Case Conference February 3, 2003

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Case ConferenceFebruary 3, 2003

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

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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
  duration

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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

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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

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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
  Cristobal
• 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.

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Case TC History

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

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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

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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

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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

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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

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Next step?

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

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Fever in the Returning Traveler

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

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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.

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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
  traveler)
• 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

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Hill DR. Health problems in a large cohort of
Americans traveling to developing countries. J
Travel Med 2000 7259.

• DURING TRAVEL
• 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

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Hill DR. Health problems in a large cohort of
Americans traveling to developing countries. J
Travel Med 2000 7259.

• ON RETURN
• 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.

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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

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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

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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
  admission.
• Final diagnosis as recorded on the discharge
  summary by the attending physician and results of
  any relevant laboratory or radiological
  investigations were recorded.

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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
  helminths
• 3 HIV

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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
  films.

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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
  exposures?
• Which of these infections is treatable or
  transmissible or both?

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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.
• http//www.cdc.gov

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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
  work-up.
• 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

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Fever in the returning travel Initial Evaluation

• LABORATORY STUDIES
• 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.

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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

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Case TC Differential Diagnosis Revisited

• Malaria
• Typhoid fever
• Hepatitis
• Rickettsial disease
• Endemic mycosis
• Etc.

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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
  children.
• Diagnosis stool culture, blood culture
• Treatment TMP/SMX, cipro, azithro

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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
  jaundice.
• Diagnosis hepatitis A serologies
• Treatment self-limited

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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

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Case TC

• Further refine differential?
• Empiric therapy?

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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
  cough
• 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
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Public Health Dispatch Update Outbreak of Acute
Febrile Respiratory Illness Among College
Students --- Acapulco, Mexico, March 2001 MMWR
50(18)359-360.

• 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
  2001.
• 44 colleges in 22 states and the District of
  Columbia reported 229 students with consistent
  symptoms/syndromes
• Initial laboratory testing indicated that most
  students had histoplasmosis
• Exposure presumed secondary to hotel construction

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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
  bats.
• 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.

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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
  them.
• 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.

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Cave-Associated Histoplasmosis -- Costa Rica.
MMWR 37(20)312-3.

• Signs and symptoms among the 15 ill persons
  included
• fever (93)
• headache (87)
• cough (80)
• dyspnea (80)
• chest pain (73)
• myalgia (53)
• Two patients were hospitalized all recovered
  without antifungal treatment.

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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
  infiltrates.
• 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.

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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
  Ecuador.

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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
  spelunking.

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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
  equator.
• 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.

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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.

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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.

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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.

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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

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Geographic distribution of Histoplasma capsulatum
(gray) and Coccidioides immitis (black)
infections in the Americas
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Clinical course TC, AT

• Admitted NCBH
• Placed empirically on ceftriaxone, doxycycline
• Remained febrile to 102, 103
• Some symptomatic improvement with increase
  appetite, energy

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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 (-)

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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

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LATE BREAKER!

• TC histoplasmosis Ag
• Serum 2.6
• Urine 17.43 high