56 Non tuberculous Mycobacteria   Diagnosis & Clinical management Session 01
31
August

By Adem Lewis / in , , /


Ah Hello I am Dr. Padmapriya and we will discuss
about Non-tuberculous Mycobacteria its diagnosis, and clinical management in the next couple
of slides. ah Non-tuberculous mycobacteria refers to
mycobacterial species other than mycobacterium tuberculous complex, M. leprae and M. lepromatosis. These are ubiquitous organisms in the environment
found in soil and water, and humans acquire the infection from the environment. Most of them are non pathogenic, but some
can cause human disease. They usually effect the lungs, lymph node,
joints, CNS, infection is also been reported from catheter as well as laparoscopic port
sites. They can also cause disseminated infection
in susceptible, or immune compromise individuals. Now what is so important about these NTM’s? Now sputum smear microscopy that is a corner
stone of diagnosis of acid fast bacilli in public health programs can detect these NTM’s
as acid fast bacilli positive. The moment AFB positive is detected, this
is diagnosis tuberculosis and in many they are treated for ah M tuberculosis. The inability to differentiate between NTM
from M tuberculosis by sputum microscopy, may lead to wrong diagnosis, and resulting
in inappropriate treatment, in turn increasing the burden on logistics infrastructures as
well as finances. Now, NTM’s are often resistant to antibiotics
and anti tuberculosis treatment that is commonly used in the national programs. It can also be misdiagnosed as multiple ah
multidrug assistant tuberculosis, when they do not respond to the regular anti TB treatment. Increasing notification of mycobacterial disease
as either relapse of TB or drug resistant can also be because of increasing a non tuberculous
mycobacterial infect. Now, what is a interaction between non tuberculous
mycobacteria and the host factor? Now NTM pathogenicity depends upon the load
of the organism in the effected host and also what the species of NTM that is causing the
infection. In the host factor susceptibility of the host
basically its immune compromise, or immune competent state as well as local defence mechanism
plays a major role. Now both the interaction of NTM pathogen as
well as the host or the bug and the host results in a variety of outcomes. It could be simple contamination of the respiratory
tract, or a any of the ah body tracts or it could be a transient colonization it can also
go on to overt disease. Now pathogenicity of NTM ah is what is listed
on the right side of the slide? The pathogenicity increases from bottom to
up it starts from intracellulare which is a least pathogenic organism and as you see
as it goes up kansasii, or malmoense is the most pathogenic ah organism ah causing human
disease. Runyon classification of NTM divides the ah
non tuberculous mycobacteria into 2 groups; slow growers and rapid growers. Among the slow growers we have M kansasii
causing pathogenic ah ah disease, scrofulaceum M avium, M intracellulare, M xenopi, all of
these are commonly encountered in human ah ah human causing lung infections, or lung
disease. Among the rapid growers we have variety of
organisms stratify M fortuitum, ah smegmatis, M abscessus, and M bollettii all of them ah
resulting in pathogenic disease in humans. NTM can present either in the form of um chronic
pulmonary disease, or lymphadenitis, or it could be post inoculation either in form of
laproscopic ports or catheter in catheter. It can also cause disseminated disease, increasing
incidence and prevalence of NTM is commonly ah seen it mainly due to improved clinician
awareness, or because of enhanced detection methods that is used to diagnose NTM and speciate
them. It is also due to variety of changing environmental
ah factors, mycobacterial, and host factors. Now, since NTM pulmonary disease has a major
impact on a public health scenario. I would like to discuss NTM pulmonary disease
ah in the next few slides. ah NTM can cause progressive inflammatory
lung damage, it can be due to both slow growing as well as rapid growers. Among the slow growers of clinical importance
are M avium complex, M kansasii, and M xenopi and among the rapid growers we have M abscessus,
and M chelonae along with M fortuitum. These vary in distribution not only between
the countries, but also within the countries even there is a variation between the north
and south of a country. The species also differ in the pathogenic
potential, and most of them present with respiratory symptoms very again to tuberculosis. So, the non tuberculous mycobacterial pulmonary
disease there are various risk factors both among the exposure as well as in the host
factors. Among the host factors a most important of
pre existing lung disease like asthma, COPD, pneumoconiosis, or bronchiectasis. Other comorbidities like rheumatoid arthritis,
or low vitamin D, low body mass index malnutrition all of them can contribute to a person getting
infected with NTM’s. Some of the medication that are commonly used
that proton pump inhibitors, or prolonged use of antibiotics can also make an individual
susceptible to NTM. So, how do we diagnose NTM pulmonary disease? When an individual presence to a clinician
ah with symptoms of cough, and fever and not responding to the regular anti tuberculous,
or anti bacterial treatment. There should be high suspicion of NTM pulmonary
disease three sputum samples are collected and sent for acid fast bacilli by smear microscopy
and also culture. Now if all the three AFB smears comes negative
ah in the culture for NTM, but the clinical suspicion still persisting. Then a city scan chest its ah in order city
