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MCF COUNSELORS
TRAINING FOR TUBERCULOSIS
HELPLINE


                VENUE:MCF OFFICE, PUNE
                5TH NOV 2012 TO 9TH NOV 2012

      www.mcf.org.in                            1
Why helpline for TB?
Tuberculosis (TB) remains a major global health
 problem.
It causes ill-health among millions of people each
 year
TB ranks as the second leading cause of death
 from an infectious disease worldwide, after HIV1
Tuberculosis is a treatable and preventable disease.
What is needed is knowledge about the disease.
Stigma, discrimination and fear : TB has all as HIV
Strong referral services available
So helpline for TB makes sense
                     www.mcf.org.in                     2
What is tuberculosis?
• TB is a chronic bacterial infection.
• The great majority of infections in people are caused
  by Mycobacterium tuberculosis (M. Tuberculosis or
  tubercle bacilli).
• M. tuberculosis and seven very closely related
  mycobacterial species like M. bovis and others
  together comprise what is known as the M.
  tuberculosis complex.
• M. Bovis can cause TB in people who drink
  unpasteurised milk from infected cows.
              www.mcf.org.in                              3
TB: Global Scenario
 • About 1 in 3 of the world’s population is infected with
  tubercle bacilli.
 • There were an estimated 12 million prevalent cases in 2011
 • 170 cases per 100 000 population
 • Incidence: 90 lakh new cases
 • Someone is newly infected every second
 • Mortality: Nearly 14 lakh TB deaths every year




                       www.mcf.org.in                        4
• About 95% of the world’s cases of TB occur
  in South East Asia, sub-Saharan Africa and
  the Western Pacific.
• The five countries with the largest number
  of incident cases in 2011 were India (approx
  2.0 million), China (approx–1 million),
  South Africa (approx 0.5 million),
  Indonesia (approx 0.5 million) and
  Pakistan (approx 0.4 million).
• India and China alone accounted for 26%
  and 12% of global cases, respectively.

                   www.mcf.org.in                5
TB in India
Nearly 40% of the Indian population is infected with the
 MTB bacillus
Approx 30 million people in India are infected with TB
In 2011, with 2 million cases of TB, India alone accounted
 for 26% of global cases.
4 lakh deaths occur from TB every year.
Everyday 5000 develop TB disease and 1000 people die of TB
TB kills more adults in India than any other infectious
 disease.
               (2 deaths every 3 minutes).


               www.mcf.org.in                                 6
Who are getting infected?
Of the 9 million incident cases in 2011



   1 million (13%) were among people living with HIV
   0.5 million were children
   3 million were women.


TB affects mostly adults in the economically productive
                       age groups.

              www.mcf.org.in                              7
Drug resistant TB
Globally, 3.7% of new cases and 20% of previously
 treated cases are estimated to have MDR-TB.
Estimated 310 000 of MDR-TB cases in 2011.
Almost 60% of these cases were in India, China and
 the Russian Federation
Of MDR-TB cases, Extensively drug-resistant XDR-TB
 is 9.0%
Treatment success rate of MDR TB is 50%



              www.mcf.org.in                          8
Microbiology
Rod-shaped bacterium of 2-4 x 0.2-0.5 μm.
Obligate aerobe found in the well-aerated
lungs.
Slow growing (dividing only every 16-20
hours)
Lives within tissue macrophages.
Humans are the only reservoir of M.
Tuberculosis



                 www.mcf.org.in             9
Microbiology
• Peculiar cell wall that consists of peptidoglycan and
  complex lipids.
• The cell wall is a major factor in the virulence of the
  organism.
• Once stained (e.g. with carbol fuchsin: Z N Staining), it
  retain dyes when treated by acidified organic compounds.
• Therefore, it is classified as an “acid–fast” bacterium.




                www.mcf.org.in                                10
How is TB transmitted?
                        Nearly all TB infection is
                         acquired by inhalation of
                         respiratory droplets from
                         people with TB in the
                         lungs or throat.
                        Air droplets 3-5 μm
                         diameter are coughed,
                         sneezed or spat-out by an
                         “open” case of TB.



       www.mcf.org.in                                 11
Other modes of transmission
Ingestion of the organisms leads to development of
 tonsillar or intestinal tuberculosis. This mode of infection
 of human tubercle bacilli is from self-swallowing of
 infected sputum of an open case of pulmonary
 tuberculosis, or ingestion of bovine tubercle bacilli from
 milk of diseased cows.
Inoculation of the organisms into the skin may rarely
 occur from infected pus tissue.
Transplacental route results in development of
 congenital tuberculosis in foetus from infected mother
 and is a rare mode of transmission.
                www.mcf.org.in                                  12
How is TB not transmitted?
People cannot get infected with TB bacteria through
Handshakes
Sitting on toilet seats
Sharing dishes , mattresses with someone who has
  TB.
From insect bites
From touching surfaces that are contaminated with
  M. tuberculosis.


              www.mcf.org.in                          13
Factors that determine transmission risk




          www.mcf.org.in             14
Characteristics of a Patient with TB Disease that
Are Associated with Infectiousness




             www.mcf.org.in                     15
Environmental Factors that Enhance the
Probability that M. tuberculosis Will Be
Transmitted




             www.mcf.org.in                16
Proximity and Length of Exposure Factors that
Can Affect Transmission of M. tuberculosis




            www.mcf.org.in                      17
What happens when TB bacilli is
inhaled?
 Between 70-90% of individuals exposed to TB will not
      develop the infection. This is because

  •     inhale too few organisms to cause infection
  •     have sufficient immunity to prevent an infection
        becoming established

 Any factor associated with impaired immunity, such as
      extremes of age, malnutrition and HIV/AIDS will
      increase the risk of developing infection.
            No infection in 70 to 90 % exposed people

                  www.mcf.org.in                           18
What happens when TB bacilli is
 inhaled?
In those 10-30% who develop infection,
 TB infection begins when the
 mycobacterium reach the lung alveoli.
In the alveoli, TB enters macrophages
 and with other cells form a shell called
 granuloma.
 The granuloma prevents dissemination
 of the mycobacteria.
Bacteria inside the granuloma can
 become dormant, resulting in a latent
 infection.
It may remain latent lifelong or may
 reactivate to active TB when immunity
 fails.
   Of the 10 to 30% of the exposed who
     develop infection, 90% people have
               latent infection
                  www.mcf.org.in            19
What happens when TB bacilli is
inhaled?
 Active TB Infection
Active TB disease occurs if the
 immune system cannot keep the
 tubercle bacilli under control.
Bacilli begin to multiply rapidly
 and break free from the shell of
 granuloma.
Active clinical disease can be
 pulmonary or may be systemic
 ( Brain Larynx Lymph node Lung
 Spine Kidney , etc)
             www.mcf.org.in          20
What are the likely outcomes
Pathogenesis
5




               following exposure to open
               TB?               Exposure to TB




                  No infection                      Infection
                  (70-90%)                          (10-30%)


