TB Infection Control

Dear Alexandru,

What I presented this morning is definitely NOT what most national
guidelines or textbooks recommend for either drug susceptible or drug
resistant TB. For drug susceptible TB, most authorities recommend the "two
week rule". This was first stated in a review paper by Annik Roullion and
colleagues based a series of household transmission studies in the 70's.
However, as I shared with you during the webinair, there is good
experimental evidence of markedly reduced infectiousness on the very day
that EFFECTIVE treatment starts. I am referring to the classic guinea pig
studies of Dr. Richard Riley. Here is a quote from Dr. Riley from the paper
(Am Rev Respir Disease 1962:85; 511-525):

Riley concluded: “The treated patients were *admitted to the ward at the
time treatment was initiated and were generally removed before the sputum
became completely negative*. Hence the decrease in infectiousness preceded
the elimination of the organisms from the sputum, indicating that the
effect was prompt as well as striking.” Regarding drug resistant TB, he
was more cautious because of the smaller numbers of patients and guinea pig
infections, concluding only that *“Drug therapy appeared to be effective
in reducing the infectivity of patients ...

Dear Alexandru,

What I presented this morning is definitely NOT what most national
guidelines or textbooks recommend for either drug susceptible or drug
resistant TB. For drug susceptible TB, most authorities recommend the "two
week rule". This was first stated in a review paper by Annik Roullion and
colleagues based a series of household transmission studies in the 70's.
However, as I shared with you during the webinair, there is good
experimental evidence of markedly reduced infectiousness on the very day
that EFFECTIVE treatment starts. I am referring to the classic guinea pig
studies of Dr. Richard Riley. Here is a quote from Dr. Riley from the paper
(Am Rev Respir Disease 1962:85; 511-525):

Riley concluded: “The treated patients were *admitted to the ward at the
time treatment was initiated and were generally removed before the sputum
became completely negative*. Hence the decrease in infectiousness preceded
the elimination of the organisms from the sputum, indicating that the
effect was prompt as well as striking.” Regarding drug resistant TB, he
was more cautious because of the smaller numbers of patients and guinea pig
infections, concluding only that *“Drug therapy appeared to be effective
in reducing the infectivity of patients with drug resistant organisms, but
the data do not permit detailed analysis of the problem”. *

*
*

On the other hand, in the early 1960's, these remarkable effects of
treatment on transmission reported were accomplished with just INH, PAS,
and SM, and in the case of drug resistant disease, just one or two of these
drugs. I would suggest that the situation was worse than MDR TB since they
did not have fluoroquinolones or other injectables. Finally, and most
importantly, Riley started therapy *on the same day that the patients were
admitted to the ward*. These results represent very little treatment with
far less effective regimens than used today.


With our South African colleagues we have replicated these observations for
MDR TB in the Mpumalanga Airborne Research Facility using guinea pigs and
will soon publish those results. It also appears that standard MDR
treatment, if effective, essentially stops transmission to guinea pigs
soon after it is started - long before sputum conversion. In our study
most transmission was from unsuspected XDR TB where MDR treatment is not
effective. Whether it is a day or two days is not the point. The message
is, as it has always been, that most TB transmission occurs from
unsuspected and, therefore, untreated cases of TB, or from ineffectively
treated cases of drug resistant TB before drug resistance is determined and
the treatment made effective according to the DST.


I have made these points here before, but happy to keep making the point
that active case finding based on cough surveillance followed by effective
treatment based on molecular DST is the most effective form of TB
transmission control - AND IT CURES PEOPLE. This is the heart of what is
called Administrative controls. What is different now is a renewed emphasis
on active case finding, the speed of diagnosis, and on DST-guided
treatment. We are calling this focused approach, FAST, for Finding cases
Actively, Separate temporarily, and Treat effectively based on a molecular
DST. Implementing this approach will require resources and commitment. For
active case finding a strategy and personnel are needed. For rapid
diagnosis, sputum must be collected promptly, taken to a nearby lab with
Xpert technology, and the results reported to the doctor within a day so
that treatment based on the DST can start almost immediately. In my
opinion, such patients need not stay in hospital and pose no risk of
transmission to the community. Again, it is the unsuspected cases that
transmit.

Our South African colleagues have a grant to further study the impact of
treatment prospectively over the next several years. Out goals are to
determine which drugs in the MDR regimen are critical to the rapidity of
effective treatment on transmission.

Dear Ed
When can we expect to read these exciting results – in a peer reviewed journal??

Still major editing going on, but will submit well before the end of April.
When they will be published is another story not under our control!

Dear Ed thank you for answer,
but how it could be explained that "...standard MDR treatment, if effective, essentially stops transmission before sputum conversion." ? If I understand right even if M.tuberculosis exist in sputum they are not infect people? Ok microscopicaly: the explanation could be that we see on microscope the died mycobacteria but if culture is positive: this means that mycobacteria are in life and if this mycobacteria go to alveoli they will trriger something ?!

