TB & HIV: A Deadly Duo

TB & HIV: A Deadly Duo

February 14, 2020 4 By Jose Scott


WELCOME TO THE CDC’S PUBLIC HEALTH GRAND ROUND. I’M TANYA POPOVICH SCIENTIFIC
DIRECTOR OF THE GRAND ROUND. I WANT TO THANK YOU FOR THOSE OF
YOU HERE IN PERSON AND THOSE OF YOU WATCHING US. IN ADDITION, I HOPE THAT THERE
ARE THOUSANDS OUT THERE WATCHING US THROUGH OUR INTERNET SITE
THAT IS PROVIDED HERE. WE HAVE JUST RECENTLY REVAMPED
OUR PUBLIC HEALTH GRAND ROUND’S WEB PAGE SO THAT NOW YOU CAN GET
YOUR CONTINUING EDUCATION CREDITS, CLICK IN ONE PLACE THAT
YOU CAN SEND US YOUR FEEDBACK, YOU CAN SUBSCRIBE AND DO A LOT
OF THINGS WITH THIS WEB PAGE. YOU CAN ALSO SEE ALL THE
ARCHIVED SESSIONS AND YOU CAN SEE THE SCHEDULE FOR THE
UPCOMING ONES. I DO WANT TO MENTION THAT,
AGAIN, WE HAVE COORDINATED OUR SCIENCE CLIP WITH THE EVENTS AT
THIS SESSION AND HAVE HAD A LITTLE-KNOWN COLLEAGUE SELECT
THE TOPICS, THE PAPERS, IN THIS TIME, DR. THOMAS FRIEDEN. WE ALLOWED HIM TO DO IT THIS
WAY. ONE THING THAT I DO WANT TO SAY
THAT WE ALL TAKE PRIDE IN HOW MANY PEOPLE CONTINUE TO VIEW OUR
EVENTS AND WITH WE ZS AND WE HAVE HAD OVER THE
PAST 18 MONTHS OVER 220,000 PEOPLE IN PERSON, DOWNLOADING
THROUGH YOUTUBE AND ALL KINDS OF EVENTS. I WOULD LIKE TO BRING YOUR
ATTENTION TO SEVERAL UPCOMING TOPICS THAT ARE GOING TO BE HERE
IN APRIL, MAY, AND A COUPLE OF MONTHS LATER. TODAY, AS OBVIOUSLY ALL OF YOU
KNOW, IS THE WORLD TV DAY AND THIS IS A MAJOR EVENT FOR OUR
AGENCY AND A LOT OF PEOPLE GLOBALLY. I’D LIKE TO ACKNOWLEDGE THAT
THERE’S GOING TO BE ADDITIONAL EVENTS TAKING PLACE LATER IN THE
AFTERNOON. TODAY WE HAVE AN UNBELIEVABLE
GROUP OF SPEAKERS. WE HAVE OUR OWN EXPERTS, SOME OF
WHOM HAVE FLOWN, LIKE JAY, FROM CHINA TO BE HERE WITH US. WE HAVE DR. MARIO RAVIONI, THE
DIRECTOR OF THE W.H.O. STOP TB PROGRAM WHO IS GOING TO BE
JOINING US VIRTUALLY IN A FEW MINUTES AND OUR OWN DIRECTOR WHO
IS GOING TO BE ONE OF THE SPEAKERS. AT THIS POINT, IN ADDITION TO
OUR NORMAL OUTLETS YOU WILL SEE AND I WILL KEEP MENTIONING IT,
THAT A LOT OF THE EVENTS THAT HAPPEN IN THE GRAND ROUND ARED
ADVERTISED AND GOING TO BE PUT ON DIFFERENT OTHER WEB SITES
SUCH AS THIS ONE, AIDS.GOV. SO PEOPLE ARE BECOMING MORE AND
MORE FAMILIAR WITH THIS PROGRAM. I WOULD ALSO LIKE TO POINT OUT
THAT OUR OWN EMERGING INFECTIOUS DISEASES JOURNAL IS DEFEAT
DWOETING A SUBSTANTIAL OF ITS MARCH ISSUE TO TOPICS OF
TUBERCULOSISES IN RECOGNITION OF THE WORLD’S DAY THAT IS
RECOGNIZING THE TIME WHEN ROBERT KOFF IDENTIFIED THE CAUSE OF THE
ORGANISM. ONE THING I WANT TO POINT OUT,
SPEAKERS HERE ARE NOT — THIS IS EXTREMELY IMPRESSIVE WE’RE ALL
SPEAKING FROM THEIR OWN PERSONAL EXPERIENCES IN THE FIELD,
DEALING WITH TU BJERKEBERCULOSIS ESPECIALLY COMBINED WITH HIV. THESE ARE PICTURES OF MARIO,
TERAZ AND KEN CASTRO IN INDIA. THIS IS TRULY AN INTERNATIONAL
TEAM THAT IS PUTTING THIS PARTICULAR TEAM TOGETHER. ONCE A LITTLE BIT OF A CHALLENGE
BECAUSE OF THE TIME DIFFERENCES. SOME PEOPLE WERE IN CHINA, SOME
PEOPLE WERE IN GENEVA. SO WE HAD LIKE 15, 16 HOURS
DIFFERENCE, BUT WE DID MANAGE TO PRACTICE BECAUSE PRACTICE MAKES
PERFECT, AND HERE ARE MY TEAM THAT WORKED DILLIGENTLY WITH ME
OVER THE PAST FEW WEEKS SO YOU CAN ENJOY THE EVENT TODAY. SO NORMALLY DR. FRIEDEN WOULD
SAY A COUPLE OF COMMENTS, BUT BECAUSE HE IS ONE OF THE
SPEAKERS TODAY, WE HAVE ASKED KEN CASTRO, DIRECTOR OF THE
TB — DIVISION FOR TB ELIMINATION TO SAY A FEW OPENING
REMARKS. [ APPLAUSE ]
>>THANK YOU, TANYA. I’LL KEEP THIS VERY BRIEF
BECAUSE I REALLY WANT TO HEAR WHAT THESE GUYS HAVE TO SAY. WELCOME TO TODAY’S PUBLIC HEALTH
GRAND ROUND. TODAY CBDC IS ANNOUNCING THAT
THE UNITED STATES CURRENTLY HAS THE
LOWEST INCIDENCE OF TUBERCULOSIS SINCE PUBLIC HEALTH REPORTING
BEGAN. WE CONTRAST THIS SITUATION WITH
THAT IN THE REST OF THE WORLD, WHERE HIV IS DRIVING A REMERGE
ENS OF TUBERCULOSIS VERY SIMILAR TO THAT EXPERIENCE IN THE UNITED
STATES BETWEEN 1985 AND 1992. AT THAT TIME, I HAD TO BRIEF
DR. JIM CURRAN, THEN CDC’S ASSOCIATE DIRECTOR FOR HIV/AIDS
AND AS YOU WELL KNOW NOW DEAN OF THE SCHOOL OF PUBLIC HEALTH
ABOUT THE BURGEONING PROBLEM OF HIV-ASSOCIATED TUBERCULOSISES
AND DRUG RESISTANCE AND AS TYPICALTIP
TAL JIM CURRAN FASHION, AT THE END OF THE BRIEFING, HE SAID, SO
WHAT YOU TELL ME TB AND HIV HANG OUT TOGTD AND THEY’RE ABAD
INFLUENCE ON EACH OTHER. HE CLEARLY DEMONSTRATED AN
UNDERSTANDING OF THE TWO PATH GENERALS. NO THOSE DAYS, OUR DIRECTOR
DR. FRIEDEN SPENT MUCH OF HIS TIME AS AN OFFICER INVESTIGATING
OUTBREAKS OF MULTIDRUG RESISTANT TUBERCULOSIS ASSOCIATED WITH HIV
INFECTION. TODAY WE WILL REVIEW SOME OF THE
CHALLENGES ASSOCIATED WITH ACCURATELY RULING OUT
TUBERCULOSIS DISEASE IN HIV-INFECTED PERSONS BEFORE
INITIATING POTENTIALLY LIFESAVING AND PREVENTIVE
THERAPY. ALSO WE’LL SEE HOW THE RESULT
OFS OF THE STUDIES PRESENTED HERE BECAME PART OF THE EVIDENCE
BASIS USED BY W.H.O. TO DERIVE NEW POLICY. IN MY OPINION, THIS REFLECTS DR
DC AT ITS BEST, WORKING WITH GLOBAL PARTNERS IN THE PRACTICAL
APPLICATION OF PUBLIC HEALTH RESEARCH TO IMPROVE PROGRAMS
WHICH BENEFIT PATIENTS. OUR FIRST PRESENTER THIS MORNING
IS DR. JAY VARMAE CHIEF OF CDC’S EMERGING PROGRAM IN CHINA. [ APPLAUSE ]
>>GOOD MORNING. MY NAME IS JAY VARMA. I WILL SET THE KUHN TEXT FOR
UNDERSTANDING WHY HIV AND TB ARE FRIENDS WITHOUT BENEFITS. THERE ARE SEVERAL COMMON
MISCONCEPTIONS. THE FIRST IS THAT TB IS A SINGLE
DISEASE. IN FACT, TB EXISTS IN TWO
DIFFERENT STATES. TB INFECTION AND TB DISEASE. AFTER EXPOSURE TO A PERSON WITH
INFECTIOUS TB DISEASE, A SUSCEPTIBLE PERSON MAY DEVELOP
TB INFECTION. A PERSON WITH TB INFECTION MAY
GO ON TO DEVELOP TB DISEASE. THE LIFETIME RISK OF DEVELOPING
TB DISEASE IS 10% TO 15%, BUT THAT RISK, HOWEVER, IS GREATLY
INCREASED IN PEOPLE WITH HIV INFECTION. THE TB SPECIALISTS THEREFORE
VIEWS THE WORLD AS THREE DISCREET POPULATIONS —
PEOPLE WITH NO TB INFECTION, PEOPLE WITH TB INFECTION, AND
PEOPLE WITH TB DISEASE. OF THE ESTIMATED 6.9 BILLION
PEOPLE IN THE WORLD, 2.3 BILLION ARE ALREADY INFECTED WITH TB. AND MORE THAN 9 MILLION DEVELOP
TB DISEASE EACH YEAR. THIS SLIDE SHOWS THE ESTIMATED
NUMBER OF NEW TB CASES THAT OCCURRED THROUGHOUT THE WORLD. INDIA AND CHINA ALONE, TOGETHER,
