Chapter W11 FINAL 121612 - ER GRM

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures
Pharmacotherapy: A Pathophysiologic Approach. 9th Edition CHAPTER W11: Emergency Preparedness and Response: Biologic Exposures Colleen M Terriff, Jason E Brouillard and Lisa T Costanigro
Key Concepts
Bioterrorism agents are organisms, such as bacteria and viruses, or toxins that can cause disease and death in humans and animals and can elicit panic, social unrest or terror. Category A bioterrorism agents include anthrax (Bacillus anthracis), tularemia (Francisella tularensis), smallpox (variola major), plague (Yersinia pestis), botulinum toxin (Clostridium botulinum), and viral hemorrhagic fevers. Anthrax is a spore-forming, toxin-producing organism, which can cause serious sequela, especially after inhalation. Rapid recognition of botulism based on clinical presentation, which mimics a variety of other conditions, is essential to prompt antitoxin therapy. Pneumonic plague can cause a rapid onset of symptoms like influenza and bacterial community-acquired pneumonia and is highly lethal if not rapidly treated. While smallpox has been globally eradicated smallpox vaccine is stockpiled in response to a suspected or confirmed outbreak.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Pharmacological treatment of viral hemorrhagic fever is predominantly supportive care. Infectious disease outbreaks following a natural disaster are not common, yet they should be monitored and anticipated with quick recognition and management.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Pharmacotherapy: A Pathophysiologic Approach. 9th Edition CHAPTER W11: Emergency Preparedness and Response: Biologic Exposures Colleen M Terriff, Jason E Brouillard and Lisa T Costanigro
[A]Introduction It has been more than a decade since the fall of 2001, a tragic time which awakened the American public to concerns about terrorism, previously only considered a threat by the military. While anxiety surrounding intentional bioterrorism attacks and the multitude of false alarms may have lessened, recent devastating natural disasters, such as tsunamis and hurricanes, have enhanced our appreciation of the power and destruction associated with Mother Nature. In addition, infectious disease outbreaks, such as the 2009 H1N1 influenza pandemic which caused an estimated 43 to 89 million cases of the flu in the U.S. and the 2012 pertussis epidemic in Washington State, impacting thousands of infants and children, will continue to occur.1, 2 Emergency managers, healthcare providers, first responders, public health officials, businesses, schools and community organizations are continuing to plan for their response to disasters and emergencies,. It is important to be aware of and anticipate which resources are or will be needed and which are available, locally, regionally and nationally. In particular, healthcare providers need to play an active role in community preparedness for biological threats.They also should be involved in the decision-making process regarding small-scale or mass vaccination or postexposure prophylaxis (PEP), and treatment of biologic exposures to help protect the public and save lives.For example, in late April of 2009 the Centers for Disease Control and Preventions (CDC)Division of the Strategic National Stockpile (SNS) released antiviral drugs, respiratory protection devices, and personal protective equipment, to help bolster local
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures stockpiles, which were quickly being depleted during the early phase of the influenza pandemic.3Vaccine development and distribution, as well as execution of immunization campaigns for recommended targeted groups, was tasked to health departments, many of which actively sought recommendations and assistance from local healthcare providers and organizations. In Spokane, Washington in response to the H1N1 pandemic over 3,500 vaccinations were administered at clinics held at the local sporting arena, YMCA, and area homeless shelters staffed predominantly by local pharmacy and nursing students and faculty. 4 Bioterrorism agentsorganisms or toxins that can cause disease and death in humans and animals for the purpose of eliciting terrorhave been used against civilians and military personnel for centuries. Thousands of years ago effective, albeit crude, methods were used as acts of bioterrorism. Filth, human cadavers, and animal carcasses were flung over city walls,
poisons were dropped in drinking wells, and contaminated clothing and blankets were offered as gifts to cause disease and, ultimately, death to enemies.5 More recently, sophisticated methods have been utilized, such as aerosolized technology for spraying plague and an umbrella-looking device used to shoot ricin toxin pellets for a targeted assassination.5,6Over the past century a variety of methods to weaponize biologic agentsenhance the shelf-life or dissemination properties (i.e., aerosolize) and/or fill munitionshave been researched.5Only a handful of countries, which include Syria, North Korea, and the United States, are believed to have active biological weapons programs, either: conducting research on the virulence of selected agents (defensive), weaponizing them (offensive) or both.7 This chapter describes the natural history, symptomatology, diagnostic procedures, and pharmacologic and nonpharmacologic treatment of biological agents of highest concern that could be used in a bioterrorism attack, such as anthrax, botulinum toxin, plague, smallpox,
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures tularemia, and viral hemorrhagic fevers. The potential consequences of infectious disease outbreaks surrounding natural disasters, which rival bioterrorist events in their devastating potential, are also discussed. An evidence-based approach evaluating the various treatment
options, including those for special populations, is presented, when the relevant data is available. Finally, information about the roles of healthcare providers in emergency preparedness and response is shared. [A]Evaluation of Risk and Development of Prevention Strategies In 2000 the CDC published their strategic plan for biological and chemical terrorism preparedness and response, advocating for a strong public health infrastructure and enhanced health-care capacity to provide early detection and control for both overt and covert attacks. 8 Preparatory steps, such as enhancing detection and diagnostic capacity, establishing communication programs delivering accurate and timely information, and providing education materials for public and education and training for health-care professionals, are still crucial and relevant today.8
Both the CDC and National Institute of Allergy and Infectious Diseases classified critical biological agents into three different categories (A, B, and C) based on their ability to be easily disseminated or transmitted person-to-person; cause high mortality, with the potential for major public health impact; cause public panic and social disruption; and require special action of public health preparedness (Table W111).8-10For example, Bacillus anthracis, the bacteria which causes anthrax, is classified in category A, since untreated inhalation anthrax has a very high mortality rate and cases would cause great stress on any medical community. Yersinia pestis (plague) and variola major (smallpox) are also examples of category A agents. While not covered in this chapter Brucella species (brucellosis), ricin toxin, and Salmonella typhimurium
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are classified as category B agents; and emerging pathogens, such as resistant bacteria, and wellestablished infections like influenza, are grouped into category C (Table W112).10Periodically this list is reviewed and revised by the National Institutes of Allergy and Infectious Diseases (NIAID), in partnership with Department of Homeland Security. Bioterrorism agents most likely will be released as a covert or hidden attack, allowing exposures to go unnoticed. Patients may present to a healthcare provider days or weeks after exposure, allowing for further spread of a contagious agent. This delayed detection and commencement of PEP and treatment may have great local, and even global, public health implications. Preparedness and response, focusing on pre-exposure vaccination, PEP and treatment, are key infection control measures where healthcare providers can make a significant impact. Preexposure vaccination is the administration of a protective vaccine to the public, military troops, or high-risk individuals prior to the potential exposure to an infectious disease. Mandatory childhood vaccinations against diphtheria, measles, tetanus, and poliomyelitis, for example, and recommended vaccination against seasonal influenza, have proven effective in protecting children and the general public. Although there are some vaccines available for category A agents, the segment of the public who would qualify for pre-exposure inoculation is exceedingly small. For example, BioThrax, an inactivated anthrax vaccine, is recommended for adults up to age 65, who are at high exposure risk.11Thisgroup may include those working directly with Bacillus anthracis in the laboratory or military personnel deployed to high risk areas as recommended by the U.S. Department of Defense. Vaccinating large numbers of people or the population of an entire region or country is an important method to curtail the spread of highly contagious agents, such as smallpox and pandemic influenza. Smallpox was successfully eradicated in 1977, a decade after mass
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures vaccination campaigns commenced.12 Global eradication of a vaccine-preventable disease is extremely challenging in part because of the rapidity of international travel, the growing world population, poor nutrition, and overcrowding, and the significant expansion of the numbers of immunocompromised individuals who now reside throughout the world. Other general challenges include increasing vaccination refusal rates; constant evolution of circulating pathogens, such as influenza; and newly recognized side effects and related liability and risk concerns. For example, there were 140 reported cases of myopericarditis, which developed during the first year of the controversial U.S. smallpox vaccination program, to protect both our military and civilian population against this theoretical bioterrorist threat. 13This rare but serious sequela contributed to the halting of the U.S. smallpox mass vaccination program. In the meantime, over 1,200,000 military forces and healthcare workers were vaccinated, and most adverse events occurred at rates lower than historical rates during this campaign.13
PEP involves dispensing or administering a medication (including a vaccine) immediately or very soon after exposure to an organism (either from primary exposure or secondary exposure, such as person-to-person transmission), so as to prevent the disease from developing and worsening or spreading to others. For instance, after an anthrax-containing letter was delivered to and opened in the Hart Senate Office Building in Washington, DC, in fall 2001, ciprofloxacin and doxycycline were dispensed to hundreds of congressional staff who had offices on the fifth and sixth floors of the southeast wing.14Some of the challenges surrounding PEP include assessing: who was truly exposed to an organism or toxin, who is at high risk of acquiring the infection if it is spread person-to-person, and who is at risk for developing the disease and its sequelae. In most cases, because of the potential lethality of category A agents like anthrax, more individuals will be given PEP than is probably necessary. An important therapeutic approach
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures surrounding prophylaxis involves prompt initiation of the regimen with the appropriate empiric antimicrobial. These concepts are no different than if there was a meningococcal outbreak on a college campus, for instance. Treatment for confirmed cases of a biologic agent exposure is challenging. People may not seek medical care until fulminant symptoms and signs are evident, which may thereby increase the
likelihood of mortality. Based on limited case reports from zoonotic infections (non-bioterrorism related) in the latter half of the 20th century, if individuals with primary pneumonic plague did not receive treatment within 24 hours of exposure, the disease was rapidly and inevitably fatal.15Adults and children may present with nondescript, albeit severe, symptoms that mimic common infections, such as community-acquired pneumonia or influenza. Treatment should not be delayed until the results of confirmatory laboratory tests become available days or weeks later. Suspected or confirmed cases require immediate treatment, including supportive care and empiric intravenous antimicrobial therapy, ideally within 24 hours, with conversion to oral regimens when appropriate. Every few years and as recently as 2011 the United States Army Medical Research Institute of Infectious Diseases or USAMRIID publishes medical information for biological agent exposure, with a focus on medical defense for the U.S. military.5 Information and recommendations for the identification and management of bioterrorist exposures in civilians as been scant until the late 1990s when the Journal of the American Medical Association started publishing a series of consensus papers on category A agents.15-20 These guidelines provided PEP and treatment recommendations for adults, children, and pregnant women. However, there still remains limited information regarding exposure management among other vulnerable groups, such as severely immunocompromised and patients with multiple co-morbid disorders or disease states.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures [A]Desired Outcomes There are multitudes of potential or theoretical individual and public health-related outcomes concerning the prophylaxis and/or treatment of suspected or confirmed cases of biological exposure. Much of what is available is historical case reports or in vitro and animal data. Global efficacy goals would include prevention of disease progression, a reduction of serious sequela and mortality, decrease in transmission (for those agents which are contagious), and decrease in anxiety and panic, with a quick restoration of normalcy for the community and country.
Maximizing safety issues and employing the most cost-effective modes of providing prophylaxis and treatment are important additional considerations. For pre-exposure (i.e. vaccination) campaigns the main goal would be to immunize those who would be deemed at risk, while minimizing adverse events. The previous mentioned smallpox vaccination campaign is an example of a pre-exposure prophylaxis attempt, which was, overall, successful, but brought to light safety concerns. Post-exposure prophylaxis data, beyond information from the anthrax exposure in Washington, D.C., is also scant. Without robust outcome data, one must turn to comparing pharmacologic, microbiology and cost for common antibiotics used for PEP. Some have considered doxycycline as the preferred agent for PEP management for many bioterrorism agents (including some category B agents), except for inhalation plague, due to comparable microbiological effectiveness, low cost, and a lower antibiotic resistance potential.21 Considering finances and effectiveness, researchers from Toronto analyzed 4 strategies deployed after a hypothetical aerosolized B. anthracis incident: no prophylaxis, antibiotics, vaccination, and combination of antibiotics and vaccination. 22Their analysis indicated that when anthrax is released over an unvaccinated urban population starting both vaccination and antibiotic therapy would be the most effective and least expensive option.
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However, administering this combination would a logistical challenge, since dispensed antibiotic quantities are large (long duration of prophylaxis) and the vaccine schedule is frequent.
[A]Biologic Agents: Category A [B]Anthrax The term anthrax is derived from the Greek word anthrakis meaning coal, because of the classic black eschar lesions caused by the cutaneous form of anthrax.23Anthrax was first described in the early biblical era of Moses and the fifth Egyptian plague in Exodus 9, and in the last three decades, numerous human cases have been reported. Poor veterinary vaccination programs in Zimbabwe lead to 6,500 human anthrax cases and 200 deaths in 1979 and 1980. An accidental exposure at a research center in what is now Ekateringburg, Russia, caused the death of 66 adults in 1979. In the fall of 2001, several envelopes containing anthrax were discovered in the United States, which led to 22 confirmed and suspected cases and five deaths.24,25
[C]Etiology