                          Dormant TB (90%)                              Active TB (10%)
                          • well                                       • ill and likely to die if
                          • no TB disease                              untreated
                          • not infectious to                          • infectious
                          others
                                             Activation of infection
                                             results in disease

                            www.mcf.org.in                                                      21
Clinical stages or states of
Mycobacterium tuberculosis infection




          www.mcf.org.in               22
www.mcf.org.in   23
Who is at risk of TB infection?
Contacts                       Low body weight
Children                        Certain medical treatments
Elderly                         (such as corticosteroid
                                 treatment
All household
                                Prisons
Workplace
                                Urban slum
HIV
                                Poor areas
Previous TB
                                Migrants
Malnourished
                                Drug abusers
Smokers
                                Diabetics

               www.mcf.org.in                                  24
Distribution of tuberculosis cases by
anatomical site in HIV-negative patients.




           www.mcf.org.in                   25
Distribution of tuberculosis cases by
anatomical site in HIV-positive patients




           www.mcf.org.in                  26
Clinical features of lung TB
Cough That Last For
 More Than Two Weeks
Chest pain
Breathlessness
Coughing up blood




             www.mcf.org.in    27
HIV AND TB




       www.mcf.org.in   28
Miliary TB
Extensive TB
May present
 only as fever
 and weight loss



         www.mcf.org.in   29
Common symptoms with TB at any
site

Weight Loss
Loss Of Appetite
Fever
Night Sweats
Weakness


         www.mcf.org.in      30
TB lymphadenitis

Painless nodes in
 neck commonly
Non-tender,
 matted together
 and rubbery
May ulcerate and
 discharge.
         www.mcf.org.in   31
Abdominal TB
Weight loss
Diarrhoea or
 constipation
Abdominal distension
 (from ascites) or
 chronic intestinal
 obstruction
Enlarged abd lymph
 nodes may be palpable
 as multiple intra-
          www.mcf.org.in   32
Pleural effusion
Extrapulmonary
Pain,
 breathlessness,
 cough




           www.mcf.org.in   33
Brain TB
Meningitis or
 intracranial
 tuberculomas
Headache, neck
 stiffness, altered
 mental status,
 and cranial nerve
 abnormalities,
 convulsions.
           www.mcf.org.in   34
TB spine
Especially seen
 in young children
Presents as a
 pain and/or
 swelling on the
 back or neck
Loss of limb
 function
          www.mcf.org.in   35
Pericardial TB
Patient presents
 with
 breathlessness
 and chest pain.
Chest x-ray
 shows cardio-
 megaly and
 pleural effusion
 Changes on
 ECG are common.
         www.mcf.org.in   36
Diagnosis of TB: Latent and
Active




        www.mcf.org.in        37
Diagnosis of active TB
Sputum Examination for pulmonary TB
Examination of ascitic fluid, pleural fluid, CSF,
 joint fluid, pus, etc for type of cells and AFB
Culture for AFB
NAAT for TB
ADA test
Urine test: LAM
Antibody tests
Breath tests

              www.mcf.org.in                         38
Sputum Smear Examination for
pulmonary TB
Sputum is a thick fluid that is produced in the lungs
Sample of sputum is usually collected by the person coughing.
Earlier 3 morning sputum samples were recommended, but
 now two spot specimens are collected on the same day.
To do the test a very thin layer of the sample is placed on a
 glass slide, and this is called a smear.
A series of special stains ( Zeihl Neelson or ZN stain) are then
 applied to the sample, and the stained slide is examined
 under a microscope for signs of the TB bacteria.
Ziehl-Nielsen stain demonstrates the presence of the acid and
 alcohol fast bacilli (AFB).

                www.mcf.org.in                               39
How to collect sputum?
Patient is instructed to inhale deeply two to three times
 with his/her mouth open, cough out deeply from the
 chest, open the container, spit out the sputum into it and
 close the container tightly
The health worker or the laboratory technician should
 stand behind the patient.
 If a patient coughs out only saliva, (s)he should be asked
 to try again to bring out sputum.
If a specimen cannot be sent to laboratory immediately, it
 should be stored in a refrigerator or in another cool place.
Sputum specimens should be examined immediately
 whenever possible and not late than a week after
 collection.
                www.mcf.org.in                                  40
Sputum Smear Examination for
pulmonary TB
 Simple, inexpensive, requires minimum training
 High specificity
 High reliability with low inter-reader variation
 Can be used for diagnosis, monitoring and defining cure
 Results are available quickly
 Feasible at peripheral health institutions
 Correlates with infectivity in pulmonary TB cases
But the sensitivity though is only about 50-60%. I.e. the
 test is often falsely negative in patients with TB.
When positive, the patient is “smear-positive” or “open
 TB” and the risk of transmission of infection to others is
 very high.
The yield of the test is higher in patients with lung
                www.mcf.org.in                                41
Sputum-smear microscopy with
LED=light-emitting diode
 Instead of simple
 microscope, benefits of low
 cost, durability, faster and
 ability to use without a
 darkroom.
WHO issued a policy
 statement recommending
 that conventional microscopy
 should be replaced by LED
 microscopy


               www.mcf.org.in   42
How is sputum smear test
interpreted?




       www.mcf.org.in      43
www.mcf.org.in   44
Sputum culture
Culturing is a method of studying bacteria by growing
 them on media containing nutrients.
It provides a definitive diagnosis of TB and can
 significantly increase the number of cases found.
Culture can also provide drug susceptibility testing,
 showing which TB drugs a person's bacteria is
 resistant to.




              www.mcf.org.in                             45
Sputum culture
Solid culture medium
 Egg-based Lowenstein
 Jensen (LJ medium) or
 Agar-based medium
Diagnosis can take 4
 weeks to get a
 conclusive result with
 another 4-6 weeks to
 produce drug
 susceptibility results.

