Jayne Ash Address TB in Your Practice: Focus on Co-Morbidities Gisela Schecter, MD, MPH CA Dept of...

Jayne Ash AddressJayne Ash AddressTBTB in Your Practice: Focus in Your Practice: Focus

on Co-Morbiditieson Co-Morbidities

Gisela Schecter, MD, MPHGisela Schecter, MD, MPH

CA Dept of Public HealthCA Dept of Public Health

May 6, 2010May 6, 2010

I have no conflicts of interest to declareI have no conflicts of interest to declare

Who was Jayne Ash?Who was Jayne Ash?

Executive Director of strategic planning for Executive Director of strategic planning for CTCA from 1998-2001CTCA from 1998-2001

Graduate of the N.C. School of PHGraduate of the N.C. School of PH Jazz singerJazz singer Great facilitatorGreat facilitator

On taskOn task Great sense of humorGreat sense of humor

Died tragically in 2001Died tragically in 2001

60 years ago60 years ago

NowNow

Highest incidence of TB is in > 65 y.o., Highest incidence of TB is in > 65 y.o., many of whom have concurrent diseasesmany of whom have concurrent diseases

A new disease has put people at A new disease has put people at increased risk of TBincreased risk of TB

New therapies that modulate immunity put New therapies that modulate immunity put people at increased risk of TBpeople at increased risk of TB

Lifestyle choices put people at risk for TBLifestyle choices put people at risk for TB Co-morbidity is the rule, not the exceptionCo-morbidity is the rule, not the exception

TB is not your patient’s only problemTB is not your patient’s only problem

Diabetes MellitusDiabetes Mellitus SmokingSmoking Chronic Kidney Disease and HemodialysisChronic Kidney Disease and Hemodialysis HIV infectionHIV infection (Immunosuppressive therapies)(Immunosuppressive therapies)

Tuberculosis and Diabetes MellitusTuberculosis and Diabetes Mellitus

LTBI and Progression to Active TBLTBI and Progression to Active TB

The frequent association of DM and TB has The frequent association of DM and TB has been observed for over 2,000 yearsbeen observed for over 2,000 years

Systematic Review from Harvard, 2008Systematic Review from Harvard, 2008 13 observational studies that reported an age-13 observational studies that reported an age-

adjusted estimate of assoc. between TB and DM adjusted estimate of assoc. between TB and DM Almost 1.8 million participantsAlmost 1.8 million participants 3 Cohort studies gave 3 Cohort studies gave RR of 3.11RR of 3.11 (CI 2.27-4.6) (CI 2.27-4.6) 10 Case/control studies Odds Ratios ranged from 10 Case/control studies Odds Ratios ranged from

1.16-7.831.16-7.83

Jeon CY, PLos Med. 2008


Diabetic ContactsDiabetic Contacts A Hong Kong study examined 4661 close A Hong Kong study examined 4661 close

contacts to TB casescontacts to TB cases Both early (within 3 months) and late (followed Both early (within 3 months) and late (followed

for 5 years) disease in contacts was strongly for 5 years) disease in contacts was strongly associated with diabetes in the contact (RR= associated with diabetes in the contact (RR= 3.44)3.44)

Lee MS, Int J Tuberc Lung Dis. 2008


Why are patients with diabetes at Why are patients with diabetes at increased risk of TB?increased risk of TB? Impaired cell-mediated immunityImpaired cell-mediated immunity Renal failureRenal failure Micronutrient deficiencyMicronutrient deficiency Pulmonary microangiopathyPulmonary microangiopathy

Harries AD, Trans Royal S of Trop Med & Hyg. 2009

Presentation and DiagnosisPresentation and Diagnosis

Diabetes and Radiological Presentation of Diabetes and Radiological Presentation of Pulmonary TBPulmonary TB Cavitary lung lesionsCavitary lung lesions