B. anthracis is a gram-positive, spore-forming rod found endemically in the soil of many regions worldwide. Domesticated and wild herbivores (e.g., sheep, camels, elephants, horses, cattle, goats) commonly acquire anthrax; humans usually become infected through contact with infected animal tissue, exposure due to an intentional release, or most recently, cutaneous infection from contaminated illicit injection drugs.26 One characteristic that separates anthrax from most other agents in category A is its ability to produce spores under adverse conditions. Endospores produced by the bacterium are resistant to most forms of sanitization and are thus capable of persisting for several years in contaminated environments; waiting for entry into the blood or tissue of an animal where they then germinate and cause disease.
[C]Pathophysiology
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Three clinical manifestations of anthrax exist: cutaneous (the most common, but least severe), inhalational (main bioterrorism concern), and gastrointestinal (very infrequent). Rare, but lifethreatening neurologic complications, such as cerebral edema and hemorrhagic meningitis, are possible sequelae of all primary forms of anthrax infections.27Anthrax spores deposited into pulmonary alveoli may not germinate until taken up by alveoli macrophages and transported to regional lymph nodes, potentially taking weeks or months, which necessitates extended durations of antibiotic coverage. Replicating bacteria, once in a host, achieve their virulence via production of two main toxins, named lethal toxin and edema toxin. Edema toxin, as its name implies, causes extensive systemic edema as the result of disruptions of electrolyte and water transport across cellular membranes, whereas lethal toxin is thought to be responsible for the tissue damage, shock, and high probability of death associated with infection.27Although anthrax is extremely virulent and pathogenic, there is no documented human-to-human transmission.
[C]Clinical Presentation
[D]Cutaneous Naturally occurring anthrax is nearly always attributable to cutaneous infection. Bacterium (acquired via handling of contaminated animal products) enters the body via abrasions on the skin and causes localized edema progressing to a small, pruritic papule 1 to 12 days after infection. Within 1 to 2 days, the papule enlarges to a round ulcer and then the characteristic painless, black eschar follows. One to 2 weeks after infection the eschar dries and sloughs away (Fig. W111). Subsequent lesions near the initial papule may occur. Once anthrax is suspected, a Gram stain of the vesicular fluid should yield gram-positive bacteria and, ideally, the stain is confirmed with culture.16 Mortality rates from the cutaneous form are relatively low at
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures approximately 5% to 20% in untreated cases and <1% in antibiotic-treated cases, with most deaths associated with disseminated disease or progression to sepsis.5, 23 [D]Gastrointestinal
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Acquiring the gastrointestinal form of anthrax is rare and usually occurs as a result of ingestion of contaminated meat. The incubation period is similar to the inhalation form and ranges from 1 to 7 days. Oropharyngeal ulcerations are common, along with sore throat and fever. Initially nausea, loss of appetite, and vomiting will predominate, transitioning into severe abdominal pain and bloody diarrhea after acute inflammation of the bowel. These typical symptoms often closely mimic other gastrointestinal maladies, making a definitive diagnosis difficult. Obtaining a thorough history and culturing ulcerations may be helpful. Mortality rates are higher, estimated at 25% to 60%, due to the difficulty in early diagnosis.23Treatment protocols should involve antibiotics and surgical intervention of the affected intestine may be indicated.27 [D]Inhalational Inhalational anthrax is the most likely form of infection encountered after intentional dispersal. The initial symptoms strongly resemble those of influenza infection; fever, nonproductive cough, myalgia, and fatigue after a short incubational period of 1 to 6 days (potentially extending out to 43 days because of endospores). One component of the prodrome not described before the bioterrorist attack in the United States in 2001 was the occurrence of profuse drenching sweats, which may prove beneficial in differentiating inhalation anthrax from viral illness. 24 Chest radiographs often reveal mediastinal widening or pleural effusions, both hallmarks of anthrax exposure (Fig. W112). The CDC recommends obtaining blood, pleural fluid, and cerebrospinal fluid, if available, for culture, Gram stain, and polymerase chain reaction (PCR). Sputum cultures are not recommended initially because of the lack of actual lung involvement. Without prompt
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures antibiotic initiation, the mortality rate may be as high as 85% within 24 to 36 hours after symptom onset.5Prompt medical attention and initiation of antibiotic treatment is imperative; alarmingly, data from the outbreak in 2001 demonstrated that victims waited an average of 3.5
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days to seek medical advice.24This lends high importance to the development of a strong clinical knowledge base regarding detection, diagnosis, and treatment.
[C]Treatment
[D]Management of Potential Exposure Once a suspected or confirmed exposure case is known, identifying at-risk individuals becomes the highest priority. Persons with exposure to an item or environment thought or known to be contaminated with B. anthracis should be offered antibiotic therapy, irrespective of laboratory test results. Nasal swabs can be used to help detect anthrax spores, but cannot rule out exposure. Based on in vitro and animal data, the CDC has published treatment guidelines to assist healthcare professionals.25, 28For PEP of inhalation anthrax (in adults, pregnant women, the immunocompromised, and children), oral doxycycline or ciprofloxacin is recommended as a first-line agent. Because spores may persist in lung tissue after aerosol exposure, antibiotic therapy must be continued for 60 days (Table W113). 27, 28 Although no controlled studies using PEP after suspected cutaneous or gastrointestinal exposures exist, doxycycline, ciprofloxacin, penicillin, and amoxicillin all have reasonably predictable activity against B. anthracis and could be used for shorter durations (714 days).23Pre-exposure vaccination regimens are available, but are usually reserved for military personnel and select groups of people with potential exposure to anthrax. The vaccination schedule is laborious, requiring five injections over 18 months, in addition to annual boosters. Data from various
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nonhuman studies show that vaccination alone is not protective postexposure, but the Food and Drug Administration (FDA) has approved the vaccination for postexposure treatment.11 [D]Treatment of Confirmed Cases Intravenous doxycycline or ciprofloxacin are indicated for use in treatment of inhalation anthrax and gastrointestinal anthrax. In addition, one to two other antibiotics with documented activity against B. anthracis (see Table W113) should be added to the therapy. This combination should be continued for 60 days (conversion to oral antibiotics is recommended once the patient becomes clinically stable).28Treatment of cutaneous cases differs in that only one antibiotic (doxycycline or ciprofloxacin) is necessary and oral products may be used initially. Clinically severe cases, such as those with extensive edema or lesions of the head or neck, require intravenous antibiotics. Regardless of whether the cutaneous infection is deemed severe or not, the selected antibiotic should be continued for 60 days, just like treatment for inhalation or gastrointestinal anthrax. The extended duration is a result of the possibility of cutaneous infections being caused by intentional release and the potential inhalational exposure.28Those treated during the outbreak of 2001 all received combination therapy (at least two antibiotics with activity against B. anthracis) and their fatality rate of 45% was slightly lower than previous observations reported in the literature.23,24In addition to antibiotic therapy, aggressive supportive care should also be pursued. Drainage of pleural effusions, correction of electrolyte imbalances, and early mechanical ventilation all appear to positively affect survival rates. One monoclonal antibody, raxibacumab, specifically directed at a component of the anthrax toxin demonstrates the impressive potential of these antibodies. When doses of raxibacumab were given in animals before aerosolized exposure to B. anthracis spores, 14- and 28-day survival rates were about 80% versus 0% in placebo groups. Fourteen- and 28-day survival rates of 50% were recorded
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures when administration of raxibacumab was delayed until serum testing confirmed anthrax toxin exposure.30Raxibacumab could potentially have a role in confirmed exposure cases or when
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initial antibiotic therapy response is perceived to be inadequate. Due to raxibacumabs potential benefits for these patients, it has been added to the SNS.31Additionally, a currently unlicensed anthrax immune globulin containing a polyclonal antibody preparation pooled from anthraxvaccinated human donors has been added to the SNS.31, 32 [D]Special Populations Treatment options generally remain similar across population groups and scenarios. Conversion from ciprofloxacin or doxycycline to penicillin or amoxicillin is recommended when antibiotic susceptibilities are known because of potential adverse effects associated with tetracycline and fluoroquinolone use in children, although the FDA has approved ciprofloxacins use in children for post-exposure prophylaxis. Children 2 years old or younger should always be initially treated with intravenous antibiotics because of limited experience in this age group.33The risks and benefits of antibiotic administration need to be discussed with pregnant women exposed to anthrax, as these medications are not normally recommended for these patients; rarely, however, do the risks of treatment exceed the risks associated with foregoing antibiotic treatment. Dosages do not necessarily need to be adjusted in the elderly population, but considerations with regard to renal function for all populations may be necessary.
[B]Botulinum Toxin
Botulinum toxin poses a major public health threat because mass production is relatively easy, and it is exceptionally potent. Large quantities of toxin can be produced by industrial scale fermentation.5The estimated lethal inhalation dose is 0.7 to 0.9 mcg, whereas the lethal ingested dose is 30 ng.34Consequently, 1 g of crystalline toxin has the potential to kill more than 1 million
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people, making botulinum the most toxic substance known to humans.5, 17In 1995, Iraq admitted to producing 19,000 L of concentrated toxin with the potential to kill more than the entire world's population by inhalation.17Missiles and bombs loaded with nearly 10,000 L of the toxin were deployed; further details are unknown.5Mass dissemination can be carried out by airborne release and from intentional contamination of food or water supplies.
[C]Etiology
Clostridium botulinum, an anaerobic, spore-forming, gram-positive bacillus, produces seven distinct botulinum neurotoxins, types A through G. Clostridium spores, naturally found in soil, fresh water, and saltwater, are extremely hardy. Yet the toxins are less stable and are inactivated by heating to 85C (185F) for 5 minutes.35 Botulism is the syndrome that occurs after exposure to these toxins. Foodborne botulism, the oldest recognized form, is acquired from ingesting illpreserved foods. Likewise, infant botulism is caused by swallowing spores carried in honey, dust particles, orsoil. The toxin is then absorbed through the gastrointestinal tract into systemic circulation. The third form of naturally occurring botulism can arise cutaneously through an open wound infected with the organism, which produces toxin. Intentional botulinum toxin exposure may result from mass dissemination via contamination of food or beverages, or aerolization.5Botulinum is not contagious and human-to-human transmission has not been reported.5, 17
[C]Pathophysiology
C. botulinum toxins enter the bloodstream either from a mucosal surface (gastrointestinal tract, lungs) or a wound. The neurotoxins irreversibly bind to cholinergic synapses, inhibiting acetylcholine release across the neuromuscular junction. The resulting neuroparalytic botulism results in progressive, flaccid paralysis, followed by respiratory failure and death.5, 17, 36
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While symptoms are similar regardless of the transmission route, disease progression and severity of symptoms depend on the size of the inoculum. Symptoms typically occur within 12 to 36 hours, but may present after several weeks, if the person was exposed to a small amount of the toxin.5Classic presentation begins with bilateral cranial nerve palsies, such as diplopia, dysphagia, dysarthria, and descending motor neuron paralysis, which can persists for weeks to months, resulting in death from respiratory muscle paralysis. Foodborne botulism is often preceded by gastrointestinal symptoms such as nausea, vomiting, diarrhea and abdominal cramps, but differs from gastroenteritis by the presence of autonomic and ocular findings. Inhalation botulism is theorized to have a similar presentation, but few cases have been reported.37Absence of fever, sensory changes, with positive symmetrical neurologic findings, are important characteristics to preclude other neuromuscular etiologies, such as stroke, and paralytic shellfish poisoning. Diagnosis is based primarily on clinical presentation, as confirmatory laboratory testing can take more than 24 hours, has low specificity, and is costly.5,
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[C]Treatment The mainstays of therapy are rapid diagnosis, prompt administration of antitoxin, and supportive care with mechanical ventilation.17, 35Extended periods of assisted ventilation may be necessary, increasing the risk of secondary bacterial infections. However, timely administration of antitoxin, ideally within 24 hours after the onset of symptoms, may decrease disease severity and duration.35The antitoxins prevent disease progression, while reversal occurs with the regeneration of nerve terminals.38The mortality rate is less than 5% if treated and approaches 60% without treatment.17With the exception of BabyBIG, an intravenous human immune
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures globulin indicated for the treatment of infant botulism, the majority of available antitoxins are derived from horse serum products and may cause serum sickness, anaphylaxis, and other infusion-related side effects. Antibiotics do not have a direct role for the treatment of botulism, but are indicated for the management of secondary bacterial infections. The use of
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aminoglycosides, clindamycin, tetracyclines, and other ribosomal antibiotics are contraindicated, as they may inhibit neuromuscular transmission and thereby exacerbate neuromuscular blockade.36It is important to note that antitoxins are toxin specific; for example, bivalent antitoxin (A and B) is not able to neutralize toxins C to G. Table W114 presents dosing information for antitoxins.38, 39Limited information is available for the treatment of special populations such as pediatric, pregnant, geriatric, and immunocompromised patients. Thus, standard treatment is recommended.17Isolation is not required as botulinum is not contagious. A bioterrorist attack with botulinum toxins has the potential to involve a vast number of victims, who will need prompt administration of antitoxins and prolonged critical care, thereby testing the healthcare infrastructure. Rapid diagnosis is key; yet the majority of the population (including healthcare practitioners) has limited awareness of botulism. Streamlined intervention guidelines are essential. A Botulism Questionnaire and a management algorithm have been published for use by the lay public and clinicians.40, 41These screening tools outline the subtle neurological symptoms of botulism, the essential treatment steps, and can be used in emergency departments, at physician clinics, or even be published in local newspapers.42 Although antitoxins can provide passive immunity for PEP, preventive treatment is not recommended, because of the high risk of adverse reactions and a limited supply of antitoxins. For pre-exposure prophylaxis, a pentavalent toxoid vaccine (A, B, C, D, and E) is only available to laboratory workers and military personnel.17In addition to the toxoid vaccine, the CDC can