              www.mcf.org.in   46
Liquid culture medium
 BACTEC MGIT
  960.This can detect
  growth of
  mycobacteria as
  early as 4 days from
  inoculation and
  drug susceptibility
  will be available in
  21-28 days.

           www.mcf.org.in   47
Microscopic observation of drug
susceptibility assay (MODS)
MODS has been described for the early detection
 of M. tuberculosis growth in liquid medium,
 allowing a more timely diagnosis and drug
 susceptibility testing.
The method is based on the observation of the
 characteristic cord formation of M.tuberculosis
 visualized microscopically in liquid medium with
 the use of an inverted Microscope
Sensitivity of MODS (92 %)
Turnaround time of nine days.
             www.mcf.org.in                         48
NAATs=nucleic acid
amplification tests (MTB PCR)
Currently available NAA tests are
 not sufficiently sensitive (detecting
 50%--80% of AFB smear-negative,
 culture-positive pulmonary TB
 cases) to exclude the diagnosis of
 TB in AFB smear-negative patients
 suspected to have TB
NAATs have high specificity.
Cannot be used for treatment
 monitoring.

 Culture, supported by microscopy,
   still remains the gold standard
                 www.mcf.org.in          49
Xpert MTB/RIF
It is rapid NAAT test
Uses PCR technique for diagnosis of Mycobacterium
 tuberculosis and rifampicin resistance
Xpert MTB/RIF has the advantage of detecting TB with
 equivalent sensitivity to culture on solid media and of
 simultaneously detecting rifampicin resistance with high
 sensitivity (95%) and specificity (98%)
Turnover time less than 2 hours
 Another advantage is that it performs equally well among
 HIV-negative and HIV-positive individuals.
It is therefore a useful tool to improve early case detection
 of MDR-TB and HIV-associated TB.

                         www.mcf.org.in                          50
CDC recommendations For
NAAT




       www.mcf.org.in     51
Serological (antibody) detection tests for
pulmonary and extrapulmonary tuberculosis

 Commercial serological tests (Ig G, Ig M
  tests) for both pulmonary and
  extrapulmonary tuberculosis produce
  highly inconsistent estimates of sensitivity
  and specificity
 None of the assays do well enough to
  replace microscopy.


             www.mcf.org.in                      52
ADA for tuberculosis pleuritis,
pericarditis, peritonitis
Measurement of ADA concentrations in
 pleural, pericardial, and ascitic fluid has high
Sensitivity and specificity for extrapulmonary
 tuberculosis.




            www.mcf.org.in                    53
Diagnosis of latent
tuberculosis



        www.mcf.org.in   54
Mantoux or tuberculin skin test (TST)
or TT or PPD TEST
0.1 ml PPD is injected
 intradermally and the
 injection site is inspected
 48-72 hours later.
Erythema and induration
 at the site signify an
 immune response and,
 therefore, previous
 exposure to mycobacteria.

            www.mcf.org.in              55
Mantoux or tuberculin skin
test (TST) or TT or PPD TEST
False positive: a skin reaction in people who do
 not have TB because of exposure to non-
 pathogenic mycobacteria and also due to the
 immune response following BCG immunisation
False negative: a negative result in a person with
 TB in early primary infection or because they are
 immunocompromised – for example, due to
 HIV/AIDS, malnutrition or people who develop
 disseminated TB.

             www.mcf.org.in                         56
Mantoux or tuberculin skin test
(TST) or TT or PPD TEST
Individuals who had received BCG vaccination
 are more likely to have a positive TST
The effect of BCG on TST results is less after 15
 years
Positive TST with indurations of >15 mm are more
 likely to be the result of tuberculosis infection
 than of BCG vaccination.
Non tuberculous mycobacterial infection can
 cause positive test, esp in areas where MTB is less.
             www.mcf.org.in                         57
IGRAs=interferon-γ release
assays.
T-SPOT.TB Test, QuantiFERON-TB Gold test
IGRAs have excellent specificity (higher than the
 TST), and are unaffected by previous BCG
 vaccination.
IGRA sensitivity varies across populations and
 tends to be lower in high-endemic countries and
 in HIV-infected individuals.



             www.mcf.org.in                          58
Diagnosis of drug-resistant
tuberculosis
The INNO-LiPA Rif assay
GenoType MTBDR assays
CRI=colorimetric redox indicator method
NRA=nitrate reductase assays
MODS=microscopically observed drug susceptibility
Xpert MTB/RIF




             www.mcf.org.in                          59
Different tests for drug
resistance
The INNO-LiPA Rif assay is a highly sensitive and
 specific test for the detection of rifampicin resistance
 in culture isolates. The test has lower sensitivity when
 used directly on clinical specimens.
GenoType MTBDR assays have excellent sensitivity
 and specificity for rifampicin resistance, even when
 directly used on clinical specimens.




               www.mcf.org.in                           60
CRI=colorimetric redox
indicator method

Colorimetric methods are sensitive and specific for
 the detection of rifampicin and isoniazid resistance in
 culture isolates.
CRIs use inexpensive non-commercial supplies
and equipment and have a rapid turnaround time (7
 days).




              www.mcf.org.in                               61
NRA=nitrate reductase assays

NRA has high accuracy when used to detect
 rifampicin and isoniazid resistance in culture isolates.
NRA is simple and inexpensive
Turnaround time 7–14 days




               www.mcf.org.in                               62
MODS=microscopically observed drug
susceptibility

