1. Vector-borne Infections
Allison Liddell, M.D.
Infectious Diseases
September 22nd, 2003

3. Clinical Vignette
28yo FBI agent on temporary assignment in the Nantahala forest in Western North Carolina presents with acute onset fever, chills, headache 3 days after Memorial Day.
Exam: confused, ill appearing, a few petechiae present on wrists and ankles
Labs: platelets=75K, mild leukocytosis, mildly elevated transaminase
LP with 75 WBC, mostly lymphocyes with protein=154

4. Tick-Borne Infections in the U.S.
Lyme disease
Rocky Mountain spotted fever
Ehrlichiosis
Tularemia
Babesiosis
Colorado tick fever
Tick-borne relapsing fever
Tick-borne encephalitis
Tick paralysis
Q Fever

5. Tick Classification

6. Questing tick

7. Rocky Mountain Spotted Fever
Described in late 1900’s in Bitter Root Valley
Caused by infection with Rickettsia rickettsii
Obligate intracellular, requires cell culture to cultivate

8. RMSF transmission Maintained transovarially in ticks
Tick vectors are hard ticks:
Dermacentor variabilis (eastern US)
D. andersoni (western US)
A. americanum (south-southwestern US)

9. Parola, Clin Infect Dis 2001 Mar 15;32(6):897-928

10. RMSF epidemiology Most cases occur May – September
Highest rate in children years
Exposure to dogs, grassy areas risk factor
8.5% mortality (Billings et al)

11. TDH Website

12. TDH Website

13. RMSF Clinical Manifestations
Incubation period days
Onset with fever, myalgias, headache
GI findings may mimic an acute abdomen
Rash appears days after onset of fever
Meningismus and CSF pleocytosis may occur
WBC usually normal, platelets may be decreased
Hyponatremia occurs in 50%

16. RMSF Diagnosis Serology IF staining of tissue specimen
PCR under development

17. RMSF Outcome N=6388 over 1981-1998 Annual case-fatality rate 3.3%
Risk factors for mortality:
Old age
Chloramphenicol only
Tetracycline not primary therapy
Treatment delayed > 5 days
Holman et al JID 2001

18. Clinical Vignette
54 yo WM farmer in Missouri presents with 3 day h/o high fevers, chills, headache and marked malaise in June
Exam notes a confused, ill-appearing man but is otherwise unremarkable
Labs note transaminases 3 x normal, platelets 115K, WBC 2.1, CSF 32WBC, protein 127

19. History of Ehrlichiosis
E. canis-hemorrhagic illness in Algerian dogs
1950s – E. sennetsu-mononucleosis-like illness in Japan
1986 – Ehrlichiosis-patient in Detroit after tick bites in Arkansas
E. chaffeensis cultured from patient at Fort Chaffee in Arkansas

23. Genus Ehrlichia
Small gram-negative bacteria closely related to Rickettsiae
Obligate intracellular parasites
Infect circulating blood elements
Reside and replicate within membrane-bound cytoplasmic vacuoles
Vertebrate reservoirs and arthropod vectors

27. Ehrlichia ewingii
First discovered in dogs with granulocytic ehrlichiosis, 1992
Disease is milder than E. canis infection
Manifestations include fever, lethargy and polyarthritis
Found to date in dogs in Missouri, Arkansas, Oklahoma and N. Carolina
Member of E. canis genogroup (cross-reactivity)
Experimental transmission by A. americanum

29. Ehrlichiae Causing Human & Veterinary Disease

30. Human Ehrlichiosis Symptoms
HME
HGE
Fever 97
94-100
Headache 81
61-85
Myalgia 68
78-98
Malaise 84 98
Rash 36
2-11
Confusion 20 17
Dumler et al, Annu. Rev. Med :

31. Human Ehrlichiosis Clinical Spectrum
DIC
Pancytopenia
Encephalitis/Meningitis
Pulmonary infiltrates/Respiratory failure
Gastrointestinal bleeding
Renal Failure

32. Human Ehrlichiosis Laboratory Findings
Leukopenia
Thrombocytopenia
Elevated transaminases
Hyponatremia
>4-fold elevation in IFA
PCR

33. RMSF/Ehrlichiosis Treatment
Adults: Doxycycline 100 mg bid
Children: Doxycycline 3 mg/kg/day in 2 divided doses
Duration: 3 days after defervescence, minimum 5-7 days

34. Clinical Vignette
34 yo WF owner of a campground presents with a nonhealing lesion on the right index finger for 2 weeks, adjacent to the nail bed.
Failed Augmentin and acyclovir by PCP for “infected paronychia”
Exam notes an ulcerated lesion and regional adenopathy

