FEVER IN TRAVELERS

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FEVER IN TRAVELERS

• Joseph G. Timpone, MD
• Associate Professor of Medicine
• Division of Infectious Diseases

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Case 1

• A 30 y.o male presents to the ER with fever, H/A,
  retro-orbital pain and severe myalgias/arthralgias
  . His physical exam reveals T40oC P120 BP
  110/80 and a diffuse macular rash on his trunk.
  Labs WBC 2.1 HCT 42 PLTs 75,000 AST 80 ALT 90 PT
  17.0 PTT 65. The pt returned from a business trip
  to Haiti 3 days ago.

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Additional Labs

• Blood CX (-)
• HIV AB (-)
• Thin smear (-)

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The most likely cause of his illness is

• A GM (-) diplococci
• A GM (-) rod
• A Flavivirus
• A Retrovirus
• A Protozoan

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Dengue Fever

• Member or Flaviviridae
• DEN V-1, DEN V-2, DEN V-3, DEN V-4
• Aedes Aegypti
• Urban/Tropical areas
• Dengue fever, Dengue Hemorrhagic fever, Dengue
  shock syndrome

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Dengue Fever Clinical

• Abrupt onset of Fever, H/A, Retro-Orbital pain,
  severe myalgias, Arthralgias
• Scalitiniform or Macular rash on trunk Petechiae
• () Tourniquet test
• Leukopenia, Hemoconcentration, Thrombocytopenia,
  prolonged PT/PTT, Abnormal LFTs
• Severe capillary leak

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Dengue Fever Diagnosis and Treatment

• Dengue fever serology
• Increases risk of DHF and DSS with prior
  infection
• Infection with DEN V-2 more severe
• Supportive care

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Case 2

• A 29 y.o. male presents to the ER with fevers,
  H/A, Myalgias, Nausea and vomiting. The pt
  returned from a trip to S.E.A where he camped and
  trekked. He reports wading through stagnant water
  and being bitten by lots of insects. He initially
  had fevers for 5 days which resolved over 48
  hours but, then recurred.

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• Phys. Exam T 39.5oC P 120 BP 100/60 Conjuctival
  suffusion, petechial rash, jaundiced
  hepatomegaly.
• Labs WBC 10.0 HCT 39 PLTS 40,000 Bili 5.0 AST
  100 ALT 120 BUN/CR 40/2.5

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The most likely diagnosis is

• Brucellosis
• Plague
• Melioidosis
• Leptospirosis
• Meningococcemia

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Leptospirosis

• Leptospira Interrogans (Spirochete)
• Worldwide distribution-Tropical areas (Hawaii)
• Water contaminated with rodent urine
• Incubation 5-14 days
• Causes endothelial/vascular injury

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Leptospirosis Clinical

• 2 types
• - Anicteric-mild flu-like illness
• - Weil disease
• Weil Disease Fever 5-7 days afebrile-fever
  (spirochetemic/ immunologic phase)
• - Fever, conjunctival suffusion petechial
  rash
• - Paraspinal/ calf myalgias
• - DIC, Abnormal LFTs, ARF
• - Meningitis

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Leptospirosis Diagnosis and Treatment

• Culture Urine (Highest yield) Fletcher media
• MAT serology
• Doxycycline
• IV penicillin g

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Case 3

• A 23 y.o. female PCV from Africa presents with a
  1 week Hx/O fevers and H/A. She is brought to the
  ER by her parents who noted that she was
  confused. Her T39 and she is unresponsive. CT of
  head (-). CSF 7 WBCs. Labs WBC 4.5 HCT 30 PLT
  50,000 LDH 300 AST 90 ALT 50 T. Bili 2.0 BUN/Cr
  35/2.8

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The most appropriate initial therapy would be

• Ceftriaxone Vancomycin
• Imipenem Gentamicin
• Amphotericin B
• Quinine Doxycycline
• Quinidine I.V.

