Resident Board Review

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Resident Board Review

• Joseph G. Timpone Jr. MD
• Georgetown University Hospital

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Case One

• An 80 y.o. female presents to the ER with a 3 day
  history of fatigue, abdominal cramps and bloody
  diarrhea. She denies any fevers and states that
  10 days ago she was at a State Fair where she ate
  hotdogs, baked beans, coleslaw, and drank fresh
  apple cider. PEX T37 BP140/90 P100 ABDON
  generalized tenderness LABS WBC 12.0 HCT 19.0
  PLTS 90,000 BUN/Cr 50/3.0 LDH 400 T.Bili 4.0

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The most likely causative pathogen is

• A) S. aureus
• B) B. Cereus
• C) Norwalk virus
• D) Listeria
• E) E.coli O157H7

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E. Coli 0157H7

• 21,000 Cases/YR 6 pts. Develop HUS 12
  Mortality
• Epidemiology Young children elderly
  undercooked ground beef, unpasteurized milk,
  apple cider, water/vegetables contaminated with
  manure.
• Incubation 3-4 days ABD. cramping bloody
  diarrhea (35 - 90) fever uncommon (30)
• HUS MAHA, Thrombocytopenia, ARF, can also see
  TTP.
• Diagnosis colorless, Sorbitol non-fermenting
  colonies on Sorbitol-Maconkey agar 0157 Antisera
  Agglutination test.
• Treatment antibiotic use may increase risk of HUS

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Case Two

• A 30 y.o. healthy male is brought to the ER by
  his co-workers after a syncopal episode at work.
  In the ER the pt is arousable and noted to be
  afebrile. BP70/40 P40 EKG3 Heart block. The
  pt states that he had recently returned from a
  hiking trip in New England one month ago.

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The most likely causative pathogen is

• A) S. aureus
• B) B. Burgdorferi
• C) S. pyogenes
• D) R. rickettsii
• E) Coxsackie virus

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Lyme Disease

• North America Borrelia Burgdorferi Europe B.
  Afzelii Asia B. Garinii
• Southern New England, Middle Atlantic, Wisconsin,
  Minnesota, California
• Ixodes Scapularis (Deer Tick) Nymphal stage must
  be attached for 72 Hrs. to result in
  transmission
• Stage 1 Viral-like illness associated with
  erythema migrans (60 - 80). Expanding annular
  lesion with central clearing (at least 5cm by CDC
  criteria)

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Acute Disseminated Lyme Disease (Stage 2)

• Neurologic (occurs in 15 of patients)
• Lymphocytic meningitis
• Cranial Neuritis (Bells Palsy)
• Motor-sensory polyradiculo neuritis
• Mono-neuritis multiplex myelitis
• Cardiac (occurs in 5 of patients)
• Atrio-ventricular block
• Myo-pericarditis
• Cardiomegaly/LV dysfunction (rare)

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Chronic Lyme Disease (Stage 3)

• Arthritis (60 of untreated patients)
• Oligo-articular/Mono-articular (Kness)
• Treatment resistant arthritis in 10
• More common in North America
• Neurologic
• Cognitive dysfunction/encephalopathy
• Polyneuropathy
• More common in Europe
• Chronic Skin Lesions
• Acrodermatitis chronicum atrophicans
• Associated with polyneuropathy

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Lyme Disease Diagnosis

• 70 - 80 pts. have () IgM by 2 - 4 wks.
• () IgG _at_ 4 wks.
• An isolated () IgM in the absence of a () IgG
  after one month of symptoms is likely a false ()
  IgM
• IgM and IgG can remain () for years
• False () endocarditis, parvovirus B19,
  syphilis, EBV, SLE, RA
• Elisa must be confirmed by W.B.
• 5 of pts. In non-endemic area can be false ()
• PCR - CSF C6 Ab

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Lyme Disease Treatment

• Stage 1 (E.M.) Doxycycline, Amoxicillin,
  Cefuroxime, Erythromycin for 14 - 21 days
• Neurologic/cardiac IV Ceftriaxone, Cefotaxime,
  PCN
• Bells Palsy - ? Doxycycline
• Arthritis Doxycycline x 30 days or IV
  Ceftriaxone x 14 - 28 days

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Lyme Disease Prevention

• Prophylaxis Doxycycline 200 mg x 1 dose has 87
  efficacy for I. scaplilaris tick bits (0.4 vs.
  3.2 - Doxy vs. placedo)
• Recombinant OspA vaccine is 78 effective (0, 1,
  12 mos. Or 0, 1, 2 mos.)
• Steere NeJM vol. 345 July 12, 2001
• Nadelman , et.al NeJM vol. 345 July 12, 2002

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Case Three

• A 75 y.o. male with a history of HTN presents
  with a 1 wk history of fevers and fatigue. His
  PCP obtains some labs which reveal WBC 5.0 HCT
  20.0 PLTS 40,000 AST 100 ALT 50 T.Bili. 3.5 LDH
  525. The pt recently returned from his summer
  home in Nantucket.

