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Jungle Fever

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Title: Jungle Fever


1
Jungle Fever
  • Phillip D. Levy, MD, MPH
  • Associate Professor of Emergency Medicine
  • Wayne State University/Detroit Receiving Hospital

2
Statement of Disclosure
  • I have no financial relationships relevant to
    this presentation

3
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

4
Focus Will Be Microbiology Not Sociology
5
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.
6
From Freedman et al. NEJM 2006354119-30.
7
From Freedman et al. NEJM 2006354119-30.
8
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

9
Aedes aegypti
10
Anopheles gambiae
11
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

12
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

13
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

14
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

15
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

16
Case 1
17
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

18
By the Numbers, Malaria is Most Likely1
1 Leder et al. Clin Infect Dis 2004391104-12.
19
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
27
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

28
Dengue Fever Distribution
29
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

30
Arthropod-borne Viruses
  • Flaviviridae
  • Yellow fever
  • Togaviridae
  • Chikungunya
  • O'Nyong-nyong fever
  • Bunyaviridae
  • Crimean-Congo fever
  • Rift valley fever

31
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

34
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

35
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.
38
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.
41
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.
44
African Trypanosomiasis Distribution
45
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

46
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

49
Case 2
50
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 (-)

51
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.
52
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.
55
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
61
Image from http//www.itg.be/itg/DistanceLearning
/LectureNotesVandenEndenE/imagehtml/ppages/CD_1004
_028c.htm
62
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

76
Sand Fly Phlebotomus and Lutzomyia spp.
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Case 3
81
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

85
Lymphatic Filariasis Distribution
86
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
89
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.
94
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
98
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 ()

99
of diarrhea
100
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.
101
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.
102
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.

103
Advice For You and Your Patients
104
From Freedman et al. NEJM 2006354119-30.
105
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

106
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

107
Which is Best?
From Fradin and Day NEJM 200234713-8.
108
Picaridin As Efficacious as DEET
From Frances et al. J Med Entomol 200441414-7.
109
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
112
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

113
Chemoprophylaxis
  • Malaria
  • Lymphatic filariasis
  • Travelers diarrhea

114
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
115
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

116
Should Climbers Take Prophylaxis?
117
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.
118
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

119
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

120
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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