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TICKBORNE DISEASES IN THE U.S.

David Jay Weber, M.D., M.P.H.

Professor of Medicine, Pediatrics & Epidemiology Associate Chief of Staff, UNC Health Care

University of North Carolina, Chapel Hill

TICKS AS VECTORS FOR INFECTIOUS DISEASES

Second only to mosquitoes as vectors of human infectious diseases

Ticks are obligate hematophagous arthropods

~900 species described

Each tick species has preferred environmental conditions and biotypes that determine the geographic distribution of the ticks and consequently the risk areas for tickborne diseases

Two major tick families: Ixodidae (hard ticks) and Argasidae (soft ticks)

4 basic life stages: egg, larval, nymph, and adult (male and female)

TICKS AS VECTORS FOR INFECTIOUS DISEASES

Transmission of infectious agents

Via feeding on host

Transstadial: One life stage to another

Transovarial: Via egg

Transovarial transmission allows a tick to serve as both a source and reservoir of infection

Preferred sites of attachment: head, neck, groin

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TICK-BORNE DISEASES, US

Bacterial

Anaplasmosis (Anaplasma phagocytophilum)

Ehrlichiosis (Ehrlichia chaffeensis, E. ewingii, E. muris-like)

Lyme disease (Borrelia burgdorferi)

Spotted fever (Rickettsia parkeri)

Rocky Mountain spotted fever (Rickettsia rickettsii)

Southern tick-associated rash illness, STARI

Tickborne relapsing fever (Borellia hermsii)

Tularemia (Francisella tularensis)

364 Rickettsiosis (Rickettsia phillipi)

Q fever (Coxiella burnetii)

TICK-BORNE DISEASES, US

Viral

Colorado tick fever (Arbovirus)

Tick-borne encephalitis (Flaviviridae)

Powassan fever

Parasitic

Babesiosis (Babesia microti, Babesia spp.)

Non-infectious

Tick paralysis

LIFE CYCLE OF HARD TICKS

4 life stages

Egg

6-legged larva

8-legged nymph

Adult

Blood meal needed at each life stage except egg

Takes up to 3 years for entire life cycle

http://www.cdc.gov/ticks/life_cycle_and_hosts.html. April 2012

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TICK LIFE CYCLE

Tick feed on mammals, birds, reptile, amphibians

Most ticks have a preferred host animal at each stage of their life

Diagram shows life cycle of blacklegged ticks that can transmit anaplasmosis, babesiosis, Lyme disease

RISK FACTORS FOR TICKBORNE DISEASES

Tick exposure

Occupation

Recreation activities

Residence

Tick infection

Failure to use insect repellants

Season

Fatal infection

Delayed therapy

Use of chloramphenicol vs a tetracycline

RISK FACTORS FOR TICK EXPOSURE

Male gender: Ehrlichiosis1

Sports (out doors)

Golfer: Ehrlichiosis1

Poor golfer: Ehrlichiosis1

Orienteers: Lyme disease5,6,7

Gardening: Lyme disease10

Workers

Forestry worker: Lyme disease2, Tick-borne encephalitis2,3, Anaplasmosis4

Farmers: Tick-borne encephalitis3

Outdoor workers: Lyme8

Pets: Lyme8, RMSF9

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RISK FACTORS FOR TICK INFECTION

Rural residence: Ehrlichiosis1, Lyme7

Tick bite: Ehrlichiosis1

Increasing number of tick bite: Ehrlichiosis1

Lack of use of insect repellents: Ehrlichiosis1, Lyme7

American Indian: RMSF2

Season: RMSF3

Younger age: (5-9) RMSF3, (10-19) Lyme7

Male gender: RMSF3

White race: RMSF3

Transfusion (contaminated): Babesia spp.4,5, A. phagocytophilum4

Failure to check of ticks: Lyme6,7

Failure to have fenced in yard: Lyme6

RISK FACTORS FOR SEVERE DISEASE AND/OR HOSPITALIZATION

Use of chloramphenicol vs a tetracycline: RMSF1

Location of illness (NC, OK): RMSF2

American Indian (OK): RMSF3

Splenectomy: Babesia spp.4,5

Immunosuppression (HIV, cancer): Babesia spp.6

RISK FACTORS FOR FATAL DISEASE

Delayed therapy (>4-5 days): RMSF1,2,4,5

Absence of rash: RMSF1,5

Early first MD visit: RMSF1

Off-season presentation: RMSF1

No history of tick attachment: RMSF2,4,5

Older age (>40 years of age): RMSF2,3,4

Younger age (<5 years of age): RMSF3

Use of chloramphenicol vs a tetracycline: RMSF2,4

Fever at presentation: RMSF2,4

Absence of headache at presentation: RMSF2,4

Increased serum creatinine on presentation: RMSF6

Presence of neurological involvement: RMSF6

African-American (g6pd deficiency): RMSF7

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PREVENING TICK BITES

Avoid direct contact with ticks

Avoid wooded and bushy areas with high grass and lead litter

Walk in center of trails

Repel ticks with DEET or permethrin

Use repellents that contain >20% DEET (N, N-diethyl-m-tolumide) on the exposed skin for protection that lasts several hours. Follow product instructions. Avoid application to eyes and mouth (hands in children)

Use products that contain permethrin on clothing. Treat clothing and gear (e.g., tents). Remains protective through several washings.

