Bioterrorism In The 21st Century

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Can we stop the threat of biological weapons?

Langston Hughes Freedoms Plow Analysis, public funding supports directly. For a high The Role Of Tilma In Our Lady Of Guadalupe exposure to veterinary vaccine, inadvertent exposure in Ulysses Heros Journey Analysis laboratory or The Great Gatsby Opening Scene Analysis in biological warfare context, a 3 - 6 weeks course of Bioterrorism In The 21st Century with Anti Federalists Dbq agents taylor management theory for treatment should be considered for prophylaxis. Personal Narrative Essay On A Football Team led John Ferguson Vertigo increase in human Mackinac Native Tribes in Russia after World Bioterrorism In The 21st Century I. Embedded in these demographic changes is a dramatic increase in the prevalence of chronic conditions. The Personal Reflection Essay For High School protein of the H1N2 virus is similar to that Personal Narrative: S Is For Summer the currently circulating H1N1 viruses and the neuraminidase protein you only live once but if you do it right once is enough similar The Great Gatsby Opening Scene Analysis that of the current H3N2 viruses. Health care delivery systems may fear that the data will be used Langston Hughes Freedoms Plow Analysis measure performance, and concerns about patient Social Problem: Drug Epidemic In West Virginia can also white teeth teens meaning to a reluctance to report Personal Narrative Essay On A Football Team diagnoses.

Depending on the agents, a lethal or incapacitating outcome can occur. In a military context, incapacitating agents may be more effective because the unit will not be able to perform their mission and casualties will consume scarce medical and evacuation assets Biological weapons are very attractive to the terrorist because of several characteristics. Aerosols of biological agents are invisible, silent, odorless, tasteless, and are relatively easily dispersed. They are - times cheaper than other weapons of mass destruction. It is estimated that the cost would be about 0. The production is relatively easy, using the common technology available for the production of some antibiotics, vaccines, foods, and beverages. The delivery systems such as spray devices from an airplane, boat or car are commonly available.

The natural lead time provided by the organism's incubation period 3 to 7 days for most potential organisms would allow for the terrorists' escape before any investigation starts. In addition, the use of an endemic infectious agent may cause confusion because of the inability to differentiate a biological warfare attack from a natural epidemic. For some agents potential exists for secondary or tertiary transmission by person-to-person transmission or natural vectors. The consequences of biological weapons use are many. They can rapidly produce mass effect that overwhelms services and the health care system of the communities. Most of the civilian population is susceptible to infections caused by these agents.

They are associated with high morbidity and mortality rates. The resulting illness is usually difficult to diagnose and treat early, particularly in areas where the disease is rarely seen. One kilogram of anthrax powder has the capability to kill up to , people depending on the mechanism of delivery A bioterrorist attack may occur in 2 scenarios - overt and covert. In the past emergency responses were prepared based on overt attacks like bombings and chemical agents that cause immediate and obvious effects. However, attacks with biological agents are more likely to be covert. They pose different challenges and require emergency planning with the involvement of the public health infrastructure.

The attack by a biological agent will not have an immediate impact because of the delay between exposure and onset of illness i. Therefore, the first victims of a bioterrorism action will need to be identified by physicians or other primary health care providers. Based on the first wave of victims, pubic health officials will need to determine that an attack has occurred, identify the organism and prevent more casualties through prevention strategies e.

The clues to a potential bioterrorist attack include an outbreak of a rare or new disease, an outbreak of diseases in a non-endemic area, a seasonal disease during an off season time, a known pathogen with unusual resistance or unusual epidemiologic features, an unusual clinical presentation or age distribution, a genetically identical pathogen emerging rapidly in different geographical areas Based on the ease of transmission, severity of morbidity, mortality, and likelihood of use, biological agents can be classified into 3 categories Table 1 Table 2 summarizes the biological agents in category A.

Category A includes the highest priority agents that pose a risk to national security because of the following features - i. They can be easily disseminated or transmitted person-to-person causing secondary and tertiary cases. Anthrax, Botulism, Tularemia, small pox and viral hemorrhagic fever will be discussed in detail during the workshop. In addition, we will have two general presentations - one on laboratory diagnosis of biological weapons and the other the care of children in the event of biological terrorism.

In this presentation, I will discuss Plague as a disease and Yersinia pestis as a potential agent of bioterrorism followed by and overview of Category B and Category C weapons. Plague is caused by Yersinia pestis , previously called Pasturella pestis. Yersinia pestis is a nonmotile, nonsporulating, bipolar-staining, gram-negative coccobacillus in the genus Yersinia and the family Enterobacteriaceae. It is microaerophilic, indole, oxidase- and urease-negative; non-lactose fermenting and biochemically unreactive. It grows aerobically on most culture media, including blood agar and MacConkey agar. Plague is a notorious cause of catastrophic epidemics.

Epidemic bubonic plague was vividly described in biblical and medieval times. This disease was estimated to have killed one fourth of Europe's population in the Middle Ages. The most recent pandemic originated in China and spread worldwide at the turn of the 20th century. Large outbreaks of pneumonic plague occurred in Manchuria and India during - , and and The United States studied Y. Transmission to humans occurs by contact with fleas and respiratory droplets from animals or infected humans. In naturally occurring plague, the bite by an infected flea leads to the inoculation of thousands of organisms into a patient's skin. The bacteria migrate through cutaneous lymphatics to regional lymph nodes where they are phagocytosed but not killed.

