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Double Trouble: Diabetes and Tuberculosis. Kris Ernst, BSN, RN, CDE Division of Diabetes Translation Centers for Disease Control and Prevention. Disclaimer. This presentation represents the opinion of the author and is not the official opinion of CDC . Tuberculosis and Diabetes: Old Foes.

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double trouble diabetes and tuberculosis

Double Trouble:Diabetes and Tuberculosis

Kris Ernst, BSN, RN, CDE

Division of Diabetes Translation

Centers for Disease Control and Prevention

disclaimer
Disclaimer
  • This presentation represents the opinion of the author and is not the official opinion of CDC
tuberculosis and diabetes old foes
Tuberculosis and Diabetes:Old Foes
  • Indian physician Susruta, in 600 A.D.

“phthisis frequently complicated diabetes”

  • Autopsy of diabetics in 1883 showed presence of TB granuloma I 50% of diabetics
  • Prior to the insulin era: Diagnosis of DM was a death sentence
    • Leading cause of death was: Tuberculosis
definitions
Definitions
  • Latent Tuberculosis Infection (LTBI)
    • Persons are infected with M. tuberculosis, but do not have active TB disease.
  • Active TB Disease
    • Persons infected with M tuberculosis bacteria that progress from latent TB infection.
background
Background
  • Diabetes increases risk for progression from latent TB infection (LTBI) to active TB disease and complicates treatment of active TB
  • Delays in diagnosis for both diabetes and TB
  • Globally, the number of people with diabetes is increasing
background8
Background
  • Pathophysiology – diabetes,especially when poorly-controlled, causes relative immunocompromise and increases likelihood of reactivation of TB
  • Epidemiology – dramatic increase of diabetes
  • Demographics – diabetes disproportionately affects lower socioeconomic groups and ethnic minorities that also have higher prevalence of TB
background9
Background

Treatment considerations – hard to treat TB in the face of poor glucose control

Hidden epidemic – estimated that ¼ of people with diabetes don’t know they have it

tb case rates united states 2008
TB Case Rates,* United States, 2008

D.C.

< 3.5 (year 2000 target)

3.6–4.2

> 4.2 (national average)

*Cases per 100,000.

reported tb cases by age group united states 2008
Reported TB Cases by Age Group, United States, 2008

<15 yrs

(6%)

>65 yrs

(19%)

15–24 yrs

(11%)

25–44 yrs (33%)

45–64 yrs

(30%)

tb case rates by race ethnicity united states 1993 2008

Asian/Pacific Islander

American Indian/Alaska Native

Black or African-American

White

Hispanic

TB Case Rates by Race/Ethnicity* United States, 1993–2008**

Cases per 100,000

*All races are non-Hispanic. In 2003, Asian/Pacific Islander category includes persons who reported race as Asian only and/or Native Hawaiian or Other Pacific Islander only.**Updated as of May 20, 2009.

reported tb cases by race ethnicity united states 2008
Reported TB Cases by Race/Ethnicity* United States, 2008

American Indian or

Alaska Native (1%)

White

(17%)

Asian

(26%)

Native Hawaiian or

Other Pacific Islander (<1%)

Hispanic or Latino

(29%)

Black or

African-American

(25%)

*All races are non-Hispanic. Persons reporting two or more races accounted for less than 1% of all cases.

reported tb cases united states 1982 2008
Reported TB Cases* United States, 1982–2008

No. of Cases

Year

*Updated as of May 20, 2009.

tb morbidity united states 2003 2008
TB MorbidityUnited States, 2003–2008

Year No. Rate*

  • 2003 14,836 5.1
  • 2004 14,500 4.9
  • 2005 14,067 4.7
  • 13,727 4.6
  • 13,288 4.4
  • 12,904 4.2

*Cases per 100,000, updated as of May 20, 2009.

transmission of m tuberculosis
Transmission of M. tuberculosis
  • Spread by airborne route; droplet nuclei
  • Transmission affected by
    • Infectiousness of patient
    • Environmental conditions
    • Duration of exposure
  • Most exposed persons do not become infected
tb pathogenesis 1 latent tb infection
TB Pathogenesis (1)Latent TB Infection
  • Once inhaled, bacteria travel to lung alveoli and establish infection
  • 2–12 wks after infection, immune response limits activity; infection is detectable
  • Some bacteria survive and remain dormant but viable for years (latent TB infection, or LTBI)
tb pathogenesis 2 latent tb infection
TB Pathogenesis (2)Latent TB Infection
  • Persons with LTBI are
    • Asymptomatic
    • Not infectious
  • LTBI formerly diagnosed only with TST
  • Now QFT-G can be used
anergy
Anergy

