Jungle Fever

1
Jungle Fever

• Phillip D. Levy, MD, MPH
• Associate Professor of Emergency Medicine
• Wayne State University/Detroit Receiving Hospital

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Statement of Disclosure

• I have no financial relationships relevant to
  this presentation

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Purpose of This Talk

• To provide a workable approach to the evaluation
  of jungle fever
• Epidemiology
• Symptomatology
• To discuss basic principles of disease management
• Pathophysiology
• Treatment
• Prevention

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Focus Will Be Microbiology Not Sociology
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Why Bother ?

• Some form of illness reported in 20-70 of
  travelers 1,2
• Majority mild
• Up to 8 seek medical care
• 0.01-0.1 require medical evacuation
• Overall mortality rate low ( 0.001)
• 3 experience fever

1 Ryan et al. NEJM 2002347505-16. 2 Freedman et
al. NEJM 2006354119-30.
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From Freedman et al. NEJM 2006354119-30.
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From Freedman et al. NEJM 2006354119-30.
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Potential Routes of Exposure

• Inhalational
• Ingestion
• Fecal-oral
• Infected foods (beef, pork, fish, snails, crabs,
  crayfish) or soil
• Intravenous
• Transdermal
• Vector mediated
• Mosquitoes, ticks, flies, mites, etc
• Contact with contaminated soil or water

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Aedes aegypti
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Anopheles gambiae
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General Approach

• Historical clues
• Location and duration of travel
• Complete itinerary important
• Incubation period
• Associated symptoms
• Diarrhea, abdominal pain
• Cough, dyspnea
• Rash, skin lesions
• Arthralgias and myalgias
• Mental status changes

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Initial Work-Up

• Blood smears
• Thin and thick necessary
• Giemsa stain preferred over Wrights stain
• Repeat testing Q 4-12h recommended until
  diagnosis is established
• Blood cultures

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Initial Work-Up

• Complete blood count
• Eosinophilia
• Stimulated by IL-5 production
• Highest values seen with migratory tissue
  helminthes
• NOT seen with most protozoal infections
• Isospora and Dientamoeba are exceptions
• Anemia
• Thrombocytopenia

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Further Lab Evaluation

• CSF analysis essential with potential CNS
  involvement
• Urinalysis and culture
• Fecal sampling
• Fecal leukocytes
• Limited sensitivity
• Stool cultures, especially in pediatric patients
• Stool O and P

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Serology and Molecular Tests

• Availability often limited
• May have to contact CDC for selected organisms
• Commercial kits exist for some protozoa
• Cross-reactivity may limit full diagnostic
  utility
• Sensitivity gtgtgt specificity
• Of limited value in individuals residing in
  endemic regions

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Case 1
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Ive Got Jungle Fever

• 32 yo female presents to the ED with a rash,
  fever, headache, and bodyaches
• Returned to the US 2 days ago after a 3 week trip
  to East Africa
• BP 110/70 HR 130 RR 20 T 40 C
• Diffuse lymphadenopathy
• Rash

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By the Numbers, Malaria is Most Likely1
1 Leder et al. Clin Infect Dis 2004391104-12.
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Malaria

• Plasmodium species falciparum malariae, vivax,
  ovale
• Cause of fever in 40 of those with travel to
  endemic regions
• For Africa incidence 2 per month
• Onset may be delayed (gt 2 months) in up to 36 1
• Majority (84) due to P. vivax
• 67 took appropriate chemoprophylaxis

1 Schwartz wt al. NEJM 20033491510-6.
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Malaria Distribution
From Baird, J. K. NEJM 20053521565-1577.
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Image from http//www.itg.be/itg/DistanceLearning
/LectureNotesVandenEndenE/imagehtml/ppages/CD_1038
_061c.htm
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Dengue Fever

• 50-100 million annual cases worldwide
• 12,000 deaths
• 4 different viral serotypes
• Type 2 most virulent
• Incubation period 4 7 days
• Most manifest typical flu-like illness
• Severe myalgias (aka break-bone fever)
• 50 develop lymphadenopathy with maculopapular or
  petechial rash

