1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:46,800 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:46,800 --> 00:00:48,640 >>OUR SPEAKERS 12 00:00:48,640 --> 00:00:50,680 TODAY ARE DR. MARY WRIGHT, 13 00:00:50,680 --> 00:00:52,240 CLINICAL INVESTIGATOR WITH THE 14 00:00:52,240 --> 00:00:53,880 NATIONAL INSTITUTE OF ALLERGY 15 00:00:53,880 --> 00:00:55,720 INFECTIOUS DISEASES, DIVISION OF 16 00:00:55,720 --> 00:01:02,440 CLINICAL RESEARCH AND DR. ARTHUR 17 00:01:02,440 --> 00:01:04,920 FREIDLANDER AND DR. NICHOLAS 18 00:01:04,920 --> 00:01:07,040 JOHN VIETRA, WITH THE BOISE 19 00:01:07,040 --> 00:01:08,840 VETERANS AFFAIRING MEDICAL 20 00:01:08,840 --> 00:01:09,440 CENTER. 21 00:01:09,440 --> 00:01:10,720 DR. WRIGHT EARNED HER MEDICAL 22 00:01:10,720 --> 00:01:11,800 DEGREE AT THE GEORGE WASHINGTON 23 00:01:11,800 --> 00:01:13,760 SCHOOL OF MEDICINE AND A PASTERS 24 00:01:13,760 --> 00:01:15,720 OF PUBLIC HEALTH WITH THE JOHNS 25 00:01:15,720 --> 00:01:17,640 HOPKINS SCHOOL OF PUBLIC HEALTH 26 00:01:17,640 --> 00:01:18,600 AND COMPLETED INTERNSHIP IN 27 00:01:18,600 --> 00:01:20,960 RESIDENCE SKPE BAKUGAN INTERNAL 28 00:01:20,960 --> 00:01:21,640 MEDICINE AT GW. 29 00:01:21,640 --> 00:01:30,880 SHE JOINED THE NIH IN 2000 AS 30 00:01:30,880 --> 00:01:33,280 A--2001, BECAME A MEDICAL 31 00:01:33,280 --> 00:01:35,280 OFFICER AND NIAID DIVISION'S OF 32 00:01:35,280 --> 00:01:37,080 CLINICAL RESEARCH, HELPING TO 33 00:01:37,080 --> 00:01:39,440 PLAN DCR'S HIGH CONTAINMENT 34 00:01:39,440 --> 00:01:41,880 INFECT YOWZ DISEASE LABORATORY 35 00:01:41,880 --> 00:01:42,880 AT FORT DIETRICH, WHILE 36 00:01:42,880 --> 00:01:45,360 COLLABORATING WITH THE UNITED 37 00:01:45,360 --> 00:01:47,960 STATES ARMY AND ALSO SERVINGOT 38 00:01:47,960 --> 00:01:51,160 FDA AND CDC DECISION MAKING 39 00:01:51,160 --> 00:01:52,000 PANELS. 40 00:01:52,000 --> 00:01:53,720 DR. WRIGHT RECEIVED MANY AWARDS 41 00:01:53,720 --> 00:01:55,240 INCLUDING OWS STANDING PERFORM 42 00:01:55,240 --> 00:01:59,120 AS OF THERAPEUTICS TO TREAT 43 00:01:59,120 --> 00:02:00,840 COVID-19 AND NIAID SPECIAL 44 00:02:00,840 --> 00:02:02,640 ACTIVE AWARDS FOR HER SPECIFIC 45 00:02:02,640 --> 00:02:03,520 COVID-19 RESPONSE AND 46 00:02:03,520 --> 00:02:06,040 EXCEPTIONAL EFFORTS IN THE 47 00:02:06,040 --> 00:02:06,440 COORDINATION OF 48 00:02:06,440 --> 00:02:07,040 BIODEFENSISHIAATIVES BETWEEN THE 49 00:02:07,040 --> 00:02:09,440 NIH AND THE DEPARTMENT OF 50 00:02:09,440 --> 00:02:09,680 DEFENSE. 51 00:02:09,680 --> 00:02:14,960 OUR SECOND SPEAKER IS DR. ARTHUR 52 00:02:14,960 --> 00:02:16,720 FRIEDLANDER, AT THE MEDICAL 53 00:02:16,720 --> 00:02:19,120 RESEARCH INSTITUTE OF INFECTIOUS 54 00:02:19,120 --> 00:02:20,080 DISEASES AND ADJUNCT PROFESSOR 55 00:02:20,080 --> 00:02:24,000 OF AT THE UNIVERSITY. 56 00:02:24,000 --> 00:02:25,200 DR. FRIEDLANDER EARNED HIS 57 00:02:25,200 --> 00:02:26,600 DEGREE FOR THE UNIVERSITY OF 58 00:02:26,600 --> 00:02:27,200 PITTSBURGH, AFTER COMPLETING 59 00:02:27,200 --> 00:02:28,520 MEDICAL TRAINING AND A POST 60 00:02:28,520 --> 00:02:31,320 DOCTORAL FELLOWSHIP AT THE NIH, 61 00:02:31,320 --> 00:02:34,400 HE COMPLETED A POST DOCTORAL NIH 62 00:02:34,400 --> 00:02:35,280 FELLOWSHIP AT THE UNIVERSITY OF 63 00:02:35,280 --> 00:02:41,000 CALIFORNIA SAN DIEGO. 64 00:02:41,000 --> 00:02:41,920 DR. FRIEDBERG, THEN WAS CHIEF OF 65 00:02:41,920 --> 00:02:44,840 THE DEPARTMENT OF PATHOBIOLOGY 66 00:02:44,840 --> 00:02:48,240 AND CHIEF OF THE BACTERIAL I 67 00:02:48,240 --> 00:02:49,920 HAVEROLOGY DEVISION, HIS 68 00:02:49,920 --> 00:02:51,320 RESEARCH IS PATHOGEN AFFECTED 69 00:02:51,320 --> 00:02:55,520 DISEASES IN VACCINE DEVELOPMENT. 70 00:02:55,520 --> 00:02:58,320 HE HAD A TARPGETTED ANTHRAX 71 00:02:58,320 --> 00:03:00,840 LETHAL TOXIN AND DEMONSTRATED 72 00:03:00,840 --> 00:03:03,440 THE EXPOSURE AND PROPHYLAXIS 73 00:03:03,440 --> 00:03:05,440 PROVIDING EVIDENCE FOR CURRENT 74 00:03:05,440 --> 00:03:06,440 HUMANS AND DIRECTIVE RESEARCH 75 00:03:06,440 --> 00:03:07,520 THAT RESULT INDEED NEW 76 00:03:07,520 --> 00:03:10,640 GENERATION OF VACCINES FOR 77 00:03:10,640 --> 00:03:12,280 ANTHRAX AND PLAGUED CURRENTLY IN 78 00:03:12,280 --> 00:03:14,240 THE HUMAN TRIALS. 79 00:03:14,240 --> 00:03:16,600 DR. FRIEDLANDER IS A FELLOW WITH 80 00:03:16,600 --> 00:03:17,640 THE INFECT YOWZ DISEASE SOCIETY 81 00:03:17,640 --> 00:03:19,200 OF AMERICA, AND A RESENT YF THE 82 00:03:19,200 --> 00:03:20,240 ARMY RESEARCH AND DEVELOPMENT 83 00:03:20,240 --> 00:03:22,720 AWARD AND THE J. P. SANFORD 84 00:03:22,720 --> 00:03:30,000 AWARD FOR INFECT YOWZ DECEASES. 85 00:03:30,000 --> 00:03:30,120 D 86 00:03:30,120 --> 00:03:30,400 E 87 00:03:30,400 --> 00:03:30,520 C 88 00:03:30,520 --> 00:03:30,640 E 89 00:03:30,640 --> 00:03:30,800 A 90 00:03:30,800 --> 00:03:31,280 SE--INFECTIOUS DISEASES, 91 00:03:31,280 --> 00:03:33,040 SPANS 1999-2008 AND WAS A 2012 92 00:03:33,040 --> 00:03:35,600 FINALIST FOR THE SERVICE TO 93 00:03:35,600 --> 00:03:36,280 AMERICA MEDAL. 94 00:03:36,280 --> 00:03:41,520 OUR FINAL SPEAKER IS 95 00:03:41,520 --> 00:03:42,880 DR. NICHOLAS VIETRI, CHAIRMAN OF 96 00:03:42,880 --> 00:03:44,840 THE BOISE MEDICAL TRUSTEES, 97 00:03:44,840 --> 00:03:46,000 RESEARCH AND INFECT YOWZ 98 00:03:46,000 --> 00:03:48,320 COMMITTEES AND A U.S. ARMY 99 00:03:48,320 --> 00:03:50,640 MEDICAL CORPS OFFICER, RETIRED. 100 00:03:50,640 --> 00:03:53,760 HE SERVED AS A CONSULTANT TO THE 101 00:03:53,760 --> 00:03:55,920 ARMY SURGEON GENERAL FOR 102 00:03:55,920 --> 00:03:57,240 BIOLOGICAL DEFENSE, AMERICAN 103 00:03:57,240 --> 00:03:59,520 CONSULTANT FOR THE COLLEGE OF 104 00:03:59,520 --> 00:04:00,640 PHYSICIANS, EDUCATION ONLINE 105 00:04:00,640 --> 00:04:03,280 MODULE FOR ANTHRAX AND A SUBJECT 106 00:04:03,280 --> 00:04:05,400 MATTER EXPERT FOR U.S. ARMY 107 00:04:05,400 --> 00:04:06,200 MEDICAL DEVELOPMENT MATERIAL 108 00:04:06,200 --> 00:04:09,560 ACTIVITY OF OR HEALTH PROTECTIVE 109 00:04:09,560 --> 00:04:10,960 PROTOCOLS INVOLVING ANTHRAX AND 110 00:04:10,960 --> 00:04:12,600 SMALL POX. 111 00:04:12,600 --> 00:04:14,280 DR. VIERKTS ETRI EARNED HIS 112 00:04:14,280 --> 00:04:17,440 DEGREE FROM THE UNIVERSITY OF 113 00:04:17,440 --> 00:04:18,640 MONTANA. 114 00:04:18,640 --> 00:04:21,680 HE COMPLETED INTERNAL MEDICINE 115 00:04:21,680 --> 00:04:23,040 RESIDENCY IN TEXAS. 116 00:04:23,040 --> 00:04:25,240 DR. VIETRI IS A FELLOW OF THE 117 00:04:25,240 --> 00:04:26,720 INFECTIOUS DISEASE SOCIETY OF 118 00:04:26,720 --> 00:04:27,000 AMERICA. 119 00:04:27,000 --> 00:04:28,960 RECIPIENT OF THE JOHN F. MAYER 120 00:04:28,960 --> 00:04:31,920 M. D. AWARD FOR RESEARCH AND 121 00:04:31,920 --> 00:04:32,520 UNIFORM RESEARCH UNIVERSITY 122 00:04:32,520 --> 00:04:34,280 DEPARTMENT OF MEDICINE AND A 123 00:04:34,280 --> 00:04:37,800 TWICE RECIPIENT OF THE ARMY 124 00:04:37,800 --> 00:04:39,320 PERFORMANCE AWARD AS THE 125 00:04:39,320 --> 00:04:41,080 MICROBIOLOGIST AT THE U.S. ARMY 126 00:04:41,080 --> 00:04:44,040 MEDICAL RESEARCH INSTITUTE OF 127 00:04:44,040 --> 00:04:46,120 INFECTIOUS DISEASES, PLEASE 128 00:04:46,120 --> 00:04:47,960 WELCOME OUR FIRST SPEAKER 129 00:04:47,960 --> 00:04:48,920 DR. WRIGHT, WHO'S TALK IS 130 00:04:48,920 --> 00:04:51,240 ENTITLED 21 YEARS AFTER ANTHRAX, 131 00:04:51,240 --> 00:04:52,240 WHAT CLINICAL QUESTIONS REMAIN. 132 00:04:52,240 --> 00:04:53,520 >>THANK YOU FOR THAT KIND 133 00:04:53,520 --> 00:04:54,560 INTRODUCTION AND THE OPPORTUNITY 134 00:04:54,560 --> 00:04:55,560 TO SHARE RESULTS AND 135 00:04:55,560 --> 00:04:57,520 OBSERVATIONS FROM OUR LONG TIME 136 00:04:57,520 --> 00:04:57,960 COLLABORATION. 137 00:04:57,960 --> 00:04:59,800 WE HAVE NO DISCLOSURES TO 138 00:04:59,800 --> 00:05:02,320 REPORT, ALL OF OUR WORK WAS DONE 139 00:05:02,320 --> 00:05:03,440 THROUGH AN INNER AGENCY 140 00:05:03,440 --> 00:05:04,840 AGREEMENT BETWEEN OUR DIVISION 141 00:05:04,840 --> 00:05:07,600 AND THE DIVISION OF CLINICAL 142 00:05:07,600 --> 00:05:11,200 RESEARCH AT NIAID AND USA MRAD 143 00:05:11,200 --> 00:05:12,920 OF THE ARMY OUR CONCLUSIONS ARE 144 00:05:12,920 --> 00:05:14,200 OUR OWN AND DON'T NECESSARILY 145 00:05:14,200 --> 00:05:15,440 REFLECT THOSE OF OUR INDIVIDUAL 146 00:05:15,440 --> 00:05:16,880 AGENCIES AND ANY DISCUSSION OF 147 00:05:16,880 --> 00:05:20,040 OFFLABEL DRUG USE IS IN THE 148 00:05:20,040 --> 00:05:21,000 CONTEXT OF RESEARCH. 149 00:05:21,000 --> 00:05:23,520 OUR OBJECTIVES ARE TO DESCRIBE 150 00:05:23,520 --> 00:05:25,560 WHAT WAS KNOWN ABOUT HUMAN 151 00:05:25,560 --> 00:05:28,280 INFECTION WITH [INDISCERNIBLE] 152 00:05:28,280 --> 00:05:31,280 AS THE 2001 ANTHRAX LETTER 153 00:05:31,280 --> 00:05:32,680 ATTACKED UNFOLDED, EXAMINE KEY 154 00:05:32,680 --> 00:05:34,160 QUESTIONS THAT AROSE FROM THE 155 00:05:34,160 --> 00:05:35,480 ATTACKS AND RESEARCH TO ADDRESS 156 00:05:35,480 --> 00:05:37,560 THEM AND BECOME AWARE OF 157 00:05:37,560 --> 00:05:38,120 RESEARCH INFRASTRUCTURE AND 158 00:05:38,120 --> 00:05:39,480 CAPACITY THAT GREW OUT OF THE 159 00:05:39,480 --> 00:05:42,560 RESPONSE TO BYEE TERRORISM. 160 00:05:42,560 --> 00:05:45,720 AND LASTLY TO IDENTIFY REMAINING 161 00:05:45,720 --> 00:05:48,240 CLINICAL QUESTIONS, REGARDING 162 00:05:48,240 --> 00:05:48,720 INHALATION OF ANTHRAX. 163 00:05:48,720 --> 00:05:51,120 SO NOW WE WILL GO BACK IN TIME, 164 00:05:51,120 --> 00:05:55,120 MORE THAN 20 YEARS AGO TO 165 00:05:55,120 --> 00:05:56,560 SEPTEMBER 2001 AND AS WE SEE 166 00:05:56,560 --> 00:05:58,360 HERE, WE'RE REMINDED THAT THE 167 00:05:58,360 --> 00:06:00,160 FIRST LETTERS WERE MAILED ON 168 00:06:00,160 --> 00:06:01,600 SEPTEMBER 18th JUST A WEEK 169 00:06:01,600 --> 00:06:04,040 AFTER 9/11 WHEN THE NATION WAS 170 00:06:04,040 --> 00:06:09,160 STILL IN SHOCK AFTER A TERRORIST 171 00:06:09,160 --> 00:06:09,520 ATTACK. 172 00:06:09,520 --> 00:06:10,600 SENATE OFFICES, HOUSE OFFICES 173 00:06:10,600 --> 00:06:12,760 HAD TO CLOSE DOWN BECAUSE THEY 174 00:06:12,760 --> 00:06:14,200 RECEIVED ANTHRAX LETTERS, AND 175 00:06:14,200 --> 00:06:21,440 THERE WAS A BIG OUTCRY 176 00:06:21,440 --> 00:06:23,520 AND--FIGURE OUT HOW TO FACE THIS 177 00:06:23,520 --> 00:06:24,280 UNCERTAINTY, WHAT WAS THE SCOPE 178 00:06:24,280 --> 00:06:28,600 GOING TO BE LIKE, HOW LONG WOULD 179 00:06:28,600 --> 00:06:29,720 THIS LAST? 180 00:06:29,720 --> 00:06:34,800 AND AS TURNS OUT, IT ENDED WITH 181 00:06:34,800 --> 00:06:37,160 22 CASES, 11 CUTANEOUS AND 182 00:06:37,160 --> 00:06:37,880 LISTEN INHALATIONAL WITH 5 183 00:06:37,880 --> 00:06:38,120 DEATHS. 184 00:06:38,120 --> 00:06:39,280 AND IT'S HARD TO BELIEVE THAT 185 00:06:39,280 --> 00:06:43,080 ALL THIS ONLY LASTED A COUPLE OF 186 00:06:43,080 --> 00:06:45,720 MONTHS WITH THE FIRST START DATE 187 00:06:45,720 --> 00:06:47,320 BEING AROUND SEPTEMBER 18th 188 00:06:47,320 --> 00:06:48,840 WITH THAT INITIAL MAILING AND 189 00:06:48,840 --> 00:06:50,600 THEN THE LAST INHALATIONAL DEATH 190 00:06:50,600 --> 00:06:52,560 BEING ON NOVEMBER 21st. 191 00:06:52,560 --> 00:06:54,760 AND LATER ON, IN CONGRESSIONAL 192 00:06:54,760 --> 00:06:56,720 TESTIMONY, IT WOULD BE BROUGHT 193 00:06:56,720 --> 00:06:58,360 OUT THAT IT COST GREATER THAN A 194 00:06:58,360 --> 00:07:01,080 BILLION DOLLARS JUST FOR THE 195 00:07:01,080 --> 00:07:01,840 DECONTAMINATION OF THE POST 196 00:07:01,840 --> 00:07:09,240 OFFICE AND GOVERNMENT BUILDINGS 197 00:07:09,240 --> 00:07:09,720 ALONE. 198 00:07:09,720 --> 00:07:11,320 ANTHRAX IS A BIOLOGICAL WEAPON 199 00:07:11,320 --> 00:07:12,520 TO BE KNOWN FOR THAT FOR YEARS 200 00:07:12,520 --> 00:07:15,200 AND GROUPS ON THE WORKING GROUP 201 00:07:15,200 --> 00:07:16,280 ON CIVILIAN BIODEFENSE HAS COME 202 00:07:16,280 --> 00:07:19,360 TOGETHER AND WRITTEN THIS 203 00:07:19,360 --> 00:07:19,960 CONSENSUS STATEMENT WITH 204 00:07:19,960 --> 00:07:21,240 RECOMMENDATIONS FOR WHAT TO DO 205 00:07:21,240 --> 00:07:24,120 IF THERE WAS A BIOLOGICAL ATTACK 206 00:07:24,120 --> 00:07:26,760 AND THEY WROTE THIS IN JAMA IN 207 00:07:26,760 --> 00:07:27,920 1999. 