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The most likely causative organism is

• A) B. Burgdorferi
• B) B. Microti
• C) F. Tularensis
• D) R. Rickettsii
• E) E. Chaffeensis

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Babesioses

• Caused by B. microti and B . equi
• Vector Ixodes scapularis
• N.E. (Cape Cod), California
• Can be transmitted by transfusions
• Elderly, splenectomized pts.
• Fever, myalgias, H/A, hemolytic anemia,
  thrombocytopenia, elevated LFTs
• Diagnosis Peripheral smear, serology, PCR
• Treatment Quinine Clindamycin Atovaquone
  Azithromycine exchange transfusion
• 20 co-infection with B. burgdorferi

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Case Four

• A 29 y.o. female presents to the ER with fevers,
  cough, and S.O.B. PEX T 39.5 BP 110/80 P 120 O2
  SAT. 88 CXR diffuse pulmonary infiltrates LABS
  WBC 25.0 HCT 55.0 PLTS 50,000 PT/PTT 16/60
• The pt recently traveled to Arizona where she
  stayed on an Indian reservation to learn how to
  make jewelry.

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The most likely causative organ

• A) S. pyogenes
• B) Listeria
• C) C. Immitis
• D) C. Neoformans
• E) Hanta Virus

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Hantavirus

• Hanta virus RNA virus Bunyaviridae(Sin NOMBRE
  virus)
• Hantavirus Pulmonary Syndrome
• S.W. U.S. (New Mexico, Arizona, Utah, Colorado)
  has been reported in all States
• Rodent exposure (Peromyscus maniculatus)
• 4 Phages febrile, shock, diuresis, convalescent
• Clinical fever, myalgias, cough, dyspnea, H/A,
  GI symptoms
• Labs leukocytosis, hemoconcentration,
  thrombocytopenia, prolonged PT/PTT
• Rapidly progressive pulmonary edema with
  hypotension
• Diagnosis IFA of sputum, lung tissue
• Treatment ? Ribavirin
• Case Fatality 76

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Case Five

• A 32 y.o. male presents to the ER with fever and
  a ulcerative skin lesion on his arm. In the ER he
  has a T103, and you notice ipsilateral axillary
  lymphadenopathy. Ten days ago he returned from a
  hunting trip where he killed and skinned a
  rabbit, fox, and deer.

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The most likely causative pathogen is

• A) B.burgdorferi
• B) B. anthracis
• C) Y. Pestis
• D) V. Vulnificus
• E) F. Tularensis

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Tularemia Francisella Tularensis

• Gm (-) coccobacillus requires cysteine for
  growth
• Contact with infected animals (rabbits,
  squirrels, cats), inhalation, tick bite
• Peak occurs with tick-borne exposure and hunting
  season
• Southcentral and Southwestern United States-
  Oklahoma, Arkansas, Texas
• Hunters, trappers, lab workers

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Amblyoma Americanum
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Tularemia Incidence

• 1990-2000 1368 cases.
• Approximately 124 cases/year reported to the CDC.
• 56 cases were reported from Arkansas, Missouri,
  South Dakota, and Oklahoma.
• Endemic on Marthas vineyard.
• 70 cases between May and August.
• (MMWR 2002 Mar 8 51 (9) 182-184)

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Endemic Regions
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Francisella Tularensis

• Small non-motile gm (-) cocci bacillus.
• Can survive for weeks at low temperatures in
  water, moist soil, hay and decaying animal
  carcasses.
• Voles, mice, rabbits, hares, squirrels are
  reservoirs.
• Vectors Ticks, flies, mosquitoes.
• Human infection
• Tick bites
• Handling infected animals or animals products.
• Ingestion.
• Inhalation.

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Tularemia Clinical

• 50 of patients with ulcer node disease
• Patients develop ulcerative lesion at site of
  exposure which is associated with ipsilateral
  lymphadenopathy
• Bacteremia, pneumonia, oculo-glandular disease
• Pneumonia in gardeners on Marthas Vineyard

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Ulceroglandular Tularemia
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Oculoglandular Tularemia
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Pneumonic Tularemia Clinical

• Fever and non-productive cough
• 3 -5 day incubation period (range 1- 14 days)
• CXR pneumonia, pleural effusion, and hilar
  lymphadenopathy

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Diagnosis, Treatment and Prevention

• Diagnosis grows on media enriched with cysteine
  serology
• Treatment streptomycin, gentamicin, doxycycline,
  ciprofloxacin
• P.E.P. doxycycline or ciprofloxacin
• Live attenuated vaccine lab workers
• Respiratory isolation not needed

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Case Six

• A 25 y.o. male presents to the ER with fevers,
  myalgias, LBP, nausea, and vomiting. In the ER he
  has a T39.5, BP 80/40, P120 and you notice a
  rash. Labs WBC 25,000, HCT 45, PLT 40,000,
  BUN/Cr 40/2.2. The patient has returned from a
  camping trip in North Carolina one week ago.