• Yes DM; 50.8%Yes DM; 50.8%• No DM; 39%No DM; 39%

Lower lobe lung lesionsLower lobe lung lesions• Yes DM; 23.5% lower lobe lesions onlyYes DM; 23.5% lower lobe lesions only• No DM; 2.4% lower lobe lesions onlyNo DM; 2.4% lower lobe lesions only

Shaikh MA, Saudi Med J, 2003

Presentation and DiagnosisPresentation and Diagnosis

More advanced diseaseMore advanced disease Patients with DM are more frequently Patients with DM are more frequently smear +smear + Cavitary findingsCavitary findings Hemoptysis is more commonHemoptysis is more common Fever more commonFever more common

Is this a result of delay in diagnosis or Is this a result of delay in diagnosis or more rapid disease progression?more rapid disease progression?

Wang CS, Epidemiol Infect, 2008

Response to TreatmentResponse to Treatment

Old Dogma: Despite increased risk of progression Old Dogma: Despite increased risk of progression to active TB if infected, diabetic patients did just as to active TB if infected, diabetic patients did just as well.well.

5 new studies5 new studies BaltimoreBaltimore: delayed culture conversion, higher : delayed culture conversion, higher

mortalitymortality TexasTexas: delayed sputum culture conversion: delayed sputum culture conversion TaiwanTaiwan: higher mortality: higher mortality IndonesiaIndonesia: slower smear and culture : slower smear and culture

conversionconversion ShanghaiShanghai: significantly higher relapse rate: significantly higher relapse rate

Response to TreatmentResponse to Treatment

Data on drug resistance is less clear with Data on drug resistance is less clear with some studies showing increased drug some studies showing increased drug resistance in patients with DM, but others resistance in patients with DM, but others notnot

Patients with DM may be at increased risk Patients with DM may be at increased risk of acquired drug resistanceof acquired drug resistance

Acquired MDR TB is infrequent in CA, but Acquired MDR TB is infrequent in CA, but anecdotally, the 2 most recent cases were anecdotally, the 2 most recent cases were among persons with DMamong persons with DM

Rifampin and DMRifampin and DM

Comparison of 17 age and sex matched Comparison of 17 age and sex matched persons with and without DM. (All had persons with and without DM. (All had TB)TB)

AUC 12.3 mgAUC 12.3 mg x h/L TB and DM x h/L TB and DM AUC 25.9 mgAUC 25.9 mg x h/L TB only x h/L TB only Peak levels also about half in DiabeticsPeak levels also about half in Diabetics Low levels associated with Low levels associated with higher body higher body

weightweight and and poor glucose controlpoor glucose control

Nijland HM, Clin Infect Dis, 2006

Case 1Case 1

64 yo Hmong woman diagnosed with 64 yo Hmong woman diagnosed with extensive, smear + pan-sensitive tuberculosis extensive, smear + pan-sensitive tuberculosis in August, 2009in August, 2009

Longstanding, poorly controlled DMLongstanding, poorly controlled DM Began RIPE 8/31/09Began RIPE 8/31/09 Smears improved gradually and became Smears improved gradually and became

negative in October, 2009negative in October, 2009 Cultures remained +Cultures remained +

Case 1Case 1

Late January 2010, smears again +Late January 2010, smears again + Culture sent for molecular beacons and DSTCulture sent for molecular beacons and DST Molecular beacon showed no INH resistance Molecular beacon showed no INH resistance

mutations in katG or inhA, results for Rif were mutations in katG or inhA, results for Rif were initially inconclusive, but repeat test showed initially inconclusive, but repeat test showed rpoB Rif mutationrpoB Rif mutation

Culture very slow growing, but DST report in Culture very slow growing, but DST report in late March showed INH and Rif resistantlate March showed INH and Rif resistant

Case 1Case 1

What happened?What happened? Without informing DOT staff, patient had Without informing DOT staff, patient had

developed almost daily vomiting after taking developed almost daily vomiting after taking TB medsTB meds

