1. Tick Borne Illness in Virginia
Thomas M. Kerkering, M.D.
Professor of Medicine & Professor
Virginia Tech Program of Public Health
Chief, Section of Infectious Diseases
VTCSOM & Carilion Clinic

3. 71 year old WM presents with three day hx “heavy chest
sensation”, fever, chills, fatigue, dull headache & dyspnea.
B/P 199/70, P =102, T = 102.3, R = 20. EKG, troponins not
indicative of cardiac ischemia. Tick bites “all the time”; last
one 7 days ago. Lyme screening antibody = 3.47
(normal < 0.9)
8/28/2010
8/31/2010
Hgb
14.2
13.8
WBC
8.3
8.1
Platelets 77
111
Sodium
131
136
BUN 23 15
Creatinine
1.31
0.8
Total Bili
1.5 1
AST 98 56
ALT
101 72
What is your
Diagnosis?

4. Ehrilichia chaffeensis IgM < 1:20
28-Aug-10
11-Oct-10
Lyme Disease Ab IgG, WB:
Negative
Positive
Lyme Disease 18 KD IgG:
Non-Reactive
Lyme Disease 23 KD IgG:
Reactive
Lyme Disease 28 KD IgG:
Lyme Disease 30 KD IgG:
Lyme Disease 39 KD IgG:
Lyme Disease 41 KD IgG:
Lyme Disease 45 KD IgG:
Lyme Disease 58 KD IgG:
Lyme Disease 66 KD IgG:
Lyme Disease 93 KD IgG:
Lyme Disease Ab IgM, WB
Lyme Disease 23 KD IgM:
Lyme Disease 39 KD IgM:
Lyme Disease 41 KD IgM:
28-Aug-2010
Ehrilichia chaffeensis IgM < 1:20
(negative < 1:20)

5. Morulae

6. 28-Aug-10
11-Oct-10
Lyme Disease Ab IgG, WB:
Negative
Positive
Lyme Disease 18 KD IgG:
Non-Reactive
Lyme Disease 23 KD IgG:
Reactive
Lyme Disease 28 KD IgG:
Lyme Disease 30 KD IgG:
Lyme Disease 39 KD IgG:
Lyme Disease 41 KD IgG:
Lyme Disease 45 KD IgG:
Lyme Disease 58 KD IgG:
Lyme Disease 66 KD IgG:
Lyme Disease 93 KD IgG:
Lyme Disease Ab IgM, WB
Lyme Disease 23 KD IgM:
Lyme Disease 39 KD IgM:
Lyme Disease 41 KD IgM:

7. Ehrilichia chaffeensis IgM = 1:80
10/11/2010
Ehrilichia chaffeensis IgM = 1:80
(negative < 1:20)
Morulae

8. Deer tick, black legged tick, Ixodes scapularis
(ehrlichiosis, Lyme disease, babesiosis)

9. Male & Female Black Legged Tick Deer tick, Ixodes scapularis
(ehrlichiosis, Lyme disease, babesiosis)

11. Male & Female American Dog Tick, (Dermacentor variabilis)
Rocky Mountain Spotted Fever

12. Male & Female Lone Star Tick, (Amblyomma americanum)
Ehrilichia chaffeensis, STARI

15. Anaplasmosis is caused by the bacterium Anaplasma phagocytophilum
Anaplasmosis is caused by the bacterium Anaplasma phagocytophilum. This organism used to be known by other names, including Ehrlichia equi and Ehrlichia phagocytophilum, and the disease caused by this organism has been previously described as human granulocytic ehrlichiosis (HGE).

16. The areas from which cases
are reported correspond with the
known geographic distribution of
the lonestar tick
(Amblyomma americanum), which is associated with transmission of both E. chaffeensis and E. ewingii.

18. RMSF The primary tick that transmits
R. rickettsii in these states is the American dog tick (Dermacentor variabilis Dermacentor andersoni).

