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Case Conference February 3, 2003


Diagnosis: stool culture, blood culture. Treatment: TMP/SMX, cipro, azithro. Hepatitis A ... Stool cx -, blood cx -, transaminitis. Diarrhea, fever, itchy eyes ... – PowerPoint PPT presentation

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Title: Case Conference February 3, 2003

Case ConferenceFebruary 3, 2003
  • Caryn G. Morse, MD
  • Fellow in Infectious Diseases
  • Wake Forest University/Baptist Medical Center

Case Presentation
  • 21 yo female college student presents to the ED
    for further evaluation of fever, malaise and
    non-productive cough of approximately one week

Case Presentation
  • Two weeks prior to presentation patient developed
    watery diarrhea and mild abdominal cramping after
    meal at road-side restaurant
  • Diarrhea symptoms lasted 7-10 days and abated
    somewhat with symptomatic therapy

Case Presentation
  • One week prior to presentation noted development
    of fever up to 103o, malaise with 3-4 day history
    of progressive non-productive cough with mild
    SOB, pleuritic chest pain

Case Presentation
  • Recently returned from anthropology/service trip
    to southern Mexico with 7 classmates

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Case History
  • Traveled by airplane to Mexico City? bus San
  • Trip dates 12/30/02-1/13/03
  • Accommodations included hotel rooms, mats on
    ground in thatched huts
  • Majority of trip spent at 9,000 ft
  • Activities included hiking, digging in dirt
    (excavating,) building, caving, bathing in river
  • Largely ate meals prepared by local people.
    Drank only bottled water.

Case TC History
  • Denied known animal exposure, sick contact,
    sexual encounter
  • Unaware of sick contacts since return
  • Some people with the flu at school

Case TC History
  • Pre-travel vaccinations flu, hepatitis A
  • No malaria prophylaxis
  • Pt. reported childhood vaccinations were
    up-to-date and included hepatitis B hx varicella

Case TC Physical Examination
  • VS T 102.1?101.8
  • BP 117/80 R 20 02 SAT 94 RA
  • WD/WN AF fatigued, mildly diaphoretic, NAD

Case TC Physical Examination
  • NEURO AO x 3 CN II-XII non-focal Nl strength
    and sensation
  • HEENT Conj pink, non-icteric, OP clear
  • NECK Supple without LAD
  • CHEST CTA with rare ant crackle
  • CV Tachy S1 S2 F audible m/g/r
  • ABD bs NT/ND F palpable OGM
  • EXT F c/c/e
  • SKIN F rash or lesion

Case TC Laboratory Studies
  • WBC 10.2 S 42 B 13
  • HGB 133
  • PLT 329
  • BMP nl with BUN/CR 7/1
  • Alk Phos 176
  • AST 413
  • ALT 388
  • U/A (-) with GPR on GS

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Differential diagnosis?
  • Viral
  • Bacterial
  • Fungal
  • AFB
  • Parasitic

Next step?
  • Admit or not admit?
  • Laboratory studies?
  • Treatment?

Fever in the Returning Traveler
  • How often does fever occur in the returning
  • What are the usual causes?
  • What are the usual outcomes?
  • How do I approach a returning traveler with fever?

Hill DR. Health problems in a large cohort of
Americans traveling to developing countries. J
Travel Med 2000 7259.
  • 2-year survey of 784 travelers (95 follow-up) of
    persons traveling for lt or 90 days.
  • At the pre-travel visit, travelers given a
    postcard to record adverse health events.
  • Following travel, standardized telephone
    interviews were performed for any positive
    responses, or if the card was not returned.
  • All travelers were contacted 2 months after
    return to determine late occurring illness and
    compliance with antimalarials.

Hill DR. Health problems in a large cohort of
Americans traveling to developing countries. J
Travel Med 2000 7259.
  • Mean age of 44 yrs trip median duration 19
    days cohort visited 123 countries.
  • Illness reported by 64 (1.6 illnesses per
  • Ill travelers were more often female, and
    traveled longer than those who were not ill
  • Depending upon destination, each day of travel
    increased by 3 to 4 the chance of becoming ill

Hill DR. Health problems in a large cohort of
Americans traveling to developing countries. J
Travel Med 2000 7259.
  • 46 diarrhea 34 met strict definition for
    traveler's diarrhea
  • 26 respiratory illness
  • 8 skin disorders
  • 6 acute mountain sickness, 5 motion sickness,
    5 accidents and injuries
  • 3 isolated febrile episodes
  • Medical care was sought by 8 of all travelers
    and 12 of those reporting illness

Hill DR. Health problems in a large cohort of
Americans traveling to developing countries. J
Travel Med 2000 7259.
  • 26 of travelers were ill, 56 of whom became ill
    after return.
  • Diarrhea, respiratory illness, skin disorders,
    and febrile syndromes were most common, and 46
    of those who were ill sought medical care.
  • Complete compliance with antimalarials was 80.
    Noncompliant individuals usually discontinued
    medications on return.
  • The incidence of documented malaria was 3.8 cases
    per 1,000 travelers.