Why?Why? Poorly controlled diabetic patients frequently Poorly controlled diabetic patients frequently

have have gastroparesisgastroparesis Rifampin levels are lower even w/o vomitingRifampin levels are lower even w/o vomiting

Effect of TB treatment on DMEffect of TB treatment on DM

Rifampin Rifampin raises blood glucoseraises blood glucose levels even in non levels even in non diabeticsdiabetics

Rifampin Rifampin activates the CYP450activates the CYP450 enzyme system enzyme system SulfonorylureasSulfonorylureas and t and thiozolidinedioneshiozolidinediones are are

metabolized by this same system.metabolized by this same system. Blood levels of these drugs significantly Blood levels of these drugs significantly lowered lowered

by Rifampinby Rifampin

When treating TB in a patient with When treating TB in a patient with DM remember:DM remember:

Both Both PZA and EMBPZA and EMB need need adjustmentadjustment for renal for renal impairment; check serum impairment; check serum CrCr (renal dys-function (renal dys-function common in DM)common in DM)

INH peripheral neuropathyINH peripheral neuropathy is more common in is more common in diabetics: always supplement diabetics: always supplement Vitamin B6Vitamin B6

Follow patients closely and Follow patients closely and monitormonitor for for sputum sputum conversionconversion

Consider Consider extending treatment to 9 monthsextending treatment to 9 months if risk if risk factors for relapse such as factors for relapse such as slow sputum conversion slow sputum conversion OR cavitary CXROR cavitary CXR are present are present


Just as we recommend screening TB patients Just as we recommend screening TB patients for HIV, for HIV, screen for DM when TB is diagnosedscreen for DM when TB is diagnosed

RepeatRepeat serum glucose after one month serum glucose after one month Monitor for polyuria/polydipsia during Monitor for polyuria/polydipsia during

treatmenttreatment Follow diabetes closely and Follow diabetes closely and adjust adjust diabetic diabetic

medications to bring medications to bring blood sugar as close to blood sugar as close to normalnormal as possible as possible


At At treatment endtreatment end, be aware that diabetic , be aware that diabetic medications may need to be adjusted medications may need to be adjusted downwarddownward

Recommendations for TB Recommendations for TB screening and LTBI treatmentscreening and LTBI treatment

ScreenScreen all diabetics at risk for TB infection for all diabetics at risk for TB infection for LTBI (and active TB), at diagnosis of DM and LTBI (and active TB), at diagnosis of DM and periodically, as local epi dictatesperiodically, as local epi dictates

Strongly Strongly encourage LTBI treatmentencourage LTBI treatment if TST if TST and/or IGRA is positive.and/or IGRA is positive.

Contacts with DMContacts with DM should be given high should be given high prioritypriority for evaluation and LTBI treatment for evaluation and LTBI treatment

TB and Diabetes Mellitus TB and Diabetes Mellitus

DM increases DM increases risk of LTBI progressingrisk of LTBI progressing to disease to disease Diabetic patients Diabetic patients need LTBI screeningneed LTBI screening and rx and rx TB may TB may present differentlypresent differently in diabetics in diabetics Diabetics Diabetics clear sputum more slowlyclear sputum more slowly and have and have higher higher

mortalitymortality Consider Consider prolonging treatment to 9 monthsprolonging treatment to 9 months if risk factors if risk factors

for relapse such as either for relapse such as either delayed sputum conversiondelayed sputum conversion OROR cavitary CXRcavitary CXR are present are present

Consider obtaining Consider obtaining Rifampin bloodRifampin blood levels levels Monitor Monitor diabetic control closelydiabetic control closely Use B6Use B6 if on INH if on INH

Tobacco and Tobacco and TuberculosisTuberculosis

Is there a problem?Is there a problem?