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The most likely causative pathogen is

• A) B. burgdorferi
• B) S. Pneumoniae
• C) R. Rickettsii
• D) B. Microti
• E) Leptospiria

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Rocky Mountain Spotted Fever

• Caused by Rickettsia rickettsii
• D. andersoni D. variabilis
• South Atlantic Coastal, western and south central
  states (North Carolina, South Carolina, Oklahoma,
  and Tennessee)
• 95 cases April - September
• Dogs, wooded areas, males

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RMSF Clinical

• Incubation 5 - 7 days (2 to 14 days)
• Fever, H/A, malaise, nausea, vomiting, abd. pain
• Rash 1 - 5 days after onset of illness macules
  on wrists ankles spread to trunk, palms, and
  soles 10 pts. without rash
• Thrombocytopenia, DIC, elevated LFTS_at_ ARF, ARDS

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RMSF Diagnosis Treatment

• Mortality 5 - 25
• Diagnosis DFA of skin biopsy - Serology
• Treatment Tetracyclines chloramphenicol

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Case seven

• A 50 y.o. male with a history of hemachromatosis
  was brought in by his friends with fevers,
  diarrhea, severe weakness. They had recently
  returned from a boating trip on the Chesapeake
  bay where they ate fresh crab and other assorted
  shellfish. On exam T39 BP 70/40 P130

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The most likely causative pathogen is

• A) S. aureus
• B) Campylobacter jejuni
• C) Shigella
• D) Mycobacterium marinum
• E) Vibrio vulnificus

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Vibrio Vulnficus

• Seawater or raw seafood/shellfish (oysters)
• Chesapeake bay, Gulf coast (hurricane Katrina)
• Liver disease, cirrhosis, hemachromatosis, ETOH
• Septicemia with metastatic skin lesions
• Diarrhea
• rapidly progressive cellulitis
• 50 mortality
• Tetracycline/doxycycline combination therapy
  with doxycycline 3rd generation sephalosporin
  (ceftriaxone, cefotaxime)

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A Trip to the Zoo

• Joseph G. Timpone, M.D.
• Division of Infectious Diseases

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A 35 year old male is brought to a NYC E.R. with
fevers H/A and (R) inguinal pain. In the E.R. he
is noted to have T 40oC, P 120, and BP
80/40. There is a 3x3 cm tense lymph node in (R)
inguinal region. WBC 25,000, PLTs 60,000,
Bun/Cr 40/2.0.
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The patient reports that he is visiting from
Colorado where he is employed as a veterinarian.
He has recently cared for a few sick cats, a
rabbit and assisted in the birth of a calf.
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The most likely causative agent would be

• a.) Sin Nombre Virus
• b.) Francisella Tularensis
• c.) Coxiella Burnettii
• d.) Yersinia Pestis
• e.) Bacillus Anthracis

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Plague Yersinia Pestis

• gm(-) Cocco-Bacillus (bipolar appearance -
  safety pin)
• Rats, ground squirrels, prairie dogs, cats
• Rodent Flea Xenopsylla cheopis
• S.W. US (New Mexico, Arizona, Colorado,
  California)
• Recreational/occupational hunting, camping,
  military

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Plague Clinical

• Incubation 2 -6 days
• Bubonic Tense, Tender, Fluctuant nodes
  (inguinal, axillary, cervical)
• Pneumonic cough, hemoptysis, watery sputum
  patchy/lobar infiltrates
• Septicemic hypotension, DIC, gangrene
• Meningitis, Pharyngitis

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Plague Diagnosis

• 50 mortality with out treatment 5 with
  treatment
• Aspirate/culture of Bubo - Waysons stain
  (bipolar staining - safety pin)
• DFA staining
• PCR
• Serology

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Plague Treatment

• Streptomycin or gentamicin
• Alternative Doxycycline, Ciprofloxacin
• P.E.P Doxycycline
• respiratory isolation x 48 - 72 hrs.