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Malaria

• P. falciparum, P. vivax, P.ovale, P. malariae
• Sub-Saharan Africa, S.E.A., Latin America, Middle
  East
• Fever in Travelers Malaria, Typhoid Fever,
  Dengue Fever, Meningococcemia
• Fever, H/A, rigors, photophobia, HSM, hemolytic
  anemia, thrombocytopenia, hyerbilirubinemia,
  hypoglycemia, ARF
• P. falciparum ARDS, Cerebral Malaria
• Prophylaxis Mefloquine, Doxycycline,
  Proguanil/Atovaquone Chloroquine in Mexico,
  Central America, Caribbean
• Treatment P. falcip. - QuinineDoxycycline
  (Quinidine for severe cases)

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Case 4

• A 28 y.o. male PCV has returned from a two year
  assignment in Africa and presents to the ER with
  a 3 day hx/o fever, nausea, vomiting, RUQ pain.
  He denies any diarrhea. Exam reveals T38.5, and
  RUQ tenderness.
• WBC 15,000, AST 80, ALT 90, ALK PHOS 250.

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The most appropriate diagnostic study would be

• Stool for O and P
• Blood cultures
• Aspiration of the liver lesion
• Serology
• ERCP

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Amebiasis

• Entamoeba histolytica causative agent
• 90 of infections asymptomatic, remaining 10
  produce spectrum of clinical syndromes
• Acquired by ingestion
• 10 of world's population is infected
• Third most common cause of death from parasitic
  disease (after schistosomiasis and malaria)
• Invasive amebiasis have unique virulence
  properties compared with noninvasive
• Entamoeba dyspar non-pathogenic

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Intestinal Amebiasis

• Asymptomatic cyst passage most common
• 10 develop invasive disease
• Symptomatic colitis develops 2 to 6 weeks after
  the ingestion of infectious cysts
• Stools contain little fecal material and consist
  mainly of blood and mucus- often hem
• Rare intestinal forms
• Fulminant intestinal colitis (malnourished,
  steroids, pregnancy, young)
• Toxic megacolon
• Chronic amebic colitis (confused with IBD)
• Ameboma

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Amebic Liver Abscess

• Always preceded by intestinal colonization
• 95 occur within 5 months of exposure
• Median 3 months
• Majority present with fever and RUQ pain
• Only 1/3 of patients have active diarrhea
• 10 to 15 present only with fever
• Complications of amebic liver abscess
• Pleuropulmonary involvement (20 to 30 )
• Rupture into peritoneum
• Rupture into pericardium

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Diagnostic Tests

• Stool examinations
• Positive test for heme
• Paucity of WBCs
• Important to examine 3 fresh stools
• Confirms diagnosis in 75 to 95 of cases
• Cysts must be differentiated from Entamoeba
  hartmanni, Entamoeba coli Endolimax nana
• Serologic tests
• 70 positive with colitis or 90 positive for
  abscess
• Suggest active disease because serologic findings
  usually revert to negative within 6 to 12 months
• Noninvasive imaging of the liver
• Stool antigen for E.Histolytica

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Amebiasis Treatment

• Metronidazole (active disease)
• Asymptomatic cyst
• - Paronomycin
• - Diloxanide Furoate (luminal agents)

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Case 5

• A 40 y.o. male from India is visiting his family
  in the U.S. He presents with a 3 wk hx/o fevers,
  H/A, and fatigue. He also complains of abdominal
  pain and hematochezia in the ER he is noted to
  have BRBPR and is hypotensive. His initial HCT
  21.