Tobacco use is the leading preventable Tobacco use is the leading preventable cause of death in the worldcause of death in the world

Tobacco use is a risk factor for 6 of the 8 leading Tobacco use is a risk factor for 6 of the 8 leading causes of death in the worldcauses of death in the world Ischemic heart disease, cerebral vascular Ischemic heart disease, cerebral vascular

disease, COPD, lower respiratory infections, disease, COPD, lower respiratory infections, lung cancerlung cancer

AND

Tuberculosis

The tobacco epidemic is about to get muchThe tobacco epidemic is about to get much worseworse

Tobacco currently kills Tobacco currently kills about 5 million/year but about 5 million/year but this will increase to 10 this will increase to 10 million/year in a few million/year in a few decadesdecades

Total deaths Total deaths attributable to tobacco attributable to tobacco in the 21in the 21stst century are century are estimated to be estimated to be 1 billion1 billion

Tobacco and DevelopmentTobacco and Development

Tobacco and Poverty: A vicious circleTobacco and Poverty: A vicious circle The poor are the ones who smoke the mostThe poor are the ones who smoke the most Smoking worsens poverty due to:Smoking worsens poverty due to:

• Money spent of tobacco can’t be used for food or Money spent of tobacco can’t be used for food or other essential itemsother essential items

• Increased illness and health care costsIncreased illness and health care costs

Smoking accounts for much of the Smoking accounts for much of the mortality gap between rich and poormortality gap between rich and poor

High burden TB countries are those High burden TB countries are those with high-burden tobacco usewith high-burden tobacco use

40% of new and relapsed TB cases live in 40% of new and relapsed TB cases live in just 2 countries, India and Chinajust 2 countries, India and China

>40% of smokers live in those same two >40% of smokers live in those same two countriescountries

So what is the association So what is the association between tobacco exposure between tobacco exposure

and tuberculosis?and tuberculosis?

A Qualitative Systematic Review Jointly A Qualitative Systematic Review Jointly Conducted by WHO and IUATLDConducted by WHO and IUATLD

Selection of articles:Selection of articles: All English language journal articles on tobacco All English language journal articles on tobacco

exposure and tuberculosis available in:exposure and tuberculosis available in:• PubMed from 1954 through 2005PubMed from 1954 through 2005• The Union data base of TB articles since 1918The Union data base of TB articles since 1918

42 articles containing 50 studies were 42 articles containing 50 studies were included in the review.included in the review.

Main Results of the Systematic Main Results of the Systematic ReviewReview

Exposure to tobacco smoke is significantly Exposure to tobacco smoke is significantly related to TB infection:related to TB infection: Eight studies investigated tuberculosis infectionEight studies investigated tuberculosis infection All of the studies of infection found significant effects All of the studies of infection found significant effects

of exposure to tobaccoof exposure to tobacco Odds ratios ranging from 1.03 to 3.20Odds ratios ranging from 1.03 to 3.20

The effects of tobacco use on TB outcomes are independent of the effects of alcohol use, SES, age, sex and other potential confounders


Passive or active exposure to tobacco Passive or active exposure to tobacco smoke is significantly associated with a smoke is significantly associated with a new and/or recurrent tuberculosis disease:new and/or recurrent tuberculosis disease: 24 studies explored the relationship between 24 studies explored the relationship between

tobacco smoke exposure and new and/or tobacco smoke exposure and new and/or recurrent tuberculosis disease:recurrent tuberculosis disease:• Of 19 studies with significant results for active Of 19 studies with significant results for active

exposure, exposure, odds ratios ranged from 1.01 to 6.26odds ratios ranged from 1.01 to 6.26• Of 4 studies with significant effects for passive Of 4 studies with significant effects for passive

exposure, exposure, odds ratios ranged from 1.6 to 9.3odds ratios ranged from 1.6 to 9.3


Active smoking is significantly associated Active smoking is significantly associated with tuberculosis mortality:with tuberculosis mortality: 5 studies investigated the role of exposure to 5 studies investigated the role of exposure to

tobacco smoke and tuberculosis mortalitytobacco smoke and tuberculosis mortality All of the mortality studies found significant All of the mortality studies found significant

relationships with tobacco use.relationships with tobacco use. Risk ratios ranging from 1.02 to 6.62Risk ratios ranging from 1.02 to 6.62

