset as small, flat, pink, nonitchy macules on wrists, forearms, and ankles and spreads to
trunk and sometimes palms/ soles; may not have rash until late
Red to purple, spotted (petechial) rash usually not seen until 6
day or later after onset, and occurs in 35-60% of patients. It is
a sign of severe progression; treatment should begin before
petechiae develop !
Rash on the palms and soles is not pathognomonic; rash might
be evanescent or localized to a part of the body
Rash is absent or atypical in up to 20% of RMSF cases
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RMSF Rash
RMSF Diagnosis
RMSF Diagnosis
IFA of two paired serum samples is “gold standard”
Antibodies not detectable in the first week in up to 85%
IgM/IgG rise simultaneously, but IgM has poor sensitivity,
less specificity, and more likely to be false (+). Always
request concurrent IgG titers !
Because of background seroprevalence, diagnosis based
on single serology could be wrong in non-RMSF cases with
historical titers from past exposures or due to crossreactive IgM antibodies
Background seroprevalence for R. rickettsii in southeast
USA can be up to 20% in adults, and 10–12% in children
RMSF Treatment
False (+) results possible due to cross-reaction
with antigens of Bartonella, Legionella, Proteus,
other rickettsias, CMV, EBV, and rheumatoid factor
ELISA is frequently used, but commercially
available ELISA tests are qualitative and cannot
be used to monitor increases or decreases in
antibody titer
Blood is not useful for detection by PCR or culture
In patient with rash, PCR and/or IHC test can be
done on a skin biopsy from the rash, or autopsy
specimens
New Research on Doxycycline
In 2013, CDC and IHS
reported that short
courses of Doxycycline
can be used in children
without causing tooth
staining or weakening of
tooth enamel
Largest sample size and
best evidence to date
that short courses do not
cause dental staining in
children < 8 years of
age
RMSF can be fatal; in untreated, median time to death is
only 8 days
Treatment must be based on clinical suspicion alone and
should always begin before laboratory results return or
severe disease develops
Doxycycline is the first line treatment for adults and children of
all ages and should be initiated immediately when RMSF is
suspected
Preventing death most effective if Doxycycline given during first
5 days of illness
Antibiotics other than Doxycycline associated with higher risk of
fatal outcome
Rickettsia parkeri Rickettsiosis
R. parkeri rickettsiosis transmitted by the
Gulf Coast tick (Amblyomma
maculatum) was first described in 2004
R. parkeri rickettsiosis appears to be a
milder illness than classical RMSF
Many common characteristics
with other rickettsiosis: 50%
of the patients received
diagnosis of RMSF and 25%
of eschar-associated
rickettsialpox at some point
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Cutaneous lesions from patients
with confirmed R. parkeri rickettsiosis
R. parkeri Rickettsiosis
•Inoculation eschars, representing the
site of primary infection following a
bite from R. parkeri infected tick.
•The rash of R. parkeri rickettsiosis is a
maculopapular or papulovesicular
eruption on the trunk and extremities,
occasionally involving the palms and
soles.
Single or multiple eschar in >90% cases. Erythematous
maculo-papular rash on the trunk, spreads to
extremities, palms and soles.
Antibodies to R. parkeri can react with R. rickettsii, R.
akari, other SFGR in conventional serological assays
PCR from skin biopsy specimens for precise diagnosis
Treatment with Doxycycline is helpful
Untreated patients with R. parkeri remained only
moderately ill after 7–10 days of fever
Paddock et al. CID, 2008;
47(1):1188-96
Rickettsia Species 364D
Tick-borne Spotted Fever Rickettsiosis
First described in 80-year-old man from rural northern
California who presented with an eschar on his forearm
(CID, 2010)
3 other area residents with similar illnesses also tested
positive, as well as ticks collected near the patient's
residence
Rickettsia 364D (Rickettsia phillipi ?) geography includes
Northern California, Pacific Coast
Vector is Dermacentor occidentalis (Pacific Coast tick)
Symptoms include fever, fatigue, headache,
lymphadenitis, eschar(s), no rash.
