Exotic Pulmonary Pathogens - Miller/Whitt

Question 1

Baccillus Anthracis
• Stucture
• Transmission
• Replication Cycle
• Disease Presentation
• Pathogenic Mechanism
• Epidemiology
• Treatment
• Mortality
• Key findings/Diagnosis

Answer 1

Structure:
Large gram-positive spore forming rod with sqaure ends, frequently found in chains. antiphagocytic capsule is composed of d-glutamate.

Transmission:
Typically happens via cutaneous transmission with animal products but can also be transmitted from person to person via aerosolized particles. If ingested can cause GI illness too.

Replication Cycle:
Exists in carriers as a Facultative Intracellular organism. Spore forming so may exist in animal feces.

Disease Presentation:
Most commonly this is a cutaneous infection, but the PULMONARY infection is most deadly. GI infections are also extremely deadly. Pneumonic Disease typically sets in between 4-6 days (spores can sit in macs for up to 6wks). Typically there is a short prodromal period (non-productive cough, sore throat, mild fever, myagia) followed by severe illness (tachycardia, hypoxia, sweating, chills, etc).

Pathogenic Mechanism:
capsule prevents direct recognition by phagocytes (PAMPS are covered and can’t be see by pattern recognition receptors), it also produces several toxins. NOTE: both capsule and toxin genes are coded for an separate plasmids.

Once established it multiplies at the site of infection and disseminates in draining lymph nodes.

Death is caused by blockage of pneumonic vessels (leading to edema and death) or by cytokine storm causing septic shock and death

Epidemiology
Cattle and Sheep carry this toxin (consider wool and other animal products made from these)

Treatment
Prophylaxis - Ciprofloxacin 60 days
Severe Dz: Cipro + Penicillins, Vancomycin, or Rifampicin

Mortality
50%-70% mortality in pulmonary form even with proper tx.

Key Findings/Diagnosis

• *CXR: Mediastinal Widening or pleural effusion**
• *Dx: Culture or Test blood for Abs. or Toxins**

Question 2

Brucellosis spp. (B. melitensis, abortus, suis)
• Stucture
• Transmission
• Replication Cycle
• Disease Presentation
• Pathogenic Mechanism
• Epidemiology
• Treatment
• Mortality
• Key findings/Diagnosis

Answer 2

Stucture
Small gram-negative coccobacillus (no capsule), intracellular (obligate)

Transmission
Infection is typically contracted from contaminated (IMPORTED) Dairy (milk, cheese) or direct animal contact. Rarely human transmission (unlike anthrax), but aerosolized transmission is possible.

Replication Cycle
Lives Intracellularly

Disease Presentation
1 to 3 weeks following exposure patients may experience typical fever, fatigue, chills, etc. Notably fever may be undulating. HEPATOSPLENOMEGALY is often observed (b/c of reticuloendothelial invasion). Pancytopenia is typical and may be related to OSTEOMYELITIS being the most common complication. Granulomas seen in lung infections.

Pathogenic Mechanism
Brucella spp. are specialized for intracellular living in macrophages thus once infection in is contracted they stay in the reticuloendothelial system (lymph nodes, bonemarrow, liver, spleen). Like TB (that also invades macrophages) it causes GRANULOMA formation in lungs in pneumonic infections. It is believed that LPS (endotoxing) is important to its pathogenesis.

Epidemiology
Exists pretty much everywhere (except N. America, because we pasturize dairy, infections in the U.S. are typically from imported dairy)

Treatment
Rifampin + Tetracycline or Doxycycline, no significant resistance reported

Mortality
Low Mortality (only 2%)

Key findings/Diagnosis
Granulomas, Osteomyelitis, Pancytopenia, Hepatospenomegaly
Dx:ANTIBODY TITER to brucella is the best. Culture not typical (requires 10% CO2)

Question 3

Burkholderia pseudomallei
• Stucture
• Transmission
• Replication Cycle
• Disease Presentation
• Pathogenic Mechanism
• Epidemiology
• Treatment
• Mortality
• Key findings/Diagnosis

Answer 3

Stucture
Small ENCAPSULATED motile gram-negative rod that is a facultative intracellular bacterium

Transmission
Occurs via Aerosolized bacteria after RAIN STORM (MOST COMMON ROUTE) => VERY TRANSMISSIBLE. Direct contact can also lead to cutaneous infections. Person-to-person transmission is possible with BODY FLUIDs.