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The most likely cause of his GI bleed is

• S. Stercoralis
• P. Falciparum
• E. Histolytica
• S. Typhi
• C. Jejuni

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Typhoid Fever

• Caused By Salmonella Enterica Serotype Typhi
• Associated With Poor Sanitation/water
• Estimated Incidence
• 16 Million Cases With 600,000 Deaths
• 198/100,000 Mekong Delta, Vietnam
• 980/100,000 Delhi, India
• 400 Cases/year In U.S. (Travelers)

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Salmonella Typhi Pathogenesis

• Ingestion 103 -106 Organisms
• Increased Risk Achlorhydria, Gastrectomy, H2
  Receptors PPIs
• Small Bowel-gt Peyers Patches -gt
  Lymphatics-gtBloodstream
• Disseminates to RES Liver, Spleen, Bone Marrow

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Typhoid Fever Clinical Presentation

• Incubation Period 7 14 Days (Range 3-60 Days)
• Symptoms Fevers, Chills, Malaise, Myalgias, Dull
  Frontal H/A
• GI Anorexia, Nausea, Abdominal Discomfort,
  Constipation More Common Than Diarrhea
• Other Sx Dry Cough, Apathetic Affect, Confusion
  Convulsions

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Typhoid Fever Physical Findings

• Low Grade to Sustained High Fever (gt 39oC)
• Relative Bradycardia (Rare)
• Rose Spots 2-4 mm Pink (Macules on the Abdomen
  (5-30))
• Hepatomegaly (AST/ALT 2-3x ULN)
• Splenomegaly
• Hematologic CBC Often Normal Can Have
  Leukopenia, Anemia, Thrombocytopenia

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Typhoid Fever Complications

• Complications Occur in 10 15
• GI Bleeding Most common (10) -gt Occurs From the
  Necrosis of Peyers Patch into a Vessel. (Severe
  GI Bleeding in 2)
• Intestinal Perforation Ileo-cecal Perforation (1
  - 3)

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Typhoid Fever Neurologic Complication

• Apathetic Affect
• Agitation, Delirium, Confusion Coma (Rare)
  Impairment of Coordination
• Typhoid Encephalpathy Meningitis
• Incidence of Neuropsychiatric Finding Varies
• 10-40 Hospitalized pts. in Indonesia and Papua,
  New Guinea
• lt2 in Pakistan and Vietnam

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Typhoid Fever Diagnosis

• Blood Cultures Sensitivity (60 - 80)
• High Volume BLD Cx (15 ml)
• Best Yield During 1st Week of Illness
• Decreased Yield in the Setting of Antibiotics
• BM Aspirate Cultures Sensitivity (80 - 95)
• Higher Organism Burden
• Can Be () in the setting of antibiotics
• Stool cultures Sensitivity 30
• Widals Test, Vi Agglutination, DNA Probe, PCR

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Typhoid Fever Treatment

• Fluoroquinolones 96 Effective (lt 2 Fecal
  Carriage or Relapse)
• Total Duration 10 - 14 Days
• Treatment of Quinolone Resistant Strains is 90 -
  95 effective if Therapy is Given For at Least 7
  -10 Days carriage Rate is 20
• 3rd Generation Cephalosporins (Ceftriaxone,
  Cefixine, Cefotaxine)
• 5 - 10 Failure Rate Relapse Rate 3 - 6
• Fecal Carriage Rate lt 3

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Typhoid Fever Treatment

• Azithromycin 95 Effective Relapse Rates and
  Carriage lt 3 5 - 7 Days of Therapy
• Chloramphenicol, Amoxicillin, TMP-SMX
• 95 Effective
• 1 - 7 Relapse Rate
• 2-10 Fecal Carriage Rate

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Typhoid Fever Relapse

• Relapse Occurs in 5 - 10 of Pts. 2 - 3 Wks.
  After Initial Symptoms
• Pts. Relapse With the Identical Organism With the
  Same Antibiotic Susceptibility Pattern
• 10 Untreated Pts. Excrete S. Typhi in Stool for
  up to 3 Mos. 1 - 4 Have Prolonged Carriage (1
  year)
• Increased Carriage Risk Females, Elderly,
  Cholelithiasis, Co-infection With Schistosomiasis

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Case 6

• A 50-yr old female presents with a 4-week hx/o
  lowgrade fevers and back pain.
• She was visiting her extended family in Sicily
  during the Christmas holidays and she
  participated in the towns tradition of the live
  animal nativity.
• As part of that tradition, she ate raw,
  unpasteurized cheeses.