Tick-borne Spotted Fever Rickettsiosis
Although the severity of infections attributable to SFGR
vary depending on causative species, all suspect
patients should be promptly treated with doxycycline as
if they have R. rickettsii infection
May use serologic assays for RMSF to confirm SFGR
In patients who present with “spotless” RMSF or have
antibodies to R. rickettsii with group-specific assays ,
SFGR should be confirmed through molecular techniques
PCR assay, immunohistochemistry (IHC), and culture
isolation of a swab or biopsy of eschar or rash site can
be used
Several other tick-borne species of Rickettsia, "Spotted
Fever group Rickettsia (SFGR)“, may cause similar to
RMSF symptoms
Many confirmed rickettsial pathogens (e.g., R. parkeri,
R. massiliae) and rickettsiae of unknown pathogenicity in
humans reside in US ticks at frequencies far greater
than those observed for R. rickettsii
Because these agents cross-react with R. rickettsii, it is
possible that true clinical spectrum, incidence, and
distribution of RMSF in the US is distorted by blending
epidemiological and clinical characteristics of several
etiologically distinct diseases
Powassan Virus (POWV)
Causes rare tick-borne neuroinvasive human disease
POWV is an RNA virus in genus Flavivirus related to
West Nile, STL, and TBE encephalitis viruses
POWV maintained in Ixodes ticks and small-tomedium-sized rodents cycle. Humans are “deadend” hosts of the virus
High morbidity; case-fatality rate ≈10-15%
No vaccines or medications to treat or prevent POW
virus infection
POWV should be considered in encephalitis cases in
the northern USA, especially during the tick season
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Powassan, neuroinvasive cases,
USA, 2004–2013
Powassan Virus Neuroinvasive Cases,
USA, 2004–2013
POWV Infection
Incubation period: 7-30 days
Infection may cause no symptoms or mild illness,
but most develop neuroinvasive disease
(meningitis, encephalitis)
≈50% survivors have permanent neurological
symptoms: HA, muscle wasting, and memory
problems
Diagnosis by detection of POW virus-specific IgM
in serum or CSF (not commercially available).
Positive IgM should be confirmed by neutralizing
antibody in acute- and convalescent-phase serum
Babesiosis
Babesiosis
Caused by protozoa in genus Babesia; it is an obligate
RBC parasite
In USA, mainly caused by Babesia microti ; endemic in
Northeast and upper Midwest
Other species (B duncani and B divergens-like) cause
babesiosis in the West and Midwest
Primary B microti reservoir in the Northeast is whitefooted mouse, and vector is I. scapularis
Babesiosis is rarely acquired through blood transfusion;
few cases of transplacental/perinatal transmission have
been described
Babesiosis Cases, USA, 2011-2013
Transfusion-transmitted babesiosis is the most frequently
reported parasitic disease due to transfusions in USA
Transfusion-associated babesiosis is not restricted to
endemic regions, and occurs during any season due to
protracted, asymptomatic parasitemia in donors
Blood-borne transmission included RBCs and platelets
In 2013, 14 cases of babesiosis in blood recipients
were transfusion associated; possible more undetected
Licensed babesiosis screening test for donors is not yet
available
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Babesiosis Cases by County of Residence,
USA, 2013
Babesiosis Cases by Age, USA, 2013
Babesiosis
Babesiosis
The likely incubation period 1-6 weeks
Spectrum of severity: (1) a mild-to-moderate viral-like
illness, (2) severe disease with fulminant course resulting
in death or relapsing course, or (3) asymptomatic
infection
Typically, hemolytic anemia and flu-like symptoms;
some have splenomegaly, hepatomegaly, or jaundice;
rarely rash. Usually lasts several weeks to months
Parasitemia may continue even after patient recovers;
rarely, persists for more than 2 years
Case-fatality 5-9%, up to 21% inimmunocompromised
In symptomatic acute patients, Babesia typically
detected by blood smears; multiple smears needed
Antibody detection and PCR useful for persons with
low levels of parasitemia (asymptomatic blood
donors), for diagnosis after infection is cleared by
therapy, and for discrimination between Plasmodium
falciparum and Babesia
IFA detects antibodies in 88-96% of patients with B.
