Disclosures. TB and CoMorbidities Challenges and Opportunities. Burden of TB. Outline of the lecture. Target testing for TB Infection TB HIV 3/25/2012

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1 Disclosures TB and CoMorbidities Challenges and Opportunities E. Jane Carter, M.D. Associate Professor of Medicine Alpert School of Medicine, Brown University Providence, Rhode Island No financial disclosures Board Involvement World Lung Foundation International Union Against TB and Lung Disease Committee Involvement Advisory Committee for the Elimination of TB-CDC International Health Committee ATS Expert Committee -TB Active Case Finding -WHO Outline of the lecture Examine three comorbiditiesassociated with TB TB/HIV TB/ *** TB/ TNF alpha blocking agents Examine the opportunities for synergism in TB control Burden of TB 9.4 million new cases of TB disease per year 2 million deaths 1 infection per second Leading cause of death in PLWHA Leading cause of death in women of child bearing years globally Target testing for TB Infection We screen populations At risk for exposure and resultant infection At risk for development of disease if infected HIV infection 100 fold Use of biologic agents 70 fold Medical conditions that influence ability to contain infection 3 fold TB HIV 1

2 TB HIV Unique Symbiosis of the two epidemics Global Burden Diagnosis HIV in TB patients TB in HIV patients Treatment Timing of therapy for each Drug Interactions and Compatibilities IRIS % Coinfection Estimated HIV Coinfection in Persons Reported with TB, United States, * Aged All Ages Total cases TB =11,182 *Updated as of July 21, 2011 Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group Treat HIV as early as possible Timing of the Initiation of Antiretroviral Drugs in Tuberculosis Therapy. Karimet. al. NEJM 2010;362: % relative reduction in deaths if ART is given simultaneous (combined integrated therapy) to TB care as opposed to sequentially Reduction seen in all Cd4 count srtat TB as a contributor to the global burden of TB Top 10 in TB India China Indonesia Nigeria Bangladesh Pakistan Ethiopia Philippines South Africa DRC Top 10 in India China USA Indonesia Japan Pakistan Russia Brazil Italy Bangladesh The preference is that the 2 populations are mutually exclusive 250 million 6m new annually Tuberculosis 14 million 9.4m new annually 2

3 Situation in a low TB incidence country Situation in a High TB incidence Country Tuberculosis TB Population where now acts as a multipler Population where now acts as a multipler Global Distribution of DM and TB 2008 South East Asia 20% Western Pacific 23% Africa 5% 70% in LIC and MIC Tuberculosis 2009 South East Asia 35% Western Pacific 20% Africa 30% 95% in LIC and MIC Does coexistence of TB and in the same patient affect the course of the other clinical condition? By sheer numbers, CoMorbiditymay contribute as much or more to TB Incidence burden than HIV despite being a weaker inducer Presentation of Disease Some studies have demonstrated more common atypical presentations Turkey Saudi Arabia Pakistan Taiwan Some studies have suggested more cavitation Outcome of Disease Possible delay in Sputum Culture conversion 8 studies comparing DM and Non DM RR but 5/8 had RR >2 Possible Increase Death 23 studies comparing risk of death Pooled RR =1.85 ( 95% confidence interval; ) Possible Risk of Recurrent Disease 4 studies Pooled RR=3.98 ( 95% CI, ) 3

4 Why might Diabetics do Worse? Drug Drug interactions Rifampin reduces levels of oral hypoglycemic is a risk factor for hepatotoxicity from TB drugs Why might Diabetics do Worse? TB risk seems to correlate with duration and severity of diabetes More post primary TB Higher bacterial burden Worse Immunopathology High Cytokine levels Slow response to treatment Synergy with other Co-morbidities Treatment Considerations Does treatment of TB in the Diabetic Patient differ than other TB? Peripheral neuropathy DM versus TB meds Diabetics should always be given B6 for prevention Drug Interactions Rifampin Oral Hypoglycemics Malabsorption Diabetics have been shown otbe at risk for malabsorption of medications Length of Therapy Cavity Risk of Relapse (Study22) Continuation phase, Control, (I/R 2x/wk) Culture positive at 2 months Yes 21.8% 6.2% No 5.0% 2.1% Culture negative at 2 months Treatment Implications Diabetics have prolonged culture positivity Extend by 3 months Diabetics may have more cavitary disease Extend by 3 months Whether itself should predict longer therapy is unclear??? If neither of the above risk factors are present 4