208 00:07:27,920 --> 00:07:30,520 BEFORE THIS, IN 1975, THE 209 00:07:30,520 --> 00:07:32,840 BIOLOGICAL WEAPONS AND TOXINS 210 00:07:32,840 --> 00:07:34,720 CONVENTION HAD BANNED OFFENSIVE 211 00:07:34,720 --> 00:07:41,000 BIOLOGICAL WEAPONS AND RESEARCH. 212 00:07:41,000 --> 00:07:42,160 NOW THERE'S ACTUALLY 182 213 00:07:42,160 --> 00:07:43,440 SIGNATTORYS ON THIS, AND BACK 214 00:07:43,440 --> 00:07:44,680 THEN THERE WERE MANY COUNTRIES 215 00:07:44,680 --> 00:07:47,400 AS WELL YOU IT WAS STILL KNOWN 216 00:07:47,400 --> 00:07:50,240 THAT SOME COUNTRIES HAD 217 00:07:50,240 --> 00:07:51,080 OFFENSIVE WARFARE PROJECTS THAT 218 00:07:51,080 --> 00:07:52,160 WERE GOING ON AND THE SOVIET 219 00:07:52,160 --> 00:07:54,000 UNION WAS 1 OF THEM. 220 00:07:54,000 --> 00:07:57,320 IN FACT, PROOF OF THIS CAME OUT 221 00:07:57,320 --> 00:08:03,680 IN 1979, THERE WAS A BIG 222 00:08:03,680 --> 00:08:04,640 OUTBREAK IN SVERDLOVSK IN APRIL 223 00:08:04,640 --> 00:08:06,040 OF THAT YEAR AND IT WAS REPORTED 224 00:08:06,040 --> 00:08:08,000 BY THE SCIENTISTS A YEAR LATER 225 00:08:08,000 --> 00:08:12,080 IN 1980 AS HAVING ORIGINATED AS 226 00:08:12,080 --> 00:08:13,600 A NATURAL OCCURRENCE FROM 227 00:08:13,600 --> 00:08:16,720 INFECTED ANIMALS THAT HAD BEEN 228 00:08:16,720 --> 00:08:18,080 INGESTED AND CAUSED 229 00:08:18,080 --> 00:08:19,640 GASTROINTESTINAL ANTHRAX AND THE 230 00:08:19,640 --> 00:08:20,960 FOLKS DIED. 231 00:08:20,960 --> 00:08:23,720 THEY REPORTED MORE THAN 90 DACES 232 00:08:23,720 --> 00:08:24,560 WITH APPROXIMATELY 66 DEATHS AND 233 00:08:24,560 --> 00:08:26,200 THEN THERE WAS A SMALL NUMBER OF 234 00:08:26,200 --> 00:08:28,520 FOLKS THAT HAD CUTANEOUS, THEY 235 00:08:28,520 --> 00:08:30,040 SAID AND DID NOT DIE. 236 00:08:30,040 --> 00:08:32,160 THERE WAS NO THORACIC PATHOLOGY 237 00:08:32,160 --> 00:08:35,840 MENTIONED IN THE PAPER. 238 00:08:35,840 --> 00:08:38,120 SO THEN WHEN THE DISSOLLIEWGZ OF 239 00:08:38,120 --> 00:08:42,120 THE SOVIET UNION UNION OCCURRED 240 00:08:42,120 --> 00:08:47,120 IN 1991, MATTHEW METHYLSON FROM 241 00:08:47,120 --> 00:08:56,040 HARVARD ASKED PER MISSION TO GO 242 00:08:56,040 --> 00:08:59,120 TO SVERDLOVSK, AND INVESTIGATE 243 00:08:59,120 --> 00:09:00,920 THIS AND HE WAS APPROVED. 244 00:09:00,920 --> 00:09:03,920 SO THIS MAP SHOWS THE GEOGRAPHIC 245 00:09:03,920 --> 00:09:04,760 DISTRIBUTION OF THE ANTHRAX 246 00:09:04,760 --> 00:09:06,120 CASES AND YOU CAN SEE THE 247 00:09:06,120 --> 00:09:08,160 STRAIGHT LINES HERE THAT ARE 248 00:09:08,160 --> 00:09:09,240 CONSISTENT BASICALLY WITH WIND 249 00:09:09,240 --> 00:09:10,400 DISTRIBUTION WITH THE ORIGIN 250 00:09:10,400 --> 00:09:15,120 COMING FROM A MILITARY FACILITY. 251 00:09:15,120 --> 00:09:18,480 AND AROUND THAT SAME TIME 2 OF 252 00:09:18,480 --> 00:09:19,560 THE PATHOLOGISTS THAT ACTUALLY 253 00:09:19,560 --> 00:09:23,200 PERFORMED OR WERE INVOLVED WITH 254 00:09:23,200 --> 00:09:24,160 THE AUTOPSIESES IN 1979, 255 00:09:24,160 --> 00:09:26,560 [INDISCERNIBLE] HAD SAVED ALL OF 256 00:09:26,560 --> 00:09:28,160 THEIR DETAILED NOTES AND THEY 257 00:09:28,160 --> 00:09:29,160 KNEW WHERE THIS SECURE LOCATION 258 00:09:29,160 --> 00:09:30,920 WAS TO LOOK AT THE SLIDES AGAIN 259 00:09:30,920 --> 00:09:36,080 AND THEY ACTUALLY PUBLISHED IN 260 00:09:36,080 --> 00:09:37,880 1993, FIND FRTION 1979 INCLUDING 261 00:09:37,880 --> 00:09:39,600 THE THORACIC FINDINGS THAT PROVE 262 00:09:39,600 --> 00:09:41,800 THAT THIS WAS INHALATIONAL 263 00:09:41,800 --> 00:09:43,200 ANTHRAX AND WAS NOT A NATURAL 264 00:09:43,200 --> 00:09:43,440 EVENT. 265 00:09:43,440 --> 00:09:45,200 AND HERE WE CAN SEE THE MOTHER 266 00:09:45,200 --> 00:09:46,360 OF SOMEONE WHO HAD BEEN KILLED 267 00:09:46,360 --> 00:09:51,880 IN WHAT WAS LATER DUBBED A 268 00:09:51,880 --> 00:09:52,480 BIOLOGICAL CHERNOBYL. 269 00:09:52,480 --> 00:09:54,600 SO WHILE WE'RE BACK IN TIME IT'S 270 00:09:54,600 --> 00:09:57,320 WORTH MENTIONING THAT CERTAINLY 271 00:09:57,320 --> 00:09:59,240 NEWS DISSEMINATION SO DIFFERENT 272 00:09:59,240 --> 00:10:00,920 NOW AT HOME AND MOST FOLKS GOT 273 00:10:00,920 --> 00:10:02,200 THEIR NEWS FROM NEWSPAPERS, 274 00:10:02,200 --> 00:10:05,120 RADIO OR THE NIGHTLY NEWS WITH 275 00:10:05,120 --> 00:10:06,640 THESE ANCHORS, THERE WASN'T 276 00:10:06,640 --> 00:10:08,120 FACEBOOK, NO SMART PHONES, THERE 277 00:10:08,120 --> 00:10:11,320 WERE NOT A MULTITUDE OF 24 HOUR 278 00:10:11,320 --> 00:10:13,200 NEWS STATIONS GIVING YOU NEWS 279 00:10:13,200 --> 00:10:16,480 MOMENT BY MOMENT AND SO HERE WE 280 00:10:16,480 --> 00:10:20,360 CAN SEE THE NIGHTLY NEWS 281 00:10:20,360 --> 00:10:21,920 ANCHORS, DAN RATHER, PETER 282 00:10:21,920 --> 00:10:24,920 JENNINGS AND TOM BROKAW, AND ALL 283 00:10:24,920 --> 00:10:27,360 OF THEM WERE TARGETED BY THE 284 00:10:27,360 --> 00:10:28,120 ANTHRAX LETTERS. 285 00:10:28,120 --> 00:10:29,520 LETTERS WENT TO THEIR OFFICES AS 286 00:10:29,520 --> 00:10:31,440 L. SO THEY'RE ALSO AT THE TIME 287 00:10:31,440 --> 00:10:33,360 GOING BACK TO 2001, WE DIDN'T 288 00:10:33,360 --> 00:10:34,800 HAVE THESE OPEN SOURCE PREPRINTS 289 00:10:34,800 --> 00:10:38,080 THAT WE COULD LOOK TO SEE WHAT 290 00:10:38,080 --> 00:10:39,920 OTHER RESEARCHERS HAD FOUND 291 00:10:39,920 --> 00:10:42,160 WHICH IS JUST SOMETHING THAT 292 00:10:42,160 --> 00:10:44,240 HAPPENS SO QUICKLY NOW. 293 00:10:44,240 --> 00:10:45,720 THEY'RE ALSO WASN'T THE 294 00:10:45,720 --> 00:10:46,800 IMMEDIATE POINT OF CARE, WHERE 295 00:10:46,800 --> 00:10:48,440 TO GO TO GET UP TO DATE 296 00:10:48,440 --> 00:10:51,400 INFORMATION ON WHAT TO DO WHEN 297 00:10:51,400 --> 00:10:55,080 SCENARIOS BACK THEN SO WE RELIED 298 00:10:55,080 --> 00:10:57,280 HEAVILYOT CDC'S MPWRs AND THEN 299 00:10:57,280 --> 00:11:00,680 REPORTS LIKE THIS 1 THAT HENRY 300 00:11:00,680 --> 00:11:01,840 MASUR, AND NIH 301 00:11:01,840 --> 00:11:02,360 ALUM[INDISCERNIBLE] WERE 302 00:11:02,360 --> 00:11:04,720 INVOLVED WITH WHICH WAS THE 2 303 00:11:04,720 --> 00:11:06,720 BRENT WOOD POSTAL WORKERS THAT 304 00:11:06,720 --> 00:11:07,760 DIED OF INHALATIONAL ANTHRAX AND 305 00:11:07,760 --> 00:11:09,160 THERE WAS A REAL NEED TO GET 306 00:11:09,160 --> 00:11:10,480 MORE OF AN UNDERSTANDING OF WHAT 307 00:11:10,480 --> 00:11:13,000 TO EXPECT WITH ANTHRAX BECAUSE 308 00:11:13,000 --> 00:11:14,200 MOST CLINICIANS HAD NEVER SEEN 309 00:11:14,200 --> 00:11:17,080 IT, THE LAST CASE HAD BEEN IN 310 00:11:17,080 --> 00:11:18,880 1976 IN THE UNITED STATES AND 311 00:11:18,880 --> 00:11:23,920 THERE HAD ONLY BEEN 18 312 00:11:23,920 --> 00:11:33,840 INHALATIONAL CASES BETWEEN 1900 313 00:11:33,840 --> 00:11:35,680 AND--AND HERE WE HAVE A CASE OF 314 00:11:35,680 --> 00:11:37,160 A 94 YEAR-OLD FEMALE WHO 315 00:11:37,160 --> 00:11:38,560 PRESENTED TO THE EMERGENCY 316 00:11:38,560 --> 00:11:41,000 DEPARTMENT OF FEVER, COUGH 317 00:11:41,000 --> 00:11:44,640 FATIGUE FOR 3 DAYS, SHE HAD 318 00:11:44,640 --> 00:11:45,960 COPD, HYPER TENSION, CHRONIC 319 00:11:45,960 --> 00:11:47,160 RENAL INSUFFICIENCY, SHE WAS ON 320 00:11:47,160 --> 00:11:48,200 THESE MEDICATIONS FOREVER WHAT 321 00:11:48,200 --> 00:11:49,520 WAS DISPRIEBED AS MILD DISEASES 322 00:11:49,520 --> 00:11:53,160 FOR ALL OF THEM AND THEN SHE WAS 323 00:11:53,160 --> 00:11:55,520 AN EX-SMOKER BUT HAD NOT SMOKED 324 00:11:55,520 --> 00:11:58,320 IN 30 YEARS AND AT THE TIME OF 325 00:11:58,320 --> 00:12:00,160 HER PRESENTATION, SHE WAS FEB 326 00:12:00,160 --> 00:12:03,480 RILE, TACKY CARDIC SO SHE MET 327 00:12:03,480 --> 00:12:06,360 THE KRIST TERIAR SERS, SHE DID 328 00:12:06,360 --> 00:12:07,680 NOT HAVE A LEUKOCYTOSIS, 329 00:12:07,680 --> 00:12:08,920 ALTHOUGH HER SEGMENT OF 330 00:12:08,920 --> 00:12:10,960 NUTRIFILLS WERE A BIT ELEVATED. 331 00:12:10,960 --> 00:12:13,960 SHE HAD AN INCREASE IN OUR V. N. 332 00:12:13,960 --> 00:12:15,640 AND KRE TINSA TIEN, SHE HAD A 333 00:12:15,640 --> 00:12:18,720 FEW WHITE CELLS IN URINE, HER 334 00:12:18,720 --> 00:12:20,800 CHEST X-RAY WAS RED AS SHOWING 335 00:12:20,800 --> 00:12:22,440 NO ACUTE PULL MONITORARY DISEASE 336 00:12:22,440 --> 00:12:23,920 AND HER SATURATION WAS 93% ON 337 00:12:23,920 --> 00:12:26,960 ROOM AIR AND SHE WAS GIVEN AN 338 00:12:26,960 --> 00:12:28,840 ADMITTING DIAGNOSIS OF VIRAL 339 00:12:28,840 --> 00:12:29,560 SYNDROME WITH DEHYDRATION AND 340 00:12:29,560 --> 00:12:31,480 THEREFORE WAS NOT STARTED ON 341 00:12:31,480 --> 00:12:36,640 ANTIMICROBIALS AT THAT TIME. 342 00:12:36,640 --> 00:12:40,320 OT NEXT DAY SATURDAY HER URINE 343 00:12:40,320 --> 00:12:42,320 CULTURE WAS GROWING OUT GRAHAM 344 00:12:42,320 --> 00:12:43,960 NEGATIVE RODS WHICH WOULD SHOW 345 00:12:43,960 --> 00:12:48,320 TO BE SIM LACK TO E.COLI AND 346 00:12:48,320 --> 00:12:49,440 OTHER SITUATIONS, IT TURNED OUT 347 00:12:49,440 --> 00:12:52,840 TO BE 4 OUT OF 4 BOTTLES 14 348 00:12:52,840 --> 00:12:55,800 HOURS AFTER THEY WERE DRAWNY, 349 00:12:55,800 --> 00:13:02,240 SHE WAS BEGUN ON CEFTAZIDIME AND 350 00:13:02,240 --> 00:13:06,680 THEN VANCOMYCIN AND THEN AMP 351 00:13:06,680 --> 00:13:11,080 SILLIN AND SULBACTAMAND ORAL 352 00:13:11,080 --> 00:13:13,120 CIPROFLOXACIN, HER CHEST X-RAY 353 00:13:13,120 --> 00:13:14,200 SHOWED LARGE PLURAL EFFUSION AND 354 00:13:14,200 --> 00:13:16,800 OVER THE NEXT COUPLE DAYS SHE 355 00:13:16,800 --> 00:13:18,520 CONTINUED TO DETERIORATE. 356 00:13:18,520 --> 00:13:21,720 ON DAY 3 SHE HAD A THOROUGH SIN 357 00:13:21,720 --> 00:13:24,080 THESIS OF THIS DONE WHICH SHOWED 358 00:13:24,080 --> 00:13:26,480 8 MILs OF HEMORRHAGIC 359 00:13:26,480 --> 00:13:28,120 INFUSION, SHE ALSO HAD TO GET 360 00:13:28,120 --> 00:13:28,720 INTERNATIONAL CLASSIFICATION 361 00:13:28,720 --> 00:13:31,800 BAITED AND PUT ON MECHANICAL 362 00:13:31,800 --> 00:13:33,320 INFLAMMATION, AND ON DAY 4, THE 363 00:13:33,320 --> 00:13:36,760 STATE WAS ABLE TO CONFIRM THAT 364 00:13:36,760 --> 00:13:38,800 THIS WAS THE [INDISCERNIBLE] 365 00:13:38,800 --> 00:13:40,360 INFECTION AND UNFORTUNATELY ON 366 00:13:40,360 --> 00:13:43,960 DAY 5 HER FIO2 REQUIREMENTS WENT 367 00:13:43,960 --> 00:13:44,280 UP TO 80%. 368 00:13:44,280 --> 00:13:46,560 SHE HAD TO HAVE A CHEST TUBE 369 00:13:46,560 --> 00:13:49,800 PLACED ON THE LEFT SIDE AND SHE 370 00:13:49,800 --> 00:13:50,520 DEVELOPED A RIGHT PLEURAL 371 00:13:50,520 --> 00:13:52,600 CERTAINLY--CERTAINLY FUSION AND 372 00:13:52,600 --> 00:14:01,240 PASSED AWAY AND ON AUTOPSY, SHE 373 00:14:01,240 --> 00:14:02,200 HAD NECROSIS AND STONEOSEIS IN 374 00:14:02,200 --> 00:14:04,240 THE LUNGS AND THE CULTURES WOULD 375 00:14:04,240 --> 00:14:04,720 BE NEGATIVE. 376 00:14:04,720 --> 00:14:07,120 SO THIS TURNED OUT TO BE THE 377 00:14:07,120 --> 00:14:08,840 LAST INHALATIONAL CASE IN 378 00:14:08,840 --> 00:14:10,920 NOVEMBER OF 2001 IN THIS 94 379 00:14:10,920 --> 00:14:12,200 YEAR-OLD LADY, EVERYBODY HAD 380 00:14:12,200 --> 00:14:14,960 ANTHRAX ON THEIR MIND, WE WERE 381 00:14:14,960 --> 00:14:16,400 FAMILIAR WITH ANTHRAX FOR MANY 382 00:14:16,400 --> 00:14:20,920 YEARS, BUT YET IT WAS NEW TO US, 383 00:14:20,920 --> 00:14:23,040 THEN, SO JUST AS A QUICK 384 00:14:23,040 --> 00:14:27,120 REFRESHER, WE KNOW THAT ANTHRAX 385 00:14:27,120 --> 00:14:32,680 IS CAUSED BY BACILLUS, 386 00:14:32,680 --> 00:14:36,000 ANTHRACIS, IT IS SPORE FORMING, 387 00:14:36,000 --> 00:14:37,400 NONMOTEILE, LARGE AND BOX CAR 388 00:14:37,400 --> 00:14:39,320 SHAPED IT'S A ZOO NOTTIC 389 00:14:39,320 --> 00:14:40,480 INFECTION THAT INFECTS CATTLE, 390 00:14:40,480 --> 00:14:41,320 SHEEP AND GOATS. 