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Management of the Febrile Neutropenic Patient

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Management of the Febrile Neutropenic Patient 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 9 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.
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