MODS for rapid detection of rifampicin and isoniazid
 resistance
MODS has high accuracy when testing for rifampicin
 resistance, but shows slightly lower sensitivity when
 detecting isoniazid resistance.
 MODS seems to do equally well with use of direct
 patient specimens and culture isolates.
MODS uses non-commercial supplies and equipment,
 and has a rapid turnaround time (10 days) compared
 with conventional methods.
              www.mcf.org.in                            63
Diagnosis using urine sample
Urine-Based Assay for Lipoarabinomannan (LAM)
Urine LAM test detects a subset of TB patients who have
 severe TB, advanced AIDS, and are not detected by
 sputum smear microscopy
The combination of smear and LAM (either positive = TB)
 detects about 75% of TB cases
Urine LAM test is promising for use in conjunction with
 smear microscopy in settings of HIV high prevalence
Lacks infection control issues of blood, sputum


               www.mcf.org.in                              64
The tuberculosis diagnostics pipeline




           www.mcf.org.in               65
Prevention of Tuberculosis




       www.mcf.org.in        66
Patients are more likely to be
infectious if they:
Have TB of the lungs or throat
Have a cavity in the lung
Are coughing or undergoing cough-inducing
 procedures
Are not covering their mouth when coughing
Have acid-fast bacilli on the sputum smear
Are not receiving adequate treatment


              www.mcf.org.in                  67
What care a TB case should take
  to prevent transmission of TB?
The most important thing is to take REGULAR medicine.
TB patients who may be infectious should be instructed to
 cover their mouth and nose with a tissue when coughing or
 sneezing. Put the tissue in a closed bag and throw it away.
Adequate (ventilated and sunny) site for sputum collection,
 preferentially outdoors
Avoiding the use of ceiling fans
Use of a standing fan either to direct the air flow towards
 the window (or door) or to produce an air "barrier" between
 the contacts and the patient

                 www.mcf.org.in                          68
What care a TB case should
take to prevent transmission
of TB?
Avoid going to work or school.
 Sleep in a bedroom away from other family
 members.
If in a hospital and also in home if possible, TB
 patient must be given a separate room, with the door
 closed and windows that can be opened.
This is to be followed for a period of 2 weeks after
 starting TB treatment after which infectiousness
 appears to decline very rapidly.
Close contacts should wear N99 masks, if available.
              www.mcf.org.in                            69
BCG Vaccine

Bacille Calmette-Guerin is an live vaccine available
 for TB.
BCG appears to reduce the risk of serious childhood
 forms of TB, including miliary TB and
 extrapulmonary TB
BCG does not seem to be highly effective as people
 move into adulthood.




              www.mcf.org.in                            70
BCG Vaccine
WHO recommends that BCG be given to infants and
 young children in countries where TB is common.
It should not be given during pregnancy or to
 children with symptomatic HIV infection.
If you were vaccinated with BCG, you may have a
 positive reaction to a TB skin test. This reaction may
 be due to the BCG vaccine itself or to a real TB
 infection.



              www.mcf.org.in                              71
Treatment of Active TB
http://www.lifehugger.com/doc/2224/RNTCP_Current_gu




            www.mcf.org.in                     72
Anti-Tuberculosis Therapy
 First-Line Drugs
   Isoniazid
   Rifampin
   Pyrazinamide
   Ethambutol
   Streptomycin




         www.mcf.org.in     73
High
                              INH
           А
           Continuous
                              (RIF, SM)
             growth                                    Special bacterial
                                                          population
                                                          hypothesis
                                   PZ          RIF     and action of the
Speed of
bacteria
                                   A                     specific drugs
 growth

                          B               C            (From Mitchison, 1985)
           D                  Acid         Spurts of
           Dormant         inhibition     metabolism
Low
           (No cure)



 Mitchison, Tubercle 66: 219-226

                         www.mcf.org.in                                   74
Side effects of ATT drugs
No appetite, nausea,         Easy bleeding
 vomiting                     Aching joints
Yellowish skin or eyes       Dizziness
Hepatitis                    Blurred or changed vision
Abdominal pain               Ringing in the ears
Skin rash                    Tingling fingers or toes
Patients on Rifampicin        or around mouth
 can have red colored
 urine, saliva, or tears.
             www.mcf.org.in                           75
Principles of Therapy
Insure that patient is taking medication properly
 (Directly Observed Therapy).
                    Therapy

Always use at least 2 drugs to which the
 organism is susceptible.

Never add a single drug to a failing regimen.

Monitor clinical response to therapy.




            www.mcf.org.in                           76
What is MDR/XDR TB?
MDR-TB occurs when the TB bacteria are resistant to
 at least isoniazid and rifampicin, the two most
 powerful anti-TB drugs.

Extensively drug-resistant tuberculosis XDR-TB
 is TB that is resistant to any fluoroquinolone, and at
 least one of three injectable second-line drugs, in
 addition to MDR-TB



              www.mcf.org.in                              77
Criteria to label a patient as
MDR-TB suspect.
A new smear-positive patient remaining smear-
 positive at the end of fifth month.
A new smear-negative patient becoming smear-
 positive at the end of fifth month.
A patient treated with regimen for previously treated
 remaining positive at fourth month
Smear-positive contacts of an established/confirmed
 MDR-TB case



              www.mcf.org.in                             78
MDR is more common in
people who
Have spent time with someone with drug-resistant
 TB disease
Do not take their medicine regularly
Do not take all of their prescribed medicine
Develop TB disease again, after having taken TB
 medicine in the past




              www.mcf.org.in                        79
Contributing Factors for MDR
TB
High prevalence of HIV.

Delayed diagnosis.

Delays in adequate therapy (in part due to unknown
 drug susceptibilities).

Inadequate isolation procedures.




              www.mcf.org.in                          80
Deadly Mistakes
 Not knowing MTB drug susceptibilities.

 Inadequate therapy.
   Ineffective drug regimen.
   Inadequate length of treatment.
   Sub-therapeutic drug level.

 Lack of patient monitoring.
   DOT.
   Clinical Response.


        www.mcf.org.in                     81
ReasonMulti-Drug Resistant TB*
    Prevalence of
                  for Alarm
6                     5.5        %

5

4
                                *The W IUATLD Global Project on Anti-
                                       HO/
3                                    TB Drug Resistance Surveillance
                  %                           (1994-1997)
2       1.6

1                                Countries with good TB control = >33%
                                            DOTS coverage.
0
    With Good TB With Poor TB
       Control      Control



                                                                    82
Management of MDR/XDR TB
For MDR
  Intensive Phase (IP) of 6 drugs should be given at
   least 6 months.
  Continuation Phase, 4 drugs are given for 18 months.
For XDR:
  At least three to four drugs to which the strain is
   sensitive need to be used for effective treatment
  Surgery of lung




               www.mcf.org.in                             83
Treatment for Latent
Tuberculosis Infection (TLTBI)

Isoniazid preventive therapy (IPT), is given to people
 who have latent TB infection to prevent them from
 developing TB disease.
The usual regimen for IPT is isoniazid given daily for
 6 months for all patients.
Patients she should be screened for activeTB (current
 cough, fever, weight loss or night sweats ) to rule out
 active TB before starting IPT.



