Articles, Blog

2018 Demystifying Medicine: Sexually Transmitted Diseases: situation getting worse…and also better

March 10, 2020


>>GOOD AFTERNOON. WE HAVE A SMALLER THAN USUAL GROUP TODAY. I GUESS WORD DIDN’T GET OUT GUT I WANT TO BRING TO YOUR ATTENTION EACH WEEK THERE’S PEOPLE WATCHING THIS PROCEEDING LIVE. SO WHEN YOU ASK QUESTIONS FOR EXAMPLE, WE ASK YOU TO USE A MICROPHONE AND SPEAK LOUDLY, NOT TO MAKE A SPEECH WRITE TO ME AND SAY WE HEARD THE ANSWER BUT WE DON’T KNOW WHAT THE QUESTION WAS. AT ANY RATE — THIS IS THE BROOKLYN BRIDGE AND THE LOGO FOR THIS COURSE. THE WHOLE IDEA IS LIFE ON THE OTHER SIDE OF THE BRIDGE IS NEVER THE SAME. I THINK PEOPLE THINK THE CHALLENGES IN SCIENCE IS TO COMMUNICATE THE CHALLENGES IN BASIC ENGINEERING AND MATHEMATICAL SCIENCES WITH HUMAN HEALTH AND WITH THAT YOU HAVE TO SPEAK SOME COMMON LANGUAGE AND THAT’S NOT ALWAYS READILY ACCESSIBLE. AND IN THESE DAYS THEY HAD TO WALK THE CATWALK. WE TRY TO PRESENT LIVE PATIENTS HALF THE TIME. INTERESTINGLY ENOUGH, AMONG MANY OF THE AUDIENCE WHICH ARE Ph.D. STUDENTS AND FELLOWS IT PUTS A HUMAN FACE ON DISEASE AND THAT’S WHAT WE’RE DOING. NOT TO INFORM YOU OR OVERLOAD YOU WITH FACT AND FIGURES YOU HAVE TO MEMORIZE. BUT TO INSTILL THE EXCITEMENT WITH THE CHALLENGES FROM A CLINICAL STANDPOINT AND FROM A BASIC FUNDAMENTAL BASIS. IT’S THAT COMMUNICATION BRIDGE WE’RE TRYING TO BRIDGE.>>SOMEWHERE ALONG THE LINES ENEREAL DISEASE CHANGE TO SEXUALLY TRANSMITTED DISEASES. JUST A COUPLE NOTES I HAVE FOUND INTERESTING HERE, THE HISTORY OF VENEREAL DISEASE IS LOADED FROM GREAT SUCCESSES AND FAILURES AND THE IMPACT ON HUMAN HISTORY. IN THE 18th CENTURY, JOHN HUNTER WHO IS FAMOUS BUT HE WAS THE FATHER OF VACCINATION. HE BELIEVED SYPHILIS AND GONORRHEA WAS THE SAME DISEASE AND INFECTED VOLUNTEERS WITH BOTH AND SO DID HE AND FOUND SYPHILIS COULD BE CONTRACT HEAVY METALS AND LED TO THE OUTCOME OF ONE NIGHT WITH VENUS AND LIFE TIME WITH MERCURY. IT WAS A FORM OF MEDICINE IN WESTERN EUROPE DURING THE 18th CENTURY. THE DISCOVERY OF POPULARIZED MAGIC THE 606th COMPOUND IN ORGANIC WHICH KILLED CULTURES AND RABBITS AND PEOPLE SHIFTED THE FIELD ENTIRELY. IT WASN’T UNTIL THE DISCOVERY OF PENICILLIN THAT SYPHILIS AND GONORRHEA TOOK A BACK SEAT. THERE WERE THINGS IN THE NERVOUS SYSTEM AND THOSE THINGS HAVE DISAPPEARED. THEY HAVEN’T SEEN IT ANYMORE. THE DISEASE IN ITSELF HAS CHANGED. SIMILARLY WITH GONORRHEA. BUT IT DID CREATE A SITUATION WHERE PEOPLE BELIEVED THAT ALL YOU HAD TO DO WAS TAKE SOME PENICILLIN AND GO ABOUT LIFE WITH FREE ABANDON WHICH HAS TURNED OUT NOT TO BE THE CASE. THEN ADD ON TOP OF IT, OF COURSE, THE GLOBAL CHALLENGES AND THE REALIZATION THAT VENEREAL DISEASES AND SEXUALLY TRANSMITTED DISEASES ARE MORE THAN BACTERIA. BY THE WAY, THE PERSON WHO DISCOVERED GONORRHEA DISCOVERED HIS ORGANISM WAS THE CAUSE OF THE DISEASE BY GIVING IT TO HUMAN VOLUNTEERS. I DON’T THINK THEY KNEW WHAT THEY WERE VOLUNTEERING FOR THAT WAS THE STATUS OF CLINICAL INVESTIGATION IN THE EARLY 18th CENTURY. AND THE DISCOVERY OF HIV AND HPV ARE ASSOCIATED WITH CANCER, BEGAN TO CHANGE THINGS BECAUSE THEY’RE IN PART SEXUALLY TRANS MITD AND — TRANSMITTED AND THE DEVELOPMENT OF CHLAMYDIA AND HERPES BEING DRUG-RESISTANT AND A LOSS IN PUBLIC EDUCATION WHERE IN SOME PARTS OF THE WORLD PEOPLE KNEW ABOUT SEXUALLY TRANSMITTED DISEASES BUT IN OTHER PARTS THEY WERE DEPRIVED OF IT INCLUDING TO SOME EXTENT HERE. AND A MAJOR TOPIC OF THIS AFTERNOON’S CONVERSATION ARE BASED ON THE DISCOVERY OF HUMAN PAPILLOMA VIRUS BY HARALD SUR HAUSEN AND BASED ON THAT THE NIH HAS SPENT THE PAST MANY YEARS TAKING ADVANTAGE OF THE DISCOVERY TO DEVELOP EFFECTIVE VACCINES AGAINST FORMS OF HPV THAT ARE PRE VEN — PREVENTATIVE IN HUMAN CANCER. BOTH SPEAKERS ARE LEADERS IN BOTH ARENAS. THE FIRST SPEAKER, TOM QUINN IS IN THE NIAID AND AN NIH DISTINGUISHED INVESTIGATOR AND HEADS THE SECTION ON INTERNATIONAL HIV AND SEXUALLY TRANSMITTED RESEARCH IN NAID AND IS ALSO A PROFESSOR AT HOPKINS AND HE’S THE DIRECTOR OF THE HOPKINS CENTER FOR GLOBAL HEALTH. HIS STUDIES HAVE BEEN EXTENSIVE BOTH EPIDEMEOLOGIC AND DOUG LOWY HAS BEEN THE DEPUTY DIRECTOR OF THE NCI FROM APRIL OF 2015 UNTIL THIS COMING OCTOBER. HE’S BEEN THE ACT BEING DIRECTOR OF THE NCI. HE GRADUATED THE NEW YORK UNIVERSITY SCHOOL OF MEDICINE THEN STANFORD AND YALE. CAME HERE IN 1975 AND SINCE THEN HE AND JOHN SCHILLER HAVE DIRECTED THEIR ATTENTION BOTH TO THE DEVELOPMENT OF EFFECTIVE HPV VACCINES AND UNDERSTANDING THE MECHANISMS BY WHICH THEY MAY ACT. WE LOOK FORWARD TO YOUR TALKS. THANK YOU FOR BEING WITH US.>>THANK YOU VERY MUCH. IT’S A PLEASURE TO BE HERE. I REALLY APPRECIATED YOUR HISTORICAL PERSPECTIVE ON THE TOPIC WE’RE GOING TO BE TALKING ABOUT FOR THE NEXT HOUR. SEXUALLY TRANSMITTED DISEASES SOMETIMES NOW REFERRED TO AS SEXUALLY TRANSMITTED INFECTIONS, AS THEY’RE NOT ALWAYS SYMPTOMATIC HAVE BEEN A MAJOR PROBLEM IN MORBIDITY AND MORTALITY IN HUMANS FOR AS LONG AS WE KNOW. THE WORLD HEALTH ORGANIZATION HAS TRIED TO ENUMERATE HOW BIG OF A PROBLEM THIS IS AND POSTULATED 1 MILLION PEOPLE WITH ACQUIRE SEXUALLY TRANSMITTED DISEASES A DAY AND OVER 350 MILLION ON AN ANNUAL BASIS. OF THE 350 MILLION, MOST OF THOSE ARE AMONG FOUR CURABLE DISEASES WE COULD DIAGNOSE AND TREAT IF THERE WAS ENOUGH PUBLIC HEALTH ATTENTION TO THESE BOTHERSOME INFECTIONS AND 500 MILLION PEOPLE IN THE WORLD ARE ESTIMATE TO HAVE GENTLE HERPES, HPV AND OVER 290 MILLION WOMEN GLOBALLY AND UNFORTUNATELY SYPHILIS WHICH HAS BEEN WITH US AS LONG AS MANKIND’S BEEN AROUND. RIGHT NOW IN THE PAST YEAR, ALMOST 1 MILLION PREGNANT WOMEN WERE INFECTED WITH SYPHILIS AND WERE NOT TREAT AND RESULT IN 350,000 ADVERSE BIRTHS BEING EXPOSED AND THE STDs ARE INCREASING RESISTANCE AND GONORRHEA HAS CAUGHT THE PUBLIC’S ATTENTION AS A SUPER BUG, AS THEY LIKE TO REFER TO IN THE PRESS, BECAUSE IT HAS ACQUIRED RESISTANCE TO OUR STANDARD ANTIBIOTIC. IF ONE LOOKS AT THE GLOBE AND THEN U.S. CHLAMYDIA A BACTERIA STD WHICH IS THE MOST COMMONLY REPORTED BACTERIAL INFECTION TO THE CDC ON AN ANNUAL BASIS WORLDWIDE EXISTS AT ABOUT $131 — 131 MILLION, GONORRHEA, 78 MILLION, SYPHILIS, 6 MILLION NEW INFECTIONS A YEAR AND A NEW PARASITIC ONE VAGINALIS, 1.4 MILLION. OF COURSE THAT DOESN’T COUNT THE VIRAL STIs I ALREADY REFERRED TO. LET’S TURN OUR ATTENTION TO OUR COUNTRY. RIGHT NOW IN THE