ACCOUNT FOR 2 MILLION CASES EACH YEAR. IN CONTRAST, AS YOU JUST HEARD
FROM DR. CASTRO, THE U.S. REPORTS LESS THAN 12,000 CASES
EACH YEAR. TB IS RESPONSIBLE FOR MORE THAN
2 MILLION DEATHS EACH YEAR AND TB CAUSES MORE DEATHS IN WOMEN
THAN PREGNANCY AND CHILD BIRTH COMPLICATION. TB, UNFORTUNATELY, IS NOT EASY
TO DIAGNOSE. ONLY TWO TESTS, THE SKIN TEST
AND RELEASE ASAY DIAGNOSE TB INFECTION BUT THESE CAN BE
DIFFICULT TO IMPLEMENT IN RESOURCE-LIMITED SETTINGS. FOR TB DISEASE, MULTIPLE TESTS
EXIST BUT NONE OF THEM ARE IDEAL. THE MOST WIDELY USED TEST IS THE
MICROSCOPIC EXAMINATION OF SPUTUM. THE GLOBAL TB STRATEGY HAS
FOCUSED ON INCREASING ACCESS TO THE TEST BECAUSE IT’S
INEXPENSIVE AND HIGHLY SPECIFIC FOR INFECTIOUS TB. CULTURE OF SPUTUM FOR TB IS THE
MOST SENSITIVE BUT IT’S CHALLENGING TO IMPLEMENT IN
RESOURCE-LIMITED SETTINGS. A SENSITIVE EEDZY TO USE ASSAY
HAS RECENTLY BEEN VALIDATED BY IT’S EXPENSIVE AND FEASIBILITY
IS STILL LACKING. LET’S NOW FOCUS ON WHY HIV AND
TB TOGETHER ARE A DANGEROUS DUO. PEOPLE WITH HIV ARE MORE LIKELY
TO DEVELOP TB. HIV MAKES TB HARDER TO DIAGNOSE
AND TREAT. AND HIV PATIENTS HAVE A HIGH
RISK OF DIEYING DURING TB TREATMENT. LET’S LOOK AT EACH CHALLENGE IN
MORE DETAIL. DATA FROM AFRICA IN THE 1990s
DEMONSTRATES THAT HIV IS THE SINGLE MOST POWERFUL RISK FACTOR
FOR PROGRESSING FROM TB INFECTION TO DISEASE. ON THE X AXIS IS HIV PREVALENCE
AMONG ADULTS FROM SEVERAL AFRICAN COUNTRIES IN 1990. LOW HIV PREVALENCE IS ON THE
LEFT, HIGH HIV PREVALENCE ON THE RIGHT. ON THE Y AXIS IS TB INCIDENCE,
LOW INCIDENCE AT THE BOTTOM AND HIGH INCIDENCE AT THE TOP. I WILL SHOW YOU NOW HOW TB
INCIDENCE CORRELATE WITH HIV PREVALENCE. WATCH HOW COUNTRIES MOVE TO THE
RIGHT AND UP, MEANING INCREASED HIV AND INCREASED TB, FROM 1990
TO 2007. AS HIV EPIDEMIC SPREAD
THROUGHOUT AFRICA, TB CASE RATES ROSE DRAMATICALLY. AS THESE SLIDES SHOW, HIV HAS
BEEN DRIVING A MAJOR EPIDEMIC OF TB IN AFRICA FOR THE PAST 20
YEARS. HIV MAKES TB EVEN HARDER TO
DIAGNOSE. PEOPLE WITH HIV AND PULLMONARY
TB ARE OFTEN SPUTUM NEGATIVE. TB OFTEN OCCURS OUTSIDE THE
LUNGS. BECAUSE TB IS BOTH COMMON AND
DIFFICULT TO DIAGNOSE, MANY PEOPLE WITH HIV FEEL ILL BUT
THEY DON’T KNOW THAT THEY HAVE TB. A RECENT SYSTEMATIC REVIEW FOUND
THAT 8% OF PATIENTS PRESENTING TO HIV CLINICS HAD UNDIAGNOSED
TB DISEASE. IN MATERNAL HEALTH CLINICS, THE
RATE OF UNDIAGNOSED TB IS LOWER BUT STILL STRIKING. HIV ALSO MAKES TB HARDER TO
TREAT. PATIENTS MUST TAKE SEVERAL PILLS
SEVERAL TIMES A DAY TO TREAT BOTH DISEASES. THESE DRUGS MAY INTERACT WITH
EACH OTHER AND HAVE OVERLAPPING TOX ISICITY
TOXICITY. AFTER TB DIAGNOSIS, PEOPLE WITH
HIV HAVE A HIGH RISK OF DYING DURING TB TREATMENT. MANY STUDIES HAVE SHOWN THAT THE
CASE FATALITY RATE HAS CONSISTENTLY BEEN VERY HIGH. WITH AS MANY AS 50% OF HIV
PATIENTS DYING DURING TB TREATMENT. IN SOUTHEAST ASIA, MOST OF THESE
DEATHS OCCUR EARLY DURING TB TREATMENT. AMONG IV INFECTED PATIENTS IN
THIS STUDY, 70% DIED DURING THE FIRST TWO MONTHS OF TB
TREATMENT. STUDIES I CONTACT KUBLGTED WHILE
IN THAILAND SHOWED THAT MOST OF THESE DEATHS ARE DUED TO DELAYED
TB DIAGNOSIS. ANY INTERVENTION TO REDUCE THE
RISK OF DEATH THEREFORE HAS TO OCCUR EITHER BEFORE TB DIAGNOSIS
OR VERY SOON THEREAFTER. PEOPLE WITH HIV DO NOT HAVE TO
DEVELOP TB. TB CAN BE PREVENTED. FIRST YOU MUST FIND AND TREAT TB
IN PEOPLE WITH HIV. SECOND, YOU CAN GIVE ICE OWE
NIGH ZID FOR AT LEAST SIX MONTHS TO PEOPLE WITH HIV WHO DO NOT
HAVE TB DISEASE. THIS IS TO TREAT TB INFECTION. BUT IN 2009, ONLY 0.2% OF PEOPLE
LIVING WITH HIV AROUND THE WORLD RECEIVED ISINIAZID THERAPY. EITHER BECAUSE FINDING TB
DISEASE IS DIFFICULT IN SETTINGS WITH LIMITED RESOURCES OR
BECAUSE THE EFFECTIVE IPT IS NOT LONG LASTING. SO HOW CAN WE IMPROVE TB
PREVENTION AMONG PEOPLE LIVING WITH HAD HIV IN RESOURCE LIMITED
SETTINGS? WE NEED ANSWERS TO TWO IMPORTANT
QUESTIONS. THE FIRST QUESTION, IN PEOPLE
WITH HIV NOT YET DIAGNOSED WITH TB, IS THERE A SIMPLE ALGORITHM
THAT FRONT LINE HEALTH CARE WORKERS CAN USE TO IDENTIFY
PATIENTS WHO DO NOT HAVE TB DISEASE? SECOND, IN PERSONS WHO ARE
SCREENED AND FOUND NOT TO HAVE TB DISEASE, CAN TREATMENT OF TB
INFECTION FOR PERIODS LONGER THAN SIX MONTHS PREVENT
REINFECTION WITH TB? THE NEXT TWO SPEAKERS WILL
DISCUSS HOW CDC RESEARCH HELPED ANSWER THESE QUESTIONS TO MOVE
GLOBAL HEALTH POLICY FORWARD. THE NEXT SPEAKER IS DR. KEVIN
CANE, CURRENTLY THE CHIEF OF THE TB/HIV TEAM WITHIN THE DIVISION
OF DUETUBERCULOSISES ELIMINATION. KEVIN?>>GOOD MORNING. THANK YOU ALL FOR COMING TODAY. IT’S MY PLEASURE TO BE HERE
TODAY TO SPEAK WITH YOU ABOUT HOW TO RULE OUT TB IN PEOPLE
WITH HIV, WHICH IS THE FIRST CRITICAL STEP TO TB DIAGNOSIS
AND PREVENTION. W.H.O. GUIDELINES IN 2007
RECOMMENDED SCREENING ALL PEOPLE FOR TB BY ASKING IF THEY HAD
CHRONIC COUGH. IF PRESENT, DIAGNOSTIC
EVALUATION FOR TB WAS INDICATED, WHILE IF ABSENT TB WAS
CONSIDERED TO BE RULED OUT. THIS APPROACH WAS BASED ON
EXPERT OPINION FROM THE PRE-HIV ERA AND HAD NOT BEEN VALIDATED
IN PEOPLE WITH HIV. SEVERAL PROBLEMS WERE QUICKLY
IDENTIFIED. FIRST, SMALL STUD COUNTRIES
SUGGESTED LOW SENSITIVITY OF CHRONIC COUGH FOR TB SCREENING
IN PEOPLE WITH HIV. UPTAKE OF THE STRATEGY WAS LOW. MOST IMPORTANTLY, IN PEOPLE WITH
HIV WHO HAD TB, THE CASE FATALITY RATE WAS VERY HIGH. TO TRY TOO DEVELOP AN
EVIDENCE-BASED ALGA RHYTHM FOR TB SCREENING AND DIAGNOSIS, WE
DESIGNED A STUDY CALLED IMPROVING DIAGNOSIS OF TB IN
PEOPLE HAD HWITH HIV. SOME OF SITES WHERE IT WAS
IMPLEMENTED ARE SU PORTED BY PAPVAR. USING STANDARDIZED LABORATORY
PROCEDURES IN ALL COUNTRIES, WE DID MICROBACTERIAL CULTURE AND
SMEAR OF SIX TO SEVEN SPECIMENS FOR EACH PATIENT. PATIENTS WITH A POSITIVE CULTURE
FOR TB FROM ANY SITE WERE DEFINED AS HAVING TB. WE COLLECT STANDARDIZED DATA ON
ALL PATIENTS INCLUDING DATA ON OVER 50 DIFFERENT SIGNS AND
SYMPTOMS. WE CALCULATED PERFORMANCE
CHARACTERISTICS OF INDIVIDUAL SAINZ AND SYMPTOMS AND ALL
POSSIBLE COMBINATIONS THEREOF, TOTALLING OVER 80 MILLION. WE THEN CALCULATED THE YIELD OF
DIFFERENT DIAGNOSTIC TESTS. HERE IS THE SCHEMATIC OF THE
GENERAL GOAL OF TB SCREENING. IT STARTS WITH ALL PEOPLE WITH
HIV. FOR EXAMPLE, EVERY PERSON