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A 28 year old male presents to the E.R. with
fevers, H/A, Rash, Dyspnea and a dry,
non-productive cough of 3 days duration. His PEx
reveals a T 40oC, P 60, and 02SAT 95.
There are crackles at the (R) Lung base ()
Splenomegaly, and a pink macular rash on his face
and trunk.
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His CXR reveals a (R) lower lobe consolidation.
He reports that he has been feeling fatigued
during the past week due to his overtime hours at
the Turkey Farm. His flag football team - The
Turkey Torturers are scheduled to play in the
Thanksgiving Turkey Bowl this week - But 3
teammates/co-workers are also sick.
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The most likely Causative Pathogen is

• a.) Histoplasma Capsulatum
• b.) Cryptococcus Neoformans
• c.) Chlamydophila Psittaci
• d.) Legionella Pneumophila
• e.) Mycoplasma Pneumoniae

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Chlamydophila

• Obligate intra-cellular pathogen
• Parrot, finch families, turkeys, pigeons, poultry
• Transmission aerosolized secretions, excrement
• Pet owners, pet shops, vets, abattoir workers,
  farmers

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C. psittaci Clinical

• Incubation 5 - 15 days post exposure
• Fever, H/A, dry cough, and SOB
• Splenomegaly
• Horders spots pink macular rash on face, trunk
• CXR lower lobe consolidation
• Labs nl WBC, elevated LFTs

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C. psittaci

• Diagnosis serology, culture (lab hazard)
• Treatment doxycycline x fourteen - 21 days
  Macrolides, quinolones
• Miscellaneous Meningitis, Myocarditis,
  Pericarditis

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Case 4

• A previously healthy male presents to the ER with
  fevers, H/A and cough. He is employed as a
  detective and his hobbies include hiking,
  camping, and hunting. His most recent camping
  trip was approximately 8weeks ago. Ten days ago,
  he was playing poker in his friends basement,
  and witnessed the birth of a litter of kittens.
  In the ER, he has a T102, P80, and BP130/60.
  Crackles are heard at the bases. WBC 5.0 Hct 42
  Plts 105,000 AST 68 ALT85. CXR reveals
  bilateral lower lobe airspace disease. The pt.
  reports that all of his buddies have been
  diagnosed with pneumonia.

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The most likely explanation for the cluster of
pneumonia cases is

• A. An act of bioterrorism
• B. Inhalation of infected birth products
• C. Ingestion of poorly cooked Mexican cheese (on
  the nachos at the poker game)
• D. Participation in a bachelor party at Good
  Guys
• E. Water exposure while camping

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Poker Players Pneumonia

• Q - Fever pneumonia (Coxiella Burnetii)
• Urban outbreak amongst poker players
• Exposure parturient Cat - kittens

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Q Fever Background

• 1935 Derrick described febrile illness in
  abattoir workers in Australia
• Q Fever - (query)
• MacFarlane-Burnet and Freeman isolated organism
  from guinea pigs inoculated with blood of febrile
  patients
• Cox and Davis isolated GM(-) organism from ticks
  in Montana
• Coxiella burnetii

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Q Fever Microbiology

• Caused by C.burnetii
• Small GM(-) bacterium that grows exclusively in
  eukaryotic cells
• Gamma subgroup of proteobacteria related to
  Legionella
• LPS - antigenic shift/phase variation
• Phase 1- infectious form

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Q Fever Epidemiology

• Cattle, goats, sheep, cats, rabbits, dogs, birds,
  ticks
• Farmers, veterinarians, abattoir workers
• Transmission via inhalation of organisms or
  ingestion of raw milk
• Parturient cats and farm animals
• Worldwide geographic distribution

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Q Fever Clinical

• 54 of cases are asymptomatic
• Incubation period 2-6 weeks
• Abrupt onset of fever and headache
• Fever (90), Pneumonia (45), and Elevated LFTs
  (69)
• Atypical Pneumonia
• Granulomatous Hepatitis
• Maculopapular/purpuric rash in 20
  (Leukocytoclastic Vasculitis)

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Q Fever Chronic

• Culture (-) endocarditis of damaged or prosthetic
  valves
• Decreased cell-mediated immune response to
  C.burnetii
• Clubbing, hepatomegaly, splenmegaly, purpuric
  rash, and arterial emboli
• Hypergammaglobulinemia, microscopic hematuria,
  elevated ESR

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Q Fever Miscellaneous

• Myocarditis/pericarditis
• Meningoencephalitis
• Osteomyelitis
• Hemolytic anemia
• Epididymitis/orchitis

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Q Fever Laboratory

• Normal white blood cell count (90)
• Thrombocytopenia (25)
• Increased transaminase levels (70)
• Smooth muscle autoantibodies (65)
• Anti-phospholipase antibodies (50)

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Q Fever Diagnosis

• Cell culture (shell vial - immunofluorescence)
• Incubation period 8-12 days
• Culture of buffy-coat and biopsy specimens
• PCR of biopsy specimens
• Granuloma doughnut appearance

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Q Fever Serology

• CF, IFA, and ELISA
• IFA phase II antigen 1200
• IgG 1200
• IgM 150
• Serology () at 2-4 weeks
• IgM serology () for 6-8 months

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Q Fever Treatment

• Doxycycline, TMP/SMX, Ciprofloxacin, Rifampin
• Acute duration 15-21 days
• Chronic duration (?) 3 years
• Relapses are common
• (?) Hydroxychloroquine Doxycycline

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Case 5

• Dan Rather presents for evaluation of a skin
  lesion. He reports that he recently returned from
  Afghanistan where he was in hot pursuit of Usama
  Bin Laden. He states that he had to sleep on the
  floors of caves, wade across some murky waters,
  an use a camel for transportation. His diet
  consisted of nuts, berries and insects. His exam
  reveals an eschar on the dorsum of his right hand
  with surrounding edema. His only other complaint
  is that he is very depressed due to some comments
  that he received in his fan mail.