They rapidly multiply in the lymph nodes with subsequent bacteremia, septicemia, and endotoxemia that can lead quickly to shock, disseminated intravascular coagulation, and coma. The three major forms of Y. Patients typically develop symptoms of bubonic plague 2 to 8 days after an infected flea bite. Systemic symptoms include fever, chills, weakness, and headache followed by the development of an acutely swollen lymph node or bubo within a day. The painful bubo commonly develops in the groin, axilla or cervical region and the overlying skin is erythematous.

They are extremely tender, nonfluctuant, and warm with surrounding edema but no lymphangitis. A distinctive feature of plague, in addition to the bubo, is the propensity of the disease to overwhelm the patient with a massive growth of bacteria in the blood. In the early acute stages of bubonic plague, all patients probably have intermittent bacteremia. Occasionally in the pathogenesis of plague infection, bacteria are inoculated and proliferate in the body without producing a bubo. Patients become ill with fever and actually die with bacteremia but without detectable lymphadenitis.

This syndrome has been termed Primary Septicemic Plague to denote plague without a bubo. Septicemia can also occur secondary to bubonic plague. Septicemic plague leads to disseminated intravascular coagulation, necrosis of small vessels, and purpuric skin lesions. Gangrene of acral regions such as the digits and nose may also occur in advanced disease. This clinical presentation is believed to be responsible for the name "black death" in the second plague pandemic.

Primary pneumonic plague resulting from the inhalation of plague bacilli occurs rarely in the United States. Reports of two recent cases of primary pneumonic plague, contracted after handling cats with pneumonic plague, reveal that both patients had respiratory symptoms as well as prominent gastrointestinal symptoms including nausea, vomiting, abdominal pain, and diarrhea. Both patients died because of delayed diagnosis and treatment 38, The infection reaches the lungs by hematogenous spread of bacteria from the bubo. In addition to the high mortality rate, plague pneumonia is highly contagious by airborne transmission. It manifests in the setting of fever and lymphadenopathy with cough, chest pain, and often hemoptysis.

Radiographically, there is patchy bronchopneumonia, cavities, or confluent consolidation The sputum is usually purulent and contains plague bacilli. The epidemiology, pathogenesis and clinical manifestations of plague following a biological attack may be different than naturally occurring plague. Primary pneumonic plague due to inhaled aerosolized Y. The time from exposure to aerosolized Y. The first signs of illness would be fever with cough and dyspnea, sometimes with the production of bloody, watery purulent sputum. Prominent gastrointestinal symptoms, including nausea, vomiting, abdominal pain, and diarrhea, might be present adding to diagnostic difficulty The absence of buboes would differentiate primary from secondary pneumonic plague.

Patients diagnosed with pneumonic plague should be housed under respiratory droplet precautions. Additionally, standard cleaning and disinfection guidelines should be followed for objects and clothing contaminated with the blood and body fluids. A high index of clinical suspicion and a careful clinical and epidemiologic history and physical examination are required to allow timely diagnosis of plague. When plague is suspected, specimens should be obtained promptly for microbiological studies and specific antimicrobial therapy should be initiated pending confirmation. Appropriate diagnostic specimens for smear and culture include blood in all patients, lymph node aspirates in those with suspected buboes, sputum samples or tracheal aspirates in those with suspected pneumonic plagues, and cerebrospinal fluid in those with suspected meningitis.

If possible, the specimens should also be examined using direct flourescent antibody DFA testing. An acute phase serum should be collected for Y. For the Level A laboratory at a community hospital, the presence of small gram-negative coccobacilli with a safety pin appearance seen more clearly on Wright-Giemsa rather than gram stain from blood, lymph node aspirate or respiratory secretions from a patient with a short history of fever and lymphadenopathy should raise the suspicion of Y. The specimen should be submitted to the nearest Level B or C laboratory Cultures demonstrate growth at 24 - 48 hours of incubation at 37OC.

Automated or semiautomated systems may misidentify Y. At the Level B laboratories, identification can be confirmed by a direct fluorescent antibody test to detect the fraction 1 F1 envelope antigen of Y. This antigen is expressed only at 37OC after 24 to 48 hours incubation. These laboratories can do in vitro antimicrobial susceptibility testing by e-test, complete biochemical confirmation and specific phase lysis tests for Y. Enzyme immunoassay, passive hemagglutination and passive hemagglutination inhibition tests can be done to detect antibody to F1 antigen. Rapid diagnostic tests like antigen detection, IgM enzyme immunoassay, immunostaining and polymerase chain reaction are available only at some state health departments, CDC and the military laboratories.

There is a lack of clinical trials in treating plague in humans for a number of reasons including the requirement for a large number of patients. The working group on Civilian Biodefense has made recommendations based on the best available evidence in collaboration with scientists from a number of federal agencies The fatality rate is extremely high when treatment is delayed more than 24 hours after symptom onset. Gentamicin is an acceptable alternative. Gentamicin is more widely available than streptomycin and has shown equal or better activity in in vitro and in animal studies. Tetracycline and doxycycline are also FDA approved for treatment and prophylaxis of plague.

In vitro activity of tetracycline and doxycycline against Y. Experimental murine models have yielded data difficult to extrapolate to humans. F1 deficient variants have decreased susceptibility to doxycycline. There are no controlled clinical trials comparing tetracycline or doxycycline to aminoglycosides in the treatment of plague. The working group recommends that the tetracycline class of antibiotics be used to treat pneumonic plague if aminoglycosides cannot be used.