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provide equine antitoxins through their Vaccine and Antitoxin Program, which supplies product for regular foodborne outbreaks and large-scale disasters.43The CDC also coordinates with the Pan-American Health Organization to provide antitoxins to other countries of the Western Hemisphere.44The Botulism Reference Service for Canada also maintains a stockpile of antitoxins, which can be mobilized by contacting the Canadian Public Health Branch. 45Other countries, such as Thailand, have received antitoxin from the World Health Organization in collaboration with the United Kingdom Department of Health.46
[B]Plague
The term plague evolved to describe the Black Death or pestilence that killed millions of people in Europe during the Middle Ages. The causative agent of Black Death was discovered to be Yersinia pestis, a zoonotic infection found in rodents and the fleas that infest them. This naturally occurring infection is transmitted to humans from bites of fleas harboring the bacteria, direct contact with infectious tissues or exudates, and, rarely, by respiratory droplets from an animal or human.47As a bioweapon plague may be aerosolized, a capability developed by the United States and the former Soviet Union, effectively removing the flea as a vector. This agent is of particular concern, because if sprayed into a population or gathering of people, it could manifest as inhalation plague, a form of the disease that is highly lethal and contagious.
[C]Etiology
Y. pestis is a gram-negative, nonspore-forming, coccobacilli in the Enterobacteriaceae family.5Rat fleas maintain the zoonotic form of plague by infecting a variety of small mammals, including rats, ground squirrels, prairie dogs, and other rodents. Worldwide, excluding pandemics, there are 1,700 reported human cases a year. In the United States, plague is endemic in the Southwest and has caused approximately 400 cases during the period 1947 to 1996.15In
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures 2006 four states reported 13 cases, including two deaths.48Thirty-eight percent of patients
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developed septicemia. A few of cases were linked to domestic dogs and cats. Unlike anthrax, Y. pestis is less hardy and can be rendered nonviable when exposed to high temperatures, sunlight, and drying.47 Also, household disinfectants can kill these bacteria in a few minutes.47
[C]Pathophysiology
Similar to anthrax and botulinum, plague can manifest in many different forms. Bubonic plague, the most common naturally occurring type, is a localized infection, named after the bubo or swollen, painful abscessed lymph node. After inoculation of thousands of organisms from the flea bite, Y. pestis then migrates from skin through cutaneous to regional nodes.47Some patients bitten by fleas will not develop a bubo, but will suffer from primary septicemic plague. Y. pestis carries a multitude of virulence factors which contribute to this extracellular proliferation, that can ultimately cause an ensuing high-grade bacteremia and inflammation in lymph nodes, liver, and spleen.49The resulting complicationssepsis, disseminated intravascular coagulopathy, multi-organ dysfunction, secondary pneumonia, and adult respiratory distress syndromeform an extensive immunologic cascade. Untreated septicemic plague is nearly 100% fatal. 5The term black death describes gangrene of fingers, toes, and tips of the nose, which may occur during the advanced stages of sepsis (Fig. W114). Other bacteremic sequela include gastrointestinal plague, abscesses in liver or spleen, generalized lymphadenopathy, and plague meningitis.47Inhalation plague most likely leads to primary pneumonic plague, which has a high fatality rate, ranging from 57% (recent outbreaks) to 100% (untreated.)5, 15, 47A less-common manifestation of inhalation of Y. pestis is pharyngitis, as evidenced by swollen tonsils and inflamed lymph nodes.47
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After a short incubation period of just a few days pneumonic plague causes a sudden onset of symptoms, similar to influenza or community-acquired bacterial pneumonia.5, 47Patient risk factors, such as travel history and exposure to rodents or fleas, should be assessed. Suspicion of a bioterrorist event should be raised when an outbreak of severe pneumonia occurs without a common source or prior rodent deaths in the area.15, 47Death quickly follows, particularly if diagnosis and treatment are delayed.15Although limited data is available from epidemics occurring prior to the era of antibiotics, time from plague inhalation exposure to death is estimated at an average of 2 to 4 days, but can occur within 24 hours.15, 47, 50 [C]Treatment [D]Management of Potential Exposure PEP is crucial for plague, not only to prevent disease but also to prevent its spread to others through coughing infectious droplets. Data elucidating which agent is best for prophylaxis is lacking in animals and limited to a few human case reports. Most of the oral antibiotics recommended for treatment are also reasonable for PEP (Table W115). Most naturally occurring strains are susceptible to a variety of antibiotics, such as fluoroquinolones, aminoglycosides, and tetracyclines. However, a multidrug-resistant strain of Y. pestis was reported in a patient from Madagascar with bubonic plague.51Bioengineering of a resistant strain of Y. pestis by terrorists should not be ruled out. Animal data confirms a critical window to start antibiotics post inhalation to prevent inhalation plague.52Duration of prophylaxis is 7 days (or duration of risk exposure plus 7 days) and should be started as soon as possible around the time of exposure.5,15 If a person develops a fever and cough, treatment course for plague should commence.5Pre-exposure prophylaxis may be warranted for individuals traveling to endemic areas when exposure to vectors or pneumonic plague is unavoidable.47
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In the past there were two types of vaccines available, but with variable activity against bubonic plague only, manufacturing was halted in 1999.5,15 Currently, while no vaccine is available to protect the general public, a live plague vaccine has been used for protection of plague researchers and people living within endemic territories, such as countries within the former Soviet Union.53Research is actively underway, focusing on vaccines with protection against inhalation plague. Promising subunit candidates, such as an F1-V (virulence factors) fusion protein vaccine, are emerging.5,53 [D]Treatment of Confirmed Cases While specimen cultures (e.g., blood or sputum) and sensitivity results are pending, empiric treatment should be started immediately. Although streptomycin is recommended for treating inhalation plague, most data is with the bubonic form and this drug has limited availability. Gentamicin is considered an acceptable alternative to streptomycin. Clinicians should monitor renal function and aminoglycoside levels while patients are on therapy. Doxycycline and fluoroquinolones are also considered options. Although doxycycline has an indication for both treatment and prophylaxis of plague, there are concerns with resistance in some Y. pestis strains and theoretical lower efficacy (based on animal data) when compared with fluoroquinolones, especially if therapy is delayed.21Fluoroquinolones like ciprofloxacin or levofloxacin only have in vitro and animal data showing activity against plague.21Like doxycycline, fluoroquinolones are available in injectable and oral dosage forms and usually require limited patient monitoring. Chloramphenicol is an option for plague, especially if meningitis has developed, yet should be avoided in children who are younger than 2 years of age.15 [D]Special Populations
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Pregnant women should be immediately started on gentamicin, the drug of choice for this vulnerable patient population.15,47 Because of the lethality of this infection, if gentamicin is not
23
available, doxycycline or fluoroquinolones are reasonable alternatives. Although clinicians have multiple therapeutic options to treat children, aminoglycosides are the preferred agent. 15,47For all patients, therapy should continue for at least 10 days or until the patient is afebrile for 2 to 3 days, whichever is longer.47 Management includes starting empiric treatment immediately, initiating supportive care measures, and adjusting antibiotics as appropriate, based on renal function and susceptibility patterns. Serum concentrations should be monitored with the goal of achieving concentrations similar to those proposed for the management of other gram-negative pneumonias.5
[B]Smallpox
Smallpox, or variola major, is an acute, contagious, viral disease that has played a deadly and important role in the shape of global history. In 1796, the concept of vaccination was introduced when Edward Jenner discovered that inoculating patients with pus from milkmaids' cowpox lesions resulted in cross-protection against the smallpox virus. As humans are the only reservoir of the disease, a global smallpox vaccination campaign initiated by the World Health Organization in the 1960s was able to successfully eradicate naturally occurring smallpox from the planet by 1980.5 At this time, national vaccination programs ended, and remaining virus samples and vaccine were maintained by laboratory research facilities in Russia and the United States.54Because of increased concern about the potential use of smallpox as a weapon of bioterrorism, the United States government has increased smallpox vaccine stockpiles in the 21st century to provide enough doses to immunize the American public in the event of an outbreak,
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures and initiated the development of smallpox healthcare teams that would respond to a smallpox emergency.55
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[C]Etiology
Smallpox is caused by the variola virus, which belongs to the Orthopoxvirus family along with cowpox (vaccinia) and monkeypox. There are two distinct types of variola, known as major and minor.5 Variola minor is a significantly milder form of the disease and has a mortality rate of 1%; whereas variola major, which is the agent of concern in a smallpox outbreak, has a mortality rate of approximately 30% in the unvaccinated.5,18 There are four principal clinical classifications of the lesions that occur in variola major: ordinary, flat or malignant, hemorrhagic, and modified. Ordinary type is the most common, responsible for 90% of smallpox cases. Both hemorrhagic and flat or malignant type are rare, severe, and often fatal (90%). Modified type smallpox occurs in previously vaccinated persons and usually is a mild form of disease.56
[C]Pathophysiology
The pathophysiology of ordinary type smallpox, the most common form, is well documented. Smallpox is transmitted from person to person via respiratory droplets, direct personal contact with an infected person (including scabs or corpses), or by exposure to fomites, such as contaminated clothing or bed linens. The infectious dose is believed to be only a few virions, though the exact dose is unknown.18Once the virus has implanted in the respiratory tract mucosa, it travels to the lymph nodes, spleen, and bone marrow where it multiplies. The patient is asymptomatic during the incubation period, which ranges from 7 to 17 days (average, 1214 days).18, 56After this time the infected cells lyse and virus is detectable in the bloodstream.
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The viral incubation period is followed by a prodrome stage (Table W116) typically lasting 2 to 4 days, during which the patient is typically prostrate with a high fever, severe body aches, and vomiting. The end of the prodrome stage is followed by the abrupt development of an enanthem in the mouth. These oral lesions grow and ulcerate rapidly, releasing large quantities of virus into the saliva. The patient is most contagious during the first week of illness once these oral lesions occur. At the same time, red spots erupt first on the face and forearms, and later spread to the trunk and legs. Lesions may erupt on the palms and soles as well. The spots progress to vesicles by day 4 or 5, and hard, deeply embedded pustules by day 7. Scab lesions typically appear around day 14. A unique characteristic of smallpox is that the skin lesions, though different sizes, are all at the same stage of development throughout the illness (Fig. W115).18,56 In addition to significant scarring and death, blindness may occur as a result of corneal damage and ulceration. Secondary bacterial and viral infections are not common, but may manifest as respiratory complications. Encephalitis or arthritis may occur. Chronic infection does not normally occur with variola virus.18 Testing and sample collection from any individual suspected to have smallpox should only be done by vaccinated and properly trained personnel. Smallpox diagnosis should be confirmed at a variola testing laboratory, which can utilize PCR technology, such as the CDC. 5,58A presumptive diagnosis may be made based on examination of vesicular scraping under an electron microscope.5The varicella zoster virus test (i.e. DFA, PCR) may be used to rule out varicella, and a Tzanck smear may also be used to rule out varicella, as well as herpes simplex virus. 58 The CDC recommends taking digital pictures of the clinical presentation and using strict droplet and contact precautions, including facemasks and negative-pressure isolation rooms. All suspected
26
and confirmed cases of smallpox should be reported immediately first to the CDC, then to state and local health departments.58 [C]Treatment There is no treatment currently available for smallpox infection other than supportive care (Table W117). Pre- and postexposure prophylaxis can only be achieved by using the smallpox vaccine, which is derived from live vaccinia virus. [D] Vaccination Smallpox vaccination is not currently available to the public, but is reserved in national stockpiles in the event of an outbreak. The original, first-generation smallpox vaccines were derived from the New York City Board of Health (NYCBH) strain of vaccinia, prepared from lymph fluid of calf skin, and stored as a lyophilized product. Until 2007, the first-generation Dryvax was the only commercially approved smallpox vaccine available for limited use in the United States, until being replaced by ACAM2000.54, 59 ACAM2000, a live vaccinia virus derived from plaque purification cloning of a Dryvax isolate that was manufactured using tissue culture system, has replaced all stores of Dryvax vaccine as of February, 2008.59 Third- and fourth-generation vaccines are being developed and studied as well.54ACAM2000 has a similar efficacy and safety profile in comparison to Dryvax, and is also acceptable as a booster for previously vaccinated patients.61 The ACAM2000 smallpox vaccinia vaccine, like the first-generation vaccine, is administered through multiple percutaneous skin pricks (intradermal) delivered with a bifurcated needle into the upper arm over the insertion of the deltoid muscle. When performed correctly, a drop of blood will form at the vaccination site. The patient will develop a major cutaneous reaction over the following 10 days characterized by a pustule at the site of inoculation, which dries and forms
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures a scab by days 14 to 21. The scab separates and leaves a pitted scar. The upper arm is the only site approved for vaccination, allowing for easy site care and management as well as easy evaluation of a proper vaccine take 6 to 8 days after vaccination (Figure W11-6).61
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An FDAapproved, current, ACAM2000 medication guide must be dispensed to every vaccine recipient; and recipients should be thoroughly educated about proper care of the vaccine site to prevent accidental vaccinia transmission to other sites or other people. Vaccine recipients should not handle infants, breastfeed, swim or use hot tubs, donate blood, receive tuberculin testing, or get pregnant until at least 4 weeks after the vaccination and not before the vaccination site has healed. Inadvertent inoculation of other sites such as the face, nose, mouth, lips, and genitalia is the most frequent complication of the vaccinia vaccination. Frequent hand washing, proper care of the vaccination site, and careful disposal of bandages can reduce the risk of these events. Malaise, fever, myalgia, and headache are also common adverse events following vaccination, though they are less common in revaccination than first-time vaccination.61 Smallpox vaccination provides effective immunity for at least 3 years after vaccination, with decreasing immunity thereafter.5, 61 If a patient is revaccinated, immunity will increase and last longer. Vaccination within 3-4 days of exposure to the virus will completely prevent or significantly modify smallpox infection in most persons, and vaccination within 4 to 7 days after viral exposure will likely offer some protection or modify the severity of the infection. 5, 61 Serious, but uncommon complications, following either primary or revaccination with live vaccinia smallpox vaccine include: myocarditis, pericarditis, encephalitis, encephalomyelitis, encephalopathy, eczema vaccinatum, progressive vaccinia, generalized vaccinia, erythema multiforme major (Figure W11-7), including Stevens-Johnson Syndrome, and death.61 Serious and severe adverse reactions are more common in immunocompromised patients and those