              www.mcf.org.in                               84
Who should be offered IPT?
ALL HIV patients should be given IPT irrespective of
 the degree of immunosuppression, and also to those
 on ART, those who have previously been treated for
 TB and pregnant women.
IPT is administered to all the children aged 6 years ,
 in risk groups such as household contacts, individuals
 with chronic renal or respiratory disease
Patients should be clinically evaluated every month
 for signs of hepatitis and other adverse reactions like
 tingling numbness in legs due to isoniazid.
              www.mcf.org.in                               85
References
www.tuberculosistextbook.com
 Revised National Tuberculosis Control Programme (RNTCP)
  Training Module for Medical Practitioners
 Extrapulmonary tuberculosis Indian J Med Res 120, October
  2004, pp 316-353
 The Situation of HIV/M. tuberculosis Co-Infection in India. The
  Open Infectious Diseases Journal, 2011, 5, (Suppl 1-M5) 51-59
 WHO Policy on TB Infection Control in Health-Care Facilities,
  congregate Settings and Households
 Biomarkers and diagnostics for tuberculosis: progress,
  needs, and translation into practice( Lancet)
 Questions and Answers About Tuberculosis, CDC 2009

                 www.mcf.org.in                                     86

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Training on tuberculosis for counselors 2012

  • 1. MCF COUNSELORS TRAINING FOR TUBERCULOSIS HELPLINE VENUE:MCF OFFICE, PUNE 5TH NOV 2012 TO 9TH NOV 2012 www.mcf.org.in 1
  • 2. Why helpline for TB? Tuberculosis (TB) remains a major global health problem. It causes ill-health among millions of people each year TB ranks as the second leading cause of death from an infectious disease worldwide, after HIV1 Tuberculosis is a treatable and preventable disease. What is needed is knowledge about the disease. Stigma, discrimination and fear : TB has all as HIV Strong referral services available So helpline for TB makes sense www.mcf.org.in 2
  • 3. What is tuberculosis? • TB is a chronic bacterial infection. • The great majority of infections in people are caused by Mycobacterium tuberculosis (M. Tuberculosis or tubercle bacilli). • M. tuberculosis and seven very closely related mycobacterial species like M. bovis and others together comprise what is known as the M. tuberculosis complex. • M. Bovis can cause TB in people who drink unpasteurised milk from infected cows. www.mcf.org.in 3
  • 4. TB: Global Scenario • About 1 in 3 of the world’s population is infected with tubercle bacilli. • There were an estimated 12 million prevalent cases in 2011 • 170 cases per 100 000 population • Incidence: 90 lakh new cases • Someone is newly infected every second • Mortality: Nearly 14 lakh TB deaths every year www.mcf.org.in 4
  • 5. • About 95% of the world’s cases of TB occur in South East Asia, sub-Saharan Africa and the Western Pacific. • The five countries with the largest number of incident cases in 2011 were India (approx 2.0 million), China (approx–1 million), South Africa (approx 0.5 million), Indonesia (approx 0.5 million) and Pakistan (approx 0.4 million). • India and China alone accounted for 26% and 12% of global cases, respectively. www.mcf.org.in 5
  • 6. TB in India Nearly 40% of the Indian population is infected with the MTB bacillus Approx 30 million people in India are infected with TB In 2011, with 2 million cases of TB, India alone accounted for 26% of global cases. 4 lakh deaths occur from TB every year. Everyday 5000 develop TB disease and 1000 people die of TB TB kills more adults in India than any other infectious disease. (2 deaths every 3 minutes). www.mcf.org.in 6
  • 7. Who are getting infected? Of the 9 million incident cases in 2011  1 million (13%) were among people living with HIV  0.5 million were children  3 million were women. TB affects mostly adults in the economically productive age groups. www.mcf.org.in 7
  • 8. Drug resistant TB Globally, 3.7% of new cases and 20% of previously treated cases are estimated to have MDR-TB. Estimated 310 000 of MDR-TB cases in 2011. Almost 60% of these cases were in India, China and the Russian Federation Of MDR-TB cases, Extensively drug-resistant XDR-TB is 9.0% Treatment success rate of MDR TB is 50% www.mcf.org.in 8
  • 9. Microbiology Rod-shaped bacterium of 2-4 x 0.2-0.5 μm. Obligate aerobe found in the well-aerated lungs. Slow growing (dividing only every 16-20 hours) Lives within tissue macrophages. Humans are the only reservoir of M. Tuberculosis www.mcf.org.in 9
  • 10. Microbiology • Peculiar cell wall that consists of peptidoglycan and complex lipids. • The cell wall is a major factor in the virulence of the organism. • Once stained (e.g. with carbol fuchsin: Z N Staining), it retain dyes when treated by acidified organic compounds. • Therefore, it is classified as an “acid–fast” bacterium. www.mcf.org.in 10
  • 11. How is TB transmitted? Nearly all TB infection is acquired by inhalation of respiratory droplets from people with TB in the lungs or throat. Air droplets 3-5 μm diameter are coughed, sneezed or spat-out by an “open” case of TB. www.mcf.org.in 11
  • 12. Other modes of transmission Ingestion of the organisms leads to development of tonsillar or intestinal tuberculosis. This mode of infection of human tubercle bacilli is from self-swallowing of infected sputum of an open case of pulmonary tuberculosis, or ingestion of bovine tubercle bacilli from milk of diseased cows. Inoculation of the organisms into the skin may rarely occur from infected pus tissue. Transplacental route results in development of congenital tuberculosis in foetus from infected mother and is a rare mode of transmission. www.mcf.org.in 12
  • 13. How is TB not transmitted? People cannot get infected with TB bacteria through Handshakes Sitting on toilet seats Sharing dishes , mattresses with someone who has TB. From insect bites From touching surfaces that are contaminated with M. tuberculosis. www.mcf.org.in 13
  • 14. Factors that determine transmission risk www.mcf.org.in 14
  • 15. Characteristics of a Patient with TB Disease that Are Associated with Infectiousness www.mcf.org.in 15
  • 16. Environmental Factors that Enhance the Probability that M. tuberculosis Will Be Transmitted www.mcf.org.in 16
  • 17. Proximity and Length of Exposure Factors that Can Affect Transmission of M. tuberculosis www.mcf.org.in 17