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The most likely causative pathogen is

• A. Bacillus anthracis
• B. Variola
• C. Bartonella henselae
• D. Borrelia burgdorferi
• E. Histoplasma capsulatum

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Anthrax Microbiology

• Aerobic
• Nonmotile
• Spore forming
• Gram bacillus
• Spores survive 30 yrs in soil

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Anthrax Epidemiology

• Zoonotic disease in herbivores
• Human infection can occur via contact with
  infected animals or animal products, ingestion or
  inhalation
• NO person-to-person transmission
• Early 1900s 130 cases annually in the US
• 95 of disease is cutaneous
• Last naturally occurring cutaneous case 1992
• 20th century 18 inhalation cases
• Last naturally occurring inhalation case 1976
• 2001 Bioterrorism threat in Postal Workers, News
  Reporters, and Federal Government Employees

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Cutaneous anthrax

• Direct contact with spores
• Does not affect intact skin
• Commonly seen on the head, forearms or hands
• Incubation 1-12 days
• Localized itching, followed by a papular lesion ?
  vesicular ? painless depressed black eschar
• Mortality up to 20 without abx rare with abx
• Abx do not change the progression of the lesion
• DDX Spider bite, Ecthyma gangrenosum, tularemia,
  plague, cellulitis
• JAMA 1999 28118

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Inhalational anthrax

• Incubation period avg 1-7d
• Flu-like prodrome
• Brief improvement
• Abrupt respiratory failure and collapse
• CXR widened mediastinum, pleural effusions,
  infiltrates, ? consolidation
• 50 hemor. meningitis
• Mortality 89
• DDX atypical pneumonia, tularemia, Q fever,
  fungal pneumonia

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TRAVEL NIBLETS

• Joseph G. Timpone Jr., MD
• Georgetown University Hospital

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• 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
• A) stool for O and P
• B) Blood cultures
• C) Aspiration of the liver lesion
• D) Serology
• E) 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

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Intestinal Amebiasis

• Asymptomatic cyst passage most common
• 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
• Rare intestinal forms
• Fulminant intestinal infection
• Toxic megacolon
• Chronic amebic colitis (confused with IBD)

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Amebic Liver Abscess

• Always preceded by intestinal colonization
• 95 occur within 5 months of exposure
• 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
• Treatment metronidazole paronomycin
• Stool antigen for E.Histolytica

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• A 20 y.o. male presents with watery diarrhea. He
  has had recurrent infections with the pathogen
  shown on the previous slide.

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• The most likely cause of recurrent infection is
• A) Neutropenia
• B) HIV infection
• C) Lymphocytopenia
• D) Compliment deficiency
• E) IgA deficiency

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Giardia lamblia

• Worldwide distribution
• Most common intestinal parasite in USA (found in
  4 to 7 of OP specimens)
• Transmission
• Water contamination most common (not killed be
  standard chlorine concentrations)
• Person-to-person (daycare, homosexual etc.)
• Foodborne
• Hypogammaglobulinemic and achlorhydric patients
  at greater risk

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Giardia lamblia

• Incubation period of 1 to 2 weeks
• Spectrum of disease varies widely
• Of 100 people ingesting cysts
• 5-15 become asymptomatic cyst passers
• 25-50 have diarrheal syndrome
• 35-70 have no trace of infection
• Diarrheal syndrome typically acute lasting 1-3
  weeks but can be chronic with weight loss
• Giardia does not invade mucosal tissue
• Lactase deficiency after infection common

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Giardia lamblia

• Diagnosis
• OP test of choice (90 yield from 3 specimens)
• Giardia stool antigen (85-98 sensitive)
• Duodenal sampling (seldom needed)
• String test
• Duodenal aspiration/biopsy
• Therapy
• Metronidazole for 7 days (efficacy 80-95)
• Furazolidone and paromomycin alternatives

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• A 24 y.o. male Marine has recently returned from
  a tour of duty in Iraq. He reports a month
  history of a non-healing skin ulcer. He was given
  two courses of antibiotics (Cephalexin,
  Levofloxacin) without any improvement. He has no
  other complains.