28
receiving primary smallpox vaccination compared with those being revaccinated. Close contacts of vaccinees are also at risk for the same complications if the live vaccinia virus is inadvertently transmitted to them.61Vaccinia immune globulin intravenous (VIGIV) and cidofovir are treatment options for serious smallpox vaccine reactions.5, 60, 62Limitations of VIGIV include its lack of effectiveness for treatment of postvaccinial encephalitis or smallpox infection and complex administration schedule. Cidofovir is considered a second-line option in part because there is limited human data, the potential for renal toxicity, and use restrictions under an Investigational New Drug protocol. Like the smallpox vaccine, both VIGIV and cidofovir are stored in the SNS.62 [C]Special Populations The ACAM2000 vaccine contains trace amounts of the antibiotics neomycin and polymyxin B and therefore should not be given to anyone with a history of anaphylaxis to these antibiotics. While there are few absolute contraindications, the smallpox vaccine is a live vaccine that should be not be administered to patients with a history of eczema, immunodeficient patients (including cancer and HIV patients), infants less than 12 months of age, and pregnant women, unless the benefit outweighs the risk (of developing vaccinia reaction) as determined by the healthcare practitioner.61 Cidofovir has IND status for treatment of vaccine reaction and is a possible treatment alternative for smallpox. Some in vitro studies suggest that cidofovir may show efficacy in preventing smallpox infection if administered within 48 hours after exposure.5,
18
However, the risk of serious side effects with cidofovir, including renal toxicity, must be
weighed against the potential benefits of treatment.
[B]Tularemia
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Tularemia is caused by a small, gram-negative rod, named Francisella tularensis. It was first isolated in Tulare County, California, by Dr. Edward Francis, who greatly contributed to the understanding of the bacteria through his research in the 1920s.Tularemia has long been investigated for use as a bioterrorism weapon. It was one of the many agents examined by Japanese germ warfare units in the 1930s and 1940s in Manchuria. The United States military
29
developed weapons capable of disseminating F. tularensis aerosols in the 1950s and 1960s, and there are reports of intentional release during World War II.19
[C]Etiology
F. tularensis is one of the most pathogenic bacteria known; as few as 10 organisms of bacteria are required to cause infection. Contact with small mammal hosts such as rabbits or exposure to contaminated environments is enough to contract infection.19Two main variants of F. tularensis exist, Type A and Type B. Type A, predominately found in North America, is the more virulent form and Type B is found in Europe and Asia.5Casesof tularemia are documented throughout the Northern Hemisphere, with at least one case reported in every state in the United States, except Hawaii.63Several pathways of transmission are possible, including direct contact with infected animals, inhalation or ingestion of contaminated water or dirt, or vector-borne infection via insects or ticks. A 1925 experiment famously described infection occurring by rubbing infected rabbit tissue on a person's arm.64
[C]Pathophysiology
Clinical and pathogenic manifestations vary depending on the subspecies involved (e.g., F. tularensistularensis is more virulent than F. tularensispalaearctica). In general F. tularensis is an intracellular parasite that, once inside its host, will progress to regional lymph nodes. The major target organs include the lung, pleura, spleen, liver, and kidney.19Interestingly, the bacteria
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures appears to intentionally avoid triggering an immune reaction, while subverting the host's macrophages to help itself replicate.
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The incubation period varies widely from a few hours to as long as 2 to 3 weeks. After an average of 3 to 6 days, a sudden influenza-like, febrile illness develops, which can be similar to those observed after anthrax exposure. Fever, chills, muscle pains, headache, and dry cough are common, with various other manifestations occurring, depending on the pathway of infection. Ulcers at the site of cutaneous or mucous membrane contact, pharyngitis, ocular lesions, and pneumonia are also possible.65Early pulmonary radiologic findings may include infiltrates, pleural effusions, and hilar lymphadenopathy. Although a study of volunteers showed incapacitation 1 to 2 days after aerosol exposure, untreated infections usually progress slowly, persisting for several weeks to months, with dissemination throughout the body and progression to sepsis possible.66 Because tularemia rarely affects humans in most areas, clinicians will likely possess a low index of suspicion when presented with this infection. While F. tularensis is rarely cultured from blood samples, cultures taken from sputum specimens or even pharyngeal washings remain the definitive means of confirming a suspected case. This bacterium grows best in cysteine-enriched broth, thioglycollate broth, buffered charcoal-yeast agar, or chocolate agar.19Direct fluorescent antibody examination or immunochemical stains of specimens should be performed promptly. F. tularensis can be differentiated from other microbes under light microscopy by its small size (0.2 micron 0.2 to 0.7 micron), pleomorphic appearance, and its faint uptake of stain.19 Mortality rates for tularemia in the pre-antibiotic era varied from 5% to 15% to upwards of 60% for those with untreated sepsis or severe pneumonia.19Mortality rates for F. tularensis infection are now
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures less than 2%. As with most infectious processes, appropriate and prompt antibiotic initiation is
31
crucial. Supportive care measures (e.g., fluid resuscitation or mechanical ventilation) should also be addressed as necessary. [C]Treatment A live-attenuated vaccine derived from the Type B variant of F. tularensis was available as an investigational drug. This vaccine is now under review by the FDA for official approval. 67The CDC has published recommendations for treatment and for PEP. An aminoglycoside, streptomycin or gentamicin, is recommended as first-line agent for treatment of symptomatic infection, with doxycycline, ciprofloxacin, and chloramphenicol listed as alternative choices for adults, children, or pregnant women (Table W118 provides more detail). Aminoglycosides are generally favored in North America and tetracyclines are generally preferred in Europe as milder strains are encountered there. Tetracyclines possess bacteriostatic activity against F. tularensis and need to be given for at least 14 days to minimize the likelihood of a relapse.19In vitro data, animal data, and several case reports show that fluoroquinolones yield positive outcomes in children and adults.21, 68, 69Fluoroquinolones possess favorable pharmacodynamic properties since they achieve high concentrations in macrophages and exhibit bacteriocidal activity. Doxycycline or fluoroquinolones are easily transitioned to oral routes when appropriate. Randomized, controlled studies are not feasible in this setting, thus making it difficult to determine which antibiotic would be preferable in which situation. Although gentamicin, doxycycline, or ciprofloxacin all appear to be effective, third-generation cephalosporins, chloramphenicol, and potentially telithromycin also have demonstrated activity. Data is lacking for macrolides, clindamycin, and cotrimoxazole, and should, therefore, be avoided.19,21,63For
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures PEP, the CDC and the literature support doxycycline or ciprofloxacin for 14 days (see Table W118 for more detail). [D]Special Populations While the FDA has not approved fluoroquinolones for use in children, short courses are not
32
associated with arthropathy.19Aminoglycosides given in short courses to pregnant women rarely pose risk to the unborn and benefits of treatment normally outweigh any potential risk. Using ciprofloxacin for PEP, however, is preferable to doxycycline in this group. Although adjustments for those persons with renal impairment should be made as appropriate, no specific recommendations exist for the elderly population. [B]Viral Hemorrhagic Fever Viral hemorrhagic fever (VHF) encompasses illness caused by a diverse group of viruses that can be dispersed and transmitted by aerosol release, resulting in severe disease associated with a high mortality rate. Hemorrhagic fever viruses were mass produced by the former Soviet Union and reportedly have been weaponized by the United States, the former Soviet Union, and possibly North Korea.20Exposure to only a few aerosolized virions is required to cause infection, and depending on the virus, can lead to severe complications and death.5, 20 [C]Etiology Hemorrhagic fever viruses comprise one of four distinct families of RNA viruses: Filoviridae, Arenaviridae, Bunyaviridae, and Flaviviridae. The Filoviridae family includes Ebola and Marburg viruses. Lassa and New WorldArenaviridae viruses are associated with Argentine, Bolivian, and Venezuelan hemorrhagic fevers. The Bunyaviridae family includes:Rift Valley fever, Crimean-Congo hemorrhagic fever, and select viruses of the Hantavirus genus. The Flaviviridae family consists of yellow fever, Omsk hemorrhagic fever, and Kyasanur forest
33
disease.5These viruses primarily reside in animal reservoirs or arthropod vectors such as rodents, mosquitoes, and ticks. With the exception of Rift Valley fever and diseases from the Flaviviridae family, these viruses can be spread by human-to-human contact. Many human cases of infection resulted from contact with blood, bodily secretions, and direct physical contact with an infected person.5 [C]Pathophysiology Transmission to humans has occurred through a variety of ways: bites from infected arthropods, direct contact with or aerosolized droplets from infected animals, inhalation of dust particles tainted with rodent excreta, and direct contact with virus-laden blood and bodily fluids.5, 20The use of improperly sterilized needles and syringes contaminated with infected bodily fluids contributed to an epidemic of Ebola virus in healthcare settings.70Infections are characterized by fever and bleeding diathesis, but the pathogenesis for infection is not completely understood. These viruses are theorized to inhibit platelet function, destroy platelets and endothelial cells, and indirectly reduce coagulation factors. Mortality rates range from 0.2% to 90%, depending on the etiologic virus.5, 20 [C]Clinical Presentation Classical symptoms of VHF are fever and hemorrhagic diathesis with capillary leak; resulting in microvascular damage and hemodynamic shock. The incubation period ranges from 2 to 21 days. Prodromal symptoms such as fever, headache, and fatigue lasting less than 1 week have been reported, followed by nonspecific symptoms including fever, hypotension, and bradycardia. Progressive hemorrhaging ensues, resulting in petechiae, conjunctival hemorrhage (see Figure 11-8), and hematuria. Disseminated intravascular coagulation and circulatory shock can occur in severe cases. Symptoms are often accompanied by renal insufficiency, neurologic changes,
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures compromised pulmonary function, and hematopoietic dysfunction. Hepatic impairment, consumptive coagulopathy, and damage to megakaryocytes may also contribute to other coagulopathies. Not all patients develop classic VHF symptoms, which may depend on hostspecific factors and the viral strain.5Laboratory abnormalities include leukopenia, anemia, thrombocytopenia, whereas elevated aminotransferases and disseminated intravascular coagulopathy are seen in severe infections. VHF should be suspected based on risk factors including travel history, sick contacts, and exposure to vectors. Lacking these characteristics,
34
multiple incidences potentially indicate a bioterrorism event. Diagnosis is confirmed by antigen detection or real-time PCR performed at specialized laboratories.5, 20 [C]Treatment [D]Management of Potential Exposure PEP is limited by the absence of clinical data and pharmacologic agents with activity against these viruses. With the exception of yellow fever, licensed vaccines are not available. Treatment with ribavirin is an option when Filoviradae or Falvavirade virus can be excluded as causative pathogens, but recommended only under select circumstances. In cases of contact with infected persons, suspected patients should be under medical surveillance for 21 days after the potential exposure. During surveillance, if a temperature of 38.3C (101F) or greater or signs and symptoms of infection develop, prompt initiation of ribavirin for presumptive VHF is indicated.20High risk exposure from contact with acutely febrile individuals may warrant immediate use of oral ribavirin. Examples include penetration of the skin by contaminated sharp objects (e.g. needlestick); contact of mucous membranes with infected blood or bodily secretions; nonuse of personal protective equipment while assisting in emergency procedures (e.g. broncoscopy), or sharing an enclosed space for prolonged for extended period of time (e.g.
35
within 6 feet for hours).71Because the clinical usefulness of ribavirin in asymptomatic patient is unknown, pre-exposure therapy is not recommended.20 [D]Treatment of Confirmed Cases Regardless of specific etiologic virus, the mainstay of treatment is supportive care. Aggressive fluid resuscitation and vasopressor support is often required due to capillary leak syndrome. Bleeding diathesis should be managed as a coagulopathy. Intramuscular injections and the use of aspirin, nonsteroidal antiinflammatory agents, and anticoagulants are contraindicated.20Antivirals specific for these viruses are not approved by the FDA, but a limited supply of intravenous ribavirin is available for compassionate use under an IND.5In the case of a massive biologic attack, oral ribavirin is an alternative. Ribavirin displays in vitro and in vivo activity against Arenaviridae and Bunyaviridae family viruses, but has poor cerebrospinal fluid penetration and is inactive against Filoviridae or Flaviviridae family viruses.5, 20Treatment should begin within the first 4 days of symptom onset. Small trials using ribavirin within 4 days of symptoms demonstrate a reduction in mortality for patients with Lassa fever and New World hemorrhagic fever (Table W119).20Healthcare providers should use strict barrier precautions when caring for patients as transmission is possible through contact with blood or bodily fluids, including vomitus, urine, and stool.20, 72 [D]Special Populations Limited data is available for the treatment of VHF in special populations and the benefits of treatment likely outweigh the risk. Ribavirin is pregnancy category X because of teratogenic effects observed in animals. However, an increased risk of mortality is associated in this patient population and vertical transmission has been reported.73A case report of a 36-week pregnant woman treated with oral ribavirin for Crimean-Congo hemorrhagic fever documented the first
36
known baby born from an infected mother to survive. In addition, the mother was cured, and the virus was not transmitted to the baby.74For pediatric patients, only the inhaled dosage form of ribavirin is approved for the treatment of respiratory syncytial viral infections. Although oral and intravenous ribavirin is not approved, treatment of VHF with either of these dosage forms is recommended. A pediatric syrup formulation is available under an IND.5, 20 [A]Infectious Disease Related to Natural Disasters Mother Nature could be considered our most menacing bioterrorist.75 Natural disasters have unleashed formidable foes throughout the centuries, including pathogenic viruses, smallpox and pandemic influenza; lethal bacteria, such as Y. pestis, multidrug-resistant tuberculosis, Staphylococcus, Escherichia coli, and a variety of disease-causing parasites, yeast, and molds. Some of these microbes were discussed in previous sections of this chapter and others in various chapters throughout this text. Infectious disease outbreaks following natural disasters, as with bioterror agent exposures, can cause panic, social unrest, and tax any country's medical and public health system. Natural disasters, such as earthquakes, hurricanes, tsunamis, and drought, are catastrophic events. Mortality associated with these events is usually caused by drowning, crush-related injury, and blunt trauma. Morbidity may include, but is not limited to, anxiety and stress-related conditions, and population displacement. However, communicable disease, related directly to outbreaks from large number of deceased, is not common, and may be limited to a few situations.76 Haiti, for example, is still responding to waves of ill and dying citizens from multiple cholera outbreaks post-earthquake. Ironically, genetic sequencing of the diarrhea-inducing, fatal cholera strains found this bacterium was most likely introduced by human activity, particularly from aid workers from countries where cholera is endemic, and not by contaminated local water supply. 77