391 00:14:41,320 --> 00:14:44,560 IT HAS 3 MAIN ROOTS OF 392 00:14:44,560 --> 00:14:46,000 INFECTION, GI, CUTANEOUS AND 393 00:14:46,000 --> 00:14:48,000 INHALATIONAL AND THERE WAS AN 394 00:14:48,000 --> 00:14:50,320 INJECTIONAL OUTBREAK IN THE U. 395 00:14:50,320 --> 00:14:52,600 K. CAUSED BY I. V. DRUG USERS 396 00:14:52,600 --> 00:14:54,920 USING HEROIN WHICH THEY DID NOT 397 00:14:54,920 --> 00:14:56,440 KNOW WAS TAINTED WITH ANTHRAX 398 00:14:56,440 --> 00:14:57,760 THAT HAD BEEN CARRIED IN ANIMAL 399 00:14:57,760 --> 00:15:01,600 HIDES SO THIS WAS A CATEGORY 400 00:15:01,600 --> 00:15:04,240 THAT WAS ALSO ADDED LATER ON. 401 00:15:04,240 --> 00:15:05,560 AND IT'S IMPORTANT TO REMEMBER 402 00:15:05,560 --> 00:15:10,120 THAT THERE'S NO PERSON-TO-PERSON 403 00:15:10,120 --> 00:15:11,240 TRANSMISSION FOR ANTHRAX. 404 00:15:11,240 --> 00:15:14,120 ANTHRAX PRODUCES 3 PROTEINS, THE 405 00:15:14,120 --> 00:15:15,360 PROTECTIVE ANTIGEN COMBINES WITH 406 00:15:15,360 --> 00:15:17,920 LETHAL FACTOR OR EDEMA FACTOR TO 407 00:15:17,920 --> 00:15:20,440 FORM THE RESPECTIVE TOXINS AND 408 00:15:20,440 --> 00:15:22,040 THIS MEANS THAT EVEN IF SOMEONE 409 00:15:22,040 --> 00:15:24,640 IS ON THE RIGHT ANTIMICROBIAL 410 00:15:24,640 --> 00:15:26,600 THAT'S EFFECTIVE, THEY CAN STILL 411 00:15:26,600 --> 00:15:27,920 HAVE A POTENTIALLY HIGH 412 00:15:27,920 --> 00:15:30,960 MORTALITY DUE TO TOXINS. 413 00:15:30,960 --> 00:15:33,600 AND 1 OF THE MOST DISCUSSED 414 00:15:33,600 --> 00:15:36,120 FEATURES BACK IN 2001 WAS THIS 415 00:15:36,120 --> 00:15:37,640 PATHOGENESIS AND THE DELAYED 416 00:15:37,640 --> 00:15:41,120 GERM NATION OF SPORES. 417 00:15:41,120 --> 00:15:42,760 DR. FRIEDLANDER WILL TALK ABOUT 418 00:15:42,760 --> 00:15:44,320 THAT IN MORE DETAIL BUT SHOWED 419 00:15:44,320 --> 00:15:46,200 IN THIS CARTOON WE SEE THAT 420 00:15:46,200 --> 00:15:48,080 SOMEONE INHALES THE SPORES, IF 421 00:15:48,080 --> 00:15:49,840 THEY'RE SMALL ENOUGH 422 00:15:49,840 --> 00:15:51,840 1-5-MICRONS, THEY GET INTO THE 423 00:15:51,840 --> 00:15:52,880 ALVERMEN INFECTED O LIAISON. 424 00:15:52,880 --> 00:15:55,360 AND THE IMMUNE SPONSE IS 425 00:15:55,360 --> 00:15:56,800 ACTIVATED AND THE MACROPHAGES 426 00:15:56,800 --> 00:15:59,560 CARRY THE SPORES TO THE MEDIA 427 00:15:59,560 --> 00:16:02,240 STIENAL LYMPHNODES THAT'S WHY WE 428 00:16:02,240 --> 00:16:04,560 SEE THIS ON THE CHEST X-RAYS AND 429 00:16:04,560 --> 00:16:07,120 FROM HERE THERE'S GERMINATION 430 00:16:07,120 --> 00:16:09,760 INTO BACTERIA AND VACTEREMMIA 431 00:16:09,760 --> 00:16:11,760 AND TOXINEMMIA AND THEN 432 00:16:11,760 --> 00:16:12,680 UNFORTUNATELY POTENTIALLY DEATH 433 00:16:12,680 --> 00:16:14,920 IF TREATMENT SUBJECT BEGUN EARLY 434 00:16:14,920 --> 00:16:15,640 ENOUGH. 435 00:16:15,640 --> 00:16:19,840 AND BECAUSE OF THIS DELAY AND 436 00:16:19,840 --> 00:16:21,120 GERMINATION AND THE 437 00:16:21,120 --> 00:16:23,720 UNPREDICTABILITY OF IT, THE 438 00:16:23,720 --> 00:16:25,720 RECOMMENDATION IN 2001 WAS TO 439 00:16:25,720 --> 00:16:35,520 TAKE ANTIBIOTICS FOR MORE THAN 440 00:16:35,520 --> 00:16:36,320 60 DAYS--APPROVAL TO TREAT 441 00:16:36,320 --> 00:16:39,680 ANTHRAX OR TO BE USED AFTER 442 00:16:39,680 --> 00:16:41,520 EXPOSURE, PENICILLIN AND DOCKS 443 00:16:41,520 --> 00:16:42,840 PSYCHE LYNN, PENICILLIN WAS NOT 444 00:16:42,840 --> 00:16:44,080 RECOMMEND BECAUSE OF THE CONCERN 445 00:16:44,080 --> 00:16:47,680 THERE COULD BE RESISTANCE. 446 00:16:47,680 --> 00:16:48,880 CIPROFLOCKSIN HAD BEEN MENTION 447 00:16:48,880 --> 00:16:50,160 INDEED THE CONSENSUS PAPER I 448 00:16:50,160 --> 00:16:52,120 SHOWED YOU EARLIER, SO THAT WAS 449 00:16:52,120 --> 00:16:55,560 STILL AN OFFLABEL USE AND SO, 450 00:16:55,560 --> 00:16:58,320 WHAT ENDED UP HAPPENING WITH THE 451 00:16:58,320 --> 00:16:59,520 PATIENTS RECEIVING, THEY RECEIVE 452 00:16:59,520 --> 00:17:02,320 THE QUINN LONE, SAW IN OUR 453 00:17:02,320 --> 00:17:05,440 YEAR-OLD LADY THAT SHE RECEIVED 454 00:17:05,440 --> 00:17:08,080 MULTIPLE MIKE ROBIALS WHICH IS 455 00:17:08,080 --> 00:17:10,320 ALL ICU AND CRITICAL CARE 456 00:17:10,320 --> 00:17:11,840 SPECIALISTS DO WITH AGGRESSIVE 457 00:17:11,840 --> 00:17:12,480 PATIENTS WITH SUPPORTIVE CARE 458 00:17:12,480 --> 00:17:14,200 BUT THERE ARE A LOT OF QUESTIONS 459 00:17:14,200 --> 00:17:16,200 AND UNKNOWNS ABOUT ANTHRAX IN 460 00:17:16,200 --> 00:17:18,760 THESE MODERN TIMES OF 2001 AND 461 00:17:18,760 --> 00:17:22,360 THEIR JUST WASN'T A ROT OF 462 00:17:22,360 --> 00:17:22,680 INFORMATION. 463 00:17:22,680 --> 00:17:24,040 THE INFRASTRUCTURE TO STUDY 464 00:17:24,040 --> 00:17:25,840 ANTHRAX DIDN'T EXIST OR FOR 465 00:17:25,840 --> 00:17:26,640 OTHER POTENTIAL AGENTS THAT 466 00:17:26,640 --> 00:17:28,920 COULD BE USED AS BIOLOGICAL 467 00:17:28,920 --> 00:17:30,480 THREATS INCLUDING SMALL POX, AND 468 00:17:30,480 --> 00:17:30,680 EBOLA. 469 00:17:30,680 --> 00:17:33,640 SO THERE WAS A LACK OF LABS WITH 470 00:17:33,640 --> 00:17:39,040 BSL 3 CAPACITY WHICH YOU NEEDED 471 00:17:39,040 --> 00:17:40,000 TO HANDLE AEROSOL, ANTHRAX AND 472 00:17:40,000 --> 00:17:42,560 SPORES AND A LACK OF BSL FOR 473 00:17:42,560 --> 00:17:44,080 OTHER TYPE OF PATHOGENS AND 474 00:17:44,080 --> 00:17:46,240 THERE WERE VERY FEW SCIENTISTS 475 00:17:46,240 --> 00:17:46,800 AND CLINICIANS WITH ANTHRAX 476 00:17:46,800 --> 00:17:48,640 EXPERIENCE AND THERE WAS AN 477 00:17:48,640 --> 00:17:49,720 INABILITY TO CONDUCT CLINICAL 478 00:17:49,720 --> 00:17:51,920 TRIALS BECAUSE YOU WEREN'T GOING 479 00:17:51,920 --> 00:17:53,000 TO ETHICALLY GIVE SOMEONE 480 00:17:53,000 --> 00:17:53,920 ANTHRAX AND COMPARE THEM TO A 481 00:17:53,920 --> 00:17:55,360 GROUP THAT DID NOT HAVE ANTHRAX. 482 00:17:55,360 --> 00:17:58,320 SO THERE WERE MANY QUESTIONS. 483 00:17:58,320 --> 00:17:59,520 AND THE QUESTIONS THAT WERE 484 00:17:59,520 --> 00:18:05,560 ESPECIALLY OF INTEREST TO DR. VI 485 00:18:05,560 --> 00:18:10,600 E TRI, FRI DEDLANDER AND I, CAN 486 00:18:10,600 --> 00:18:14,200 HOW MANY DAYS OF ANTIBIOTICS ARE 487 00:18:14,200 --> 00:18:16,560 NEEDED AFTER ANTHRAX EXPOSURE, 488 00:18:16,560 --> 00:18:18,920 CAN EABT BIOTICS DURATION BE 489 00:18:18,920 --> 00:18:19,760 SHORTENED AFTER SYSTEMIC 490 00:18:19,760 --> 00:18:22,920 INFECTION AND DOES THE ADDITION 491 00:18:22,920 --> 00:18:24,320 OF CLINDA MICEIN MAKE A 492 00:18:24,320 --> 00:18:25,320 DIFFERENCE IN SURVIVAL. 493 00:18:25,320 --> 00:18:31,520 SO NOW I WILL TURN IT OVER TO 494 00:18:31,520 --> 00:18:32,640 DR. FREIDLANDER AND SHE WILL 495 00:18:32,640 --> 00:18:35,520 EXPLORE THE ANSWER TO THAT. 496 00:18:35,520 --> 00:18:36,400 >> THANK YOU FOR THE OPPORTUNITY 497 00:18:36,400 --> 00:18:38,200 TO TELL YOU ABOUT THIS LONG 498 00:18:38,200 --> 00:18:41,160 COLLABORATION IN ADDRESSING HOW 499 00:18:41,160 --> 00:18:45,000 TO MEASURE AN AEROSOLEXPOSURE TO 500 00:18:45,000 --> 00:18:45,320 ANTHRAX. 501 00:18:45,320 --> 00:18:49,000 SPECIFICALLY WHAT'S THE BEST 502 00:18:49,000 --> 00:18:50,040 POST EXPOSURE PROPHYLAXIS? 503 00:18:50,040 --> 00:18:53,040 HOW MANY DAYS OF ASPECT BIOTICS 504 00:18:53,040 --> 00:19:01,320 PROPHYLAXIS COMBINED WITH POST 505 00:19:01,320 --> 00:19:02,120 -VACCINATION POST EXPOSURE 506 00:19:02,120 --> 00:19:05,360 ARE NEEDED FOR PROTECTION 507 00:19:05,360 --> 00:19:06,200 AGAINST INHALATIONAL ANTHRAX? 508 00:19:06,200 --> 00:19:09,680 IN THE 19th CENTURY, IT WAS AN 509 00:19:09,680 --> 00:19:11,720 ECONOMICALLY IMPORTANT DISEASE 510 00:19:11,720 --> 00:19:14,040 OF DOMESTICATED ANIMALS, THAT 511 00:19:14,040 --> 00:19:15,640 ENGAGED THE BEST MEDICAL 512 00:19:15,640 --> 00:19:17,400 SCIENTISTS OF THE TIME AND WAS 513 00:19:17,400 --> 00:19:21,880 ASSOCIATED WITH THE ORIGINS OF 514 00:19:21,880 --> 00:19:22,720 MICROBIOLOGY, AND IMMUNOLOGY. 515 00:19:22,720 --> 00:19:25,800 AND NOW IT IS UNFORTUNATELY OF 516 00:19:25,800 --> 00:19:27,120 CONCERN BECAUSE OF ITS POSSIBLE 517 00:19:27,120 --> 00:19:31,480 USE AS AS A BIOWEAPON. 518 00:19:31,480 --> 00:19:34,880 A TRULY DISASTROUS SITUATION. 519 00:19:34,880 --> 00:19:40,280 THE CASES OF INHALATIONAL 520 00:19:40,280 --> 00:19:41,680 INFECTION IN ABOUT 1979, ABOUT 521 00:19:41,680 --> 00:19:43,080 WHICH THE RUSSIANS YET TO THIS 522 00:19:43,080 --> 00:19:44,360 DAY HAVE YET TO SHARE ANY 523 00:19:44,360 --> 00:19:46,520 INFORMATION ABOUT THE CLINICAL 524 00:19:46,520 --> 00:19:49,320 MANAGEMENT OR THE DISEASE THEY 525 00:19:49,320 --> 00:19:49,640 SAW. 526 00:19:49,640 --> 00:19:53,040 AND THEN THE WEAPONIZATION OF 527 00:19:53,040 --> 00:19:55,120 ANTHRAX IN THE FIRST GULF WAR 528 00:19:55,120 --> 00:19:56,080 HEIGHTENED THE AWARENESS OF THE 529 00:19:56,080 --> 00:19:59,320 THREAT OF USING ANTHRAX AS A 530 00:19:59,320 --> 00:20:01,080 BIOLOGICAL WEAPON AND LED TO THE 531 00:20:01,080 --> 00:20:03,480 DECISION FOR THE FIRST TIME IN 532 00:20:03,480 --> 00:20:06,880 HISTORY TO VACCINATE A 533 00:20:06,880 --> 00:20:09,720 POPULATION, THIS IS THE U.S. 534 00:20:09,720 --> 00:20:11,720 ARMED FORCES IN 1998 NOT AGAINST 535 00:20:11,720 --> 00:20:12,800 A NATURALLY OCCURRING DISEASE, 536 00:20:12,800 --> 00:20:16,200 BUT AGAINST THE THREAT OF USING 537 00:20:16,200 --> 00:20:19,920 A MICROORGANISM TO INTENTIONALLY 538 00:20:19,920 --> 00:20:20,280 CAUSE DISEASE. 539 00:20:20,280 --> 00:20:23,320 BUT IT WAS THE USE OF MAIL IN 540 00:20:23,320 --> 00:20:25,680 THE FALL OF 2001 TO SPREAD 541 00:20:25,680 --> 00:20:27,920 ANTHRAX THAT GALVANIZED THE 542 00:20:27,920 --> 00:20:28,960 BIOMEDICAL AND PUBLIC HEALTH 543 00:20:28,960 --> 00:20:31,400 COMMUNITIES AS WAS ALLUDED TO. 544 00:20:31,400 --> 00:20:34,160 THE HORRENDOUS POSSIBILITY OF 545 00:20:34,160 --> 00:20:36,200 USING MICROBES TO INTENTIONAL 546 00:20:36,200 --> 00:20:39,040 CAUSE DISEASE WAS REALIZED, 547 00:20:39,040 --> 00:20:41,880 REVEALING THE DARK SIDE OF 548 00:20:41,880 --> 00:20:42,120 SCIENCE. 549 00:20:42,120 --> 00:20:43,680 IT CHANGED THE FACE OF PUBLIC 550 00:20:43,680 --> 00:20:46,120 HEALTH AND THAT WE WERE NOW 551 00:20:46,120 --> 00:20:48,120 FOCUSED ON PROVIDING MEDICAL 552 00:20:48,120 --> 00:20:49,120 COUNTERMEASURES, AGAINST THE 553 00:20:49,120 --> 00:20:52,120 THREAT OF SOMEONE USING A MY 554 00:20:52,120 --> 00:20:53,720 KROAB TO INTENTIONAL CAUSE 555 00:20:53,720 --> 00:20:58,720 DISEASE. 556 00:20:58,720 --> 00:21:00,240 NEXT SLIDE, PLEASE. 557 00:21:00,240 --> 00:21:01,440 NEXT--OH, YES. 558 00:21:01,440 --> 00:21:03,320 THESE OBSERVATIONS,OT USE OF 559 00:21:03,320 --> 00:21:05,400 ANIMALS TO MODEL HUMAN DISEASE 560 00:21:05,400 --> 00:21:08,480 ARE AT THE HEART OF A DILEMMA 561 00:21:08,480 --> 00:21:12,320 FOR THE LICENSURE OF VACCINES OR 562 00:21:12,320 --> 00:21:13,880 THERAPEUTICS AGAINST 563 00:21:13,880 --> 00:21:14,520 BIOTERRORRISTS, AGENTS THAT 564 00:21:14,520 --> 00:21:15,960 OCCUR SO RARELY THAT CLINICAL 565 00:21:15,960 --> 00:21:19,120 TRIALS CAN'T BE CARRIED OUT, OR 566 00:21:19,120 --> 00:21:20,200 WOULD BE UNETHICAL BECAUSE OF 567 00:21:20,200 --> 00:21:22,520 THE SERIESNESS OF THE INFECTION. 568 00:21:22,520 --> 00:21:27,680 --SERIOUSNESS OF THE INFECTION. 569 00:21:27,680 --> 00:21:29,360 THE EVENTUALLY RESULTED IN THE 570 00:21:29,360 --> 00:21:32,240 ANIMAL RULE BY FDACIN 2002 FOR 571 00:21:32,240 --> 00:21:32,880 SUCH PRODUCTS. 572 00:21:32,880 --> 00:21:34,040 THEREFORE WE MUST TEST PRODUCTS 573 00:21:34,040 --> 00:21:39,840 IN THE BEST ANIMAL MODELS 574 00:21:39,840 --> 00:21:42,160 AVAILABLE AND THE MODELS ARE NOT 575 00:21:42,160 --> 00:21:45,040 NECESSARILY INDICATIVE OF HUMAN 576 00:21:45,040 --> 00:21:45,280 DISEASE. 577 00:21:45,280 --> 00:21:52,080 THAT'S PART OF THE DILEMMA. 