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• The most likely causative pathogen would be
• A) Group A streptococcus
• B) MRSA
• C) Bacillus anthracis
• D) Herpes simplex
• E) Leishmania

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Leishmaniasis

• Obligate intracellular protozoa (genus
  Leishmania)
• Syndrome caused by 21 leishmanial species
• Vector is the sandfly (30 species)
• 1.5 to 2 million new cases yearly
• Three clinical syndromes caused by replication of
  parasite inside macrophages
• Visceral
• Cutaneous
• Mucocutaneous

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Cutaneous Leishmaniasis

• Traditionally classified as New World or Old
  World
• Most cases occur in men who have forest-related
  occupational exposures
• chiclero ulcer

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Leishmaniasis

• Types Cutaneous, Mucocutaneous, Visceral
• Old world L. tropica New world L.
  braziliensis
• Cutaneous Leishmaniasis Chronic non-healing
  ulcer or nodule
• Visceral fevers, N.S. wt. Loss, massive
  splenomegaly
• caused by L. donvani (can see L.tropica in Gulf
  War Vets.)
• AIDS - defining illness in Southern Europe
• Treatment Antimony, AMB, Pentamidine

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• A 40 y.o. Peruvian female is brought to the ER by
  her family because of new onset seizures. Shes
  currently employed as a daycare worker. She
  denies any fevers, night sweats, weight loss or
  other symptoms. She has a negative PPD. In the ER
  the patient is a febrile and post-ictal.

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• The most likely cause of her seizures would be
• A) MTB
• B) N. meningitidis
• C) T. cruzii
• D) T. solium
• E) HSV

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T. Solium And Cysticercosis

• Pork tapeworm T. solium causative agent
• Two distinct forms of infection
• Intestinal tapeworms by ingesting undercooked
  pork
• Cysticercosis (larval forms in tissues) follows
  ingestion of T. solium eggs
• Usually from fecally contaminated food
• Autoinfection
• Reflux from intestine into the stomach.
• Exists worldwide (10 prevalence in some areas)

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Clinical Manifestations

• Intestinal infection
• Usually asymptomatic
• Tapeworm 3 meters in length
• Normally, only one worm (live up to 25 years)
• Fecal passage of proglottids may be noted
• Cysticercosis
• Larvae location (most commonly brain and muscle)
  and size determine clinical presentation
• Neurologic manifestations most common

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Diagnosis

• Intestinal infections
• Detection of eggs or
  proglottids by OP
• Cysticercosis
• Definitive diagnosis requires examination of
  larvae in involved tissue
• Diagnosis often based on clinical presentation
  with radiographic studies and serologic tests

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Treatment

• Intestinal infection treated with praziquantel
• Asymptomatic patients with calcified lesions
  generally require no treatment
• Symptomatic neurocysticercosis
• Albendazole treatment of choice (better CSF
  levels)
• Praziquantel alternative
• Treatment provokes inflammation around dying
  cysticerci ? hospitalize and give glucocorticoids
• Ventricular obstruction may need VP shunting

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• A 30 y.o. female has returned from a safari in
  Kenya. She presents with the abrupt onset of
  fevers, photophobia, H/A, and diarrhea 48 hours
  upon return to the US. On the Exam her T39.5.
  There is no meningimus or rash. WBC 5.0, HCT 29,
  PLT 55,000, LDH 400, bili 3.0, BUN/Cr 25/1.8.

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• The most appropriate therapy would be
• A) Ceftriaxone Vancomycin
• B) Chloroquine
• C) Mefloquine
• D) Quinine Doxycycline
• E) Primaquine

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Fever in Travelers

• Malaria
• Dengue Fever
• Typhoid Fever
• Meningococcemia
• MTB
• Leptospirosis
• SARS

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Malaria

• P. falciparum, P. vivaz, 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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• A 60 y.o. male with AML is s/p induction
  chemotherapy and has fevers and neutropenia.
  Blood cultures reveal E.coli, K. pneumonia, Ps.
  Aeruginosa. The patient has immigrated from
  Vietnam 20 years ago.

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• Stool for O P would most likely yield
• A) S. stercoralis
• B) E. histolytica
• C) G. lamblia
• D) A. lumbricoides
• E) A. duodenale

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Strongyloidiasis

• Strongyloides Stercoralis
• Clinical diarrhea, ADB. Pain, urticaria, larva
  currens, pulmonary, infiltrates, eosinophilia
• OP, duodenal aspirate (string test)
• Strongloidis AB
• Hyperinfection steroids, chemotherapy, AIDS,
  transplantation, HTLV infection
• polymicrobial gm(-) bacteremia
• Treatment Ivermectin, Thiabendazole, Albendazole

