Introduction: Bioterrorism is the utilization of microorganisms or toxins in order to produce a disease and/or death in human beings, animals or plants. Different from conventional weaponry, relatively economic means are used that allow the elimination of living beings without destroying the surrounding atmosphere.

The most probably method for spread of bioweapons is aerial transmission, continuing into water supplies and food. The CDC (US Centers for Disease Control and Prevention, Atlanta) has subdivided into three categories the aggressiveness of "Bioweapons".

Category A comprises:

Plague, Anthrax, Smallpox, Botulism, Tularemia, Viral Hemorrhagic Fevers (Ebola, Marpurg).

The Plague. The data reported from the WHO refer to the presence of approximately 1000/3000 cases per year of the plague, distributed mostly between Africa, South America and Asia. In the United States the last city epidemic of plague was in 1924-25, in Los Angeles, and from there the disease manifested in the rural areas with a 10-15 cases the year, above all in the New Mexico, Arizona north and south Colorado region, and also in the California, souther Oregon and western Nevada regions.

In Asia the plague is diffused in the the Caucasus and also in Russia, China, and in some zones of south-western and Southeastern Asia. The plague is present in Uganda (November 1988, 49 cases), Malawi (July 1999, 74 cases), Namibia (May 1999, 39 cases) in Madagascar and Sudafrica.

The plague is absent in Europe and Australia.

Never as hour has been taken in consideration, in our history, the requirement to one preparation in sight of an eventual terroristic attack. A terroristic attack could be put in action to means of crews of mass destruction, of chemical products, therefore like by means of crews of biological nature which virus, bacteria and other germs. In case of attack with use of products chemical and/or radioactive , the effects would be immediate.

Many hours, instead, even days, could pass silently before stating the devastating effects of an attack of biological nature.
CDC declare that the plague is a possible biological weapon because the bacterium occurs in nature and could be isolated and grown in quantity in a laboratory .

To understand a potential act of bioterrorism, it is important to recognize the presentation of naturally disease.

Bubonic Plague: incubation period is 2-6 days. Early symptoms are lymphadenopathy and fever. Patients develop swollen lymph nodes, which are called buboes. If bubonic plague is not treated, the bacteria can scatter through the bloodstream causing septicemia or infect the lungs.

Pneumonic Plague: incubation period is 2-4 days with range of 1-6 days. Symptoms are acute attack of fever, myalgias associated with progressive lack of energy. It is caused by direct inhalation of infective respiratory droplets or aerosolized bacteria. Chest radiographs of untreated patients show rapidly expanding bronchopneumonic infiltrates. Without early diagnosis and therapy in less than 24 hours, pneumonic plague is generally fatal.

Septicemic Plague is frequently fatal also when treated. Occurs when Yersinia Pestis increase in the blood. Symptoms are acute attack of fever, prostration,vomit,nausea, abdominal pain,purpura. Subsequently the disease may develop disseminated intravascular coagulation (DIC).
(Abstract)

Prof. Camillo O. Di Cicco, MD. Presented at the 15th Congress of the European Academy of Dermatology and Venereology. Rhodes - Greece.







THE PLAGUE - POSTEXPOSURE PROPHYLAXIS - THERAPY




PLAGUE - Courtesy of " US Centers for Disease Control and Prevention "(CDC)



POSTEXPOSURE PROPHYLAXIS



Doxycycline is the first choice antibiotic for postexposure prophylaxis. Once plague is suspected or confirmed in a particular region, anyone in that region with fever of 38.5°C or higher, with cough, shortly should be treated with antimicrobic for plausible pneumonic plague. Asymptomatic persons who have had contact with persons with untreated pneumonic plague should receive postexposure prophylaxis for 7 days and should be observed consequently for fever and cough. Antimicrobic recommended for these individuals: tetracycline, doxycycline, sulfonamides and chloramphenicol.

Adults Preferred choices: Doxycycline, 100 mg orally twice daily; Ciprofloxacin, 500 mg orally twice daily Alternative choices: Chloramphenicol, 25 mg/kg orally 4 times daily

Children Preferred choices: Doxycycline, If >=45kg give adult dosage If <45 kg then give 2.2 mg/kg orally twice daily Ciprofloxacin, 20 mg/kg orally twice daily Alternative choices: Chloramphenicol, 25 mg/kg orally 4 times daily

Pregnant Women Preferred choices: Doxycycline, 100 mg orally twice daily and Ciprofloxacin, 500 mg orally twice daily Alternative choices: Chloramphenicol, 25 mg/kg orally 4 times daily.



THERAPY



Adults Preferred choices: Streptomycin, 1g IM twice daily; Gentamicin, 5 mg/kg IM or IV once daily or 2 mg/kg loading dose followed by 1.7 mg/kg IM or IV three times daily. Alternative choices: Doxycycline, 100 mg IV twice daily or 200 mg IV once daily; Ciprofloxacin, 400 mg IV twice daily; Chloramphenicol, 25 mg/kg IV 4 times daily.



Children Preferred choices: Streptomycin, 15 mg/kg IM twice daily (maximum daily dose 2 g); Gentamicin, 2.5 mg/kg IM or IV 3 times daily. Alternative choices: Doxycycline, If >= 45 kg, give adult dosage If < 45 kg, give 2.2 mg/kg IV twice daily (maximum 200 mg/dl); Ciprofloxacin, 15 mg/kg IV twice daily; Chloramphenicol, 25 mg/kg IV 4 times daily.



Pregnant Women Preferred choice: Gentamicin, 5 mg/kg IM or IV once daily or 2 mg/kg loading dose followed by 1.7 mg/kg IM or IV three times daily. Alternative choices: Doxycycline, 100 mg IV twice daily or 200 mg IV once daily Ciprofloxacin, 400 mg IV twice daily.

THE PLAGUE VACCINE

Waldemar Nordecai Haffkine (1860-1930), Russian bacteriologist, has prepared for the first time a vaccine against plague,  that experienced on his person. The vaccine was prepared in a laboratory set up in a corridor of the Grant Medical College, Mumbai (India). The Hospital was founded in 1845 and whose motto was "mens sana in corpore sano”. The vaccine had significant side effects, but reduced, about 50%, the risk of plague bubonic, being however ineffective in the pulmonary form. 

In Vietnam was used the vaccine, product by Kolle and Otto in 1904, with live attenuated strains of Yersinia pestis, and widely used even in the epidemics of plague in Madagascar and Indonesia. However being unsafe, was never used in the West. 

The plague vaccine, administered intramuscularly, (2 billion of Yersinia pestis for ml - strain 195 / P) is able to create immunity for a short period of 6-12 months and, moreover, appears to be active to prevent the bubonic plague, but  have no efficacy in the pneumonic plague. 

At last, although the research is actively engaged in the produce an effective vaccine against the various forms of plague, currently the prophylaxis and the possible therapy with antibiotics, is the more timely and convenient in case of attack bioterrorist. 

In 2000, the U.S. authorities have carried out a test that has reproduced the spread of plague, by aerosol bacteriological of yersinia pestis. The test, which was code-named "TOPOFF", could produce in a few days, four thousand patients infected with plague, with 2.000 dead persons. As reported in the Archive of U.S. Department of State, the first test, TOPOFF 1, came in Denver, Colorado and Portsmouth, New Hampshire. While in Denver was a simulated chemical attack, in New Hampshire was simulated a biological attack. Followed other tests, in 2003 TOPOFF 2, TOPOFF 3 in 2005, TOPOFF 4 in 2007, to prepare populations against possible terrorist attack.