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Dengue Fever Distribution
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Dengue Hemorrhagic Fever

• Rare among travelers
• Secondary manifestation
• Results from immune system priming by prior
  infection with alternative strain
• Produces enhancement of infection
• Characterized by DIC-like picture
• Shock syndrome may develop with induction of
  vascular permeability

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Arthropod-borne Viruses

• Flaviviridae
• Yellow fever
• Togaviridae
• Chikungunya
• O'Nyong-nyong fever
• Bunyaviridae
• Crimean-Congo fever
• Rift valley fever

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Related Non-Arboviruses

• Arenaviridae
• Lassa fever
• Bolivian, Argentinean, Venezuelan HF
• Bunyaviridae
• Hantavirus
• Filoviridae
• Ebola, Marburg HF
• Rhabdoviridae
• Rabies virus

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Typhus

• Louse borne rickettsial infection
• Epidemic (R. prowazekii)
• Murine (R. typhi)
• Incubation period 7-14 days
• High fevers, headache, confusion, photophobia,
  vomiting, rash
• Fatal in 10-60
• Symptoms may reoccur years later
• Brill-Zinsser disease
• Easy to treat with doxycycline

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Other Rickettsial Infections

• Spotted fevers (tick borne)
• African tick-bite fever (R. africae)
• Mediterranean (R. conorii)
• Scrub typhus (mites)
• Orientia tsutsugamushi
• Painless eschar at innoculation site
• Incubation 5-7 days
• Fever, headache, myalgias, rash, lymphadenopathy
• Treatment doxycycline

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Relapsing Fever

• Spirochete infection
• Tick borne (Borrelia spp.)
• Louse borne (Borrelia recurrentis)
• Incubation period 2-18 days
• Fever (chill and flush), myalgias, arthalgias,
  rash
• Episodes last 2-7 days
• Cyclical recurrence every 4-14 days
• Up to 10 times without treatment
• Also treat with doxycycline
• Jarisch-Herxheimer reaction in 50

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Typhoid FeverSalmonella typhi

• 74 of cases in US linked to travel 1
• Incidence 3-30 per 100,000/month
• Highest risk regions
• India
• Pakistan
• Mexico
• Bangladesh
• The Philippines
• Haiti

1 Steinberg et al. Clin Infect Dis
200439186-91.
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Typhoid Fever

• Septicemia not gastroenteritis
• Endotoxin-mediated SIRS
• Greater inoculation shorter incubation
• Symptoms include fever, abd. pain, constipation
• Relative bradycardia and rose-spots
• Dx stool, blood or bone marrow culture
• Serologic test available, but less reliable

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Tsetse Fly Glosinna sp.
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African Trypanosomiasis

• Trypanosomal chancre at bite site
• Clinical illness divided
• Stage I Hemolymphatic only
• Stage II CNS invasion (sleeping sickness)
• Early diagnosis by blood smear or biopsy
• Found later in CSF
• LP essential for ALL cases
• Repeat at 2-4 months to assess treatment response
  

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African Trypanosomiasis

• Trypanosoma brucei
• T. brucei rhodesiense (East Africa)
• Fulminant course
• T. brucei gambiense (West Africa)
• Indolent course
• Only 30 cases reported in US since 1967 1

1 Harris et al. NEJM 20023462069-76.
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African Trypanosomiasis Distribution
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American Trypanosomiasis(Chagas Disease)

• Trypanosoma cruzi
• Reduviid bug
• Chagoma at bite site
• Fever, lymphadenopathy, hepatosplenomegaly
• Chronic myocarditits and dysrrythmias
• Megaesophagus/colon
• Blood smear, xenodiagnosis or serology
• Treatment nifurtimox
• 2-2.5 mg/kg po qid x 90-120 days
• Not effective for chronic disease

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Reduviid Bug Triatominae spp.
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Other Conditions (not necessarily jungle related)