PRESENTING FOR EVALUATION AFTER HIV DIAGNOSIS. IT THEN SEEKS TO DIVIDE THIS
LARGE POPULATION INTO TWO GROUPS, THOSE FOR WHOM TB IS
EXCLUDED BASED ON SCREENING ALONE FOR WHOM PREVENTIVE
THERAPY MAY BE CONSIDERED AND THOSE FOR WHOM TB IS SUSPECTED
AND FURTHER DIAGNOSTIC EVALUATION IS NEEDED. FOR THIS SCREENING STEP, HIGH
SENSITIVITY IS CRITICAL TO AVOID MISSING PATIENTS WITH TB. SIMPLICITY IS NEEDED TO ENSURE
IT CAN BE USED ANYWHERE. HERE WE SHOW THE RESULTS OF OUR
TB CULTURES. OF 1,748 PEOPLE WITH HIV, 267 OR
15% OF THEM HAD AT LEAST ONE POSITIVE CULTURE FOR TB. FOR COMPARISON, THE PREVALENCE
OF TB DISEASE IN THE U.S. POPULATION IS ABOUT 5 PER
100,000. THE 15% PREVALENCE IN OUR STUDY
POPULATION EQUATES TO 15,000 PER 100,000. WHILE THE CULTURE-BASED APPROACH
IS BY DEFINITION VERY SENSITIVE, IT LACKS SIMPLICITY, AS CULTURE
IS OFTEN NOT AVAILABLE. THEREFORE, WE SOUGHT SIMPLER,
SENSITIVE APPROACHES TO SCREENING. COUGH GREATER THAN TWO WEEKS,
THE QUESTION RECOMMENDED FOR TB SCREENING IN THE W.H.O. GUIDELINE WAS SHOWN TO BE 33%
SENSITIVE. THAT MEANS THAT 67% OF PATIENTS
WITH TB WILL NOT BE DETECTED THIS WAY AND WILL HAVE
UNDIAGNOSED TB. NO SINGLE SYMPTOM HAD
SUFFICIENTLY HIGH SENSITIVITY. WE FOUND THAT THE BEST
COMBINATION WAS TO ASK PATIENTS IF THEY HAD EXPERIENCED COUGH OR
FEVER OF ANY DURATION OR NIGHT SWEATS FOR LONGER THAN THREE
WEEKS. PATIENTS WITH AT LEAST ONE OF
THOSE THREE SYMPTOMS ARE SUSPECTED OF HAVING TB AND NEED
DIAGNOSTIC EVALUATION. WHILE FOR PATIENTS WITH NO
SYMPTOMS TB IS EXCLUDED. THE SENSITIVITY OF THIS APPROACH
IS 93%. SYMPTOM-BASED SCREENING IS
CLEARLY SIMPLE, BUT IT IS NOT ALWAYS SENSITIVE. WHEN THE W.H.O. 2007 GUIDELINES
WHICH BASE TB SCREENING ON CHRONIC COUGH ARE APPLIED, 67%
OF PATIENTS WITH TB WILL BE MISCLASSIFIED AS NOT HAVING TB. A POTENTIALLY DEADLY ERROR. NOW, IF WE APPLY THE COMBINATION
OF OUR THREE PREDICTORS, COUGH OR FEVER OF ANY DURATION OR
NIGHT SWEATS FOR AT LEAST THREE WEEKS, ONLY 7% OF TB PATIENTS
ARE MISCLASSIFIED AS NOT HAVING TB. THIS INCREASED SENSITIVITY DOES
COME AT A COST AS MORE PATIENTS SCREEN POSITIVE AND WILL REQUIRE
FURTHER DIAGNOSTIC EVALUATION. THE DIAGNOSTIC EVALUATION FOR TB
RELIES HEAVILY ON SMEAR MEI CROSS COP COPY IN MOST RESOURCE
LIMITED SETTINGS, HOWEVER, WE FIND THAT IN PEOPLE WITH HIV,
JUST 31% OF TB PATIENTS ARE DIAGNOSED WITH TB WHEN TWO
SPUTUM SMEARS ARE USED. A THIRD SMEAR DETECTS ONLY AN
ADDITIONAL 1% OF CASES, DEMONSTRATING THAT SMEAR ALONE
IS NOT ENOUGH FOR DIAGNOSING TB IN PEOPLE WITH HIV. ADDING LIQUID CULTURE OF TWO
SPUTUM SPECIMENS MORE THAN DOUBLES THE YIELD. IF SMEAR AND CULTURE OF TWO
SPECIMENS ARE DONE, 76% OF ALL TB CASES WILL BE DETECTED A
LARGE IMPROVEMENT OVER SMEAR ALONE. TO SUMMARIZE THIS STUDY, 15% OF
PEOPLE WITH HIV HAD TB DISEASE, AN IMPORTANT FINDING BECAUSE
UNDIAGNOSED TB IS FREQUENTLY FATAL IN PEOPLE WITH HIV. WE SUCCEEDED IN IDENTIFIED A
SIMPLE, SENSITIVE APPROACH USING THREE SYMPTOMS TO RULE OUT TB. SCREENING BASED ON CHRONIC COUGH
FAILED TO DETECT MOST TB PATIENTS AND SHOULD NOT BE USED
ALONE FOR TB SCREENING IN PEOPLE WITH HIV. WE DID NOT IDENTIFY A SIMPLE
APPROACH TO RULING IN TB DISEASE, BUT WE DID FIND THAT
SMEAR IS INADEQUATE FOR THIS PURPOSE AND THAT SPUTUM CULTURE
IS GENERALLY NEEDED. THE CHALLENGE IS THAT LIQUID
CULTURE IS RARELY AVAILABLE AND IS DIFFICULT TO IMPLEMENT,
REQUIRING HIGH LEVELS OF TRAINING, BIOSAFETY AND
SUPERVISION. A NEW SELF-CONTAINED PCR-BASED
TEST WAS RECENTLY RELEASED AND ENDORSED BY W.H.O. AS THE
INITIAL DIAGNOSTIC TEST OF CHOICE IN PEOPLE WITH HIV
BECAUSE OF ITS SIMPLICITY AND SENSITIVITY. WE DO NOT KNOW YET, HOWEVER, IF
IT CAN BE EFFECTIVELY SCALED UP. TO DETERMINE WHETHER DATA FROM
THIS STUDY COULD BE EXTRAPOLATED GLOBALLY, W.H.O. AND CDC
COLLABORATED ON AN INDIVIDUAL PATIENT DATA META ANALYSIS WHICH
SUPPORTED OUR RESULTS, FINDING THAT A VERY SIMILAR COMBINATION
OF SYMPTOMS HAD A HIGH SENSITIVITY FOR TBMENT THE
EVIDENCE WAS TRANSLATED INTO GLOBAL POLICY. W.H.O. RECENTLY RELEASED NUD
GUIDELINES WHICH INCORPORATES THE COMBINATION OF PREDICTORS
IDENTIFIED IN THE META ANALYSIS. THE NEXT SPEAKER WILL TALK ABOUT
THIS IN MORE DETAIL. PERSONALLY, WHAT I FIND MOST
ENCOURAGING IS TO SEE THAT THESE SCIENTIFIC FINDINGS ARE ALREADY
IMPACTING PATIENTS. THE REVISED W.H.O. POLICY IS
BEING SCALED UP GLOBALLY AND WITH SUBSTANTIAL FINANCIAL
INVESTMENT FROM PAPVAR AND HARD WORK FROM MANY CDC FIELD STAFF,
MANY OF WHOM ARE IN THIS ROOM TODAY, THESE FINDINGS ARE BEING
BROUGHT TO PATIENTS. EFFECTIVE COLLABORATIONS WITHIN
AND OUTSIDE OF THE U.S. GOVERNMENT WERE ESSENTIAL TO
ADDRESSING AN IMPORTANT KNOWLEDGE GAP, NAMELY, HOW TO
SCREEN FOR TB IN PEOPLE WITH HIV. TO TRANSLATING THESE FINDINGS
INTO GLOBAL POLICY AND RAPIDLY BRINGING THESE LIFESAVING
ADVANCES TO PATIENTS. NOW THAT YOU HAVE SEEN THE
APPROACHES TO SCREENING FOR TB IN PEOPLE WITH HIV, THE NEXT
SPEAKER WILL FOCUS ON THE NEXT MAJOR ISSUE, AND THAT IS TB
PREVENTION IN PEOPLE WITH HIV. [ APPLAUSE ]
>>GOOD MORNING. THIS PRESENTATION REFLECTS MY
SERVICES AS A MEMBER OF CDC’S DIVISION OF TUBERCULOSIS
ELIMINATION. BENJAMIN FRANKLIN REPORTEDLY
SAID, AN OUNCE OF PREVENTION IS WORTH A POUND OF CURE. GIVEN THE TREMENDOUS MORBIDITY
AND MORTALITY INFLICTED BY TB UPON HIV PATIENTS, IT IS VITAL
TO PREVENT TB DISEASE. AS DR. VARMA MENTIONED, AFTER
EXPOSER YOU’RE TO TUBERCULOSISES, SOME PEOPLE
BECOME INFECTED, ONLY SOME OF THESE WILL EVER BECOME SICK WITH
TB, BUT THE RISK IS VERY HIGH IN PEOPLE WITH HIV WHO HAVE TB
INFECTION. THE TU BJERKE LAN SKIN TEST
IDENTIFIES PEOPLE WITH TB INFECTION. THE PROVISION OF IPT TO PATIENTS
WITH A POSITIVE SKIN TEST CURES TB INFECTION SO THAT THE RISK OF
TB DISEASE IS REDUCED. ANTIRETRO VIRAL THERAPY IS A KEY
INTERVENTION THAT DRAMATICALLY IMPROVES MORTALITY IN HIV
INFECTED PERSONS AND ALSO REDUCES THEIR RISK OF TB. AS THEIR IMMUNE SYSTEM RECOVERS,
INCREASED PROTECTION FROM TB IS CONFERRED. HOWEVER, IN ENDEMIC SETTINGS,
THE ANNUAL RATE OF TB RATING FROM TWO TO SEVEN TB CASES FOR
EVERY 100 PERSONS REMAINED UNACCEPTABLY HIGH IN
HIV-INFECTED PERSONS RECEIVING ANTIRETRO VIRAL THERAPY. SO WHAT ELSE COULD BE DONE? IN THE PRE-ANTIRETROVIRAL
THERAPY ERA, IPT WAS EFFECTIVE IN PREVENTING TB DISEASE IN