UNITED STATES IT’S ESTIMATED MORE THAN 20 MILLION PEOPLE WILL AREQUIRE BOTH BACTERIAL AND VIRAL STIs EACH YEAR. 2 MILLION CASES OF THE THREE NATIONALLY REPORTED STLs, CHLAMYDIA AND GONORRHEA AND CIVIL IS WERE REPORTED. THAT’S THE HIGHEST REPORTED EVER. SO WE ARE SEEING RISES AND THAT’S WHAT I WANT TO SPEND MOST OF MY TIME COMING ACROSS IN HAVING AN IMPACT OF WHAT THESE DISEASES ARE DOING. WHO GETS THEM IS THE FIRST QUESTION? MOSTLY PEOPLE UNDER 25 YEARS OF AGE. MORE THAN HALF ARE IN THE YOUNG ADOLESCENT, YOUNG ADULT AGES. UNFORTUNATELY, THEY ALSO HAVE A DIRECT IMPACT OR SIGNIFICANT HEALTH DISPARITY WITH THE RATES OFTEN TEN TIMES HIGHER IN AFRICAN AMERICANS AND THEY INCREASE THE BACTERIAL AND SOME OF THE OTHER VIRAL ONES LIKE HERPES, INCREASE THE RISK OF ACQUIRING HIV WHICH WE HAVE ALREADY HEARD FROM DR. FAUCHI AND OTHERS ABOUT ITS IMPACT. THE COST, IF ONE WAS TO TAKE THIS TO CAPITOL HILL, HOW MUCH ARE WE SPEND ONG THESE STDs TO DIAGNOSE AND TREAT IN THE ADVERSE COMPLICATIONS. THE ECONOMISTS COME UP WITH THE RANGE OF $16 BILLION ANNUALLY. UNFORTUNATELY, BECAUSE OF SHIFTS IN FEFS EMPHASIS IN SCREENING IS POSING A PROBLEM AND COULD BE CONTRIBUTING TO THE RISE IN STDs. THIS MIXED THE STDs AND STIs. SUCHLY TRANSMITTED INFECTION. AT THE TOP IS SYPHILIS. HIV, SOMEWHERE BETWEEN 40,000 AND 55,000 CASES AS A VIRAL STI. THEN HAVE YOU HEPATITIS B THOUGH WE HAVE A GREAT VACCINE WE STILL SEE 70,000 TO 80,000 NEW CASES. MOST ACQUIRED THROUGH SEXUAL MEANS. THEN WE ALREADY TALKED ABOUT GONORRHEA, CHLAMYDIA, HERPES, WE’RE GOING HEAR ABOUT HUMAN PAPILLOMA VIRUS AND THEN OF COURSE THE ORGANISM THAT CAUSES VAGINITIS TRICHOMONIS. WE KNOW THE FILOVIRUSES ARE BEING TRANSMITTED SEXUALLY AND NOW BEING LISTED ALONG WITH 30 OTHER PATHOGENS AS NEWLY RECOGNIZED STIs. SO EBOLA AND MARBURG HAVE BEEN SHOWN TO PERSIST IN SEMEN OF MEN AND SHOWN TO TRANSMIT MOSTLY FROM MEN TO WOMEN. ZIKA VIRUS, WHICH CAUGHT THE PUBLIC’S ATTENTION, THERE’S BEEN STUDIES DOCUMENTING SEXUAL TRANSMISSION AND PRESENCE IN THE SEMEN FOR OVER 180 DAYS AND SOME LONGER. THIS ONE PAPER I THOUGHT I’D BRING OUT IS EBOLA HAS BEEN SHOWN TO BE TRANSMIT AND PRESENT IN THE SEMEN OVER 500 DAYS IN THE SURVIVORS OF EBOLA. SO EBOLA DOESN’T KILL YOU WHEN YOU SURVIVE FROM IT AND WE’VE INCREASED THE SURVIVAL RATE. IT PERSIST IN THOSE DEVELOPEDS IN IMMUNOLOGICALLY PRIVILEGED SITE AND BEING TRANSMIT. THIS SAY PAPER RECENTLY PUBLISHED IN THE NEW ENGLAND JOURNAL OF MEDICINE SHOWN IN THE RED. AND THEN IT STARTS TO DROP OFF AS YOU GET OUT 13, 15 MONTHS OUT. YOU HAVE TO ASSUME THE POTENTIAL FOR TRANSMISSION SEXUALLY COULD OCCUR FOR AT LEAST ONE YEAR AND YOU TAKE THE PROPER PRECAUTIONS TO PREVENTING THAT. THEY NEED TO ABSTAIN FROM SEX FOR A MINIMUM OF THREE MONTHS, IF NOT LONGER, NOW THE RECOMMENDATIONS ARE BEING REVIVED CASE I JUST MENTION. IF ACCIDENTS ARE IMPOSSIBLE, CONDOMS ARE MANDATORY IN THOSE CASE. WHAT ABOUT ZIKA. THERE’S BEEN MULTIPLE CASES IN IN THE LITERATURE ABOUT SEXUAL TRANSMISSION OF ZIKA. IN THE U.S., 5 CLEAR-CUT DOCUMENTED CASES BUT MANY OTHER COUNTRIES BESIDES THE U.S. HAVE REPORTED CASES. WHERE THAT’S A CONCERN IS IF A COUPLE IS PLANNING ON CONCEIVING PREGNANCY AND WHAT THEY NEED TO DO IF THE MAN — IN THIS CASE, HAS TRAVELED ABROAD AND MAY HAVE GOTTEN EXPOSED TO THE DEE — ZI ZIKA VIRUS. IT SHOWS YOU SHOULD DELAY PREGNANCY IF THE MAN HAS BEEN SHOWN TO HAVE ACQUIRED ZIKA. TO PLAY IT SAFE. THEY SHOULD ABSTAIN OR USE CONDOMS. AND AFTER A PERIOD THEY COULD RECHECKED AND THEN ATTEMPTS OF THE COUPLE CAN BE STARTED AGAIN. THAT’S THE EPIDEMIOLOGIC PIECE. THE NEXT PART IS WHAT DO THEY CAUSE? THE VAST MAJORITY ARE ASYMPTOMATIC. AND THE NATIONAL ACADEMY OF MEDICINE CAME OUT WITH THE HIDDEN PROBLEM OF TRANSMITTED INFECTIONS IN THE LATE ’90s. SOME, AS SHOWN ON THE SLIDES, DO CAUSE SYMPTOMATIC DISEASE, SYPHILIS, HERPES, CERVIXITIS AND PROCTITIS AND THE SAME BACTERIAL STDs AS IN HERPES AND SYPHILIS AND EVEN THOSE WHO ENGAGE IN ORAL GENITAL SEX YOU CAN GET FARN — FARN WE DON’T HAVE THE TIME TO GO THROUGH EVERY ONE. AND THE SECOND TALK WILL REALLY FOCUS IN ON THE CLINICAL SYNDROMES OF HPV AND HOW THEY CAN BE PREVENTED. WHY SHOULD THEY BE A CONCERN FOR YOUNG PEOPLE? BESIDES THE CLINICAL SYNDROMES, STDs CAN MIGRATE TO THE UPPER FALLOPIAN TUBE AND CAUSE A TRACT INFECTION ESPECIALLY FOR WOMEN AND IF THERE’S SCARRING IT LEADS TO INFERTILITY AND ECTOPIC PREGNANCY AND PELVIC PAIN AND CAN CAUSE LOW BIRTH WEIGHT FOR PREGNANT WOMEN OR ABORTION. OF COURSE, STIs CAN ENHANCE THE TRANSMISSION OF AND THAN BE TRANSLATED IN THE CASE OF SYPHILIS TO THE NEWBORNS CLASSIFIED AS CONGENITAL INFECTION AND HPV AND PERHAPS OTHER STIs CAN CAUSE A VARIETY OF CANCERS IN THE CASE OF HPV, CERVICAL CANCER. THIS IS NOT DECLINING OR FLAT LINING, IT’S CONTINUING TO GO UP. WHEN I REFER TO STIs I REFER TO GRAPHICS AND IT’S INCREASING MORE IN WOMEN THAN IN MEN BUT ALSO INCREASING IN MEN AS WELL. WE TALKED ABOUT THE NUMBERS WORLDWIDE. AND THERE’S HIGH RATES OF PARTNERS AND INFFECTED INDIVIDUALS. AND YOU CAN GET PERREE PERINATAL TRANSMISSION AND YOU CAN GET ECTOPIC PREGNANCY AND THAT PELVIC PAIN. I MENTIONED IT’S MORE COMMON IN WOMEN THAN IN MEN. THIS IS AN AGE DISTRIBUTION. IF YOU LOOK HERE, THIS IS 15 TO 19-YEAR-OLDS, ALREADY YOU’RE SEEING A PREVALENCE — I CAN TELL YOU IN BALTIMORE, OF ALREADY 10% GOING UP TO 20% IN 20 TO 24-YEAR-OLDS. SO IT HITS THE YOUNG WOMEN AND DROP OFF IN THE OLDER E IT DOES