• Meningococcal meningitis
• Endemic in certain regions of Africa
• Fatal if not treated.
• Preventable by vaccination

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Case 2
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Shes Got Jungle Fever

• A 27 yo female presents to the ED with fever,
  abdominal pain and intermittent diarrhea
• Works for the Peace Corps
• Just returned from Brazil after a 2 year
  assignment
• BP 115/70 HR 120 RR 26 T 39.6º C
• Abd. distended with RUQ tenderness
• Stool heme (-)

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Viral Hepatitis 1

• Hepatitis A most frequent
• Fecal-oral
• Incubation period 15-45 days
• Risk 300 per 100,000/month
• 5 7 times higher in rural travelers
• Vaccine confers immunity 95 at 4 weeks
• No vaccine IVIG (0.2 ml/kg IM) if 14 d
• Hepatitis B, C and E may also be contracted

1 Ryan and Kain NEJM 20003421716-25.
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Hepatitis A Distribution
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Schistosomiasis (Blood Flukes)

• Maculopapular dermatitis at entry site
• Katayama fever - acute febrile illness after
  14-84 day incubation 1
• Immune complex mediated
• May manifest interstitial pneumonitis
• Accelerated process with concurrent HBV or HCV
• Chronic symptoms due to granulomas and fibrotic
  reaction to embedded eggs

1 Ross et al. NEJM 20023461212-20.
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Schistosomiasis

• Gastrointestinal infection
• Schistosoma mansoni, japonicum
• Africa, South America, Far East
• Urinary tract infection (Bilharzia)
• Schistosoma haematobium
• Contracted by with swimming in infected water
• Lake Malawi, Zambese River, Lake Kariba
• Middle East, Africa

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Schistosomiasis Life Cycle

• Cercarial skin penetration
• Hematogenous spread to portal circulation
• Maturation into adult worms in liver
• Adult worms migrate to mesenteric or bladder
  venuoles and produce eggs
• Migration produces intense pruritis
• Eggs penetrate liver parenchyma or bladder/ureter
  wall
• Also shed in feces or urine

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Schistosomiasis Distribution
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Image from http//www.itg.be/itg/DistanceLearning
/LectureNotesVandenEndenE/imagehtml/ppages/CD_1004
_028c.htm
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Stronygloidiasis

• Strongyloides stercoralis
• Larval skin penetration
• Hematogenous spread to lungs
• Swallowed to reach small intestine
• Enter mucosa, release eggs autoinfection
• Intestinal discomfort with hypomotility sepsis
  if significant bowel wall damage
• Diagnosis larvae in feces or ELISA
• Treatment Ivermectin 200 µ/kg x 2d
• Alt Albendazole or thiabendazole

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Ascariasis

• Ascaris lumbricoides
• Fecal-oral transmission
• Worms penetrate intestinal mucosa and spread to
  lungs
• Diagnosis by identification of eggs in stool
  occ. passage of worm
• Treatment Albendazole 400 mg po x 1
• Alt Mebendazole or pyrantel pamoate
• Surgical resection of bolus may be required

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Löfflers Syndrome

• Eosinophillic pneumonitis
• Migration of larval helminthes through lungs
• Larvae enter alveoli, ascend bronchial tree
  causing hypersentivity response with respiratory
  symptoms
• Worms travel back down esophagus to intestines
• Shed in stool

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Amoebiasis

• Entamoeba histolytica (worldwide)
• Fecal-oral transmission
• Ingested cysts become trophozoites
• Invade colonic epithelium, producing dysentery
• Deeper penetration into submucosa with spread via
  portal circulation
• May result in liver abscess formation
• Diagnosis
• Identification of cysts or trophozoites in stool
  sample
• Microbial analysis of abscess aspirate

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Visceral Leishmaniasis

• Leishmania donovani
• Clinical
• Initial fever, weakness, wt loss
• Delayed hepatosplenomegaly, pancytopenia
• Diagnosis
• Biopsy (spleen, bone marrow, or lymph node)
• Serology
• Skin leishmanin testing