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Brucellosis Etiology

• Small, aerobic gram (-) coccobacilli
• Catalase () oxidase (), urease (), H2S
  production
• May require CO2 enrichment for growth
• Fastidious organisms - may not grow in routine
  blood cultures
• Bi-Phasic (Ruiz-Castaneda) media
• Cultures held for 30 days

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Brucellosis Species

• Six species with multiple biotypes
• B. abortus - cattle
• B. melitensis - goats and sheep
• B. suis - swine
• B. canis dogs
• B. neotomae - desert rats
• B. ovis rams
• B. maris marine mammals

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Brucellosis Transmission

• Inoculation through abrasion of skin or
  conjunctivae (contact with animal hides and
  secretions)
• Inhalation of infectious aerosols (lab exposure)
• Ingestion via GI tract (raw or unpasteurized
  dairy products and cheeses)

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Brucellosis Epidemiology

• Brucellosis exist worldwide
• Mediterranean basin, Arabian gulf, Indian
  subcontinent, Mexico, Central South America
• Approximately 100 case/year reported to CDC most
  cases from California and Texas
• Livestock workers, farmers, ranchers, abattoir,
  travelers, veterinarians, lab exposure

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Brucellosis Clinical

• Symptoms nonspecific
• Insidious 2 - 3 weeks after exposure
• Fevers, sweats, anorexia, abdominal pain, back
  pain, fatigue, depression
• Lymphadenopathy and hepatosplenomegaly
• Undulant Fever

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Brucellosis Complications

• Osteoarticular up to 40 of cases
  sacro-ileitis, arthritis, spondylitis,
  osteomyelitis SI most common and can be dxd by
  CT bone scan in 90 cases
• Gastrointestinal anorexia, Wt. Loss, n/v, abd.
  Pain
• Hepatic LFTs only mildly elevated granulomas
  mononuclear cell infiltrate

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Brucellosis Complications

• Cardiovascular lt 2 of cases endocarditis
• Neurologic lt 2 of cases meningitis
  depression CVA
• Genitourinary epididymo-orchitis
• Pulmonary Pneumonitis

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Brucellosis Diagnosis

• Bacteriologic
• Blood isolated in 15-70 of cases
• Bone marrow aspirate higher yield than blood
• Incubation time 30 days
• BACTEC isolation automated biochemical I.D. (b.
  melitensis confused with Moraxella/haemophilus)
• PCR

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Brucellosis Diagnosis

• Serologic
• Serum Agglutination Test (SAT)
• IgM () _at_ 1 week
• IgG () _at_ 2 weeks
• Titers disappear at 2 years
• SAT () gt 1160
• False (-) prozone effect
• False () vibrio, tularemia, yersinia

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Brucellosis Treatment

• Doxycycline (6 weeks) Streptomycin (3 weeks)
• lt 5 relapse rate
• Doxycycline Rifampin (6 weeks)
• TMP/SMZ (6 weeks, high relapse rate)
• Ofloxacin Rafampin (6 weeks)
• Endocarditis/Meningitis 6-9 mos.

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Fever in Travelers

• Malaria (always think malaria)
• Dengue Fever (mosquitos, urban settings)
• Typhoid Fever (food and water)
• Leptospirosis (water exposure, adventure
  travelers)
• Brucella (unpasteurized dairy products)
• MTB (usually immigrants)
• Amebiasis
• Meningococcemia
• Fever/Diarrhea E.coli, salmonella, shigella,
  campylobacter (15 with fever)
• Tick-borne illnesses R. africae, R. conorii

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ATBF Clinical

• Mild clinical illness
• Headache, Fever, Myalgias
• Solitary or multiple eschars
• Regional lymphadenopathy
• Rash Maculo-Papular or vesicular (may be
  overlooked)
• Treatment Doxycycline (5-7 days)