Pretreated clothing is available and remains protective for up to 70 washings

http://www.cdc.gov/ticks/avoid/on_people.html. April 2012

FINDING TICKS

Bathe or shower as soon as possible after coming indoors (preferably within 2 hours) to wash off and more easily find ticks that are not attached

Conduct a full-body tick check using a mirror to view all parts of the body upon return from a tick-infested area. Check children for ticks under arms, in and around ears, inside the belly button, behind knees, between legs, around waist, and especially the hair

Examine gear and pets

Tumble clothes in a dryer on high heat for an hour to kill remaining ticks

Post-tick removal - Antibiotics do NOT prevent RMSA, erhlichiosis, or anaplasmosis; they will prevent Lyme but are generally not indicated

REMOVING TICKS

Use fine-tipped tweezers to grasp the tick as close to the skin’s surface as possible

Pull upward with steady even pressure. Don’t twist or jerk the tick; this can cause mouth parts to break off and remain in the skin. If this occurs, remove the mouth parts with tweezers. If you are unable to remove the mouth easily with clean tweezers, leave it alone and let the skin heal

After removing the tick, thoroughly clean the bite area and your hands with rubbing alcohol, an iodine scrub, or soap and water

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AMERICAN DOG TICK (RMSF, TULAREMIA)

Larvae and nymphs feed on small rodents; adults feed on dogs and medium-sized mammals

BLACKLEGGED TICK

(ANAPLASMOSIS, BABESIOSIS, LYME)

Larvae and nymphs feed on mammels and birds; adults feed on dogs and larger mammals

BROWN DOG TICK (RMSF)

All life stages feed primarily on the dog

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GULF COAST TICK (SPOTTED FEVER {R. parkeri})

Larvae and nymphs feed on birds and small rodents; adults feed on deer and other wildlife

LONE STAR TICK

(EHRLICHIOSIS, TULAREMIA, STARI)

Larvae and nymphs feed on birds and deer; adults feed primarily on deer

ROCKY MOUNTAIN

SPOTTED FEVER

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RICKETTSIA RICKETTSII

Member of spotted fever group of Rickettsiae

Small (0.2-0.5 by 0.3-2.0 um) coccobacilli

Obligate, intracellular bacteria

Pathogenic for humans

May be demonstrated in human tissue by Gimenez method or in tissue sections stained by

immunofluorescence

Poorly visualized by Gram stain (ultrastructure similar to Gram-negative bacilli)

EPIDEMIOLOGY

RMSF is a vector-borne disease transmitted by certain species of ticks

Ticks serve as the reservoir or natural host

Infection acquired via bite of infected tick

Cases have been acquired by lab personnel via inoculation or inhalation of aersols

Cases have been acquired via transfusion or needlestick injury from an infected patient

FEEDING TICK

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EPIDEMIOLOGY: INCIDENCE

Varies among states

Secular trends

Seasonal disease: 95% cases April 1 to September 30

Highest incidence in children: persons age 5 to 9 years

High incidence in adults: persons age 55 to 59

Highest mortality: persons >60 years

Higher incidence associated with male gender, living in a wooded area, exposure to dogs

http://www.cdc.gov/rmsf/stats/. April 2012

http://www.cdc.gov/rmsf/stats/. April 2012

(10)

http://www.cdc.gov/rmsf/stats/. April 2012

http://www.cdc.gov/rmsf/stats/. April 2012

CLINICAL MANIFESTATIONS

RMSF is a multisystem disease

Most patients have moderate or severe illness

Incubation period: 2-14 days (average, 7 days)

Onset may be gradual or abrupt

Initial symptoms nonspecific: fever, malaise, headache (often severe), and myalgias

Other symptoms: rash, nausea, vomiting, anorexia,

abdominal pain, and photophobia

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RMSF: CUTANOUS MANIFESTATIONS

MORBIDITY AND MORTALITY

Complications: 40% (reporting bias likely)

Severe neurologic dysfunction, coagulopathy, renal failure, noncardiac pulmonary edema, cardiovascular dysfunction, hepatic disease, gangrene

Mortality

Untreated or inappropriately treated: 15-20%

Treated appropriately: now <0.5%

Fulminant disease associated with G6PD deficiency

TREATMENT

Early treatment with appropriate antibiotics dramatically reduces mortality associated with the disease

If patient treated within first 5 days of disease, fever generally subsides within 24-72 hours (failure to respond in this time period suggests patient has another diagnosis)

Therapy

Doxycycline 100 mg orally 2x/day (first choice!!)