MacLean et al. Fever from the tropics. Travel
Medicine Advisor 1994 5271-27
  • 587 consecutive travel clinic outpatients with
    fever seen in Montreal, Canada between 1981-1987

MacLean et al. Fever from the tropics. Travel
Medicine Advisor 1994 5271-27
  • Malaria 32
  • Undiagnosed 25
  • Other tropical 10.5
  • Diarrheal illness 4.5
  • Dengue 2
  • Enteric fever 2
  • Rickettsia 1
  • Amebic liver abscess 1
  • Cosmopolitan 26
  • Hepatitis 6
  • URI 11
  • UTI 4
  • Meningitis 1
  • Miscellaneous 6

Doherty JF et al. Fever as the presenting
complaint of travelers returning from the
tropics. QJM 1995 88(4) 277-81.
  • Prospective observational investigation of cause
    of fever in patients requiring hospitalization
    after return from the tropics.
  • Enrolled all consecutive admissions (n195) with
    oral temperature gt 37.0oC at the time of
  • Final diagnosis as recorded on the discharge
    summary by the attending physician and results of
    any relevant laboratory or radiological
    investigations were recorded.

Doherty JF et al. Fever as the presenting
complaint of travelers returning from the
tropics. QJM 1995 88(4) 277-81.
  • 42 Malaria
  • 25 Non- specific viral infection
  • 9 Cosmopolitan infections UTI, CAP,
    strep pharyngitis
  • 16 Coincidental infections
    schistosomiasis, filariasis, intestinal
  • 3 HIV

Doherty JF et al. Fever as the presenting
complaint of travelers returning from the
tropics. QJM 1995 88(4) 277-81.
  • Most useful investigation malaria film, positive
    in 45 of cases in which it was performed.
  • Combination of thrombocytopenia (platelets lt 100)
    and hyperbilirubinemia (bili gt 18 IU/ml) useful
    predictive markers of malaria 23/23 patients
    with both abnormalities had positive malaria

Fever in the Returning Traveler Approach
  • Evaluation should focus on 3 basic questions
  • What infections are possible given where the
    patient has lived or traveled and the time when
    exposures may have occurred?
  • Which of these infections is more probable given
    the patient's clinical findings and potential
  • Which of these infections is treatable or
    transmissible or both?

Fever in the returning traveler History
  • Time of onset of various signs and symptoms
  • Dates of travel
  • Mode(s) of transportation, stop-overs
  • Duration of stay
  • Accommodations, activities and exposures
  • Information about the host, including underlying
    medical conditions, preparation for travel
    (vaccinations, precautions, prophylaxis)
  • Establish if patient has visited malaria-endemic
    areas, especially during the past 12 months. Both
    the location and time of travel are important.
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Fever in the returning travel Initial Evaluation
  • Identify special risk factors, exposures, or
    focal findings that will help to focus the
  • Thorough physical examination
  • special attention for skin lesions,
    lymphadenopathy, retinal or conjunctival changes,
    enlargement of liver or spleen, genital lesions,
    and neurologic findings
  • Markers on physical examination or screening
    laboratory studies can help point to more
    probable diagnoses

Fever in the returning travel Initial Evaluation
  • CBC with differential, liver enzymes, blood
    cultures, thick and thin blood smears for
    malaria, and chest x-ray.
  • Additional studies depend upon exposures and
    other factors.
  • Tests for malaria should be carried out urgently
    (same day) in persons who may have falciparum
    malaria. Blood smears should be repeated if the
    initial smears are negative.

Fever in the returning traveler
  • Patients with unrevealing initial w/u but with a
    history of recent travel to a tropical or
    developing country must be evaluated for possible
    malaria, typhoid fever (even after receipt of
    typhoid vaccine), and rickettsial infections, all
    of which are treatable and relatively common
    causes of fever in returned travelers.
  • Patients with dengue fever may also have a
    similar clinical presentation.

