3 Clinical Vignette28yo FBI agent on temporary assignment in the Nantahala forest in Western North Carolina presents with acute onset fever, chills, headache 3 days after Memorial Day.Exam: confused, ill appearing, a few petechiae present on wrists and anklesLabs: platelets=75K, mild leukocytosis, mildly elevated transaminaseLP with 75 WBC, mostly lymphocyes with protein=154
4 Tick-Borne Infections in the U.S. Lyme diseaseRocky Mountain spotted feverEhrlichiosisTularemiaBabesiosisColorado tick feverTick-borne relapsing feverTick-borne encephalitisTick paralysisQ Fever
13 RMSF Clinical Manifestations Incubation period daysOnset with fever, myalgias, headacheGI findings may mimic an acute abdomenRash appears days after onset of feverMeningismus and CSF pleocytosis may occurWBC usually normal, platelets may be decreasedHyponatremia occurs in 50%
16 RMSF Diagnosis Serology IF staining of tissue specimen PCR under development
17 RMSF Outcome N=6388 over 1981-1998 Annual case-fatality rate 3.3% Risk factors for mortality:Old ageChloramphenicol onlyTetracycline not primary therapyTreatment delayed > 5 daysHolman et al JID 2001
18 Clinical Vignette54 yo WM farmer in Missouri presents with 3 day h/o high fevers, chills, headache and marked malaise in JuneExam notes a confused, ill-appearing man but is otherwise unremarkableLabs note transaminases 3 x normal, platelets 115K, WBC 2.1, CSF 32WBC, protein 127
19 History of Ehrlichiosis E. canis-hemorrhagic illness in Algerian dogs1950s – E. sennetsu-mononucleosis-like illness in Japan1986 – Ehrlichiosis-patient in Detroit after tick bites in ArkansasE. chaffeensis cultured from patient at Fort Chaffee in Arkansas
23 Genus EhrlichiaSmall gram-negative bacteria closely related to RickettsiaeObligate intracellular parasitesInfect circulating blood elementsReside and replicate within membrane-bound cytoplasmic vacuolesVertebrate reservoirs and arthropod vectors
27 Ehrlichia ewingiiFirst discovered in dogs with granulocytic ehrlichiosis, 1992Disease is milder than E. canis infectionManifestations include fever, lethargy and polyarthritisFound to date in dogs in Missouri, Arkansas, Oklahoma and N. CarolinaMember of E. canis genogroup (cross-reactivity)Experimental transmission by A. americanum
30 Human Ehrlichiosis Symptoms HMEHGEFever9794-100Headache8161-85Myalgia6878-98Malaise8498Rash362-11Confusion2017Dumler et al, Annu. Rev. Med :
31 Human Ehrlichiosis Clinical Spectrum DICPancytopeniaEncephalitis/MeningitisPulmonary infiltrates/Respiratory failureGastrointestinal bleedingRenal Failure
32 Human Ehrlichiosis Laboratory Findings LeukopeniaThrombocytopeniaElevated transaminasesHyponatremia>4-fold elevation in IFAPCR
33 RMSF/Ehrlichiosis Treatment Adults: Doxycycline 100 mg bidChildren: Doxycycline 3 mg/kg/day in 2 divided dosesDuration: 3 days after defervescence, minimum 5-7 days
34 Clinical Vignette34 yo WF owner of a campground presents with a nonhealing lesion on the right index finger for 2 weeks, adjacent to the nail bed.Failed Augmentin and acyclovir by PCP for “infected paronychia”Exam notes an ulcerated lesion and regional adenopathy
35 Tularemia History McCoy & Chapin 1910 “plague-like disease” of rodents in Tulare Co. CABacterium TularenseEdwards Franciscasesisolated organismproved vectornamed the diseasedeveloped culture and serology methodsnoted risk to workers
36 Parola, Clin Infect Dis 2001 Mar 15;32(6):897-928
37 Tularemia Epidemiology 1368 casesAll states except Hawaii, but predominately MO, AK, OK & SDReinstated on nationally notifiable list 2000 (n=142)Type A (biogroup tularensis)Multiple vectors (tick, deerfly)>250 animal speciesrabbitsharesmuskratsOther transmissioncarnivoresdirect contactinhalation/ingestionPeak incidence 1939