– POPULATION. EITHER THEIR SEXUAL PATTERNS HAVE CHANGE ORDER IT’S A REFLECTION OF IMMUNITY BECAUSE SO MANY PEOPLE GOT EXPOSED. I STARTED WORK HERE IN THE NIH ON MALARIA AND SHIFT TO CHLAMYDIA AND I WAS SHOCKED BY HOW SIM LOOR THE — SIMILAR THE LIFE CYCLE WAS. THE LIFE CYCLE FOR BOTH IS LIKE 48 TO 72 HOURS, GOES THROUGH A LIFE CYCLE WHERE IT’S TAKEN UP AND CONVERTED. WE CALL IT AN ELEMENTARY BODY ANDRETICULATE BODY AND LYSIS THE CELL. THIS ONE IS IN A DIFFERENT CELLULAR MAKE UP. IT’S EPITHELIAL CELLS AND WHAT YOU’LL FIND IS THESE TINY ELEMENTARY BODIES. AND THERE’S SECRETIONS OF THE GENIT GENITALIA DURING INTERCOURSE THEY’RE TRANSMITTED AND THUS YOU GET THE INFECTION. WE CAN TAG IT AND YOU SEE THE ELEMENTARY BODIES PRESENT AND WHAT WE CALL CERVICAL SWAP OR YOU’RE URETHRA SWAP. MOST MEN AND WOMEN, PROBABLY 80% ARE ASYMPTOMATIC. THEY DON’T GO RUNNING TO THE PHYSICIAN OR HEALTH CARE PROVIDER TO GET DIAGNOSED OR TREATMENT BECAUSE OF A DISCHARGE OR SOME OTHER AILMENT. SO IF YOU DON’T DO ROUTINE SCREENING FOR INDIVIDUALS ESPECIALLY THE YOUNG GROUP, YOU’LL MISS IT. SOME DEVELOP AN URETHRAL DISCHARGE. AND WE DON’T HAVE A VACCINE TO PREVENT EITHER OF THESE CLINICAL SYNDROMES OF CHLAMYDIA. FOR WOMEN, THE MAJORITY, NO SIGNS OR SYMPTOMS BUT SOME, 20% WILL DEVELOP CERVICITIS AND IT CAN MIGRATE AND CALL IN INFLAMMATORY DISEASE IN THE FALLOPIAN TUBE. AND THIS SHOWS THE THREE AREAS CHLAMYDIA LOVE TO INFECT. THIS RIGHT HERE CAUSING THE CERVICITIS OR MIGRAINES UP IN THE ASYMPTOMATIC PEOPLE AND MAY CAUSE A MORE SYSTEMATIC DISEASE ANALYST UPPER REPRODUCTIVE TRACT CAUSING THE INFERTILITY OR ECTOPIC PREGNANCY. THIS IS WHAT HAPPENS TO THOSE INDIVIDUALS. THESE ARE UNIQUE PHOTOGRAPHS LOOK INSIDE THE FALLOPIAN TUBE OR THE TOP DOME OF THE RIVER SHOWING THE ADHESIONS WE CALL FITZ-HUGH SYNDROME AND THE SYNDROME HAS TO GO IN AND LYSOL THESE AND IN THE FALLOPIAN TUBE THEY’LL CLEARLY CAUSE INFERTILITY AND PROBLEMS OR ALONG THOSE LINES. WE BELIEVE WE KNOW THE IMMUNOLOGIC MAKEUP THAT CAUSE THE SCAR. HOW TO PREVENT THAT FROM HAPPENING IS WHAT’S BEEN MORE PROBLEMATIC AND THE BEST WAY OF PREVENTING IT IS EARLY DIAGNOSIS AND TREATMENT. SO P.I.D. IS THE BIGGEST MORBIDITY. IT’S AN EMERGENCY IF A WOMAN COMES IN AND HAS LOWER QUADRANT ABDOMINAL PAIN AND FEVER AND CERVICAL MOTION AND TENDERNESS, SHED SHOULD BE PUT ON INTRAVENOUS ANTIBIOTICS BECAUSE LEFT UNTREATED COULD CAUSE A RUPTURE IN THE FALLOPIAN TUBE OR PREGNANCY OR INFERTILITY. THAT’S PELVIC INFLAMMATORY DISEASE AND THERE’S OTHER STDs THAT ALSO CAUSE IT. WE USE BROAD SPECTRUM ANTIBIOTICS WHEN MAKING THE DIAGNOSIS OF THIS. IT’S THE MOST COMMON CAUSE OF A GYNECOLOGIC VISIT. NOW SOME MEN, ESPECIALLY MEN WHO HAVE SEX WITH MEN HAVE AT RISK OF THESE SHOWN IN THE RIGHT. IF THEY ENGAGE IN ANAL SEX IT CAN CAUSE PROCTITIS. WE GIVE THEM AN ANTIBIOTIC, DOXY DOXYCYCLINE AND TREAT FOR THREE WEEKS AND OTHER CHLAMYDIA IS TREAT WITH A ONE-DAY DOSE OF OTHER MEDICATIONS. YOUNG WOMEN ARE AT RISK OF THIS INFECTION AND RECOMMEND EVERY SINGLE YOUNG SEXUALLY ACTIVE WOMAN UNDER 24 YEARS OF AGE SHOULD BE SCREENED ANNUALLY WITH CHLAMYDIA. IT COULD BE DONE WAY URINE TEST AND SELF-APPLIED VAGINAL SWAB. ALL WOMEN UNDER 24 SHOULD BE SCREENED AND OVER 24 THERE’S RISK FACTORS WE APPLY WHETHER THEY SHOULD BE SCREENED OR NOT. DID THEY CHANGE PARTNER. ARE THEY PRACTICING UNPROTECTED SEX? DO THEY HAVE MULTIPLE PARTNERS. TREATMENT IS SO EASY AND THIS HAS NO RESISTANCE THAT WE KNOW OF. IT’S A SINGLE DOSE OF AZITHROMYCIN. AND YOU CAN GIVE THAT WOMAN AN EXTRA DOSE GIVE TO HER SEXUAL PARTNER. PIS IS NOW BEEN DONE. IT’S PARTNER TREATMENT BY THE PARTNER AND IT STARTED OUT CONTROVERSIAL BUT HAS NOW BEEN GENERALLY ACCEPTED AS ONE WAY OF GETTING TREATMENT TO THE MEN. BECAUSE MEN ARE NOT ROUTINELY SCREENED. THERE’S NO RECOMMENDATIONS THEY SHOULD BE. AND IT MAY BE WHY CHLAMYDIA KEEPS GOING UP BECAUSE WE LEFT OUT THE OTHER GENDER IN OUR PUBLIC HEALTH CONTROL. SHOULD WE DO A TEST OF CURE? SO WE DO RECOMMEND IN A PLACE LIKE INNER CITY BALTIMORE OR WASHINGTON, D.C., THEY SHOULD BE RETESTED ANYWHERE FROM THREE TO 12 MONTHS. NOW I COVERED CHLAMYDIA. I CAN’T LEAVE WITHOUT CALLING IT GONORRHEA. I CALL IT ITS TWIN BECAUSE THEY PRESENT WHEN THEY’RE SYSTEMATIC. THE SAD STORY AND I KNOW I’M THROWING A LOT OF STATISTICS AT YOU BUT THE UNITED STATES HAS THE HIGHEST CASE RATE OF GONORRHEA OF ANY INDUSTRIALIZED COUNTRY. IT’S 50 TIMES HIGHER THAN THAT OF SWEDEN. EIGHT TIMES HIGHER THAN CANADA. IT IS A NATIONAL EMBARRASSMENT, IF I CAN BE SO CLEAR. DURING THE EARLY AIDS EPIDEMIC. PEOPLE WERE WORRIED THEY PRACTICED SAFE SEX AND SAW EVERYBODY GETTING SCREENED FOR GONORRHEA AND CHLAMYDIA AND IT STARTED GOING DOWN THEN WE STARTED TREATING HIV AND THE FEAR OF THAT FROM HIV STARTED TO WANE A BIT. THEN ALL OF A SUDDEN WE START SEEING A RISE IN GONORRHEA. I’LL GIVE YOU AN EXAMPLE WHY THAT IS. IT’S DOUBLED IN MEN WHO HAVE SEX WITH MEN AT THE RISK FOR HIV. AND CHLAMYDIA IS SKYROCKETING. SO HERE’S THE EPIDEMIC CURVE GOING FROM 1941 OUT TO 2016. SO YOU CAN SEE IT’S HAD ITS PEAKS AND VALLEYS. THE PEAK WAS REALLY IN THE MID-70s. THE DECADE OF LOVE, FREE LOVE AND LOTS OF PARTNERS AND WHEN I HIV START TO SPREAD. THEN COMES THE AIDS EPIDEMIC AND YOU CAN SEE IT REALLY DID DROP IN THE ’80s AND ’90s. LEVELLED OFF AND NOW IT’S GOING UP. IT’S GOING UP IN MEN MOSTLY BUT ALSO TO SOME DEGREE IN WOMEN. LAST YEAR WE SAW AN ALMOST 20% INCREASE IN GONORRHEA. UP IN MEN AND WOMEN. IT’S HAPPENING IN BOTH. UNLIKE CHLAMYDIA WHERE WE HAD HIGH RATES IN THE YOUNG WOMEN, HERE IT’S EQUAL, SLIGHTLY HIGHER, ACTUALLY IN THE MEN. THE KEY AGE GROUP 20-30. IF YOU TAKE THE MEN AND BREAK IT OUT TO MEN WHO HAVE SEX WITH WOMEN VERSUS MEN WHO HAVE SEX WITH MEN, CAN YOU SEE THE GONORRHEA RATE FOR THE LAST THREE YEARS IS DEFINITELY INCREASING IN THIS POPULATION. ONE REASON AND ONLY ONE REASON, THERE’S OTHER REASONS BUT I’M ONLY GOING TO TALK ABOUT ONE, IS THAT WE ARE NOW RECOMMENDING GAY MEN TAKE PRE-EXPOSURE PROPHLYACTIC BUT LOOK AT THE RATES OF CHLAMYDIA, GONORRHEA OR ANY STI. THEY’RE GOING UP. WE’RE PREVENTING- WHICH IS THE GOOD NEWS. THE BAD NEWS IS THAT THEY STOPPED USING SEXUAL PROTECTION FROM THE STDs. SO THE CONDOM USED HAS DROPPED POCH MULTIPLE PARTNERS HAS INCREASED. IT’S A VERY COMPLEX SCENARIO. THE PEOPLE WHO ARE PUT ON PREP ARE USUALLY AT A HIGH RISK GROUP ANYWAY. THEY’RE GETTING STIs. WE HAVE TO BUILD IN MESSAGES TO PREVENT STIs FROM OCCURRING WHEN WE’RE MAKING PRESCRIPTIONS FOR PREEXPOSURE PROPHYLAXIS. WE STARTED USING STANDARD ANTIBIOTICS IN THE 1940s AND GONORRHEA DEVELOPED RESISTANCE TO THE FIRST ANTIBIOTICS WE WERE USING, THEN PENICILLINS AND THEN WE STARTED USING TETRACYCLINES AND THEN RESISTANCE. THEN WE STARTED USING FLUROQUINOLONES AND AZITHROMYCIN AND NOW CEPHALOSPORIN. AND THIS HAS BEEN COLLECTED ACROSS THE U.S., 2016, JUST LAST YEAR, YOU CAN SEE THAT ALMOST A THIRD TO A HALF OF THE STRAINS ARE RESISTANT TO ANY ONE OF THESE ANTIBIOTICS THAT I’M SHOWING IN THE LEGEND THERE. NOW, HALF ARE STILL SUSCEPTIBLE STILL TO PENICILLIN WHICH IS GOOD NEWS. BUT WE DON’T — IF THE OTHER HALF ARE RESISTANT, WE’RE NOT RECOMMENDING PENICILLIN. THE STANDARD IS WE RECOMMEND TWO DRUGS. NOW, I TOLD YOU WE USE AZITHROMYCIN FOR CHLAMYDIA. SINGLE DOSE. IT WORKS. IT ALSO