PEOPLE WITH HIV. TB WAS REDUCED BY 64% IN PERSONS
WITH POSITIVE SKIN TESTS OR TST. TST NEGATIVE PERSONS DID NOT
BENEFIT SIGNIFICANTLY FROM IPT. IF THE TST WAS NOT TAKEN INTO
ACCOUNT AND IPT WAS PROVIDED TO ALL HIV ISSUE FEKTED PERSONS,
THERE WAS A 33% REDUCTION IN THE RISK OF TTB. IN 1998, THESE RESULTS LEDDED
WORLD HEALTH ORGANIZATION TO RECOMMEND SIX MONTHS FOR IPT FOR
TB INFECTED PERSONS. OPERATIONAL CONCERNS ABOUT THE
IMPLEMENTATION OF THE TST LEFT THE W.H.O. TO ADD THAT IF
GREATER THAN 30% OF THE POPULATION WAS INFECTED WITH TB,
THE TST NEED NOT BE PERFORMED. HOWEVER, IN LATER STUDIES IN
AFRICA, WE FOUND THAT THE BENEFIT OF IPT WANED WITHIN SIX
TO 18 MONTHS AFTER IPT COMPLETION. AND SUBSEQUENT MOLECULAR STUDIES
IN ENDEMIC COUNTRIES SUGGESTED THAT THE REASON PLAY BE
INFECTION WITH NOW STRAINS OF TB BECAUSE OF ONGOING HIGH LEVELS
OF TB EXPOSURE. ACCORDING TO ONE TB PREVENTION
RESEARCHER, SO LONG AS IT’S RAINING, YOU NEED AN UMBRELLA. HERE IS A CLINICAL TRIAL CDC
CONDUCTED NO COOPERATION WITH THE GOVERNMENT WITH BOTSWANA TO
SEE WLO WHETHER CONTINUOUS IPT WORKED BETTER THAN THE OTHER
COURSE. IPT WITHOUT SKIN TESTING AND
PROVIDED FREE ANTIRETROVIRAL THERAPY FOR ELIGIBLE PERSONS. WE ENROLLED HIV-INFECTED ADULTS
AND HALF RECEIVED SIX MONTHS OF IPT AND THE OTHER HALF RECEIVED
36 MONTHS OF IPT. I SHALL REFER TO THESE TWO STUDY
ARMS AS 6 IPT FOR THE STANDARD DURATION AND 36 IPT FOR THE
CONTINUOUS TREATMENT ARM. WE OBSERVED THAT 36 MONTHS IPT
WAS SUPERIOR TO 6 MONTHS IPT IN REDUCING THE RISK OF TB. HOUGH, THIS BENEFIT WAS ROW
STRICTED TO TST POSITIVE PARTICIPANTS SHOWN IN RED. TST NEGATIVE PARTICIPANTS SHOWN
IN BLUE RECEIVED NO SIGNIFICANT BENEFIT. ADDITIONALLY, ABOUT 200 DAYS
AFTER THE INITIAL SIX MONTHS OF IPT THE RISK OF TB ESCALATED. STATED IN NUMBERS, WE OBSERVED
THAT FOR ALL PARTICIPANTS OEN ROLLED 36 MONTHS OF IPT REDUCED
TB BY 43% AND THAT LIMITED TO TST POSITIVE PARTICIPANTS, 36
MONTHS IPT REDUCED THEIR RISK BY 74%. ANTIRETROVIRAL THERAPY REDUCED
THE RISK OF TB BY 50% IN ADDITION TO THE BENEFIT OF IPT. IN THE RECENTLY RELEASED W.H.O. GUIDELINES REFERRED TO BY
DR. CANE, THE WORLD HEALTH ORGANIZATION ALSO RECOMMENDED 36
MONTHS OF IPT IN REGIONS WHERE THERE IS HIGH TB TRANSMISSION
AND FURTHERMORE INDICATED THAT IF FEASIBLE THE TST WOULD
IDENTIFY THOSE WHO WOULD MOST BENEFIT. WHAT IS THE POTENTIAL PUBLIC
HEALTH IMPACT OF CONTINUOUS IPT IN SUCH TB ENDEMIC COMMUNITIES
WHERE ART IS ALSO PROVIDED. IN BOTSWANA, A COUNTRY WITH
POPULATION UNDER 2 MILLION, THERE ARE APPROXIMATELY 10,000
CASES OF TB EACH YEAR. 80% OF THEM ARE HIV INFECTED. AND OF THESE HIV INFEKTSED
PERSONS, 70% ARE TST POSITIVE BY THE TIME OF THEIR TB DIAGNOSIS. IF CONTINUOUS IPT IS PROVIDED
ONLY TO TST POSITIVE PEOPLE LIVING WITH HIV, ONE COULD
EXPECT AN OVERALL REDUCTION OF 45% IN THE INCIDENCE OF THIS
NATIONAL EPIDEMIC. OTHER STUDIES HAVE SHOWN THAT
NISHTION OF ANTIRETROVIRAL THERAPY AT THRESHOLDS HIGHER
THAN 250 MAY FURTHER REDUCE TB. SO THE QUESTION ARISES WHETHER
IT IS NECESSARIES TO INCLUDE IPT. ADDITIONALLY, THE TST ITSELF IS
NOT WITHOUT COST. IS IT COST EFFECTIVE TO
IMPLEMENT THE TST? WE CONDUCTED A
COST-EFFECTIVENESS ANALYSIS IN BOTSWANA FOR 10,000 PEOPLE
LIVING WITH HIV OVER THREE YEARS AND SHOWED THAT COMBINING THREE
YEARS OF IPT WITH ANTIRETROVIRAL THERAPY WILL REDUCE TB JUST AS
WELL AS INITIATED ANTITROETVIRAL THERAPY AT HIGHER THRESHOLDS
WHILE SAVING $2 MILLION TO $4 MILLION. WE ALSO FOUND THAT THE ADDITION
OF THE TST WILL INCREASE COSTS SLIGHTLY BUT THE TARGETING OF
THREE YEARS OF IPT WILL SUBSTANTIALLY REDUCE TB
INCIDENCE WHILE CONSERVING HUMAN RESOURCES. THERE ARE MANY ADDITIONAL
RESEARCH QUESTIONS TO BETTER PREVENT TB IN PEOPLE LIVING WITH
HIV. FWR THIS LIST, TWO ARE HOW CAN
THE TST BE USED OPTIMALLY IN RESOURCE LIMITED SETTINGS? AND HOW DO WE IMPROVE TB CONTROL
AT THE COMMUNITY LEVEL IN HIGHLY ENDEMIC SETTINGS WHERE THE RAIN
CONTINUES? NOW DR. MARIO WILL PROVIDE
FURTHER COMMENT AEARYCOMMENTARY. THANK YOU. [ APPLAUSE ]
>>THANK YOU VERY MUCH. I HOPE YOU CAN HEAR ME, AND YOU
CAN SEE ME. WE ARE ALL WEARING OUR DRESSES
FOR WORKDAY. I’M VERY GLAD TO BE CONNECTED. NEXT ONE, PLEASE. I WILL PROVIDE THE W.H.O. PERSPECTIVE ON THE SCIENCE OF
HIV, THE POTENTIAL OF INTERVENTION AND THE CHALLENGE
TO BE FACED TO ELIMINATE TB IN GENERAL. NEXT ONE. FIRST OF ALL, HOW DO WE DEVELOP
GUIDELINES AT W.H.O.? IT’S HIGHLY RIGOROUS. WE HAVE A GUIDELINE OF A NEW
COMMITTEE THAT INSTRUCTS ON THE DEVELOPMENT PROCESS. WITH WE START WITH AN EXTERNAL
PANEL THAT HAS TO DECLARE ANY CONFLICT OF INTEREST. THE MAIN QUESTIONS ARE THEN
FORMULATED. THE EVIDENCE IS ASSESSED AND
GRADED, USING THE GRADE SYSTEM THAT LOOKS AT DIFFERENT ASPECTS
OF THE EVIDENCE. RECOMMENDATIONS ARE THEN DEFINED
AS EITHER STRONG OR CONDITIONAL. IN THE AREAS OF FURNL RESEARCH
ARE DESCRIBED IN THIS PROCESS. FINALLY, AFTER FURTHER PEER
REVIEW, WE MAY INVOLVE OUR STRATEGIC ADVISORY GROUP, BODY,
OR OTHER ADVISORY COMMITTEES. THE GUIDELINES ARE THEN
FINALIZED WITH AN EXPIRATION DATE. IT MEANS WE HAVE TO UPDATE THAT
AFTER A FEW YEARS. A GOOD EXAMPLE OF THE GUIDELINE
PRODUCTION IS THE PROCESS WE HAVE FOLLOWED TO DEFINE NEW
TB/HIV INTERVENTION RECOMMENDATION. IT’S PART OF OUR COOPERATION
WITH CDC ON TB/HIV, WE HAVE RECENTLY WORKED TO FIND THE
STANDARDIZED SCREENING RULE FOR TB IN PEOPLE LIVING WITH HIV. THIS META ANALYSIS HAS ALLOWED
US TO DEVELOP NEW GUIDELINES FOR INTENSIFIED CASE FINDINGS AND
INH PREVENTIVE THERAPY HAS BEEN RECENTLY PUBLISHED. AND HERE YOU ALSO CAN SEE AS A
REMINDER OF INCLUSION CRITERIA. THE NEXT ONE. AND AS YOU JUST HEARD FROM
DR. CANE, THE END RESULTS OF THE ANALYSIS HAS BEEN CRUCIAL IN THE
DEVELOPMENT OF THE GUIDELINES THAT ARE POSTED LAST DECEMBER ON
OUR WEB SITE. IN THE NEXT FOUR SLIDES I’LL GO
THROUGH THE CRUCIAL RECOMMENDATIONS FROM THE
GUIDELINES. NEXT ONE. THE FIRST RECOMMENDATION IS A
STRONG ONE WHICH IS FOR ROUTINE CLINICAL PRACTICE. IN SHORT, IT REFERS TO THE
SCREENING OF ADULTS AND ADOLESCENTS LIVING WITH HIV. EVIDENCE SHOWS THAT THOSE WHO DO
NOT REPORT ANY SYMPTOMS AMONG COUGH, FEVER, WEIGHT LOSS OR
NIGHT SWEATS ARE HIGHLY UNLIKELY TO HAVE TB AND THEREFORE SHOULD