578 00:21:52,080 --> 00:21:55,160 AS FELIX D'HERELLE 1 OF THE 579 00:21:55,160 --> 00:21:58,360 FOUNDERS OF INFECTIOUS DISEASE 580 00:21:58,360 --> 00:22:01,000 SAYS, POINTED OUT, THE STUDY OF 581 00:22:01,000 --> 00:22:02,960 IMMUNITY IN ARTIFICIALLY 582 00:22:02,960 --> 00:22:03,720 PRODUCED INFECTIOUS DISEASES 583 00:22:03,720 --> 00:22:04,720 DOES NOT NECESSARILY MEAN THAT 584 00:22:04,720 --> 00:22:07,280 THE SAME CONDIPGZS WILL PREVAIL 585 00:22:07,280 --> 00:22:07,840 UNDER NATURAL INFECTION. 586 00:22:07,840 --> 00:22:10,280 SO THAT EVEN THE BEST ANIMAL 587 00:22:10,280 --> 00:22:11,880 MODELS ARE ONLY THAT AND MAY 588 00:22:11,880 --> 00:22:16,000 WELL BE DIFFERENT FROM THE HUMAN 589 00:22:16,000 --> 00:22:16,360 DISEASE. 590 00:22:16,360 --> 00:22:17,640 NEVERTHELESS, ANIMAL MODELS MAY 591 00:22:17,640 --> 00:22:20,040 BE NECESSARY BECAUSE AS WE 592 00:22:20,040 --> 00:22:21,240 MENTIONED, THE INFREQUENCY OF 593 00:22:21,240 --> 00:22:26,080 SOME DISEASES SUCH AS ANTHRAX 594 00:22:26,080 --> 00:22:27,520 HAS NOTED BY KLEIN AND WHAT HE 595 00:22:27,520 --> 00:22:30,320 SAID WAS THAT BECAUSE OF THE 596 00:22:30,320 --> 00:22:32,200 INFREQUENCY OF OCCURRENCE OF 597 00:22:32,200 --> 00:22:34,400 ANTHRAX, IT IS PROBABLE, 598 00:22:34,400 --> 00:22:35,720 RELATIONSHIP BETWEEN ANTIBODY 599 00:22:35,720 --> 00:22:37,280 TITER AND RESISTANCE TO 600 00:22:37,280 --> 00:22:39,600 INFECTION IN HUMAN POPULATIONS, 601 00:22:39,600 --> 00:22:42,520 WILL NEVER BE CONCLUSIVELY 602 00:22:42,520 --> 00:22:42,760 SHOWN. 603 00:22:42,760 --> 00:22:45,480 WE MUST THEREFORE RELY LARGELY 604 00:22:45,480 --> 00:22:47,760 IF NOT ENTIRELY ON EXTRAPOLATION 605 00:22:47,760 --> 00:22:51,920 OF RESULTS FROM EXPERIMENTAL 606 00:22:51,920 --> 00:22:52,920 HOSTS TO FURNISH INFORMATION ON 607 00:22:52,920 --> 00:22:53,120 MAN. 608 00:22:53,120 --> 00:22:59,000 AND THE SAME HOLDS TRUE FOR 609 00:22:59,000 --> 00:23:02,200 THERAPEUTICS AND VACCINES. 610 00:23:02,200 --> 00:23:06,200 AND FINALLY MAURICE HILLEMAN THE 611 00:23:06,200 --> 00:23:08,520 DISCOVERY OF VACCINES MAKERS 612 00:23:08,520 --> 00:23:09,840 THIS INSIGHTFUL REMARK ABOUT 613 00:23:09,840 --> 00:23:10,680 VACCINES, PROTECTION AND THE 614 00:23:10,680 --> 00:23:12,440 BEST MARKER FOR PROTECTION, NOT 615 00:23:12,440 --> 00:23:13,960 STUDIES IN ANIMALS MORE IN THE 616 00:23:13,960 --> 00:23:19,240 TEST TUBE. 617 00:23:19,240 --> 00:23:19,880 NEXT SLIDE. 618 00:23:19,880 --> 00:23:21,920 THIS IS ANOTHER CONTINUING ISSUE 619 00:23:21,920 --> 00:23:23,320 WE FACE IN INFECTIOUS DISEASES, 620 00:23:23,320 --> 00:23:25,320 NAMELY THE DIFFICULTY IN MAKING 621 00:23:25,320 --> 00:23:26,200 AN EARLY DIAGNOSIS. 622 00:23:26,200 --> 00:23:29,920 ONE APPRECIATED VERY LONG AGO IN 623 00:23:29,920 --> 00:23:32,240 THIS QUOTE ASCRIBED TO 624 00:23:32,240 --> 00:23:35,000 MACHIAVELLY IN THE 16th 625 00:23:35,000 --> 00:23:35,240 CENTURY. 626 00:23:35,240 --> 00:23:38,120 HE SAID THE PHYSICIANS SAY, IT 627 00:23:38,120 --> 00:23:40,440 HAPPENS IN HECTIC FEVER, THAT IN 628 00:23:40,440 --> 00:23:42,120 THE BEGINNING OF THE MALADY IT 629 00:23:42,120 --> 00:23:44,320 IS EASIER TO CURE BUT DIFFICULT 630 00:23:44,320 --> 00:23:44,600 TO DETECT. 631 00:23:44,600 --> 00:23:47,320 BUT IN THE COURSE OF TIME, NOT 632 00:23:47,320 --> 00:23:48,960 HAVING BEEN EITHER DETECTED OR 633 00:23:48,960 --> 00:23:52,920 TREATED IN THE BEGINNING, IT 634 00:23:52,920 --> 00:23:56,520 BECOMES EASY TO DETECT BUT 635 00:23:56,520 --> 00:23:57,400 DIFFICULT TO CURE. 636 00:23:57,400 --> 00:23:59,560 IT IS PARTICULARLY RELEVANT IN 637 00:23:59,560 --> 00:24:03,000 THE SITUATION OF AN AEROSOL 638 00:24:03,000 --> 00:24:05,120 EXPOSURE BEFORE SIGNS OF ILLNESS 639 00:24:05,120 --> 00:24:05,720 HAVE OCCURRED. 640 00:24:05,720 --> 00:24:06,920 HOW DO YOU DIAGNOSE SOMEONE 641 00:24:06,920 --> 00:24:07,120 EARLY? 642 00:24:07,120 --> 00:24:10,240 AND HOW DO YOU TRIAGE THOSE 643 00:24:10,240 --> 00:24:10,480 EXPOSED? 644 00:24:10,480 --> 00:24:13,120 OF COURSE THIS IS VERY MUCH LIKE 645 00:24:13,120 --> 00:24:17,320 THE SITUATION WITH COVID. 646 00:24:17,320 --> 00:24:19,520 ALTHOUGH FOR AN AEROSOL EXPOSURE 647 00:24:19,520 --> 00:24:21,040 IT WOULD BE A MASSIVE EVENT 648 00:24:21,040 --> 00:24:25,280 OCCURRING ALL AT ONCE. 649 00:24:25,280 --> 00:24:27,160 NEXT SLIDE. 650 00:24:27,160 --> 00:24:29,160 AS DISCUSSED EARLIER, ANTHRAX 651 00:24:29,160 --> 00:24:30,880 REPRESENTS A UNIQUE PROBLEM IN 652 00:24:30,880 --> 00:24:32,640 THE MANAGEMENT OF AN AEROSOL 653 00:24:32,640 --> 00:24:35,720 EXPOSURE BECAUSE OF ITS BIOLOGY. 654 00:24:35,720 --> 00:24:38,360 WHERE IN SPORES DO NOT GERMINATE 655 00:24:38,360 --> 00:24:40,720 ALL AT ONCE. 656 00:24:40,720 --> 00:24:44,720 THIS WAS APPRECIATED BY BARNES, 657 00:24:44,720 --> 00:24:44,960 1947. 658 00:24:44,960 --> 00:24:47,720 THAT GERMINATION OF SPORES IS 659 00:24:47,720 --> 00:24:49,000 NOT SYNCHRONOUS. 660 00:24:49,000 --> 00:24:51,120 THAT SPORES MAY REMAIN DORMANT 661 00:24:51,120 --> 00:24:54,840 FOR EXTENDED PERIODS OF TIME IN 662 00:24:54,840 --> 00:24:58,040 THE HOST. 663 00:24:58,040 --> 00:24:59,200 IMPORTANTLY, ANTIBIOTICS ONLY 664 00:24:59,200 --> 00:25:04,120 ACT ON GERMINATED SPORES AND 665 00:25:04,120 --> 00:25:10,880 BACILLI, NOT ON DORMANT SPORES, 666 00:25:10,880 --> 00:25:15,520 THUS SPORES REMAINING FOLLOWING 667 00:25:15,520 --> 00:25:17,280 DISCONTINUANCE OF ANTIBIOTICS 668 00:25:17,280 --> 00:25:18,520 MAY GERMINATE RESULT NOTHING 669 00:25:18,520 --> 00:25:19,120 INFECTION AND DEATH. 670 00:25:19,120 --> 00:25:19,440 NEXT SLIDE. 671 00:25:19,440 --> 00:25:21,000 IN OUR WORK ON ANTHRAX, WE ARE 672 00:25:21,000 --> 00:25:25,520 FOLLOWING ON THE SEMINAL 673 00:25:25,520 --> 00:25:27,920 EXPERIMENTS BY HENNEDDERSON 674 00:25:27,920 --> 00:25:28,960 ET AL, REPORT INDEED 1956. 675 00:25:28,960 --> 00:25:31,720 THEY STUDIED THIS PHENOMENON OF 676 00:25:31,720 --> 00:25:34,280 RETAINED SPORES IN NONHUMAN 677 00:25:34,280 --> 00:25:37,160 PRIMATES OR GIVEN POST EXPOSURE 678 00:25:37,160 --> 00:25:41,160 PROPHYLAXIS, FOR 5 OR 10 DAYS 679 00:25:41,160 --> 00:25:43,120 WITH PENICILLIN, BEGINNING 1 DAY 680 00:25:43,120 --> 00:25:48,200 AFTER AN AEROSOL EXPOSURE. 681 00:25:48,200 --> 00:25:51,320 THEY FOUND THAT 5 OR 10 DAYS OF 682 00:25:51,320 --> 00:25:53,480 POST EXPOSURE PROPHYLAXIS WITH 683 00:25:53,480 --> 00:25:54,560 ANTIBIOTICS PROTECTS NONHUMAN 684 00:25:54,560 --> 00:25:57,280 PRIMATES WHILE THEY ARE ON 685 00:25:57,280 --> 00:25:59,720 ANTIBIOTICS, BUT IS ASSOCIATED 686 00:25:59,720 --> 00:26:02,760 WITH SIGNIFICANT MORTALITY 687 00:26:02,760 --> 00:26:04,520 FOLLOWING DISCONTINUATION OF 688 00:26:04,520 --> 00:26:05,120 ANTIBIOTICS. 689 00:26:05,120 --> 00:26:09,200 THAT IS 8 OF 10 ANIMALS DIED 690 00:26:09,200 --> 00:26:16,200 AFTER DISCONTINUING 5 DAYS OF 691 00:26:16,200 --> 00:26:18,600 PEN SILLEN AND 10 AFTER 10 DIES 692 00:26:18,600 --> 00:26:21,960 AFTER STOPPING OPINION SILLIN. 693 00:26:21,960 --> 00:26:25,280 THEY FIND THAT VACCINATION AFTER 694 00:26:25,280 --> 00:26:27,280 POST EXPOSURE RESULTS IN A 695 00:26:27,280 --> 00:26:28,320 SIGNIFICANT INCREASE IN 696 00:26:28,320 --> 00:26:29,240 SURVIVAL. 697 00:26:29,240 --> 00:26:33,080 SO THESE EXPERIMENTS DID CONFIRM 698 00:26:33,080 --> 00:26:35,440 THE HYPOTHESIS OF BARNES, THAT 699 00:26:35,440 --> 00:26:36,920 AFTER EXPOSURE, RETAINED 700 00:26:36,920 --> 00:26:38,120 UNGERMINATED SPORES MAY 701 00:26:38,120 --> 00:26:39,520 GERMINATE AFTER THE ANTIBIOTICS 702 00:26:39,520 --> 00:26:48,160 ARE DISCONTINUED AND LEAD TO--WE 703 00:26:48,160 --> 00:26:51,560 EXTENDED THE STUDIES OF 704 00:26:51,560 --> 00:26:54,000 HENDERSON TO SEE IF A MORE 705 00:26:54,000 --> 00:26:56,920 PROLONGED PERIOD OF JUST POST 706 00:26:56,920 --> 00:26:58,520 EXOAZURE ANTIBIOTICS ALONE WOULD 707 00:26:58,520 --> 00:26:59,160 INCREASE SURVIVAL. 708 00:26:59,160 --> 00:27:04,240 NEXT SLIDE. 709 00:27:04,240 --> 00:27:04,480 PLEASE. 710 00:27:04,480 --> 00:27:07,200 OUR EXPERIMENTS ON POST EXPOSURE 711 00:27:07,200 --> 00:27:08,120 ANTIBIOTIC PROPHYLAXIS SHOWED 712 00:27:08,120 --> 00:27:10,920 THAT A MORE PROLONGED PERIOD OF 713 00:27:10,920 --> 00:27:14,680 30 DAYS OF ANTIBIOTICS, COULD 714 00:27:14,680 --> 00:27:16,440 PROTECT ANIMALS, WHILE ON 715 00:27:16,440 --> 00:27:18,400 ANTIBIOTICS AGAIN AND 716 00:27:18,400 --> 00:27:21,560 IMPORTANTLY OFFERED SIGNIFICANT 717 00:27:21,560 --> 00:27:23,800 LONG-TERM PROTECTION AFTER 718 00:27:23,800 --> 00:27:25,880 DISCONTINUING ANTIBIOTICS BUT 719 00:27:25,880 --> 00:27:29,560 SOME STILL DIED AFTER THE 720 00:27:29,560 --> 00:27:30,200 ANTIBIOTICS WOULD DISCONTINUE. 721 00:27:30,200 --> 00:27:32,680 WE DID FIND THAT THE ADDITION OF 722 00:27:32,680 --> 00:27:34,800 POST EXPOSURE VACCINATION DID 723 00:27:34,800 --> 00:27:37,160 IMPROVE SURVIVAL BUT IT WAS NOT 724 00:27:37,160 --> 00:27:37,800 STATISTICALLY SIGNIFICANT IN 725 00:27:37,800 --> 00:27:42,240 THIS STUDY. 726 00:27:42,240 --> 00:27:43,040 NEXT SLIDE. 727 00:27:43,040 --> 00:27:45,520 NOW THIS SLIDE SHOWS THE OVERALL 728 00:27:45,520 --> 00:27:46,240 RESULTS. 729 00:27:46,240 --> 00:27:47,920 ANIMALS WERE TREATED 1 DAY AFTER 730 00:27:47,920 --> 00:27:54,960 A LOW DOSE AEROSOL EXPOSURE WITH 731 00:27:54,960 --> 00:27:56,680 PEN SILLEN, CIPRFLOXIN, OR 732 00:27:56,680 --> 00:27:58,480 DOXYCYCLINE FOR 30 DAYS. 733 00:27:58,480 --> 00:28:00,760 ANOTHER GROUP RECEIVED 734 00:28:00,760 --> 00:28:04,920 DOXYCYCLINE PLUS A LICENSED 735 00:28:04,920 --> 00:28:06,920 HUMAN ANTHRAX VACCINE AVA, THE 736 00:28:06,920 --> 00:28:08,480 PERCENT SURVIEWFAL IS SHOWNOT 737 00:28:08,480 --> 00:28:10,320 Y-AXIS AND DAYS AFTER CHAL 738 00:28:10,320 --> 00:28:10,720 EVENLGOT X-AXIS. 739 00:28:10,720 --> 00:28:14,120 OT LEFT, YOU CAN SEE THAT 9 OF 740 00:28:14,120 --> 00:28:19,120 10 CONTROLS IN THE CLOSED 741 00:28:19,120 --> 00:28:21,280 CIRCLES DIED BUT THAT NO ANIMALS 742 00:28:21,280 --> 00:28:24,400 DIED OF ANTIBIOTICS WHILE ON THE 743 00:28:24,400 --> 00:28:28,160 THIRD DAYS OF TREATMENT. 744 00:28:28,160 --> 00:28:30,560 THERE WERE 3 ANIMALS THAT DIED 745 00:28:30,560 --> 00:28:31,520 OF OTHER CAUSES. 746 00:28:31,520 --> 00:28:33,520 NOW UPON STOPPING THE 747 00:28:33,520 --> 00:28:36,040 ANTIBIOTICS AFTER THIRTD DAYS, 3 748 00:28:36,040 --> 00:28:42,920 OF 10 ON PENICILLIN SHOWED IN 749 00:28:42,920 --> 00:28:44,640 THE CLOSED TRIANGLES DIED. 750 00:28:44,640 --> 00:28:48,320 ONE OF 9 IN THE CIPROFLOXIN 751 00:28:48,320 --> 00:28:50,000 GROUP, IN THE OPEN TRIANGLES 752 00:28:50,000 --> 00:28:53,920 DIED AND 1 OF 10 IN THE 753 00:28:53,920 --> 00:28:55,320 DOXYCYCLINE GROUP SHOWED 754 00:28:55,320 --> 00:28:58,120 ENCLOSED SQUARES DIED ON DAY 28 755 00:28:58,120 --> 00:28:58,720 AFTER STOPPING ANTIBIOTICS. 756 00:28:58,720 --> 00:29:03,720 THAT IS TO SAY, 59 DIES AFTER 757 00:29:03,720 --> 00:29:06,240 THE EXPOSURE, THE RESULTS SHOW 758 00:29:06,240 --> 00:29:08,320 THAT PROLONGED EABT BIOTICSS 759 00:29:08,320 --> 00:29:11,440 ALONE COULD RESULT IN 760 00:29:11,440 --> 00:29:12,720 SIGNIFICANT LONG-TERM PROTECTION 761 00:29:12,720 --> 00:29:16,000 AND THIS BECAME THE BASIS FOR 762 00:29:16,000 --> 00:29:18,920 THE 60 DAY RECOMMENDATION FOR 763 00:29:18,920 --> 00:29:20,240 POST EXPOSURE ANTIBIOTICS, 764 00:29:20,240 --> 00:29:23,400 HOWEVER, THIS WAS A LOW 765 00:29:23,400 --> 00:29:25,800 CHALLENGE DOSE, AND MODELING 766 00:29:25,800 --> 00:29:27,920 SUGGESTED THAT YOU MIGHT REQUIRE 767 00:29:27,920 --> 00:29:32,320 MORE THAN 4 MONTHS OF POST 768 00:29:32,320 --> 00:29:33,400 EXPOSURE PROPHYLAXIS WITH 769 00:29:33,400 --> 00:29:33,720 ANTIBIOTICS. 770 00:29:33,720 --> 00:29:39,520 IF A LARGER DOSE OF SPORES WERE 771 00:29:39,520 --> 00:29:39,880 INHALED? 772 00:29:39,880 --> 00:29:41,520 INDEED, HENDERSON IN THEIR 773 00:29:41,520 --> 00:29:43,520 STUDIES FOUND TRACES OF SPORES 774 00:29:43,520 --> 00:29:46,680 100 DAYS AFTER EXPOSURE. 