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Multiple communicable diseases have been associated with displaced populations and should be considered as an integral part of post-disaster patient assessment.76 (see Table W1110) Healthcare providers responding to a disaster should focus on preventing illness and injury, ensuring food and water safety, and recreating medical records. Dissemination of accurate and up-to-date information on personal and public safety topics, such as types of disasters and weather emergencies, health and safety concerns such as cleanup and mold, and information for certain groups, such as evacuees and volunteers, is an important role for health care providers.78Ideally, advanced planning for provision of continuing maintenance medications and medical supplies, particularly for patients with special needs, such as children, pregnant women, and people with disabilities, mental illness, or chronic medical conditions, has occurred.Finally, the administration of immunizations to both the displaced population and the healthcare providers traveling to the affected area(s) is an important mode of illness prevention. [A]Healthcare Providers in Emergency Preparedness The CDC has described five main areas of preparedness and response to acts of biologic terrorism: preparedness and prevention; detection and surveillance; diagnosis and characterization of agents; response; and communication.8Healthcare providers play an integral role in many of these general categories. Diagnosis and characterization of agents involved and securing therapeutic options for some of the main bioterrorist threats are critical. The leadership and administrative role and responsibilities of healthcare professionals during a biologic emergency are also paramount. A variety of providers may be asked to assist with triage/screening, obtaining medical resources, administration of vaccinations, dispensing PEP and chronic medications and supplies, providing acute treatment and monitoring for side effects of medications and vaccinations during and after
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures a disaster response. Healthcare providers are key to accurate and timely communication, notifying appropriate authorities of potential bioterrorism case or cases, sending samples and receiving diagnostic test results, and educating the public. Table W1111 elaborates on the specific areas of planning, education, response, and volunteer opportunities.
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Abbreviations APAP: acetaminophen ASA: aspirin CBC: complete blood count CDC: Centers for Disease Control and Prevention ELISA: enzyme-linked immunosorbent assay FDA: Food and Drug Administration FEMA: Federal Emergency Management Agency HBAT: heptavalent equine antitoxin IM: intramuscular
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IND: investigational new drug IV: intravenous NIAID: National Institute Allergy and Infectious Diseases NSAIDs: nonsteroidal anti-inflammatory drugs NYCBH: New York City Board of Health PCR: polymerase chain reaction PEP: postexposure prophylaxis PO: by mouth SNS: Strategic National Stockpile USAMRIID: United States Army Medical Research Institute of Infectious Diseases VIGIV: Vaccinia immune globulin intravenous VIGIM: Vaccinia immune globulin intramuscular
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VHF: viral hemorrhagic fever
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures References 1. Centers for Disease Control and Prevention. Updated CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April 2009- April 10, 2010. 2010, http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm. Last accessed, August 29, 2012. 2. CDC. Pertussis Epidemic- Washington, 2012. MMWR [electronic version] 2012,
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http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6128a1.htm. Last accessed, August 29, 2012. 3. H1N1 Flu. CDC Health Update: Swine Influenza A (H1N1) Update: New Interim Recommendations and Guidance for Health Directors about Strategic National Stockpile Material; April 26, 2009. http://www.cdc.gov/h1n1flu/HAN/042609.htm.Last accessed, August 29, 2012. 4. Woodard LJ, Bray BS, Williams D, Terriff CM. Call to action: integrating students pharmacists, faculty, and pharmacy practitioners into emergency preparedness and response. J Am Pharm Assoc 2010;50:158-164. 5. U.S. Army Medical Research Institute of Infectious Diseases. USAMRIID's Medical Management of Biological Casualties Handbook, 7th ed. Ft. Detrick, MD: U.S. Army Medical Research Institute of Infectious Diseases, September 2011. http://www.usamriid.army.mil/education/bluebookpdf/USAMRIID%20BlueBook%207th%20 Edition%20-%20Sep%202011.pdf. Last accessed, August 29, 2012. 6. Riedel S. Biological warfare and bioterrorism: A historical review. Proc (BaylUniv Med Cent) 2004;17:400406.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures 7. Arms Control Association. Chemicals and Biological Weapons Proliferation at a Glance. Arms Control Association, 2010. http://www.armscontrol.org/factsheets.cbwprolif. Last accessed, August 29, 2012. 8. Centers for Disease Control and Prevention. Biological and chemical terrorism: Strategic plan for preparedness and response. Recommendations of the CDC Strategic Planning Workgroup. MMWR Morb Mortal Wkly Rep 2000;49(RR04):114. 9. Centers for Disease Control and Prevention, Emergency Preparedness and Response. Bioterrorism Agents/Diseases. http://www.bt.cdc.gov/agent/agentlist-category.asp.Last accessed, August 29, 2012. 10. National Institute of Allergy and Infectious Diseases. Biodefense and Emerging Infectious Diseases. NIAID Category A, B & C Priority Pathogens. Last updated, February 27, 2012.
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http://www.niaid.nih.gov/topics/biodefenserelated/biodefense/pages/cata.aspx. Last accessed, August 29, 2012. 11. BioThrax (Anthrax Vaccine Adsorbed) [package insert]. Lansing, MI: Emergent BioDefense Operations Lansing Inc.; May 2012. http://www.biothrax.com/prescribinginformation_biothrax_us.pdf. 12. Strassburg MA. The global eradication of smallpox. Am J Infect Control 1982;10:5359. 13. Smallpox Vaccination Program. Smallpox Vaccination Safety Summary. Military Vaccine Agency; May 17, 2007. http://www.smallpox.mil/event/SPSafetySum.asp. Last accessed, August 29, 2012. 14. Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax, 2001. MMWR Morb Mortal Wkly Rep 2001;50:10081010.
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15. Inglesby TV, Dennis DT, Henderson DA, et al. Plague as a biological weapon: Medical and public health management. JAMA 2000;283:22812290. 16. Inglesby TV, O'Toole T, Henderson DA, et al. Anthrax as a biological weapon, 2002: Updated recommendations for management. JAMA 2002;287:22362252. 17. Arnon SS, Schechter R, Inglesby TV, et al. Botulinum toxin as a biological weapon: Medical and public health management. JAMA 2001;285:10591070. 18. Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a biological weapon: Medical and public health management. JAMA 1999;281:21272137. 19. Dennis DT, Inglesby TV, Henderson DA, et al. Tularemia as a biological weapon: Medical and public health management. JAMA 2001;285:27632773. 20. Borio L, Inglesby T, Peters CJ, et al. Hemorrhagic fever viruses as biological weapons: Medical and public health management. JAMA 2002;287:23912405. 21. Brouillard JE, Terriff CM, Tofan A, Garrison MW. Antibiotic selection and resistance issues with fluoroquinolones and doxycycline against biological agents. Pharmacother 2006;26:3 14. 22. Fowler RA, Sanders GD, Bravata DM, et al. Cost-effectiveness of defending against bioterrorism: a comparison of vaccination and antibiotic prophylaxis against anthrax. Ann Intern Med. 2005;142:601-610. 23. Centers for Disease Control and Prevention. Anthrax. In: Atkinson W, Hamborsky J, McIntyre L, Wolfe S, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases, 9th ed. Washington, DC: Public Health Foundation, 2006:307322. 24. Jernigan JA, Stephens DS, Ashford DA, et al. Bioterrorism-related inhalation anthrax: The first 10 cases reported in the United States. Emerg Infect Dis 2001;7:933944.
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25. Centers for Disease Control and Prevention. Update: Investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001. MMWR Morb Mortal Wkly Rep 2001;50:889893. 26. Hicks CW, Sweeney DA, Cui X, et al. An overview of anthrax infection including the recently identified form of disease in injection drug users. Intensive Care Med 2012;38:10921104. 27. Kyriacou DN, Adamski A, Khardori N. Anthrax: From antiquity and obscurity to a frontrunner in bioterrorism. Infect DisClin North Am 2006;20:227251. 28. Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep 2001;50:909919. 29. Brysker A. Bacillus anthracis and antibacterial agents. ClinMicrobiol Infect 2002;8:467. 30. Migone T, Subramanian MG, Zhong J, et al. Raxibacumab for the treatment of inhalational anthrax. N EnglJ Med 2009;361:135144. 31. Artenstein AW and Opal SM. Novel approaches to the treatment of systemic anthrax. Clin Infect Dis 2012;54:1148-61. 32. Walsh JJ, Pesik N, Quinn CP, et al. A case of naturally acquired inhalational anthrax: clinical care and analyses of anti-protective antigen immunoglobulin G and lethal factor. Clin Infect Dis 2007;44:968-71. 33. American Academy of Pediatrics. The Child with a Suspected Anthrax Exposure or Infection. 2001, http://www2.aap.org/advocacy/releases/anthraxsusp.htm. Last accessed, September 1, 2012.
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34. Dhaked RK, Singh, MF, Singh P, Gupta P. Botulin toxin: bioweapon & magic drug. Indian J Med Res 2010;132:489-503. 35. Sobel J. Botulism. Clin Infect Dis 2005;41:11671173. 36. Caya JG, Agni R, Miller JE. Clostridium botulinum and the clinical laboratorian: a detailed review of botulism, including biological warfare ramifications of botulinum toxin. Arch Pathol Lab Med 2004;128:653662. 37. Villar RG, Elliott SP, Davenport KM. Botulism: The many faces of botulinum toxin and its potential for bioterrorism. Infect DisClin North Am 2006;20:313327. 38. Centers for Disease Control and Prevention. Botulism: Treatment Overview for Clinicians. Atlanta, GA. 2006, http://www.bt.cdc.gov/agent/Botulism/clinicians/treatment.asp . Last accessed, September 1, 2012. 39. Centers for Disease Control and Prevention. Investigational heptavalent botulinum antitoxin (HBAT) to replace licensed botulinum antitoxin AB and investigational botulinum antitoxin E. MMWR Morb Mortal Wkly Rep. 2010;59:299. 40. Rega, P, Budd C, Burkholder-Allen. Botulism Tool Kit. Emergency Recognition, Response and Anti-Terrorism Training Associates (ERRATA, LLC.), 2007. http://botulismtoolkit.com/wp-content/media/botkit_1.0.pdf.Last accessed, September 1, 2012. 41. Rega P, Burkholder-Allen K, Bork C. An algorithm for the evaluation and management of red, yellow, and green zone patients during a botulism mass causality. Am J Dis Med 2009;4:192198. 42. Burkholder-Allen K, Rega P, Bork C, Budd C. Botulism Questionnaire: A tactical tool for community use in a mass casualty incident. Nurs Health Sci 2009;11:374377.
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43. Centers for Disease Control and Prevention. Formulary: Products Distributed by the Centers for Disease Control and Prevention, 2010.http://www.cdc.gov/laboratory/drugservice/formulary.html. Last accessed, August 30, 2012. 44. Villar RG, Shapiro RL, Busto S, et al. Outbreak of type A botulism and development of botulism surveillance and antitoxin release system in Argentina. JAMA 1999;281:1334 1338. 45. Health Canada. Botulism- Guide for Healthcare Professionals, 2012.http://www.hcsc.gc.ca/fn-an/legislation/guide-ld/botulism-botulisme-prof-eng.php. Last accessed, September 6, 2012. 46. Centers for Disease Control and Prevention. Botulism from home-canned bamboo shoots Nan Province, Thailand, March 2006. MMWR Morb Mortal Wkly Rep 2006;55:389392. 47. Koirala J. Plague: Disease, management, and recognition of act of terrorism. Infect Dis Clin North Am 2006;20:273287. 48. Centers for Disease Control and Prevention. Human plague-four states, 2006. MMWR Morb Mortal Wkly Rep 2006;55:940944. 49. Butler T. Plague in the 21st century. Clin Infect Dis 2009;49:736742. 50. Dennis DT, Chow CC. Plague. Pediatr Infect Dis J 2004;23:6971. 51. Galimand M, Guiyoule A, Gerbaud G, et al. Multidrug resistance in Yersinia pestis mediated by a transferable plasmid. N Engl J Med 1997;337:677680. 52. Peterson JW, Moen ST, Healy D, et al. Protection afforded by fluoroquinolones in animal models of respiratory infections with Bacillus anthracis, Yersinia pestis, and Francisella tularensis. The Open Microbiology Journal. 2010;4:34-46.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures 53. Feodorova VA, Corbel MJ. Prospects for new plague vaccines. Expert Rev 2009;8:1721 1738. 54. Jacob BL, Langland JO, Kibler KV, et al. Vaccinia virus vaccines: past, present and future. Antiviral Res 2009;84:113. 55. Centers for Disease Control and Prevention. Smallpox Fact Sheet: Vaccine Overview. Atlanta, GA: Centers for Disease Control and Prevention, Emergency Preparedness and Response, 2004.http://emergency.cdc.gov/agent/smallpox/vaccination/facts.asp. Last accessed, August 31, 2012. 56. Centers for Disease Control and Prevention. Smallpox Fact Sheet: Smallpox Disease Overview. Atlanta, GA: Centers for Disease Control and Prevention, Emergency Preparedness and Response, 2004. http://www.emergency.cdc.gov/agent/smallpox/overview/disease-facts.asp. Last accessed, August 31, 2012. 57. Centers for Disease Control and Prevention. Smallpox: Disease, Prevention, and Intervention. [Training Course] Atlanta, GA: Centers for Disease Control and Prevention, Emergency Preparedness and Response, 2003. http://www.bt.cdc.gov/agent/smallpox/training/overview/. Last accessed, August 31, 2012. 58. Centers for Disease Control and Prevention. Smallpox: Diagnosis/Evaluation. Acute,
47
Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States. Atlanta, GA: Centers for Disease Control and Prevention, Emergency Preparedness and Response, 2003. http://www.bt.cdc.gov/agent/smallpox/diagnosis/#diagnosis/. Last accessed, August 31, 2012.
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Vaccine Adverse Reactions: Vaccinia Immune Globulin and Cidofovir. Atlanta, GA: Centers for Disease Control and Prevention, Emergency Preparedness and Response, 2009. http://www.bt.cdc.gov/agent/smallpox/vaccination/mgmt-adv-reactions.asp. Last accessed, August 31, 2012 63. Eliasson H, Broman T, Forsman M, Back E. Tularemia: Current epidemiology and disease management. Infect Dis Clin North Am 2006;20:289-311. 64. Ohara H. Experimental inoculation of disease of wild rabbits into the human body, and its bacteriological study. The Japan Medical World 1926;11:299-304. 65. Centers for Disease Control and Prevention. TularemiaUnited States, 19902000. MMWR Morb Mortal Wkly Rep 2002;51:182-184. 66. Alluisi EA, Beisel WR, Bartonelli PJ, Coates GD. Behavioral effects of tularemia and sandfly fever in man. J Infect Dis 1973;128:710-717.
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49
69. Aranda EA. Treatment of tularemia with levofloxacin. ClinMicrobiol Infect 2001;7:167-168. 70. Centers for Disease Control and Prevention. Update: Management of patients with suspected viral hemorrhagic feverUnited States. MMWR Morb Mortal Wkly Rep 1995;44;475-479. 71. Bausch, DG, Hadi CM, Khan SH, Lertora JJ. Review of the literature and proposed guidelines for the use of oral ribavirin as postexposure prophylaxis. Clin Infect Dis 2010;51:1435-1441. 72. Centers for Disease Control and Prevention. Interim Guidance for Managing Patients with Suspected Viral Hemorrhagic Fever in U.S. Hospitals, 2005. www.cdc.gov/HAI/pdfs/bbp/VHFinterimGuidance05_19_05.pdf. Last accessed, August 30, 2012. 73. Ergonul O, Celikbas A, Yildirim U, et al. Pregnancy and Crimean-Congo haemorrhagic fever. ClinMicrobiol Infect 2010;16:647-650. 74. Dizbay M, Atas F, Gaygisiz U, et al. Crimean-Congo hemorrhagic fever treated with ribavirin in a pregnant woman. J Infect 2009;59:281-283. 75. Drexler M. Secret Agents: The Menace of Emerging Infections. Washington, DC: Joseph Henry Press, 2002.
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78. Centers for Disease Control and Prevention, Emergency Preparedness and Response. Natural Disasters and Severe Weather. Atlanta, GA. http://www.bt.cdc.gov/disasters. Last accessed: August 30, 2012.
TABLES
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W11-1 Priority Categorization of Biological Threat Agents Category A