Chlorampenicol (use only in doxycline allergic patients)

Avoid sulfa drugs (may worsen RMSF)

Therapy administered for 5-7 days (until afebrile and clinically improved for 3 days); standard duration of treatment is 7-14 days

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LYME DISEASE

EPIDEMIOLOGY

Pathogen (US): Borrelia burgdorferi

Vectors

Northeastern, North-central US: Black-legged tick or deer tick (Ixodes scapularis)

Pacific coast: Western black-legged tick (Ixodes pacificus)

No transmission via American/brown dog ticks, Rocky Mountain wood tick

Transmission

Via tick bite (cats and dogs can carry ticks)

No transmission via person-to-person (contact, sex, kissing, breast milk), blood (B. burgdorferi can survive in stored blood), air, milk, food, water, or bites from mosquitoes, flies, fleas, lice

http://www.cdc.gov/lyme/stats/maps/map2010.html. April 2012

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LYME DISEASE CASES REPORTED TO CDC, NC

0 20 40 60 80 100 120 140 160 180

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

LYME DISEASE, BY AGE AND GENDER

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EM RASHES

LYME DISEASE, BY SYMPTOMS

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EHRLICHIOSIS

OVERVIEW OF EHRLICHIOSIS AND ANAPHLASMOSIS

Thomas RJ, et al. Expert Rev Anti Infect Ther 2009;7:709-11

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MICROBIOLOGY

Pathogens

Ehrlichia chaffeensis, E. ewingii, E. muris-like

Small, obligate intracellular, Gram-negative bacilli

Characteristic ultrastructure dimorphic appearance and cell wall morphology

Reside in cytoplasmic vacuoles, generally within monocyte (E.

chaffeensis) or granulocyte (E. ewingii)

Due to the resemblance of an azure-eosin-strained vacuolar microcolony of ehrlichiae to a mulberry, this structure termed

“morula”, the Latin word for mulberry

Vectors

Lone star tick (A. americanum)

SYMPTOMS

Symptoms usually develop 1-2 weeks after tick bite

Fever, headache, chills, malaise, muscle pain,

nausea/vomiting/diarrhea, confusion, conjunctival injection, rash (up to 60% of children, <30% of adults)

Rash should NOT be used to rule in or out infection

Rash may range from maculopapular to petechial and is usually non- pruritic

Usually spares the face, but may spread to palms and soles

Appearance may be that of erythroderma

Rash may resemble that of RMSF

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ANAPLAMOSIS

MICROBIOLOGY

Pathogen

Anaplasma phagocytophilum (previously human granulocytic ehrlichiosis)

Small, obligate intracellular, Gram-negative bacilli

Characteristic ultrastructure dimorphic appearance and cell wall morphology

Reside in cytoplasmic vacuoles, within PMNs

Due to the resemblance of an azure-eosin-strained vacuolar microcolony of ehrlichiae to a mulberry, this structure termed

“morula”, the Latin word for mulberry

Vectors

Black-legged tick (Ixodes scapularis), western black-legged tick (I.

pacificus)

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SYMPTOMS

Symptoms usually develop 1-2 weeks after tick bite

Fever, headache, malaise, muscle pain, nausea, abdominal pain, cough, confusion, rash (rare)

Severe clinical presentations may include difficulty breathing, hemorrhage, renal failure, or neurological problems

Rash is rarely reported (consider another disease)

SUMMARY

The most important tick-borne diseases in the US are RSMF, Lyme disease, ehrlichiosis, and anaplasmosis

Prevention is superior to treat – persons should take action to prevent tick bites

RMSF is a multisystem disease with high mortality unless treated

Most deaths due to RMSF are due to the failure of the medical provider to consider the diagnosis; patients know they are sick and seek medical care

The classic descriptions of RMSF are representative of late disease not the initial presentation

SUMMARY

The two most important human ehrlichial-like diseases are ehrlichiosis which is caused by Ehrlichia spp. and anaplasmosis human which is caused by Anaplasma phagocytophilum.

The principle vector of ehrlichiosis is the Lone Star tick (Amblyomma americanum) and the vectors of A. phagocytophilum is Ixodes scapularis in the eastern United States and I. pacificus in the western United States.

Both forms of these diseases typically present as an acute illness with an incubation period of one to two weeks; most patients are febrile, with nonspecific symptoms such as malaise, myalgia, headache, and chills.

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SUMMARY

The clinical and epidemiologic features of both ehrlichiosis and anaplasmosis overlap with those of Rocky Mountain spotted fever (RMSF), often making it difficult to distinguish between these three disorders

The preferred treatment for ehrlichiosis, anaplasmosis and RMSF is doxycycline even in children and pregnant women

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