35. Tularemia History McCoy & Chapin 1910
“plague-like disease” of rodents in Tulare Co. CA
Bacterium Tularense
Edwards Francis
cases
isolated organism
proved vector
named the disease
developed culture and serology methods
noted risk to workers

36. Parola, Clin Infect Dis 2001 Mar 15;32(6):897-928

37. Tularemia Epidemiology
1368 cases
All states except Hawaii, but predominately MO, AK, OK & SD
Reinstated on nationally notifiable list 2000 (n=142)
Type A (biogroup tularensis)
Multiple vectors (tick, deerfly)
>250 animal species
rabbits
hares
muskrats
Other transmission
carnivores
direct contact
inhalation/ingestion
Peak incidence 1939

38. Outbreak 2001 Pneumonic Tularemia
15 patients in Martha’s Vineyard
11 primary pulmonary
1 death
Feldman et al, N Engl J Med 2001 Nov 29;345(22):1601-6

39. Tularemia Clinical Manifestations
Ulceroglandular
black based ulcer
tender regional lymphadenopathy  bubo
Typhoidal
Oculoglandular
Primary pulmonary

42. Tularemia Diagnosis Titers 4-fold increase single > 1:160 Skin test
Culture – notify laboratory

43. Tularemia Treatment Streptomycin 1 gm iv q12h for 10 days
Gentamicin 5 mg/kg/d for 10 days
Tetracycline/chloramphenicol
associated with 15-20% relapse
Quinolones
Excellent in vitro activity
Limited data, anecdotal experience suggests efficacy
Live attenuated vaccine for high risk groups

44. Tularemia Complications
Pneumonia  abscess, effusion
Rhabdomyolysis
Acute renal failure
Meningitis
Pericarditis

45. Lyme Most commonly reported tick-borne infection in U.S.
, mean 12,451 annual cases (CDC)

46. Lyme History Cluster of cases near Lyme, CT 1975
Johnson RC, Schmid GP, Hyde FW, Steigerwalt AG, Brenner DJ. Borrelia burgdorferi sp. nov.: etiological agent of Lyme disease. Int J Syst Bacteriol 1984; 34:496 7.

47. Lyme epidemiology B. burgdorferi sensu lato Tick vector
Black-footed mouse reservoir
White-tailed deer host
Birds and mammals implicated in Europe

48. Lyme Disease Early Manifestations
Erythema migrans (90%)
Occurs 8-14 days after bite
Single lesion, average size 15cm
Systemic symptoms may be present
Secondary lesions may occur
Carditis
Aseptic meningitis
Bell’s palsy

49. Lyme Disease Late Manifestations
Arthritis
Knees involved in 90%
Usually resolves, 1-2 weeks
May recur
CNS disease (rare in children)

50. Lyme Disease Diagnosis
Serology
ELISA
Western blot
Culture on BSK-II media
57-85% sensitive skin
Blood, CSF, synovial fluid
Warthin-Starry stain
PCR

51. Lyme Disease Treatment of Early Disease
Doxycycline (  8 years of age)
Ampicillin
Penicillin allergic: cefuroxime axetil or erythromycin
Duration days

52. Lyme Disease Treatment-Disseminated & Late Disease
Multiple skin lesions Oral, 21 days
Isolated facial palsy Oral, days
Arthritis Oral, 28 days
Persistent arthritis Parenteral, days
Carditis Parenteral, days
CNS Parenteral, days

53. Lyme Disease Vaccine
recombinant B. burgdorferi lipidated outer-surface protein A (rOspA)
Antigen not expressed in host
Antibody is taken up into tick and bacteria destroyed in vector
0, 1 and 12 months
As of February 25, 2002 LYMErix™ off the market

54. Southern Tick-Associated Rash Illness (STARI)
Similar EM rash
Long-term and serious complications not reported
Responds to doxycycline
Organism by PCR B. lonestari
No culture
639 cases in Texas

55. Clinical Vignette
25yo male camper in Montana presents with a 2 week history of intermittent fevers. Initially he had a high fever with headache, red eyes, jaundice, severe body aches, and after about 3 days a diffuse red rash on his trunk. The fever resolved, then about a week later recurred without the other symptoms.