775 00:29:46,680 --> 00:29:49,800 AND WE HAVE FOUND SPORES AS LONG 776 00:29:49,800 --> 00:29:54,120 AS 180 DAYS AFTER EXPOSURE. 777 00:29:54,120 --> 00:29:55,880 IMPORTANTLY IN THIS EXPERIMENT, 778 00:29:55,880 --> 00:30:00,720 NONE OF THE ANIMALS DEVELOPED AN 779 00:30:00,720 --> 00:30:03,040 IMMUNE RESPONSE TO THE EXPOSURE 780 00:30:03,040 --> 00:30:05,160 SO IT APPEARED THAT THE 781 00:30:05,160 --> 00:30:06,760 ANTIBIOTICS SUPPRESSED THE 782 00:30:06,760 --> 00:30:07,040 INFECTION. 783 00:30:07,040 --> 00:30:10,440 INDEED AS SHOWN ON THE RIGHT 784 00:30:10,440 --> 00:30:13,880 CHANNEL, THE RIGHT PANEL IN B, 785 00:30:13,880 --> 00:30:15,360 WHEN ANIMALS WOULD CHALLENGE 786 00:30:15,360 --> 00:30:17,640 ABOUT 4 MONTHS AFTER 787 00:30:17,640 --> 00:30:19,520 DISCONTINUING ANTIBIOTICS THEY 788 00:30:19,520 --> 00:30:23,720 WERE NOT PROTECTED, ONLY 1 OF 23 789 00:30:23,720 --> 00:30:31,640 SURVIVORS SURVIVED THE 790 00:30:31,640 --> 00:30:32,080 RECHALLENGE. 791 00:30:32,080 --> 00:30:35,720 IN CONTRAST THE GROUP GIVEN 792 00:30:35,720 --> 00:30:36,800 DOXYCYCLINE POST EXPOSURE 793 00:30:36,800 --> 00:30:39,160 VACCINATION IN THE SQUARES DID 794 00:30:39,160 --> 00:30:40,600 SURVIVE THE RECHALLENGE AND THIS 795 00:30:40,600 --> 00:30:43,040 IS LIKELY DUE TO THE LOW INITIAL 796 00:30:43,040 --> 00:30:44,520 CHALLENGE DOSE WHERE THE 797 00:30:44,520 --> 00:30:45,440 INFECTION WAS TOTALLY SUPPRESSED 798 00:30:45,440 --> 00:30:46,160 BECAUSE AS WE WILL SLEEP APNEA 799 00:30:46,160 --> 00:30:48,040 AND OBESITYY IN THE SUBSEQUENT 800 00:30:48,040 --> 00:30:50,600 STUDY, IN ANIMALS CHALLENGED 801 00:30:50,600 --> 00:30:53,400 WITH A DOSE, 200 TIMES GREATER, 802 00:30:53,400 --> 00:30:57,760 AND TREATED FOR 14 DAYS, WITH 803 00:30:57,760 --> 00:31:00,760 CIPRO FLOXIN, 4 OF THE 9 ANIMALS 804 00:31:00,760 --> 00:31:02,320 THAT SURVIVED DID DEVELOP 805 00:31:02,320 --> 00:31:04,680 ANTIBODIES AND WERE RESISTANT TO 806 00:31:04,680 --> 00:31:05,920 RECHALLENGE. 807 00:31:05,920 --> 00:31:10,760 NOW IT WAS THE DATA IN THIS 808 00:31:10,760 --> 00:31:11,400 EXPERIMENT DONE, PUBLISHED 1993 809 00:31:11,400 --> 00:31:14,200 THAT FORMED THE BASIS OF THE 810 00:31:14,200 --> 00:31:16,640 ANIMAL RULE ADOPTED BY THE FDA 811 00:31:16,640 --> 00:31:21,600 AND IT LED TO THE LICENSURE OF 812 00:31:21,600 --> 00:31:23,560 CIPRFLOXIN FOR POST EXPOSURE 813 00:31:23,560 --> 00:31:28,320 PROPHYLAXIS OF ANTHRAX. 814 00:31:28,320 --> 00:31:29,480 NEXT SLIDE. 815 00:31:29,480 --> 00:31:32,320 THUS, THESE RESULTS SUGGEST THAT 816 00:31:32,320 --> 00:31:34,960 THERAPY FOR AN UNIMMUNIZED 817 00:31:34,960 --> 00:31:36,960 PERSON EXPOSED TO AN AEROSOL OF 818 00:31:36,960 --> 00:31:40,840 ANTHRAX SPORES SHOULD CONSIST OF 819 00:31:40,840 --> 00:31:42,120 LONG-TERM SUPPRESSIVE 820 00:31:42,120 --> 00:31:42,520 ANTIBIOTICS. 821 00:31:42,520 --> 00:31:44,120 AND VACCINATION MAY PROVIDE AN 822 00:31:44,120 --> 00:31:51,520 ADDITIONAL DEGREE OF PROTECTION 823 00:31:51,520 --> 00:31:53,080 AGAINST RELAPSE AFTER ANTIBIOTIC 824 00:31:53,080 --> 00:31:55,080 TREATMENT AND WOULD PROTECT 825 00:31:55,080 --> 00:31:56,160 AGAINST A SUBSEQUENT EXPOSURE. 826 00:31:56,160 --> 00:31:57,120 NEXT SLIDE. 827 00:31:57,120 --> 00:31:58,320 AS MENTIONED, THIS STUDY WAS THE 828 00:31:58,320 --> 00:32:00,520 GENESIS OF THE ANIMAL RULE BY 829 00:32:00,520 --> 00:32:05,880 THE FDA, AND RESULTED IN THE 830 00:32:05,880 --> 00:32:07,960 APPROVAL OF CIPROFLOXIN, FOR 831 00:32:07,960 --> 00:32:09,320 POST EXPOSURE PROLAXIS, THIS IS 832 00:32:09,320 --> 00:32:09,960 THE ANIMAL RULE. 833 00:32:09,960 --> 00:32:11,920 AS INDICATE INDEED THE SECOND 834 00:32:11,920 --> 00:32:14,440 PARAGRAPH, THIS RULE WILL PERMIT 835 00:32:14,440 --> 00:32:18,200 THE DEMONSTRATION OF EFFICACY, 836 00:32:18,200 --> 00:32:20,840 USING ANIMAL STUDIES IN LIEU OF 837 00:32:20,840 --> 00:32:22,360 HUMAN CLINICAL TRIALS IN THOSE 838 00:32:22,360 --> 00:32:24,560 INSTANCES WHERE HUMAN TRIALS 839 00:32:24,560 --> 00:32:26,640 WOULD BE UNETHICAL BECAUSE OF 840 00:32:26,640 --> 00:32:29,320 THE SERIOUS CLINICAL EFFECTS OF 841 00:32:29,320 --> 00:32:32,080 THE AGENT OR WHERE SUCH TRIALS 842 00:32:32,080 --> 00:32:34,880 WOULD BE UNFEASIBLE BECAUSE OF 843 00:32:34,880 --> 00:32:36,240 THE INFREQUENCY OF HUMAN 844 00:32:36,240 --> 00:32:37,000 EXPOSURE TO THE [INDISCERNIBLE] 845 00:32:37,000 --> 00:32:40,320 AND OF COURSE, BOTH OF THESE ARE 846 00:32:40,320 --> 00:32:43,120 WITH ANTHRAX. 847 00:32:43,120 --> 00:32:44,400 NEXT SLIDE. 848 00:32:44,400 --> 00:32:45,680 THE PREVIOUS EXPERIMENTS 849 00:32:45,680 --> 00:32:47,520 PROMPTED US TO UNDERTAKE THE 850 00:32:47,520 --> 00:32:51,000 FOLLOWING STUDY TO DETERMINE 851 00:32:51,000 --> 00:32:53,920 WHETHER A SHORT COURSE POST 852 00:32:53,920 --> 00:32:55,640 EXPOSURE EABT BIOTICS 853 00:32:55,640 --> 00:32:58,120 PROPHYLAXIS, WHEN COMBINED WITH 854 00:32:58,120 --> 00:33:00,080 VACS NATION POST EXPOSURE COULD 855 00:33:00,080 --> 00:33:02,640 PROTECT AGAINST DISEASE DUE TO 856 00:33:02,640 --> 00:33:04,640 GERMINATION OF RETAINED SPORES 857 00:33:04,640 --> 00:33:07,200 AFTER DISCONTINUATION OF 858 00:33:07,200 --> 00:33:07,520 ANTIBIOTICS. 859 00:33:07,520 --> 00:33:12,920 RECALL THAT AFTER THE 2001 860 00:33:12,920 --> 00:33:13,560 ANTHRAX ATTACK, ABOUT 10,000 861 00:33:13,560 --> 00:33:17,720 PEOPLE WERE PUT ON 60 DAYS POST 862 00:33:17,720 --> 00:33:19,600 EXPOSURE ANTIBIOTIC PROPHYLAXIS 863 00:33:19,600 --> 00:33:24,640 BUT THE ADHERENCE WAS ONLY 44%. 864 00:33:24,640 --> 00:33:25,960 NEXT SLIDE. 865 00:33:25,960 --> 00:33:27,600 THE OBJECTIVE OF THIS EXPERIMENT 866 00:33:27,600 --> 00:33:28,800 WAS TO DETERMINE WHETHER 867 00:33:28,800 --> 00:33:32,440 SURVIVAL CAN BE ENHANCED BY 868 00:33:32,440 --> 00:33:36,080 ADDITION OF VACCINATION TO A 869 00:33:36,080 --> 00:33:39,240 SHORT COURSE OF POST EXPOSURE 870 00:33:39,240 --> 00:33:39,920 ANTIBIOTIC PROPHYLAXIS. 871 00:33:39,920 --> 00:33:43,520 THAT IS CAN VACS NATION SHORTEN 872 00:33:43,520 --> 00:33:48,120 THE DURATION OF PROPHYLAXIS? 873 00:33:48,120 --> 00:33:48,960 NEXT SLIDE. 874 00:33:48,960 --> 00:33:52,160 THIS SLIDE SHOWS EXPERIMENTAL 875 00:33:52,160 --> 00:33:52,680 DESIGN. 876 00:33:52,680 --> 00:33:56,720 TEN ANIMALS RECEIVE 877 00:33:56,720 --> 00:33:58,440 CIPROFLOXACIN AT DAY 0 WITHIN 2 878 00:33:58,440 --> 00:33:59,800 HOURS OF AEROSOL CHALLENGE AND 879 00:33:59,800 --> 00:34:05,680 CONTINUES FOR 14 DAYS. 880 00:34:05,680 --> 00:34:08,280 TEN OTHER ANIMALS RECEIVE 881 00:34:08,280 --> 00:34:10,120 CIPROFLOXACIN ACCORDING TO 882 00:34:10,120 --> 00:34:11,640 SCHEDULE AS FIRST GROUP BUT WERE 883 00:34:11,640 --> 00:34:14,040 ALSO VACCINATED WITH THE HUMAN 884 00:34:14,040 --> 00:34:16,080 ANTHRAX VACCINE ON DAYS 0, 14 885 00:34:16,080 --> 00:34:16,480 AND 28. 886 00:34:16,480 --> 00:34:18,880 THERE WERE 4 ADDITIONAL ANIMALS 887 00:34:18,880 --> 00:34:20,600 USED AS UNTREATED CONTROLS. 888 00:34:20,600 --> 00:34:22,120 AND IN THIS EXPERIMENT AS I 889 00:34:22,120 --> 00:34:23,880 MENTIONED THERE WAS THE DOSE, 890 00:34:23,880 --> 00:34:26,520 THE CHALLENGE DOSE WAS 200 TIMES 891 00:34:26,520 --> 00:34:28,640 GREATER THAN IT WAS IN THE 892 00:34:28,640 --> 00:34:29,680 EXPERIMENT WHERE ANIMALS ARE 893 00:34:29,680 --> 00:34:35,480 TREATED FOR 30 DAYS. 894 00:34:35,480 --> 00:34:36,360 NEXT SLIDE. 895 00:34:36,360 --> 00:34:38,560 ALL 4 TREATED CONTROL ANIMALS 896 00:34:38,560 --> 00:34:38,720 DIE. 897 00:34:38,720 --> 00:34:42,440 NO ANIMALS IN EITHER THE 898 00:34:42,440 --> 00:34:44,720 CIPROFLOXACIN ALONE OR THE 899 00:34:44,720 --> 00:34:45,960 CIPROFLOXACIN PLUS VACCINE 900 00:34:45,960 --> 00:34:50,320 GROUPS DIED WHILE ON ANTIBIOTIC 901 00:34:50,320 --> 00:34:50,800 THERAPY. 902 00:34:50,800 --> 00:34:54,360 AND WHILE ON ANTIBIOTIC THERAPY 903 00:34:54,360 --> 00:34:55,840 4 ANIMALS IN THE CIPROFLOXACIN 904 00:34:55,840 --> 00:34:59,160 ALONE GROUP AND 3 IN THE 905 00:34:59,160 --> 00:35:00,440 CIPROFLOXACIN PLUS VACCINE GROUP 906 00:35:00,440 --> 00:35:06,640 HAD POSITIVE BLOOD CULTURES FOR 907 00:35:06,640 --> 00:35:06,880 ANTHRAX. 908 00:35:06,880 --> 00:35:07,320 NEXT SLIDE. 909 00:35:07,320 --> 00:35:11,280 THIS SLIDE SHOWS THE RESULTS 910 00:35:11,280 --> 00:35:13,840 GRAPHICALLY, SURVIVAL AGAIN IS 911 00:35:13,840 --> 00:35:15,520 SHOWN ON THE Y-AXIS AND DAYS 912 00:35:15,520 --> 00:35:18,320 AFTER CHALLENGE ON THE X-AXIS. 913 00:35:18,320 --> 00:35:20,720 THE UNTREATED CONTROLS SHOWN IN 914 00:35:20,720 --> 00:35:24,960 THE CLOSED SQUARES DIED. 915 00:35:24,960 --> 00:35:28,720 WHILE ON ANTIBIOTICS FOR THE 14 916 00:35:28,720 --> 00:35:30,000 DAYS WERE NO DEATHS IN EITHER 917 00:35:30,000 --> 00:35:32,280 GROUP BUT AFTER THE ASPECT 918 00:35:32,280 --> 00:35:33,280 BIOTICSS WERE DISCONTINUED, ONLY 919 00:35:33,280 --> 00:35:38,920 4 OF 9 ANIMALS, 44% SURVIVED IN 920 00:35:38,920 --> 00:35:40,920 THE CIPROFLOXACIN GROUP SHOWN 921 00:35:40,920 --> 00:35:42,760 INDEED CLOSED CIRCLES. 922 00:35:42,760 --> 00:35:45,440 THIS WAS COMPARED TO 10 OF 10 923 00:35:45,440 --> 00:35:48,680 ANIMALS IN THE GROUP ALSO GIIVE 924 00:35:48,680 --> 00:35:52,280 VACCINATION SHOWN IN THE CLOSED 925 00:35:52,280 --> 00:35:52,600 TRIANGLES. 926 00:35:52,600 --> 00:35:55,160 THAT DIFFERENCE IN SURVIVAL WAS 927 00:35:55,160 --> 00:35:59,800 HIGHLY SIGNIFICANT. 928 00:35:59,800 --> 00:36:00,960 NEXT SLIDE. 929 00:36:00,960 --> 00:36:02,080 AN ADDITIONAL FINDING WAS THAT 930 00:36:02,080 --> 00:36:06,400 THE 4 ANIMALS IN THE 931 00:36:06,400 --> 00:36:09,680 CIPROFLOXACIN GROUP THAT 932 00:36:09,680 --> 00:36:10,520 SURVIVES DEVELOPED ANTIBODY 933 00:36:10,520 --> 00:36:13,720 TITERS TO THE PROTECTIVE ANTIGEN 934 00:36:13,720 --> 00:36:15,320 COMPONENT OF THE TOXIN AND 935 00:36:15,320 --> 00:36:17,680 IMPORTANTLY THESE SURVIVING 936 00:36:17,680 --> 00:36:21,560 ANIMALS WERE RESISTANT TO AN 937 00:36:21,560 --> 00:36:24,520 AEROSOL SPORE RECHALLENGE, 8 TO 938 00:36:24,520 --> 00:36:27,360 11 MONTHS LATER AND AS POINTED 939 00:36:27,360 --> 00:36:29,520 OUT BEFORE THIS, IS A CONTRAST 940 00:36:29,520 --> 00:36:32,000 TO THE 1943 STUDY WHERE THE 941 00:36:32,000 --> 00:36:34,320 ANIMALS RECEIVED A LOW CHALLENGE 942 00:36:34,320 --> 00:36:36,160 DOSE AND DID NOT DEVELOP AN 943 00:36:36,160 --> 00:36:39,360 IMMUNE RESPONSE AND WERE NOT 944 00:36:39,360 --> 00:36:40,280 PROTECTED AGAINST RECHALLENGE. 945 00:36:40,280 --> 00:36:41,520 SO IT'S LIKELY DUE TO THE FACT 946 00:36:41,520 --> 00:36:45,200 THAT WITH A LOW CHALLENGE DOSE, 947 00:36:45,200 --> 00:36:46,720 THE ANTIBIOTICS, POST EXPOSURE 948 00:36:46,720 --> 00:36:48,480 CAN SUPPRESS THE INFECTION IN 949 00:36:48,480 --> 00:36:50,080 THE DEVELOPMENT OF IMMUNITY. 950 00:36:50,080 --> 00:36:58,760 BUT WITH A HIGH CHALLENGE DOSE, 951 00:36:58,760 --> 00:37:03,720 THIS DOES NOT--NEXT SLIDE. 952 00:37:03,720 --> 00:37:07,320 IN CONCLUSION, THE ADDITION OF 953 00:37:07,320 --> 00:37:09,040 VACCINATION TO A SHORT 14 DAY 954 00:37:09,040 --> 00:37:12,160 COURSE OF POST EXPOSURE 955 00:37:12,160 --> 00:37:13,600 ANTIBIOTIC PROPHYLAXIS RECULTED 956 00:37:13,600 --> 00:37:15,720 IN A STATISTICALLY SIGNIFICANT 957 00:37:15,720 --> 00:37:17,760 INCREASE IN SURVIVAL COMPARED TO 958 00:37:17,760 --> 00:37:19,800 THOSE GIVEN ANTIBIOTICS ONLY. 959 00:37:19,800 --> 00:37:24,560 THAT IS A SHORT COURSE OF POST 960 00:37:24,560 --> 00:37:26,640 EXPOSURE ANTIBIOTIC PROPHYLAXIS, 961 00:37:26,640 --> 00:37:28,240 COMBINED WITH VACCINATION, 962 00:37:28,240 --> 00:37:34,440 RESULT INDEED 100% SURVIVAL. 963 00:37:34,440 --> 00:37:35,120 NEXT SLIDE. 