WORKS AGAINST 90%, 95% OF GYNOCOCCAL STRAIN AND IT SHOWS HOW QUICKLY THE ORGANISM DEVEL DEVELOPS RESISTANCE ALREADY WE’RE IN 3% RESISTANCE TO THIS STRONG EFFECTIVE DRUG AGAINST OTHER STRAINS OF BACTERIA BUT BUT THESE ORGANISMS CAN DELIVER RESISTANCE EASILY. THESE ARE THE NEW RECOMMENDATION CAME OUT THE END OF 2015, IT’S SAD TWO DRUG REGIMENT AND WE FEAR WE’RE GOING TO A THREE-DRUG REGIMENT FOR A COMMON ORGANISM WHERE WE SEE 600,000 CASES A YEAR IN THE U.S. SO THE CEFTRIAXONE AND THE ALTERNATIVE IS CEFIXIME. IF THEY HAVE TREATMENT FAILURE TO THE CEFIXIME YOU MUST DO A TEST-TO-CURE. WE DON’T WANT TO LOSE THESE TWO DRUGS. AND JUST THIS LAST YEAR, 2017, THERE WAS A CASE EVERYONE WANTS TO GO TO HAWAI’I. WHEN THEY GO TO HAWAI’I, THEY ENGAGE IN SEXUAL PRACTICES, AND UNFORTUNATELY THERE’S A CASE OF A CLUSTER OF MULTIPLE INDIVIDUALS THAT ACTUALLY HAD COMPLETE RESISTANCE AGAINST THE AZITHROMYCIN AND THE CEFTRIAXONE WHICH IS MORE TOXIC. THERE’S MULTIPLE DRUGS ON THE HORIZON COMING ALONG IN AN INVESTIGATION BUT THEY’RE AT PHASE TWO. WE WON’T SEE THESE DRUGS FOR FIVE MORE YEARS. WE SORT OF HAVE TO HANG ON TO THESE TWO DRUGS RIGHT NOW. AND IF THOSE ANTIBIOTICS RUN DRY, IN THE OLD DAYS, POST WORLD WAR II THIS IS WHAT YOU WOULD SEE. WHY IT’S NEXT TO A FIRE HYDRANT, I DON’T KNOW, BUT HERE’S YOUR PENICILLIN. GO AND GET TREATED AND BE CURED. NOW WE HAVE THAT RESISTANCE. SO IF THAT RESISTANCE KEEPS GOING ON, WHAT I FEAR IS WE’LL GO BACK TO THE SNAKE OIL OLD TREATMENT CURES OR EVEN WORSE, THE WAY IT WAS TREATED BEFORE ANTIBIOTICS, AND CURITAGE OF THE URETHRA WHICH IS PAINFUL AND SO THIS COURSE OFTEN HAS A CASE. THIS SAY 58-YEAR-OLD MAN WHO PRESENTED TO US WITH RIGHT EYE PAIN COMING TO THE HOPKINS EMERGENCY ROOM. IT’S BEEN GOING ON ABOUT FOUR DAYS. HE’S HAD NO MEDICAL CARE FOR THE PAST 20 YEARS AND HAS HAD NO SEX FOR THE PAST FOUR YEARS AND HIS RIGHT EYE HAS PANUVEITIS. IT’S PAINFUL. SOMEONE HAD THE STARTS TO DO AN RPR AND HE’S POSITIVE, 1-28. NEXT STEP IS THEY DO A LUMBAR PUNCTURE AND IT IS ALSO RPR POSITIVE AND HE’S DIAGNOSED WITH SYPHILIS. WE’LL COME BACK TO A DESCRIPTION ABOUT THAT. TWO WEEKS LATER ANOTHER INDIVIDUAL CAME IN, 36-YEAR-OLD GAY MAN OF ONSET OF FLUCTUATING BILATERAL HEARING LOSS AND TINNITUS. HE HAD A MACULOW AND THE ANSWER WAS HE WHO KNOWS SYPHILIS KNOWS MEDICINE. IT’S BECAUSE SYPHILIS CAN PRESENT IN ANY SHAPE OR MANNER OF CLINICAL DISEASE OR NO DISEASE. THE ORGANISM, AS YOU KNOW, STARTS OUT AS A SHANKER. YOU CAN DO A DARK FIELD OR FLORESCENT STAIN AND SEE THE ORGANISM. IT CAN THEN PROGRESS TO SECONDARY FORM OF THE INFECTION AND THEN TERTIARY. THESE ARE MULTIPLE PHOTOS OF INDIVIDUALS WITH SECONDARY SYPHILIS. THEY COULD BE MISS — MISTAKE TAKEN FOR HUMAN PAPILLOMA VIRUS AND CAN BE PRESENT. ALWAYS LOOK AT THE SOULS AND PALMS OF INDIVIDUALS YOU MIGHT SUSPECT. WHO IS GUESSING SYPHILIS. MSM. MEN HAVING SEX WITH MEN. SHOWING A BIS RISE OF INFECTION. WHAT’S SCARY ABOUT THIS, IS WHEN YOU LOOK AT THE MSM AND YOU LOOK AT THEIR HIV STATUS, YOU FIND ALMOST AS MANY HIV POSITIVE PEOPLE COMING DOWN WITH SYPHILIS AS THE HIV NEGATIVE INDIVIDUALS. SO THESE ARE HIV POSITIVE PEOPLE. THEY COULD BE ON ANTIRETRO VIRAL DRUG AND INFECTIOUS FOR SYPHILIS. THIS SAY MAJOR CONCERN. IT INCREASED DRAMATICALLY IN BOTH MEN AND WOMEN. WHEN IT INCREASES IN WOMEN, YOU WORRY ABOUT CONGENITAL INFECTION. UNFORTUNATELY FUNDING FOR SCREENING OF PREGNANT WOMEN HAS DROPPED TO ALMOST ZERO ESPECIALLY IN THE SOUTHERN STATES. AS A RESULT SHOWN IN THE BLUE BARS, CONGENITAL SYPHILIS IS NOW INCREASING TO THE HIGHEST RATE OF THE 21st CENTURY. AND CONTINUING TO GO UP. PNS IS PRIMARY AND SECONDARY SYPHILIS IN WOMEN. IT’S AN EASY ORGANISM TO TREAT. IT IS NOT RESISTANT TO PENICILLIN. WE TREAT IT WITH BENZOTHINE PENICILLIN WHICH THERE’S A SHORTAGE OF. THAT’S GOT TO CHANGE. WE CAN GIVE IT ONCE TO THE PRIMARY DISEASE. SECONDARY WE GIVE IT OVER THREE WEEKS AND NEUROSYPHILIS PENICILLIN. THAT’S EXACTLY WHAT WE DID WITH THAT OCULAR CASE. WE WENT AHEAD AND WE TREATED THAT INDIVIDUAL. IT’S DIFFICULT TO KNOW WHETHER THERE’S NEUROSYPHILIS INVOLVED. ANY PART OF THE EYE CAN BE INVOLVED AND WE TREAT THE NEUROSYPHILIS WITH 24 UNITS OF PENICILLIN BECAUSE YOU NEED MORE TO PENETRATE IN. THE SAME IS TRUE FOR THE HEARING LOSS. THOUGH THAT INDIVIDUAL HAS SECONDARY SYPHILIS BECAUSE OF THE NEURAL SYSTEM WE TROETED HIM AS WELL. I’VE BEEN IN THE FIELD MAYBE 50 YEARS OR 40 YEARS. TO BE HONEST WITH YOU, I’VE NEVER SEEN SO MANY CASES OF OCULAR SYPHILIS AS I HAVE IN THE LAST YEAR. I’M GOING SHOW QUICKLY WHAT WE NEED TO DO TO CHANGE THIS PARADIGM. STD PREVENTION AND CONTROL, NUMBER ONE, PREVENTION. WE’LL HEAR ABOUT THE VACCINE FOR HPV AND HEPATITIS B. THEY’RE THE ONLY TWO STIs WE HAVE A GOOD VACCINE FOR. USE THEM. DETECT AND LINK TO CARE. THAT MEANS DOING A LOT OF SCREENING OF ASYMPTOMATIC AND DIAGNOSIS OF THE ASYMPTOMATIC PEOPLE AND THE CASE/PARTNER MANAGEMENT. IF YOU’VE IDENTIFIED A PERSON WHO’S INFECTED YOU NEED TO FIND OUT HOW THEY GOT IT AND WHO THEY GOT IT FROM. THERE’S WAYS TO INCREASE SCREENING. WE’VE DEVELOPED AN INTERNET-BASED SYSTEM CALLED I WANT THE KIT. IT’S ONLINE. PEOPLE CAN JUST GO ON THEIR COMPUTER. THEY GET THE KITS SENT TO THEM AND DO A SELF-ADMINISTERED SWAB. THE MEN CAN SWAB THE EXTERNAL PART OF THEIR YOUR EITHURETHRA
AND LOG WIN A CODE AND IF POSITIVE THEY’RE GIVEN THE INSTRUCTIONS HOW TO GET TREATED AND FULLY DIAGNOSED. WE’RE TRYING TO GET TO RAPID DIAGNOSIS. WE’VE OPENED UP A VERY NEW TREATMENT. A DIAGNOSIS AND TREATMENT IN THE PHARMACY ACROSS THE STREET FROM US, WALGREENS. YOU CAN GO TO WALGREENS AND GETS SCREENED AND IF YOU GET DIAGNOSED, YOU CAN GET TREAT. IT’S EXPERIMENTAL. OUT OF 80 PEOPLE 8 WERE IDENTIFIED AND THESE ARE THE DIAGNOSTICS THAT CAN BE DONE IN THE PRIVACY OF YOUR PHARMACY OR HOME. I WANT TO CONCLUDE AND THANK THOSE WHO CONTRIBUTE TO THE TALK. I’M INDEBT TO MY FOUR COLLEAGUES WHO ARE THE REAL STD EXPERTS UP AT JOHNS HOPKINS. THANKS VERY MUCH. [APPLAUSE]>>SO I’M FAMILIAR WITH THE DOXY CYCLINE FOR MY SKIN IT’S UNNERVING TO THINK I TOOK IT FOR MY SKIN BUT WHAT’S THE SIMILARITY — OR WHAT’S IN DOXYCYCLINE THAT TREATS THE TWO THINGS?