56. Tick-borne Relapsing Fever
Dutton JE, Todd JL. The nature of tick fever in the eastern part of the Congo Free State, with notes on the distribution and bionomics of the tick. Br Med J 1905; 2:
Described tick relapsing fever
Borrelia duttonii
transmitted by Ornithodoros moubata in W. Africa
13 species of Borrelia
genus Ornithodoros
Noctural feeder
Short attachment
worldwide

57. Parola, Clin Infect Dis 2001 Mar 15;32(6):897-928

58. Tick-borne Relapsing Fever
acute onset of high fever with chills, headache, myalgia, arthralgia, and coughing
Hemorrhage, iritis or iridocyclitis, hepatomegaly, or splenomegaly
rash at the end of the first febrile episode
Primary episode 3 days
neurological findings
B. turicatae (U.S.)
B. duttonii (Africa)
Jaundice ( 7%)
case-fatality rate 2%-5%
intensity of episodes decreases with time
Mean period between episodes 8 days

59. Tick-borne Relapsing Fever
Borreliae in peripheral blood of febrile patients. Sensitivity 70% (darkfield microscopy or Giemsa or Wright's stain).
Quantitative buffy coat
Serology not useful
PCR
Jarisch-Herxheimer reaction
doxycycline (Penicillin, erythromycin, or ceftriaxone)

60. Tick-Transmitted Diseases Prevention
Avoid tick-infested areas
Wear protective clothing that covers exposed areas
Use DEET - containing insect repellants
Spray permethrin on clothes
Remove attached ticks promptly Do not squeeze

61. Clinical Vignette
45yo BM with h/o Hodgkin’s in remission 5 years after chemo/XRT for Stage 4 disease, presents with acute fever, fatigue, abdominal pain, SOB/DOE, in June in New Jersey.
Exam: hepatosplenomegaly, hyperdynamic precordium, pale.

62. Babesiosis Hemoprotozoan Babesia microti and Babesia divergens
similar vector, animal reservoir and geographic distribution as Lyme
Multiplication of the blood stage parasites is responsible for the clinical manifestations of the disease

63. Babesiosis
more severe in patients who are immunosuppressed, splenectomized, and/or elderly
diagnosis by thick and thin smear
Treatment with clindamycin + quinine or atovaquone + azithromycin
exchange transfusion has been used in severely ill patients with high parasitemias

64. Babesiosis

65. Clinical Vignette
48 yo male presents with acute onset episodic fever abdominal pain, headache, myalgias and nausea/vomiting, then profuse sweats.
Recent trip to Thailand looking for exotic bird species.
Exam notes tender right and left upper quadrant and splenomegaly
Labs note pancytopenia

66. Malaria
300–500 million infections worldwide and approximately 1 million deaths annually (CDC)
Plasmodium falciparum, P. vivax, P. ovale, or P. malariae
infected female Anopheles mosquito
blood transfusion or congenital
Fatal cases are due to falciparum (“knobs”)
P. vivax and P. ovale parasites can persist in the liver (natural infection only)
P. malariae acute illness rare in normal hosts, causes chronic infection (GN)

69. Malaria Chloroquine-susc mefloquine resistance
Dominican Republic, Haiti
Central America west of the former Panama Canal Zone
Egypt
some countries in the Middle East
mefloquine resistance
borders of Thailand with Burma (Myanmar) and Cambodia
western provinces of Cambodia
eastern states of Burma (Myanmar)
Fansidar resistance
Amazon River Basin area of South America,
Southeast Asia
other parts of Asia
large parts of Africa

70. Malaria fever and influenzalike symptoms
chills, headache, myalgias, and malaise
Classic paroxysm
Chill
Spike
Sweat
can occur at intervals
Falciparum less exact
Vivax/ovale tertian
Malariae quartian
anemia and jaundice,
seizures, mental confusion
kidney failure, coma, and death
6 days after initial exposure to several months after chemoprophylaxis

71. Malaria Diagnosis Peripheral smear Hypoglycemia Lactic acidosis
Vivax/ovale
Falciparum
No mature forms
High parasitemia (directly related to mortality in nonimmune)
Multiple ring forms/cell
Infects all ages
Hypoglycemia
Lactic acidosis
Hemolysis
Acute renal failure
Pancytopenia

73. Malaria Treatment Hospitalize if nonimmune and suspect falciparum
Different drug than prophylaxis
Halofantine cross resistant w/mefloquine
Start 2nd drug later
If vivax/ovale need Primaquine
Artemisin if mefloquin/cholorquine resistance
Exchange transfusion if parasitemia >15% in nonimmune

74. Malaria Prevention transmission occurs primarily between dusk and dawn
well-screened areas, mosquito nets, clothes that cover
DEET (N,N-diethylmetatoluamide)
pyrethroid-containing flying-insect spray in living and sleeping areas