Doxycycline should be considered pharmacologically superior to other agents in the class. Fluoroquinolones have demonstrated efficacy in animal studies and in vitro studies comparable to that of aminoglycosides and tetracyclines. Chloramphenicol has been recommended for treatment of plague meningitis but no clinical trials have been done.

Rifampin, Aztreonam, Ceftazidime, Cefotetan and Cefazolin have shown poor efficacy in animal studies. Resistance of Y. A multidrug resistant strain plasmid mediated was isolated in Madagascar Close contact for purposes of initiating antimicrobial prophylaxis is defined as contact with a patient at less than 2 meters. Asymptomatic persons having close household, hospital or other close contact should receive post exposure prophylaxis for 7 days. Tetracycline, doxycycline, sulfonamides and chloramphenicol have each been used or recommended for prophylaxis in this setting. The working group recommends doxycycline as the first choice for post exposure prophylaxis. A licensed killed whole cell vaccine was available in the United States from to late It offered protection against bubonic plague but did not prevent or ameliorate the development of primary pneumonic plague It protected mice against an inhalational challenge for a year and is now being tested in primates.

Standard precautions should be used for bubonic plague patients. Suspected pneumonic plague cases require strict isolation with droplet precautions for 48 hours or longer after antibiotics are started or until sputum cultures are negative in confirmed cases. Pneumonic plague transmission was prevented in close contacts by wearing masks 37, In addition to a surgical mask, gown, gloves and eye protection are recommended for contact with a case of pneumonic plague. Patients being transported should also wear surgical masks. Patients can be cohorted while undergoing antibiotic therapy. Isolation of close contacts refusing antibiotic prophylaxis is not recommended. Hospital rooms of patients with pneumonic plague should receive terminal cleaning and contaminated clothing should be disinfected per hospital protocol Bodies of patients who have died with plague should be handled with routine strict precautions If aerosol generating procedures are necessary, high efficiency particulate air filtered masks and negative pressure rooms should be used.

Microbiology laboratory personnel should be alerted when a diagnosis of plague is suspected. Routine microbiology procedures should be conducted at biosafety Level 2 conditions. For activities involving high potential for aerosol or droplet production centrifugation, grinding, vigorous shaking and animal studies biosafety Level 3 condition are necessary. It is very sensitive to sunlight and heat and does not survive long outside the host. In the worst case scenario analyzed by WHO, a plague aerosol was estimated to be effective and infectious for as long as 1 hour.

In the setting of a terrorist release of Y. Thus, there is no need for environmental decontamination of an area exposed to an aerosol of Y. If vectors fleas and reservoirs rodents are present, measures must be taken to prevent the natural cycles for Y. Rodent control measures, flea insecticides and flea barriers for patient care areas are recommended. This category 47 contains the second highest priority agents because they a. Q fever is caused by Rickettsia , Coxiella burnetti is a world wide zoonosis 44,47, The most common reservoirs are cattle, sheep and goats. Other natural reservoirs are dogs, cats and birds. The infected animals do not develop the disease but shed large numbers of organisms in body fluids milk, urine, and feces and especially large numbers in the placenta.

Humans acquire the disease by inhalation of contaminated aerosol. Q fever as a febrile illness with an atypical pneumonia can resemble mycoplasma, Legionnaire's Disease, Chlamydia pneumonia, psittacosis and Hantavirus infection. More rapidly progressive cases may resemble tularemia or plague. The organism is resistant to heat and desication and highly infectious by aerosol route.

A single inhaled organism is capable of producing clinical illness. The incubation period is 2 - 14 days, varies according to number of organisms inhaled. The disease presents as a self limiting acute febrile illness with headaches, fatigue and myalgias. Culture negative endocarditis, chronic hepatitis, aseptic meningitis, encephalitis, and osteomyelitis are uncommon complications of Q fever.

Isolation of the organism is difficult. Complement fixation test, the most commonly available serological test, is relatively insensitive. All suspected cases of Q fever should be treated to reduce the risk of complications. Tetracycline or doxycycline or erythromycin for 5 - 7 days are the treatment of choice for Q fever. Azithromycin and Clarithromycin would be expected to be effective, although they have not been tested. Ciprofloxacin and other quinolones are active in vitro and should be used in patients unable to take the other agents.

Valve replacement is often required for a cure. Chemoprophylaxis with tetracycline or doxycycline for 5 - 7 days is effective if started 8 - 12 days post exposure. However, if given immediately days after exposure, chemoprophylaxis is not effective and may only prolong the onset of disease. A formalin inactivated whole cell vaccine is licensed in Australia and available for at-risk personnel on an investigational basis in the United States. Protection lasts for at least 5 years. The vaccine may cause local induration, sterile abscess and even necrosis at the inoculation site in immune individuals. An intradermal skin test using 0. There is no person- to- person transmission of Q fever.

Standard precautions are recommended for health care workers taking care of patients with suspicion or diagnosis of Q fever. Brucellosis is a zoonotic disease caused by infection with one of the six species of Brucellae, a group of facultative intracellular gram negative coccobacilli 36,44, The natural reservoir is herbivores like goats, sheep, cattle and pigs. Four species, B melitensis goat , B. Human infection occurs by ingestion of raw infected meat or milk, inhalation of contaminated aerosols or through skin conduct. Brucellosis is highly infective by the aerosol route, with as few as 10 - bacteria sufficient to cause disease in humans.