964 00:37:35,120 --> 00:37:38,880 SO SHORTENING THE DURATION OF 965 00:37:38,880 --> 00:37:42,720 ANTIIC POST EXPOSURE IN A 966 00:37:42,720 --> 00:37:43,920 BIOTERRORRISM EVENT INVOLVING AX 967 00:37:43,920 --> 00:37:45,640 THRAKS BY ADDING POST EXPOSURE 968 00:37:45,640 --> 00:37:47,720 VACCINATION WOULD BE OF GREAT 969 00:37:47,720 --> 00:37:49,960 BENEFIT BECAUSE OF NONCOMPLIANCE 970 00:37:49,960 --> 00:37:51,760 WITH TAKING THE ANTIBIOTICS AND 971 00:37:51,760 --> 00:37:57,840 THE SIDE EFFECTS ASSOCIATED WITH 972 00:37:57,840 --> 00:38:00,040 PROLONGED THERAPY. 973 00:38:00,040 --> 00:38:02,440 THESE STUDIES PUBLISH THE ADD 974 00:38:02,440 --> 00:38:08,440 VALUE OF POST EXPOSURE 975 00:38:08,440 --> 00:38:10,120 VACCINATION AND ANTIBIOTIC 976 00:38:10,120 --> 00:38:12,520 PROPHYLAXIS AND PROVIDED THE 977 00:38:12,520 --> 00:38:14,520 EVIDENCE FOR THE CDC AND PUBLIC 978 00:38:14,520 --> 00:38:17,080 HEALTH RESPONSE TO BIOTERRORRISM 979 00:38:17,080 --> 00:38:17,920 EVENTS INVOLVING ANTHRAX. 980 00:38:17,920 --> 00:38:20,120 AND FINALLY THE NEXT SLIDE, THE 981 00:38:20,120 --> 00:38:21,400 DEVELOP OF A SUBCLINICAL 982 00:38:21,400 --> 00:38:22,680 INFECTION IN THIS EXPERIMENT 983 00:38:22,680 --> 00:38:25,000 AFTER A HIGH CHALLENGE DOSE, THE 984 00:38:25,000 --> 00:38:25,960 SUBSEQUENT DEVELOPMENT OF AN 985 00:38:25,960 --> 00:38:28,480 IMMUNE RESPONSE AND THE 986 00:38:28,480 --> 00:38:31,000 RESISTANCE TO RECHALLENGE OF THE 987 00:38:31,000 --> 00:38:34,360 SURVIVING ANIMALS STREETED WITH 988 00:38:34,360 --> 00:38:37,120 CIPROFLOCKSIN ALONE SUPPORTS THE 989 00:38:37,120 --> 00:38:38,840 SUGGESTION THAT INDIVIDUALS 990 00:38:38,840 --> 00:38:41,920 TREATED FOR SYMPTOMATIC 991 00:38:41,920 --> 00:38:43,280 ESTABLISHED INHALATIONAL ANTHRAX 992 00:38:43,280 --> 00:38:45,920 AND WHO RECOVER AND SERO-CONVERT 993 00:38:45,920 --> 00:38:51,200 MAY NOT REQUIRE AN ADDITIONAL 60 994 00:38:51,200 --> 00:38:52,640 DAYS OF ANTIBIOTIC THERAPY AS 995 00:38:52,640 --> 00:38:55,520 RECOMMENDED BY THE CURRENT 996 00:38:55,520 --> 00:38:58,080 GUIDELINES AND DR. VIETRI, WILL 997 00:38:58,080 --> 00:38:59,560 ADDRESS THE STUDY ABOUT THIS 998 00:38:59,560 --> 00:38:59,840 ISSUE. 999 00:38:59,840 --> 00:39:06,560 >> THANK YOU DR. FRIEDLANDER. 1000 00:39:06,560 --> 00:39:07,080 NEXT SLIDE, PLEASE. 1001 00:39:07,080 --> 00:39:09,320 >> THE PRESENCE OF RETAINED 1002 00:39:09,320 --> 00:39:10,840 SPORES AFTER AEROSOL EXPOSURE 1003 00:39:10,840 --> 00:39:12,360 HAS ALSO GENERATED UNCERTAINTY 1004 00:39:12,360 --> 00:39:13,840 REGARDING DURATION OF ANTIBIOTIC 1005 00:39:13,840 --> 00:39:17,480 THERAPY REQUIRED TO TREAT AND 1006 00:39:17,480 --> 00:39:20,200 ESTABLISHED INHALATIONAL ANTHRAX 1007 00:39:20,200 --> 00:39:21,840 INFECTION, NEXT SLIDE. 1008 00:39:21,840 --> 00:39:23,360 NOW THE INHALATIONAL ANTHRAX 1009 00:39:23,360 --> 00:39:24,720 TREATMENT RECOMMENDATIONS HAVE 1010 00:39:24,720 --> 00:39:27,000 EVOLVED BUT IN 2002,LET 1011 00:39:27,000 --> 00:39:28,320 GUIDELINES STATED THE 1012 00:39:28,320 --> 00:39:30,160 COMBINATION THERAPY SHOULD BE 1013 00:39:30,160 --> 00:39:31,520 DELIVERED INTRANSLATIONAL 1014 00:39:31,520 --> 00:39:33,080 RESEARCH VENEIOUSLY FOR 2-3 1015 00:39:33,080 --> 00:39:35,400 WEEKS FOLLOWED BY TRANSITION TO 1016 00:39:35,400 --> 00:39:37,360 A SINGLE ORAL ANTIBIOTIC AFTER 1017 00:39:37,360 --> 00:39:39,920 THE PATIENT HAS SHOWN CLINICAL 1018 00:39:39,920 --> 00:39:40,240 IMPROVEMENT. 1019 00:39:40,240 --> 00:39:41,840 THE RECOMMENDED TOTAL DURATION 1020 00:39:41,840 --> 00:39:42,920 OF ANTIBIOTIC TREATMENT WAS 60 1021 00:39:42,920 --> 00:39:44,920 DAYS OR LATER A HUNDRED DAYS OR 1022 00:39:44,920 --> 00:39:47,680 A HUNDRED DAYS PLUS 3 DOSES OF 1023 00:39:47,680 --> 00:39:49,520 THE AVA VACCINE. 1024 00:39:49,520 --> 00:39:49,960 NEXT SLIDE, PLEASE. 1025 00:39:49,960 --> 00:39:51,880 BUT WE KNOW THAT INDIVIDUALS WHO 1026 00:39:51,880 --> 00:39:56,840 RECOVER FROM ESTABLISHED ANTHRAX 1027 00:39:56,840 --> 00:39:58,520 AFTER TREATMENT, DEVELOP A 1028 00:39:58,520 --> 00:40:00,560 SEROLOGICAL RESPONSE AND IF WE 1029 00:40:00,560 --> 00:40:02,600 LOOK IN THE LITERATURE REPEAT 1030 00:40:02,600 --> 00:40:03,480 CUTANEOUS ANTHRAX INFECTIONS 1031 00:40:03,480 --> 00:40:04,960 HAVE RARELY BEEN REPORTED AND IF 1032 00:40:04,960 --> 00:40:06,880 REPORTED TEND TO BE MUCH MILDER 1033 00:40:06,880 --> 00:40:10,880 THAN THE ORIGINAL CASE. 1034 00:40:10,880 --> 00:40:11,640 NEXT SLIDE, PLEASE. 1035 00:40:11,640 --> 00:40:13,640 SO THE HYPOTHESIS WE HAD WAS A 1036 00:40:13,640 --> 00:40:15,440 SHORT COURSE OF ANTIBIOTIC 1037 00:40:15,440 --> 00:40:17,240 THERAPY 10 DAYS, SUFFICIENT TO 1038 00:40:17,240 --> 00:40:19,120 TREAT AND ESTABLISH INHALATIONAL 1039 00:40:19,120 --> 00:40:20,920 ANTHRAX AND INFECTION AND THAT 1040 00:40:20,920 --> 00:40:21,600 THOSE ANIMALS THAT SURVIVE WOULD 1041 00:40:21,600 --> 00:40:23,840 NOT BE AT RISK OF DEVELOPING 1042 00:40:23,840 --> 00:40:25,200 DISEASE FOR RETAINED SUPPOSES 1043 00:40:25,200 --> 00:40:28,720 DUE TO DEVELOPMENT OF A 1044 00:40:28,720 --> 00:40:29,560 PROTECTIVE IMMUNE RESPONSE. 1045 00:40:29,560 --> 00:40:30,760 NEXT SLIDE, PLEASE. 1046 00:40:30,760 --> 00:40:33,760 SO WE DESIGNED AN EXPERIMENT 1047 00:40:33,760 --> 00:40:36,000 THIS HAD 20 ADULT RECESS 1048 00:40:36,000 --> 00:40:37,400 Mc CABBINGS THAT WERE IN 2 1049 00:40:37,400 --> 00:40:39,160 DIFFERENT GROUPS,A I PROPHYLAXIS 1050 00:40:39,160 --> 00:40:41,040 GROUP AND A TREATMENT GROUP. 1051 00:40:41,040 --> 00:40:42,920 THE SPORES WERE ADMINISTERED AND 1052 00:40:42,920 --> 00:40:45,760 THE AEROSOL DOSE WAS LARGE, 1053 00:40:45,760 --> 00:40:48,560 GREATER THAN 400 LV50S, BLOOD 1054 00:40:48,560 --> 00:40:49,960 CULTURES WERE OBTAINED EVERY 12 1055 00:40:49,960 --> 00:40:54,520 HOURS FOR ALL ANIMALS AT 7 DAYS 1056 00:40:54,520 --> 00:40:55,920 AFTER EXPOSURE, TISSUES FOR 1057 00:40:55,920 --> 00:40:56,520 HISTOPATHOLOGY WERE 1058 00:40:56,520 --> 00:40:58,840 ABNORMALITIES TIANYLED AND SERUM 1059 00:40:58,840 --> 00:41:00,160 FOR IGG ANTIBODIES WERE MEASURED 1060 00:41:00,160 --> 00:41:10,800 ON STUDY DAYS 14, 21, 28, AND 42 1061 00:41:10,800 --> 00:41:11,960 WITHIN EL ISA. 1062 00:41:11,960 --> 00:41:16,160 >> NEXT SLIDE, ANIMALS IN THE 1063 00:41:16,160 --> 00:41:19,320 GROUP RECEIVED 100 MG EVERY 2 1064 00:41:19,320 --> 00:41:21,760 HOURS, 1-2 HOURS AFTER AEROSOL 1065 00:41:21,760 --> 00:41:23,360 EXPOSURE, ANIMALS IN THE 1066 00:41:23,360 --> 00:41:26,240 TREATMENT GROWM BEGAN ANTIBIOTIC 1067 00:41:26,240 --> 00:41:27,880 THERAPY WITH CIPROFLOXACIN AFTER 1068 00:41:27,880 --> 00:41:30,040 2 CONSECUTIVE BLOOD CULTURES 1069 00:41:30,040 --> 00:41:32,320 WERE POSITIVE PER ANTHRAX, THE 1070 00:41:32,320 --> 00:41:36,120 DURATION OF THE PROVE LAX AXIS 1071 00:41:36,120 --> 00:41:37,960 GROUP WAS--PROPHYLAXIS GROUP WAS 1072 00:41:37,960 --> 00:41:40,080 LINKED TO THE TREATMENT GROUP SO 1073 00:41:40,080 --> 00:41:43,080 ONCE THE ANIMAL HAD COMPLETED 10 1074 00:41:43,080 --> 00:41:44,520 DAYS ANTIBIOTIC THERAPY, 1075 00:41:44,520 --> 00:41:45,440 ANTIBIOTICS WERE DISCONTINUED IN 1076 00:41:45,440 --> 00:41:47,080 THAT ANIMAL AND THE MATCHED PAIR 1077 00:41:47,080 --> 00:41:48,840 IN THE PROPHYLAXIS GROUP. 1078 00:41:48,840 --> 00:41:49,440 NEXT SLIDE, PLEASE. 1079 00:41:49,440 --> 00:41:52,520 SO LET'S LOOK ATY THE SURVIVAL 1080 00:41:52,520 --> 00:41:53,640 RESULTS WHILE ON ANTIBIOTIC. 1081 00:41:53,640 --> 00:41:55,920 AS CAN BE SEEN BY THE GREEN 1082 00:41:55,920 --> 00:41:58,760 BARS, ALL 10 ANIMALS IN THE 1083 00:41:58,760 --> 00:42:05,360 PROPHYLAXIS GROUP SURVIVE AND 1084 00:42:05,360 --> 00:42:06,360 REMAIN--BLUE BARS, 3 OF 10 OR 1085 00:42:06,360 --> 00:42:08,480 30% OF THE ANIMALS IN THE 1086 00:42:08,480 --> 00:42:09,880 TREATMENT GROUP DIED, WHILE 1087 00:42:09,880 --> 00:42:17,200 RECEIVING THEIR 10 DAY COURSE OF 1088 00:42:17,200 --> 00:42:17,360 OF 1089 00:42:17,360 --> 00:42:18,280 CIPROFLOXACIN TREATMENT. 1090 00:42:18,280 --> 00:42:21,840 THESE ANIMALS DIED ON DAYS 5, 8 1091 00:42:21,840 --> 00:42:23,520 AND 9 AFTER STARTING TREATMENT, 1092 00:42:23,520 --> 00:42:25,160 ALL 3 ANIMALS DEMONSTRATED THE 1093 00:42:25,160 --> 00:42:28,520 GROWTH OF THE ANTHRAX. 1094 00:42:28,520 --> 00:42:30,200 AND AT NECROPSY, ALL 3 ANIMALS 1095 00:42:30,200 --> 00:42:34,000 HAD EVIDENCE OF ANTHRAX AS 1096 00:42:34,000 --> 00:42:36,400 MANIFESTED BY THE TRACHIO 1097 00:42:36,400 --> 00:42:40,720 BRONCHIAL LYMPHNODE SAYS AND 1098 00:42:40,720 --> 00:42:41,360 HEMORRHAGIC MEDIA STINNITEIS. 1099 00:42:41,360 --> 00:42:41,840 NEXT SLIDE. 1100 00:42:41,840 --> 00:42:43,600 THE NEXT SLIDE SHOWS SURVIVAL 1101 00:42:43,600 --> 00:42:45,440 RESULTS AFTER THE COMPLETION OF 1102 00:42:45,440 --> 00:42:46,840 ANTIBIOTIC THERAPY. 1103 00:42:46,840 --> 00:42:53,760 IN THE PROPHYLAXIS GROUP, 8 OF 1104 00:42:53,760 --> 00:42:57,440 THE ANIMALS DIED AFTER SECESSION 1105 00:42:57,440 --> 00:42:58,320 OF ANTIBIOTIC THERAPY. 1106 00:42:58,320 --> 00:42:59,520 THESE DEATHS OCCURRED BETWEEN 4 1107 00:42:59,520 --> 00:43:01,720 AND 9 DAYS AFTER ANTIBIOTICS 1108 00:43:01,720 --> 00:43:02,040 WERE STOPPED. 1109 00:43:02,040 --> 00:43:05,200 ALL 8 OF THESE ANIMALS HAD 1110 00:43:05,200 --> 00:43:07,120 POSITIVE CULTURES FOR ANTHRAX IN 1111 00:43:07,120 --> 00:43:08,800 THEIR BLOOD, SPLEEN, BRAIN, LUNG 1112 00:43:08,800 --> 00:43:13,160 AND LYMPHNODES AND ALL HAD 1113 00:43:13,160 --> 00:43:15,240 NEUROECTODERMAL KRONISH MEDIAL 1114 00:43:15,240 --> 00:43:16,520 HEMRITIS ON AUTOPSIES, ON 1115 00:43:16,520 --> 00:43:18,520 CONTRAST THE TREATMENT GROUP, 1116 00:43:18,520 --> 00:43:20,520 BLUE BARS, NONE OF THE 7 ANIMALS 1117 00:43:20,520 --> 00:43:22,600 DIED AFTER COMPLETING A 7 DAY 1118 00:43:22,600 --> 00:43:24,360 COURSE OF ANTIBIOTIC THERAPY AND 1119 00:43:24,360 --> 00:43:27,680 THIS DIFFERENCE WAS HIGHLY 1120 00:43:27,680 --> 00:43:28,400 STATISTICALLY SIGNIFICANT. 1121 00:43:28,400 --> 00:43:30,440 THERE WERE NO ILLNESSES IN THESE 1122 00:43:30,440 --> 00:43:32,320 ANIMALS FOR AS LONG AS 120 DAYS 1123 00:43:32,320 --> 00:43:35,440 AFTER EXPOSE AND YOU ARE ALL 7 1124 00:43:35,440 --> 00:43:37,840 ANIMALS DEVELOP DETECTABLE 1125 00:43:37,840 --> 00:43:40,400 LEVELS OF ANTIPA AND 1126 00:43:40,400 --> 00:43:41,560 IGG ANTIBODIES AFTER DAY 14 OF 1127 00:43:41,560 --> 00:43:42,120 EXPOSURE. 1128 00:43:42,120 --> 00:43:42,920 NEXT SLIDE, PLEASE. 1129 00:43:42,920 --> 00:43:44,920 HERE'S THE DATA PRESENTED AS A 1130 00:43:44,920 --> 00:43:45,400 SURVIVAL CURVE. 1131 00:43:45,400 --> 00:43:47,960 AS CAN BE SEEN IN THE OPEN 1132 00:43:47,960 --> 00:43:49,440 TRIANGLES, WHILE ON ANTIBIOTIC 1133 00:43:49,440 --> 00:43:50,640 THERAPY THERE WERE 3 DEATHS IN 1134 00:43:50,640 --> 00:43:53,080 THE TREATMENT GROUP. 1135 00:43:53,080 --> 00:43:54,400 HOWEVER, AFTER COMPLETING 10 1136 00:43:54,400 --> 00:43:55,240 DAYS OF ANTIBIOTIC THERAPY THAT 1137 00:43:55,240 --> 00:43:58,120 WAS STARTED AFTER THE BIG 1138 00:43:58,120 --> 00:43:58,880 DEVELOPMENT OF BACTERIAEREMMIA, 1139 00:43:58,880 --> 00:44:04,520 THERE WERE NO FURTHER DEATHS IN 1140 00:44:04,520 --> 00:44:05,880 THE GROUP. 1141 00:44:05,880 --> 00:44:07,880 THE HIGHER CIRCLES EXPERIENCED 1142 00:44:07,880 --> 00:44:09,960 HIGH MORTALITY RATE DUE TO 1143 00:44:09,960 --> 00:44:11,400 SHORTAGE OF PROPHYLAXIS WHICH 1144 00:44:11,400 --> 00:44:12,320 AVERAGED ABOUT 13 DAYS. 1145 00:44:12,320 --> 00:44:12,880 NEXT SLIDE. 1146 00:44:12,880 --> 00:44:16,280 IN SUMMARY AS PREVIOUS WORK SHOZ 1147 00:44:16,280 --> 00:44:16,920 SHOWN, RECESS Mc CABBINGS 1148 00:44:16,920 --> 00:44:20,200 GIIVE A SHORT COURSE OF 1149 00:44:20,200 --> 00:44:22,320 ANTIBIOTICS FOR INHALATIONAL 1150 00:44:22,320 --> 00:44:24,480 ANTHRAX EXPERIENCED MORTALITY 1151 00:44:24,480 --> 00:44:26,480 ONCE THE ANTIBIOTICS WERE 1152 00:44:26,480 --> 00:44:27,960 DISCONTINUED, IN CONTRAST 1153 00:44:27,960 --> 00:44:29,840 MACAQUES TREATED WITH A SHORT 1154 00:44:29,840 --> 00:44:32,720 COURSE OF ANTIBIOTIC THERAPY FOR 1155 00:44:32,720 --> 00:44:34,720 INHALATIONAL ANTHRAX AFTER THE 1156 00:44:34,720 --> 00:44:35,880 ONSET OF BACTERIAEREMMIA WERE 1157 00:44:35,880 --> 00:44:37,920 NOT AT RISK FOR DEVELOPING 1158 00:44:37,920 --> 00:44:41,280 DISEASE AFTER THE CESSATION OF 1159 00:44:41,280 --> 00:44:42,720 ANTIBIOTIC THERAPY. 