However, because plague, unlike smallpox, is spread by large respiratory droplets, close contact is required for transmission Clinical Manifestations Bubonic plague is characterized by the classic bubo, a tender, enlarged, fluctuant lymph node in the distribution of the infected flea bite Fever and malaise are usually present Bubonic plague may progress to septicemia as bacteria gain access to the circulation; 80% of bubonic plague victims have positive blood cultures Petechiae, purpura, and overwhelming disseminated intravascular coagulation (DIC) may develop Pneumonic plague may arise secondarily after blood-borne seeding of the lungs or may be seen primarily after aerosol exposure Symptoms include high fever, chills, malaise, fatigue, headache, and cough Chest radiographs may reveal a patchy or consolidated bronchopneumonia, and the classic clinical finding is one of blood-streaked sputum; DIC and an overwhelming sepsis may develop as the disease progresses Meningitis develops in 6% of cases Untreated pneumonic plague has a mortality rate approaching 100% A presumptive diagnosis of plague can be made by observing the classic bipolar-staining “safety pin”—like rods in Gram or Wayson stains of sputum, aspirated lymph node material, or cerebrospinal fluid Confirmation is obtained via blood, sputum, or aspirate culture Management Droplet precautions should be employed in cases of suspected pneumonic plague Such precautions should be continued in confirmed cases until sputum cultures are negative Standard precautions are adequate in managing bubonic plague victims Given the incubation period, decontamination would not be necessary in a clinical setting See Table 132.3B for detailed treatment recommendations for children Smallpox CLINICAL PEARLS AND PITFALLS Smallpox is contagious day prior to the onset of rash In contrast to chickenpox, the rash of smallpox starts on the face and extremities and spreads centrally The smallpox rash develops synchronously such that lesions are all in the same stage Strict airborne, droplet, and contact precautions should be instituted immediately for smallpox victims and should continue until all scabs have separated Smallpox is associated with a high mortality and there is no specific therapy available Background The global eradication of smallpox represents one of the great success stories of public health, with the last endemic case occurring in Somalia in 1977 Since then, research stockpiles of variola virus have been consolidated into two World Health Organization (WHO)–approved stores at the CDC in Atlanta and at a Russian institute in Koltsovo This achievement would seem to make terrorist use of this virus impossible; however, several factors give cause for concern First is the fear that other stockpiles already exist in the hands of belligerent nations unbeknownst to WHO Astonishingly, in 2014, vials containing the smallpox virus were discovered in a storage room of an FDA laboratory in Bethesda, Maryland Second, the entire viral genomic sequence is known and published; therefore, it is likely only a matter of time before technology permits reconstruction of the virus (the related horsepox virus has already been synthesized de novo) Finally, although the virulence factors of variola virus are poorly understood, it may be possible for someone to manipulate related orthopoxviruses such as monkeypox to enhance their virulence in humans and create a disease similar to smallpox In light of these considerations, the CDC in 2003 recommended a strategy of reintroducing vaccination in the United States after a nearly 30-year hiatus, with the initial goal of vaccinating up to 10,000,000 front-line EMS and healthcare providers This program has subsequently proven controversial and has been suspended; probably fewer than 50,000 civilians were vaccinated The U.S military, however, has vaccinated several hundred thousand service members and serious adverse events have been rare Several factors might make smallpox an attractive weapon to potential belligerents First, the duration of immunity after vaccination is a matter of controversy, with some studies suggesting a duration of only to years, while other studies suggest the possibility of lifelong immunity Second, following cessation of universal vaccination within the United States in 1972, vaccine had been out of production until the 2007 licensing of a new product (ACAM2000, Acambis Corporation); although the CDC now controls enough ACAM2000 to vaccinate every American, susceptibility to the disease is nearly universal Also, effective therapy is lacking and healthcare providers are unfamiliar with the disease Finally, the potential for rapid spread potentially permits a terrorist to cause widespread disease and panic with a minimum of infectious material Pathophysiology Although infectivity is highest when the smallpox rash first appears, the disease may be spread by exposed persons about 24 hours before the exanthem manifests During the 7- to 17-day long incubation period, the virus replicates in upper respiratory