75. Chemoprophylaxis mefloquine or chloroquine 1–2 weeks before
doxycycline and atovaquone/proguanil 1–2 days before
continuously while in malaria-endemic areas
4 weeks (chloroquine, doxycycline, or mefloquine) after
7 days (atovaquone/proguanil) after
Terminal prophylaxis with Primaquine final 14 days
fatal hemolysis in those who are G6PD deficient

76. Chemoprophylaxis pregnancy
Long history of chloroquine and quinine use
Data supports safety of mefloquine in 2nd an 3rd trimester
Data in first trimester sketchy, patient must weigh risks
No Doxycycline or Primaquine
No data for Malarone

77. Malaria Information http://www.cdc.gov/travel
Voice information service FYI-TRIP
CDC Malaria Hotline ( ) from 8:00 a.m. to 4:30 p.m. Eastern time
CDC Emergency Operation Center at
page person on call for the Malaria Epidemiology Branch.

78. Clinical Vignette
72 yo WM alcoholic with CAD presents with 3 day h/o fever, myalgias, headache followed by acute onset confusion and tremulousness
Works as a nursery sales rep and travels frequently to East Texas
No improvement on levaquin
EKG afib
CSF notes elevated protein and lymphocytic pleiocytosis

79. Viral Encephalitis arthropod-borne
Alphaviridae
Eastern Equine
Western Equine
Bunyaviridae
LaCrosse
Flaviviridae
St. Louis
Powassan (ticks)
Japanese
Tick-borne (ticks)
West Nile
Culex

82. Arboviral Activity Louisiana 2001
SLE Human Cases
EEE Equine Cases
EEE Human Cases
SLE Avian Cases
EEE Mosquito Pools
WNV Equine Cases
WNV Human Cases
WNV Avian Cases
SLE 5 Human Cases
Outbreak or Cluster with Human Case(s)

83. Eastern Equine Eastern US Ave. 4 cases/year
Togaviridae, genus Alphavirus
35% mortality
35% permanent neuro defect

84. St. Louis Encephalitis Aseptic meningitis or encephalitis
Majority subclinical or mild illness
Intermittent epidemic transmission - up to 3,000 cases per year (1975)
Culex mosquitoes
Elderly - biological risk factor
Low SES areas - environmental risk factor
Outdoor occupation - exposure risk factor

85. St. Louis Encephalitis Largest outbreaks in 15 years occurred in 1990
Urban transmission in west first recognized in 1987
Deterioration of inner cities, global warming may increase vector abundance and transmission
Unpredictable and intermittent occurrences of outbreaks
Multiple environmental, biological and social factors contributing to disease occurrence
Virus maintenance and overwintering cycle

86. La Crosse Encephalitis
Frank encephalitis progressing to seizures, coma
majority of infections subclinical or mild
70 cases/year
Case-fatality ratio <1%
Social costs from adverse effects on IQ and school performance
woodland habitats in treehole mosquito (Aedes triseriatus) and vertebrate hosts (chipmunks, squirrels); survives winter in mosquito
Vector uses artificial containers (tires, buckets, etc.) in addition to treeholes

87. La Crosse Encephalitis
Children <16 years old: biological risk factor
Residence in woodland habitats environmental risk factor
Containers at residence environmental risk factor
Outdoor activities: behavioral risk factor
Traditional endemic foci in the great-Lakes states
Increased case incidence in mid-Atlantic states
Rural poor most affected
Disease is considerably under-reported

88. West Nile Virus
First isolated from a febrile adult woman in the West Nile District of Uganda in 1937
Ecology was characterized in Egypt in the 1950s.
Cause of severe human meningoencephalitis in elderly patients during an outbreak in Israel in 1957
Equine disease first noted in Egypt and France in early 1960s.
Outbreak of West Nile-Like Viral Encephalitis -- New York, MMWR, 1999:48(38);845-9
Update: West Nile-Like Viral Encephalitis -- New York, MMWR, 1999:48(39);890-2

89. West Nile Virus in the U. S. September 19, 2003

90. Clinical Epidemiology
Incubation period days
20% develop “West Nile fever”
1 in 150 develop meningoencephalitis
Advanced age primary risk factor for severe neurological disease and death

91. West Nile Fever: Classic Clinical Description
Mild dengue-like illness of sudden onset
Duration days
Fever, lymphadenopathy, headache, abdominal pain, vomiting, rash, conjunctivitis, eye pain, anorexia
Symptoms of West Nile fever in contemporary outbreaks not fully studied

92. Symptoms of Hospitalized Patients with West Nile Virus, New York City, 1999
Fever
90%
Weakness
56%
Nausea
53%
Vomiting
51%
Headache
47%
Change in mental status
46%
Diarrhea
27%
Rash
19%
Lymphadenopathy 2%