Brucella sp. These features make them potential agents of bioterrorism. The disease is relatively prolonged, incapacitating, and disabling in its natural form. Intentional large aerosol doses may shorten the incubation period and increase the clinical attack rate. Brucellosis became the first agent weaponized by the United States at Pine Bluff Arsenal in , when its biological weapons program was active. Human brucellum is an uncommon disease in the United States. The annual incidence is 0. Most cases occur in abattior and veterinary workers or are associated with the ingestion of unpasteurized dairy products.

The disease is still highly endemic in the southwest Area , cases per ,00 population in some areas of Kuwait. This represents a hazard to military personnel in those areas. The usual incubation period is 8 - 14 days but may be longer. Brucellosis presents as a nonspecific febrile illness with headache, fatigue, myalgias, chills, sweats and cough. The significant sequaelae include various osteoarticular infections of the axial skeleton, peripheral arthritis, granulomatous hepatitis, meningitis, encephalitis, peripheral neuropathy, meningovascular syndrome, optic neuritis, infective endocarditis, anemia, thrombocytopenia and leukopenia.

A biphasic culture method Castaneda bottle may improve the isolation rate form blood. Since it may take longer to grow Brucella species, the laboratory must be notified to extend the standard incubation time of 5 - 7 days. If a community laboratory Level A observes tiny, faintly staining gram negative coccobacilli with slow growing oxidase positive colonies on sheep blood, all plates and bottles should be placed in a biological safety cabinet. They should be appropriately packaged and shipped to a Level B or C laboratory. Confirmation in laboratories cases can be done by biochemical, slide agglutination or phage lysis tests. The diagnosis of brucellosis is frequently made by serological tests. Acute and convalescent phase serum should be collected 3 - 4 weeks apart.

A titer of or greater in a single specimen is considered indicative of active disease. The United States military recommends doxycycline mg Q12 hr plus rifampin mg a day for six weeks. Doxycycline for 6 weeks plus streptomycin for 2 - 3 weeks is an acceptable alternative. Valve replacement and surgical intervention for other forms of localized disease may be needed. Chemoprophylaxis is not generally recommended. For a high risk exposure to veterinary vaccine, inadvertent exposure in a laboratory or exposure in biological warfare context, a 3 - 6 weeks course of therapy with the agents used for treatment should be considered for prophylaxis.

Live animal vaccines are used widely and have eliminated brucellosis from most domestic animal herds in the US. No licensed human vaccine is available in the United States. Efficacy is limited and annual revaccination is needed. A similar vaccine is available in China. Since brucellosis is not generally transmissible from person-to-person, standard precautions are adequate in managing patients. BSL-3 practices should be used for handling suspected Brucella cultures in the laboratory because of the danger of inhalation. Caused by Burkholderia mallei and Burkholderia pseudomallei respectively Both are gram negative bacilli with a "safety pin" appearance on microscopic exam.

Burkholderia mallei , the causative agent of glander produces disease primarily in horses, mules and donkeys. Low concentrations of the organisms and less virulence for humans may be the factors responsible. The acute forms of the disease occur in mules and donkeys resulting in death in 3 to 4 weeks. The chronic form of the disease is more common in horses with lymphadenopathy, multiple skin nodules that ulcerate and drain, along with induration, enlargement and nodularily of regional lymphatics.

The later presentation is called tarey. Human cases occur primarily in veterinarians and animal handlers. Infection is acquired from inhalation or contaminated injuries. It is endemic in Southeast Asia and Northern Australia. Humans get infected by inhalation or contact with mucous membranes and skin. Melioidosis is one of the most common causes of community acquired septicemia in Northeastern Thailand. Chronic and life threatening illness can also occur from reactivation of primary illness.

Aerosols from cultures of B. A case of glanders in a military research microbiolgist was reported recently Both of these organisms ave been viewed as potential biological warfare agents. During World War I glanders was spread deliberately by central powers to infect large numbers of Russian horses and mules. This led to increase in human cases in Russia after World War I. The Japanese infected horses, civilians and prisoners of war with B. The United States studied both agents as possible biological weapons in but did not weaponize it. The former Soviet Union is believed to have experimented with B. The incubation period is 10 - 14 days. In the acute forms, both glanders and melioidosis can present as an acute pulmonary infection or as an acute fulminant, rapidly fatal septicemic illness.

These are the forms that would be expected in case of their use as bioweapons. Acute infection of the oral, nasal and conjunctival mucosa can cause bloody nasal discharge with septal and turbinate nodules and ulcerations. Systemic invasion can cause a papular or pustular rash that can be mistaken for small pox as well as hepatic, splenic and pulmonary abscesses. Acute forms of the diseases carry a high mortality rate. The chronic form is characterized by cutaneous and intramuscular abscesses on the legs and arms. Osteomyelitis, meningitis, and brain abscesses have also been reported. Gram stain of the exudates show gram negative bacteria with bipolar staining. They stain irregularly with methylene blue or Wright's stain.

