Infectious Diseases Conference March 21 2012 Negin Blattman UW Infectious Diseases Maricopa Integrated Health Systems Arizona State University Biodesign Institute Initial Presentation at OSH 62 yr old female Fevers to 102° , generalized malaise for several days, severe headaches, abdominal pain, nausea, and vomiting. In ED was hypotensive, febrile, AMS Initial work up concern for UTI; started on ceftriaxone and imipenem then transferred on dopamine drip Upon arrival Patient began exhibiting seizure like activity at which time she was sedated and intubated Febrile to 103° Work up: Blood cultures CXR and head and abdominal CT LP Abx switched to ceftriaxone, ampicillin, and acyclovir Patient stabilized and moved to ICU History PMHx HTN Hypercholesterolemia Obesity Meds HCTZ Simvastatin Drug Allergies: NKDA Family History Unremarkable History Continued Social History Lives alone with two dogs on the Tohono O'odham Indian reservation 60 pack year smoking history No alcohol No illicit drug use Retired school teacher Sexually active with a male marizona.gif Physical Exam VITALS: T 103; P 105; BP 97/58; GEN: obese female intubated/sedated RESP: ventilated breath sounds, course CV: rrr no mrg, strong peripheral pulses, 2+ peripheral edema ABD: NT/ND, +BS, no organomegaly GU: foley, no genital lesions MSK: normal tone and bulk Laboratory Studies 131 4.5 112 21 35 2 145 15.5 33 46 AST 64 ALT 96 Alk Phos 120 INR 1.3 HIV neg Hepatitis serologies pending CXR: diffuse pulmonary infiltrates CT head and abdomen: unremarkable CSF WBC 85 (PMN predominance) protein 105 glucose 120 Viral studies pending Gram stain neg Cultures pending Therapy Are you happy with her antibiotics? What would you add or change? Therapy Are you happy with her antibiotics? What would you add or change? Laboratory Studies 131 4.5 112 21 35 2 145 15.5 33 46 AST 64 ALT 96 Alk Phos 120 INR 1.3 HIV neg Hepatitis serologies pending CXR: diffuse pulmonary infiltrates CT head and abdomen: unremarkable CSF WBC 85 (PMN predominance) protein 105 glucose 120 Viral studies pending Gram stain neg Cultures pending Therapy Are you happy with her antibiotics? What would you add or change? Further History Four days prior to presentation developed severe nausea, vomiting, and diarrhea Day prior to presentation daughter was doing all care- she was unable to do any ADLs Rash started that same day on her ankles then over night spread all over her body This was in October 1159 14.jpg *** Also present on PALMS and SOLES*** Therapy Now are you happy with her antibiotics? What would you add or change? Therapy Now are you happy with her antibiotics? What would you add or change? Doxycycline DDx for rash on palms and soles DDx for rash on palms and soles Chicken pox Gonococcal disseminated/arthritis Bacterial endocarditis Meningococcal meningitis/meningococcemia Primary HIV Syphilis Kawasaki Disease Measles RMSF; other Rickettsial disease Ehrlichiosis Hand food and mouth disease Tuleremia Small pox DDx for rash on palms and soles Chicken pox Gonococcal disseminated/arthritis Bacterial endocarditis Meningococcal meningitis/meningococcemia Primary HIV Syphilis Kawasaki Disease Measles RMSF; other Rickettsial disease Ehrlichiosis Hand food and mouth disease Tuleremia Small pox Rocky Mountain Spotted Fever: Rickettsia ricketssia Additional Laboratory Studies Initial negative Day 8 IgM 1:128 IgG 1:512 At three weeks IgM 1: 2304 IgG: 1: 4608 RMSF Gram negative Obligate intracellular Tropism for endothelial cells Individual strain variation in virulence (unclear how or why) Same strain can cause varying diseases in humans and appears to be identical in animal models Spotted Fever Rickettsia group Rickettsia rickettsii (Western hemisphere): Rocky Mountain spotted fever Rickettsia akari (USA, former Soviet Union): Rickettsialpox Rickettsia conorii (Mediterranean countries, Africa, Southwest Asia, India): Boutonneuse fever Rickettsia sibirica (Siberia, Mongolia, northern China): Siberian tick typhus or North Asian tick typhus Rickettsia australis (Australia): Australian tick typhus Rickettsia felis (North and South America, Southern Europe, Australia): Flea-borne spotted fever Rickettsia japonica (Japan): Oriental spotted fever Rickettsia africae (South Africa): African tick bite fever Rickettsia hoogstraalii (Croatia, Spain and Georgia USA): Unknown pathogenicity Presentation Fevers, headaches, malaise, myalgias, arthralgias, nausea with or without vomiting, especially children may present with prominent abdominal pain Rash: usuallly occurs between 3-5 days 10% of patients have spot less RMSF- may be more severe and fatal Typically starts on ankles and wrists and spread centrally and to palms and soles Confusion and focal neurological symptoms can occur including seizures EKG abnormalities may rarely occur Host Factors Increasing age Children and male gender Glucose-6-phosphate dehydrogenase deficiency Black race and alcohol have been associated with more severe disease and higher fatality Host Factors Increasing age Children and male gender Glucose-6-phosphate dehydrogenase deficiency Black race and alcohol have been associated with more severe disease and higher fatality Emerging infection in AZ 1981-2001 3 cases 2002-2004 16 patients (E Arizona) Introduction of Rhipicephalus sanguineus (brown dog tick into E Arizona) 2011 52 cases Overall 8% mortality vs 0.5% nation wide Spread of the tick into Southwestern AZ Host Factors Increasing age Children and male gender Glucose-6-phosphate dehydrogenase deficiency Black race and alcohol have been associated with more severe disease and higher fatality Emerging infection in AZ 1981-2001 3 cases 2002-2004 16 patients (E Arizona) Introduction of Rhipicephalus sanguineus (brown dog tick into E Arizona) 2011 52 cases Overall 8% mortality vs 0.5% nation wide Spread of the tick into Southwestern AZ Diagnosis CLINICAL, CLINICAL, CLINICAL “Diagnostic tests for this disease, especially tests based on the detection of antibodies, will frequently appear negative in the first 7-10 days of illness. Due to the complexities of this disease and the limitations of currently available diagnostic tests, there is no test available at this time that can provide a conclusive result in time to make important decisions about treatment”. AZ DHS Treatment Doxycycline is the first line treatment for adults and children of all ages: Adults - 100mg every 12 hours Children under 45kg (100lbs) - 2.2 mg/kg body weight given twice a day Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 5-14 days. Diagnosis CLINICAL, CLINICAL, CLINICAL “Diagnostic tests for this disease, especially tests based on the detection of antibodies, will frequently appear negative in the first 7-10 days of illness. Due to the complexities of this disease and the limitations of currently available diagnostic tests, there is no test available at this time that can provide a conclusive result in time to make important decisions about treatment”. AZ DHS Treatment Doxycycline is the first line treatment for adults and children of all ages: Adults - 100mg every 12 hours Children under 45kg (100lbs) - 2.2 mg/kg body weight given twice a day Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 5-14 days. Vectors Rhipicephalus sanguineus af_americandogtick.jpg Unknown-1.jpeg Dermacentor variabilis (American dog tick)* Dermacentor andersoni (Rocky Mountain wood tick)*