  • 18. What happens when TB bacilli is inhaled?  Between 70-90% of individuals exposed to TB will not develop the infection. This is because • inhale too few organisms to cause infection • have sufficient immunity to prevent an infection becoming established  Any factor associated with impaired immunity, such as extremes of age, malnutrition and HIV/AIDS will increase the risk of developing infection. No infection in 70 to 90 % exposed people www.mcf.org.in 18
  • 19. What happens when TB bacilli is inhaled? In those 10-30% who develop infection, TB infection begins when the mycobacterium reach the lung alveoli. In the alveoli, TB enters macrophages and with other cells form a shell called granuloma.  The granuloma prevents dissemination of the mycobacteria. Bacteria inside the granuloma can become dormant, resulting in a latent infection. It may remain latent lifelong or may reactivate to active TB when immunity fails. Of the 10 to 30% of the exposed who develop infection, 90% people have latent infection www.mcf.org.in 19
  • 20. What happens when TB bacilli is inhaled? Active TB Infection Active TB disease occurs if the immune system cannot keep the tubercle bacilli under control. Bacilli begin to multiply rapidly and break free from the shell of granuloma. Active clinical disease can be pulmonary or may be systemic ( Brain Larynx Lymph node Lung Spine Kidney , etc) www.mcf.org.in 20
  • 21. What are the likely outcomes Pathogenesis 5 following exposure to open TB? Exposure to TB No infection Infection (70-90%) (10-30%) Dormant TB (90%) Active TB (10%) • well • ill and likely to die if • no TB disease untreated • not infectious to • infectious others Activation of infection results in disease www.mcf.org.in 21
  • 22. Clinical stages or states of Mycobacterium tuberculosis infection www.mcf.org.in 22
  • 24. Who is at risk of TB infection? Contacts Low body weight Children  Certain medical treatments Elderly (such as corticosteroid treatment All household Prisons Workplace Urban slum HIV Poor areas Previous TB Migrants Malnourished Drug abusers Smokers Diabetics www.mcf.org.in 24
  • 25. Distribution of tuberculosis cases by anatomical site in HIV-negative patients. www.mcf.org.in 25
  • 26. Distribution of tuberculosis cases by anatomical site in HIV-positive patients www.mcf.org.in 26
  • 27. Clinical features of lung TB Cough That Last For More Than Two Weeks Chest pain Breathlessness Coughing up blood www.mcf.org.in 27
  • 28. HIV AND TB www.mcf.org.in 28
  • 29. Miliary TB Extensive TB May present only as fever and weight loss www.mcf.org.in 29
  • 30. Common symptoms with TB at any site Weight Loss Loss Of Appetite Fever Night Sweats Weakness www.mcf.org.in 30
  • 31. TB lymphadenitis Painless nodes in neck commonly Non-tender, matted together and rubbery May ulcerate and discharge. www.mcf.org.in 31
  • 32. Abdominal TB Weight loss Diarrhoea or constipation Abdominal distension (from ascites) or chronic intestinal obstruction Enlarged abd lymph nodes may be palpable as multiple intra- www.mcf.org.in 32
  • 34. Brain TB Meningitis or intracranial tuberculomas Headache, neck stiffness, altered mental status, and cranial nerve abnormalities, convulsions. www.mcf.org.in 34
  • 35. TB spine Especially seen in young children Presents as a pain and/or swelling on the back or neck Loss of limb function www.mcf.org.in 35
  • 36. Pericardial TB Patient presents with breathlessness and chest pain. Chest x-ray shows cardio- megaly and pleural effusion  Changes on ECG are common. www.mcf.org.in 36
  • 37. Diagnosis of TB: Latent and Active www.mcf.org.in 37
  • 38. Diagnosis of active TB Sputum Examination for pulmonary TB Examination of ascitic fluid, pleural fluid, CSF, joint fluid, pus, etc for type of cells and AFB Culture for AFB NAAT for TB ADA test Urine test: LAM Antibody tests Breath tests www.mcf.org.in 38
  • 39. Sputum Smear Examination for pulmonary TB Sputum is a thick fluid that is produced in the lungs Sample of sputum is usually collected by the person coughing. Earlier 3 morning sputum samples were recommended, but now two spot specimens are collected on the same day. To do the test a very thin layer of the sample is placed on a glass slide, and this is called a smear. A series of special stains ( Zeihl Neelson or ZN stain) are then applied to the sample, and the stained slide is examined under a microscope for signs of the TB bacteria. Ziehl-Nielsen stain demonstrates the presence of the acid and alcohol fast bacilli (AFB). www.mcf.org.in 39
  • 40. How to collect sputum? Patient is instructed to inhale deeply two to three times with his/her mouth open, cough out deeply from the chest, open the container, spit out the sputum into it and close the container tightly The health worker or the laboratory technician should stand behind the patient.  If a patient coughs out only saliva, (s)he should be asked to try again to bring out sputum. If a specimen cannot be sent to laboratory immediately, it should be stored in a refrigerator or in another cool place. Sputum specimens should be examined immediately whenever possible and not late than a week after collection. www.mcf.org.in 40
  • 41. Sputum Smear Examination for pulmonary TB  Simple, inexpensive, requires minimum training  High specificity  High reliability with low inter-reader variation  Can be used for diagnosis, monitoring and defining cure  Results are available quickly  Feasible at peripheral health institutions  Correlates with infectivity in pulmonary TB cases But the sensitivity though is only about 50-60%. I.e. the test is often falsely negative in patients with TB. When positive, the patient is “smear-positive” or “open TB” and the risk of transmission of infection to others is very high. The yield of the test is higher in patients with lung www.mcf.org.in 41
  • 42. Sputum-smear microscopy with LED=light-emitting diode  Instead of simple microscope, benefits of low cost, durability, faster and ability to use without a darkroom. WHO issued a policy statement recommending that conventional microscopy should be replaced by LED microscopy www.mcf.org.in 42
  • 43. How is sputum smear test interpreted? www.mcf.org.in 43
  • 45. Sputum culture Culturing is a method of studying bacteria by growing them on media containing nutrients. It provides a definitive diagnosis of TB and can significantly increase the number of cases found. Culture can also provide drug susceptibility testing, showing which TB drugs a person's bacteria is resistant to. www.mcf.org.in 45