tract mucosa, giving rise to a primary viremia The liver and spleen are then seeded, further amplification of the virus occurs, and a secondary viremia ultimately develops The skin is seeded with this secondary viremia, and the classic exanthem of smallpox develops Clinical Manifestations Clinical illness has an abrupt onset during the phase of secondary viremia and is characterized by fever, malaise, rigors, vomiting, headache, and backache The classic exanthem typically begins to days later as macules on the face and extremities These lesions progress in synchronous fashion to papules, vesicles, and then to pustules, which finally form scabs As scabs separate, survivors are left with disfiguring depigmented scars The rash spreads centrally to the trunk but remains more abundant at the periphery This centrifugal distribution and synchrony distinguish smallpox from chickenpox, which has a centripetal distribution of lesions in varying stages of development An enanthem usually accompanies the characteristic exanthem, and internal organs become viral targets as well Death historically occurred in approximately 30% of variola major (the predominant form of smallpox in the past) patients and typically resulted from hypotension and immune complex–associated toxemia Eye involvement led to blindness in a small number of victims Uncommon variants with lesser (variola minor) or greater (hemorrhagic and flat-type variants) mortality also existed Ominously, a 1971 smallpox outbreak in Aralsk, in the former Kazakh Soviet Republic, is thought by some to have originated from a bioweapons accident All three fatalities in this small outbreak involved unvaccinated individuals who contracted rare and universally fatal hemorrhagic disease, raising the specter of genomic manipulation for increased virulence Management The diagnosis of smallpox should be suspected on clinical grounds Laboratory confirmation (e.g., electron microscopy, PCR) is best effected in a biosafety level laboratory by emergent notification and specimen transport to the CDC Based on past experience, vaccination (with vaccinia, an orthopoxvirus closely related to variola) of smallpox-exposed persons within the first days after exposure may prevent the development of overt disease Although the vaccine has been used safely and successfully in even young infants, it has a relatively high rate of serious complications in certain patients Notably, fetal vaccinia and resultant fetal demise can occur when pregnant women are vaccinated Vaccinia gangrenosa, a frequently fatal complication, occurred when immunocompromised persons were inadvertently vaccinated Eczema vaccinatum may occur in those with pre-existing skin conditions and can be serious Myocarditis and pericarditis may occur A severe postvaccinal encephalitis was well known, albeit relatively rare, during the era of widespread vaccination, because this complication occurs only after primary vaccination, it would disproportionately affect pediatric patients Autoinoculation can occur when virus from the primary lesion arising at the site of vaccination is transferred by scratching or rubbing to other areas of the skin or to the eye To manage these complications, vaccinia immune globulin (VIG) should be available when undertaking a vaccination campaign VIG (0.6 mg/kg intramuscular [IM]) may be given to vaccine recipients who experience severe complications or to significantly immunocompromised individuals exposed to smallpox in whom vaccination would be unsafe Today, stocks of vaccine and VIG are controlled by the CDC There is also a nonreplicating smallpox vaccine (IMVAMUNE) for immune-compromised patients that is not yet FDA approved but is stocked by the CDC for emergency use Even a single case of smallpox occurring anywhere in the world today would represent a grave public health emergency A suspected case should thus prompt immediate notification and consultation with health authorities Strict airborne, droplet, and contact precautions should be instituted immediately for victims and should continue until all scabs have separated Decontamination of symptomatic patients is unnecessary Contacts must be observed closely for 17 days following their last potential exposure The development of fever during this period would be a cause for isolation Multiple victims would ideally be managed as a cohort at dedicated sites removed from conventional hospital facilities Botulism Background Botulism occurs as a result of exposure to one of eight botulinum neurotoxins (A through H) Only types A, B, E, and, rarely, F appear to cause human botulism in nature Botulinum toxin was included in the U.S biologic ... approved but is stocked by the CDC for emergency use Even a single case of smallpox occurring anywhere in the world today would represent a grave public health emergency A suspected case should thus... because this complication occurs only after primary vaccination, it would disproportionately affect pediatric patients Autoinoculation can occur when virus from the primary lesion arising at the site