38 Outbreak 2001 Pneumonic Tularemia 15 patients in Martha’s Vineyard11 primary pulmonary1 deathFeldman et al, N Engl J Med 2001 Nov 29;345(22):1601-6
42 Tularemia Diagnosis Titers 4-fold increase single > 1:160 Skin test Culture – notify laboratory
43 Tularemia Treatment Streptomycin 1 gm iv q12h for 10 days Gentamicin 5 mg/kg/d for 10 daysTetracycline/chloramphenicolassociated with 15-20% relapseQuinolonesExcellent in vitro activityLimited data, anecdotal experience suggests efficacyLive attenuated vaccine for high risk groups
45 Lyme Most commonly reported tick-borne infection in U.S. , mean 12,451 annual cases (CDC)
46 Lyme History Cluster of cases near Lyme, CT 1975 Johnson RC, Schmid GP, Hyde FW, Steigerwalt AG, Brenner DJ. Borrelia burgdorferi sp. nov.: etiological agent of Lyme disease. Int J Syst Bacteriol 1984; 34:496 7.
47 Lyme epidemiology B. burgdorferi sensu lato Tick vector Black-footed mouse reservoirWhite-tailed deer hostBirds and mammals implicated in Europe
48 Lyme Disease Early Manifestations Erythema migrans (90%)Occurs 8-14 days after biteSingle lesion, average size 15cmSystemic symptoms may be presentSecondary lesions may occurCarditisAseptic meningitisBell’s palsy
49 Lyme Disease Late Manifestations ArthritisKnees involved in 90%Usually resolves, 1-2 weeksMay recurCNS disease (rare in children)
53 Lyme Disease Vaccinerecombinant B. burgdorferi lipidated outer-surface protein A (rOspA)Antigen not expressed in hostAntibody is taken up into tick and bacteria destroyed in vector0, 1 and 12 monthsAs of February 25, 2002 LYMErix™ off the market
54 Southern Tick-Associated Rash Illness (STARI) Similar EM rashLong-term and serious complications not reportedResponds to doxycyclineOrganism by PCR B. lonestariNo culture639 cases in Texas
55 Clinical Vignette25yo male camper in Montana presents with a 2 week history of intermittent fevers. Initially he had a high fever with headache, red eyes, jaundice, severe body aches, and after about 3 days a diffuse red rash on his trunk. The fever resolved, then about a week later recurred without the other symptoms.
56 Tick-borne Relapsing Fever Dutton JE, Todd JL. The nature of tick fever in the eastern part of the Congo Free State, with notes on the distribution and bionomics of the tick. Br Med J 1905; 2:Described tick relapsing feverBorrelia duttoniitransmitted by Ornithodoros moubata in W. Africa13 species of Borreliagenus OrnithodorosNoctural feederShort attachmentworldwide
57 Parola, Clin Infect Dis 2001 Mar 15;32(6):897-928
58 Tick-borne Relapsing Fever acute onset of high fever with chills, headache, myalgia, arthralgia, and coughingHemorrhage, iritis or iridocyclitis, hepatomegaly, or splenomegalyrash at the end of the first febrile episodePrimary episode 3 daysneurological findingsB. turicatae (U.S.)B. duttonii (Africa)Jaundice ( 7%)case-fatality rate 2%-5%intensity of episodes decreases with timeMean period between episodes 8 days
59 Tick-borne Relapsing Fever Borreliae in peripheral blood of febrile patients. Sensitivity 70% (darkfield microscopy or Giemsa or Wright's stain).Quantitative buffy coatSerology not usefulPCRJarisch-Herxheimer reactiondoxycycline (Penicillin, erythromycin, or ceftriaxone)
60 Tick-Transmitted Diseases Prevention Avoid tick-infested areasWear protective clothing that covers exposed areasUse DEET - containing insect repellantsSpray permethrin on clothesRemove attached ticks promptly Do not squeeze
61 Clinical Vignette45yo BM with h/o Hodgkin’s in remission 5 years after chemo/XRT for Stage 4 disease, presents with acute fever, fatigue, abdominal pain, SOB/DOE, in June in New Jersey.Exam: hepatosplenomegaly, hyperdynamic precordium, pale.
