Shmuel C. Shapira, MD and Joshua Shemer
Rami Sagi, MD, Eyal Robenshtok, MD, Lior H. Katz, MD, Shmuel Reznikovich, MMHF, Israel Hendler, MD, Lior Poles, MD, Ariel Hourvitz, MD, Boaz Tadmor, MD, Meir Oren, MD, Giora Martonovich, MD and Boaz Lev, MD
The threat of a disease outbreak resulting from biologic warfare has been of concern for the Israeli health system for many years. In order to be prepared for such an event the health system has formulated doctrines for various biologic agents and defined the logistic elements for the procurement of drugs. During the last 4 years, and especially after the West Nile fever epidemic in 2000, efforts to prepare the healthcare system and the relevant organizations were accelerated. The Director-General of the Ministry of Health nominated a Supreme Steering Committee to fill in the gaps and upgrade the preparedness of the health system for an unusual disease outbreak. This committee and its seven subcommittees established appropriate guidelines, communication routes among different organizations, and training programs for medical personnel. The anthrax outbreak in the United States found the healthcare system in the hub of the preparation process, and all modes of action were intensified. Further work by hospitals, primary care clinics and all other institutes should be initiated to maintain a state of proper preparedness.
Manfred S. Green, MD, PhD and Zalman Kaufman, MSc
The appearance of “new” infectious diseases, the reemergence of “old” infectious diseases, and the deliberate introduction of infectious diseases through bioterrorism has highlighted the need for improved and innovative infectious disease surveillance systems. A review of publications reveals that traditional current surveillance systems are generally based on the recognition of a clear increase in diagnosed cases before an outbreak can be identified. For early detection of bioterrorist-initiated outbreaks, the sensitivity and timeliness of the systems need to be improved. Systems based on syndromic surveillance are being developed using technologies such as electronic reporting and the internet. The reporting sources include community physicians, public health laboratories, emergency rooms, intensive care units, district health offices, and hospital admission and discharge systems. The acid test of any system will be the ability to provide analyses and interpretations of the data that will serve the goals of the system. Such analytical methods are still in the early stages of development.
Stephen A. Berger, MD and Itzhak Shapira, MD
Raymond Kaempfer, PhD, Gila Arad, PhD, Revital Levy, BA and Dalia Hillman, BA
Background: Superantigens produced by Staphylococcus aureus and Streptococcus pyogenes are among the most lethal of toxins. Toxins in this family trigger an excessive cellular immune response leading to toxic shock.
Objectives: To design an antagonist that is effective in vivo against a broad spectrum of superantigen toxins.
Methods: Short peptide antagonists were selected for their ability to inhibit superantigen-induced expression of human genes for cytokines that mediate shock. The ability of these peptides to protect mice against lethal toxin challenge was examined.
Results: Antagonist peptide protected mice against lethal challenge with staphylococcal enterotoxin B and toxic shock syndrome toxin-1, superantigens that share only 6% overall amino acid homology. Moreover, it rescued mice undergoing toxic shock. Antagonist peptides show homology to a β-strand/hinge/a-helix domain that is structurally conserved among superantigens, yet remote from known binding sites for the major histocompatibility class II molecule and T cell receptor that function in toxic T cell hyperactivation.
Conclusions: The lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells occurs. Superantigenic toxin antagonists may serve not only as countermeasures to biologic warfare but may be useful in the treatment of staphylococcal and streptococcal toxic shock, as well as in some cases of septic shock.
Itzhak Braverman, MD, David Wexler, MD and Meir Oren, MD
Eyal Robenshtok, MD, Shay Luria, MD, Zeev Tashma, PhD and Ariel Hourvitz, MD
Atropine is the drug of choice for treatment of organophosphate (OP) nerve agent and insecticide intoxication and has been used for this indication for several decades. Adverse reactions to atropine may occur, and are of two types: toxic and allergic. Toxic reaction, the most common form, results from the anti-muscarinic effects of the drug. Since it is most probably related to interpersonal variation in sensitivity to atropine, toxic effects may appear at the usual therapeutic doses. The second type, allergic reaction, includes local manifestations, usually after the administration of eyedrops, and systemic reaction in the form of anaphylaxis. Since most patients manifest only a mild reaction, allergy testing is not performed and the prevalence of allergy to atropine is therefore not known. Severe allergic reaction to atropine is rare, as evidenced by the small number of case reports in the literature despite the drug's extensive use. Alternative anti-muscarinic drugs recommended for OP poisoning include glycopyrrolate and scopolamine. Glycopyrrolate is a peripheral anti-muscarinic drug that has been studied in comparison to atropine for many clinical indications, while scopolamine is an anti-muscarinic drug with both peripheral and central effects. An acceptable alternative regimen for patients with proven allergy to atropine is a combination of glycopyrrolate with centrally active drugs such as benzodiazepines or scopolamine.
Ronen Rubinshtein, MD, Eyal Robenshtok, MD, Arik Eisenkraft, MD, Aviv Vidan, MD and Ariel Hourvitz, MD
Recent events have significantly increased concern about the use of biologic and chemical weapons by terrorists and other countries. Since weapons of mass destruction could result in a huge number of casualties, optimizing our diagnostic and therapeutic skills may help to minimize the morbidity and mortality. The national demands for training in medical aspects of nuclear, biologic and chemical warfare have increased dramatically. While Israeli medical preparedness for non-conventional warfare has improved substantially in recent years especially due to extensive training programs, a standardized course and course materials were not available until recently. We have developed a core curriculum and teaching materials for a 1 or 2 day modular course, including printed materials.
Gidon Almogy, MD, Arnon Makori, MD, Oded Zamir, MD, Alon J. Pikarsky, MD and Avraham I. Rivkind, MD