Replication Cycle
See pathogenic mechanism

Disease Presentation => Whitmore’s disease
Disease may present as acute, subacute, or chronic. Due to latency diseas symtoms of HIGH fever, muscle soreness, chest pain, cough (productive or non-prod.) may present in 2-3 days or in years. Sepsis is very possible.

Pathogenic Mechanism
Avoiding phagocytosis via its anti-phagocytic capsule, Burkholderia moves into macrophages (hence granuloma formation) and replicates. Once replicated it can spread via 1. lysing the host and releasing progeny 2. propelling itself via ACTIN network into adjacent cells to avoid detection. It is also able to lay latent for many years Vietanamese time-bomb.

_Epidemiology_ 
Southeast Asia (Thialand and N. Australia) found in rice, soil, and muddy H2O (**can live in H2O for a LONG time** - by inhabiting amoebas). Many farm animals can also harbor this infection. 

Treatment
Ceftazidime for at least 8 weeks, or 6 months if immunocompromised (intrinsically resistant Gentamicin and Colistin)

Mortality
20-50% of cases result in sepsis or death

Key findings/Diagnosis
CXR shows UPPER lobe consolidation or Abscess with GRNAULOMAS and may resemble MTB.
Dx: 2 steps - Isolate and culture AND look at antibodies in convelscent serum

Question 4

Coxiella brunetii
• Stucture
• Transmission
• Replication Cycle
• Disease Presentation
• Pathogenic Mechanism
• Epidemiology
• Treatment
• Mortality
• Key findings/Diagnosis

Answer 4

AKA - Q-fever

Stucture
Gram-negative bacillus that is an obligate intraceullular parasite (similar to legionella)

Transmission
Usually happens when humans handle contaminated viscera (during birth) or drink raw milk. TICKS also carry this pathogen. Aerosolized SPORES are also very infective. EASILY transmitted (very low infectious dose).

Replication Cycle
see pathogenic mechanism

Disease Presentation
30-50% of cases are asymptomatic, others experience 2-4 weeks of ATYPICAL pneumonia with HIGH FEVER. Sometimes the liver and heart are involved which can lead to endocarditis or granulomatous hepatitis.

Pathogenic Mechanism
Very well adapted for living in macrophages (obligate intracellular), allowing it to escape immune detection.

Epidemiology
Affect GOATS mainly, but also infects cattle, and sheep. Seen in almost every country.

Treatment
Doxycycline can be used but most infections resolve spontaneously

Mortality
Very low, below 2% , but 100% if left untreated

Key findings/Diagnosis
Granulomatous liver dz, or endocarditis
Dx: SEROLOGICAL - look for increasing titers to Coxiella b.

Question 5

Francisella tularensis
• Stucture
• Transmission
• Replication Cycle
• Disease Presentation
• Pathogenic Mechanism
• Epidemiology
• Treatment
• Mortality
• Key findings/Diagnosis

Answer 5

Stucture
small pleomorphic Gram-negative rod, obligate intracellular (w/ significant extracellular portion of life cycle), 2 type exist

Transmission
Ticks are the most common vector of transmission and also mice and lice. Lives in amoebas and survives a long time in H2O, but can also be transmitted via blood blood or ingestion. (blood-blood is most common - ulceroglandular form). VERY VERY Transmissible in aerosol.

Replication Cycle
Disease Presentation

Pathogenic Mechanism
LPS that cannot be recognized by TLR-4. It can infect skin (lymph), GI, or eye and disseminate to the lungs or it can go directly their depending on the mode of transmission.