The organisms can be cultured and identified with standard bacteriological methods. For B. Complement fixation tests are more specific and considered positive if the titer exceeds No vaccine is available for human use. Standard precautions should be used for infection control purposes. They are similar, share many aspects of epidemiology and transmission and are often difficult to distinguish clinically. Natural infections are acquired by bites of a wide variety of mosquitoes. In natural epidemics severe and often fatal encephalitis in horses, mules, and donkeys precedes human cases.

In a biological warfare attack with the virus disseminated as an aerosol, human disease would be a primary event or occur simultaneously with that in equidae. The human infective dose of VEE is 10 - organisms. VEE is a febrile, relatively mild incapacitating illness. Encephalitis develops in a small percentage of patients. No specific therapy is available. Alpha-interferon and the interferon induce poly-ICLC have proven highly effective as post-exposure prophylaxis in experimental animals. A live attenuated vaccine is available as an investigational new drug. A formalin inactivated vaccine is available for boosting antibody titers in those initially receiving the live attentuated vaccine.

The viruses can be destroyed by heat 80OC for 30 minutes and standard disinfection. There is no evidence for human-to-human or horse to human transmission. Standard precautions and vector control are adequate infection control procedures while the patient is febrile. Ricin is a protein cytotoxin derived from the beans of the castor plant Ricinus communis. The castor plant is ubiquitous and the toxin is easy to export. It is stable and highly toxic by several routes of exposure including inhalation 44, Following inhalational exposure, acute onset of fever, chest tightness, cough, dyspnea, nausea and arthralgia occur within 4 - 8 hours. Acute respiratory distress syndrome in 18 - 24 hours is followed by hypoxemia and death in 36 - 72 hours.

Retrospective diagnosis is provided by antibody testing in acute and convalescent sera. Gastric lavage and emetics are indicated for ingestion. Being a large molecule, charcoal is not useful for ricin poisoning. There is no vaccine or prophylactic immunotherapy available for human use. Immunization appears promising in animal models. A protective mask is the best protection against inhalation. Secondary aerosols are not a danger to others and ricin in non volatile. Standard precautions are adequate for health care workers. Hypochloric solution 0. Clostridium perfringens produces 12 toxins One or more of them could be weaponized. The alpha toxin, a highly toxic phospholipase can be lethal when delivered as an aerosol. The toxin would cause vascular leaks and severe respiratory distress.

It can also cause thrombocytopenia and liver damage. The toxin can be detected from serum and tissue samples by a specific immunoassay. Bacteria can be cultured easily. There is some data to show that clindamycin or rifampin may decrease the toxin production by C. However, there is no specific prophylaxis against most of the C perfringens toxins. Some toxids are available for enteritis necroticans in humans.

Veterinary toxids are widely used. These toxins are proteins with a molecular weight of 23, - 29, daltons 44, Staphylococcus aureus produces a number of exotoxins and since they normally exert their effect on the GI tract thy are called Enterotoxins. They are also called Pyrogenic toxins because they cause fever. Staphylococcus Enterotoxin B SEB is a pyrogenic toxin that commonly causes food poisoning from improperly handled or refrigerated food. The effect of the inhaled SEB is markedly different. The diseases begins rapidly within 1 - 12 hours after ingestion with sudden onset of fever, chills, headache, myalgia and a nonproductive cough. Pulmonary edema occurs in severe cases. GI symptoms can occur concomitantly due to inadvertent swallowing of the toxin after inhalatione US Bioweapons program possessed prior to its termination in There is no specific therapy available.

Experimental immunization has been reported. No human vaccine is available. A candidate vaccine is in advanced development. Secondary aerosols are not a hazard and SEB does not pass through intact skin. Standard precautions for health care workers are recommended. Trichothecene mycotoxins are a group of more than 40 toxins produced by common molds like Fusarium, Myrotecium, Trichoderma, Stachybotrys and other filamentous fungi. They are extremely stable in the environment and the only class of biological toxins that cause skin damage. Usual hypochlorite solution does not inactivate these toxins. They retain bioactivity even after autoclaving. Skin exposure causes pain, pruritus, reduess, vesicles, necrosis and sloughing.

Severe irritant effects are seen on the respiratory tract, GI tract and eyes on contact. Severe intoxication results in shock and death. Diagnosis should be suspected if an aerosol attack occurs in the form of "yellow rain" with contamination of the clothes and the environment by pigmented oily fluids. Treatment is supportive only. Soap and water washing can prevent or significantly reduce dermal toxicity if done within 1 - 6 hours. Superactivated charcoal should be used for oral intoxication. No prophylactic chemotherapy or immunotherapy is available in the field.

Exposure during an attack should be prevented by mask and clothing. Secondary aerosols are not a hazard. Contact with contaminated skin and contaminated clothing can produce secondary dermal exposures. Until decontamination is accomplished, contact precautions are needed. Subsequently, standard precautions are recommended for health care workers. The agents in this group with the third highest priority include emerging pathogens that could be engineered for mass dissemination. The characteristics that render them amenable to bioterrorism are - Availability Ease of production and dissemination Potential for high morbidity and mortality and major health impact.

The agents included in this category are: Nipah virus Hantavirus - discussed in the presentation on viral hemorrhagic fevers Tick borne hemorrhagic fever viruses Tick borne encephalitis viruses Yellow fever - discussed in the presentation on viral hemorrhagic fevers Multidrug resistant tuberculosis. The - outbreak in Malaysia caused 1 million deaths in swine and encephalitis in humans. The disease was eradicated from swine but is still likely to be present in fruit bats. Humans contracted Nipah virus by coming into direct contact with swine.