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Case TC
  • Diarrheal illness while traveling followed by
    fever, malaise, cough
  • Laboratory evidence of bandemia, hepatitis
  • CXR with diffuse nodular densities and
    interstitial opacities

Case TC Differential Diagnosis Revisited
  • Malaria
  • Typhoid fever
  • Hepatitis
  • Rickettsial disease
  • Endemic mycosis
  • Etc.

Typhoid Fever
  • Caused by Salmonella typhi, or Salmonella
    paratyphi A, B, or C
  • Typically presents as a febrile illness 5-21 days
    after ingestion of the causative microorganism in
    contaminated food or water.
  • Incubation period and inoculum needed to cause
    disease vary depending upon host factors such as
    age, gastric acidity, and immunologic status.
  • Symptom complex includes sustained fever,
    malaise, abdominal tenderness, and
    hepatosplenomegaly. Pneumonia more common in
  • Diagnosis stool culture, blood culture
  • Treatment TMP/SMX, cipro, azithro

Hepatitis A
  • Fecal oral transmission
  • Incubation period averages 30 days (range 15 to
    49 days)
  • Can vary in severity from a mild flu-like illness
    to fulminant hepatitis. Typically, abrupt onset
    of prodromal symptoms including, fatigue,
    malaise, nausea, vomiting, anorexia, fever, and
    right upper quadrant pain progressing to
  • Diagnosis hepatitis A serologies
  • Treatment self-limited

Rickettsial Disease
  • Endemic typhus
  • louse-borne, exanthematous disease caused by
    Rickettsia prowazekii
  • Rare Burundi, Rwanda, Ethiopia, and in a few
    remote rural regions of the mountains of South
    and Central America
  • Symptoms Fever 100, HA 91-100, tachypnea 97,
    chills 82, rash 64, abdominal tenderness 60,
    cough 38, nausea 32
  • Diagnosis serologic
  • Treatment of choice doxycycline

Case TC
  • Further refine differential?
  • Empiric therapy?

Case AT
  • Presented to the ED with Case TC with nearly
    identical complaints-- development of
    n/v/diarrhea on final day of trip followed by
    fever, HA, malaise, non-productive cough 1 week
    prior to presentation
  • Had been seen in ED 4 days earlier for fever, HA.
    LP (-).

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Additional Case History
  • Two girls report that all members of the trip
    group had developed diarrheal symptoms and now
    most were experiencing fever, malaise and
  • Entire group placed on ciprofloxacin empirically
    for travelers diarrhea 1/22 (Wed) with azithro
    added 1/24 (Fri) after one group members stool
    cx returned Campylobacter

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Epidemic Illness in the Returning Traveler
Public Health Dispatch Update Outbreak of Acute
Febrile Respiratory Illness Among College
Students --- Acapulco, Mexico, March 2001 MMWR
  • Acute febrile respiratory illness characterized
    by fever, chills, dry cough, chest pain, and
    headache noted among college students who
    traveled to Acapulco during spring break, March
  • 44 colleges in 22 states and the District of
    Columbia reported 229 students with consistent
  • Initial laboratory testing indicated that most
    students had histoplasmosis
  • Exposure presumed secondary to hotel construction

Cave-Associated Histoplasmosis -- Costa Rica.
MMWR 37(20)312-3.
  • Outbreak of histoplasmosis among a group of
    university students who entered a cave in Santa
    Rosa National Park, Guanacaste Province, Costa
    Rica, January 1988.
  • Cave inhabited by about 500 bats, including three
    species of fruit bats and one species of vampire
  • Cave consisted of two entrances to a single
    chamber 20 x 75 x 5 feet in size. Bat guano
    covered the floor of the cave, and the ground was
    noted to be exceptionally dry for the season.

Cave-Associated Histoplasmosis -- Costa Rica.
MMWR 37(20)312-3.
  • 17 students entered the cave to observe the bats
    and photograph a small boa constrictor feeding on
  • Students were in the cave an average of 26
    minutes (range, 3-90 minutes).
  • 15/17 (88) became acutely ill within 9-24 days
    (mean, 14.4 days) 12 remained ill 14 days after
    onset of symptoms.
  • One student, who did not enter the cave, did not
    become ill.

Cave-Associated Histoplasmosis -- Costa Rica.
MMWR 37(20)312-3.
  • Signs and symptoms among the 15 ill persons
  • fever (93)
  • headache (87)
  • cough (80)
  • dyspnea (80)
  • chest pain (73)
  • myalgia (53)
  • Two patients were hospitalized all recovered
    without antifungal treatment.