A Nationally Representative Case-A Nationally Representative Case-Control Study of Smoking and Death in Control Study of Smoking and Death in

IndiaIndia

Smoking will cause about 930,000 deaths Smoking will cause about 930,000 deaths in India in 2010 and smoking could also be in India in 2010 and smoking could also be a cause of many of the deaths from TBa cause of many of the deaths from TB

38% of total numbers of deaths38% of total numbers of deaths associated associated with smoking will be caused by TBwith smoking will be caused by TB

Prabhat, NEJM 2008

Mechanisms underlying the Association Mechanisms underlying the Association between Tobacco and TBbetween Tobacco and TB

Smoking may attenuate mycobactericidal Smoking may attenuate mycobactericidal activities including oxidative stress in the activities including oxidative stress in the lung tissueslung tissues

Mechanical disruption of cilia function and Mechanical disruption of cilia function and other clearance mechanisms in the other clearance mechanisms in the tracheobronchial systemtracheobronchial system

Nicotine turns off the production of TNF-Nicotine turns off the production of TNF-alpha by macrophages in the lungs alpha by macrophages in the lungs (decreasing local levels of TNF-alpha might reactivate LTBI)(decreasing local levels of TNF-alpha might reactivate LTBI)

1) Pai, Expert Rev Anti Infect Ther, 2007; 2) Davis, Trans Roy Soc Trop Med Hygiene, 2006

The New Stop TB StrategyThe New Stop TB Strategy

WHO developed a new Stop TB strategy WHO developed a new Stop TB strategy in 2006, recognizing that prevention of the in 2006, recognizing that prevention of the most frequent risk factors is an important most frequent risk factors is an important contributor to TB controlcontributor to TB control

Any reduction in the prevalence of tobacco Any reduction in the prevalence of tobacco smoking should benefit TB controlsmoking should benefit TB control

We in the health care system must play an We in the health care system must play an important role in reducing both of these important role in reducing both of these epidemicsepidemics

What can we do?What can we do?

MPOWER: Six policies to Reverse MPOWER: Six policies to Reverse the Tobacco Epidemicthe Tobacco Epidemic

MMonitor tobacco use and prevention onitor tobacco use and prevention policiespolicies

PProtect people from tobacco smokerotect people from tobacco smoke OOffer help to quit tobacco useffer help to quit tobacco use WWarm about the dangers of tobaccoarm about the dangers of tobacco EEnforce bans on tobacco advertising, nforce bans on tobacco advertising,

promotion, and sponsorshippromotion, and sponsorship RRaise taxes on tobaccoaise taxes on tobacco

Treatment of tobacco dependence Treatment of tobacco dependence is effectiveis effective

InterventionsInterventions ComparatorComparator Odds RatioOdds RatioSelf-helpSelf-help No interventionNo intervention 1.241.24

Physician advicePhysician advice No adviceNo advice 1.741.74

Physician intensive Physician intensive adviceadvice

Minimal adviceMinimal advice 1.441.44

Group behavior rxGroup behavior rx No interventionNo intervention 2.172.17

NRTNRT Placebo or non-ARTPlacebo or non-ART 1.581.58

Telephone counselingTelephone counseling No telephone c.No telephone c. 1.411.41

Effectiveness data for smoking cessation interventions (abstinence for at least 6 months) Cochrane Reviews

Can we reduce both morbidity and Can we reduce both morbidity and mortality from TB by increasing our efforts mortality from TB by increasing our efforts to reduce smoking?to reduce smoking?

DOTS +MPOWER

=

TBTB

Raviglione, M.Raviglione, M.