93. Neurological Presentations of West Nile Virus Infection
New York City 1999
Encephalitis/meningoencephalitis 62%
Meningitis 32%
Complete flaccid paralysis 10%
Confused with Guillain-Barre syndrome
EMG and nerve conduction velocity-both axonal and demyelinating lesions, with axonal lesions most prominent
Preliminary data 2002
Complaints of weakness out of proportion to exam
Myoclonus nearly a universal finding
Some patients have Parkinsonian
Previous series
Ataxia, extrapyramidal signs, cranial nerve abnormalities, myelitis, optic neuritis, seizures

94. West Nile Virus 489 WNV-viremic donors as of 9/16/03
two cases of blood transfusion-associated WNV in 2003, (TX and Nebraska). Both encephalitis and are recovering.
In 2003, all blood banks screening for West Nile virus and will not take donations from people w/fever and headache in the week prior

95. Serological Analysis of A WN Case
Days
IgM
IgG
Patient WN
SLE
DEN2 JE
P.I.
(WN)
(SLE)
CSF 8
26.91
1.78 nd nd nd nd S1 9
9.1
4.16
160 20
<10 10 S2 34
6.7
4.62
1280 20
<10 20
Positive
n.a. 9
6.5
>5120
2560
2560
320
Control

96. 1999 and 2000 Serosurvey Results
Location
Participants
Positives
Seroprevalence (%)
NYC 1999
Queens
677 19
2.6
NYC 2000
Staten Is.
871 4
0.46
NYS 2000
Suffolk Co.
834 1
0.12
CT 2000
Fairfield Co.
731
0.0

97. Clinical Vignette
59 yo Mexican immigrant admit with 3 month history of progressive shortness of breath, PND, orthopnea, LE edema.

98. Chagas’ Disease American trypanosomiasis (Trypanosoma cruzi)
16-18 million people are infected
50,000 will die each year.
poorly constructed houses found in the rural areas of the above-mentioned countries are at elevated risk of infection. Houses constructed from mud, adobe, or thatch present the greatest risk.

99. Chagas’ Disease
Reduviid bugs, or "kissing bugs" in South and Central America
deposits feces on a person's skin at night
rubs the feces into the bite wound, an open cut, the eyes, or mouth.
Transplacental, congenital or breastfeeding.
By blood transfusion
Uncooked food contaminated with infective feces of "kissing bugs."
one-third chronic symptoms develop after years.
average life expectancy decreases by an average of 9 years.

100. Chagas’ Disease Acute: Indeterminate (asymptomatic): Chronic:
1% of cases.
Romaña's sign
fatigue, fever, enlarged liver or spleen, and swollen lymph glands.
rash, loss of appetite, diarrhea, and vomiting occur.
infants and in very young children cerebral edema
symptoms last for 4-8 weeks.
Indeterminate (asymptomatic):
Chronic:
CHF
megaesophagus, megacolon
in immune compromised, including persons with HIV/AIDS, Chagas disease can be severe.

101. Chagas’ Disease
Diagnosis
smear
serology

102. Clinical Vignette
September 9, 1981, a 72-year-old male from Edinburg, Texas, developed fever and weakness 16 days after being bitten by tsetse flies during a hunting trip in northwest Tanzania. Several days after onset of fever, he noticed a raised, tender, erythematous nodule (6-8 cm in diameter) on the posterior aspect of his right arm.

103. East African Trypanosomiasis
six patients have shared several characteristics:
exposure to infected tsetse flies while visiting game parks in eastern or southern Africa,
development of acute, febrile illness consistent with Trypanosoma brucei rhodesiense infection 1-21 days after visiting
detectable typanosomes on peripheral blood smears, and
recovery after appropriate therapy.
Only 2/5 showed clear evidence of central nervous system (CNS) involvement; both patients had elevated CSF protein, increased CSF cell count, and trypanosomes in the CSF.

104. East African Trypanosomiasis
Suramin is recommended for hemolymphatic stage
does not cross the blood-brain barrier,
Melarsoprol, (relatively toxic) +/- suramin when infection involves the CNS
trypanosomes are observed in the CSF
morula cells of Mott or an elevated CSF IgM is strongly suggest CNS involvement
elevated CSF cell count usually
should be monitored for CNS involvement during treatment and at regular intervals for 1-2 years thereafter

105. Don’t forget Dengue Plague Yellow fever Onchocerciasis Loaiasis
West African Trypanosomiasis
Typhus
Q fever
Louse-borne relapsing fever
Leischmaniasis