As already noted, the more
novel enhanced case-finding (ECF) strategy didn’t have any impact at all on TB
prevalence. Enhanced case-finding scaled up community-wide efforts to identify TB
cases. with activities to increase access to a timely diagnosis for smear-positive
TB, and a host of interventions to get people to seek out an early diagnosis so
that they would get on treatment earlier and consequently would be less likely
to spread TB. In fact, the communities randomised to that intervention did a
little worse, though it wasn’t a statistically significant finding.
sure the team will spend many hours trying to figure out why the
community-based interventions did not work; and why the incidence really didn’t
come down as much as I think we would all have liked to see it come down,” said
“They’re not exactly the results that we’d
hoped for,” Prof. Peter Godfrey-Faussett of the London School Hygiene & Tropical Medicine, told HATIP. “We’d
all hoped that ECF would show an effect. And yet we are very proud that our
study has shown that an intervention, intensified household counselling, can
reduce the prevalence of TB at the community level, the first RCT to do this in
the era of HIV.”
But what had attracted
most people’s attention about the ZAMSTAR study was its testing of an enhanced
case-finding model that promised to involve communities. It was colourful and
exciting: there was the innovation of sputum collection posts being installed
in rural communities and informal settlements, the creativity in the social
mobilisation campaigns with drama, radio and other media. And there were
projects in elementary schools in which children were trained to look out for
symptoms of TB in their family members, and then haul, push or pull their loved
one to the sputum collection post if necessary.
But perhaps what was
most engaging was the sense that ECF was empowering communities to take charge
of their own health. So in some ways, the failure of ECF was a bit of a moral
defeat. It also raises the stakes for
other studies to demonstrate that increasing case detection will have an impact
on the TB epidemic.
“I’m gutted,” Dr Liz
Corbett of the London School Hygiene & Tropical Medicine
told HATIP, when asked how she felt about the results. “I’m so disappointed
that the enhanced case finding in such a major study didn’t show an effect.”
Dr Corbett was hopeful
that Zamstar would support the case for scaling up more aggressive case finding
interventions that she believes are needed to reduce the burden of TB in
Dr Corbett was not
involved in ZAMSTAR, but has been very involved in researching different
approaches to case finding and TB prevention in the community. At
the Union Conference two years ago, she reported the results of DetecTB, which
evaluated two periodic case finding interventions (a week every six months),
providing TB diagnostic services with either a mobile van visiting the
neighbourhood, or via door-to-door screening. The mobile van appeared to
find a higher yield of TB cases, but together both interventions diagnosed
about 41% of the TB cases in the community during the study period, presumably
earlier than the cases would have been diagnosed otherwise. Consequently, this
was followed by a substantial reduction in the prevalence of TB at the population
level within a few years — with a more marked reduction seen in the
HIV-negative than HIV-positive members of the community.
Dr Corbett did wonder whether there weren’t too many differences
between the urban sites in the Western Cape with exceptionally high burdens of
TB and Zambia’s sites, noting that “one size does not fit all when it comes to
case finding”. Differences between community structure and local transport
could serve as more of a barrier to health services in one setting than
In addition, ECF
couldn’t really be standardised across the communities, as Dr Beyers noted
during the Zamstar symposia.
“ECF was done locally
by the local community, and while everything was carefully documented, it was
heterogeneous. It was easier to standardise the household intervention,” she
But it is also
possible, that for one reason or another, the Zamstar ECF intervention may not
have been aggressive enough, only contributing to about a quarter of the smear
positive diagnoses in the community. There is little information, as yet, about
how well the enhanced case-finding intervention succeeded in getting people
diagnosed and onto treatment earlier.
It is also worth
pointing out that ECF relied on smear microscopy aiming for a 48-hour
diagnosis, and smear microscopy misses a lot of cases, especially among people
living with HIV who are far more likely to have smear-negative TB. The
prevalence survey at the end of the study screened for culture-positive TB,
which would include smear-negative cases that might have been more likely to go
undiagnosed in the ECF arm.
One member of the
audience drew attention to the fact that communities randomised to ECF actually
had a higher TB prevalence than those without it. Had any of the
investigators considered whether the intervention had a harmful
Prof. Godfrey-Faussett pointed
out that the confidence interval on that observation crosses 1, so this could
well have been chance. But he also said that they had thought about it, and
hadn’t yet come up with any plausible way for the ECF intervention to do harm.
However, they had only had the results for about a week at the time, and with
more time to look at the data (it would be interesting to see a comparison of each
arm of the study for instance), and analyses, someone may come up with at least
a partial possible explanation.
It might be useful to
consider exactly who was using those sputum collection centres in the ECF
communities. Some of those cases were indeed the people investigators were
hoping for, with highly infectious smear-positive TB presenting earlier, and
being put on treatment sooner than they would otherwise. If that was all that was happening in the
community, one would certainly think it should reduce the burden of TB, with
the magnitude of the effect depending on how much earlier and how many more of
the cases in the community they were picking up.