RR if factor RR if factor presentpresent

Prevalence of Prevalence of factorfactor

Population Population attributable riskattributable risk

Malnutrition Malnutrition 3.03.0 17%17% 25%25%

D. M.D. M. 3.03.0 3.4%3.4% 6%6%

SmokingSmoking 2.62.6 18%18% 23%23%

HIVHIV 8.38.3 1%1% 7%7%

TB and Renal DiseaseTB and Renal Disease

Impaired CMIImpaired CMI with cutaneous with cutaneous anergyanergy rates of rates of 30-80% in ESRD30-80% in ESRD

Risk of active TB Risk of active TB 7-52 X7-52 X higher than general higher than general populationpopulation

2004 Kaiser Permanente study: Active TB in 2004 Kaiser Permanente study: Active TB in their dialysis patients their dialysis patients 11.3 X11.3 X rate in California rate in California population as a wholepopulation as a whole

Renal DiseaseRenal DiseaseTB Treatment PrincipalsTB Treatment Principals

For For CrCl < 30CrCl < 30 ml/min: ml/min: INH and RIF not affected and dose adjustments are INH and RIF not affected and dose adjustments are

not necessary (metabolized by the liver)not necessary (metabolized by the liver) EMB, PZA and levofloxacin: use usual daily dose, EMB, PZA and levofloxacin: use usual daily dose,

but but decrease frequency to 3 X weeklydecrease frequency to 3 X weekly Give all drugs immediately after dialysisGive all drugs immediately after dialysis Always use vitamin Always use vitamin B6B6 with INH with INH

For For CrCl > 30, but <70CrCl > 30, but <70 ml/min: ml/min: Monitor closely for EMB optic neuropathyMonitor closely for EMB optic neuropathy

First Line Agents and HemodialysisFirst Line Agents and Hemodialysis

DrugDrug Change Change frequency?frequency?

Removed by Removed by hemodialysishemodialysis

IsoniazidIsoniazid NONO ++

RifampinRifampin NONO NONO

EthambutolEthambutol YESYES ++

PyrazinamidePyrazinamide YESYES ++++++


Resources:Resources: http://www.ctca.org/guidelines/New_Renal_Dialysis_Guidhttp://www.ctca.org/guidelines/New_Renal_Dialysis_Guid

elines_02_22_08.pdfelines_02_22_08.pdf http://www.thoracic.org/sections/publications/statements/phttp://www.thoracic.org/sections/publications/statements/p

ages/mtpi/rr5211.htmlages/mtpi/rr5211.html

TB Treatment Doses and Intervals in ESRDTB Treatment Doses and Intervals in ESRD


Prevention is the key!Prevention is the key! All patients with renal impairment should have All patients with renal impairment should have

baseline TST or IGRA to assess for LTBI, baseline TST or IGRA to assess for LTBI, ideally before CrCL < 30 ml/minideally before CrCL < 30 ml/min

If LTBI present, must be very strongly If LTBI present, must be very strongly encouraged to complete LTBI Rxencouraged to complete LTBI Rx• INH 300 mg daily or 900 mg twice or thrice weekly INH 300 mg daily or 900 mg twice or thrice weekly

after dialysis for 9 monthsafter dialysis for 9 months• Rifampin 600 mg daily or twice or thrice weekly for Rifampin 600 mg daily or twice or thrice weekly for

4 months4 months

HIV related TuberculosisHIV related Tuberculosis

WHO estimates that TB is cause of death WHO estimates that TB is cause of death for 13% of persons with AIDSfor 13% of persons with AIDS

Risk of progression to active TB if LTBI Risk of progression to active TB if LTBI present is about 10% per annumpresent is about 10% per annum

Occurs even with relatively high CD4 Occurs even with relatively high CD4 countscounts

Presentation influenced by degree of Presentation influenced by degree of immunodeficiencyimmunodeficiency

CXR Pattern: Early vs. Advanced HIVCXR Pattern: Early vs. Advanced HIV

Early HIVEarly HIV

(CD4 >200)(CD4 >200)

Advanced HIV Advanced HIV

(CD4 <200)(CD4 <200)

PatternPattern ““Typical” Typical” (Reactivation)(Reactivation)

““Atypical”Atypical”(Primary)(Primary)