microti during first weeks
Cross-reactivity between Babesia species is variable;
cross-reactions may occur in patients with malaria
Babesiosis
Most asymptomatic persons do not require treatment even if
smears are positive, unless parasitemia persists > 3 months
Treat at least 7-10 days with: atovaquone (Mepron) PLUS
azithromycin; OR clindamycin PLUS quinine (standard for
severe cases)
Children, including infants, can be safely treated with
azithromycin plus atovaquone (safe in children ≥ 5 kg)
Exchange transfusion indicated for all babesiosis patients
with heavy parasitemia (>10%) or pulmonary, renal, or
hepatic compromise
Babesia parasites in red blood cells on a stained blood smear
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Tularemia
Reported tularemia cases by year – –
United States, 1950-2013
Disease of animals and humans caused by highly
infectious bacterium Francisella tularensis. Humans are
infected through:
-Biting vectors: tick and deer fly bites; mosquitoes,
fleas, mites also possible
-Skin contact with infected animals;
-Ingestion of contaminated food and water;
-Laboratory exposure;
-Inhalation of contaminated dusts or aerosols
In the US, cottontail rabbits and ticks (dog tick, wood
tick, and Lone Star tick) transmit tularemia type A to
humans. Deer flies transmit tularemia in the western
United States
Tularemia cases, United States, 2004-2013
162
AR
108
OK
MO
231
Tularemia cases by state, United States, 2001 - 2010
Reported cases of tularemia by
month, United States, 2001 - 2010
Reported tularemia cases by age and
sex – United States, 2001-2010
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Tularemia
Incubation period 2-10 days (range, 1-21)
Presentation varies depending on how the bacteria
enters the body; ranges from mild to life-threatening
All forms of tularemia are accompanied by fever:
Ulceroglandular (most common),
Glandular , Oculoglandular , Oropharyngeal,
Pneumonic (most serious form)
No documented transmission from person to person
Overall case-fatality in the CDC study was 9% for
type A (14% “east” and 0% “west” subtype); fatality
was 7% for type B.
Tularemia Diagnosis
Growth of F. tularensis in culture is definitive confirmation
Presumptive with DFA of specimens, IHC staining, or PCR
Serologic diagnosis by tube agglutination or
microagglutination (more sensitive); single elevated titer
is presumptive positive but can reflect past infection
Antibodies 2-3 weeks from symptom onset; low titers
may persist for years
When tularemia suspected, promptly collect specimens
and alert laboratory for special diagnostic and safety
procedures
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Tularemia Treatment
Streptomycin (primarily), Gentamicin or Amikacin is drug
of choice; 7-10 days. Low relapse with aminoglycosides
Tetracyclines (14 days) an alternative to aminoglycosides
for patients who are less severely; may result in relapses.
Ciprofloxacin (10-14 days) and other fluoroquinolones
are not FDA-approved for treatment but have shown good
efficacy in vitro, in animals, and in humans
In a high-risk situation, such as laboratory accident or
bioterrorism event, 14-days of Doxycycline or
Ciprofloxacin is recommended
Clinical Recognition and
Management of
Tularemia in Missouri: A
Retrospective Records
Review of 121 Cases
November 15, 2012 55 (10)
Tick-borne Relapsing Fever (TBRF)
Retrospective Missouri Tularemia Study
Tularemia is frequently initially misdiagnosed !
Among patients with ulceroglandular, glandular, and
oropharyngeal tularemia, 68% were initially
diagnosed with common infections other than tularemia
All pneumonic cases were initially diagnosed as
community-acquired pneumonia
For 90% of patients with culture positive specimen,
culture results were available before suspicion of
tularemia was documented in the chart !
