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
1 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
2 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
3 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
4 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
5 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
6 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
7 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
8 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
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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
10 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
11 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
12 LYME DISEASE CASES REPORTED TO CDC, NC
180 160 140 120 100 80 60 40 20 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
LYME DISEASE, BY AGE AND GENDER
13 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
15 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
16 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)
17 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.
18 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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