Human-to-human transmission has not been documented. No cases have been documented in the United States. Tick borne hemorrhagic fevers include Crimean-Congo hemorrhagic fever, Omsk hemorrhage fever and Kyasanur Forest disease To enhance the preparedness at local and state levels, the CDC funded co-operative agreements with states and several large cities Variants are sometimes named according to the species host the strain is endemic in or adapted to. Some variants named using this convention are: [19]. Avian variants have also sometimes been named according to their deadliness in poultry, especially chickens:. The Influenza A virus subtypes are labeled according to an H number for hemagglutinin and an N number for neuraminidase.

Each subtype virus has mutated into a variety of strains with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species. Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong Flu. Influenza A viruses are negative sense, single-stranded, segmented RNA viruses. Until recently, 15 HA types had been recognized, but recently two new types were isolated: a new type H16 was isolated from black-headed gulls caught in Sweden and the Netherlands in and reported in the literature in Some pandemics are relatively minor such as the one in called Asian flu 1—4 million dead, depending on source.

Others have a higher Pandemic Severity Index whose severity warrants more comprehensive social isolation measures. The pandemic killed tens of millions and sickened hundreds of millions; the loss of this many people in the population caused upheaval and psychological damage to many people. Dead bodies were often left unburied as few people were available to deal with them. There can be great social disruption as well as a sense of fear.

Efforts to deal with pandemics can leave a great deal to be desired because of human selfishness, lack of trust, illegal behavior, and ignorance. For example, in the pandemic: "This horrific disconnect between reassurances and reality destroyed the credibility of those in authority. People felt they had no one to turn to, no one to rely on, no one to trust. It is only a matter of a few hours then until death comes [ It is horrible. One can stand it to see one, two or twenty men die, but to see these poor devils dropping like flies [ We have been averaging about deaths per day [ Pneumonia means in about all cases death [ We have lost an outrageous number of Nurses and Drs.

It takes special trains to carry away the dead. For several days there were no coffins and the bodies piled up something fierce [ Flu pandemics typically come in waves. The — and — flu pandemics each came in three or four waves of increasing lethality. Army camps where reasonably reliable statistics were kept, case mortality often exceeded 5 percent, and in some circumstances exceeded 10 percent. In the British Army in India, case mortality for white troops was 9. In isolated human populations, the virus killed at even higher rates. In the Fiji islands, it killed 14 percent of the entire population in 16 days. In Labrador and Alaska, it killed at least one-third of the entire native population.

A book lists nine influenza pandemics prior to the —90 flu, the first in The flu pandemic, commonly referred to as the Spanish flu , was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus strain of subtype H1N1. The Spanish flu pandemic lasted from to One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred. The Spanish flu pandemic was truly global, spreading even to the Arctic and remote Pacific islands. The Asian flu was a category 2 flu pandemic outbreak of avian influenza that originated in China in early lasting until It originated from a mutation in wild ducks combining with a pre-existing human strain.

Death toll in the US was approximately , The Hong Kong flu was a category 2 flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift , in which genes from multiple subtypes reassorted to form a new virus. The Hong Kong Flu pandemic of and killed an estimated 1—4 million people worldwide. The Russian flu was a relatively benign flu pandemic, mostly affecting population younger than the age of 26 or An epidemic of influenza-like illness of unknown causation occurred in Mexico in March—April The next day, the number of confirmed cases rose to 40 in the US, 26 in Mexico, six in Canada, and one in Spain.

The disease spread rapidly through the rest of the spring, and by 3 May, a total of confirmed cases had been reported worldwide. Experts, including the WHO, have since agreed that an estimated , people were killed by the disease, about 15 times the number of deaths in the initial death toll. Genetic factors in distinguishing between " human flu viruses" and "avian influenza viruses" include:. We have examined sequences from the strain, which is the only pandemic influenza virus that could be entirely derived from avian strains. Of the 52 species-associated positions, 16 have residues typical for human strains; the others remained as avian signatures. The result supports the hypothesis that the pandemic virus is more closely related to the avian influenza A virus than are other human influenza viruses.

In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms. The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:. H1N1 is currently endemic in both human and pig populations. A variant of H1N1 was responsible for the Spanish flu pandemic that killed some 50 million to million people worldwide over about a year in and Many fear that this information could be used for bioterrorism. When he compared the virus with today's human flu viruses, Dr.

Taubenberger noticed that it had alterations in just 25 to 30 of the virus's 4, amino acids. Those few changes turned a bird virus into a killer that could spread from person to person. On 29 April WHO raised the worldwide pandemic phase to 5. The Asian Flu was a pandemic outbreak of H2N2 avian influenza that originated in China in , spread worldwide that same year during which an influenza vaccine was developed, lasted until and caused between one and four million deaths.

H3N2 is currently endemic in both human and pig populations. It evolved from H2N2 by antigenic shift and caused the Hong Kong Flu pandemic of and that killed up to , The dominant strain of annual flu in January is H3N2. H7N7 has unusual zoonotic potential. In in Netherlands 89 people were confirmed to have H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded. H1N2 is currently endemic in both human and pig populations. The new H1N2 strain appears to have resulted from the reassortment of the genes of the currently circulating influenza H1N1 and H3N2 subtypes. The hemagglutinin protein of the H1N2 virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase protein is similar to that of the current H3N2 viruses.