51
High mortality rate Greatest potential for major public health and medical impact Easily disseminated or transmitted from person-to-person Might cause public panic and social disruption Require special action for public health preparedness
Category B

Result in moderate morbidity rates and low mortality Lower medical and public health impact Moderately easy to disseminate Require specific enhancements of diagnostic capacity and disease surveillance
Category C
Emerging infections that could be engineered for mass dissemination in future because of:
o o o
availability ease of production and dissemination potential for high morbidity and mortality rates and major health impact
Data from references 9 and 10.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W112 Bioterrorism Pathogen List Category A

52
Anthrax (Bacillus anthracis) Botulism (Clostridium botulinum toxin) Plague (Yersinia pestis) Smallpox (variola major) and other related pox viruses Tularemia (Francisella tularensis) Viral hemorrhagic fevers
o
Arenaviruses

Lassa fever LCM, Junin virus, Machupo virus, Guanarito virus
Bunyaviruses

Hantaviruses Rift Valley fever
Flaviviruses
Dengue
Filoviruses

Ebola Marburg
Category B

Brucellosis (Brucella species) Glanders (Burkholderia mallei) Melioidosis (Burkholderiapseudomallei)

53
Psittacosis (Chlamydia psittaci) Epsilon toxin of Clostridium perfringens Q fever (Coxiellaburnetii) Ricin toxin from Ricinuscommunis (castor beans) Typhus fever (Rickettsia prowazekii) Staphylococcal enterotoxin B Food- and waterborne pathogens
o
Bacteria

Campylobacter jejuni DiarrheagenicEscherichia coli Listeria monocytogenes Salmonella typhimurium Shigella species Pathogenic Vibrios Vibrio cholerae Yersinia enterocolitica
Viruses