But that wasn’t the
only thing going on in these communities. Most of the people leaving specimens
at the sputum collection centre didn’t have smear-positive TB, yet they were
leaving their specimens anyway, which must have increased the workload for the
smear microscopist. That would have meant processing more specimens and more
time looking at slides through the microscope, which could have delayed timely
diagnosis, and the turnaround of results of cases likely to be positive.
Studies have found that the efficiency and accuracy of smear microscopists
falls with larger volumes of slides (their eyes get tired reading
slide after slide after slide, day in, day out). But the microscopists in the
communities without ECF may have had a lighter workload. So laboratory-related
delays in diagnosis are one potential problem that could reduce the impact of
In addition to
possibly flooding the lab with specimens, what else was going on with these
other people who left their specimens at the drop off centre? What was their
story? Obviously, they must have had a cough or some symptoms, or they wouldn’t
have done it.
Many of them could in
fact have had smear-negative TB, especially if they were HIV-positive. (In
fact, it seems likely that the household intervention with its prolonged
contact and linkage to health services may have resulted in smear-negative
cases being diagnosed sooner). Many of
the TB suspects could have had some other respiratory infection, or condition,
and again might be HIV-positive. Some of them could have been quite ill with
other HIV-related complications.
So what would have
happened to these people? If everything goes according to protocol, they should
know in a few days that they don’t have TB. In practice, Prof Ayles noted that
they had trouble turning around results that quickly, succeeding only 50% of
the time in Zambia, and only 25% of the time in the Western Cape.
But once sick people
know that they don’t have TB, what do they do? One would hope that they would
eventually present to the clinic and receive diagnosis and care. But believing
that they don’t have TB, will going to the clinic to get a diagnosis seem to be
as pressing, or will they try to self-medicate, or visit their sangoma instead?
Could getting that negative TB result actually reduce further health-seeking
behaviour, and delay diagnosis?
Many probably never
make their way to the health services, so the sputum collection centre might
have been their one effort to get diagnosed by Western medicine.
Those who do present
to heath facilities may go later than they would have otherwise. For these
people, sputum drop off/collection centres could have actually introduced
another step before presenting for care. In settings where the drop-off centres
weren’t available, it is possible that more people would have gone to the clinic
for diagnosis, possibly sooner if still motivated by fear that they have TB.
Given the improving standard of care, there is a good chance that, they would
have also received provider-initiated testing and counselling in the clinic,
and gotten their HIV diagnosed. And once the HIV diagnosis was made, they
should have received a more thorough examination, and had their other
conditions, potentially smear-negative TB, diagnosed as well. On top of that, a
proportion of the people who test HIV positive would hopefully have been put on
ART, which would in turn decrease their risk of TB over the long run.
By not providing this
opportunity for HIV diagnosis, ECF and the sputum collection centres may not do
as good a job of getting people living with HIV into care and reducing their TB
risk, as health facilities that offered more than just a TB diagnosis.
Consequently, communities randomised to ECF could have had a larger pool of the
very people who are most susceptible to TB, which could have undermined TB
control in that district, possibly leading to a higher prevalence of TB. Which
is just what the study found (though it was not statistically significant).
That’s compared to the arm that had no intervention, other than general health
system and laboratory strengthening.
For the communities
that had the enhanced household counselling intervention on top of standard
clinical care, there would have been an even smaller pool of people at high
risk of TB. One thing that the counselling intervention excelled at was finding
large numbers of individuals with HIV in the index case’s household, even
though it did not appear to reduce the burden of TB within the households at
the time point when this was assessed. Households receiving some continuity in
care could have been more likely to receive early and effective treatment, and
less likely to spread TB within the broader community.
This is supposition
and the evidence in fact may turn out not to support it — nevertheless, in complex
systems, interventions can have unintended consequences. There could be a
danger with ECF approaches that are too narrowly focused primarily on smear-positive
TB as though that is the primary problem in the communities. The DOTS strategy
that successfully contained TB in the rest of the world ran into the same
problem — even the best performing DOTS programmes in Southern Africa failed in
the context of HIV. And even with the higher case detection rates that ECF may
deliver, focussing on smear- positive TB alone, without increasing HIV case
detection and treatment, may not be enough in a setting with a high burden of
In fact, in a recently
published paper in the South African
Medical Journal by Wood et al describe how TB control policy based on passive
case detection and the DOTS strategy has failed in the region, partly because
is detection of active TB disease among symptomatic patients presenting to
medical services, and is promoted in developing countries as part of the
WHO-recommended DOTS strategy,” they wrote, but, “The DOTS strategy is
insufficient in high HIV-burdened settings. In high transmission settings where
effective contact numbers are high, lower case-finding rates and delays in
diagnosis and initiation of chemotherapy result in ongoing transmission.”
Wood et al call for a
new more aggressive approach to go into the worst affected communities, using
new diagnostic technologies and intensified case finding. Despite the the efforts to encourage case detection using enhanced case-finding in this setting, it remains
passive. A number of other studies at the conference generated more promising
results to increase case finding — though none of these have looked at
population level impacts as yet. These
are described in a separate article.