19. RMSF

21. Percent of RMSF Cases Reported by Month

22. Tick Borne Diseases in Virginia
Babesiosis
Ehrlichiosis
Lyme Disease
Rocky Mountain Spotted Fever
STARI
Tick Paralysis
Tularemia

23. Cases of Ehrlichiosis / Anaplasmosis
By Year in Virginia
Significance of Trend p =
Source: VDH

24. Cases of Spotted Fever
By Year
In Virginia
Significance of Trend p = 0.01
Source: VDH

25. Cases of Lyme Disease
By Year in Virginia
Significance of Trend p =
Source: VDH

26. Cases of Tularemia
By Year in Virginia
Significance of Trend p = 0.5
Source: VDH

27. Total cases of each disease for the 10 years

29. Rickettsial Infections at CRMH 2005-2010

30. Total Rickettsial Infections at CRMH by Month 2005-2010

31. Babesiosis
B. microti on
peripheral smear

33. Babesiosis incubation period of 1 to 4 weeks
the disease can last several weeks. 
more severe in patients who are immunosuppresed,
splenectomized, and/or elderly
infections caused by B. divergens tend to be more
severe (frequently fatal if not appropriately treated)
than those due to B. microti, where clinical recovery
usually occurs.

34. Clinical Features of Babesiosis
Most infections are probably asymptomatic
  Manifestations of disease include
Fever
Chills
Sweating
Myalgias
Fatigue
Hepatosplenomegaly
Hemolytic anemia

35. Diagnosis of Babesia infection
Made by detection of parasites in patients' blood smears. 
Antibody detection tests are useful for:
detecting infected individuals with very low levels of parasitemia (such as asymptomatic blood donors in transfusion-associated cases),
for diagnosis after infection is cleared by therapy, and for discrimination between Plasmodium falciparum and Babesia infection in patients whose blood smear examinations are inconclusive and whose travel histories cannot exclude either parasite.
The indirect fluorescent antibody test (IFA) 88-96% of patients with B. microti infection.  Patients' titers generally rise to >1:1024 during the first weeks of illness and decline gradually over 6 months to titers of 1:16 to 1:256 but may remain detectable at low levels for a year or more. 

36. PCR Testing for the presence of B. microti DNA is available.

37. Treatment of Babesiosis

38. Ehrlichia chaffeensis primarily infects mononuclear leukocytes (predominantly monocytes and macrophages),
The pathogen that causes human granulocytic ehrlichiosis (HGE) (Anaplasmosis) primarily infects granulocytes (neutrophils and rarely eosinophils).

39. Ehrlichia ewingii primarily infects neutrophils and occasionally eosinophils and produces a disease clinically similar to HME and HGE. Most patients with this form of ehrlichiosis have also had other medical conditions causing immunosuppression (e.g., HIV infection, splenectomy, transplantation,

40.  Lone star tick  (Amblyomma americanum)   
Ehrlichia chaffeensis is principally transmitted by the lone star tick (Amblyomma americanum) White-tailed deer are a major host of lone star ticks and appear to represent one natural reservoir for E. chaffeensis.

41.  Blacklegged tick (Ixodes scapularis)         
The HGE agent (Anaplasmosis) has been associated with the blacklegged tick (Ixodes scapularis). Deer, elk, and wild rodents are likely reservoirs.

42. Ehrlichiosis incubation period of about 5-10 days after the tick bite
Patients with ehrlichiosis generally visit a physician
in their first week of illness
Initial symptoms generally include
- fever
- headache
- malaise
- myalgias

43. Ehrlichiosis Other signs and symptoms may include - nausea - vomiting
- diarrhea
- cough
- joint pains
- confusion
- occasionally rash.
In contrast to Rocky Mountain spotted fever, rash is relatively uncommon in adult patients with HME, and is rarely reported with HGE. However, rash has been described in approximately 60% of pediatric patients infected with E. chaffeensis.