Caliciviruses Hepatitis A
Protozoa

Cryptosporidium parvum Cyclosporacayetanensis Entamoebahistolytica

o
54
Giardia lamblia Microsporidia Toxoplasma
Fungi
Microsporidia
Additional viral encephalitides

o o o o o o o o
California encephalitis Eastern equine encephalitis Japanese Encephalitis Virus KyasanurForest Virus LaCrosse Venezuelan equine encephalitis West Nile Virus Western equine encephalitis
Category C
Antimicrobial resistance, excluding research on sexually transmitted organisms

o o
Research on mechanisms of antimicrobial resistance Studies of the emergence and/or spread of antimicrobial resistance genes within pathogen populations
Studies of the emergence and/or spread of antimicrobial-resistant pathogens in human populations
o o
Research on therapeutic approaches that target resistance mechanisms Modification of existing antimicrobials to overcome emergent resistance
55
Antimicrobial research, as related to engineered threats and naturally occurring drugresistant pathogens, focused on development of broad-spectrum antimicrobials
Chikungunya virus Coccidioidesimmitis Coccidioidesposadasii Emerging infectious disease threats such as Nipah virus and additional hantaviruses Innate immunity, defined as the study of nonadaptive immune mechanisms that recognize, and respond to, microorganisms, microbial products, and antigens
Influenza Other Rickettsia bacteria Rabies Prions Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) Tickborne hemorrhagic fever viruses
o
Crimean-Congo Hemorrhagic fever virus
Tickborne encephalitis viruses Tuberculosis (TB), including drug-resistant TB Yellow fever
Data from reference 10.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W113 Treatment and Prophylaxis for Anthrax (Bacillus anthracis) Postexposure Treatment Prophylaxis (Symptomatic) (Prevention) Duration: 60 days Duration: minimum of 60 days after last Life-threatening (inhalational, systemic or serious cutaneous) Pre-exposure Adults: Ciprofloxacin 400 mg IV q 12 h or Adults: prophylaxis:BioThrax Ciprofloxacin 500 mg (Anthrax Vaccine PO q 12 h or Doxycycline 200 mg IV, then 100 mg IV q 12 h or Doxycycline 100 mg PO q 12 h or Levofloxacin 500750 indicated mg PO daily Postexposure Children: Ciprofloxacin 1015 mg/kg IV q 12 h (maximum 400 mg/dose) or Children: prophylaxis:BioThrax Ciprofloxacin 1015 (Anthrax Vaccine mg/kg PO q 12 h Adsorbed) 0.5 mL SC (maximum 500 at 0, 2, 4 wk mg/dose) or postexposure (IND) postexposure (treatment and Modify antimicrobials products) Adsorbed) 0.5 mL IM at 0 and 4 weeks; 6, release): Fluoroquinolone aor Cutaneous anthrax exposure Pregnancy and Vaccination Comments
56
immunocompromised: same recommendations
treatment (intentional
doxycycline for 60 days 12, 18 months with (1014 days for contact annual booster, as with contaminated animal
Levofloxacin 750 mg IV daily
prophylaxis) as indicated by susceptibility testing
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures along with 60-day Doxycycline IV (maximum 100 mg/dose): Doxycycline PO course of appropriate (maximum 100 antimicrobials mg/dose): Vaccine is not readily >8 y and >45 kg: 100 mg q 12 h >8 y and 45 kg: 2.2 mg/kg q 12 h 8 years: 2.2 mg/kg q 12 h plus 12 additional: >8 y and >45 kg: 100 available to general mg q 12 h public and mass specialist advised >8 y and 45 kg: 2.2 mg/kg q12h 8 y: 2.2 mg/kg q 12 h vaccination is not practical infectious disease Consultation with appropriate when clinically
57
Change from IV to PO
SQ anthrax vaccine injection could also be considered for someone with contraindications to
ampicillin, IM injections. chloramphenicol, clindamycin, imipenem, linezolid, meropenem, macrolide (erythro-/clarithro/azithromycin), penicillin, rifampin, vancomycin
Supportive
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures therapy:aggressive and early) for shock, fluid volume deficit, and adequacy of airway may be indicated
a
58
Fluoroquinolone: ciprofloxacin, levofloxacin.
Data from references 5, 11, 16, 22 and 29.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W114 Treatment and Prophylaxis for Botulism (Clostridium botulinum) Postexposure Treatment Prophylaxis (Symptomatic) (Prevention) Type-specific None; antitoxin Pentavalent toxoid Risk of anaphylaxis and Vaccination Comments
59
antitoxin diluted and not recommended vaccine (AE) for high- serum sickness to equine administered by slow Observe and IV infusion per product insert Adults:HBAT (heptavalent equine monitor risk individuals; preexposure prophylaxis antigens requires skin test Positive test requires desensitization before antitoxin administration Diphenhydramine and epinephrine should be readily available during administration for treatment of adverse reactions Information regarding skin Children age 1 y: refer to adult dose Children age <1 y: Human-derived botulinum antitoxin (serotypes A, B), BabyBIG testing, desensitization, preparation and administration available in product specific package insert After skin testing, a single dose of antitoxinis
Prompt treatment (investigational new with antitoxin for drug) first signs and
antitoxin, serotypes A symptoms G) Dose: single 20ml vial
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Dose: 50 mg/kg slow IV infusion recommended. Subsequent doses of antitoxin are not needed in most cases due to the antioxin half-life of 5-8 days. Data from references 5, 17, 38, 39.
60
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W115 Treatment and Prophylaxis for Plague (Yersinia pestis) Postexposure Treatment Prophylaxis (Symptomatic) (Prevention) Duration: 10 days or Duration: 7 days until afebrile for 23 after last exposure days, whichever is longer Adults: of symptoms onset). Treatment should be initiated Vaccination Comments
61
immediately (within 18-24 hours
Treatment with doxycycline may Plague pneumonia: Ciprofloxacin 500 mg PO q 12 h or Adults: vaccine no Doxycycline 100 mg Streptomycin 1 gm IM PO q 12 h or q 12 h Levofloxacin 500 Gentamicin 2 mg/kg 750 mg PO daily load, 1.7 mg/kg IV/IM q 8 h (or 5 mg/kg once Alternatives: daily) or Chloramphenicol 25 Ciprofloxacin, levofloxacin, or Tetracycline 500 mg doxycycline IV (see PO q 6 h doses under anthrax women. not recommended for pregnant mg/kg PO q 6 h or concentrations and CBC (bone marrow suppression); use cautiously in children age <2 y; under Chloramphenicol requires development monitoring of serum New vaccine measured serum concentrations available should be determined based on longer renal function; optimal dosing Adjust aminoglycoside dose for Former need longer duration of therapy (1014 days)
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures section) or Children: Chloramphenicol 25 Ciprofloxacin 1520 mg/kg IV q 6 h mg/kg PO q 12 h Children: (maximum 500 mg/dose) or Streptomycin 15 mg/kg IM q 12 h (maximum dose 2 g) or Doxycycline 2.2 mg/kg/day PO q 12 h (maximum 100 Gentamicin 2.5 mg/kg mg/dose) or IV/IM q 8 h or Tetracycline 2050 Ciprofloxacin or mg/kg/day PO q 6 h doxycycline IV (see or pediatric doses in anthrax table) or Chloramphenicol 25 mg/kg PO q 6 h Chloramphenicol 25 mg/kg IV q 6 h
62
Plague meningitis:
Adults:
Chloramphenicol IV 25
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures mg/kg load, then 12.5 mg/kg q 6 h
63
Children:
Chloramphenicol 25 mg/kg IV load, then 15 mg/kg q 6 h Data from references 5, 15, 47.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W116 Differentiating Smallpox from Chickenpox Presentation Smallpox Prodrome Chickenpox
64
Severe, lasting 14 days with fever 38.3C Short and mild or no prodrome (101F), headache, prostration, and other symptoms
Lesion development
All lesions are at the same stage of development and maturation throughout body
Lesions are at different stages of development
Lesion location
Centrifugal distribution with highest
Higher concentration on the trunk;
concentration on distal extremities and face; rarely occurs on palms or soles of also on palms and soles of hands and feet hands or feet.
Lesion presentation
Pustules occur deep in the dermis and have a Lesions are superficial and rarely hard, bead-like texture and a wellcircumscribed border; vesicles may show umbilication or become confluent show umbilication or become confluent; border of lesions is less circumscribed
Data from reference 57.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W117 Treatment and Prophylaxis for Smallpox (Variola major) Postexposure Treatment Prophylaxis (Symptomatic) (Prevention) Supportive care Commence mass vaccination Review contraindications and precautions prior to smallpox vaccination (refer to most Limited information recent ACIP or CDC with vaccinia recommendations) immune globulin may be considered if VIGIV for severe complications of vaccinia vaccination: Vaccination Comments
65
6,000 U/kg (9,000 U/kg
patient does not respond (VIG) vaccine for VIG is indicated for certain to initial dose) post-exposure vaccine complications and vaccinia exposures in immunocompromised persons 2 mL/min VIGIMIND (max: 4 mL/min) VIGIVlicensed; pediatrics < 50 kg: max rate- 0.04 and >65 yrs of ageIND mL/kg/min VIGIV infusion:
Cidofovir (IND): secondline
VIG-IM 0.6 mL/kg: third-line
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Data from references 5,18, 60.
66
67
Table W118 Treatment and Prophylaxis for Tularemia (Francisella tularensis) Postexposure Treatment (Symptomatic) Prophylaxis (Prevention) Duration: Streptomycin, gentamicin, or fluoroquinolone: 1014 days Doxycycline or chloramphenicol: 1421 days Duration: 14 days after Live-attenuated last exposure vaccine under review by FDA Adults: Vaccination
Adults:
Ciprofloxacin 500 mg PO q 12 h or
Streptomycin 1 g IM q 12 h or Doxycycline 100 mg PO Gentamicin 5 mg/kg IV/IM daily or q 12 h or Levofloxacin 500750 mg PO daily
Ciprofloxacin or levofloxacin IV daily (see doses in anthrax table); or doxycycline 100 mg IV q 12 h; or chloramphenicol 15 mg/kg IV q 6 h
Children:
Children:
Doxycycline 2.2 mg/kg PO q 12 h (max. 100
Streptomycin 15 mg/kg IM q 12 h or
mg/dose) or Ciprofloxacin 1015
Gentamicin 2.5 mg/kg IV/IM q 8 h or
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures mg/kg PO q 12 h (max. Ciprofloxacin or doxycycline IV (see doses in 500 mg/dose) anthrax table)
68
Chloramphenicol 15 mg/kg IV q 6 h
Data from references 5, 19, and 21.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W119 Treatment and Prophylaxis for Viral Hemorrhagic Fevers Postexposure Treatment Prophylaxis (Symptomatic) (Prevention) Duration and route of therapy: IV: Treatment of contained casualties, for 6 days Orally: Treatment of Definitive, high risk contacts (Arenavirusaor Bunyavirusb): Yellow fever vaccine Ribavirin PO: 35 only VHF vaccine mass casualties, a for mg/kg (maximum 2.5 available. Not 10 days Arenavirusbor Bunyavirusc: Adults Ribavirin IV (IND): 30 mg/kg (maximum 2 g) load, then 16 g), then 15 mg/kg recommended for (maximum 1 g) three infants <6 mo, and if times a day for 10 possible, wait until days infant is 9 mo. Not High risk contacts: recommended for Observe/monitor for pregnant and immunomg/kg IV (maximum signs and symptoms of compromised patients 1 g/dose) q 6 h 4 days, then 8 mg/kg illness for 21 days after exposure; if fever edema), vasopressors, APAP (for fever) Nile virus activity against West Ribavirin may have category X Ribavirin: pregnancy identification of virus appropriate before Vaccination Comments
69
Ribavirin does not have activity against Filovirusdand Flaviviruse; empiric treatment may be
Supportive care: Fluids (monitor for pulmonary
(max. 500 mg/dose) q 38.3C (101F) treat 8 h 6 days Ribavirin po: 2,000 with ribavirin
Contraindications: IM injections, NSAIDs/ASA, and
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures mg load, then if 75 kg: 600 mg twice daily if 75 kg: 1,000 mg daily (400 mg in AM and 600 mg in PM) Children Ribavirin IV: same weight-based dosing as adults Ribavirin PO: 30 mg/kg load, then 7.5 mg/kg twice daily Filovirusdand Flavivirusese: Supportive care
a
70
anticoagulants
Mass casualty defined as threshold number of cases that exhaust supply of ribavirin IV and IV
treatment would not be possible.

b
Arenaviruses: Lassa fever, Machupo, Junin, Guanarito, Sabia.
Bunyaviruses: Rift Valley fever, Congo-Crimean hemorrhagic fever, hantaviruses. Filoviruses: Ebola, Marburg.
Flaviviruses: Yellow fever, Dengue, Omsk hemorrhagic fever, Kyasansur forest disease, West
Nile virus.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Data from references 5, 20, and 71.
71
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W1110 Natural Disaster Epidemics Categories of Organism(s)/Condition Disease Water related Vibrio cholerae Escherichia coli Norovirus Salmonella Cryptosporidium Hepatitis A and E Leptospirosis Associated with crowding Measles Neisseria meningitidis Acute respiratory infections Vector borne Malaria Dengue Power outages Others Diarrhea Tetanus (Clostridium tetani) Coccidioidomycosis Data from reference 76. Disruption of refrigeration Disturbed earth/soil Facilitated transmission Comments
72
Contaminated drinking water or a lack of access to safe water and sanitation
Affected breeding sites and disease transmission
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Table W1111 Role of Healthcare Providers for Emergency Preparedness and Response Planning

73
Join health systems or community disaster/emergency response planning committees Help write disaster plans Research availability of antitoxins, vaccines, and antimicrobials Develop treatment and prophylaxis algorithms for first responders and healthcare providers
Assist with local and regional stockpiling decisions Sign up for terrorism and emergency response updates and training opportunities (through the CDC)
Complete healthcare incident command system training (through FEMA)
Education

Understand emergency management and role of healthcare providers Enhance knowledge of healthcare providers and public about potential acts of terrorism and disasters
Response