BE OFFERED IPT SYSTEMATICALLY. THIS IS IN ADVANCE SINCE IT
SIMPLIFY THE PROCESS TO SCALE OUT IPT IN ENDEMIC COUNTRIES. THE NEXT ONE. THE SECOND RECOMMENDATION IS THE
MIRROR IMAGE OF THE PREVIOUS ONE. IT SAYS ESSENTIAL SLI THAT THOSE
WHO REPORTED AT LEAST ONE OF THE FOUR SYMPTOMS MAY HAVE ACTIVE
TB. THEREFORE, THEY SHOULD BE
EVALUATED FOR TB OR FOR OTHER MEDICAL CONDITIONS. THE NEXT ONE. THE THIRD RECOMMENDATION DEALS
WITH THE DURATION OF IPT. IT SPELLS OUT AS A STRONG
RECOMMENDATION WITH CLEAR EVIDENCE THAT PEOPLE LIVING WITH
HIV OR WHO ARE TST POSITIVE OR UNKNOWN AND ARE UNLIKELY TO HAVE
ACTIVE TB AS DEFINED IN THE RECOMMENDATION NUMBER ONE I
MENTION MENTIONED SHOULD RECEIVE INH FOR
AT LEAST SIX MONTHS. FINALLY, THE FOURTH
RECOMMENDATION, STILL IS ON THE DURATION OF IPT. IT REFERS MORE SPECIFICALLY TO
SETTINGS WITH HIGH TB TRANSMISSION AND SPELLS OUT THAT
AT LEAST 36 MONTHS OF IPT IS THE PROXY FOR LIFELONG PREVENTION
SHOULD ADMINISTER. THESE ARE RECOMMENDATIONS,
HOWEVER, STILL CONDITIONAL AND RELIES LARGELY UPON THE BOTSWANA
STUDY THAT WAS JUST PRESENTED. THE MAIN NAME OF THIS
RECOMMENDATION IS THAT OF SIMPLY PROCEDURES IN SUCH A WAY THAT
TB/HIV INTERVENTION CAN BE SCALED UP WHERE THEY’RE NEEDED. THE SENTENCE FROM WALDEN BY
HENRY THAT ROW TELLS OF THE IMPORTANCE OF BEING SIMPLE. SIMPLICITY, SIMPLICITY AND
SIMPLICITY. THE NEXT ONE. IN SUMMARY, IN THIS SET OF
RECOMMENDATIONS, WHAT ARE WE SAYING NOW? THAT WE RECOMMEND EFGTIVELY THAT
ALL COUNTRIES PUT IN PLACE AS THEIR POLICY FOR TB/HIV? FIRST, SCREENING FOR TB CAN BE
SIMPLY FACE B.A.S.E.ASED ON A CLINICAL
ALGA RINL IMTHAT IS SUFFICIENT TO START THERAPY WITH PEOPLE
LIVING WITH HIV. SECOND, CHEST X-RAYS AND TST ARE
NOT MANDATORY. THIRD, PEOPLE LIVING WITH HIV
MUST UNDERGO REGULAR SCREENING AT EVERY VISIT, EVEN MORE SO IF
THEY ARE ON IPT. FOURTH, PREGNANT WOMEN,
CHILDREN, THOSE ON ANTIRETRO IS ISVIRAL THERAPY AND OTHERS
SHOULD RECEIVE IPT. FINALLY, THERE IS THIS
CONDITIONAL RECOMMENDATION OF AT LEAST 36 MONTHS OF IPT WHERE THE
TRANSMISSION IS HIGH. THE NEXT QUESTION IS, HOWEVER,
WHAT THE POTENTIAL IMPACT OF THESE RECOMMENDATIONS IF
IMPLEMENTED ON THE GENERAL TB — WE KNOW IPT IS HIGHLY EFFECTIVE
IN REDUCING INCIDENCE AMONG PEOPLE WITH HIV WHO ARE TO BE
INFECT INFECTED WITH THE REACTION OF
64% OF INCIDENCE IN UP TO 50% IN DEATHS. THIS HOWEVER IS ON ITS
FEASIBILITY UNDER FIELD CONDITIONS. AT THE MOMENT, WE DO NOT EXACTLY
KNOW WHAT CAN BE GENERATED FROM A LARGE-SCALE INTERVENTION. A MATHEMATICAL MODEL THAT WAS
PUBLISHED SIX, SEVEN YEARS AGO SHOWED ACTUALLY LITTLE IMPACT
FROM IPT. HOWEVER, THE ASSUMPTIONS USED
FOR THAT MODEL MAY NOT HAVE BEEN FAVORABLE. A NEW MODEL THAT WE ARE VP
DEVELOPING AS WE SPEAK USED FOR INSTANCE AN EARLIER START OF
IPT. STUDIES HAVE SHOWN THAT THE
POTENTIAL IMPACT ON REDUCING TB INCIDENCE NOW OF ART IN PEOPLE
LIVING WITH HIV CAN BE AS HIGH AS 64% UP TO 92%. IT WILL BE QUITE INTERESTING TO
USE A MATHEMATICAL MODEL TO ASSESS THE COMBINED
INTERVENTION. THAT’S WHAT WE ARE TRYING TO DO
EFFECTIVE EFFECTIVELY. NEXT ONE. NOW, LET’S SHIFT RAPIDLY TO THE
GLOBAL TB INCIDENCE SITUATION. IF LARGE-SCALE A.R.T. AND IPT
MAY HAVE A STRONG EFFECT ON TB INCIDENCE IN AFRICA WHERE 80% OF
THE TB/HIV CASES ARE, WE SHOULD SEE EVENTUALLY SOME EFFECT ON
THE GLOBAL TB INCIDENCE CURVE, SINCE AFRICA IS RESPONSIBLE,
AFTER ALL, FOR ABOUT 30% OF THE GLOBAL TB. SO ON THE TOP OF THE GRAPH YOU
CITE TB INCIDENCE GLOBALLY THAT INCREASED UNTIL 2004 MAINLY BY
THE AFRICAN TB/HIV EPIDEMIC. THANKS TO THE PEAKING OF THE
AIDS EPIDEMIC IN AFRICA AROUND 2000 OR 1999, THE INCIDENCE OF
TB ALSO PEAKED IN 2004. AND BEGAN A DECLINE, HOWEVER,
UNFORTUNATELY, IS VERY SLOW, ESTIMATED AT LESS THAN 1% PER
YEAR. SO IF TB/HIV INTERVENTIONS THAT
WE DISCUSSED WORK, THEN THE IMPACT ON THE GLOBAL TB EPIDEMIC
WOULD ALSO BE OF SIGNIFICANCE. THE NEXT ONE. THIS IS WHAT WE PROJECT COULD
HAPPEN. THE TOP LINE IN GREENISH
REFLECTS THE CURRENT RATE OF TB DECLINE. THE LESSES THAN 1% PER YEAR. THE RED LINE REFLECTS WHAT MAY
HAPPEN IF THE GLOBAL PLAN TO STOP TB IS FULLY IMPLEMENTED. THIS PLAN THAT’S ENDORSED BY
EVERY AGENCY IN THE WORLD NOT ONLY FORESEES THAT THE
PERFORMANCE OF BASIC TESTS FURTHER IMPROVE WITH HIGHER CASE
DETECTION AND HIGHER CURE RATES BUT ALSO THAT THE TB/HIV
INTERVENTIONS WE’RE TALKING ABOUT ARE FULLY IMPLEMENTED. THE RED LINE TELLS US THAT THE
INCIDENCE MAY DECLINE TEN TIMES BY 2050, BUT STILL BE 100 TIMES
HIGHER THAN THE TARGET OF ONE CASE PER MILLION IN 2050. TO REACH THAT, SHOWN BY THE
PURPLE LINE AT THE BOTTOM, ONE WOULD NEED TO TARGET ADDITIONAL
ACTION ON TOP OF THE AVAILABLE INTERVENTIONS WE HAVE TODAY. NEXT ONE. NOW, IN THIS ARTICLE THAT WAS
PUBLISHED IN MAY OF 2010, WE ARGUED THAT TB CONTROL MUST BE
BASED ON FOUR AREAS IF WE HAVE TO MAKE INCIDENCE DECLINE MORE
QUICKLY AND SERIOUSLY TARGET ELIMINATION. THE FIRST IS OBVIOUSLY THE CORE
BUSINESS OF TB CONTROL PROGRAMS. THE FOCUS MUST BE IN THIS CASE
ON EARLY AND INCREASED CASE DETECTION TO STOP TRANSMISSION
AS SOON AS POSSIBLE. THIS IS WHY TB/HIV
INTERSENSATION THAT CAN PREVENT TB OR DETECT IT VERY EARLY ARE
SO CRUCIAL. SECONDLY, A TB CONTROLLED
PROGRAM CANNOT OPERATE IN ISOLATION. SERVICE AND ACCESS TO ALL IS
CRUEL, ESPECIALLY RELEVANT HERE WOULD BE ROBUST LABORATORY
NETWORK WITH MORE TB BEING IDENTIFIED, THERE WOULD BE A
GREATER NEED TO ENSURE ACCESS TO SENSITIVE DIAGNOSTIC TESTS AND
ULTIMATELY REGULATED PRIVATE CARE AND SO ON. THE THIRD AREA BELONGS TO THE
DEVELOPMENT AGENDA AND IS BEYOND THE REACH OF THE SECTOR IN MOST
CASES. HISTORY TELLS US THAT WHEN
DEVELOPMENT TESTS AND IS SUSTAINABLE, THE SOCIAL AND
ECONOMIC SECTORS MAINTAINED IN COMMUNITIES ARE PROGRESSIVELY
MITIGATED. THE FOUFRNL AREA ISRTH AREA IS
RESEARCH. WE NEED THE TOOLS. MATHEMATICAL MODELS HAVE SHOWN
THAT THE POINT OF CARE DIAGNOSTIC IS SHORTER REGIMENT
FOR TREATMENT AND PROVO LAX IS AND ULTIMATELY IMPORTANT PRE AND
POST POST-EXPOSURE VACCINE WILL BE
CRUCIAL. IN CONCLUSION, MY LAST SLIDE,
NEW GUIDELINES, NEW INTENSIFIED CASE FINDING AND IPT INCORPORATE
THE OUTCOMES OF THE LATEST RESEARCH AND SIMPLIFY THE
INTERVENTIONS. I REPEAT THE MODEL OF
SIMPLICITY. SECOND, POTENTIAL IMPACT OF
TB/HIV INTERVENTIONS ON INCIDENCE AND MORTALITY COULD BE