1160 00:44:42,720 --> 00:44:44,040 AND THE DEVELOPMENT OF ROUGH 1161 00:44:44,040 --> 00:44:45,240 ATOM A PROTECTIVE IMMUNE 1162 00:44:45,240 --> 00:44:45,520 RESPONSE. 1163 00:44:45,520 --> 00:44:46,800 SO PATIENT WHO IS TREATED FOR 1164 00:44:46,800 --> 00:44:48,120 ANTHRAX AND RECOVER, WE 1165 00:44:48,120 --> 00:44:49,520 RECOMMENDED OR SUGGEST TODAY 1166 00:44:49,520 --> 00:44:51,640 SHOULD BE TESTED FOR A 1167 00:44:51,640 --> 00:44:52,560 DEVELOPMENT OF AN IMMUNE 1168 00:44:52,560 --> 00:44:54,200 RESPONSE TO THE ANTHRAX, BECAUSE 1169 00:44:54,200 --> 00:44:56,280 THE PRESENCE OF AN ANTIP 1170 00:44:56,280 --> 00:44:58,400 ANTIBODIES MAY BE USEFUL FOR 1171 00:44:58,400 --> 00:44:59,840 DETERMINING WHEN ANTIBIOTIC CANS 1172 00:44:59,840 --> 00:45:01,880 SAFELY BE DISCONTINUED IN SUCH 1173 00:45:01,880 --> 00:45:02,160 INDIVIDUALS. 1174 00:45:02,160 --> 00:45:12,840 NOW I WILL TURN IT BACK OVER TO 1175 00:45:12,840 --> 00:45:14,320 DR. WRIGHT. 1176 00:45:14,320 --> 00:45:14,720 >> THANKS, NICK. 1177 00:45:14,720 --> 00:45:16,600 SO WE IN THE THIRD QUESTION 1178 00:45:16,600 --> 00:45:19,000 DECIDED TO TAKE A LOOK AT CLIND 1179 00:45:19,000 --> 00:45:22,200 O MICEIN TO SEE IF IT MADE A 1180 00:45:22,200 --> 00:45:25,520 DIFFERENCE IN SURVIVAL. 1181 00:45:25,520 --> 00:45:27,720 SO WE KNOW THAT CLIND O MICEIN 1182 00:45:27,720 --> 00:45:29,920 IS A PROTEIN SIPGHT SIS 1183 00:45:29,920 --> 00:45:31,800 INHIBITOR AND IT HAS TOXIN 1184 00:45:31,800 --> 00:45:34,640 ACTIVITY AGAINST OTHER 1185 00:45:34,640 --> 00:45:35,480 GRAM-POSITIVE ORGANISMS AND IT 1186 00:45:35,480 --> 00:45:37,800 HAD BEEN USED DURING THE 2001 1187 00:45:37,800 --> 00:45:39,680 ATTACKS BUT SINCE THAT TIME, 1188 00:45:39,680 --> 00:45:40,920 ANIMAL DATA HAD BEEN CONFLICTING 1189 00:45:40,920 --> 00:45:43,120 IN SOME OF THE RESULTS, SO, WE 1190 00:45:43,120 --> 00:45:46,880 DECIDED TO TAKE A LOOK IN 1191 00:45:46,880 --> 00:45:49,320 NONHUMAN PRIMATES HAVE A CLINDA 1192 00:45:49,320 --> 00:45:50,240 MICEIN ONLY GROUP, A 1193 00:45:50,240 --> 00:45:51,440 CIPROFLOXACIN GROUP AND A 1194 00:45:51,440 --> 00:45:53,080 COMBINATION ARM TO LOOK AT TOXIN 1195 00:45:53,080 --> 00:45:54,040 LEVELS AND SURVIVAL AND AS CAN 1196 00:45:54,040 --> 00:45:58,760 YOU SEE ON THIS SURVIVAL CURVE, 1197 00:45:58,760 --> 00:46:02,920 IN THE CLOSED CIRCLES, THAT'S 1198 00:46:02,920 --> 00:46:05,440 THE CIPRO-ONLY GROUP, THERE WAS 1199 00:46:05,440 --> 00:46:07,520 A HUNDRED PERCENT SURVIVAL, OPEN 1200 00:46:07,520 --> 00:46:11,200 SQUARES YOU 8 OUT OF 11, 73% 1201 00:46:11,200 --> 00:46:12,280 SURVIVEAR FOR CLINDA MICEIN ONLY 1202 00:46:12,280 --> 00:46:15,160 AND FOR THE CLOSED TRIANGLES, 1203 00:46:15,160 --> 00:46:16,160 THE COMBINATION ARM SIMILAR 1204 00:46:16,160 --> 00:46:19,360 SURVIVAL SO THERE WAS NOT A 1205 00:46:19,360 --> 00:46:20,120 SIGNIFICANCE SURVIVAL BETWEEN 1206 00:46:20,120 --> 00:46:23,960 THE DIFFERENT ARMS BUT THIS WAS 1207 00:46:23,960 --> 00:46:27,120 THE FIRST ANIMAL STUDY LOOKING 1208 00:46:27,120 --> 00:46:28,120 AT CLINDA MICEIN AND NONHUMAN 1209 00:46:28,120 --> 00:46:30,200 PRIMATES TO LOOK AT ANTHRAX, SO 1210 00:46:30,200 --> 00:46:33,320 WE DID SHOW THAT CLINDA MICEIN 1211 00:46:33,320 --> 00:46:34,520 DID IMPROVE SURVIVAL BY ITSELF 1212 00:46:34,520 --> 00:46:36,600 JUST BECAUSE OF THE SMALL 1213 00:46:36,600 --> 00:46:38,240 NUMBERS AND THE HUNDRED PERCENT 1214 00:46:38,240 --> 00:46:39,800 SURVIVAL IN THE CIPRO GROUP, AND 1215 00:46:39,800 --> 00:46:42,440 WE'RE NOT ABLE TO SHOW WHETHER 1216 00:46:42,440 --> 00:46:44,440 THE ADDITION OF CLINDA MICEIN 1217 00:46:44,440 --> 00:46:45,960 ADDED BENEFIT AND AGAIN FOR 1218 00:46:45,960 --> 00:46:49,000 TREATMENT, IT WAS COUNTED AS 2 1219 00:46:49,000 --> 00:46:50,320 CONSECUTIVE POSITIVE BLD BLOOD 1220 00:46:50,320 --> 00:46:52,320 CULTURES 12 HOURS APART WAS THE 1221 00:46:52,320 --> 00:46:58,200 TRIGGER FOR STARTING 1222 00:46:58,200 --> 00:46:58,520 ANTIBIOTICS. 1223 00:46:58,520 --> 00:47:00,280 SO IN THE LAST FEW MINUTES I 1224 00:47:00,280 --> 00:47:04,600 WOULD LIKE TO TOUCH ON THESE 1225 00:47:04,600 --> 00:47:07,600 OBJECTIVES, BECOME AWARE OF 1226 00:47:07,600 --> 00:47:08,920 RESEARCH INFRASTRUCTURE AND 1227 00:47:08,920 --> 00:47:11,280 CAPACITY AS WELL AS IDENTIFY 1228 00:47:11,280 --> 00:47:14,520 REMAINING CLINICAL QUESTIONS 1229 00:47:14,520 --> 00:47:15,520 REGARDING INHALATIONAL ANTHRAX 1230 00:47:15,520 --> 00:47:19,320 AND ANTIBIOTICS THAT WERE FDA 1231 00:47:19,320 --> 00:47:20,080 A APPROVED, PENICILLIN AND 1232 00:47:20,080 --> 00:47:21,200 DOXYCYCLINE AND THERE WERE SO 1233 00:47:21,200 --> 00:47:22,720 MANY QUESTIONS AND THERE WERE 1234 00:47:22,720 --> 00:47:24,120 ONT ENOUGH PEOPLE OR PLACES TO 1235 00:47:24,120 --> 00:47:25,520 POTENTIALLY LOOK AT THIS, SO 1236 00:47:25,520 --> 00:47:30,680 THERE WAS A BLUE RIBBON PANEL IN 1237 00:47:30,680 --> 00:47:32,560 2002 WHICH IDENTIFIED A HIGH 1238 00:47:32,560 --> 00:47:34,520 PRIORITY TO INCREASE 1239 00:47:34,520 --> 00:47:36,760 INFRASTRUCTURE AND TO ADDRESS 1240 00:47:36,760 --> 00:47:39,400 THE SERIOUS SHORTAGE OF 1241 00:47:39,400 --> 00:47:46,560 FACILITIES TO SAFELY CONDUCT 1242 00:47:46,560 --> 00:47:48,120 RESEARCH ON EMERGING INFECTIOUS 1243 00:47:48,120 --> 00:47:48,400 DISEASES. 1244 00:47:48,400 --> 00:47:51,120 AND 1 THING I WANTED TOADAAD IS 1245 00:47:51,120 --> 00:47:53,120 THE FACILITY FORT DIETRICH, 1246 00:47:53,120 --> 00:47:57,200 BECAUSE IT WAS THE FIRST LAB TO 1247 00:47:57,200 --> 00:47:59,080 INTEGRATE THAT HOSPITAL TYPE 1248 00:47:59,080 --> 00:48:02,080 IMAGING EQUIPMENT INTO A 1249 00:48:02,080 --> 00:48:03,000 BSL3/BSL4 SPACE FOR RESEARCH. 1250 00:48:03,000 --> 00:48:06,880 THE LAB IS PART OF THE NATIONAL 1251 00:48:06,880 --> 00:48:09,440 INTERAGENCY BIODEFENSE CAMPUS AT 1252 00:48:09,440 --> 00:48:11,880 FORT DETRICK, ALONG WITH THE 1253 00:48:11,880 --> 00:48:13,440 ARMY'S USAM RIN, IN ADDITION AT 1254 00:48:13,440 --> 00:48:14,920 THE CLINICAL CENTER, A SPECIAL 1255 00:48:14,920 --> 00:48:16,360 CLINICAL STUDIES UNIT WAS 1256 00:48:16,360 --> 00:48:22,560 CONSTRUCTED THAT WAS ENABLE HIGH 1257 00:48:22,560 --> 00:48:23,600 CONTAINMENT INFECTION, ISOLATION 1258 00:48:23,600 --> 00:48:24,960 OTHERS PROPER AIR FLOW ROOMS TO 1259 00:48:24,960 --> 00:48:26,600 TAKE CARE OF PATIENTS AND 1260 00:48:26,600 --> 00:48:28,840 CONDUCT RESEARCH ON PEOPLE THAT 1261 00:48:28,840 --> 00:48:30,200 MIGHT HAVE MORE TRANSMISSIBLE 1262 00:48:30,200 --> 00:48:32,840 INFECTIONS, AND WHEN THE EBOLA 1263 00:48:32,840 --> 00:48:37,600 OUTBREAK IN 2014 HIT, THE SES U 1264 00:48:37,600 --> 00:48:40,160 WAS USED TO CARE FOR SOME OF THE 1265 00:48:40,160 --> 00:48:42,040 HEALTHCARE WORKERS WHO HAD 1266 00:48:42,040 --> 00:48:43,360 GOTTEN EBOLA FROM THE EBOLA 1267 00:48:43,360 --> 00:48:48,120 PATES THAT HAD COME TO THE 1268 00:48:48,120 --> 00:48:49,240 UNITED STATES. 1269 00:48:49,240 --> 00:48:50,520 SO THE MANY CLINICAL RESEARCH 1270 00:48:50,520 --> 00:48:51,360 QUESTIONS THAT WE STILL HAVE 1271 00:48:51,360 --> 00:48:55,520 THAT I WANTED TO MENTION 1272 00:48:55,520 --> 00:48:58,640 SEVERAL, CAN NONINVASIVE IMAGING 1273 00:48:58,640 --> 00:49:00,160 FINDINGS BE USED TO CHARACTERIZE 1274 00:49:00,160 --> 00:49:01,880 STAGES OF ANTHRAX INFECTION? 1275 00:49:01,880 --> 00:49:04,520 WELL THE ACTUAL CATALYST FOR THE 1276 00:49:04,520 --> 00:49:06,720 RESEARCH FACILITY WAS QUESTIONS 1277 00:49:06,720 --> 00:49:09,560 JUST LIKE THIS AND IMAGING HAS 1278 00:49:09,560 --> 00:49:10,240 EVOLVED OVER'RE SIGNIFICANCE 95 1279 00:49:10,240 --> 00:49:12,960 CANTILY OVER THE YEARS AND AT 1280 00:49:12,960 --> 00:49:14,240 THE THEY PUBLISHED THINGS 1281 00:49:14,240 --> 00:49:17,320 LOOKING AT EBOLA AND SARS-COV-2, 1282 00:49:17,320 --> 00:49:20,080 AND THE QUESTION ABOUT HOW MANY 1283 00:49:20,080 --> 00:49:21,800 ANTIBIOTICS NEEDED DURING ACUTE 1284 00:49:21,800 --> 00:49:23,560 INFECTION IS IMPORTANT, WHEN IS 1285 00:49:23,560 --> 00:49:25,360 THE BEST TIME TO GIVE ANTITOXIN 1286 00:49:25,360 --> 00:49:27,200 TREATMENT AND WHAT IS THE 1287 00:49:27,200 --> 00:49:29,320 LONG-TERM SUPPLY OF INHALATIONAL 1288 00:49:29,320 --> 00:49:29,520 ANTHRAX? 1289 00:49:29,520 --> 00:49:30,600 AND ALL THESE ARE QUESTIONS WE 1290 00:49:30,600 --> 00:49:32,600 LOOK AT IN ANY PATHOGEN IS 1291 00:49:32,600 --> 00:49:36,400 CERTAINLY COVID HAS BEEN STUDIED 1292 00:49:36,400 --> 00:49:36,720 EXTENSIVELY. 1293 00:49:36,720 --> 00:49:37,440 FOR THE SECOND QUESTION ABOUT 1294 00:49:37,440 --> 00:49:39,040 THE NUMBER OF ANTIBIOTICS TO 1295 00:49:39,040 --> 00:49:42,120 USE, THIS GETS COVERED WITH THE 1296 00:49:42,120 --> 00:49:45,680 PERIODIC UPDATES BY THE CDC 1297 00:49:45,680 --> 00:49:47,680 GUIDELINES AND THE LAST SET 1298 00:49:47,680 --> 00:49:49,320 GUIDELINES WAS ISSUED IN 2014, 1299 00:49:49,320 --> 00:49:51,200 THE PANEL MET LAST YEAR AND WILL 1300 00:49:51,200 --> 00:49:52,360 BE ISSUING ANOTHER 1 SOON. 1301 00:49:52,360 --> 00:49:54,600 BUT AT THAT TIME, THE EMPHASIS 1302 00:49:54,600 --> 00:49:56,240 WAS PLACED ON LOOKING AT 1303 00:49:56,240 --> 00:49:58,400 SYSTEMIC ANTHRAX AND THE CONTEXT 1304 00:49:58,400 --> 00:50:02,000 OF WHETHER THERE WAS MENINGITIS 1305 00:50:02,000 --> 00:50:04,560 OR NOT MENINGITIS AND THE OLD 1306 00:50:04,560 --> 00:50:05,280 LITERATURE SUGGESTS THAT 1307 00:50:05,280 --> 00:50:08,240 BASICALLY IF HAVE YOU SYSTEMIC 1308 00:50:08,240 --> 00:50:11,200 ANTHRAX, HAVE YOU A HIGH 1309 00:50:11,200 --> 00:50:12,120 LIKELIHOOD OF HAVING MENINGITIS 1310 00:50:12,120 --> 00:50:14,360 AND IT'S IMPORTANT TO COVER OR 1311 00:50:14,360 --> 00:50:16,000 HAVE CNS PENETRATION WITH THE 1312 00:50:16,000 --> 00:50:17,920 DRUGS YOU ARE CHIEWZING SO IF 1313 00:50:17,920 --> 00:50:19,760 YOU THINK THERE'S MENINGITIS, 1314 00:50:19,760 --> 00:50:21,520 THERE'S 3 DRUGS VERSUS 2 IF YOU 1315 00:50:21,520 --> 00:50:24,320 RULED IT OUT AND ALSO EMPHASIZED 1316 00:50:24,320 --> 00:50:25,560 ABOUT ADDING ANTITOXINS TO 1317 00:50:25,560 --> 00:50:26,920 ANTIBIOTICS FOR PEOPLE WHO 1318 00:50:26,920 --> 00:50:28,400 REALLY HAVE SYSTEMIC 1319 00:50:28,400 --> 00:50:30,720 INVOLVEMENT, AND TO CONTINUE 1320 00:50:30,720 --> 00:50:31,880 AGGRESSIVE PLURAL FLUID 1321 00:50:31,880 --> 00:50:32,720 MANAGEMENT BECAUSE YOU'RE 1322 00:50:32,720 --> 00:50:38,200 BASICALLY GETTING RID OF THE 1323 00:50:38,200 --> 00:50:38,440 TOXIN. 1324 00:50:38,440 --> 00:50:41,400 THE THIRD QUESTION, TIMING OF 1325 00:50:41,400 --> 00:50:43,160 TREATMENTS REMAINS UNKNOWN. 1326 00:50:43,160 --> 00:50:44,880 THERE'S BEEN EXTENSIVE 1327 00:50:44,880 --> 00:50:46,320 DISCUSSION ON THAT AMONGST 1328 00:50:46,320 --> 00:50:48,120 EXPERTS OVER THE YEARS AND THIS 1329 00:50:48,120 --> 00:50:49,880 IS ALWAYS A QUESTION FOR ANY 1330 00:50:49,880 --> 00:50:50,120 PATHOGEN. 1331 00:50:50,120 --> 00:50:53,360 BUT TO UPDATE YOU SINCE 2001, IF 1332 00:50:53,360 --> 00:50:56,920 YOU LOOK AT THE GREEN, THESE ARE 1333 00:50:56,920 --> 00:50:57,840 THERAPEUTICS OR ANTIMICROBIALS 1334 00:50:57,840 --> 00:50:59,520 THAT HAVE BEEN APPROVED BY THE 1335 00:50:59,520 --> 00:51:11,200 FDA WITH ANTHRAX, MICROBIALS OFF 1336 00:51:11,200 --> 00:51:12,720 LABEL COULD BE NECESSARY FOR 1337 00:51:12,720 --> 00:51:13,680 SICK PATIENTS, THERE'S THE 1338 00:51:13,680 --> 00:51:16,120 CRITICAL ROLE OF COURSE IN TCs 1339 00:51:16,120 --> 00:51:18,400 AND CHEST DIEWBS BUT HERE WE SEE 1340 00:51:18,400 --> 00:51:20,200 2 MONOCLONAL ANTIBODIES AND 1341 00:51:20,200 --> 00:51:22,720 ANTHRAX IMMUNE GLOBUE LYNN WHICH 1342 00:51:22,720 --> 00:51:25,200 WERE ALL APPROVED UNDER THE 1343 00:51:25,200 --> 00:51:27,600 ANIMAL RULE. 1344 00:51:27,600 --> 00:51:29,000 THERE'S ALL STRATEGIC STOCK PILE 1345 00:51:29,000 --> 00:51:30,160 NOW AND IT'S IMPORTANT TO 1346 00:51:30,160 --> 00:51:32,240 REMEMBER THAT NONE OF THEM 1347 00:51:32,240 --> 00:51:33,920 CROSSLET BLOOD BRAIN BARRIER SO 1348 00:51:33,920 --> 00:51:36,760 AGAIN, BEING ABLE TO COVER FOR 1349 00:51:36,760 --> 00:51:37,440 POTENTIAL MENINGITIS IS 1350 00:51:37,440 --> 00:51:37,720 IMPORTANT. 