scan chest is suggestive of ah NTM, you can do a bronchoscopic aspirate and lavage send
it for culture again. If the city scan chest is negative for ah
lung pathology consider alternate diagnosis. The same time if all the ah two if any two
of the three sputum comes is positive for NTM species you can still order a HRCT. And if the HRCT is positive for NTM then you
consider treatment for non tuberculous mycobacteria. If HRCT is negative then you think for other
diagnosis ah alternate diagnosis of this pulmonary infection. Now, of the three sputum samples what to do
if we have only one sputum sample that is positive for NTM? These are the cases where HRCT is recommended
strongly, if HRCT is negative for NTM, CT directed bronchoscopy is ah very much warranted
the aspirate or lavage is sent for NTM culture. At the same time if HRCT shows positivity,
then the patient ah cultures are negative it is warranted to follow up the patient regularly
with repeats sputum, and HRCT. And if any of those culture becomes positive
ah patient has to be treated for NTM pulmonary disease. What are the clinical criteria for diagnosing
ah NTM pulmonary disease? So, this is from the ATS guide lines as well
as the British Thoracic guidelines for management NTM disease. In clinical there are clinical criteria as
well as microbiological criteria. The clinical criteria all the all the criteria
should be positive and they are pulmonary symptoms um plus chest x-ray showing nodular,
or cavitary opacities, AND city scan showing multifocal bronchiectasis, with multiple small
nodules, all of this plus exclusion of other diagnosis of pulmonary disease. Looking at the microbiological criteria we
have three criterias and they are alternate ah criterias. We should have positive culture from at least
two separate expectorated sputum sample, or one positive culture from bronchial wash or
lavage, or a transbroncial or other lung biopsys with a mycobacterial histopathological features,
and positive culture for NTM. So, we need to have a clinical criteria as
well as some microbiological criteria positive to diagnose a case of NTM. The sputum could be an induced sputum and
the induced sputum you need to have minimum of two early morning sputum samples collected
on two separate days and sent for culture. Now the sputum collection to be done after
thorough thoroughly gargling his mouth, and ruling out oral candidiasis. Now if you remember immune compromised state
is one of the very important state where you diagnose NTM pulmonary disease, therefore,
it is very important to rule out oral candidiasis before a sputum is collected for NTM. The sample collected to be processed within
twenty four hours of collection and if it is not possible to refrigerate the sputum
sample at four degree if ah delay is anticipated ah. Looking at the investigations chest x-ray
is a mandatory investigation for NTM pulmonary disease individuals with positive cultures
of M kansasii or MAC, chest x ray evidence of lung cavitation is an important prognostic
factor during the a treatment follow up. As we discussed before CT scan is Another
important diagnostic ah tool for NTM pulmonary disease. Now coming to the microbiological test most
important test for diagnosing NTM is the identification of the species. All NTM isolates from the sample should be
identified at least to the species level using validated techniques, few of the techniques
that are commonly used are line probe assays, and MALDI TOF mass spectrometry. These two tests help us to identify the species
level of non tuberculous mycobacteria. Whole genome sequencing is also now being
more commonly used more detail of these test where discussed in the previous lecture on
diagnosis of M mycobacterium. Now, the yellow ah yellow picture that you
see on this slide is nothing, but a culture of M kansasii. Now, multiple techniques have been used to
speciate these which includes ah as I said PCR technique, or HPLC methodology um these. And also 16S ribosomal DNA defines NTM species
more accurately many of these test may not be available in all centres. Ah But they can always be sent to a tertiary
level before we start treating a patient of NTM pulmonary disease. ah
This this slide shows various banding um so these are the bands that you see these are
very fixed bands on a line probe assay. And they diagnose ah it is a predefined bands
which diagnose the species of the NTM. So, we cannot stop just with that identification
of the species of non tuberculous mycobacteria. What we also have to do is? Drug susceptibility profile of these NTM because
they vary for each organism and they are very much different from M tuberculosis. The rapidly growing NTM are usually resistant
to rifampicin and isoniazid; while they are sensitive to other kinds of macrolides and
cephalosporins. Susceptibility testing for M abscess also
varies and they need to have a larger group of drugs where a DST has to be ordered. Other important reason why you should have
a drug susceptibility profile? Some of the drug susceptibility pattern may
not correlate so well with the clinical response of a patient. And they also form a prognostic indicator
for the treat ah for the management of these patients. Especially in cases of MAC or M avium complex
resistance to macrolide as well as to amikacin is ah has been shown to be associated with
treatment failure. Also M kansasii the in vitro resistant to
rifampicin is a very high prognostic marker for treatment failure to M kansasii pulmonary
disease. Thank you with this we come to the end of
session one.


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