Download A Deadly Duo: Diabetes and Tuberculosis

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
• 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
• 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
• 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
Number (in Millions) of Persons with
Diagnosed Diabetes, United States, 1980–2007
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
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
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
<15 yrs
(6%)
>65 yrs
(19%)
45–64 yrs
(30%)
15–24 yrs
(11%)
25–44 yrs
(33%)
TB Case Rates by Race/Ethnicity* United
States, 1993–2008**
Cases per 100,000
50
40
30
20
10
0
1993
1996
1999
2002
2005
Asian/Pacific Islander
American Indian/Alaska Native
Black or African-American
Hispanic
White
*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.
2008
Reported TB Cases by Race/Ethnicity*
United States, 2008
White
(17%)
Native Hawaiian or
Other Pacific Islander (<1%)
Hispanic or Latino
(29%)
American Indian or
Alaska Native (1%)
Asian
(26%)
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
28,000
No. of Cases
26,000
24,000
22,000
20,000
18,000
16,000
14,000
12,000
10,000
1984
1987
1990
1993
Year
*Updated as of May 20, 2009.
1996
1999
2002
2005
2008
TB Morbidity
United States, 2003–2008
Year
2003
2004
2005
2006
2007
2008
No.
14,836
14,500
14,067
13,727
13,288
12,904
*Cases per 100,000, updated as of May 20, 2009.
Rate*
5.1
4.9
4.7
4.6
4.4
4.2
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
• 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
• Persons with LTBI are
– Asymptomatic
– Not infectious
• LTBI formerly diagnosed only with TST
• Now QFT-G can be used
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
• 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
• 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
• 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
• 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
Give LTBI Treatment to
If M. tuberculosis Test
Result Is
Highest risk groups
≥5 mm
• Immunocompromised
• Recent contacts
• X-ray indicates previous TB
Other high-risk groups
≥10 mm
Patients with no risks
≥15 mm
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)
• Coughing
• Undergoing cough-inducing or aerosolgenerating procedure
• Failing to cover cough
• Having cavitation on chest radiograph
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
Infectiousness related to
– Cough >3 weeks
– Cavitation on chest radiograph
– Positive sputum smear results
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
First-Line Drugs
Second-Line Drugs
• Isoniazid
• Streptomycin
• Rifampin
• Cycloserine
• Pyrazinamide
• p-Aminosalicylic acid
• Ethambutol
• Ethionamide
• Rifabutin*
• Amikacin or kanamycin*
• Rifapentine
• Capreomycin
• Levofloxacin*
• Moxifloxacin*
• Gatifloxacin*
* Not approved by the U.S. Food and Drug Administration for use in the
treatment of TB
Drug Abbreviations
Ethambutol
Isoniazid
Pyrazinamide
Rifampin
Rifapentine
Streptomycin
EMB
INH
PZA
RIF
RPT
SM
Treatment Regiments for LTBI
Drugs
INH
Months of
Duration
9*
INH
6
RIF
4
*Preferred
INH=isoniazid; RIF=rifampin
Interval
Minimum
Doses
Daily
270
2x wkly
76
Daily
180
2x wkly
52
Daily
120
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 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)
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
• 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
• 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 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)
Algorithm to Guide Treatment of
Culture-Negative TB
Is
initial
culture
positive?
NO
NO
Was
there
symptomatic
or chest x-ray
improvement after
2 months of
treatment?
• Discontinue treatment
• Patient presumed to
have LTBI
• Treatment completed
YES
YES
Continue
treatment for culturepositive TB
Give continuation- phase
treatment
of INH/RIF daily
or twice weekly for
2 months
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 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
Common Adverse Reactions to
Drug Treatment
Drug
Any drug
Adverse Reaction
Signs and Symptoms
Allergy
Skin rash
Ethambutol
Eye damage
Isoniazid,
Hepatitis
Pyrazinamide,
or
Rifampin
Blurred or changed vision
Changed color vision
Abdominal pain
Abnormal liver function test
results
Fatigue
Lack of appetite
Nausea
Vomiting
Yellowish skin or eyes
Dark urine
Common Adverse Reactions to
Drug Treatment
Drug
Isoniazid
Adverse Reaction
Peripheral
neuropathy
Pyrazinamide Gastrointestinal
intolerance
Streptomycin
Signs and Symptoms
Tingling sensation in hands and
feet
Upset stomach, vomiting, lack
of appetite
Arthralgia
Joint aches
Arthritis
Ear damage
Gout (rare)
Balance problems
Hearing loss
Ringing in the ears
Kidney damage
Abnormal kidney function test
results
Common Adverse Reactions to
Drug Treatment
Caused by
Rifamycins
Adverse Reaction
Signs and Symptoms
Thrombocytopenia Easy bruising
• Rifabutin
Slow blood clotting
• Rifapentine Gastrointestinal
intolerance
• Rifampin
Drug interactions
Upset stomach
Interferes with certain
medications, such as birth
control pills, birth control
implants, and methadone
treatment
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
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
• 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 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
• 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 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
• 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 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 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
• 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
Special Treatment Situations
Renal Insufficiency and End-Stage
Renal Disease
• 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 Situations
Hepatic Disease
• Must consider regimens with fewer hepatotoxic
agents for patients with liver disease
• Recommended regimens:
1) Treatment without PZA
Initial phase (2 months): INH, RIF, and EMB
Continuation phase (7 months): INH and RIF
2) Treatment without INH
Initial phase (2 months): RIF, PZA, and EMB
Continuation phase (4 months): RIF, EMB, and PZA
Special Treatment Situations
Hepatic 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
• 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
• 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 online
http://www.cdc.gov/nchstp/tb/pubs/mmwrhtml/
Errata_table.pdf
Guidelines for Preventing the Transmission
of M. tuberculosis in Health-Care Settings,
2005
Division of Tuberculosis Elimination
December 2006
note: Slide #123 has been edited.
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
For additional information on TB, visit the
CDC Division of Tuberculosis Elimination
website at
http://www.cdc.gov/tb
Thank You!
[email protected]