44. Ehrlichiosis
Laboratory findings indicative of ehrlichiosis include - leukopenia
- thrombocytopenia
- elevated liver enzymes
If a lumbar puncture is performed the CSF is abnormal
- a few to WBC (predominately lymphs)
- a few RBCs
- normal glucose
- normal to slightly elevated protein

45. Ehrlichiosis
Ehrlichiosis can be a severe illness, especially if untreated, and as many as half of all patients require hospitalization. Severe manifestations of the disease may include:
- prolonged fever
- renal failure
- disseminated intravascular coagulopathy
- meningoencephalitis
- adult respiratory distress syndrome -
- seizures, or coma
It is estimated that 2%-3% of patients may die from the infection.  Preliminary evidence suggests that E. chaffeensis infection may become more severe than other Ehrlichia infections.

46. Ehrlichiosis
The severity of ehrlichiosis may be related in part to the immune status of the patient.  Persons with compromised immunity caused by immunosuppressive therapies e.g.,
- corticosteroids
- cancer chemotherapy
- HIV infection
- splenectomy
appear to develop more severe disease, and case-fatality ratios for these individuals are characteristically higher than case-fatality ratios reported for the general population.

47. Ehrlichiosis
The organisms can be demonstrated in blood smears by staining with Diff-Quik or Giemsa stains

48. Ehrlichiosis
Although IFA remains the principal diagnostic tool for the detection of ehrlichial infection, there is no standardized antigen, conjugate, or agreement on what constitutes a positive result among the various laboratories providing these tests
Most patients demonstrate increased IgM or IgG titers by the second week of the illness. However, patients may lack diagnostic IgG antibody titers in the first 7 days of illness. This is an important consideration, because patients seek health care at a median of 3 days after onset of the illness.

49. Ehrlichiosis
PCR is the next most frequently used method for detecting infection. This test is available through CDC and some state health laboratories, as well as a number of research and commercial laboratories.  PCR tests remain unstandardized, and analytical and diagnostic sensitivity and specificity may vary among individual assays.
Direct isolation of the organism remains the gold standard for confirmatory diagnosis, but is the most difficult and time-consuming approach. Both E. chaffeensis and the HGE agent have been recovered from the blood of acutely ill patients by using a variety of cell lines.

50. Ehrlichiosis Doxycycline 100 mg twice daily for adults
4.4 mg/kg body weight per day in two divided doses for children under 45.4 kgs (100 lbs)
treat for at least 3 days after the fever subsides and until evidence of clinical improvement, for a minimum total course of 5 to 7 days
severe or complicated disease may require longer treatment courses.
rifampin has been used successfully in a limited number of pregnant women with documented HGE.

52. R. rickettsii in
cell culture

53. (Dermacentor variabilis)
American dog tick
(Dermacentor variabilis)
Dogs and medium-sized mammals are the preferred hosts of adult D. variabilis, although it feeds readily on other large mammals, including humans. This tick is the most commonly identified species responsible for transmitting R. rickettsii to humans.

54. The frequency of reported cases of Rocky Mountain spotted fever is highest among males, Caucasians, and children. Two-thirds of the Rocky Mountain spotted fever cases occur in children under the age of 15 years, with the peak age being 5 to 9 years old   Individuals with frequent exposure to dogs and who reside near wooded areas or areas with high grass may also be at increased risk of infection.

56. Rocky Mountain Spotted Fever
Initial symptoms may include:
fever
nausea
vomiting
severe headache
muscle pain
lack of appetite 
Later signs and symptoms include:
rash
abdominal pain
joint pain
diarrhea

57. Rocky Mountain Spotted Fever
rash appears 2-5 days after the onset of fever
often not present or very subtle when the patient is initially seen
younger patients usually develop the rash earlier than older
patients
most often it begins as small, flat, pink, non-itchy spots (macules)
on the wrists, forearms, and ankles
macules turn pale when pressure is applied and eventually
become raised on the skin

58. Rocky Mountain Spotted Fever
the characteristic red, spotted (petechial) rash of Rocky
Mountain spotted fever is usually not seen until the sixth
day or later after onset of symptoms, and this type of rash
occurs in only 35% to 60% of patients with Rocky Mountain
spotted fever
the rash involves the palms or soles in as many as 50% to
80% of patients; however, this distribution may not occur
until later in the course of the disease
as many as 10% to 15% of patients may never develop a
rash.