>>IT’S THE ANTIBIOTIC. SO WHEN YOU’RE TAKING IT FOR YOUR SKIN IT’S THE BACTERIAL PRESENCE WITHIN THE PORES OF THE SKIN. AND THE DOXYCYCLINE CLEANS THAT UP. SO THE SKIN GETS BETTER. IT ALSO DOES MAKE IT INTO THE URETHRA AND CERVIX AND VAGINA AND OTHER PLACES. IF THE PERSON IS INFECTED WITH CHLAMYDIA, IF THEY WERE, IT ALSO IMPACTS THAT. IT’S ACTUALLY CONCENTRATED. I SHOWED THAT LIFE CYCLE. THE ANTIBIOTIC IS CONCENTRATES IN THE EPITHELIAL CELLS AND HITS THE ORGANISM AS IT TRIES TO REPLICATE. IT CAN’T. IT STOPS.>>I HAVE A QUESTION QUESTION, WITH THE INCREASED TESTING BY WEBSITE AND ELECTRONIC MEANS, HOW DO RESULTS GET TO CDC? HOW DO THEY GET HOLD OF THE ACTUAL SPREAD OF THE DISEASE?>>SO GREAT QUESTION. SO ALL LABORATORIES THAT MAKE A DIAGNOSIS MUST RECORD. THAT’S NUMBER ONE. C.D.C. KEEPS TRACK IT’S NOT ALL INCUMBENT THE PHYSICIAN MAKES THE REPORT. THEY WORKED IT OUT AND TRY TO MAKE SURE REPORTING IS DONE CORRECTLY LIKE THE WALGREEN EXPERIMENT WE’RE DOING, THEY ALSO TABULATED ON A FORM THAT GOES TO THE STATE DIAGNOSIS OF CHLAMYDIA AND FORWARDED TO C.D.C. THE REPORT IS PRETTY GOOD. IT’S THE REASON WE MAKE ESTIMATES TWICE AS HIGH AS WHAT’S REPORTED BECAUSE THAT’S THE PEOPLE WHO DON’T GET DIAGNOSED. WE IS A 1.5 PEOPLE WITH CHLAMYDIA AND MAYBE 1.2 GET REPORTED. THE DIFFERENCE IS THE NUMBERS WE’RE MISSING.>>GOOD AFTERNOON. I’M DOUG LOWY AND I’M PLEASED TO HAVE BEEN INVITED HERE TO TELL YOU ABOUT THE HPV VACCINE AND TELL ABOUT HPV ASSOCIATED INFECTIONS AND DISEASES CAUSED BY HPV. I AM INVOLVED AS AN INVENTOR OF THE VACCINE AND THE VACCINE HAS BEEN LICENSED TO THE TWO COMPANIES THAT MAKE THE VACCINE MERCK AND GLAXOSMITHKLINE AND WILL DISCUSS POTENTIAL OFF-LABEL USES OF THE APPROVED VACCINES ONE POTENTIALLY PROTECTING AGAINST HIP POSITIVE OR ADVANCED CANCER AND THE OTHER IS FEWER DIAGNOSIS THAT ARE FDA APPROVED. I’VE BEEN INVOLVED IN SOME ADDITIONAL TECHNOLOGY LICENSE TO A NUMBER OF DIFFERENT COMPANIES. THIS SLIDE TELLS YOU PERHAPS ONE OF THE REASONS WHY I DON’T HAVE A PATIENT TO PRESENT TO YOU. THAT’S BECAUSE MORE THAN 40% OF MEN AND WOMEN BETWEEN THE AGES OF 18 AND 59 HAVE GENITAL HPV INFECTION. IF YOU SEE A REPRESENTATIVE GROUP OF PEOPLE WHO ARE BETWEEN THOSE AGES JUST UNDER HALF OF THEM STATISTICALLY WILL HAVE HPV INFECTION. THE OTHER REASON IS THAT I’M GOING TO BE TALKING WITH YOU ABOUT PRIMARY PREVENTION AND ONE OF THE GREAT THINGS ABOUT PRIMARY PREVENTION IS THERE ARE NO GRATEFUL PATIENTS. ONE OF THE LIABILITIES, ESPECIALLY WHEN YOU ARE A CANCER RESEARCHER IS NOBODY GETS THE INFECTION OR DISEASE, HAVE YOU NO GRATEFUL PATIENTS. SO IT IS TO SOME DEGREE A DOUBLE-EDGED SWORD. THE ISSUE OF HPV-ASSOCIATED CANCER SAY DIFFERENT ISSUE IN THE DEVELOPING WORLD AND IN THE INDUSTRIALIZED WORLD AND THE NEXT TWO SLIDES TELL YOU ABOUT THOSE DIFFERENCES. IN THIS SLIDE, WHICH REALLY IS FOCUSSED ON LOW AND MIDDLE INCOME COUNTRIES, WE’RE FOCUSSED ON CERVICAL CANCER. THE REASON IS BECAUSE ABOUT 90% OF HPV ASSOCIATED CANCER IN LOW AND MIDDLE INCOME COUNTRIES IS CERVICAL CANCER AND ABOUT 95% OF HPV ASSOCIATED CANCER IN THE DEVELOPING WORLD OCCURS IN WOMEN. SO ONLY ABOUT 5% OCCURS IN MEN SHOWN IN BLUE OVER THE NEXT 15 YEARS. THE MORTALITY RATE AMONG WOMEN FROM CERVICAL CANCER IN LOW AND MIDDLE INCOME COUNTRIES IS EXPECT TO GO UP BY MORE THAN 50%. AND THIS IS A PROJECTION FROM THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER WHEREAS SHOWN IN RED IS MORTALITY RATES FROM CERVICAL CANCER IN THE INDUSTRIALIZED WORLD AND HIGH-INCOME COUNTRIES WHERE IT IS PROJECTED TO REMAIN MORE OR LESS A CONSTANT. SO THE BIG PUBLIC HEALTH PROBLEM FROM THE POINT OF VIEW OF DEATHS FROM HPV ASSOCIATED CANCER IS FROM LOW AND MIDDLE INCOME COUNTRIES. I’LL REPEAT MYSELF, IT IS ALMOST ENTIRELY ATTRIBUTABLE TO CERVICAL CANCER. THIS IS THE PROFILE, HOWEVER, IN THE UNITED STATES, WHICH IS DRAMATICALLY DIFFERENT. ON THE RIGHT SIDE SHOWN IN GREEN ARE THE HPV POSITIVE CANCERS OCCURRING IN WOMEN. ON THE LEFT SIDE IN BLUE ARE THE HPV POSITIVE CANCERS OCCURRING IN MEN. CERVICAL CANCER VIRTUALLY 100% IS ATTRIBUTABLE TO HPV INFECTION BUT IN THE UNITED STATES, OF THE 31,000 ESTIMATED HPV POSITIVE CANCERS, ABOUT TWO-THIRDS OF THEM OCCUR IN WOMEN AND ABOUT ONE-THIRD OCCUR IN MEN. AND ACTUALLY, THERE ARE MORE NON-CERVIC NON-CERVICAL CANCERS HPV POSITIVE THAN JUST CERVICAL CANCER. AND HPV16 AND 18 WHICH ARE THE TWO HPV TYPES IN THE FIRST GENERATION VACCINE COUNTS FOR 70% OF CERVICAL CANCER AND 90% OF THE NON HFR NON-CERVICAL CANCERS. WE HAVE HPV SCREENING AND ORAL PHARNGEAL CANCER IS PREDOMINANTLY A CANCER OF MEN. THREE-QUARTERS OF THE CASES ARE IN MEN AND IN THE RECENT PERIOD THE INCIDENTS ROSE MORE THAN THREE-FOLD. SO LET ME TELL YOU ABOUT THE FIRST GENERATION HPV VAKS — VACCINES. JOHN SCHILLER AND I HAVE WORKED TOGETHER MORE THAN 30 YEARS AND WE’VE HAD WONDERFUL PEOPLE WORKING IN THE LABORATORY AND TREMENDOUS PEOPLE COLLABORATING. I LIKE THIS AFRICAN SAYING WHICH IF YOU WANT TO GO QUICKLY, GO ALONE BUT IF YOU WANT TO GO FAR, GO TOGETHER. WE HAVE WORKED A LOT OF WOFRL WONDERFUL PEOPLE. SOME ARE MENTIONED HERE. IF YOU ARE THINKING MUCH MAKING A VACCINE AGAINST HPV, LICENSED VACCINES ARE PREVENTATIVE. THEY NEUTRALIZE ANTIBODIES AND CONTAIN VIRAL ONCAGENES. WANT A SUBUNIT VACCINE LACKING IN ONCAGENES AND THERE’S TWO PROTEINS THAT CAN PRODUCE NEUTRALIZING ANTIBODIES. L1 CONTAINS THE MOST IMMUNOGENIC EPITOPES AND THEY’RE TOP FORMATIONAL TWO MEANS THE TERTIARY STRUCTURE IS IMPORTANT AND OUR HYPOTHESIS IS L-1 BY SELF WOULD SELF-ASSEMBLE AND INDUCE HIGH LEVELS OF NEUTRALIZING ANTIBODIES. IF THIS WAS WRONG DR. ARIAS WOULD NOT HAVE INVITED ME. WHEN THE DERMATOLOGIST AT THE UNIVERSITY OF VIENNA, AUSTRIA. HE INSERTED L-1 IN AN A VIRUS IN SEX CELLS AND SAW THERE WAS SELF-ASSEMBLY, SPONTANEOUSLY, INTO VIRUS-LIKE PARTICLES AND WHEN HE IMMUNIZED RABBITS HE COULD INDUCE HIGH ANTIBODIES. HE SHOWED IT FIRST FOR THE BOVINE PAPILLOMA VIRUS BECAUSE WE HAD THE NECESSARY AGENTS TO MONITOR NEUTRALIZING ANTIBODIES AND HAD A SOURCE OF INFECTIOUS VIRUS AND HAD AN ASSAY PREVIOUSLY. WE DID THINGS FIRST WITH BPV AND THEN WENT TO PHV16 RESPONSIBLE FOR 50% OF CERVICAL CANCER IN THE WORLD AND FOR ABOUT OVER 80% OF THE NON-CERVICAL HPV ASSOCIATED CANCERS. IT TURNED OUT THE HPV16 EVERYONE WAS USING WAS A MUTANT AND DID NOT SELF-ASSEMBLE WELL BUT THANKS TO THE ASSISTANCE OF COLLEAGUES WHO TOOK HP16 AND GAVE IT US TO FROM NON-PROGRESSIVE LEGIONS, NON-MAG NON-MAG — MALIGNANT LESIONS WAS AWARDED 10 YEARS AGO WAS IMPORTANTLY AND WHEN WE HAD THE NON-PROGRESSED ONES