InfiltrateInfiltrate Upper lobesUpper lobesLower lobes, Lower lobes,

multiple sites, multiple sites, or miliaryor miliary

CavitationCavitation CommonCommon UncommonUncommon

AdenopathyAdenopathy UncommonUncommon CommonCommon

EffusionEffusion UncommonUncommon More commonMore common

Adenitis and ConsolidationAdenitis and Consolidation

Courtesy M. Gotway, MD


When CD4 < 200, extra pulmonary TB When CD4 < 200, extra pulmonary TB (lymphadenitis, pleuritis, pericarditis, and (lymphadenitis, pleuritis, pericarditis, and meningitis) with or without pulmonary meningitis) with or without pulmonary disease found > 50% of patientsdisease found > 50% of patients

Can present with high fevers, rapid Can present with high fevers, rapid progression, sepsis syndromeprogression, sepsis syndrome


Screen all persons for LTBIScreen all persons for LTBI at time of HIV at time of HIV diagnosisdiagnosis

If initial CD4 < 200 and LTBI test negative, If initial CD4 < 200 and LTBI test negative, repeat screeningrepeat screening after ART begun and CD4 > after ART begun and CD4 > 200200

Annual screening only if at risk for repeated or Annual screening only if at risk for repeated or ongoing exposure to persons with active TB ongoing exposure to persons with active TB

Screening Tests:Screening Tests: TST; 5 mm or greater reaction is positiveTST; 5 mm or greater reaction is positive IInterferon nterferon GGamma amma RRelease elease AAssays (IGRAs)ssays (IGRAs)


Treat for LTBITreat for LTBI if no evidence of active TB if no evidence of active TB AND:AND: Any positive diagnostic testAny positive diagnostic test for LTBI without for LTBI without

prior treatmentprior treatment Close contactClose contact of infectious TB case, of infectious TB case,

regardless of TST or IGRA resultregardless of TST or IGRA result History of untreated or inadequately treated History of untreated or inadequately treated

healed TB (healed TB (old fibrotic lesionsold fibrotic lesions on CXR) on CXR) Preferred regimen is INH 300 mg daily for Preferred regimen is INH 300 mg daily for

9 months9 months


Initiation of ART in Patients with Active TB:Initiation of ART in Patients with Active TB: Always start TB treatment immediatelyAlways start TB treatment immediately

CD4 countCD4 count Timing of ART InitiationTiming of ART Initiation

<100<100 After 2 or more weeks of TB rxAfter 2 or more weeks of TB rx

100-200100-200 After 2-8 weeks of TB rxAfter 2-8 weeks of TB rx

201-350201-350 During maintenance phase of TB rxDuring maintenance phase of TB rx

> 350> 350 After completion of TB rxAfter completion of TB rx

CDC: MMWR, Guidelines for Prev/Treat of Opp Inf in HIV-infected Adults and Adolescents. April, 2009


EfavirenzEfavirenz based ART is preferred based ART is preferred If pregnant or under 3 years of age, If pregnant or under 3 years of age,

Nevirapine Nevirapine is the NNRTI of choiceis the NNRTI of choice If patient is already on a If patient is already on a protease inhibitorprotease inhibitor

based regimen or a PI must be used, then based regimen or a PI must be used, then RifabutinRifabutin may be used instead of Rifampin may be used instead of Rifampin

Case 2Case 2

A 40 year-old man presents with fever for 4 A 40 year-old man presents with fever for 4 weeks, cough with bloody sputum, night weeks, cough with bloody sputum, night sweats and weight loss of 7kgsweats and weight loss of 7kg

Chest X-ray shows right mid lung infiltrateChest X-ray shows right mid lung infiltrate Sputum AFB is positiveSputum AFB is positive His HIV test is positive and CD4 is180 cell/cu His HIV test is positive and CD4 is180 cell/cu

mmmm RIPE is begunRIPE is begun

Case 2Case 2

When seen after 8 weeks When seen after 8 weeks of treatment, his fevers, of treatment, his fevers, night sweats, and cough night sweats, and cough have stopped and he has have stopped and he has gained 5kggained 5kg

