33: Bioterrorism – Anthrax & Smallpox

advantages of biological agents as weapons
easy to obtain (in soil!), inexpensive to produce, can disseminate over large geo area, overwhelm medical services and create panic, perpetrators escape easily

ideal bioterrorism microbe
infectious via aerosol, stable in environment, susceptible civial population, high morbidity and mortality, person-to-person transmission (plague, smallpox), difficult to Dx/Tx, previously developed for biowarfare

Bacillus anthracis: microbial characteristics
large aerobic spore-forming gram (+) rod

bacillus vs corynebacterium on gram stain
both gram (+) rods, but corynebacteria cluster together, vs bacillus are clean and separated

cutaneous anthrax: transmission
contact with spore-contaminates: textile, raw hides, etc.

Dx: textile worker develops eschar
cutaneous anthrax

Dx: hide sorter develops painless black wound
cutaneous anthrax

cutaneous anthrax: clinical course
inoculation > papular lesion > vesicular with surrounding edema > painless black eschar

GI anthrax: transmission
ingestion of contaminated/undercooked meat > spores germinate in intestine > after up to 1 week incubation, bloody diarrhea/fever/vomiting (severe gastroenteritis) with TREATED case fatality up to 75%!

*inhalational anthrax: clinical course
inhalation of anthrax spores > 3-40 day incubation period > nonspecific flu Sx >* TRANSIENT IMPROVEMENT > rapid deterioration: high fever, dyspnea, shock > death if untreated

form of anthrax with transient improvement
inhalational anthrax

inhalational anthrax: pathogenesis
inhalation of 2 um particles > ingestion by alveolar M0’s > move to hilar LNs > germination, production of anthrax toxin > hemorrhagic necrosis of nodes and mediastinum (WIDENS); gelatinous pleural effusion, producing atelectasis (anthrax PS) > bacteremic seeding of other organs > hemorrhagic meningitis

B. anthracis: virulence factors
capsule (antiphagocytic) and 3 toxins: PA: B part of A-B toxin, cleaved on surface to provide channel for entry of EF (edema factor: activates adenylate cyclase > cAMP > EDEMA) and LF (MAPKK pathway > cell death)

*telltale signs of inhalational anthrax
widened mediastinum WITHOUT pulmonary infiltrates (pneumonia) since germination of spores occurs in hilar LNs, not lung; accompanying fever, tachycardia, tachypnea, “toxic” appearance

how to confirm inhalational anthrax Dx
sputum culture/PCR, CSF gram stain/culture (hemorrhagic meningitis), serology: IgG

hemorrhagic mediastinal LNs on CT: Dx, and how to confirm
inhalational anthrax; confirm with sputum culture/PCR, CSF gram stain/culture (hemorrhagic meningitis), serology: IgG

patient with widened mediastinum on CXR: Dx, and how to confirm
inhalational anthrax; confirm with sputum culture/PCR, CSF gram stain/culture (hemorrhagic meningitis), serology: IgG

inhalational anthrax: treatment approach
ciprofloxacin or doxycycline, PLUS additional Abx (vancomycin, Pen G) – treat for long enough to prevent germination of additional spores (2 months)

cutaneous anthrax: treatment approach
ciprofloxacin or doxycycline, no additional Abx, and only for 7-10 days

anthrax: treatement and prevention for different types
cutaneous: ciprofloxacin or doxycycline for 7-10 days; if inhalational, ADD additional Abx and extend for 60 days (logn enough to prevent germination of additional spores); PROPHYLAXIS: same Rx, > 60 days because spores can germinate well after exposure

anthrax vaccine: component, and demographic
against protective antigen; reserved for military and occupational exposures

anthrax patients who require isolation
NONE – not spread person-to-person (but spores remain viable for decades – an issue for vets and animal husbandry)

cousins of smallpox virus
vaccinia, molluscum contagiosum, cowpox

smallpox virus: genome

eradication success of Smallpox
success using vaccinia vaccine, but repositories maintained at CDC and Russia (possible bioterror agent because high potential for morbidity, mortality, person-to-person transmission, and unpreparedness)

smallpox: transmission
*infectious during rash, which follows fever (isolate at fever stage); person-to-person spread via aerosols/droplets, stays in fomites but dies in environment: up to 10 new cases per original case

*when to isolate smallpox patients
keep them at home, but stay away once they get fever – precedes rash stage, which is infectious

smallpox: clinical course and infectivity
1-3 week incubation, fever, then 2-3 days later: monomorphic nodular rash appears on mouth/face first, then spreads to trunk and legs; most infectious during first week of rash, when oral lesions (enanthem) ulcerate > ++ virus in saliva; no longer infectious after all scabs of rash have fallen off (3-4 weeks after rash onset)

when is smallpox patient most infectious?
oral rash (enanthem) – the lesions ulcerate and produce ++ virus in saliva

smallpox: treatment, prognosis
NO Rx (unlike anthrax); case-fatality ~ 30%

*Dx: monomorphic nodular rash
smallpox (vs chicken pox – different stages of maturity)

major* vs minor features of smallpox
*MAJOR: fever prodrome 1-4 days before nodular RASH that is MONOMORPHIC anywhere on body; minor criteria: first appears on mouth/face/forearms, with slow evolution; toxic appearance

first sign of smallpox illness
fever – when contacts need to be isolated

chickenpox vs smallpox
TIMELINE: similar incubation periods, but fever first in smallpox; LOCATION: chicken pox = trunk, smallpox = face/extremities, *including palms/soles; RASH: chicken pox: different stages, vs smallpox: monomorphic throughout body; DX: both can use culture/PCR of vesicular fluid, but smallpox Dx at CDC, vs chickenpox can also be Dx with serum IgM, Tzanck smear

features of vaccinia virus
live (unattenuated) strain that provides cross-immunity to smallpox virus

*how to determine that smallpox vaccination was succsesful
must be evidence that vaccinia virus has replicated in recipient: get “Jennerian vesicle” after ~ 1 week, which evolves to form a scab and falls off with scarring at week 3

*side effects of smallpox vaccine
flu-like with tender regional LNs; serious side-effects possible: viremia, encephalitis, eczema vaccinatum, myocarditis, autoinnoculation of other sites on body

smallpox vaccine: contraindications
patient or household contacts have immunosuppression, eczema (vaccine causes eczema vaccinatum); also allergy to Rx within vaccine

smallpox public health approach
isolate suspected cases in home and notify Health Dept; vaccinate during first few days after exposure – could be protective; then isolate when fever occurs