  • 46. Sputum culture Solid culture medium Egg-based Lowenstein Jensen (LJ medium) or Agar-based medium Diagnosis can take 4 weeks to get a conclusive result with another 4-6 weeks to produce drug susceptibility results. www.mcf.org.in 46
  • 47. Liquid culture medium BACTEC MGIT 960.This can detect growth of mycobacteria as early as 4 days from inoculation and drug susceptibility will be available in 21-28 days. www.mcf.org.in 47
  • 48. Microscopic observation of drug susceptibility assay (MODS) MODS has been described for the early detection of M. tuberculosis growth in liquid medium, allowing a more timely diagnosis and drug susceptibility testing. The method is based on the observation of the characteristic cord formation of M.tuberculosis visualized microscopically in liquid medium with the use of an inverted Microscope Sensitivity of MODS (92 %) Turnaround time of nine days. www.mcf.org.in 48
  • 49. NAATs=nucleic acid amplification tests (MTB PCR) Currently available NAA tests are not sufficiently sensitive (detecting 50%--80% of AFB smear-negative, culture-positive pulmonary TB cases) to exclude the diagnosis of TB in AFB smear-negative patients suspected to have TB NAATs have high specificity. Cannot be used for treatment monitoring. Culture, supported by microscopy, still remains the gold standard www.mcf.org.in 49
  • 50. Xpert MTB/RIF It is rapid NAAT test Uses PCR technique for diagnosis of Mycobacterium tuberculosis and rifampicin resistance Xpert MTB/RIF has the advantage of detecting TB with equivalent sensitivity to culture on solid media and of simultaneously detecting rifampicin resistance with high sensitivity (95%) and specificity (98%) Turnover time less than 2 hours  Another advantage is that it performs equally well among HIV-negative and HIV-positive individuals. It is therefore a useful tool to improve early case detection of MDR-TB and HIV-associated TB. www.mcf.org.in 50
  • 51. CDC recommendations For NAAT www.mcf.org.in 51
  • 52. Serological (antibody) detection tests for pulmonary and extrapulmonary tuberculosis Commercial serological tests (Ig G, Ig M tests) for both pulmonary and extrapulmonary tuberculosis produce highly inconsistent estimates of sensitivity and specificity None of the assays do well enough to replace microscopy. www.mcf.org.in 52
  • 53. ADA for tuberculosis pleuritis, pericarditis, peritonitis Measurement of ADA concentrations in pleural, pericardial, and ascitic fluid has high Sensitivity and specificity for extrapulmonary tuberculosis. www.mcf.org.in 53
  • 54. Diagnosis of latent tuberculosis www.mcf.org.in 54
  • 55. Mantoux or tuberculin skin test (TST) or TT or PPD TEST 0.1 ml PPD is injected intradermally and the injection site is inspected 48-72 hours later. Erythema and induration at the site signify an immune response and, therefore, previous exposure to mycobacteria. www.mcf.org.in 55
  • 56. Mantoux or tuberculin skin test (TST) or TT or PPD TEST False positive: a skin reaction in people who do not have TB because of exposure to non- pathogenic mycobacteria and also due to the immune response following BCG immunisation False negative: a negative result in a person with TB in early primary infection or because they are immunocompromised – for example, due to HIV/AIDS, malnutrition or people who develop disseminated TB. www.mcf.org.in 56
  • 57. Mantoux or tuberculin skin test (TST) or TT or PPD TEST Individuals who had received BCG vaccination are more likely to have a positive TST The effect of BCG on TST results is less after 15 years Positive TST with indurations of >15 mm are more likely to be the result of tuberculosis infection than of BCG vaccination. Non tuberculous mycobacterial infection can cause positive test, esp in areas where MTB is less. www.mcf.org.in 57
  • 58. IGRAs=interferon-γ release assays. T-SPOT.TB Test, QuantiFERON-TB Gold test IGRAs have excellent specificity (higher than the TST), and are unaffected by previous BCG vaccination. IGRA sensitivity varies across populations and tends to be lower in high-endemic countries and in HIV-infected individuals. www.mcf.org.in 58
  • 59. Diagnosis of drug-resistant tuberculosis The INNO-LiPA Rif assay GenoType MTBDR assays CRI=colorimetric redox indicator method NRA=nitrate reductase assays MODS=microscopically observed drug susceptibility Xpert MTB/RIF www.mcf.org.in 59
  • 60. Different tests for drug resistance The INNO-LiPA Rif assay is a highly sensitive and specific test for the detection of rifampicin resistance in culture isolates. The test has lower sensitivity when used directly on clinical specimens. GenoType MTBDR assays have excellent sensitivity and specificity for rifampicin resistance, even when directly used on clinical specimens. www.mcf.org.in 60
  • 61. CRI=colorimetric redox indicator method Colorimetric methods are sensitive and specific for the detection of rifampicin and isoniazid resistance in culture isolates. CRIs use inexpensive non-commercial supplies and equipment and have a rapid turnaround time (7 days). www.mcf.org.in 61
  • 62. NRA=nitrate reductase assays NRA has high accuracy when used to detect rifampicin and isoniazid resistance in culture isolates. NRA is simple and inexpensive Turnaround time 7–14 days www.mcf.org.in 62
  • 63. MODS=microscopically observed drug susceptibility MODS for rapid detection of rifampicin and isoniazid resistance MODS has high accuracy when testing for rifampicin resistance, but shows slightly lower sensitivity when detecting isoniazid resistance.  MODS seems to do equally well with use of direct patient specimens and culture isolates. MODS uses non-commercial supplies and equipment, and has a rapid turnaround time (10 days) compared with conventional methods. www.mcf.org.in 63
  • 64. Diagnosis using urine sample Urine-Based Assay for Lipoarabinomannan (LAM) Urine LAM test detects a subset of TB patients who have severe TB, advanced AIDS, and are not detected by sputum smear microscopy The combination of smear and LAM (either positive = TB) detects about 75% of TB cases Urine LAM test is promising for use in conjunction with smear microscopy in settings of HIV high prevalence Lacks infection control issues of blood, sputum www.mcf.org.in 64
  • 65. The tuberculosis diagnostics pipeline www.mcf.org.in 65
  • 66. Prevention of Tuberculosis www.mcf.org.in 66
  • 67. Patients are more likely to be infectious if they: Have TB of the lungs or throat Have a cavity in the lung Are coughing or undergoing cough-inducing procedures Are not covering their mouth when coughing Have acid-fast bacilli on the sputum smear Are not receiving adequate treatment www.mcf.org.in 67