5 The preference is that the 2 populations are mutually exclusive Situation in a low TB incidence area 250 million 6m new annually Tuberculosis 14 million 9.4m new annually Tuberculosis Population where now acts as a multipler Situation in a High TB incidence Area Reported TB Cases by Origin and Race/Ethnicity,* United States, 2010 TB White (33%) U.S.-born Hispanic or Latino (19%) American Indian or Alaska Native Asian Black or African American (13%) Foreign-born** White (5%) Hispanic or Latino (37%) Native Hawaiian or Other Pacific Islander (2%) Black or African American (40%) Asian (45%) Population where now acts as a multipler *All races are non-hispanic. Persons reporting two or more races accounted for less than 1% of all cases. ** American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander accounted for less than 1% of foreign-born cases and are not shown. White (33%) Native Hawaiian or Other Pacific Islander (2%) Reported TB Cases by Origin and Race/Ethnicity,* United States, 2010 U.S.-born Hispanic or Latino (19%) American Indian or Alaska Native Black or African American (40%) Asian Black or African American (13%) Asian (45%) White (5%) *All races are non-hispanic. Persons reporting two or more races accounted for less than 1% of all cases. ** American Indian or Alaska Native and Native Hawaiian or Other Pacific Islander accounted for less than 1% of foreign-born cases and are not shown. Foreign-born** Hispanic or Latino (37%) Countries of Birth of Foreign-born Persons Reported with TB, United States, 2010 Other Countries 38% Haiti Guatemala China (5%) Mexico (23%) India (9%) Vietnam (8%) Philippines (11%) 5

6 The TNF alpha Inhibitors TB and TNF alpha Inhibitors Infliximab( Remicade) 1998 Etanercept(Embrel)** 1999 Adalimumab(Humira) 2002 Certolizumab(Cimzia) 2009 Golimumab(Simponi) 2009 Pentoxiphylline Adenosine Thalidomide Disease that Respond to TNF alpha Inhibitors Rheumatoid Arthritis Psoriatic Arthritis Plaque Psoriasis Ankylosing Spondylitis Juvenile Idiopathic Arthritis Crohn s Disease Ulcerative Arthritis Behcet s Disease Sarcoidosis TNF Alpha is vital in the development and maintenance of Granulomas TB Associated with Infliximab Challenges with TNF alpha Inhibitors 147,000 patients who received Infliximabin USA and Europe 70 cases of TB at a median of 12 weeks 40 (57%) with EP 17 disseminated 48 cases after 3 or fewer infusions 55 patients received > 1 other immunosuppressive agent Comparison using estimated USA rates in RA 24.2 vs6.2 cases per 100,000 persons/ year Screening for LTBI TST or IGRA or Both? TST >/=5mm History is always KEY. Treatment of LTBI Yes Preferentially before TNF alpha use Diagnosis of TB Needs high level of suspicion Can occur even on LTBI therapy Treatment of TB Standard TB Regimens Hold TNF alpha Inhibitors ( at least until TB under control) Keane, NEJM 2001; 345:1098 6

7 No. of Cases 30,000 25,000 20,000 15,000 10,000 5,000 Reported TB Cases United States, * Do opportunities in synergy exist for health care systems not for the diseases? 0 *Updated as of July 21, 2011 Year TB HIV CDC recommendations TB All TB suspects should be screened for HIV HIV Routine Screening for HIV in all health care settings unless the patient declines RI TB Clinic For years close to 100% testing of all patients with TB disease THEN year old female referred with LTBI/pregancy Had been part of a contact investigation 10 years earlier without completion of treatment CXR normal- no symptoms Cleared for delivery and booked postpartum to return for treatment HOWEVER Post TB visit, HIV test done in prenatal clinicpositive Sent for HIV care for PMTC with success Did not return post partum for LTBI therapy Presented 6 months postpartum with fevers, ascites = peritoneal TB 7

8 RI TB Clinic 821/1060 ( 77.5%) of first time visitors had an HIV assessment 706 ( 86%) were foreign born 410 ( 50%) had no health insurance 30 ( 3.7%)refused testing not at risk 1 newly diagnosed case of HIV Described herself as not at risk Recent immigrant from former Soviet Union Country CD4 count >800 HIV Testing Survey NTCA Conference attendees, National TB Nurse Controllers and the DCD TB-educate list serv 92% always test for HIV In Tb disease 41% test for HIV in LTBI 38 % reported written consent necessary in their state whereas only 12% of states require written consent Caitlin Naureckas Brown Honors Thesis, Biology 10 Saipan Experience TB DIABETES recorded in the TB clinic data base Most common co-morbidity 30% of all cases Over 70% of Pacific Island Cases Development of Protocols for the TB Clinic DM Guidelines Every person with TB over age 18 should be screened for All Pacific Islanders with DM who are at risk for TB should be screened for LTBI and active TB Diabetics with LTBI should be encouraged to take INH for 9 months Ensure that TB treatment is appropriately adjusted for B6 supplementation; Kidney function assessment ( Cr) Ensure that TB treatment is appropriately adjusted for B6 supplementation Kidney function assessment ( Cr) Be aware of drug interactions Be aware of poor absorption of some TB medications Be aware of the possibility of relapse in treatment not extended Repeat glucose monitoring during the course of treatment Appointments and DOT visits can be used as DM Teachable Moments 8

9 Universal TB Screening of all Diabetics? Remember-you do have to have TB infection for to increase the risk of disease Targeted Testing In Diabetic Services who deliver care to TB risk populations All (TB) Epiis Local. Certainly represents an Opportunity for Synergy QUESTIONS? 9