Anergy is the immune system’s failure to respond to injected reagents or antigens

Persons with compromised immunity may not react to tuberculin

A few persons with normal immunity also do not react

Thus, absence of TST reaction does not rule out LTBI or TB disease

Anergy testing not recommended as adjunct to TST, because TST results alone cannot guide clinical decision making

what s new
What’s New
  • QuantiFERON-TB Gold test (QFT-G)
  • QFT-G is a type of blood assay for M. tuberculosis (BAMT)
    • Measures the patient’s immune system reaction to M. tuberculosis
    • Blood samples must be processed within 12 hours
    • Interpretation of QFT-G results is influenced by the patient’s risk for infection with M. tuberculosis
    • An alternative to TST
clinical diagnosis
Clinical Diagnosis

Obtain medical history and physical exam

Place patients with suspected or known infectious TB disease under AII precautions until determined to be noninfectious

Evaluate persons with extrapulmonary TB for concurrent pulmonary TB disease

Although normally not infectious, children should be evaluated for infectiousness

diagnosis of latent tb infection
Diagnosis of Latent TB Infection
  • Persons with LTBI
    • Are asymptomatic
    • Do not feel sick
    • Cannot spread TB to others
  • Diagnostic procedures
    • Positive TST with medical evaluation to exclude TB
      • Evaluation includes assessing symptoms and signs, x-ray, and sputum tests
    • Blood assay for M. tuberculosis (BAMT) now available
treatment for ltbi
Treatment for LTBI
  • Treating LTBI reduces the risk that M. tuberculosis infection will develop into TB disease
  • Certain groups have higher risk for developing TB disease after infection; should be treated
  • Before beginning treatment for LTBI
    • Exclude diagnosis of TB
    • Ensure patient has no history of adverse reactions resulting from prior LTBI treatment
candidates for treatment for ltbi
Candidates for Treatment for LTBI

The frequency of TB testing for HCWs will be determined by the risk classification for the setting.

tb patient characteristics that increase risk for infectiousness 1
TB Patient Characteristics That Increase Risk for Infectiousness (1)
  • Coughing
  • Undergoing cough-inducing or aerosol-generating procedure
  • Failing to cover cough
  • Having cavitation on chest radiograph
tb patient characteristics that increase risk for infectiousness 2
TB Patient Characteristics That Increase Risk for Infectiousness (2)
  • Positive acid-fast bacilli (AFB) sputum smear result
  • Disease of respiratory tract and larynx
  • Disease of respiratory tract and lung or pleura
  • Inadequate TB treatment
characteristics of infectiousness
Characteristics of Infectiousness

Infectiousness related to

  • Cough >3 weeks
  • Cavitation on chest radiograph
  • Positive sputum smear results
characteristics of infectiousness29
Characteristics of Infectiousness
  • Respiratory tract disease involving lung, airway, or larynx
  • Failure to cover mouth and nose when coughing
  • Inadequate treatment
  • Undergoing cough- or aerosol-producing procedures
antituberculosis drugs
Isoniazid

Rifampin

Pyrazinamide

Ethambutol

Rifabutin*

Rifapentine

Streptomycin

Cycloserine

p-Aminosalicylic acid

Ethionamide

Amikacin or kanamycin*

Capreomycin

Levofloxacin*

Moxifloxacin*

Gatifloxacin*

Antituberculosis Drugs

First-Line Drugs

Second-LineDrugs

*Not approved by the U.S. Food and Drug Administration for use in the treatment of TB

drug abbreviations
Ethambutol EMB

Isoniazid INH

Pyrazinamide PZA

Rifampin RIF

Rifapentine RPT

Streptomycin SM

Drug Abbreviations
treatment for tb disease
Treatment for TB Disease
  • TB treatment regimens must contain multiple drugs to which M. tuberculosis is susceptible
  • Treating TB disease with a single drug can lead to resistance
  • Also, adding a single drug to a failing regimen can lead to drug resistance
treatment for tb disease34
Treatment for TB Disease
  • Preferred regimen
    • Initial phase: 2 months isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol
    • Continuation phase: 4 months INH and RIF
  • In patients with cavitary pulmonary TB and positive culture results at end of initiation phase, continuation phase should be 7 months
  • TB patients with HIV who are taking anti-retrovirals (ARVs) should be managed by TB/HIV disease experts
    • TB treatment regimens might need to be altered
factors guiding treatment initiation
Epidemiologic information

Clinical, pathological, chest x-ray findings

Microscopic examination of acid-fast bacilli (AFB) in sputum smears

Nucleic acid amplification test (when performed)