IMPORTANT BUT THERE IS A NEED FOR RESEARCH AND FIELD
ASSESSMENT BEYOND THE MATHEMATICAL MODEL WE HAVE
AVAILABLE TODAY. THIRD, TB INCIDENCE GLOBALLY
WILL DEPEND ON QUALITY OF EFFORT INCLUDING RAPID AND EARLY
DETENTION IN ORDER TO LIMIT TRANSMISSION BUT ALSO ON BOLD
POLICIES, ON SOCIOECONOMIC DEVELOPMENT AND ULTIMATELY OF
AVAILABILITY OF NEW TOOLS. THANK YOU VERY MUCH. AND NOW OUR FINAL SPEAKER, MY
FRIEND DR. TOM FRIEDEN. [ APPLAUSE ]
>>THANK YOU VERY MUCH, EVERYBODY. ONE OF THE GREATEST THINGS ABOUT
THIS JOB IS I GET TO LEARN ALL THE TIME AND IN PREPARING FOR
THIS SESSION I’VE GONE GOTEN TO REVISIT THE WORLD OF
TUBERCULOSISES CONTROL WHICH WAS MY WORLD FOR ABOUT TEN YEARS. I’VE LEARNED A GREAT DEAL FROM
MY FELLOW PRESENTERS. I THANK THEM FOR THE HARD WORK
IN PREPARING. I’D LIKE TO BRING SOME OF THIS
TOGETHER AS WE CONCLUDE WITH THE THEME THAT FUNDAMENTALS ARE
FUNDAMENTAL. WE FIRST HAVE TO ASK, WHAT IS
THE ESSENTIAL THING THAT WE ARE TRYING TO DO? AND GERTRUDE STEIN WHEN SHE WAS
BEING ROLLED INTO AN OPERATING ROOM AND CONCERNED SHE MAY NOT
SURVIVE ASKED HER PARTNER WHAT IS THE ANSWER? AND RECEIVING NO REPLY, SHE
ASKED, WELL, THEN WHAT IS THE QUESTION? SO THE QUESTION HERE IS, FIRST,
HOW CAN WE SAVE THE MOST LIVES? OR IS IT HOW CAN WE PREVENT
MULTI MULTIDRUG-RESISTANT TUBERCULOSIS
OR IS IT HOW CAN WE REDUCE TB INCIDENCE? AND FOR EACH OF THESE THINGS
THERE ARE DIFFERENT APPROACHES AND DIFFERENT INFORMATION. IN TERMS OF SAVING LIVES, WE
HAVE THE GREAT FORTUNE OF LIVING IN AN ERA WHERE WE HAVE VERY
EFFECTIVE TREATMENT FOR TUBERCULOSIS. WILLIAM FARR SAID IN THE 1800s
THAT THE DEATH RATE IS A FACT, EVERYTHING ELSE IS AN INFERENCE. DEATHS CAN BE REDUCED
DRAMATICALLY AND OVER THE PAST 15 YEARS MORE THAN 6 MILLION
DEATHS HAVE BEEN PREVENTED THROUGH THE WIDESPREAD
IMPLEMENTATION OF THE DOT STRATEGY. I’LL GIVE YOU AN EXAMPLE FROM
NEW YORK CITY. THE TB DEATH RATE DECLINED
DRAMATICALLY DURING MOST OF THE 20th CENTURY. IT THEN INCREASED SHARPLY WITH
THE HIV EPIDEMIC AND LOW RATES OF TB DIAGNOSIS AND CURE BUT
THEN WAS ABLE TO BE RAPIDLY BROUGHT UNDER CONTROL WITH
EFFECTIVE DIAGNOSIS, TREATMENT, TREATMENT OBSERVATION, AND
INFECTION CONTROL. TB CONTROL EFFORTS ARE SAVING
LIVES BUT WE CAN SAVE EVEN MORE LIVES. PROMPT DIAGNOSIS OF BOTH TB AND
HIV IS CRITICALLY IMPORTANT. PEOPLE WHO KNOW THEY’RE HIV
POSITIVE CAN TAKE THE IPT THAT YOU’VE HEARD ABOUT AND PEOPLE
WHO ARE WITH TUBERCULOSIS IF NOT PROMPTLY TREATED CAN PROGRESS TO
SEVERE ILLNESSES AND DEATH. IN FACT, NOW THAT WE’RE
IMPROVING THE ABILITY OF COUNTRIES TO SCREEN TB PATIENTS
FOR HIV, THE DIAGNOSIS OF TB CAN BE AN ENTRY POINT INTO HIV CARE. MORE IDEALLY WE WOULD BE ABLE TO
HAVE SCREENING OF HIV IN THE POPULATION MORE BROADLY SO THAT
WE COULD PREVENT HIV IN A LARGER NUMBER OF PEOPLE. REDUCING THE SPREAD OF
TUBERCULOSIS IS PARTICULARLY IMPORTANT, ESPECIALLY IN
FACILITIES — HEALTH CARE FACILITIES WHERE THERE CAN BE AN
AMPLIFICATION EFFECT AS WE SEE WITH MEASLES AND OTHER
CONDITIONS. IPT, PERHAPS SHOULD BE THE
NEW — PERHAPS JUST AS AN HIV POSITIVE PERSON IN AFRICA SHOULD
TAKE THE DRUGS FOR LIFE THEY SHOULD INSTEAD TAKE A COMBINED
DRUGS IF THEY ARE TST POSITIVE. AND PREVENTING BOTH TB AND HIV
WILL BE GREATLY ENHANCED THE EARLIER HI V IS TREATED IN THE
COURSE OF ILLSNESSILLNESS. IMPROVING TREATMENT CAN ALSO
SAVE LIVES. A.R.T. TREATMENT FOR HIV
PATIENTS WITH TB, ADJUNCTIVE TREATMENT FOR PEOPLE WITH SEVERE
TB AND PERHAPS MOST OF ALL IMPROVED CASE MANAGEMENT OF ALL
PATIENTS INCLUDING DIRECT OBSERVATION OF EVERY PERSON WITH
TUBERCULOSIS DISEASE. THIS STUDY FROM THE U.S. SHOWED
THAT EVEN WITH STATE-OF-THE-ART DRUGS, SHORT-COURSE
CHEMOTHERAPY, PATIENTS HIV POSITIVE HAD A MORE THAN TWOFOLD
INCREASE, NEARLY A THREEFOLD INCREASE IN THE RICK OF DEATH IF
THEY DID NOT RECEIVE DIRECT OBSERVATION. THOSE WHO CANNOT REMEMBER THE
PAST ARE CONDEMNED TO REPEAT IT. AND UNFORTUNATELY THOSE OF US
WHO HAVE WORKED IN THE TUBERCULOSIS CONTROL FIELD ARE
CONCERNED THAT THE INTEREST IN TUBERCULOSIS TENDS TO WANE AS
SOON AS THE HEADLINES ARE NO LONGER PRESENT. THE NEXT ISSUE TO ADDRESS IS
PREVENTING MULTIDRUG-RESISTANT TB. THOUGH WE HAVEN’T DISCUSSED
MDRTB, IT’S CRITICALLY IMPORTANT BECAUSE IF MDRTB SPEDS AND
BECOMES MORE DOMINANT IN THE COMMUNITY, CONTROL BECOMES
EXPONENTIALLY MORE DIFFICULT. A SINGLE PATIENT CAN INFECT MANY
OTHERS AND CLUSTERING IS OUR WAY OF DETERMINING THIS. THE MOLECULAR EPIDEMIOLOGY OF TB
SUGGESTS WHAT PROPORTION OF PATIENTS HAVE DISEASE FROM
RECENT TRANSMISSION. IN A STUDY DONE IN NEW YORK CITY
OVER A ONE-MONTH PERIOD, WHICH WOULD GREATLY UNDERESTIMATE THE
PROPORTION OF PATIENTS WHO HAVE RECENT INFECTION, ABOUT 30% OF
ALL PATIENTS HAD CLUSTERED INFECTIONS AND MORE THAN HALF OF
THOSE WITH MDRTB HAD CLUSTORRING OR LIKELY RECENT TRANSMISSION
AND 41% OF THOSE WITH HIV, RECENT STUDIES SUGGEST THAT AS
MANY AS 60% TO 80% OF HIV POSITIVE TB PATIENTS MAY HAVE
OBTAINED THEIR INFECTIONS AND THEREFORE PROGRESSED THE DISEASE
FROM RECENT INFECTION. THIS IS BOTH A CONDEMNATION OF
OUR CONTROL PROGRAMS AND A MESSAGE OF HOPE BECAUSE IF WE
CAN CONTROL DISEASE RAPIDLY AND TREAT DISEASE EFFECTIVELY WE CAN
BRING THE INCIDENCE RATE DOWN. PREVENTING MDRTB IS EXTREMELY
IMPORTANT FOR ETHICAL REASONS, BECAUSE TREATMENT CAN SAVE
LIVES, BUT IF WE TREAT IN AN ENVIRONMENT WHERE TREATMENT OF
MDRTB DETRACTS FROM THE ATTENTION OF PATIENTS WITH
DRUG-SUSCEPTIBLE TB, MOLTDS SHOW THIS MAY RESULT IN A NET
INCREASE OF THE NUMBER OF PATIENTS WHO DIE FROM TB. IT CRITICAL FOR A PUBLIC HEALTH
REASON PARTICULARLY IN AREAS WHERE HIV IS COMMON, WHERE
CROWDING IS COMMON BECAUSE IT SPREADS VERY RAPIDLY AND CAUSES
LARGE OUTBREAKS. TESTING FOR DRUG RESISTANCE CAN
REDUCE TREATMENT COSTS AND PREVENT OUTBREAKS. IT’S IMPORTANT. THE ESSENTIAL CONCEPT HERE IS
THAT NO PROGRAM CAN TREAT MDRTB AS RAPIDLY AS A POORLY DESIGNED
PROGRAM CAN CREATE MDRTB. SO THE PRIORITY ALWAYS HAS TO BE
TO IMPROVE THE PERFORMANCE OF THE PROGRAM IN THE FUNDAMENTALS. NOW, REDUCING INCIDENCE IS THE
MOST CHALLENGING AREA. AS YOU CAN SEE FROM THE GRAPH,
GLOBAL TB INCIDENCE HAS BARELY DECREASED OVER THE PAST SEVERAL
YEARS, EVEN THOUGH DEATHS FROM TB HAVE DECREASED BY ABOUT A