Supervise technicians, students, interns, residents, colleagues Select appropriate pre-exposure, postexposure, and treatment regimens Encourage patient adherence to regimens Advocate for diagnostic tests, cultures, and sensitivities, when appropriate Assist with screening, triage, drug information, administration of vaccines, dispensing medications, patient education, monitoring side effects
74
Join community assistance and emergency response teams
75
Figure Legends
Figure W111 Anthrax eschar. (Courtesy of the CDC.Anthrax lesion on the neck.CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
Figure W112 Anthrax chest radiograph. (Courtesy of the CDC and Arthur E. Kaye. This posteroanterior (PA) chest x-ray was taken 4 months after the onset of anthrax in a 46-year-old male, revealing bilateral pulmonary effusion, and a widened mediastinum, which are hallmarks of the disease process. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
Figure W113 Botulinum facial weakness. (Source: Grey MR, Spaeth KR. The Bioterrorisim Sourcebook: http://www.accessmedicine.com. Courtesy of Department of Health and Human Services/Office of Public Health Emergency Preparedness.)
Figure W114 Necrotic toes from plague. (Courtesy of the CDC and William Archibald. This patient presented with symptoms of plague that included gangrene of the right foot causing necrosis of the toes. In this case, the presence of systemically disseminated plague bacteria Y. pestis, i.e., septicemia, predisposed this patient to abnormal coagulation within the blood vessels of his toes. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp?pid=4139. Last accessed August 31, 2012)
Figure W115 Smallpox rash. (Courtesy of the CDC and Jean Roy. This 1974 image depicted a young male Bangladesh villager who'd contracted smallpox and was displaying the classic
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures maculopapular rash covering his entire body with pustules. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
76
Figure W116Progression of major cutaneous reaction after primary vaccination and a take. (Picture source: ACAM2000, (Smallpox (Vaccinia) Vaccine, Live,) [package insert]. Cambridge, MA: AcambisInc; 2009. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm180810.htm, Last accessed, August 31, 2012)
Figure W117Serious vaccine reaction. (Courtesy of the CDC and Allen W. Mathies. After receiving a smallpox vaccination this 1 yr. old child developed erythema multiforme. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
Figure W118Viral hemorrhagic fever hemorrhagic conjunctiva. (Courtesy of the CDC.A conjunctival hemorrhage of the right eye of this patient with infectious mononucleosis.CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures CURRENT CONTROVERSIES Current Controversy: Anthrax Some clinicians question the need for a full 60-day course of antibiotics for post-exposure prophylaxis. Continuous therapy for long time periods poses multiple problems such as; side effects, resistance emergence, poor adherence, and adverse events like C. difficile infection. Current data does not support shorter durations however.
77
Current Controversy: Smallpox Once smallpox was globally eradicated, smallpox vaccination programs halted. However, with bioterrorism concerns, mass vaccination and revaccination programs may need to commence after a suspected or confirmed smallpox case or threat.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures CLINICAL PRESENTATION Clinical Presentation of Anthrax General
78
Depending on route of exposure to anthrax, persons can present with some or all of the constellation of symptoms described below.
Signs and Symptoms
Inhalational prodrome normally consists of fever, malaise, dry cough, and shortness of breath.
Cutaneous forms produce the distinctive painless, black-crusted ulcer.
Gastrointestinal anthrax is distinguished by abdominal pain, fever, and bloody diarrhea or emesis.
Rhinorrhea is rarely reported with anthrax, thus assisting in differentiation from other influenza-like illnesses.
Complaints of drenching sweats were reported in the 2001 anthrax outbreak in the United States.
Diagnostic Tests
Standard, routine blood cultures before antibiotic administration.
Gram stain (from blood, cerebrospinal fluid, ulcer, pleural fluid).
Confirmatory assays (PCR, enzyme-linked immunosorbent assay, or
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures immunohistochemistry).
79
Chest radiography will often demonstrate pleural effusions or mediastinal widening.
Sputum cultures are rarely beneficial early in the course of inhalational cases.
Leukocyte counts are normal or only mildly elevated.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Clinical Presentation of Botulism General
80
Lethargy, acute respiratory distress, depending on the time between exposure and presentation.
Signs and Symptoms
Weakness, blurred vision, dry mouth, diplopia, dyspnea, and dysphagia.
Temperature will be normal or only mildly elevated.
Symmetrical descending flaccid paralysis and bulbar palsies such as dysphagia, dysarthria, and facial nerve dysfunction are common (Fig. W113).
Paralysis often continues to the limbs and thoracic muscles, resulting in respiratory failure.
Laboratory Tests
Complete blood count is normal.
Other laboratory tests, such as a cerebrospinal fluid sample and toxicology screening may be needed to rule out other neuromuscular etiologies.
Other Diagnostic Tests
Confirmatory serum toxin identification is available through public health facilities but results typically require days to complete. Sample must be obtained prior to the administration of antitoxin.
81
Clinical Presentation of Inhalation Plague General
Similar to severe community-acquired bacterial or influenza-like pneumonia.
Signs and Symptoms
Sudden onset of fever, chills, headache, body aches, chest discomfort, and weakness.
Productive cough, shortness of breath, hypoxia, and hemoptysis.
Watery, frothy, blood-tinged, bloody, or purulent sputum.
Gastrointestinal symptoms (nausea, vomiting, diarrhea, and abdominal pain) may be present.
Chest radiograph may show segment or lobar infiltrates or consolidation, which may evolve bilaterally; cavitary lesions, pleurisy, or adult respiratory distress syndrome may be evident.
Laboratory Tests
Gram stain and culture from affected tissue- lymph node, blood, cerebral spinal fluid, or sputum aspirate.
Rapid and confirmatory diagnostic tests, ELISA and PCR; limited availability.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Clinical Presentation of Tularemia General
82
Sudden onset of an influenza-like illness.
Signs and Symptoms

Fever, chills, muscle pains, headache, and dry cough. Ulcers around mucous membranes. Untreated infections tend to progress slowly.
Diagnostic Tests
Chest radiography may detect pulmonary infiltrates, pleural effusions, and hilar lymphadenopathy.
Collect respiratory secretions and blood cultures before antibiotic administration. Differentiated on light microscopy by small size and pleomorphic appearance. Examination of secretions or exudates via direct fluorescent antibody or immunochemical stains.
Growth in culture is the definitive confirmatory test (can be grown from sputum collections, pharyngeal washings, or even fasting gastric aspirate); normally visible after 24 to 48 hours
Rarely cultured from blood samples.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Clinical Presentation of Viral Hemorrhagic Fever General
83
Acute distress with various bleeding manifestations.
Signs and Symptoms
Fever, often accompanied by myalgia, malaise, and abdominal pain.
Signs of bleeding from a variety of sites such as mucous membranes and bloody diarrhea (Fig. W11-98).
Maculopapular rash and jaundice may be found depending on the etiologic virus.
Laboratory Tests
Thrombocytopenia is common, and may be profound (<10,000 /mm3 [<10 109/L]).
Leukopenia or leukocytosis may occur.
As infection progresses, evidence of disseminated intravascular coagulation may be found (e.g., prolonged bleeding time, elevated fibrin degradation products, decreased fibrinogen).
Hepatic enzymes, amylase may be increased in infections caused by Marburg, Lassa, and Rift Valley viruses. Bilirubin also increases in Rift Valley virus.
Other Diagnostic Tests
Real-time PCR, or ELISA tests to identify the causative virus can be performed at
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures specialized laboratories.
84
DESIRED OUTCOMES There are none for this chapter because it is obvious that cure of the infectious disease is what is desired. Abbreviations
APAP: acetaminophen ASA: aspirin CBC: complete blood count CDC: Centers for Disease Control and Prevention ELISA: enzyme-linked immunosorbent assay FDA: Food and Drug Administration FEMA: Federal Emergency Management Agency HBAT: heptavalent equine antitoxin IM: intramuscular IND: investigational new drug IV: intravenous NIAID: National Institute Allergy and Infectious Diseases NSAIDs: nonsteroidal anti-inflammatory drugs NYCBH: New York City Board of Health PCR: polymerase chain reaction PEP: postexposure prophylaxis
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures PO: by mouth SNS: Strategic National Stockpile USAMRIID: United States Army Medical Research Institute of Infectious Diseases VIGIV: Vaccinia immune globulin intravenous VIGIM: Vaccinia immune globulin intramuscular VHF: viral hemorrhagic fever
85
LEARNING OBJECTIVES AND SELF ASSESSMENT QUESTIONS Are in a separate file.

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures FIGURES
86
Figure W111 Anthrax eschar. (Courtesy of the CDC.Anthrax lesion on the neck.CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
For publisher- hi-resolution image available. ID# 1934. This is the same figure as 8th edition.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Figure W112 Anthrax chest radiograph. (Courtesy of the CDC and Arthur E. Kaye. This posteroanterior (PA) chest x-ray was taken 4 months after the onset of anthrax in a 46-year-old
87
male, revealing bilateral pulmonary effusion, and a widened mediastinum, which are hallmarks of the disease process. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
For publisher- hi resolution image available. ID# 5146. This is the same as 8th edition figure.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Figure W113 Botulinum facial weakness. (Source: Grey MR, Spaeth KR. The Bioterrorisim Sourcebook: http://www.accessmedicine.com. Courtesy of Department of Health and Human Services/Office of Public Health Emergency Preparedness.)
88
This is the same as 8th edition figure.
89
Figure W114 Necrotic toes from plague. (Courtesy of the CDC and William Archibald. This patient presented with symptoms of plague that included gangrene of the right foot causing necrosis of the toes. In this case, the presence of systemically disseminated plague bacteria Y. pestis, i.e., septicemia, predisposed this patient to abnormal coagulation within the blood vessels of his toes. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp?pid=4139. Last accessed August 31, 2012)
90
Figure W115 Smallpox rash. (Courtesy of the CDC and Jean Roy. This 1974 image depicted a young male Bangladesh villager who'd contracted smallpox and was displaying the classic maculopapular rash covering his entire body with pustules. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
91
Figure W116 Progression of major cutaneous reaction after primary vaccination and a take. (Picture source: ACAM2000, (Smallpox (Vaccinia) Vaccine, Live,) [package insert]. Cambridge, MA: AcambisInc; 2009. http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm180810.htm, Last accessed, August 31, 2012)
This is the same as 8th edition figure.
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Figure W117 Serious vaccine reaction. (Courtesy of the CDC and Allen W. Mathies. After receiving a smallpox vaccination this 1 yr. old child developed erythema multiforme. CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
92
CHAPTER W11Emergency Preparedness and Response: Biologic Exposures Figure W118 Viral hemorrhagic fever hemorrhagic conjunctiva. (Courtesy of the CDC.A conjunctival hemorrhage of the right eye of this patient with infectious mononucleosis.CDC Public Health Image Library.http://phil.cdc.gov/phil/home.asp.)
93
For publisher- hi resolution image available. ID#2862. This is the same as 8th edition figure.

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CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

weighed against the potential benefits of treatment.

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

VHF: viral hemorrhagic fever

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

Data from references 9 and 10.

Lassa fever LCM, Junin virus, Machupo virus, Guanarito virus

Hantaviruses Rift Valley fever

Brucellosis (Brucella species) Glanders (Burkholderia mallei) Melioidosis (Burkholderiapseudomallei)

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

Cryptosporidium parvum Cyclosporacayetanensis Entamoebahistolytica

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

Giardia lamblia Microsporidia Toxoplasma

Additional viral encephalitides

Antimicrobial resistance, excluding research on sexually transmitted organisms

Studies of the emergence and/or spread of antimicrobial-resistant pathogens in human populations

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

Crimean-Congo Hemorrhagic fever virus

Tickborne encephalitis viruses Tuberculosis (TB), including drug-resistant TB Yellow fever

Data from reference 10.

immunocompromised: same recommendations

Levofloxacin 750 mg IV daily

prophylaxis) as indicated by susceptibility testing

Fluoroquinolone: ciprofloxacin, levofloxacin.

Data from references 5, 11, 16, 22 and 29.

antitoxin, serotypes A symptoms G) Dose: single 20ml vial

immediately (within 18-24 hours

Lesions are at different stages of development

Centrifugal distribution with highest

Higher concentration on the trunk;

Data from reference 57.

6,000 U/kg (9,000 U/kg

Cidofovir (IND): secondline

VIG-IM 0.6 mL/kg: third-line

CHAPTER W11Emergency Preparedness and Response: Biologic Exposures

Doxycycline 2.2 mg/kg PO q 12 h (max. 100

mg/dose) or Ciprofloxacin 1015

Gentamicin 2.5 mg/kg IV/IM q 8 h or

Data from references 5, 19, and 21.

Supportive care: Fluids (monitor for pulmonary

Contraindications: IM injections, NSAIDs/ASA, and

treatment would not be possible.

Arenaviruses: Lassa fever, Machupo, Junin, Guanarito, Sabia.