63. Rocky Mountain Spotted Fever
Abnormal laboratory findings seen in patients with Rocky Mountain spotted fever may include:
- thrombocytopenia
- hyponatremia
- elevated liver enzyme levels
- abnormal CSF

64. Rocky Mountain Spotted Fever
severe manifestations of this disease may involve:
- respiratory system
- central nervous system
- gastrointestinal system
- renal system.
Due to infection of the endothelial cells and resulting vasculitis

65. Rocky Mountain Spotted Fever
Host factors associated with severe or fatal Rocky Mountain spotted fever include:
- advanced age
- male sex
- African-American race
- chronic alcohol abuse
- glucose-6-phosphate dehydrogenase (G6PD)
deficiency. 
Deficiency of G6PD is a sex-linked genetic condition affecting approximately
12% of the U.S. African-American male population; deficiency of this enzyme
is associated with a high proportion of severe cases of Rocky Mountain
spotted fever.  This is a rare clinical course that is often fatal within 5 days
of onset of illness. 

66. Rocky Mountain Spotted Fever
Long-term health problems following acute Rocky Mountain spotted fever infection include:
- partial paralysis of the lower extremities - gangrene requiring amputation of fingers, toes, or arms or legs
- hearing loss
- loss of bowel or bladder control
- movement disorders
- language disorders
These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations.

67. Rocky Mountain Spotted Fever
Laboratory Detection
There is no widely available laboratory assay that provides rapid confirmation of early Rocky Mountain spotted fever. 
Therefore, treatment decisions should be based on epidemiologic and clinical clues, and should never be delayed while waiting for confirmation by laboratory results.
Fundamental understanding of the signs, symptoms, and epidemiology of the disease is crucial in guiding requests for tests for Rocky Mountain spotted fever and interpretation of results.

68. Rocky Mountain Spotted Fever
The indirect immunofluorescence assay (IFA) is generally considered the reference standard in Rocky Mountain spotted fever serology.
Blood samples taken early (acute) and late convalescent) in the disease are the preferred specimens for evaluation.
Most patients demonstrate increased IgM titers by the end of the first week of illness. Diagnostic levels of IgG antibody generally do not appear until 7-10 days after the onset of illness.

69. Rocky Mountain Spotted Fever
It is important to consider the amount of time it takes for antibodies to appear when ordering laboratory tests, especially because most patients  visit their physician relatively early in the course of the illness, before diagnostic antibody levels may be present. 
The value of testing two sequential serum or plasma samples together to show a rising antibody level is considerably more important in confirming acute infection with rickettsial agents because antibody titers may persist in some patients for years after the original exposure.

70. Immunostaining is used by taking a skin biopsy of the rash from an infected patient prior to therapy or within the first 48 hours after antibiotic therapy has been started. 
Because rickettsiae are focally distributed in lesions of Rocky Mountain spotted fever, this test may not always detect the agent.  The sensitivity is only about 70% on biopsied tissues. 
This assay may also be used to test tissues obtained at autopsy and has been used to confirm Rocky Mountain spotted fever in otherwise unexplained deaths

71. Rocky Mountain Spotted Fever
Doxycycline
100 mg twice daily for adults
4.4 mg/kg body weight per day in two divided doses for children under 45.4 kgs (100 lbs)
treat for at least 3 days after the fever subsides and until evidence of clinical improvement, for a minimum total course of 5 to 10 days
Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever;

72. Southern Tick-Associated Rash Illness

73. Southern Tick-Associated Rash Illness
In 2001, a patient with evidence of B. lonestari infection was reported in the medial literature. This patient had exposure to ticks in Maryland and North Carolina and developed a rash indistinguishable from erythema migrans after an A. americanum tick bite. DNA analysis indicated the presence of B. lonestari in a skin biopsy taken at the leading edge of the rash and in the tick removed by the physician. Serologic testing for Lyme disease was negative. The patient was treated with an oral antibiotic and returned to normal health.