Median interval between symptom onset and effective
antibiotic treatment was nearly two weeks
Cases of TBRF, United States, 1990–2011
Ingrid B. Weber, George Turabelidze,
Sarah Patrick, Kevin S. Griffith,
Kiersten J. Kugeler, and Paul S. Mead
3 Borrelia species cause TBRF in the US: B. hermsii
(most common), B. parkerii, and B. turicatae
Transmitted by soft ticks living in the rodent nests at
high elevations (1,500-8,000 feet)
Occurs in the western US; usually associated with
sleeping in rustic, rodent-infested cabins in mountains
Outbreaks linked to rental cabins near national
parks/common vacation locations. Tick-infested
cabins can remain source of infection for many years
TBRF
Incubation period ≈ 7 days (range, 2-18 days)
TBRF spirochetes have unique antigenic variation, and
evade host immune system causing relapsing fever
Recurring febrile episodes ~3 days separated by afebrile
periods of ~7 days
Typically, no specific findings. May have macular rash or
petechiae on the trunk/extremities. Less frequently,
jaundice, hepatosplenomegaly, meningismus, and
photophobia
Patients who are not treated will experience 1-4 episodes
of fever before illness resolves
TBRF during pregnancy can cause spontaneous abortion,
premature birth, and neonatal death
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TBRF Borrelia
TBRF
Normal/increased WBCs with left shift, mildly increased serum
bilirubin, thrombocytopenia, elevated ESR, slightly prolonged PT/ PTT
Definitive diagnosis by observation of Borrelia in blood smears, bone
marrow, or CSF in symptomatic person; best detected in blood while
person is febrile
Serum antibody testing is not valuable in acute setting but useful for
retrospective identification; false(+) Lyme test possible
TBRF spirochetes susceptible to PCN and other beta-lactams,
tetracyclines, macrolides, and possibly fluoroquinolones
Tetracycline (10 days) preferred oral regimen for adults. Ceftriaxone
(10-14 days) preferred for CNS involvement
Borrelia miyamotoi
B. miyamotoi, a spirochete related to TBRF borrelia
First detected in 2001 in I. scapularis ticks from Connecticut;
later in all areas of US endemic for LD
First human cases (46 cases) of B. miyamotoi infection
reported from Russia in 2011
Viral-like illness with fever, fatigue, headache, myalgia,
nausea; some with sweats, anorexia, vomiting, cough, sore
throat, adenopathy. Meningoencephalitis in older
immunocompromised patients
≈10% had relapsing fever, and 10% with EM type rash (? coinfection with B. burgdorferi )
Colorado tick fever (CTF)
Borrelia miyamotoi
In 2013, 3 cases in NE USA
Serological study in New England reported in NEJM,
2013, found seroprevalence of 1% in healthy population
and 3.2% in those evaluated for LD. 3/14 cases
evaluated for “viral illness” (no respiratory or GI
symptoms) tested positive for B. miyamotoi antibodies
Diagnosis by PCR; serological assays need more
validation
Recommended treatment: PO Doxycycline or IV Rocephin
for 14 days, or IV PenG QD for 30 days
Geographic Distribution of Dermacentor andersoni
Ticks and CTF Cases, United States, 2002–2012
Caused by RNA-virus, genus Coltivirus, through bites of
infected Rocky Mountain wood ticks; small rodents reservoir
Living/visiting in western US or western Canada
4,000‒10,000 feet above sea level is a risk factor for CTF
Most cases during spring and summer
No person-to-person transmission
Self-limited infection with sudden onset of fever, chills,
headache, myalgia, and malaise. Sore throat, vomiting,
abdominal pain, and a maculo-papular or petechial rash also
reported. Death is rare.
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CTF
Laboratory diagnosis by viral RNA or virus-specific
Ig M and neutralizing antibodies
Antibody production can be delayed for 14–21
days after disease onset
RT-PCR is more sensitive test early in the course
No medications for treatment; management is
supportive
No vaccines are available; prevention of CTF
depends on personal protective measures to
decrease exposure to infected ticks
STARI
The average incubation period 6-9 days
STARI presents with an expanding circular rash at the
tick attachment site. Lesions are usually solitary.
Rash is usually accompanied by mild illness with fatigue,
headache, stiff neck, and occasionally fever
Patients with STARI have much less severe arthritis and
recover more rapidly than patients with Lyme disease
STARI isn’t reportable, and the incidence is unknown
Lyme-like Lesions
Southern Tick–associated Rash Illness
(STARI)
STARI or Masters disease is a Lyme-like illness in the southern US
not caused by B. burgdorferi
Lone Star tick, the most common cause of tick bites in the southcentral US, is a vector
First described in Missouri in1984; etiology largely unknown
B. lonestari recovered from patient with EM-like lesion following
bite of a Lone Star tick in one report (James AM, et al. J Infect Dis 2001).