62 Babesiosis Hemoprotozoan Babesia microti and Babesia divergens similar vector, animal reservoir and geographic distribution as LymeMultiplication of the blood stage parasites is responsible for the clinical manifestations of the disease
63 Babesiosismore severe in patients who are immunosuppressed, splenectomized, and/or elderlydiagnosis by thick and thin smearTreatment with clindamycin + quinine or atovaquone + azithromycinexchange transfusion has been used in severely ill patients with high parasitemias
65 Clinical Vignette48 yo male presents with acute onset episodic fever abdominal pain, headache, myalgias and nausea/vomiting, then profuse sweats.Recent trip to Thailand looking for exotic bird species.Exam notes tender right and left upper quadrant and splenomegalyLabs note pancytopenia
66 Malaria300–500 million infections worldwide and approximately 1 million deaths annually (CDC)Plasmodium falciparum, P. vivax, P. ovale, or P. malariaeinfected female Anopheles mosquitoblood transfusion or congenitalFatal cases are due to falciparum (“knobs”)P. vivax and P. ovale parasites can persist in the liver (natural infection only)P. malariae acute illness rare in normal hosts, causes chronic infection (GN)
69 Malaria Chloroquine-susc mefloquine resistance Dominican Republic, HaitiCentral America west of the former Panama Canal ZoneEgyptsome countries in the Middle Eastmefloquine resistanceborders of Thailand with Burma (Myanmar) and Cambodiawestern provinces of Cambodiaeastern states of Burma (Myanmar)Fansidar resistanceAmazon River Basin area of South America,Southeast Asiaother parts of Asialarge parts of Africa
70 Malaria fever and influenzalike symptoms chills, headache, myalgias, and malaiseClassic paroxysmChillSpikeSweatcan occur at intervalsFalciparum less exactVivax/ovale tertianMalariae quartiananemia and jaundice,seizures, mental confusionkidney failure, coma, and death6 days after initial exposure to several months after chemoprophylaxis
71 Malaria Diagnosis Peripheral smear Hypoglycemia Lactic acidosis Vivax/ovaleFalciparumNo mature formsHigh parasitemia (directly related to mortality in nonimmune)Multiple ring forms/cellInfects all agesHypoglycemiaLactic acidosisHemolysisAcute renal failurePancytopenia
73 Malaria Treatment Hospitalize if nonimmune and suspect falciparum Different drug than prophylaxisHalofantine cross resistant w/mefloquineStart 2nd drug laterIf vivax/ovale need PrimaquineArtemisin if mefloquin/cholorquine resistanceExchange transfusion if parasitemia >15% in nonimmune
74 Malaria Prevention transmission occurs primarily between dusk and dawn well-screened areas, mosquito nets, clothes that coverDEET (N,N-diethylmetatoluamide)pyrethroid-containing flying-insect spray in living and sleeping areas
75 Chemoprophylaxis mefloquine or chloroquine 1–2 weeks before doxycycline and atovaquone/proguanil 1–2 days beforecontinuously while in malaria-endemic areas4 weeks (chloroquine, doxycycline, or mefloquine) after7 days (atovaquone/proguanil) afterTerminal prophylaxis with Primaquine final 14 daysfatal hemolysis in those who are G6PD deficient
76 Chemoprophylaxis pregnancy Long history of chloroquine and quinine useData supports safety of mefloquine in 2nd an 3rd trimesterData in first trimester sketchy, patient must weigh risksNo Doxycycline or PrimaquineNo data for Malarone
77 Malaria Information http://www.cdc.gov/travel Voice information service FYI-TRIPCDC Malaria Hotline ( ) from 8:00 a.m. to 4:30 p.m. Eastern timeCDC Emergency Operation Center atpage person on call for the Malaria Epidemiology Branch.
