Miller - Exotic Bugs

Question 1

What are the important properties of Bacillus anthracis?

Answer 1

• Large, non-motile, gram (+) rod with square ends, freq found in chains
• Anti-phagocytic capsule composed of D-glutamate (unique) -> encoded on a plasmid
• Expresses anthrax toxins encoded on a different plasmid
• Spore former
• Causes high morbidity/mortality illness (anthrax)

Question 2

What are the epi and transmission of B. anthracis?

Answer 2

• Common, worldwide enzootic bacterium that infects primarily cattle and sheep
• Transmission:
  1. Typically from cutaneous contact w/animal products (e.g., wool, aka, woolsorter’s disease)
  2. Can be via aerosolized droplets containing spores (pneumonic disease)
  3. Can be person-to-person
  4. Vector transmission very rare

Question 3

What are the important B. anthracis virulence factors?

Answer 3

• Anti-phagocytic capsule is an important virulence factor that prevents direct recognition of the bac via phagocytes (no pattern recognition receptor engagement because PAMPS are “hidden” under the capsule)
• Anthrax toxins are also important virulence factors, but we do not need to know them -> small victory

Question 4

What is the pathogenesis of B. anthracis?

Answer 4

• Multiplies at site of infection and disseminates to draining lymph nodes
• Most common (95%) form of disease cutaneous, and has 5-20% mortality rate if left untreated (
• Pneumonic disease has highest fatality rate, and is believed to require a relatively high infectious dose (8k-40k spores) -> mortality rate bt 90-100% if untreated (tx can lower this rate if given early enough)
• GI anthrax can occur w/ingestion of copious amts of spores, but is not well characterized (mortality bt 25-75%)
• Overall, 5-15% of pts die w/o tx, and

Question 5

What are the clinical findings for B. anthracis?

Answer 5

• Pneumonic disease: onset of disease typically bt 4-6 days post-exposure, but can be up to 6 wks (spores can persist in macros for up to 100 days)
  1. Short prodromal period, then initial sxs include non-productive cough, sore throat, mild fever, muscle ache, headache -> soon afterward, more pronounced sxs suddenly appear, incl. high fever, chills, profuse sweating, dyspnea, hypoxia, tachycardia
  2. X-rays: widened mediastinum w/infiltrates and pleural effusions
  3. Mortality rates bt 50-75% w/adequate tx (w/o tx, almost 100% of pts succumb to infection)

Question 6

What are 2 ways that anthrax can cause death?

Answer 6

• Blockage of pneumonic lymphatic vessels can result in progressive pulmonary edema, eventually causing death
• Macrophages responding to the infection make cytokines that can result in septic shock and death

Question 7

How do you diagnose and treat B. anthracis?

Answer 7

• Diagnosis:
  1. If inhalation anthrax is suspected, chest x-rays or CT scans can confirm if pt has mediastinal widening or pleural effusion (characteristic findings)
  2. Confirmation: A) test directly for B. anthracis in a sample (blood, skin lesion swab, spinal fluid, or resp secretion) and/or B) measure Ab’s or toxins in blood
• Treatment: preferred tx is a long course w/Ciprofloxacin (60-day course chemoprophylaxis bc spores can survive in macros) -> in severe cases, cipro can be given IV, and in combo w/other drug: ampicillin, penicillin G, meropenem, rifampicin or vancomycin

Question 8

Why do we need to know about these diseases?

Answer 8

• Low incidence diseases, but it is important to be able to recognize the symptoms bc:
  1. If aerosolized, these diseases can cause a high morbidity and mortality
  2. Prime candidates for biological weapon (Tier 1 select agent by CDC and USDA): possession/use closely monitored, BSL-3 containment practices
• If you can recognize the rare case that does come into the office, you will know how careful all of the staff must be with the pt and samples collected from him/her
• Being able to recognize this disease will help your pts as well as you and the other medical professionals that come in contact with this case

Question 9

What are the important properties of Brucella spp.?

Answer 9

• Small, gram (-) coccobacillus w/o a capsule -> IC bacterium
• 3 species that are human pathogens, and their animal reservoirs are:
  1. Brucella melitensis (goats and sheep)
  2. Brucella abortus (cattle)
  3. Brucella suis (pigs)

Question 10

What are the epi and transmission of Brucella spp.?

Answer 10

• Endemic in Asia, Africa, parts of Europe, Central/South Am
• Transmission:
  1. Typically contracted from contaminated dairy products (cheese, milk) or direct contact w/secretions of infected animals
  2. Imported cheese made from unpasteurized goats’ milk made in Mexico or the Mediterranean has been a source of B. melitensis in the US -> occurs worldwide, but rare in US bc pasteurization of milk kills the org
  3. Person-to-person transmission is rare

Question 11

What is the pathogenesis of Brucella?