  • 68. What care a TB case should take to prevent transmission of TB? The most important thing is to take REGULAR medicine. TB patients who may be infectious should be instructed to cover their mouth and nose with a tissue when coughing or sneezing. Put the tissue in a closed bag and throw it away. Adequate (ventilated and sunny) site for sputum collection, preferentially outdoors Avoiding the use of ceiling fans Use of a standing fan either to direct the air flow towards the window (or door) or to produce an air "barrier" between the contacts and the patient www.mcf.org.in 68
  • 69. What care a TB case should take to prevent transmission of TB? Avoid going to work or school.  Sleep in a bedroom away from other family members. If in a hospital and also in home if possible, TB patient must be given a separate room, with the door closed and windows that can be opened. This is to be followed for a period of 2 weeks after starting TB treatment after which infectiousness appears to decline very rapidly. Close contacts should wear N99 masks, if available. www.mcf.org.in 69
  • 70. BCG Vaccine Bacille Calmette-Guerin is an live vaccine available for TB. BCG appears to reduce the risk of serious childhood forms of TB, including miliary TB and extrapulmonary TB BCG does not seem to be highly effective as people move into adulthood. www.mcf.org.in 70
  • 71. BCG Vaccine WHO recommends that BCG be given to infants and young children in countries where TB is common. It should not be given during pregnancy or to children with symptomatic HIV infection. If you were vaccinated with BCG, you may have a positive reaction to a TB skin test. This reaction may be due to the BCG vaccine itself or to a real TB infection. www.mcf.org.in 71
  • 72. Treatment of Active TB http://www.lifehugger.com/doc/2224/RNTCP_Current_gu www.mcf.org.in 72
  • 73. Anti-Tuberculosis Therapy First-Line Drugs Isoniazid Rifampin Pyrazinamide Ethambutol Streptomycin www.mcf.org.in 73
  • 74. High INH А Continuous (RIF, SM) growth Special bacterial population hypothesis PZ RIF and action of the Speed of bacteria A specific drugs growth B C (From Mitchison, 1985) D Acid Spurts of Dormant inhibition metabolism Low (No cure) Mitchison, Tubercle 66: 219-226 www.mcf.org.in 74
  • 75. Side effects of ATT drugs No appetite, nausea, Easy bleeding vomiting Aching joints Yellowish skin or eyes Dizziness Hepatitis Blurred or changed vision Abdominal pain Ringing in the ears Skin rash Tingling fingers or toes Patients on Rifampicin or around mouth can have red colored urine, saliva, or tears. www.mcf.org.in 75
  • 76. Principles of Therapy Insure that patient is taking medication properly (Directly Observed Therapy). Therapy Always use at least 2 drugs to which the organism is susceptible. Never add a single drug to a failing regimen. Monitor clinical response to therapy. www.mcf.org.in 76
  • 77. What is MDR/XDR TB? MDR-TB occurs when the TB bacteria are resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. Extensively drug-resistant tuberculosis XDR-TB is TB that is resistant to any fluoroquinolone, and at least one of three injectable second-line drugs, in addition to MDR-TB www.mcf.org.in 77
  • 78. Criteria to label a patient as MDR-TB suspect. A new smear-positive patient remaining smear- positive at the end of fifth month. A new smear-negative patient becoming smear- positive at the end of fifth month. A patient treated with regimen for previously treated remaining positive at fourth month Smear-positive contacts of an established/confirmed MDR-TB case www.mcf.org.in 78
  • 79. MDR is more common in people who Have spent time with someone with drug-resistant TB disease Do not take their medicine regularly Do not take all of their prescribed medicine Develop TB disease again, after having taken TB medicine in the past www.mcf.org.in 79
  • 80. Contributing Factors for MDR TB High prevalence of HIV. Delayed diagnosis. Delays in adequate therapy (in part due to unknown drug susceptibilities). Inadequate isolation procedures. www.mcf.org.in 80
  • 81. Deadly Mistakes Not knowing MTB drug susceptibilities. Inadequate therapy. Ineffective drug regimen. Inadequate length of treatment. Sub-therapeutic drug level. Lack of patient monitoring. DOT. Clinical Response. www.mcf.org.in 81
  • 82. ReasonMulti-Drug Resistant TB* Prevalence of for Alarm 6 5.5 % 5 4 *The W IUATLD Global Project on Anti- HO/ 3 TB Drug Resistance Surveillance % (1994-1997) 2 1.6 1 Countries with good TB control = >33% DOTS coverage. 0 With Good TB With Poor TB Control Control 82
  • 83. Management of MDR/XDR TB For MDR Intensive Phase (IP) of 6 drugs should be given at least 6 months. Continuation Phase, 4 drugs are given for 18 months. For XDR: At least three to four drugs to which the strain is sensitive need to be used for effective treatment Surgery of lung www.mcf.org.in 83
  • 84. Treatment for Latent Tuberculosis Infection (TLTBI) Isoniazid preventive therapy (IPT), is given to people who have latent TB infection to prevent them from developing TB disease. The usual regimen for IPT is isoniazid given daily for 6 months for all patients. Patients she should be screened for activeTB (current cough, fever, weight loss or night sweats ) to rule out active TB before starting IPT. www.mcf.org.in 84
  • 85. Who should be offered IPT? ALL HIV patients should be given IPT irrespective of the degree of immunosuppression, and also to those on ART, those who have previously been treated for TB and pregnant women. IPT is administered to all the children aged 6 years , in risk groups such as household contacts, individuals with chronic renal or respiratory disease Patients should be clinically evaluated every month for signs of hepatitis and other adverse reactions like tingling numbness in legs due to isoniazid. www.mcf.org.in 85
  • 86. References www.tuberculosistextbook.com  Revised National Tuberculosis Control Programme (RNTCP) Training Module for Medical Practitioners  Extrapulmonary tuberculosis Indian J Med Res 120, October 2004, pp 316-353  The Situation of HIV/M. tuberculosis Co-Infection in India. The Open Infectious Diseases Journal, 2011, 5, (Suppl 1-M5) 51-59  WHO Policy on TB Infection Control in Health-Care Facilities, congregate Settings and Households  Biomarkers and diagnostics for tuberculosis: progress, needs, and translation into practice( Lancet)  Questions and Answers About Tuberculosis, CDC 2009 www.mcf.org.in 86