THEY SELF-ASSEMBLED THE SAME AS BPV AND PRODUCED HIGH LEVELS OF ANTIBODIES IN CONTRAST TO THE MUTANT WHICH WOULD NOT HAVE BEEN USEFUL FOR A VACCINE. THE VIRUS-LIKE PARTICLES WHICH YOU SEE ON THE RIGHT, THEY’RE NON-INFECTIOUS AND NON-ONCOGENIC. THE FIRST GENERATION OF VACCINES WERE MADE THE BY GLAXOSMITHKLINE. IT’S VIRUS-LIKE PARTICLES FOR 16 AND 18. IN PRINCIPAL CAN PROTECT. GAURDASIL ALMOST MOST PEOPLE RECEIVED GUARDASIL AND THE FIRST ONE IS NO LONGER SOLD IN THE UNITED STATES BUT IN OTHER COUNTRIES. THE VACCINE FOR PARTICLES 16 AND 18 HAS PARTICLES FOR 6 AND 11 AND THEY ACCOUNT FOR 90% OF GENITAL WARTS. I’LL SHOW YOU DATA FROM AUSTRALIA THAT LOOKS AT GENITAL WARTS BECAUSE THE PEOPLE IN AUSTRALIA ALMOST EXCLUSIVELY GOT GUARDASIL. YOU CAN SEE WHAT HAPPENS TO THE IMMUNITY. THAT IS TO LOOK AT GENITAL WARTS IN MALES THOUGH ONLY WOMEN WERE IMMUNIZED WITH THE VACCINE. INITIALLY THE VACCINE WAS GIVEN IN THREE INTRAMUSCULAR INJECTIONS OVER SIX MONTHS. WHY? BECAUSE THE TRACK RECORD FOR THE SEXUALLY TRANSMITTED INFECTIONS WAS NOT GOOD. HERP HERPES SIMPLEX MODELS WORKED WELL BUT DIDN’T WORK WELL WHEN TESTED IN PEOPLE. THE SITUATION YOU WERE IN HERE WAS AN AND — AN ANIMAL MODEL WORK WELL AND THEY MAXIMIZED THE IMMUNE RESPONSE BY GIVING THREE INTRAMUSCULAR INJECTIONS. THERE WERE EFFORTS TO TRY TO REDUCE THE TOTAL NUMBER OF DOSES PEOPLE NEED BECAUSE IT IS LOGISTICALLY MORE EFFICIENT AND MORE COST EFFECTIVE TO GIVE FEWER DOSES. WHAT ABOUT SAFETY? THERE’S BEEN SAFETY TESTINGS IN THE UNITED STATES AND ELSEWHERE. THERE’S NO RELATED INCREASED RISK TO PRE-SPECIFIED OUTCOMES. THE RATE OF ANAPHYLAXIS DOSES WERE ONE CASE AND SIMILAR TO OTHER VACCINES. FOR THOSE INTERESTED IN READING MORE WITH THE SAFETY STUDIES I STRONGLY RECOMMEND THE ARTICLE PUBLISH PUBLISHED IN 2016. IT’S AN EXCELLENT OPINION. WHAT ABOUT THE SHORT-TERM POPULATION LIFE OF VACCINATION FOR HPV. IT’S TO REDUCE THE INFECTION AND DISEASE IN THE VACCINEES AND TO INTERDIRECTLY REDUCE THE RISK — INDIRECTLY REDUCE THE RISK IN THE GENERAL POPULATION. IT’S USUALLY REFERRED TO AS HERD IMMUNITY. I’M GOING TO SHOW YOU THREE SLIDES FROM AUSTRALIA WHICH WAS AN EARLY HIGH-ADOPTER COUNTRY. THE AUSTRALIAN GOVERNMENT HAD THE VACCINE AND OFFERED IT FREE OF CHARGE TO WOMEN WHO WERE OF THE APPROPRIATE AGE RANGE ESSENTIALLY FROM ABOUT 10 TO 26. SO MORE THAN 75% OF ELIGIBLE WOMEN UNDER THE AGE OF 20 WERE VACCINATE. NOW, IF YOU LOOK HERE AT THE INCIDENTS OF GENITAL WARTS FOR 21 YEARS OR YOUNGER THE VERTICAL UNINTERRUPTED LINE IS WHEN THE VACCINE WAS STARTED IN AUSTRALIA. IT WAS APPROVED IN 2006. WHAT YOU CAN APPRECIATE IS A DRAMATIC REDUCTION IN GENITAL WARTS IN THE NEXT FEW YEARS IN AUSTRALIA. IF YOU LOOK AT WOMEN OVER 30 THE UNINTERRUPTED LINE, THERE’S NO SUCH CHANGE AND WOMEN BETWEEN 21 AND 30, SOME OF WHOM WERE VACCINED THERE WAS A DECREASE BUT NOT AS DRAMATIC AS THE WOMEN UNDER 21. WHAT ABOUT MALES OF COMPARABLE AGE RANGE WHO WERE VACCINATED AND WERE SEXUAL PARTNERS OF THE WOMEN. LOOKING IN THE BLUE/GREEN LINE, A DRAMATIC REDUCTION IN THE INCIDENTS OF GENITAL WARTS AMONG THE YOUNG MEN, 21 YEARS OF AGE AND YOUNGER. IF YOU LOOK AT THE MEN 30 OR OLDER, THERE’S NO SUCH DECLINE AND THE MEN 21-30 IN THE RED INTERRUPTED LINE, THEY’RE IN BETWEEN THE 21-YEAR-OLD AND MORE THAN 30-YEAR-OLD. LET ME REPEAT, THESE MEN WERE NOT VACCINATE. THEY’RE BENEFIT FROM THE DECREASE OF EXPOSURE THEY’RE GET FROM THE WOMEN. THIS IS PRESUMPTIVE IMMUNITY. THEY PUBLISHED THIS DATA WHICH IS LOOKING AT THREE DIFFERENT CLASSES OF HPV. LET’S FIRST LOOK AT BLUE WHICH IS INFECTION WITH MANY HPV TYPES BECAUSE MANY ARE NOT ATTRIBUTE TO HPV 6, 11, 16 AND 18. AND THERE’S NO CHANGE IN THOSE INFECTIONS. HOWEVER, WHEN YOU LOOK AT THE PREVALENCE OF P — HPV6 AND 11 THE PREVALENCE GOES DOWN TO TO ZERO. I’M SHOWING DATA FOR MEN. THEY HAD NOT BEEN VACCINATE. THE GREEN IS HPV 16 AND 18. IT TAKES LONGER FOR THE PREVALENCE TO GO DOWN BUT BEFORE AUSTRALIA STARTED MALE VACCINATION WHICH WAS IN 2013 THE PREVALENCE OF HPV 16 AND 18 HAD GONE DOWN DRAMATICALLY FOR THE MEN AND AS YOU CAN IMAGINE EVEN BETTER THAN FOR THE MEN. THIS IS DIRECT EVIDENCE FOR HERD IMMUNITY IN THE GENERAL POPULATION AMONG THE HETEROSEXUAL MEN. WHAT ABOUT THE UNITED STATES? THE FIRST UPTAKE OF THE HPV VACCINE HAS NOT BEEN AS ROBUST AS IN AUSTRALIA. THIS IS THE COMPLICATED SLIDE FROM THE C.D.C. THIS IS LOOKING AT DATA THROUGH 2016. THEY GO THROUGH THE END OF DECEMBER OF THE PRIOR YEAR. LET’S FIRST TAKE THE GIRLS VACCINED. AND THE LOWER LINE IS LOWER. 65% OF THE GIRLS ELIGIBLE NOR VACCINE HAVE RFSD ONE DOSE AND ABOUT TWO-THIRDS OF THAT NUMBER RECEIVED ALL THREE DOSES. IF YOU LOOK AT THE RED INTERRUPTED LINES, THOSE ARE BOYS 13-17. CANCER REVENTION RECOMMENDATION FROM THE FDA AND STRONG RECOMMENDATION FROM THE AMERICAN C.D.C. WAS 2007 AND 2006 FOR GIRLS. SO ONE DOSE IS 50%, THREE DOSES A LITTLE LESS THAN TWO-THIRDS. SHOWN HERE IN BLACK ARE THE TWO OTHER ADOLESCENT VACCINES. THE C.D.C. PUBLISHED THE PRINCIPLE REASONS AND ASKING PARENTS OF BOYS AND GIRLS WHO HAD NOT BEEN VACCINATED WHY THEY WEREN’T. YOU CAN GO THROUGH THIS IN DETAIL BUT BASICALLY FOR PARENTS OF GIRLS, SAFETY WAS A VERY IMPORTANT ISSUE NOT NECESSARILY PARENTS THOUGHT THEIR CHILDREN WERE NOT SEXUALLY ACTIVE. MANY PARENTS ARE NOT CORRECT IN THOSE ASSESSMENTS AND LACK OF KNOWLEDGE ABOUT THE VACCINE AND IT WAS NOT RECOMMENDED. PARENTS OF BOYS, NOT RECOMMENDED WAS THE NUMBER ONE THING OR LACK OF KNOWLEDGE. AND SAFE CONCERNS MUCH LESS AMONG THE PARENTS OF BOYS 7%, WHERE THE SAFETY CONCERNS OF GIRLS. NEVERTHELESS, THERE IS EVIDENCE OF HERD IMMUNITY AMONG YOUNG GIRLS SINCE THE VACCINE WAS INSTITUTED IN THE U.S. THIS SLIDE WHICH IS ADAPTED FROM A PAPER PUBLISHED FROM VTHDERS FROM THE DISEASE CONTROL. IN BLUE HERE SHOWS YOU THE PERCENTAGE OF GIRLS AGE 14 TO 19 POSITIVE FOR HPV16 AND 18. THIS IS 2009 THROUGH 2012. BASICALLY FROM THREE YEARS TO SIX YEARS AFTER THE VACCINE WAS INTRODUCED AND THERE’S A 60% DECREASE IN THE PREVALENCE OF HPV 16 AND 18. LOOKING AT THE OTHER ONCO GENIC TYPES THERE WAS A 10% DECREASE. SO THERE’S SOME HERD IMMUNITY IN THE U.S. BUT NOT AS STRIKE AGENCIES IN AUSTRALIA. TO WHAT MIGHT YOU ATTRIBUTE THE EFFICACY OF THE VIRUS-LIKE PARTICLE VACCINE? IN BOYS AND GIRLS WHO ARE NOT INFECTED AND GET THE VACCINE THE PROTECTION IS OVER 95%. MOST PEOPLE IT’S STERILIZING