QUARTER GLOBALLY. IN NEW YORK CITY, A SUBSTANTIAL
DECREASE IN TB WAS SEEN AS MORE PATIENTS WERE TREATED WITH
DIRECTLY OBSERVE OBSERVATION. DIRECT OBSERVATION IS JUST ONE
COMPONENT OF THE D.O.T. STRATEGY BUT IT IS ESSENTIAL. IT’S ESSENTIAL BECAUSE IT BUILDS
A HUMAN BOND BETWEEN THE PATIENT AND AN OUTREACH WORKER. IT IS ESSENTIAL BECAUSE IT IS
THE ONLY WAY TO ENSURE CURE AND THE ONLY WAY TO ENSURE THE
PREVENTION OF DRUG RESISTANCE. IN INDIA, A RIGOROUS ANALYSIS IN
AN AREA THAT HAS BEEN UNDER CONTINUOUS SURVEILLANCE FOR
TUBERCULOSIS, A POPULATION OF ABOUT 500,000, SHOWED THAT
BEFORE USING THE CURRENT SHORT COURSE THERAPY DRUGS AND IT’S
ONLY TB EXPERTS BY THE WAY WHO DESCRIBE SIX MONTHS AS TREATMENT
AS SHORT COURSE. BUT BEFORE THESE MODERN DRUGS
WERE USED, THERE WAS A VERY GRADUAL DECLINE OF 1% OR 2% IN
TUBERCULOSIS. AND THEN IN THE CURRENT ERA,
WHEN WE WERE ABLE TO IMPLEMENT NOT ONLY SHORT COURSE
TREATMENT — WELL, IN THE MIDDLE ERA, YOU SAW SHORT COURSE
TREATMENT USED SO THE RIGHT DRUGS BUT WITHOUT THE DOT
STRATEGY. THEY WERE SIMPLY ONLY ABOUT A 1%
TO 4% DECLINE IN TUBERCULOSIS PREVALENCE. HOWEVER, IN THE LAST PHASE OF
THIS GRAPHIC, DURING THE DOTS PERIOD, DURING AN ADEQUATELY
IMPLEMENTED DOTS PROGRAM, THERE WAS A 12% DECLINE IN BOTH SMEAR
POSITIVE AND CULTURE POSITIVE TU TUBERCULOSIS AND 6% ANNUAL
DECLINE IN THE ANNUAL RISK OF BECOMING INFECTED WITH
TUBERCULOSIS. SO DOTS WAS SHOWN IN THIS
POPULATION, WHICH DID NOT HAVE A HIGH RATE OF HIV, TO BE ABLE TO
DRAMATICALLY ACCELERATE THE DECREASE IN BOTH PREVALENCE AND
THE RISK OF INFECTION. HOWEVER, WE ARE NOT IN INDIA OR
IN OTHER PLACES OF THE WORLD SEEING A DRAMATIC DECLINE IN
INCIDENCE. IN FACT, THE ESTIMATED TB
INCIDENCE HAS REMAINED UNCHANGED DESPITE INCREASING CASE
DETECTION AND CURE RATES OVER THE PAST FEW YEARS. WHY IS THIS? WHY IS TB FALLING ONLY
GRADUALLY? IS IT BECAUSE DOTS IS NOT BEING
IMPLEMENTED WELL? BECAUSE OF REACTIVATION OF
DISEASE — INFECTION THAT WAS TRANSMITTED DECADES EARLIER? OR IS IT BECAUSE OF THE SOCIAL
CONDITIONS THAT TB ARISES FROM? AND REALLY THE ANSWER IS NOT
WHICH OF THESE BUT WHAT PROPORTION OF EACH APPLIES IN
ANY ONE COMMUNITY? WELL, IS IT BAD DOTS? THIS WOULD BE LIKE RAIN
CONTINUING TO FALL IN THE MEMORABLE ANALOGY THAT SHIRLEY
OF THE PUBLIC HEALTH SERVICE STATED EARLIER. THIS MAY WELL BE THE CASE. WE’RE NOT FINDING CASES PROMPTLY
ENOUGH. WE’RE NOT FINDING ENOUGH OF
THEM. OR ONCE WE DIAGNOSE THEM WE’RE
NOT PUTTING THEM ON TREATMENT. ALL OVER THE WORLD THERE’S A GAP
BETWEEN THE NUMBER OF PATIENTS DIAGNOSED AND STARTED ON
TREATMENT THAT’S INSUFFICIENTLY ADDRESSED. PERHAPS WE’RE NOT ADEQUATELY
ENSURING TREATMENT COMPLETION OR PERHAPS WE’RE NOT STOPPING THE
SPREAD OF INFECTION ESPECIALLY IN HEALTH CARE FACILITIES AS
WELL AS IN THE COMMUNITY. AND THE IMPLICATION OF THIS IS
THE NEED TO IMPROVE DIAGNOSIS, TREATMENT AND INFECTION CONTROL. OR IS IT REACTIVATION, WAVES
CRASHING ON THE BEACH IN THE MEMORABLE ANALOGY OF RANDY
SCHULTZ FROM THE BOOK “THE BAND PLAYED ON” FROM A BOAT THAT
PASSED AND IS NOW OUT OF SIGHT. THIS WOULD BE A CHALLENGE
BECAUSE THE NUMBER OF PEOPLE WITH TB INFECTION IS VERY LARGE
AND SO PREVENTING THESE CASES FROM ARISING WOULD BE VERY
DIFFICULT. IN HONG KONG AS WELL AS PARTS OF
EUROPE THIS IS NOW THE DOMINANT FORM OF TUBERCULOSIS. THE APPLICATION HERE IS TO TRY
TO IDENTIFY WAYS TO GIVE PREVENTIVE TREATMENT TO THE
INDIVIDUALS TO FIND NEW WAYS TO IDENTIFY AND TREAT THOSE MOST AT
RISK OF REACTIVATEING AND TO PERSIST, TO RECOGNIZE THAT
RESULTS MAY NOT BE IMMEDIATE. OR IS THE PERSISTENCE OF TB A
REFLECTION OF SOCIAL PATTERNS. THE SOCIAL DETERMINANCE OF
HEALTH ARE WELL DESCRIBED IN TUBERCULOSIS, ABOUT A QUARTER OF
TUBERCULOSISES CAN BE ATTRIBUTED TO UNDERNUTRITION, INDOOR AIR
POLLUTION, ABOUT A SIXTH TO SMOKING AS WELL AS 11% TO HIV,
10% TO ALCOHOL. ADDRESSING THIS WILL REQUIRE
LONG-TERM SUSTAINABLE CHANGE. DOTS IS THE FOUNDATION OF
EFFECTIVE TB TREATMENT. IT HAS BEEN EFFECTIVE AT
IMPROVING DIAGNOSIS, TREATMENT AND ADHERENCE. THERE ARE POWERFUL INFORMATION
SYSTEMS WHICH ALLOW US TO DO OBSERVATIONAL RESEARCH, AND IT
IS I THINK A GREAT MODEL FOR OTHER DISEASE CONTROL PROGRAMS. TO FURTHER STRENGTHEN DOTS WE
NEED TO OPTIMIZE DIAGNOSIS WITH NEW TOOLS SUCH AS L.E.D. MIKE
ROSS COPY, TO IMPROVE CASE MANAGEMENT THROUGH RAPID TESTING
FOR DRUG RESISTANCE AS WELL AS PATIENT-CENTERED TREATMENT
OBSERVATION, TO ENSURE THE REGULAR SUPPLY OF HIGH-QUALITY
DRUGS, SOMETHING THAT’S SO BASIC AND YET REMAINS OUT OF REACH FOR
PATIENTS WITH TB AROUND THE BORLD. AND TO REINFORCE PATIENT
MONITORING AND SUPERVISION, WHICH IS ESSENTIAL TO SUCCESS. EARLY DIAGNOSIS IS ESSENTIAL. TB CONTROL PROGRAMS HOWEVER HAVE
BEEN LESS EFFECTIVE THAN EXPECTED IN REDUCING
TRANSMISSION BECAUSE PATIENTS ARE NOT DIAGNOSED AND CURED
QUICKLY ENOUGH. THE PRIORITY NOW IS NOT TO
ABANDON THE BASIC PRINCIPLES OF CHEMOTHERAPY BUT TO IMPLEMENT
THEM WITH GREATER VIGOR. THERE ARE IMPORTANT CHALLENGES
IN THE FUTURE. HIV CONTINUES TO DRIVE THE TB
EPIDEMIC IN AFRICA. STRENGTHENING DIAGNOSIS AND
TREATMENT OF TB AND HIV IS BOTH POSSIBLE AND NECESSARY. EFFECTIVE CASE MANAGEMENT IS
ESSENTIAL AND INFECTION CONTROL IS UNDERAPPRECIATED. A FOCUS ON THE BASICS PLUS NEW
STRATEGIES AND TOOLS CAN LEAD TO SIGNIFICANT FURTHER PROGRESS IN
TUBERCULOSIS CONTROL. THERE HAS BEEN TREMENDOUS
PROGRESS OVER THE PAST DECADE, SAVING 6 MILLION LIVES AND
NEARLY 1 MILLION LIVES THIS YEAR ALONE
ALONE. BETTER APPLICATION OF EXISTING
TOOLS CAN FURTHER DECREASE DEATH AND TO SOME EXTENT FURTHER
DECREASE INCIDENCE. PERSISTENCE, PATIENT
CENTEREDNESS AND ZEALOUS ADHERENCE TO TECHNICAL RIGOR AND
PROGRAM EXCELLENCE ARE ALL ESSENTIAL. BUT THE CURRENT TOOLS AND XRAT
SFRI JIS ARE INSUFFICIENT TO ELIMINATE TUBERCULOSIS. NEW APPROACHES WILL BE NEEDED TO
CONTROL TB IN AFRICA AND GLOBALLY IN ORDER TO REDUCE TB
DRA MALTMATICALLY DRAMATICALLY. THANK YOU ALL VERY MUCH. [ APPLAUSE ]
>>THANK YOU, DR. FRIEDEN. THAT COMPLETES OUR TALKS FOR
THIS SESSION. WE’LL NOW MOVE ON TO THE
QUESTION AND ANSWER PERIOD. AND WE WILL TAKE TWO QUESTIONS. WE JUST ASK THAT YOU PLEASE TRY
TO KEEP THEM CONCISE BECAUSE OF LIMITED TIME AND ALSO PLEASE