Factors Guiding Treatment Initiation
persons at higher risk for exposure to and infection with m tuberculosis
Persons at Higher Risk for Exposure to and Infection with M. tuberculosis

HCWs unknowingly exposed to TB patient

Low-income, medically underserved groups

Locally defined high-risk groups

Young persons exposed to high-risk adults

when to consider treatment initiation
When to Consider Treatment Initiation
  • Positive AFB smear
  • Treatment should not be delayed because of negative AFB smears if high clinical suspicion:
    • History of cough and weight loss
    • Characteristic findings on chest x-ray
    • Emmigration from a high-incidence country
other examinations to conduct when tb treatment is initiated
Other Examinations to Conduct When TB Treatment Is Initiated
  • Counseling and testing for HIV infection
  • CD4+ T-lymphocyte count for HIV-positive persons
  • Hepatitis B and C serologic tests, if risks present
other examinations to conduct when tb treatment is initiated39
Other Examinations to Conduct When TB Treatment Is Initiated
  • Measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, alkaline phosphatase, serum creatinine, and platelet count
  • Visual acuity and color vision tests (when EMB used)
slide40

Algorithm to Guide Treatment of Culture-Negative TB

Isinitial culture positive?

NO

YES

Wastheresymptomaticor chest x-ray improvement after

2 months of treatment?

Continue treatment for culture-positive TB

NO

YES

  • Discontinue treatment
  • Patient presumed to have LTBI
  • Treatment completed

Give continuation- phase treatment of INH/RIF dailyor twice weekly for2 months

role of new drugs
Role of New Drugs

Rifabutin: For patients receiving medications having unacceptable interactions with rifampin (e.g., persons with HIV/AIDS)

Rifapentine: Used in once-weekly continuation phase for HIV-negative adults with drug-susceptible noncavitary TB and negative AFB smears at completion of initial phase of treatment

role of new drugs42
Role of New Drugs
  • Fluoroquinolones (Levofloxacin, Moxifloxacin, Gatifloxacin): Used when

-first-line drugs not tolerated;

-strains resistant to RIF, INH, or EMB; or

-evidence of other resistance patterns with fluoroquinolone susceptibility

drug interactions
Drug Interactions
  • Relatively few drug interactions substantially change concentrations of antituberculosis drugs
  • Antituberculosis drugs sometimes change concentrations of other drugs

-Rifamycins can decrease serum concentrations of many drugs, (e.g., most of the HIV-1 protease inhibitors), to subtherapeutic levels

-Isoniazid increases concentrations of some drugs (e.g., phenytoin) to toxic levels

prevention of tb in persons with dm
Prevention of TB in persons with DM
  • Persons with diabetes mellitus (DM) who are at increased risk of tuberculosis (TB) should be screened for latent TB infection (LTBI)
    • TST or IGRA should be done at time of DM diagnosis
  • Patients with DM who are found to have LTBI should be encouraged to take INH for 9 months
    • Patients with DM on INH should receive vitamin B6 to prevent INH induced neuropathy
screening for dm in persons with tb
Screening for DM in persons with TB
  • Every patient with TB over the age of 18 should be screened for DM
    • A fasting plasma glucose > 125 mg/dl = DM
    • A random plasma glucose > 200 mg/dl = DM
    • A Hemoglobin A1c > 6.5% = DM
  • Abnormal glucose values should be repeated in patients who have no symptoms of DM
screening for dm in persons with tb49
Screening for DM in persons with TB
  • Glucose should be repeated after 2-4 weeks of TB Rx or if symptoms of hyperglycemia develop
    • Rifampin and INH can markedly elevate glucose levels
    • Use the same criteria to diagnose DM as at initial evaluation
  • Ask about polyuria/polydipsia at TB clinic visits
management of dm in patients receiving tb treatment
Management of DM in patients receiving TB treatment
  • Use the frequent contact with the patient during TB treatment to help manage his/her DM in the TB clinic
    • There should be a glucose meter in every TB clinic and blood glucose should be frequently checked in the clinic for those with DM
    • All clinical staff should reinforce lifestyle changes at TB clinic visits
    • If available, refer persons with diabetes to a diabetes specialty clinic or clinician comfortable with treating DM
management of dm in patients receiving tb treatment51
Management of DM in patients receiving TB treatment
  • DOT workers should encourage lifestyle changes at every encounter
    • Dietary changes and physical activity are most important in this effort
    • Use available structured diabetes education materials i.e. NDEP available at: www.YourDiabetesInfo.org
    • Consider delivering DM meds with TB meds via DOT
treatment of tb in persons with dm
Treatment of TB in persons with DM
  • Ensure that TB treatment is appropriately adjusted in persons with DM
    • Check creatinine for diabetic nephropathy
    • May need to adjust frequency of PZA and EMB administration
    • Give B6 to prevent INH induced peripheral neuropathy
treatment of tb in persons with dm53
Treatment of TB in persons with DM
  • Ensure that TB treatment is appropriately adjusted in persons with DM
    • Persons with DM have a relative immune suppression and often a higher burden of disease
    • Consider extending treatment to 9 months for persons with DM and caviatary disease OR delayed sputum clearance.
    • Upon completion of therapy, obtain smear and culture for AFB
    • Follow up the patient at 6 months and one year after treatment completion
treatment of tb in persons with dm54
Treatment of TB in persons with DM
  • Observe closely for treatment failure
    • Be aware of poor absorpti0on of some TB meds in DM
    • Manage the many interactions between TB and DM meds
    • There may be a slight increase in diabetic retinopathy in persons with DM
special treatment situations renal insufficiency and end stage renal disease
Special Treatment SituationsRenal Insufficiency and End-Stage Renal Disease