Currently, B. lonestari not considered an agent of STARI
Other Borrelia species, or even non-Borrelia organism are
possibilities
STARI
Difficult to visually differentiate lesions from LD rash
due to overlap and range of appearances. In a
comparative study, a nearly perfect EM rash was four
times as likely to be from Missouri as from New York
(CID, 2005)
Overall, STARI skin lesions tend to be smaller, more
circular in appearance and more likely to have
central clearing
Long-term sequelae of STARI are unknown
STARI
Since the disease agent is unknown, diagnostic tests
for STARI cannot be developed
Conventional tests such as ELISAs and Western blots
based on B. burgdorferi are usually negative
Cross-reactivity with B. burgdorferi can occur with
ELISA test, but LD Western blots on Lyme-like illness
patients are usually negative
Some evidence that doxycycline is therapeutically
helpful, but it is questionable
Masters et al. Infect Dis Clin N Am 22 (2008) 361–376
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Heartland Virus
In 2009, two patients in NW Missouri hospitalized with
fever, fatigue, anorexia, myalgia, diarrhea, leukopenia,
and thrombocytopenia; both had multiple tick exposures
In 2011, NGS identified virus as Phlebovirus, but the viral
sequence was never seen in North America before
Heartland virus later found in Lone Star ticks in the area
The novel phlebovirus is most closely related to Severe
Fever with Thrombocytopenia Syndrome (SFTS) virus first
isolated in 2011from patients in China. Clinical signs of
SFTS include fever, thrombocytopenia, leukopenia, and
multiorgan dysfunction
Bourbon Virus (EID, 2015)
A previously healthy Bourbon County, KS, USA resident
hospitalized in 2014 with history of tick bite, fever, and fatigue
Patient had thrombocytopenia and leukopenia and was given
Doxycyclin. He did not improve, and died 11 days later
Testing results for known TBDs negative, but PRNT for Heartland
virus indicated presence of another virus. NGS and
phylogenetic analysis identified a novel member of genus
Thogotovirus
7 human infections previously associated with thogotoviruses
showed neurologic dysfunction, but it was absent in this patient
Currently not known how many human infections and disease
cases might be attributable to this novel pathogen
Comparative efficacy of insect/tick repellents
Heartland Virus
6 additional Heartland virus disease cases identified in
2012–13 (symptom onset May to September)
All cases present with fever, leukopenia, and
thrombocytopenia
Diagnosis by 1) detection of viral RNA by RT-PCR on
blood or tissue or 2) a ≥4-fold rise in virus-specific
PRNT antibody titers in paired serum
Since no vaccine or medication is available, tick bite
prevention is most important
TBD Prevention
Reducing burden TBDs requires two main strategies:
treatment of currently infected patients and
prevention of transmission
Because effective vaccines for humans are not
currently available, prevention strategies can be
grouped into two approaches:
- focus on human behavior such as the use of
repellants and protective clothing, avoidance of
risky activities and habitats, etc.
- environmental including interventions that target
ticks, their hosts, and the pathogens they transmit
TBD in USA: Key Points
New TBDs have been identified in USA, and more
is likely to emerge in the future
TBD should be considered in a person with
infectious illness of unclear etiology, with or
without history of known tick exposure
Presumptive treatment is often required while
awaiting testing results
Short courses of Doxycycline can be used in
children <8 years of age without causing tooth
staining or weakening of tooth enamel
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Tick-borne Diseases: Clinical Syndromes
Fever and rash,
with or w/o neurological symptoms
SFGR, Ehrlichiosis, Anaplasmosis,
TBRF
Fever with sepsis or hypotension,
with or w/o rash
Rickettsioses, Ehrlichiosis,
Anaplasmosis, Tularemia
Meningitis/meningoencephalitis
RMSF, Ehrlichiosis, Anaplasmosis,
TBRF, CTF, Powassan, B. miyamotoi
Constitutional symptoms and leucopenia,
thrombocytopenia, hyponatremia, elevated
transaminases
Rickettsioses, Ehrlichiosis,
Anaplasmosis
Constitutional symptoms with anemia and
thrombocytopenia
Babesiosis
Fever with rash and eschar
Rickettsioses, Tularemia
Relapsing fever with constitutional symptoms
TBRF
Skin ulcer with lymphadenopathy,
with or w/o fever
Tularemia
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