1351 00:51:37,720 --> 00:51:39,360 SO THE QUESTION OF TIMING OF 1352 00:51:39,360 --> 00:51:42,000 TREATMENTS IS SEEN WITH SURVIVE 1353 00:51:42,000 --> 00:51:43,320 AG SEPSIS CAMPAIGNS AND HOW 1354 00:51:43,320 --> 00:51:44,640 EARLY TO GIVE ANTIBIOTICS WILL 1355 00:51:44,640 --> 00:51:46,040 CONTINUE TO BE IMPORTANT AS WELL 1356 00:51:46,040 --> 00:51:49,720 AS KNOWING ABOUT TARGETS OTHER 1357 00:51:49,720 --> 00:51:51,600 THAN JUST INHIBITING THE 1358 00:51:51,600 --> 00:51:53,520 PROTECTIVE ANTIGEN LOOKING FOR 1359 00:51:53,520 --> 00:51:54,160 OTHER TARGETS. 1360 00:51:54,160 --> 00:51:59,120 AND FINALLY WITH THE FOURTH 1361 00:51:59,120 --> 00:52:00,720 QUESTION, THE SEQUELAE, WE HAD A 1362 00:52:00,720 --> 00:52:02,400 PROTOCOL IN PLACE AT OUR CLINIC 1363 00:52:02,400 --> 00:52:03,720 AT NIH FOR MANY YEARS AND 1364 00:52:03,720 --> 00:52:06,520 FOLLOWED A SUBSET OF THE 2001 1365 00:52:06,520 --> 00:52:07,440 SURVIVORS. 1366 00:52:07,440 --> 00:52:09,920 WE SEE WITH 4 ADULT MALES ALL 4 1367 00:52:09,920 --> 00:52:17,920 OF OUR ADULT MALES SHOWED 1368 00:52:17,920 --> 00:52:18,640 EVIDENCE OF SUSTAINED--LOW 1369 00:52:18,640 --> 00:52:20,120 GROWTH HORMONE AND THIS WAS SEEN 1370 00:52:20,120 --> 00:52:23,000 AS EARLY AS 4 MONTHS AFTER 1371 00:52:23,000 --> 00:52:24,280 INFECTION AND PERSISTED AS LONG 1372 00:52:24,280 --> 00:52:25,920 AS 10 YEARS WITHOUT TREATMENT 1373 00:52:25,920 --> 00:52:27,520 AND CERTAINLY THIS HAS BEEN 1374 00:52:27,520 --> 00:52:30,080 OBSERVED AFTER OTHER INFECT YOWZ 1375 00:52:30,080 --> 00:52:31,480 DISEASES AND AFTER TRAUMATIC 1376 00:52:31,480 --> 00:52:34,440 BRAIN INJURY BUT IT'S THE FIRST 1377 00:52:34,440 --> 00:52:36,000 TIME DESCRIBED IN ANTHRAX. 1378 00:52:36,000 --> 00:52:37,320 SO IN SUMMARY, YOU KNOW WE WOULD 1379 00:52:37,320 --> 00:52:41,320 LIKE TO SAY, THAT THE ANTHRAX 1380 00:52:41,320 --> 00:52:44,000 LETTER ATTACKS OF 2001 REVEALED 1381 00:52:44,000 --> 00:52:45,840 THE URGENT NEED TO UNDERSTAND 1382 00:52:45,840 --> 00:52:48,640 OLD PATHOGENS USING CURRENT 1383 00:52:48,640 --> 00:52:49,560 MEDICAL TOOLS WHICH CHANGE OVER 1384 00:52:49,560 --> 00:52:53,120 TIME AND WHEN WE LOOK AT TODAY 1385 00:52:53,120 --> 00:52:53,960 COMPARED TO 2001 FOR EXAMPLE. 1386 00:52:53,960 --> 00:52:56,920 IN THE ABSENCE OF HUMAN TRIALS, 1387 00:52:56,920 --> 00:52:58,640 ANIMAL STUDIES PLAY A PIVOTAL 1388 00:52:58,640 --> 00:53:00,600 ROLE IN INFORMING PUBLIC HEALTH 1389 00:53:00,600 --> 00:53:02,080 POLICY DECISIONS, THE INVEST 1390 00:53:02,080 --> 00:53:04,640 EXPMENT BIODEFENSE AND EMERGING 1391 00:53:04,640 --> 00:53:05,480 INFECTIOUSS RESEARCH STRUCTURE 1392 00:53:05,480 --> 00:53:08,080 AND IN MECHANISMS SUCH AS THE 1393 00:53:08,080 --> 00:53:09,640 ANIMAL ROLE HAVE MADE RAPID 1394 00:53:09,640 --> 00:53:12,800 DISCOVERY POSSIBLE YEARS LATER 1395 00:53:12,800 --> 00:53:14,200 IN EBOLA AND SARS-COV-2 1396 00:53:14,200 --> 00:53:15,040 RESEARCH. 1397 00:53:15,040 --> 00:53:17,440 WE WOULD LIKE TO ACKNOWLEDGE ALL 1398 00:53:17,440 --> 00:53:19,720 OF OUR COLLABORATORS AT USA 1399 00:53:19,720 --> 00:53:21,440 MRID, AND CDC, WE WERE 1400 00:53:21,440 --> 00:53:23,080 ESPECIALLY INVOLVED WITH THE 1401 00:53:23,080 --> 00:53:24,000 CLINDA MICEIN PAPER. 1402 00:53:24,000 --> 00:53:28,440 OUR GROUP AT NIAID AND THE 1403 00:53:28,440 --> 00:53:30,320 CLINIC AND THE TEAM WHICH 1404 00:53:30,320 --> 00:53:31,120 CLASSIFIES FOLKS FROM 1405 00:53:31,120 --> 00:53:33,240 ENDOCRINOLOGY AND OTHER GROUPS, 1406 00:53:33,240 --> 00:53:34,240 ANTHRAX STUDY PARFISCHER PANTS 1407 00:53:34,240 --> 00:53:36,600 AND THEN I WOULD LIKE TO 1408 00:53:36,600 --> 00:53:42,520 PERSONALLY THANK DR. VIETRI AND 1409 00:53:42,520 --> 00:53:44,240 DR. FRIEDLANDER, FOR ALL OF YOUR 1410 00:53:44,240 --> 00:53:44,920 COLLABORATION, VISION, HOURS 1411 00:53:44,920 --> 00:53:46,200 TOGETHER AND OUR FRIENDSHIP. 1412 00:53:46,200 --> 00:53:50,080 THANK YOU AND WITH THAT, WE WILL 1413 00:53:50,080 --> 00:53:51,600 TURN IT OVER FOR ANY QUESTIONS 1414 00:53:51,600 --> 00:53:54,960 IF THERE'S ENOUGH TIME 1415 00:53:54,960 --> 00:53:56,080 REMAINING. 1416 00:53:56,080 --> 00:53:57,040 >> THERE ACTUALLY IS, DR. WRIGHT 1417 00:53:57,040 --> 00:54:00,720 AND THANK YOU DR. WRIGHT, 1418 00:54:00,720 --> 00:54:02,800 DR. FRIEDLANDER AND DR. VIETRI, 1419 00:54:02,800 --> 00:54:04,480 THIS WAS OBVIOUSLY TO ME A 1420 00:54:04,480 --> 00:54:07,280 FASCINATING TOPIC AND I THINK 1421 00:54:07,280 --> 00:54:08,920 YOUR PRESENTATION ILLUSTRATED 1422 00:54:08,920 --> 00:54:11,520 WELL THE COMPLEXITY OF ANTHRAX, 1423 00:54:11,520 --> 00:54:13,120 NOT JUST THE SYMPTOMS BUT THE 1424 00:54:13,120 --> 00:54:14,080 REGAFERREDS TO TREATMENT, ISSUES 1425 00:54:14,080 --> 00:54:17,360 OF TIMING THROUGHOUT THE 1426 00:54:17,360 --> 00:54:18,160 TREATMENTS, PATIENTS AND THE 1427 00:54:18,160 --> 00:54:21,520 LENGTH AND COURSE OF THERAPIES. 1428 00:54:21,520 --> 00:54:26,680 SO, A COUPLE OF QUESTIONS, 1, SO 1429 00:54:26,680 --> 00:54:29,120 AND THIS GETS TO SOMETHING I'M A 1430 00:54:29,120 --> 00:54:35,640 LITTLE FAMILIAR WITH, WITH THIS 1431 00:54:35,640 --> 00:54:36,440 OCCURRING VACCINE SCHEDULE, IT'S 1432 00:54:36,440 --> 00:54:38,880 NOT 1 AND DONE, IF INVOLVES A 1433 00:54:38,880 --> 00:54:39,720 SERIES, COULD YOU DESCRIBE LAWN 1434 00:54:39,720 --> 00:54:40,720 MOWER A CURRENT LOOKS LIKE AND 1435 00:54:40,720 --> 00:54:42,280 FOR THOSE THAT ARE INFECTED, 1436 00:54:42,280 --> 00:54:45,960 WHAT WOULD THAT LOOK LIKE? 1437 00:54:45,960 --> 00:54:51,440 >> SO MAYBE I CAN ANSWER THAT OR 1438 00:54:51,440 --> 00:54:53,040 START. 1439 00:54:53,040 --> 00:54:57,440 THE CURRENT RECOMMENDATIONS ARE 1440 00:54:57,440 --> 00:55:02,560 FOR PROPHYLACTIC USE OF THE 1441 00:55:02,560 --> 00:55:04,920 VACCINATION. 1442 00:55:04,920 --> 00:55:07,640 THE SCHEDULE IS NOW 0. 1443 00:55:07,640 --> 00:55:09,600 THE FIRST DOSE IS FOLLOWED BY A 1444 00:55:09,600 --> 00:55:12,120 DOSE 1 MONTH LATER, THEN 6 1445 00:55:12,120 --> 00:55:14,440 MONTHS LATER AND 12 MONTHS LATER 1446 00:55:14,440 --> 00:55:16,520 AND THEN 18 MONTHS LATER. 1447 00:55:16,520 --> 00:55:21,080 SO IT'S 0, 1, 6 MONTHS. 1448 00:55:21,080 --> 00:55:24,200 AND IT'S GIVEN INTRA MUSCULARLY. 1449 00:55:24,200 --> 00:55:26,080 NOW, FOR POST EXPOSURE 1450 00:55:26,080 --> 00:55:29,000 PROPHYLAXIS, SO THIS RESULTS IN 1451 00:55:29,000 --> 00:55:31,480 A--IN AN IMMUNE RESPONSE THAT 1452 00:55:31,480 --> 00:55:34,840 DEVELOPS, BUT FOR POST EXPOSURE 1453 00:55:34,840 --> 00:55:37,760 PROPHYLAXIS, THE RECOMMENDATION 1454 00:55:37,760 --> 00:55:40,880 STILL REMAIN TO GIVE THE VACCINE 1455 00:55:40,880 --> 00:55:44,720 MORE FREQUENTLY, THAT IS AT 0 1456 00:55:44,720 --> 00:55:48,840 DAYS, AT 2 WEEKS, AND AT 1 1457 00:55:48,840 --> 00:55:51,640 MONTH, THEN 6 MONTHS, 12 MONTHS, 1458 00:55:51,640 --> 00:55:57,080 18 MONTHS AND THAT ROUTE IS 1459 00:55:57,080 --> 00:55:58,520 GIVEN SUBCUTANEOUSLY BECAUSE 1460 00:55:58,520 --> 00:56:03,720 BOTH THE EXTRA DOSE AT 2 WEEKS 1461 00:56:03,720 --> 00:56:06,800 AND THE ROUTE SUBCUTANEOUS 1462 00:56:06,800 --> 00:56:08,360 VERSUS INTRA MUSCULAR RESULTS IN 1463 00:56:08,360 --> 00:56:13,480 A MORE RAPID AND HIGHER IMMUNE 1464 00:56:13,480 --> 00:56:14,080 RESPONSE. 1465 00:56:14,080 --> 00:56:17,280 SO, FOR PROPHYLAXIS AS I SAID 01 1466 00:56:17,280 --> 00:56:20,480 FOR MONTH FOR I. M. AND MOST 1467 00:56:20,480 --> 00:56:22,040 EXPOSURE VACCINATION AS WE 1468 00:56:22,040 --> 00:56:26,120 DESCRIBE IN THESE STUDIES, IT'S 1469 00:56:26,120 --> 00:56:29,520 STILL 02 AND THEN 4 WEEKS GET IN 1470 00:56:29,520 --> 00:56:31,920 SUBCUTANEOUSLY, NOW THERE IS 1471 00:56:31,920 --> 00:56:35,320 EFFORT UNDERWAY USING ADDITIONAL 1472 00:56:35,320 --> 00:56:40,400 VACCINE FORMULATIONS WITH OTHER 1473 00:56:40,400 --> 00:56:41,320 ADJUVANTS. 1474 00:56:41,320 --> 00:56:44,440 TO TRY TO DEVELOP A NEW VACCINE, 1475 00:56:44,440 --> 00:56:46,280 THAT'S NOT GIVEN SUBCUTANEOUSLY 1476 00:56:46,280 --> 00:56:54,560 AND THAT'S A GIVEN IN A LESS 1477 00:56:54,560 --> 00:56:55,240 FREQUENT DOSAGE. 1478 00:56:55,240 --> 00:56:55,760 >> THANK YOU VERY MUCH. 1479 00:56:55,760 --> 00:57:00,520 ONE OTHER QUESTION HERE, SO 1480 00:57:00,520 --> 00:57:02,200 ANTHRAX ENTERED THE PUBLIC 1481 00:57:02,200 --> 00:57:04,520 CONSCIOUSNESS WITH THE ANTHRAX 1482 00:57:04,520 --> 00:57:08,440 ATTACKS OF 2001, SO WHAT IS THE 1483 00:57:08,440 --> 00:57:09,360 SOPHISTICATION OF MANUFACTURING 1484 00:57:09,360 --> 00:57:13,680 CAPABILITY THAT'S REQUIRED TO 1485 00:57:13,680 --> 00:57:14,520 CREATE SIGNIFICANT QUANTITIES OF 1486 00:57:14,520 --> 00:57:15,920 SPORES AND WHAT'S THE CURRENT 1487 00:57:15,920 --> 00:57:24,920 RISK OF A ROGUE LABORATORY-- 1488 00:57:24,920 --> 00:57:28,400 >> DO YOU WANT TO TAKE THAT? 1489 00:57:28,400 --> 00:57:31,600 >> YEAH, WELL, THAT'S A BIG 1490 00:57:31,600 --> 00:57:33,120 UNKNOWN. 1491 00:57:33,120 --> 00:57:36,760 I THINK UNFORTUNATELY THERE'S A 1492 00:57:36,760 --> 00:57:39,040 LONG, LONG HISTORY OF THE USE OF 1493 00:57:39,040 --> 00:57:43,480 NOT JUST ANTHRAX BUT CERTAINLY 1494 00:57:43,480 --> 00:57:44,880 ANTHRAX THAT GOES BACK 1495 00:57:44,880 --> 00:57:48,360 UNFORTUNATELY A VERY LONG TIME 1496 00:57:48,360 --> 00:57:50,040 FROM MANY COUNTRIES INCLUDING 1497 00:57:50,040 --> 00:57:53,120 THE U.S. IN TERMS OF USING 1498 00:57:53,120 --> 00:57:55,240 POTENTIALLY USING IT AND THEN OF 1499 00:57:55,240 --> 00:57:58,280 COURSE, THE BIOLOGICAL WEAPONS 1500 00:57:58,280 --> 00:57:58,720 CONVENTION WAS SIGNED. 1501 00:57:58,720 --> 00:58:01,000 SO IN TERMS OF--WE'VE SEEN WHAT 1502 00:58:01,000 --> 00:58:03,640 THE LETTER VS DONE IN JUST A 1503 00:58:03,640 --> 00:58:04,280 HANDFUL OF LETTERS. 1504 00:58:04,280 --> 00:58:11,200 I THINK THE CONSENSUS IS FOR A 1505 00:58:11,200 --> 00:58:12,560 LARGE SCALE EXPOSURE THAT 1506 00:58:12,560 --> 00:58:19,480 REQUIRES A GREAT DEAL OF 1507 00:58:19,480 --> 00:58:19,840 SOPHISTICATION. 1508 00:58:19,840 --> 00:58:21,440 >> OKAY, I DON'T BELIEVE WE HAVE 1509 00:58:21,440 --> 00:58:26,040 ANY MORE QUESTIONS COMING IN. 1510 00:58:26,040 --> 00:58:29,520 AND WE STILL HAVE 2 MINUTES TO 1511 00:58:29,520 --> 00:58:31,160 SPARE, SO, YOU HAVE ANSWERED ALL 1512 00:58:31,160 --> 00:58:33,920 THE QUESTIONS FOR OUR AUDIENCE, 1513 00:58:33,920 --> 00:58:36,920 AND SO WITH THAT I WILL GIVE IT 1514 00:58:36,920 --> 00:58:42,040 BACK FOR 2 MINUTES TO SET UP OUR 1515 00:58:42,040 --> 00:58:43,680 CLOSING, AGAIN, I WANT THANK ALL 1516 00:58:43,680 --> 00:58:46,640 OF YOU ON BEHALF OF THE 1517 00:58:46,640 --> 00:58:47,280 COMMUNITY FOR SHARING YOUR 1518 00:58:47,280 --> 00:58:49,760 RESEARCH AND MANY YEARS OF 1519 00:58:49,760 --> 00:58:51,840 COLLABORATION WHICH CLEARLY ARE 1520 00:58:51,840 --> 00:58:54,160 SIGNIFICANT IMPORTANCE NOT ONLY 1521 00:58:54,160 --> 00:58:56,600 FOR THE RESEARCH INFECTIOUS 1522 00:58:56,600 --> 00:58:58,520 DECEASE DISEASES BUT ALSO FOR 1523 00:58:58,520 --> 00:59:00,360 PUBLIC AND BI ONY EEIVETS. 1524 00:59:00,360 --> 00:59:01,520 SO THANK YOU VERY MUCH AND I 1525 00:59:01,520 --> 00:59:02,000 WISH EVERYBODY A GOOD AFTERNOON. 1526 00:59:02,000 --> 01:00:27,520 >> THANK YOU.