Thanks for this further question. The explanation that Riley and
colleagues came up with is that antibiotics are concentrated in respiratory
droplets as they evaporate into droplet nuclei, causing their concentration
to escalate dramatically and possibly rendering organisms in the air
non-infectious even though in sputum samples, where there is no stress from
evaporation or concentration of antibiotics, organisms may continue to
grow. Remember that in culture we do everything possible to support growth
whereas the human host or guinea pig has host defenses doing whatever
possible to resist infection. There are major differences between airborne
organisms and those in culture. The early household contact literature is
very clear on the "discordance" between infectiousness of patients and
their smear and culture status once on effective treatment - whereas smear
and culture predict infectiousness when not on effective treatment. We
already incorporate this thinking in the "two week rule" for drug
susceptible TB. Even though it usually takes 2 months on average for
sputum culture to become negative on effective treatment, we declare them
non-infectious at 2 weeks, when many will still have positive sputum smears
and cultures. The two week rule was based on epidemiological studies that
were not sensitive enough ...

Thanks for this further question. The explanation that Riley and
colleagues came up with is that antibiotics are concentrated in respiratory
droplets as they evaporate into droplet nuclei, causing their concentration
to escalate dramatically and possibly rendering organisms in the air
non-infectious even though in sputum samples, where there is no stress from
evaporation or concentration of antibiotics, organisms may continue to
grow. Remember that in culture we do everything possible to support growth
whereas the human host or guinea pig has host defenses doing whatever
possible to resist infection. There are major differences between airborne
organisms and those in culture. The early household contact literature is
very clear on the "discordance" between infectiousness of patients and
their smear and culture status once on effective treatment - whereas smear
and culture predict infectiousness when not on effective treatment. We
already incorporate this thinking in the "two week rule" for drug
susceptible TB. Even though it usually takes 2 months on average for
sputum culture to become negative on effective treatment, we declare them
non-infectious at 2 weeks, when many will still have positive sputum smears
and cultures. The two week rule was based on epidemiological studies that
were not sensitive enough to say how much more quickly infectiousness might
be interrupted by treatment. Annik actually said something like, most
patients on effective treatment are likely to become non-infectious in less
than two weeks - but was unable to speculate further. Again, the data for
a same day effect for drug susceptible TB does not depend on our
unpublished data, but is in the Riley data already cited. Our data simply
supports those conclusions and suggests (does not yet prove) that it may
apply to MDR TB as well.

There is no new data that I am aware of to explain the rapid impact of
treatment on transmission, and one older study by Louden failed to show
that INH in culture media at low concentrations would inhibit grown when
aerosolized - but again that is culture growth, not infectiousness for a
living host with host defenses. Finally, TB bacilli respond to antibiotic
stress almost immediately with RNA transcriptional changes. We are not yet
able to measure those changes in airborne organisms, but an effort to do
just that is underway. Those efforts may better explain how antibiotics
rapidly inhibit transmission, apparently independently of their less rapid
impact on numbers of viable bacteria in sputum. It would make a terrific
PhD thesis.

Dear Ed,
Thank you for clear explanation on GHD online. I am thinking that of course usually we help that Mycobacteria to grow and is diference between “vitro” and “vivo” - where is present the host defenses. But really we need more study’s for demonstration.

I agree that more data is needed and we, and hopefully others, have those
studies planned.

We have got data from 2008. We are going to print shortly. Makes interesting reading.
Shaheen
Sent via my BlackBerry from Vodacom - let your email find you!

Data on what, Shaheen? Can you elaborate?

Sorry Ed. We have been following up Occupationally Acquired TB since 2008 and some of our findings are quite interesting. That was the data I was referring to.
Cheers
S

Prof Shaheen Mehtar

Buitengewoon Professor (Waarnemende Hoof: UIPC) / Extraordinary Professor (Acting Head: UIPC)

[cid:image001.png@01CE271F.8C9BC010]

Eenheid vir Infeksievoorkoming en Beheer / Unit for Infection Prevention and Control
Fakulteit Geneeskunde en Gesondheidswetenskappe /
Faculty of Medicine and Health Sciences
Universiteit Stellenbosch University
Posbus / PO Box 19063; Francie van Zijl Rylaan / Drive
TYGERBERG 7505
Suid-Afrika / South Africa
Tel: +27 21 938-5054; Faks / fax: +27 21 931-5065
e-pos / e-mail: <mailto:>
Visit our website at www.sun.ac.za/uipc<http://www.sun.ac.za/uipc>

Dear Dr. Nardell,
I am very interested with "cough surveillance" method that you offered. Could you please give me the link of the resources for me to study?
And in congregate setting like prisons where we have lack of resources, no isolation room, if we found MDR TB patient but we need time to move the patient to PMDT Hospital site (around 1 - 2 weeks), which means effective treatment cannot be started right away, what kind of TB IC methode would you suggest to lower the risk of further transmission ?

Thank you

Regina Loprang

I am in South Africa with limited internet access. Cough
surveillance.iswidely used and you should have no trouble finding
references. Can someone help Regina?

Here is one that we have just published.
http://www.ingentaconnect.com/content/iuatld/pha/2013/00000003/00000001/art00014

There are numerous others. If you send your email address to <mailto:>, I can send you the articles.
Best,
Sheela