Renal insufficiency complicates management of TB because some antituberculosis medications are cleared by the kidneys

Dosage should not be decreased because peak serum concentrations may be too low; smaller doses may decrease drug efficacy

slide56
Dosing interval of antituberculosis drugs should be decreased

Most drugs can be given 3 times weekly after hemodialysis; for some drugs, dose must be adjusted

Special Treatment SituationsRenal Insufficiency and End-Stage Renal Disease

special treatment situations hepatic disease
Must consider regimens with fewer hepatotoxic agents for patients with liver disease

Recommended regimens:

Treatment without PZAInitial phase (2 months): INH, RIF, and EMBContinuation phase (7 months): INH and RIF

Treatment without INHInitial phase (2 months): RIF, PZA, and EMBContinuation phase (4 months): RIF, EMB, and PZA

Special Treatment SituationsHepatic Disease
special treatment situations hepatic disease58
Special Treatment SituationsHepatic Disease
  • Recommended regimens: (continued)
    • 3) Regimens with only one potentially hepatotoxic drug
      • RIF should be retained
      • Duration of treatment is 12-18 months
    • 4) Regimens with no potentially hepatotoxic drugs
      • Duration of treatment is 18-24 months
treatment failure
Treatment Failure

Defined as positive cultures after 4 months of treatment in patients for whom medication ingestion was ensured

Single new drug should never be added to a failing regimen; it may lead to acquired resistance to the added drug

Add at least three new drugs (e.g., fluoroquinolone, ethionamide, and an injectable drug: SM, amikacin, kanamycin, or capreomycin) to the existing regimen being cognizant of the possibility of drug resistance

references
References
  • Centers for Disease Control and Prevention. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR 2005; 54 (No. RR-17): 1–141.

http://www.cdc.gov/nchstp/tb/pubs/mmwrhtml/ Maj_guide/infectioncontrol.htm

  • Errata (August 2006) available onlinehttp://www.cdc.gov/nchstp/tb/pubs/mmwrhtml/ Errata_table.pdf
guidelines for preventing the transmission of m tuberculosis in health care settings 2005

Guidelines for Preventing the Transmission of M. tuberculosis in Health-Care Settings, 2005

Division of Tuberculosis Elimination

December 2006note: Slide #123 has been edited.

additional tb guidelines
Additional TB Guidelines

CDC. Prevention and Control of Tuberculosis in Correctional and Detention Facilities: Recommendations from CDC.MMWR 2006; 55 (No. RR-09): 1–44.

CDC. Guidelines for the investigation of contacts of persons with infectious tuberculosis: recommendations from the National Tuberculosis Controllers Association and CDC. MMWR 2005; 54 (No. RR-15): 1-37.

CDC. Guidelines for using the QuantiFERON-TB Gold Test for detecting Mycobacterium tuberculosis infection, United States. MMWR 2005; 54 (No. RR-15): 49-55.

CDC. Controlling tuberculosis in the United States: recommendations from the American Thoracic Society, CDC, and the Infectious Diseases Society of America. MMWR 2005; 54 (No. RR-12): 1-81.

CDC. Guidelines for infection control in dental health-care settings—2003. MMWR 2003; 52 (No. RR-17).

CDC. Treatment of tuberculosis. American Thoracic Society, CDC, and Infectious Diseases Society of America. MMWR 2003; 52 (No. RR-11).

CDC. Guidelines for environmental infection control in health-care facilities: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC).MMWR 2003; 52 (No. RR-10).

additional resources
Additional Resources

For additional information on TB, visit the CDC Division of Tuberculosis Elimination website at

http://www.cdc.gov/tb

slide64

Thank You!

kce0@cdc.gov