78 Clinical Vignette72 yo WM alcoholic with CAD presents with 3 day h/o fever, myalgias, headache followed by acute onset confusion and tremulousnessWorks as a nursery sales rep and travels frequently to East TexasNo improvement on levaquinEKG afibCSF notes elevated protein and lymphocytic pleiocytosis
82 Arboviral Activity Louisiana 2001 SLE Human CasesEEE Equine CasesEEE Human CasesSLE Avian CasesEEE Mosquito PoolsWNV Equine CasesWNV Human CasesWNV Avian CasesSLE 5 Human CasesOutbreak or Cluster with Human Case(s)
83 Eastern Equine Eastern US Ave. 4 cases/year Togaviridae, genus Alphavirus35% mortality35% permanent neuro defect
84 St. Louis Encephalitis Aseptic meningitis or encephalitis Majority subclinical or mild illnessIntermittent epidemic transmission - up to 3,000 cases per year (1975)Culex mosquitoesElderly - biological risk factorLow SES areas - environmental risk factorOutdoor occupation - exposure risk factor
85 St. Louis Encephalitis Largest outbreaks in 15 years occurred in 1990 Urban transmission in west first recognized in 1987Deterioration of inner cities, global warming may increase vector abundance and transmissionUnpredictable and intermittent occurrences of outbreaksMultiple environmental, biological and social factors contributing to disease occurrenceVirus maintenance and overwintering cycle
86 La Crosse Encephalitis Frank encephalitis progressing to seizures, comamajority of infections subclinical or mild70 cases/yearCase-fatality ratio <1%Social costs from adverse effects on IQ and school performancewoodland habitats in treehole mosquito (Aedes triseriatus) and vertebrate hosts (chipmunks, squirrels); survives winter in mosquitoVector uses artificial containers (tires, buckets, etc.) in addition to treeholes
87 La Crosse Encephalitis Children <16 years old: biological risk factorResidence in woodland habitats environmental risk factorContainers at residence environmental risk factorOutdoor activities: behavioral risk factorTraditional endemic foci in the great-Lakes statesIncreased case incidence in mid-Atlantic statesRural poor most affectedDisease is considerably under-reported
88 West Nile VirusFirst isolated from a febrile adult woman in the West Nile District of Uganda in 1937Ecology was characterized in Egypt in the 1950s.Cause of severe human meningoencephalitis in elderly patients during an outbreak in Israel in 1957Equine disease first noted in Egypt and France in early 1960s.Outbreak of West Nile-Like Viral Encephalitis -- New York, MMWR, 1999:48(38);845-9Update: West Nile-Like Viral Encephalitis -- New York, MMWR, 1999:48(39);890-2
89 West Nile Virus in the U. S. September 19, 2003
90 Clinical Epidemiology Incubation period days20% develop “West Nile fever”1 in 150 develop meningoencephalitisAdvanced age primary risk factor for severe neurological disease and death
91 West Nile Fever: Classic Clinical Description Mild dengue-like illness of sudden onsetDuration daysFever, lymphadenopathy, headache, abdominal pain, vomiting, rash, conjunctivitis, eye pain, anorexiaSymptoms of West Nile fever in contemporary outbreaks not fully studied
92 Symptoms of Hospitalized Patients with West Nile Virus, New York City, 1999 Fever90%Weakness56%Nausea53%Vomiting51%Headache47%Change in mental status46%Diarrhea27%Rash19%Lymphadenopathy2%