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Sand Fly Phlebotomus and Lutzomyia spp.
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Case 3
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Weve Got Jungle Fever

• Three brothers come to be evaluated in the clinic
  where you work in northern Ghana complaining of
  groin swelling
• They report intermittent fevers, especially ay
  nighttime

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Lymphatic Filariasis

• Wuchereria bancrofti, Brugia malayi (Tropics)
• Mosquito vector transmission (Culex spp.)
• Bite releases larvae which enter lymphatic system
• Multiple bites required for infection
• Adult worms cause lymphatic inflammation/obstructi
  on
• Nocturnal microfilarial migrations
• Filarial fevers, lymphangitis, elephantitis

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Lymphatic Filariasis Distribution
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Lymphatic Filariasis

• Diagnosis by thick blood smear at night or
  filarial antigen identification
• Suspicion supported by high eosinophil counts
• Treatment Diethylcarbamazine 6 mg/kg po per day
  x 12 days
• Alternative Albendazole 400 mg PO plus
  ivermectin 400 mcg/kg po x 1 dose
• Clearance of adult worms may be problematic

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Black Fly Simulium yahense
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River Blindness

• Onchocerca volvulus
• Second leading cause of infectious blindness
• Blackfly vector transmsission
• Larvae enter subcutaneous tissue, forming
  onchocercomata
• Microfilariae migrate to eyes
• Keratitis, anterior uveitis chorioretinits
• Diagnosis by nodule or skin biopsy
• Treatment Ivermectin 150mcg/kg po semiannually

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Deer Fly Chrysops spp.
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Loiasis

• Loa loa (West and Central Africa)
• Mango or deer fly vector transmission
• Larvae enter subcutaneous tissue and mature
• Migration produces Calabar swellings and
  subconjunctival eye worms
• Encephalitis may develop (often post-treatment)
• Diagnosis by blood smear, worm isolation or
  subcutaneous biopsy
• Treatment same as lymphatic filariasis

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Case 4
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Were in Love

• A couple in their mid-40s presents to your
  clinic complaining of abdominal cramping with
  profuse watery, non-bloody diarrhea
• Just returned from a 3 week honeymoon cruise
  around the Caribbean
• Vitals signs normal
• Increased bowel sounds
• Stool heme ()

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of diarrhea
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Epidemiology 1

• Most common illness among travelers
• Experienced by 10 - 60
• 20 experience brief incapacitation
• 40 alter itineraries as a result
• Self limited in most
• Persists 2 weeks in 5 10
• Lasts gt 1 month in 1 3
• Causative organism found in 50 75

1 Ryan and Kain. NEJM 20003421716-25.
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Common Offenders 1,2,3

• Bacterial ( 85)
• E. coli ( 50)
• Campylobacter
• Shigella
• Salmonella
• Cholera
• Viral ( 10)
• Norwalk agent
• Rotavirus

• Parasitic
• Acute sx 1-5
• Chronic sx 30
• Giardia
• Cryptosporidia
• Entamoeba
• Cyclospora
• Isospora

1 DuPont and Ericsson. NEJM 19933281821-7. 2
Hoge et al. JAMA 1996275533-8.. 3 Steffen et
al. JAMA 1999281811-7.
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Bacterial Incubation Periods

• 2-6 hours
• Staph aureus
• Bacillus cereus
• Type I
• Type II ( 12h)
• 8-24 hours
• Clostridium perfringes
• Salmonella spp.

• 24-72 hours
• E. coli
• Shigella spp.
• Vibrio cholera
• 1-7 days
• Campylobacter jejuni
• Yersinia spp.