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Cryptosporidiosis

• Caused by C. parvum
• Immunocompromised (AIDS) Immunocompetent
  patients
• Water borne illness (Milwaukee, WI 400,000 cases)
• Watery diarrhea, abd. Pain, n/v, cholangiopathy
  in AIDS patients
• Diagnosis modified AFB stain
• Treatment ? Paronomycin, azithromycin
  Nitazoxanide

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PUTTING THE FUN IN FUNGUS

• Joseph G. Timpone, Jr. M.D.
• Georgetown University Hospital

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CASE ONE

• A 45 y.o. male with DM and ESRD s/p renal
  transplant three months ago presents with fevers,
  n.s. and S.O.B. His meds include CYA, MMF,
  Prednisone. In the ER T39, BP80/40, there are
  oral ulcers. CXR reveals interstitial
  infiltrates. WBC 2.0, PLT 50K, INR 3.0, LDH 400.
  The patient is employed as a chicken farmer.

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Histoplasmosis Etiology

• Histoplasma capsulatum
• Dimorphic fungus
• Grows in soil
• Chicken, starling, bat excrement

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Histoplasmosis Epidemiology

• Endemic in east/central U.S.
• Ohio and Mississippi River Valleys
• Farming, rural, urban settings
• High rate of infection in endemic regions

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Histoplasmosis Clinical Features

• 90 asymptomatic
• Fever, night sweats, weight loss
• Cough, pleurisy, SOB
• Arthralgias, myalgias
• Lymphadenapathy
• E. nodosum/multiforme

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Risk Factors for Progressive Disseminated
Histoplasmosis (PDH)

• Depressed cell mediated immunity
• Advanced HIV disease
• Corticosteroids, Methotrexate
• Infliximab, Etanercept (Anti-TNF-Alpha therapies)
• Solid organ transplantation
• Elderly
• Defects in the IFN-GAMMA-ILI2 Pathway
• DM, ESLD, ESRD

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PDH Clinical Features

• Fulminant course in AIDS/Transplant pts.
• Most common AIDS defining illness in endemic
  areas
• Can occur as acute exogenous infection and as
  reactivation
• Fever, night sweats, wt. Loss, oral ulcers,
  lymphadenopathy, Hepatosplenomegaly
• Pulmonary involvement CXR with diffuse
  interstitial infiltrates
• GI involvement (ILEO-CECAL region can mimic IBD)
• Adrenal insufficiency
• Leukopenia, anemia, thrombocytopenia, DIC,
  elevated LDH

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PDH Diagnosis and Treatment

• Urinary serum histoplasma Ag (90 urine 70
  serum)
• 95 sensitivity in HIV ()
• 82 in non-HIV immunosuppressed patients
• Treatment Amphotericin B (Lipid preparation
  Itraconazole)

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CASE TWO

• A 35 y.o. male lumber jack from Wisconsin
  presents to the ER with a two week history of
  cough and sputum production. His CXR reveals a
  dense alveolar inflitrates.

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Blastomycosis Etiology Epidemiology

• Caused by Blastomyces dermatitides
• Isolated from soil and decaying wood
• Midwest near Great Lakes, Canada, South central
  states bordering Ohio Mississippi River Valleys
• Occupational recreational exposure near
  waterways
• Inoculation via inhalation, skin, dog bites

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Blastomycosis Clinical

• Acute Pulmonary Blastomycosis fever, chills,
  myalgias, arthralgias, cough, sputum production
• CXR alveolar infiltrates in lower lobes
• Chronic complications
• Pulmonary
• Skin verrucous ulcerative lesions (40-80)
• Bone joint disease
• Genitourinary prostatitis, epididymitis

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Blastomycosis Treatment

• Acute pulmonary
• Treatment indicated for severe disease only
• Amphotericin B, 1.5-2.5 gm
• Chronic
• Ketoconazole, 400-800 mg/day x 6 months
• Itraconazole, 200 mg BID x 6 months

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CASE THREE

• A 30 y.o. male construction worker presents with
  fevers and H/A of two weeks duration. His PMH is
  significant for HIV with a CD475. He has refused
  all medication. In the ER an LP reveals WBC100,
  5 PMN, 70 LY, 25 EOS, T.P100, GLU20. His PPD
  is negative.
• His most recent work was at a site in Phoenix.