IDENTIFY YOURSELVES. YOU CAN PROCEED TO ONE OF THE
TWO MICROPHONES WHICH YOU SEE STANDING UP HERE IN THE
AUDITORIUM. WHILE WOE AREE’RE WAITING FOR
PEOPLE TO COME FORWARD, IF THERE ARE
ANY QUESTIONS FROM ENVISION, THAT WOULD ALSO BE — WE CAN
ALSO TAKE THOSE.>>THANK YOU FOR A SPECTACULAR
SERIES OF PRESENTATIONS. KEVIN DECOKH, GLOBAL HEALTH. MY QUESTION IS ABOUT ANTIRETRO
ANTIRETROVIRALS. YOU RIGHTLY POINTED OUT THE
ISSUE OF THE CD-4 INITIATION CUTOFF. BUT YOU MADE COMMENTS ABOUT COST
EFGTIVENESS. BUT WE REALLY DON’T HAVE THE
DATA I DON’T THINK ON REALLY WHAT WOULD HAPPEN TO TB
INCIDENCE IF WE START ANTIRETROVIRAL THERAPY REALLY
EARLY. I THINK THAT’S ACTUALLY RESEARCH
THAT URGENTLY NEEDS TO BE DONE. BUT I VALUE YOUR COMMENTS. IF WE’RE ALLOWED THREE QUESTIONS
OR SOMEONE ELSE CAN AT LEAST ASK ONE, I’D LOVE TO ASK
DR. FRIEDEN, THAT’S A WONDERFUL EXPOSE, BUT SLIGHTLY SOBERING. YOUR CONCLUSIONS. I WONDER WHAT YOUR THOUGHTS ARE
ON WHAT ARE THE TOOLS THAT WE NEED AND ARE THEY COMING?>>THANK YOU FOR THE QUESTION. I VERY MUCH AGREE THAT WE DO
NEED TO DO THE STUDIES, THAT THERE HAVE BEEN RESULTS FROM THE
HAITI STUDY THAT TALKED ABOUT — SHOWED THE RESULTS OF STARTING
ANTIRETRO VIRAL THERAPY EARLIER AND A SOUTH AFRICAN STUDY AS
WELL LAST YEAR. THEY GIVE US SOME GOOD
PRELIMINARY IDEAS AND I THINK A KEY THING THAT CAME THROUGH FOR
ME IS STARTING A.R.T. EARLIER YOU’RE GOING TO CERTAINLY CUT
DOWN ON MORTALITY, ALSO CUT DOWN ON TB. HOWEVER, THE GAP BETWEEN TB AND
MORTALITY BECOMES MORE VISIBLE WHEN YOU START A.R.T. EARLIER,
TB STAYS HIGH. JUST IN THE FIRST YEAR OF
ACQUIRING HIV INFECTION THE RISK OF TB INFECTION DOUBLES.>>I DON’T THINK IT’S SOBERING
ACTUALLY. I THINK WE’RE FORTUNATE THAT WE
CAN DRASTICALLY REDUCE THE DEATH RATE FROM TB AND DRASTICALLY
REDUCE THE INFECTIONS FROM TB, THE DATA FROM THE TB RESEARCH
CENTER IS VERY ENCOURAGING THAT WE CAN BRING DOWN THE INFECTION
RATE. BUT CLEARLY RENEED TO DO BETTER
AND I THINK WE HAVE TO DEFINE THE POPULATION THAT WE’RE
WORKING IN. IN TB EPIDEMICS WHICH ARE
ARISING PRIMARILY IN HIV NEGATIVE POPULATIONS, WE NEED TO
DO BETTER IN TERMS MORE PROMPT DIAGNOSIS AND A HIGHER RATE OF
DIAGNOSIS. 70% IS THE TARGET FOR CASE
DETECTION WAS SELECTED BECAUSE IN TEN YEARS, IF YOU ACHIEVE
THOSE TARLT TARGETS YOU’LL CUT TB IN HALF IN A HIV NEGATIVE POP
HAITIAN. BUT THAT LEAVES A THIRD OF
PEOPLE UNDIAGNOSED AND ON A SUBNATIONAL LEVEL IT’S
PROBLEMATIC AS A TARGET. THIS IS WHY I THINK W.H.O. HAS
GOTTEN AWAY FROM IT, BECAUSE YOU REALLY WANT PEOPLE TO DIAGNOSE
AS MANY PATIENTS AS POSSIBLE. AND THE INSUFFICIENT DIAGNOSIS
PROBABLY QUITE IMPORTANT. POOR QUALITY TREATMENT
OBSERVATION AND POOR QUALITY SUPERVISION IS I THINK ALLOWING
THE CONTINUED SPREAD IN MANY PARTS OF THE WORLD. WHERE THERE IS A HIGH RATE OF
HIV IN THE POPULATION, IT’S GOING TO BE PARTICULARLY
IMPORTANT TO TRY TO SCALE UP IPT AND TO SEE IF WE CAN GET 20% TO
40% DECLINE IN INCIDENCE THROUGH THAT. THEY MAY BE SELF-REPLICATING
REALLY BECAUSE IF YOU PREVENT ONE CASE YOU’RE PREVENTING
OTHERS. AND DO BETTER WITH INFECTION
CONTROL. BUT IN TERMS OF BETTER TOOLS,
THERE’S A LOT THAT WE WOULD NEED. WOULDN’T IT BE WONDERFUL IF WE
HAD A FINGER STICK POINT OF CARE TEST FOR TB INFECTION SO WE
DIDN’T HAVE TO DEAL WITH THE TST? I THINK SOME OF THE EXISTING
TOOLS CAN BE RETROFITTED TO GREAT EFFECT USING FLUORESCENCE
L.E.D. MICROCOPY, OF COURSE, IS SOMETHING THAT WOULD DOUBLE THE
ACCURACY OF SMEAR AND KEEP COSTS ABOUT CONSTANT OVER THE MEDIUM
TERM. BUT ULTIMATELY WHAT WE WOULD
MOST LIKE TO SEE OF COURSE IS A VACCINE.>>LAST QUESTION. DR. NELSON?>>YEAH. LISA NELSON FROM CDC. THANKS ALL FOR EXCELLENT
PRESENTATIONS. I GUESS ONE OF THE THINGS WE’VE
LEARNED IN RECENT YEARS FROM THE IV EPIDEMIC IS BY FOCUSING ON A
GENERALIZED EPIDEMIC WE FAIL TO ACKNOWLEDGE THERE ARE HIGH-RISK
POPULATIONS WITHIN THAT EPIDEMIC. I’M WONDERING ABOUT THOUGHTS
ABOUT HOW WE TARGET OUR INTERVENTIONS TO PERSONS MOST AT
RISK. I’M THINKING, TB CASES ARE
CLUSTERED IN HOUSEHOLDS AND OTHER SETTINGS. T, ESPECIALLY POPULATIONS AS
CHILDREN OR WOMEN OF REPRODUCTIVE AGE, MALNOURISHED
PEOPLE. IF WE COULD THINK IN THE CONTEXT
OF BROADER TB CONTROL HOW WE REACH SPECIAL POPULATIONS.>>I CAN TRY TO ANSWER. I THINK THIS IS REALLY AN
EXTENSION OF DR. FRIEDEN’S POINT ABOUT THE ORIGINAL W.H.O. CASES
TARGET THAT WAS SET YEARS AGO AT 70%, BUT IN FACT WE KNOW SECOND
ONLY TO HIV, THE NUMBER ONE RISK FACTOR FOR GOING FROM INFECTION
TO DISEASE IS RECENT INFECTION. SO I THINK WE’VE BEEN SOMEWHAT
REMISS GLOBALLY IN TERMS OF OUR INEFFECT OVERNESS AT DOING
CONTACT TRACING. WE DON’T REALLY KNOW THE EXACT
YIELD OF THIS IN TERMS OF A GLOBAL IMPACT, EITHER IN A LARGE
HIV UNINFECTED OR INFECTED POPULATION. BUT IT IT’S CLEAR THAT
PREVENTING TB INFECTION IN CHILDREN WOULD BE HIGHLY
EFFECTIVE. ALSO PREVENTING LONG-TERM
DEVELOPMENT OF TB DISEASE AS WELL AS LOOKING IN CONVICT GRA
GAT SETTINGS WHERE THERE’S CLEARLY A LOT OF CLUSTERING,
INCLUDING NOT JUST HOSPITALS BUT ALSO PRISONS OR OTHER SETTINGS.>>JUST VERY, VERY QUICKLY, THIS
IS ACTUALLY THE MOST CHALLENGING QUESTION THAT WE HAVE TODAY,
GLOBALLY. WE BELIEVE THAT — THAT’S WHY WE
LEAD THE ANALYSIS ON THE SOCIOECONOMIC AND THIS WHOLE
RISK FACTORS OF TB SHOWN IN THE SLIDES. I THINK WE BELIEVE THAT IN ORDER
TO REALLY TARGET EARLY CASE DETECTION AND CUT TRANSMISSION
WE HAVE TO FOCUS ON THE VULNERABLE POPULATION. THERE ARE SOME WELL DEFINED. IF YOU HAVE A GOOD INFORMATION
SYSTEM IN A COUNTRY AND YOU ARE CAPABLE AT IDENTIFYING THE
POPULATIONS, THAT’S WHERE YOU CAN TARGET INTERVENTION. WE ARE TALKING NOT JUST ABOUT
CONTACTS WHICH ARE OBVIOUS BUT — PARTS OF HIV POSITIVE
PEOPLE LIVING ACROSS THE COUNTRY, SLUM PEOPLE, DWELLERS,
DIE BAABETIC PAISHGTS. WE KNOW IN SOME COUNTRIES,
MEXICO, FOR INSTANCE, THERE IS A LOT OF DIABETES. MATERNAL SERVICES AND SO ON. THESE ARE VULNERABLE POPULATIONS
THAT NEED TO BE TARGETED. THAT’S WHERE PROBABLY EARLY
DETECTION CAN BE IMPLEMENTED. BUT AT THE SAME TIME CONSIDER
IPT ON WHICH WE KNOW VERY LITTLE, IPT IN THIS PARTICULARLY
HIGH RISK GROUPS.>>AND WITH THAT WE CONCLUDE OUR
SESSION. THANK YOU ALL FOR COMING. HOPE TO SEE YOU IN FOUR WEEKS,
AND I’D LIKE ANOTHER ROUND OF APPLAUSE. THANK YOU.