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Advice For You and Your Patients
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From Freedman et al. NEJM 2006354119-30.
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General

• Know the destination and plan prophylaxis
  accordingly !
• Avoid eating uncooked or unwashed food
• Dont eat food from street vendors
• Use bottled water for drinking and brushing teeth
• Do not use ice cubes
• Do not swim in contaminated water
• Avoid walking in soil or sand barefoot

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Insect Protection

• Skin repellents
• N,N-diethyl-3-methylbenzamide (DEET)
• Picaridin (KBR 3023)
• 2-(2-hydroxyethyl)-1-piperidinecarboxylic acid
  1-methylpropyl ester
• Piperidine derivative
• IR 3535
• 3-N-Butyl-N-acetyl-aminopropionic acid, ethyl
  ester
• p-Menthane 3,8-diole (PMD)
• Oil of lemon eucalyptus

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Which is Best?
From Fradin and Day NEJM 200234713-8.
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Picaridin As Efficacious as DEET
From Frances et al. J Med Entomol 200441414-7.
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Insect Protection

• Permethrin impregnantion of clothing
• Lasts 4 weeks with up to 6 washings
• Insecticide treated mosquito netting
• Conventional
• Dipped
• Long-lasting insecticide nets (LLIN)
• Incorporated within or bound around the fibres
• Must retain effectiveness with gt 20 washings and
  for a minimum of 3 years
• Polyethylene preferred over polyester

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Soft Power Health Malaria Outreach
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Water Purification

• Filtration highly effective
• Pore size requirements
• Parasites 1-2 microns
• Bacteria 0.2 micron
• Viruses 0.03 micron
• Boiling also sufficient
• Drinking 1 min at sea level, 3 min at altitude
• Bathing ? 5 min
• Halogenation least reliable method and should not
  be used alone

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Chemoprophylaxis

• Malaria
• Lymphatic filariasis
• Travelers diarrhea

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Malaria Chemoprophylaxis

• Impractical for residents in endemic regions
• Mefloquine most widely recommended
• 250 mg po Q week (start 1-2 weeks prior to
  travel, cont. 4 weeks after return)
• Tolerability limited by neuropsychological
  effects
• Reported incidence as high as 1/140-1/250 1
• No significant difference in adverse events
  demonstrated in any trial to date 2

1 Ryan and Kain. NEJM 20003421716-25 2 Croft et
al. BMJ 19971421-6
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Mefloquine Alternatives

• Atovaquone/proguanil 250/100 mg po QD
• Start 1-2 d prior to travel, cont. 1 week after
  return
• Doxycycline 100 mg po QD
• Start 1-2 d prior to travel, cont. 4 weeks after
  return
• Primaquine 30 mg po QD
• Start 1-2 d prior to travel, cont. 1 week after
  return
• Effective against hepatic stages of P. ovale and
  P. vivax

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Should Climbers Take Prophylaxis?
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Recommended Vaccinations

• Hepatitis A and B
• Yellow fever
• Mild adverse reaction reported in 25
• Severe viscerotropic rxn in 4 per million 1
• Documentation of vaccination often required
• Typhoid
• Live oral or IM polysaccharide preferred
• Influenza

1 MMWR Aug 3, 200150643-5.
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Other Vaccinations

• Meningococcus
• With travel to endemic regions
• Must be tetra-valent (A,C, Y, W135)
• Cholera
• Risk of illness low to travelers
• Rabies
• Consider if prolonged travel planned
• Japanese encephalitis
• If traveling to rural Asia

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Self Treatment

• Acetaminophen
• Ibuprofen
• Benadryl
• Steroids
• Topical and oral
• Epi-Pen
• Mupirocin ointment
• Floxin otic
• Ciloxan ophthalmic

• Cephalexin
• Doxycycline
• Loperamide
• Fluoroquinolone or azithromycin
• Others ?
• Metronidazole
• Albendazole
• Ivermectin
• Diethylcarbamazine

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Helpful Resources

• The Centers for Disease Control
• http//www.cdc.gov/travel/
• 877-FYI-TRIP
• The Yellow Book
• The World Health Organization
• http//www.who.int/topics/travel/en/
• International Travel and Health
• The Intl Society of Travel Medicine
• http//www.istm.org
• GeoSentinel database

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