Cave-Associated Histoplasmosis -- Costa Rica.
MMWR 37(20)312-3.
  • CXR obtained for 12 of the 15 patients 10 had
    bilateral diffuse fluffy nodular parenchymal
  • Late acute-phase and early convalescent-phase
    serum specimens (3 and 5 weeks after cave
    exposure) and urine specimens (5 weeks after
    exposure) were obtained from all 15 patients.
  • 12/15 patients had evidence of histoplasmosis by
    complement fixation test, immunodiffusion test,
    or urinary antigen detection test.

Valdez H, Salata RA. Bat-associated
histoplasmosis in returning travelers case
presentation and description of a cluster. J
Travel Med 1999 Dec 6(4)258-60.
  • Cluster of cave-associated acute histoplasmosis
    that occurred in college students returning from

Lottenberg et al. Pulmonary histoplasmosis
associated with exploration of a bat cave. Am J
Epidemiology 1979 Aug 110(2) 156-61.
  • 29 members of a church-sponsored youth group
    explored north-central Florida cave.
  • 23/29 later became ill with c/o of cough, fever,
    sweats, chest discomfort, and dyspnea on
    exertion. An 18yo female and an 18yo male
    required hospitalization and later died.
  • Histoplasmin skin tests in 18 of 24 tested.
    Serum for complement fixation (CF) in 12 of 26.
    Testing of area residents revealed a low
    incidence of skin test and CF positivity (7 and
    0, respectively).
  • At the time, the largest reported outbreak of
    acute pulmonary histoplasmosis associated with

Bat-cave associated histoplasmosis
  • Skin test surveys show that the infectious agent
    is present worldwide in the areas between 45
    degrees north and 30 degrees south of the
  • Clusters of cases may occur because of the
    disturbance of soil contaminated with H.
    capsulatum, or by visiting bat caves.
  • Cave-associated histoplasmosis has been reported
    from the Americas, Africa, Oceania, and Africa.
    Recently, cave-associated histoplasmosis has been
    reported in travelers returning from Costa Rica
    and Peru.

Bat-cave associated histoplasmosis
  • Advice regarding histoplasmosis prevention should
    be given to travelers planning to visit
    bat-infested caves
  • Histoplasmosis should be considered in the
    differential diagnosis of febrile illness in
    returning travelers with a history of
    epidemiologic or geographic exposure.

Cairns L et al. Outbreak of coccidioidomycosis
in Washington state residents returning from
Mexico. CID 2000 30 61.
  • Seattle, Washington July 1996
  • Flu-like, rash-associated illness in a 126 member
    church group, many adolescents.
  • Group had recently returned from Tecate, Mexico,
    where members had assisted with construction
    projects at an orphanage.

Cairns L et al. Outbreak of coccidioidomycosis
in Washington state residents returning from
Mexico. CID 2000 30 61.
  • After 1 member dxd with coccidioidomycosis,
    Washington State Dept. of Health identified 21
    serologically confirmed cases of
    coccidioidomycosis (minimum attack rate, 17).
  • 20 cases (95) occurred in adolescents, and 13
    patients (62) had rash.
  • 16 symptomatic patients saw 19 health care
    providers 1 health care provider correctly
    diagnosed coccidioidomycosis.
  • Coccidioides immitis isolated from soil samples
    from Tecate by use of the intraperitoneal mouse
    inoculation method.

Panacakal et al. Fungal Infections in the
Returning Traveler. CID 2002 Nov 351088-95.
  • GeoSentinel, communications and data collection
    provider network consisting of 25 tropical and
    travel medicine clinics throughout the world
  • Recorded 32 cases of systemic mycosis from
    4/1998-3/2002 23 histoplasmosis, 3
    coccidioidomycosis, 3 cryptococcosis, 2
    blastomycosis, 1 paracoccidioidomycosis

Geographic distribution of Histoplasma capsulatum
(gray) and Coccidioides immitis (black)
infections in the Americas
Clinical course TC, AT
  • Admitted NCBH
  • Placed empirically on ceftriaxone, doxycycline
  • Remained febrile to 102, 103
  • Some symptomatic improvement with increase
    appetite, energy

Clinical course TC, AT
  • Laboratory studies unrevealing including
  • routine blood, urine and stool cxs (-)
  • stool OP (-)
  • stool Giardia Ag (-)
  • stool AFB (-)
  • acute and chronic hepatitis panels (-)

Clinical course TC, AT
  • TC underwent bronchoscopy 1/29/03
  • BAL protected brush with lt 1000 org/ml, routine,
    viral, fungal, AFB cultures all (-) to date
  • Histoplasmosis, leptospira Ag and Ab pending

  • TC histoplasmosis Ag
  • Serum 2.6
  • Urine 17.43 high
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