His TB regimen is His TB regimen is changed to isoniazid and changed to isoniazid and rifampin rifampin

Atripla is begun Atripla is begun (efavirenz, tenofovir, (efavirenz, tenofovir, emtricitabine)emtricitabine)

X-ray shows improvement

Case 2Case 2

The patient returns 1 month after starting The patient returns 1 month after starting Atripla Atripla

He says that his fever, cough and night He says that his fever, cough and night sweats have “come back” “sweats have “come back” “

He has taken the Atripla as prescribed but He has taken the Atripla as prescribed but thinks they are making him more sick and thinks they are making him more sick and would like to stop themwould like to stop them

Case 2Case 2

The patient has had The patient has had excellent adherence and excellent adherence and denies nausea, vomiting denies nausea, vomiting or diarrhea or diarrhea

His oxygen saturation His oxygen saturation comes back at 96% on comes back at 96% on room airroom air

Heart rate, respiratory Heart rate, respiratory rate and other vital signs rate and other vital signs are normalare normal

Some axillary nodes are Some axillary nodes are presentpresent

Sputum smear is 1+ AFBSputum smear is 1+ AFB NSAIDS givenNSAIDS given

NEW CHEST X RAY

Case 2Case 2 2 weeks later he is worse2 weeks later he is worse Sputum cultures have Sputum cultures have

converted to negativeconverted to negative Sputum smear is still 1+ Sputum smear is still 1+

AFBAFB On physical exam is On physical exam is

tachypneictachypneic Respiratory rate is elevated Respiratory rate is elevated

and oxygen saturations is and oxygen saturations is 90% on room air90% on room air

Crackles heard in right lung Crackles heard in right lung fieldfield

X-ray shows worsening

IImmune mmune RReconstitution econstitution IInflammatory nflammatory SSyndrome (IRIS)yndrome (IRIS)

Paradoxical worsening of symptoms after Paradoxical worsening of symptoms after initiating ART (or sometimes TB rx itself)initiating ART (or sometimes TB rx itself)

Remains a major problem, particularly if Remains a major problem, particularly if initial CD4 count lowinitial CD4 count low

Usually occurs 1-3 months into ARTUsually occurs 1-3 months into ART Greatest risk if ART started in first 2 Greatest risk if ART started in first 2

months of TB rx, and/or CD4 < 100months of TB rx, and/or CD4 < 100


Signs/symptomsSigns/symptoms High feversHigh fevers Worsening respiratory status, parenchymal Worsening respiratory status, parenchymal

infiltrates, pleural effusionsinfiltrates, pleural effusions Increase in lymphadenopathyIncrease in lymphadenopathy Breakthrough meningitis or CNS lesionsBreakthrough meningitis or CNS lesions

Evaluate thoroughly for other possible Evaluate thoroughly for other possible causes, especially TB treatment failurecauses, especially TB treatment failure


Treat with NSAIDS if mild to moderateTreat with NSAIDS if mild to moderate Use steroids if severe (1mg/kg of Use steroids if severe (1mg/kg of

prednisone daily with gradual taper)prednisone daily with gradual taper) Try not to change anti-TB or ARV therapyTry not to change anti-TB or ARV therapy

In SummaryIn Summary

Many, if not most of our TB patients now Many, if not most of our TB patients now have significant co morbiditieshave significant co morbidities

Our colleagues in the private sector will need Our colleagues in the private sector will need to remember TB in order to promptly to remember TB in order to promptly diagnose, or better yet, prevent TBdiagnose, or better yet, prevent TB

Epidemics of DM and HIV, and ongoing Epidemics of DM and HIV, and ongoing tobacco use place large numbers of patients tobacco use place large numbers of patients at risk for TBat risk for TB

Co morbid conditions complicate the Co morbid conditions complicate the treatment of TBtreatment of TB

TB Prevention is keyTB Prevention is key

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