Epidemiology
2 types - type A - American strain - more virulent, type B - Europe - less virulent. Most cases are in Arkansas, Missouri, and Massachusetts.

Treatment

• *Streptomycin (resistance not an issue)**
• *Live VACCINE is available to military personnel**

Mortality
1-3% mortality rate without treatment, survivors have lifelong immunity

Key findings/Diagnosis
CXR: Spotted infiltrates or Lobular, pleural exudation possible
Severe Conjunctivitis, BUBO-LIKE LYMPHADENOPATHY (in surrounding regions)
Dx: Serology

Question 6

Hantavirus (for hantavirus pulmonary syndrome)
• Stucture
• Transmission
• Replication Cycle
• Disease Presentation
• Pathogenic Mechanism
• Epidemiology
• Treatment
• Mortality
• Key findings/Diagnosis

Answer 6

Stucture
Bunyavirus - Spherical, enveloped particles with Trisegmented, negative-sense RNA genome

Transmission
Rodents are asymptomatic carriers that pass it to humans via AIR containng particles of rat saliva, urine or feces. Opening and cleaning vacant buildings (barns, cabins, etc) after winter. Low risk of person-person transmission.

Replication Cycle
Not mentioned here

Disease Presentation
Patients are infected and the virus incubates for 14-17 days before they develop flu-like symptoms (3-5 day) and abdominal pain that rapidly progress to life-threatening pneumonia (days 4-10). Non-cardiogenic pulmonary edema (ARDS-like). Hospitalization and ventilation are typically required.

Pathogenic Mechanism
Increased vascular permeability will lead to bilateral pulmonary infiltrates and pleural effusions

Epidemiology
4 corners - Mexico, Arizona, Colorado, Utah - sin nombre variant

Treatment
Ribaviron (maybe), mostly supportive treatment is needed to AVOID Hypoxia, and Maintain Electrolyte Balance, BP, Etc.

Mortality
~50% mortality

Key findings/Diagnosis
NON-cardiogenic Pulmonary Edema (normal heart size on CXR with bilateral infiltrates)

Question 7

Yersinia pestis
• Stucture
• Transmission
• Replication Cycle
• Disease Presentation
• Pathogenic Mechanism
• Epidemiology
• Treatment
• Mortality
• Key findings/Diagnosis

Answer 7

PLAGUE/BLACK DEATH

​Stucture
small encapsulated gram-negative rod (lost upon passage in vitro) that lives intracellularly (in macs) and exibits bipolar staining to resemble a SAFETY PIN

Transmission
INSANELY transmissible (1-10 bugs). Rats and Prairie dogs carry and Fleas bite them and then bite people to transmit. AEROSOLIZED particles are also transmissible (most virulent).

Replication Cycle
No specifics

Disease Presentation
Lymph nodes where the Flea bit get very swollen and people get SEVERE flu-like symptoms, and collapse is commonly seen. Nodes continue to enlarge and Septic Shock and pneumonia (via septic emboli) are they typical killers.

Pathogenic Mechanism
Fleas bite and the infection spreads to lymph nodes causing buboes to form (bubonic plague). Typically the infection becomes bacteremic due to protection from the ¹polysaccharide protein capsule and hematogenous spread to many organs occurs. ²LPS (ENDOTOXIN may aid in this spread. ³V and W proteins also allow this guy to live and grow in macrophages. ⁴Yersinia outer proteins (Yops) are injected (type III secretion) into host cells to inhibit phagocytosis and cytokine production. ⁵Also produces exotoxin which cause DIC an hemorrhage. Disease may affect the lungs regardless of how it was introduced.

Epidemiology
99.9% of cases occur in Southeast Asia - found in rodents everywhere

Treatment
TREAT IMMEDIATELY with Streptomycin or Tetracycline
Vaccines are available for military for bubonic form only

Mortality
50% (bubonic), 100% (pneumonic) without tx.

Key findings/Diagnosis
BULBULAR Lymphadenopathy,
Dx: Giemsa or Wayson stains will show safety pin appearance, Serology can also be used.