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Coccidioidamycosis Etiology Epidemiology

• Caused by Coccidioides immitis
• Endemic to Southwestern U.S. Mexico
• 100,000 new infections per year
• Arid climate, low altitudes, alkaline soil

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Coccidioidomycosis Acute Infection

• 60 of patients are asymptomatic
• 40 have viral-like illness (fever, myalgias,
  H/A, non-productive cough lasting 1-3 weeks)
• CXR alveolar infiltrate or solitary pulmonary
  nodule (5 have persistent CXR abnormalities)
• Most commonly a self-limited illness
• Allergic manifestations E. nodosum multiforme
  are good prognostic indicators

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Coccidioidomycosis Disseminated Disease

• Occurs in
• Increased risk
• African-Americans, Filipinos, Latinos
• Pregnant women
• Cytotoxic chemotherapy
• Glucocorticoids
• Organ transplantation
• HIV disease
• Disseminates to skin, bone, meninges
• Severe pulmonary disease

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Coccidioidomycosis Meningitis

• Often occurs 6 months after initial infection
• Causes a basilar meningitis
• Fever, H/A, confusion
• CSF
• Mononuclear cell pleocytosis with eosinophils
• () CF Ab in 70
• () Culture in 1/3 of cases

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Coccidioidomycosis Diagnosis

• Skin test
• Culture () in sputum, joint fluid, CSF
• Giant spherule on HE, Pap, KOH prep
• Serology
• 75 Have () IgM _at_ 2-3 weeks
• 90 Have () IgG CF Ab _at_ 3 months
• 95 of patients without disseminated disease with
  

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Coccidioidomycosis Treatment

• Acute No therapy consider therapy in high risk
  groups (Amphotericin B, 0.5-1.5 gm or
  fluconazole, 400-800 mg qd)
• Single cavitary disease No therapy
• Chronic fibrocavitary disease Ketaconazole or
  fluconazole
• Disseminated Amphotericin B, 2.5 gm
• Meningitis Amphotericin B, IV Intrathecal
  fluconazole
• Skin Bone Ketoconazole or fluconazole

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CASE FOUR

• A 50 y.o. male with ESLD due to HCV is three
  months S/P OLT. The patient presents with a one
  week history of low grade fevers and H/A. Hes
  also noted to have several papular skin lesions.
  His meds include Tacrolimus and Prednisone. He
  recently received high dose steroids for a bout
  of rejection.

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Recommended Management of Cryptococcal Meningitis
in AIDS Patients Initial Rx

• Medical
• Ampho B, 0.7 mg/kg/day x 14 days
• Flucytosine, 100 mg/kg/day orally in 2-4 divided
  doses x 14 days
• Consolidation from week 2-10 w/fluconazole, 400
  mg once daily

• Suspected acute cerebral hypertension
• CT or MRI scan to assess obstructive
  hydrocephalus
• If absent, lumbar puncture if present,
  ventriculostomy
• If cerebrospinal fluid pressure 25 cm, use
  large-bore needle to lower CSF pressure until
  it's stable

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Recommended Management of Cryptococcal Meningitis
in AIDS Patients

• Chronic suppressive management from week 1 0
  continued indefinitely fluconazole, 200 mg qd
  po.
• Use of Cryptococcal antigen
• Serum Diagnostic only, should prompt lumbar
  puncture. If no antigen in CSF and culture of CSF
  is negative, consider starting fluconazole, 200
  mg per day to prevent CNS disease.
• CSF Pre-treatment titer1,1024associatedw/
  adverse outcome Post-treatment titer stable or
  rising suggests relapse

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CASE FIVE

• A 40 y.o. female with AML is S/P induction
  chemotherapy and has had an ANC three weeks. She has been treated with Impenem,
  Vancomycin, and Amphotericin B. Shes developed a
  cough with hemoptysis.

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Aspergillosis

• Risk factors prolonged neutropenia,
  immunosuppressive therapy, corticosteroids, BMT,
  organ transplant, hematologic malignancies
• Highest risk in allogeneic BMT with GVHD
• Invasive pulmonary disease
• CNS involvement
• Diagnosis BAL, biopsy, serum galactomannan
• Therapy Voriconazole, liposomal amphotericin B,
  itraconazole, caspofungin, surgical resection

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CASE SIX

• A 60 y.o. diabetic male is brought to the ER by
  his wife because of mental confusion. She reports
  that he has been complaining of sinus congestion.
  In the ER the patient is obtunded and
  unresponsive. Labs GLU450, HCO 314, Anion
  gap17.

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The most likely causative organism is

• A) Nocardia
• B) Candida albicans
• C) Rhizopus species
• D) Pseudomonas aeruginosa
• E) MRSA

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Zygomycosis/ Mucormycosis

• Rhizopus, Absidia, Cunninghamella
• Broad hyphae (5-15 Mm) without septations
• Have an enzyme keton-reductase which allows it to
  thrive in high glucose/ acidic environments
• Iron overload deferoxamine therapy promote
  growth
• DM, Hematologic malignancies, metabolic acidosis,
  steroids, AIDS, IDU, trauma/burns, malnutrition

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Mucormycosis

• DM (DKA), leukemia/neutropenia, transplant,
  deferoxamine therapy
• Rhinocerebral Mucormycosis
• Fever, sinus/facial pain/edema, H/A, CN palsies,
  retinal vein thrombosis, cavernous sinus
  thrombosis
• Surgical debridement Amphotericin B
  Posaconazole (60 response rate)