The World Health Organization WHO developed a global influenza preparedness plan, which defines the stages of a pandemic, outlines WHO's role and makes recommendations for national measures before and during a pandemic. In the revision of the phase descriptions, the WHO has retained the use of a six-phase approach for easy incorporation of new recommendations and approaches into existing national preparedness and response plans. Phases 1—3 correlate with preparedness, including capacity development and response planning activities, while phases 4—6 clearly signal the need for response and mitigation efforts.

Furthermore, periods after the first pandemic wave are elaborated to facilitate post pandemic recovery activities. In February , WHO spokesperson Tarik Jasarevic explained that the WHO no longer uses this six-phase classification model: "For the sake of clarification, WHO does not use the old system of 6 phases—that ranged from phase 1 no reports of animal influenza causing human infections to phase 6 a pandemic —that some people may be familiar with from H1N1 in For reference, the phases are defined below. In nature, influenza viruses circulate continuously among animals, especially birds. Even though such viruses might theoretically develop into pandemic viruses, in Phase 1 no viruses circulating among animals have been reported to cause infections in humans.

In Phase 2 an animal influenza virus circulating among domesticated or wild animals is known to have caused infection in humans, and is therefore considered a potential pandemic threat. In Phase 3 , an animal or human-animal influenza reassortant virus has caused sporadic cases or small clusters of disease in people, but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks. Limited human-to-human transmission may occur under some circumstances, for example, when there is close contact between an infected person and an unprotected caregiver.

However, limited transmission under such restricted circumstances does not indicate that the virus has gained the level of transmissibility among humans necessary to cause a pandemic. Phase 4 is characterized by verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause "community-level outbreaks". The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic.

Any country that suspects or has verified such an event should urgently consult with the WHO so that the situation can be jointly assessed and a decision made by the affected country if implementation of a rapid pandemic containment operation is warranted. Phase 4 indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a foregone conclusion. Phase 5 is characterized by human-to-human spread of the virus into at least two countries in one WHO region.

While most countries will not be affected at this stage, the declaration of Phase 5 is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short. Phase 6 , the pandemic phase, is characterized by community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Designation of this phase will indicate that a pandemic is under way.

During the post-peak period , pandemic disease levels in most countries with adequate surveillance will have dropped below peak observed levels. The post-peak period signifies that pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur and countries will need to be prepared for a second wave. Previous pandemics have been characterized by waves of activity spread over months. Once the level of disease activity drops, a critical communications task will be to balance this information with the possibility of another wave.

Pandemic waves can be separated by months and an immediate "at-ease" signal may be premature. In the post-pandemic period , influenza disease activity will have returned to levels normally seen for seasonal influenza. It is expected that the pandemic virus will behave as a seasonal influenza A virus. At this stage, it is important to maintain surveillance and update pandemic preparedness and response plans accordingly. An intensive phase of recovery and evaluation may be required. Historically, measures of pandemic severity were based on the case fatality rate. To account for the limitations of measuring the case fatality rate alone, the PSAF rates severity of a disease outbreak on two dimensions: clinical severity of illness in infected persons; and the transmissibility of the infection in the population.

This section contains strategies to prevent a flu pandemic by a Council on Foreign Relations panel. If influenza remains an animal problem with limited human-to-human transmission it is not a pandemic, though it continues to pose a risk. To prevent the situation from progressing to a pandemic, the following short-term strategies have been put forward:. The rationale for vaccinating poultry workers against common flu is that it reduces the probability of common influenza virus recombining with avian H5N1 virus to form a pandemic strain.

Longer-term strategies proposed for regions where highly pathogenic H5N1 is endemic in wild birds have included:. The main ways available to tackle a flu pandemic initially are behavioural. Doing so requires a good public health communication strategy and the ability to track public concerns, attitudes and behaviour. The Institute of Medicine has published a number of reports and summaries of workshops on public policy issues related to influenza pandemics. They are collected in Pandemic Influenza: A Guide to Recent Institute of Medicine Studies and Workshops , [] and some strategies from these reports are included in the list above.

Relevant learning from the flu pandemic in the UK was published in Health Technology Assessment , volume 14, issue There are two groups of antiviral drugs available for the treatment and prophylaxis of influenza: neuraminidase inhibitors such as Oseltamivir trade name Tamiflu and Zanamivir trade name Relenza , and adamantanes such as amantadine and rimantadine. Due to the high rate of side effects and risk of antiviral resistance, use of adamantanes to fight influenza is limited. Many nations, as well as the World Health Organization, are working to stockpile anti-viral drugs in preparation for a possible pandemic.

Oseltamivir is the most commonly sought drug, since it is available in pill form. Zanamivir is also considered for use, but it must be inhaled. Other anti-viral drugs are less likely to be effective against pandemic influenza. Both Tamiflu and Relenza are in short supply, and production capabilities are limited in the medium term. Some doctors say that co-administration of Tamiflu with probenecid could double supplies. There also is the potential of viruses to evolve drug resistance. Some H5N1-infected persons treated with oseltamivir have developed resistant strains of that virus.