IMMUNITY. THEY DON’T EVEN GET INFECT. MANY VACCINES WORK BECAUSE THEY INDUCE THE LEVEL OF INFECTION AND THERE BE REDUCE THE DEVELOPMENT OF DISEASE. MOST OF THE PROTECTION IN MOST PEOPLE WITH THE HPV VACCINE IS THEY DON’T EVEN GET INFECTED. WE THINK THERE’S THREE FACTORS THE TISSUE ASSOCIATED WITH NEUTRALIZING ANTIBODIES ARE A SECOND REASON. BECAUSE THE LEVELS OF THE ANTIBODIES ARE HIGH NOT THE LOWER LEVELS OF THE NON-DISRUPTED GENITAL TRACT AND THIRD, HPV IS HIGHLY SUSCEPTIBLE TO NEUTRALIZING ANTIBODIES. FOR MORE THAT WANT TO READ WE PUBLISHED A PAPER A COUPLE WEEKS AGO IB VACCINE THAT ZHISZ ISSUE IN MORE DEPTH. THIS SHOWS YOU THIS SAY VIRUS PARTICLE. IT’S A RECONSTRUCTION OF AN ELECTRON MICROGRAPH AND THIS IS BOUND TO THE VIRUS PARTICLE. YOU CAN EASILY IMAGINE HOW THE ANTIBODY BOUND VIRUS WILL NOT INTERACT WITH THE TARGET CELL. SO YOU PREVENT INFECTION AS A THRIFT — RESULT YOU PRODUCE ANTIBODIES TO THE INCOMING VIRUS. WHAT A SECOND GENERATION OF VACCINES? MERCK HAS DEVELOPED A SECOND GENERATION VACCINE CALLED GAURDISIL 9. THIS WOULD PROTECT AGAINST 70% OF THE CANCERS AND GIVES PROTECTION AGAINST THE TWO TYPES. WHAT MERCK DID WAS TO ADD THE NEXT FIVE MOST COMMON HPV TYPES FOUND IN CERVICAL CANCER. IT’S THE SEVEN ONCOGENIC TYPES PLUS HPV-7 FOR THE GENITAL WARTS. THEY COMPARED THE ORIGINAL GUARDISIL WITH GUARDISIL 9 AND USED IT AS THE MAIN END POINT OF CERVICAL DYSPLASIA ACCORDING THE HPV TYPES NOT PRESENT IN GUARDISIL 4. THERE WAS 95% PROTECTION WITH GUARDISIL 9 COMPARED TO GUARDISIL 4 BUT THERE’S STILL A FEW POTENTIALLY ONCO GENIC INFECTIONS NOT PROTECTED BY GUARDISIL 9 BUT IT CLEARLY PROTECTS AGAINST MANY MORE THAN GUARDISIL 4. THE LAST PART WHICH IS DIVIDED INTO TWO PARTS TALKING ABOUT INCREASING VACCINE UPTAKE BY SAFELY PRODUCING THE NUMBER OF DOSES. THE FIRST IS WHAT IS CURRENT STANDARD OF CARE. IT TURNED OUT THE IMMUNE RESPONSE IN BOYS AND GIRLS UNDER 15 WAS STRONGER THAN IN OLDER TEENAGERS AND THE YOUNGER WOMEN IN WHOM THE CLINICAL ETHICAL TRIALS WERE CARRIED OUT WOMEN 18 TO 23 OR 25 WERE DOING THE TRIALS. IT TURNED OUT IN YOUNG ADOLESCENTS UNDER 15, TWO DOSES SEPARATE BY SIX MONTHS PRODUCED AN IMMUNE RESPONSE EVEN GREATER THAN THE EFFICACY IN THE TRIALS. THIS CITATION IS FOR GUARDISIL 9 PUBLISHED A YEAR AND A HALF AGO. IF YOU WANT TO SEE THE PRIMARY DATA. THIS LED TO THE ADVISORY COMMITTEE ON THE C.D.C. TO MAKE A STRONG RECOMMENDATION FOR IT. SO BOYS AND GIRLS UNDER THE AGE OF 15, TWO DOSES. BOYS AND GIRLS OVER THE AGE OF 14 IT’S STILL THREE DOSES. THE HOPE IS THAT BY GOING TO TWO DOSES IT WILL BE EASIER TO VACCINATE MORE PEOPLE. THE LAST PART IS CAN ONE DOSE CONFER YEARS OF PROTECTION. I’LL SHOW YOU POST-HOC DATA BUT FIRST I WANT TO SET FOUR WHAT THE PROBLEM IS. THERE’S A PROJECTED LIMITED IMPACT OF WORLDWIDE CERVICAL CANCER FROM THE CURRENT GLOBAL HPV VACCINATION RATES. WHY DO I SAY THAT? ONLY 3% OF ELIGIBLE WOMEN IN LOW AND MIDDLE INCOME COUNTRIES HAVE BEEN VACCINATED WHERE A THIRD OF ELIGIBLE WOMEN IN THE INDUSTRIALIZED WORLD HAVE BEEN VACCINATED. AS WE SAW BEFORE THE WOMEN IN LOW AND MIDDLE INCOME COUNTRIES ACCOUNT FOR 90% OF WORLDWIDE CANCER AND DEATH FROM CERVICAL CANCER. SO WE THINK WIDESPREAD GLOBAL UPTAKE MAY REQUIRE DECREASED COST AND SIMPLIFIED LOGISTICS AND TWO SIMPLE DOSES AND I WILL NOT DISCUSS SEVERAL VACCINES BUT THERE ARE REGIONAL MANUFACTURERS WHERE THIS IS UNDER DEVELOPMENT BUT I WILL DISCUSS THE NIEFGS — NIEFGS SINGLE DOSE. THERE WAS A TRIAL OF THE VACCINE IN COSTA R COSTARY H COSTA RICA AND THE MORTALITY RATE HAS GONE DOWN MORE THAN ONE HALF BUT THERE’S BEEN DETAILED STUDIES. THIS SAY RANDOMIZED CONTROL PLACEBO CONTROLLED TRIAL THAT HAS FINISHED BUT IT WAS STARTED LONG BEFORE THE EITHER VACCINE WAS FDA APPROVED. LET ME FIRST SHOW YOU THE DATA ON THE RIGHT WHICH IS IN THE PLACEBO GROUP. THE GREEN REPRESENTS THE HPV TYPES THAT ARE NOT PROTECT. THE RED REPRESENTS HPV 31, 33 AND 35 WHERE THERE’S GOOD PROTECTION WITH THE VACCINE. THAT’S NOT VIEW OF THE MERCK VACCINE. NOW IF WE GO OVER TO THE LEFT, THIS IS WOMEN IN THE TRIAL WHO GOT ALL THREE DOSES OF THE VACCINE. YOU CAN APPRECIATE IN GREEN, NO DIFFERENCE IN THE HPV PREVALENCE WITH THE TYPES NOT TARGETED BY THE VACCINE BUT A SUBSTANTIAL DECREASE IN THE BLUE AND RED COMPARED WITH THE CONTROL GROUPS BUT IF YOU NOW LOOK AT THE WOMEN WHO GOT TWO DOSES OR ONE DOSE, YOU CAN APPRECIATE THAT THE PERCENTAGE OF EFFICACY IS NO WORSE IN THE WOMEN WHO GOT ONE DOSE OR TWO DOSES COMPARED TO THE WOMEN WHO GOT THREE DOSES. AND I’LL POINT OUT THEY’RE EXPOSURE WAS VERY SIMILAR BECAUSE THE PREVALENCE IS JUST THE SAME. THE BIGGER SURPRISE IS WHEN WE LOOKED AT ANTIBODY LEVELS OF WHERE WE’VE BEEN ABLE TO FOLLOW WOMEN OVER SEVEN YEARS AND THEY HAVE STABLE ANTIBODY LEVEL AGAINST HPV 16 AND 18 FROM A SINGLE DOSE. 16 IS THE INTERRUPTED AND THE ANTIBODY LEVELS ARE LOWER WITH THE WOMEN WHO GOT ALL THREE DOSES BUT SUBSTANTIALLY HIGHER OF THE WOMEN NATURALLY INFECTED WITH HPV 16 AND 18. I’LL REITERATE, THE WOMEN WHO GOT ONE DOSE APPEAR TO BE FULLY PROTECTED AGAINST THE DEVELOPMENT OF HPV 16 AND 18 INFECTION. THIS IS NOT SUFFICIENT TO CHANGE STANDARD OF CARE BUT WE THINK THE DATA ARE ENCOURAGING OR SUFFICIENTLY ENCOURAGING TO DO A TRIAL TO SEE WHETHER A SINGLE DOSE MIGHT BE EFFECTIVE IN PREVENTING HPV INFECTION. SO WHAT WE’RE DOING IN COSTA RICA IS A TRIAL IN 12 TO 16-YEAR-OLD GIRLS COMPARED PROTECTION FROM ONE TWO TO TWO DOSES OF THE VACCINE AND GUARDISIL 9. IT’S UNETHICAL TO HAVE A PLACEBO SO WE’RE MEASURING CURRENT HPV PREVALENCE IN WOMEN IN THE SAME AREA TOO OLD TO BE ELIGIBLE TO GET THE VACCINE AND THAT SHOULD GIVE ACE REASONABLE NOTION OF WHAT THE EFFICACY. THE HYPOTHESIS IS PROTECTION IS INCREASED BY ONE DOSE NOT INFERIOR TO THE PROTECTION OF TWO DOSES. THE SECOND HYPOTHESIS IS PROTECTION WILL BE SIMILAR FROM ONE DOSE OF EITHER VACCINE AND MERCK USES SOMETHING MORE IMMUNOGENIC WHICH PROBABLY ACCOUNTS FOR MORE ANTIBODY LEVELS AND PROTECTION. AND THE PRINCIPLE INVESTIGATOR WROTE A PAPER TWO AND A HALF YEARS AGO TALKING ABOUT TALKING ABOUT CRIMINAL TRIALS AND THIS IS THE IDENTIFIER. THE POTENTIAL IMPACT OF IF THE ONE DOSE WORKS FIRST COULD ESTABLISH THE AND TIE — ANTIBODY PROTECTION. IT COULD PROVIDE A STRONG RATIONAL FOR REPETITIVE STRUCTURE AND SAVE MORE THAN $300 MILLION A YEAR IN VACCINE COSTS IN THE UNITED STATES