74. A rash similar to the rash of Lyme disease has been described in humans residing in southeastern and south-central states and is associated with the bite of the lone star tick, Amblyomma americanum. This Lyme disease-like rash has been named Southern tick-associated rash illness (STARI).

75. Southern Tick-Associated Rash Illness
Research indicates that live spirochetes are observed in only 1-3% of A. americanum.
Even though spirochetes have been seen in A. americanum ticks by microscopy, attempts to culture it in the laboratory have consistently failed. Modified BSK (Barbour-Stoenner-Kelly) is the best medium for cultivating the Lyme disease spirochete, B. burgdorferi, but is apparently not suitable for cultivating the spirochete found in A. americanum. However, a spirochete has been detected in A. americanum by DNA analysis and was given the name Borrelia lonestari.

76. Reported cases of tularemia, United States, 2001-2010

77. Tularemia is a disease of animals and humans caused by the bacterium Francisella tularensis. Rabbits, hares, and rodents are especially susceptible and often die in large numbers during outbreaks. Humans can become infected through several routes, including:
Tick and deer fly bites
Skin contact with infected animals
Ingestion of contaminated water
Laboratory exposure
Inhalation of contaminated dusts or aerosols

78. Steps to prevent tularemia include:
Use of insect repellent
Wearing gloves when handling sick or dead animals
Avoiding mowing over dead animals
In the United States, naturally occurring infections have been reported from all states except Hawaii.

79. Ulceroglandular This is the most common form of tularemia and usually occurs following a tick or deer fly bite or after handing of an infected animal. A skin ulcer appears at the site where the organism entered the body. The ulcer is accompanied by swelling of regional lymph glands, usually in the armpit or groin.
Glandular Similar to ulceroglandular tularemia but without an ulcer. Also generally acquired through the bite of an infected tick or deer fly or from handling sick or dead animals.
Oculoglandular This form occurs when the bacteria enter through the eye. This can occur when a person is butchering an infected animal and touches his or her eyes. Symptoms include irritation and inflammation of eye and swelling of lymph glands in front of the ear.

80. Oropharyngeal This form results from eating or drinking contaminated food or water. Patients with orophyangeal tularemia may have sore throat, mouth ulcers, tonsillitis, and swelling of lymph glands in the neck.
Pneumonic This is the most serious form of tularemia. Symptoms include cough, chest pain, and difficulty breathing. This form results from breathing dusts or aerosols containing the organism. It can also occur when other forms of tularemia (e.g. ulceroglandular) are left untreated and the bacteria spread through the bloodstream to the lungs.

82. The recommended approach to preventing tick-borne illness is quite simple.
1. Avoiding ticks - whenever possible, stay out of weedy areas. Use paths in wooded areas. Wear light-colored clothing. If you are wearing long pants, tuck them into your socks Spray repellents on your socks and pants legs. Never use repellents on skin covered by clothing.
2. Routine inspection - inspection of yourself and other family members, particularly if anyone has spent significant time outdoors in areas where ticks are likely to be found.

83. The recommended approach to preventing tick-borne illness is quite simple.
3. Prompt removal of ticks - use tweezers to gently pull the tick loose. Do not apply vaseline, kerosene, nail polish or other similar products.
4. Monitoring - if you find a tick on yourself or someone else, circle the date on the calendar and watch for the symptoms of tick-borne illness (i.e., flu-like symptoms) which typically develop within 10 to 14 days. If these symptoms develop, contact your physician immediately. Do not rely solely on watching for the expected physical signs of the rash (Rocky Mountain Spotted Fever) or the Bull's eye for Lyme disease.