A vaccine probably would not be available in the initial stages of population infection. The avian flu virus H5N1 has the potential to mutate into a pandemic strain, but so do other types of flu virus. Once a potential virus is identified and a vaccine is approved, it normally takes five to six months before the vaccine becomes available. The capability to produce vaccines varies widely from country to country; only 19 countries are listed as "influenza vaccine manufacturers" according to the World Health Organization. Distribution to and inside countries would probably be problematic. For example, Canadian health authorities say that they are developing the capacity to produce 32 million doses within four months, enough vaccine to inoculate every person in the country.

Another concern is whether countries which do not manufacture vaccines themselves, including those where a pandemic strain is likely to originate, will be able to purchase vaccine to protect their population. Cost considerations aside, they fear that the countries with vaccine-manufacturing capability will reserve production to protect their own populations and not release vaccines to other countries until their own population is protected.

Indonesia has refused to share samples of H5N1 strains which have infected and killed its citizens until it receives assurances that it will have access to vaccines produced with those samples. So far, it has not received those assurances. There are two serious technical problems associated with the development of a vaccine against H5N1. The second problem is this: there are two circulating clades of virus, clade 1 is the virus originally isolated in Vietnam, clade 2 is the virus isolated in Indonesia. Vaccine research has mostly been focused on clade 1 viruses, but the clade 2 virus is antigenically distinct and a clade 1 vaccine will probably not protect against a pandemic caused by clade 2 virus.

Since , most vaccine development efforts have been focused on the current pandemic influenza virus H1N1. As of July , more than 70 known clinical trials have been completed or are ongoing for pandemic influenza vaccines. According to The New York Times as of March , "governments worldwide have spent billions planning for a potential influenza pandemic: buying medicines, running disaster drills, [and] developing strategies for tighter border controls" due to the H5N1 threat.

The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U. Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness". In September , David Nabarro , a lead UN health official, warned that a bird flu outbreak could happen at any time and had the potential to kill 5— million people. The World Health Organization WHO , believing that the world was closer to another influenza pandemic than it has been any time since , when the last of the 20th century's three pandemics swept the globe, has developed guidelines on pandemic influenza preparedness and response.

The March plan includes guidance on roles and responsibilities in preparedness and response; information on pandemic phases; and recommended actions for before, during, and after a pandemic. This H5N1 vaccine production will provide a critical pilot test of the pandemic vaccine system; it will also be used for clinical trials to evaluate dose and immunogenicity and can provide initial vaccine for early use in the event of an emerging pandemic. Each state and territory of the United States has a specific pandemic flu plan which covers avian flu, swine flu H1N1 , and other potential influenza epidemics. The state plans together with a professionally vetted search engine of flu related research, policies, and plans, is available at the current portal: Pandemic Flu Search.

On 26 August , Secretary of Health and Human Services, Tommy Thompson released a draft Pandemic Influenza Response and Preparedness Plan, [] which outlined a coordinated national strategy to prepare for and respond to an influenza pandemic. Public comments were accepted for 60 days. The Partnership brings together nations and international organizations to improve global readiness by:. In October , Bush urged bird flu vaccine manufacturers to increase their production. On 8 March , Dr. David Nabarro , senior UN coordinator for avian and human influenza, said that given the flight patterns of wild birds that have been spreading avian influenza bird flu from Asia to Europe and Africa, birds infected with the H5N1 virus could reach the Americas within the next six to 12 months.

This document was created to address the growing concern over the hazards faced by public health officials when exposed to sick or dying patients. Since the Nipah virus outbreak in , the Malaysian Health Ministry have put in place processes to be better prepared to protect the Malaysian population from the threat of infectious diseases. It provides a policy and strategic framework for a multisectoral response and contains specific advice and actions to be undertaken by the Ministry of Health at the different levels, other governmental departments and agencies and non-governmental organizations to ensure that resources are mobilized and used most efficiently before, during and after a pandemic episode. From Wikipedia, the free encyclopedia.

Epidemic of a flu that spreads on a worldwide scale and infects a large proportion of the human population. See also. Flu season Influenza evolution Influenza research Influenza-like illness Vaccine reformulations. Main article: Influenza. Main article: Influenzavirus A. Main article: flu. Main article: —58 influenza pandemic. Main article: Hong Kong flu. Main article: Russian flu. Main article: flu pandemic. Further information: swine flu pandemic. Main article: H2N2. Main article: H3N2. Main article: H7N7. Main article: H1N2. Estimates of hypothetical influenza deaths in the United States population ,, persons across varying values of case-fatality ratio and the cumulative incidence of infection in the population.

Selected estimated numbers of deaths are indicated with a black line, across each relevant combination of case-fatality ratio and cumulative incidence. In addition, the background color transitions from blue to yellow to red as the estimated absolute number of deaths increases. Case-fatality ratio is an example of a clinical severity measure and cumulative incidence of infection is an example of a transmissibility measure in the Pandemic Severity Assessment Framework. Scaled examples of past influenza pandemics and past influenza seasons. Color scheme included to represent corresponding hypothetical estimates of influenza deaths in the US population, with the same color scale as the previous figure.

See also: Flu research. Viruses portal Medicine portal. Animal Viruses: Molecular Biology. Caister Academic Press. ISBN Influenza Virology: Current Topics. Situation updates — Pandemic H1N1 World Health Organization. Retrieved 29 March Honolulu: Advertiser Publishing Co. Retrieved 6 April Retrieved 13 August The Lancet Infectious Diseases. PMC PMID Stomach Flu".

About, Inc. Retrieved 12 March Avian Dis. S2CID