ALONE. IT COULD MAKE IT FEASIBLE TO CONTROL THE WORLDWIDE PUBLIC HEALTH PROBLEM OF CERVICAL CANCER AND OTHER HPV ASSOCIATED CANCER. I DON’T HAVE A PATIENT BUT I HAVE A SAD STORY. MANY ARE FAMILIAR WITH THE HENRIETTA LACKS CERVICAL ADENOCARCINOMA AND THE HELA CELLS GAVE RISE TO OPRAH WINFREY BEFORE SHE WAS RUNNING FOR PRESIDENT, START IN A TV MOVIE ABOUT IT. SHE HAD HPV18. DIED QUICKLY, A SERIOUS DISEASE. HPV 18 CARCINOMA IS NOT USUALLY DETECTIBLE BUT IT WAS BEFORE PAP SMEAR SCREENING HAS BECOME POPULAR AND IT’S DONE A WONDERFUL JOB LOOKING THE THE SQUAMOUS CELL SO HER CANCER SHOULD NOW BE PREVENTIBLE BY PHV VACCINATION OR HPV-BASED SCREEN. I HAVEN’T TALKED ABOUT SCREENING BUT THERE’S BEEN SIMILAR ADVANCES IN CERVICAL CANCER SCREENING AS WITH VACCINATION. LET ME JUST LEAVE YOU WITH WHAT I HOPE WILL BE THE PARADIGM IN A NUMBER OF YEARS IN COUNTRIES THAT DON’T YET HAVE A CONTROL OF CERVICAL CANCER. THERE WOULD BE A COHORT OF YOUNG WOMEN WHO WOULD BE VACCINATE TO GIVE THEM PRIMARY PREVENTION BUT BECAUSE THE VACCINE DOESN’T HAVE THERAPEUTIC PROPERTIES IT WON’T BENEFIT THE WOMEN ALREADY INFECTED. FOR THEM WE’RE DEVELOPING COST-EFFECTIVE SCREENING FOR THE DEVELOPING WORLD AND THOSE WOMEN WOULD RECEIVE CERVICAL CANCER SCREENING AND THAT WAY WE HOPE TEN YEARS FROM NOW, WE WILL BE STARTING TO CONTROL CERVICAL CANCER INCIDENTS AND MORTALITY ON A GLOBAL BASIS. LET ME SUMMARIZE, BASIC RESEARCH HAS BEEN DETERMINED AS THE CAUSE OF SEVERAL CANCERS AND THE CAUSE OF THE VACCINE. IT’S HIGHLY EFFECTIVE IN PREVENTING NEW INFECTIONTION — ININFECTION IN DISEASE AND COULD INDUCE LONG-TERM PROTECTION WITH A SINGLE DOSE BUT WE DON’T KNOW THAT, THAT IS WHY WE DO RESEARCH AND CONTROL OF HPV ASSOCIATED CANCER AS A WORLDWIDE PROBLEM MAY SOON BE FEASIBLE. THANK YOU VERY MUCH. I LOOK FORWARD TO YOUR COMMENTS AND QUESTIONS. [APPLAUSE]>>AND IF HAVE YOU A QUESTION FOR DR. QUINN, HE STILL HERE AND CAN HANDLE HIS QUESTIONS MUCH BETTER THAN I COULD.>>I WAS WONDERING IF YOU’RE CONCERNED THE VACCINE WILL THEN SHIFT THE STRAIN AND YOU’LL SEE A NEW RISE OF A DIFFERENT HPV NOT COVERED?>>THE QUESTION IS WILL THERE BE AN EMERGENCE OF OTHER HPV TYPES THAT WILL BE CAUSING DISEASE. THE ANSWER SO IN THE SHORT-TERM — AT LEAST LOOKING OUT AT A 10-YEAR LEVEL, BOTH COMPANIES ARE USING WOMEN IN SCANDINAVIA TO LOOK AT THIS PROBLEM AND DOESN’T SEEM TO BE PRESENT. THEY’LL CONTINUE TO LOOK FOR IT. IF THERE WERE SUCH AN EMERGENCE IT WOULD BE FAIRLY STRAIGHTFORWARD TO ESSENTIALLY MAKE VIRUS-LIKE PARTICLES FOR THOSE TYPES AND INCORPORATE THAT INTO THE VACCINE. I SHOULD ALSO POINT OUT HPV 16 AND 18 ARE THE WORST ACTORS. IF THERE WERE AN EMERGENCE OF ANOTHER HPV TYPE IT WOULDN’T BE AS ONCO GENIC AS 16 AND 18. [INAUDIBLE] >>SO I THINK YOU’LL GET TWO DIFFERENT ANSWERS FROM ME AND DR. QUINN. THE REASON IS BECAUSE WHEN IT COMES TO HPV INFECTION, WE CAN DO SOMETHING FOR PRIMARY INFECTION AND DO SOMETHING FOR THE RISK OF CERVICAL CANCER BUT WE DON’T HAVE AN INFECTED INTERVENTION SUCH AS THE ANTI-MICROBIAL AGENT THAT EFFECTIVELY TREATS THE INFECTION. SO I THINK SO TO ME THE EDUCATION IS PRIMARILY AT THE LEVEL OF THE HEALTH CARE PROVIDER FOR CERVICAL CANCER SCREENING AND FOR VACCINATION. BUT DR. QUINN MAY HAVE A VERY DIFFERENT VIEW BECAUSE PEOPLE NEED TO KNOW THAT THEY MIGHT HAVE BACTERIAL INFECTIONS FOR WHICH THERE IS NO TREATMENT.>>SO AS I’M MENTIONED, PREVENTION IS BY FAR THE DEPENDENT ON EDUCATION. HAVING INDIVIDUALS VERY EARLY ON KNOW WHAT THE CONSEQUENCES OF HAVING UNPROTECTED SEX AND MULTIPLE SEX PARTNERS PUTS THEM AT RISK FOR ACQUIRING ONE OF THESE STDs. SCREENING AND TREATMENT IS ONE SIDE. IT’S ALREADY A LITTLE BIT TOO LATE FOR SOME OF THOSE — NOT TOTALLY LATE BUT WE DIDN’T PREVENT THEM FROM ACQUIRING THE STD. SO IT IS DIFFERENT WITH HPV WHICH CAN BE TRANSMITTED SO MANY DIFFERENT WAYS. SO I WOULD SAY YOU START DURING THE PRIMARY SCHOOL. AT WHAT GRADE I CAN’T ANSWER BUT PRIMARY SCHOOL IS WHERE INDIVIDUALS SHOULD BE MADE AWARE OF THE CONSEQUENCES OF SEXUAL ACTS AND SEXUAL TRANSMISSION OF THESE AGENTS. AS YOU MOVE INTO HIGH SCHOOL, BECAUSE I POINTED OUT CHLAMYDIA IS VERY COMMON IN THE HIGH SCHOOLS, THERE’S IT’S ROUTINE SCREENING AND GETTING AND KEEPING THE EDUCATION GOING. CONSEQUENCES.EASES HAVE YOU WANT TO PREVENT THOSE CONSEQUENCES SO BE SCREENED EARLY AND GET TREATED. WE DON’T HAVE FOR MOST OF THEM, JUST TWO INFECTIONS THAT CAN BE PREVENT VACCINE. THAT’S DIFFERENT BECAUSE YOU CAN APPLY THE VACCINE AT HEALTH VISITS BUT THE OTHERS DON’T HAVE A VACCINE. THE ONLY WAY WE CAN TRY TO INFLUENCE THEIR TRANSMISSION IS THROUGH EDUCATION, BACK TO EDUCATION. CHANGE OF BEHAVIOR OR INFLUENCING BEHAVIOR THE WAY WE’VE DONE IT WITH SMOKING AND CAR SEATS AND OTHER PUBLIC HEALTH INTERVENTIONS AND THEY DO HAVE AN IMPACT OVER TIME.>>I THINK IN A VERY IMPORTANT DIFFERENCE IS FOR THE BACTERIAL DISEASES, YOU REALLY NEED TO CHANGE BEHAVIOR AND YOU NEED EDUCATION TO CHANGE THE BEHAVIOR WHEREAS FOR BETTER OR WORSE, WHEN HAVE YOU A VACCINE THE ONLY BEHAVIOR YOU NEED TO CHANGE IS TO GET PEOPLE TO COME IN AND GET VACCINATE.>>I HAVE ANOTHER QUESTION TO DR. LOWY. I KNOW [INDISCERNIBLE] DIFFICULT TO TREAT AND IN THE LATE STAGES AS WELL, HOW IS THE VACCINE BEING FOLLOWED FOR HPV INFECTION AND FOR PHARYNGEAL INCIDENTS.>>THERE WERE LESIONS PREVENTED BY THE VACCINE. THERE ARE NO SUCH CLEARLY IDENTIFIED LESIONS IN THE ORAL CAVITY OR THE ORAL PHARYNX. THEREFORE THERE’S NO FDA APPROVAL FOR THE VACCINE IN THE ORAL FAVPHARYNX. THE ONLY CONTROLLED TRIAL IS OF THE WOMEN OF COSTA RICA ARE WE SHOWED PROTECTION IN THE WOMEN IN TERMS OF PROTECTION AGAINST HPV 16 BUT THAT IS POST-ANALYSIS. IT’S UNCLEAR THE INFECTION RATE IS UNCLEAR HOW LONG IT MAY TAKE TO SEE A DIFFERENCE IN ORAL PHARYNX CANCER. SAY THE VACCINE WAS INTRODUCED 10 YEARS AGO AND HAD AN UPTAKE FIVE YEARS AGO AND MAINLY IT’S OCCURRING IN PEOPLE WHO ARE SAY 50 YEARS OLD OR OLDER. SOO SO YOU’LL HAVE TO WAIT OVER 30 YEARS BEFORE YOU HOPE TO SEE A SUBSTANTIAL DIFFERENCE. SO IT REALLY IS AN AMBIGUOUS AREA BUT THERE’S EVERY REASON TO ASSUME THE VACCINE WORKED BECAUSE THE VACCINE WAS GIVEN AND IT WORKS CLEARLY IN THE TRACT AND [INDISCERNIBLE] IF THERE’S AN IMMUNITY IT SHOULD DECREASE THE PREVALENCE OF THE VIRUS AND DECREASE EXPOSURE.>>THANK YOU BOTH VERY MUCH. [INAUDIBLE]

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