93 Neurological Presentations of West Nile Virus Infection New York City 1999Encephalitis/meningoencephalitis 62%Meningitis 32%Complete flaccid paralysis 10%Confused with Guillain-Barre syndromeEMG and nerve conduction velocity-both axonal and demyelinating lesions, with axonal lesions most prominentPreliminary data 2002Complaints of weakness out of proportion to examMyoclonus nearly a universal findingSome patients have ParkinsonianPrevious seriesAtaxia, extrapyramidal signs, cranial nerve abnormalities, myelitis, optic neuritis, seizures
94 West Nile Virus 489 WNV-viremic donors as of 9/16/03 two cases of blood transfusion-associated WNV in 2003, (TX and Nebraska). Both encephalitis and are recovering.In 2003, all blood banks screening for West Nile virus and will not take donations from people w/fever and headache in the week prior
95 Serological Analysis of A WN Case DaysIgMIgGPatientWNSLEDEN2JEP.I.(WN)(SLE)CSF826.911.78ndndndndS199.14.1616020<1010S2346.74.62128020<1020Positiven.a.96.5>512025602560320Control
97 Clinical Vignette59 yo Mexican immigrant admit with 3 month history of progressive shortness of breath, PND, orthopnea, LE edema.
98 Chagas’ Disease American trypanosomiasis (Trypanosoma cruzi) 16-18 million people are infected50,000 will die each year.poorly constructed houses found in the rural areas of the above-mentioned countries are at elevated risk of infection. Houses constructed from mud, adobe, or thatch present the greatest risk.
99 Chagas’ DiseaseReduviid bugs, or "kissing bugs" in South and Central Americadeposits feces on a person's skin at nightrubs the feces into the bite wound, an open cut, the eyes, or mouth.Transplacental, congenital or breastfeeding.By blood transfusionUncooked food contaminated with infective feces of "kissing bugs."one-third chronic symptoms develop after years.average life expectancy decreases by an average of 9 years.
100 Chagas’ Disease Acute: Indeterminate (asymptomatic): Chronic: 1% of cases.Romaña's signfatigue, fever, enlarged liver or spleen, and swollen lymph glands.rash, loss of appetite, diarrhea, and vomiting occur.infants and in very young children cerebral edemasymptoms last for 4-8 weeks.Indeterminate (asymptomatic):Chronic:CHFmegaesophagus, megacolonin immune compromised, including persons with HIV/AIDS, Chagas disease can be severe.
102 Clinical VignetteSeptember 9, 1981, a 72-year-old male from Edinburg, Texas, developed fever and weakness 16 days after being bitten by tsetse flies during a hunting trip in northwest Tanzania. Several days after onset of fever, he noticed a raised, tender, erythematous nodule (6-8 cm in diameter) on the posterior aspect of his right arm.
103 East African Trypanosomiasis six patients have shared several characteristics:exposure to infected tsetse flies while visiting game parks in eastern or southern Africa,development of acute, febrile illness consistent with Trypanosoma brucei rhodesiense infection 1-21 days after visitingdetectable typanosomes on peripheral blood smears, andrecovery after appropriate therapy.Only 2/5 showed clear evidence of central nervous system (CNS) involvement; both patients had elevated CSF protein, increased CSF cell count, and trypanosomes in the CSF.
104 East African Trypanosomiasis Suramin is recommended for hemolymphatic stagedoes not cross the blood-brain barrier,Melarsoprol, (relatively toxic) +/- suramin when infection involves the CNStrypanosomes are observed in the CSFmorula cells of Mott or an elevated CSF IgM is strongly suggest CNS involvementelevated CSF cell count usuallyshould be monitored for CNS involvement during treatment and at regular intervals for 1-2 years thereafter