Answer 11

• Transmission typically via ingestion or through the skin by occupational contact w/contaminated dairy or livestock
• Bacteria localize in the reticuloendothelial system (lymph nodes, liver, spleen, bone marrow)
• Many orgs killed by macros, but some survive inside macros, where they are protected from Ab
• Host response is GRANULOMATOUS, w/lymphos and epithelioid giant cells, which can form local abscesses -> mech of pathogenesis not well understood, but believed that endotoxin (LPS) is important player (no exotoxins)
  1. Inhalation infection -> granuloma formation (often evident on CXR)
• Morbidity high, but mortality relatively low at approx 2%

Question 12

What are the clinical findings with Brucellosis? Differential?

Answer 12

• Incubation period 1 to 3 wks, w/acute or gradual onset
• Sym: fever, chills, fatigue, malaise, anorexia, weight loss
  1. Enlarged lymph nodes, spleen, liver usually
  2. Pancytopenia (DEC #’s all blood cell types) typical
  3. Fever has undulating pattern (rising and falling) in a minority of pts
• B. melitensis infections tend to be more severe/prolonged
  1. B. abortus infections typically self-limited
• Osteomyelitis (bone infection) is most freq complication
• In pneumonic cases, nodules (granulomas) typically noted on lung x-rays
• Differential: TB, histoplasmosis, cryptococcis, typhoid fever, infectious mono, various forms of hepatitis, flu

Question 13

How do you diagnose and treat brucellosis?

Answer 13

• Diagnose:
  1. Bacteria can be cultured, but need enriched culture media + incubation in 10% CO2 (not typically done)
  2. Presumptive ID via slide agglutination test with Brucella antiserum, and species can be ID’d via biochemical tests
  3. Rise in Ab titer to Brucella can be used (best dx); in absence of acute-phase serum specimen, titer of at least 1:160 in convalescent phase sample is diagnostic
  4. No vaccine for humans, so titers result of infection
• Treatment: tx of choice is Tetracycline or Doxycycline, plus Rifampin -> no significant resistance in this case

Question 14

What are the important properties, epi, and transmission of Burkhoderia pseudomallei (meliodosis or Whitmore’s disease)?

Answer 14

• Small, motile, gram (-) bac and a facultative IC pathogen
• Epi: endemic in SE Asia, esp. Thailand & N. Australia
  1. Environmental bacterium found in soil, rice paddies, and muddy waters
• Transmission:
  1. Typically from inhalation of aerosolized bacteria; outbreaks often after rain storms that aerosolize Bp from the soil in endemic areas
  2. Cutaneous via contact of abrasions w/contaminated soil or water
  3. Person-to-person via body fluid transfer
  4. Ingestion of contaminated water (can survive in water for long periods bc it can inhabit amoebas)
  5. Enzootic pathogen: sheep, goats, horses, swine

Question 15

What is the pathogenesis of Burkholderia pseudomallei (Bp)?

Answer 15

• Thin polysaccharide capsule that is anti-phagocytic (virulence factor)
• Encodes # of proteins involved in invasion of cells
• Well-adapted for living, replicating in macros & classified as IC bacterium (shielded from humoral response)
• Can mediate lysis of host cell that it replicates in as a means of escape, so it can infect other cells
• Can use actin network of infected cells to propel itself into adjacent cells w/o being released into EC space
• Latency mech that allows it to remain dormant in host for many years (Vietnamese time bomb)

Question 16

What are the clinical findings associated with Burkholderia pseudomallei (Bp)?

Answer 16

• Disease can be subacute, acute, or chronic
• Incubation can be as short as 2-3 days, or disease can be latent and asymptomatic for many years
• Most common form of disease is pneumonic via inhalation infection (acute)
  1. Symptoms: high fever, headache, anorexia, general muscle soreness, chest pain, and either a productive (with normal sputum) or non-productive cough
  2. CXR: consolidations of upper lobe w/small nodules (granulomas); progressive disease can produce cavities (clinical picture resembles tuberculosis)
• Bp infection can become septic
• Melioidosis is a very serious disease that results in death in 20-50% of cases, even with appropriate treatment

Question 17

How do you diagnose and treat Burkholderia pseudomallei (Bp)?

Answer 17

• Diagnosis:
  1. Isolation of Bp from blood, urine, sputum, or skin lesions (if cutaneous infection) -> careful to prevent exposure of lab personnel to aerosolized bac bc LD50 of Bp via pneumonic route very low (<100 CFU)
  2. Measuring Bp-specific Ab’s in either acute-phase or convalescent-phase serum
• Treatment:
  1. AB of choice is Ceftazidime -> at least 8 wks, unless pt is immunosuppressed (6 months, in that case)
  2. Intrinsically resistant to many AB’s (e.g., Gentamicin and Colistin) -> helpful in organism identification