Dr Lönnroth listed five programmatic elements — including
some specific tools, approaches and interventions — where transformation could
increase the provision of TB diagnostic services and treatment to those who are
most difficult to reach. This list
serves as the framework for listing a number of related studies and innovations
described at the conference.
Diagnostics
As Prof. Golub noted, there have been a host of
diagnostic advances, including high-quality culture, liquid culture,
drug-sensitivity testing and line-probe assays that could improve access to more
timely treatment for many of the people with smear-negative, extrapulmonary and
drug-resistant TB.
Clearly, the most transformative diagnostic test so far is
the Gene Xpert MTB/RIF assay, which can diagnose TB within hours, faster and
more reliably than smear-microscopy, though clearly it is much more expensive
and introducing it into many countries will put a strain on resources for
health.
GeneXpert is recommended to detect possible cases of MDR-TB
(potentially useful in algorithms with drug susceptibility testing, that would
have a better chance of getting the patient on an effective treatment regimen
sooner). It is also recommended by WHO for first-line diagnosis of people
living with HIV, and is much more likely to identify smear negative cases,
especially if more than one specimen is run in these patients). However, if its
use is limited just to the detection of possible MDR-TB or for diagnosis of TB
in people living with HIV, it won’t benefit the vast majority of people living
with TB (85% of estimated TB is neither MDR, nor HIV-related). In South Africa,
it is being scaled up as the first-level diagnostic test for all TB suspects,
but this is a massive and expensive undertaking. Several presentations were
made on the implementation and real world costs of the test — along with
complaints that it is diagnosing much more MDR-TB than South Africa has hospital beds for,
in settings where there aren’t enough decentralised teams to deliver MDR-TB
treatment.
Although the GeneXpert assay can produce a result in record
time, its expense limits the number of reader units that countries can afford
to have installed, and most facilities will have to ship specimens to the
centralised labs, adding transport delays to the time it takes to get a
diagnosis.
“It’s a big jump from the microscope to GeneXpert, it is a
really useful test. But we are not yet at the point of care,” said Dr Ditiu.
The conference reports on diagnostics and the operational
aspects of introducing Gene Xpert into clinical practice, will be discussed in
a forthcoming edition of HATIP.
Dr Lönnruth also believes that chest x-ray remains an important screening tool that could help
improve access to timely diagnosis for some patients.
“X-ray has been rightfully vilified as a diagnostic tool
because it has poor specificity and the inter-operator variability is huge,” he
said, referring to the problem that different specialists reading chest x-rays
have been shown to interpret them differently. “But a number of studies have
recently shown that as a screening tool it can be highly useful in many
prevalence surveys.
There were a number of studies on intensified case finding
at the conference that reported that adding chest-x-ray increased the
likelihood of identifying culture positive TB in people living with HIV who
would not have otherwise been detected by screening algorithms or smear
microscopy.
There have also been some recent advances in technology and
practice that make chest x-rays easier to use, according to Dr Lönnroth. These
include quality assured equipment and reading, digital X-ray and telemedicine.
“You can send the picture off to a call centre in Hyderabad, where there is a radiologist and
you’ll have the results in 5 minutes,” he said. There have also been advances
in automated reading (Computer Aided Diagnostics – CAD) that he said could
allow chest x-ray to be used as a screening tool, where a positive result would
need to be verified by a proper diagnostic test, such as GeneXpert.
“Finally, better diagnostics for latent TB infection are needed.
This needs to go hand in hand with better treatments and more feasible
treatments,” he said.
Transform Public-Private mixes from projects to national scale up
In many countries, people seek and access care for TB
outside the public health system, for instance, from private doctors,
pharmacists or non-governmental organisations.
Public-private mix (PPM) is a comprehensive approach for systematic involvement of all the
relevant health care providers in TB which tries to make certain that they all
adhere to International Standards for TB Care and help the country achieve
national and global TB control targets. PPM encompasses a range of diverse
collaborative strategies, and there are many PPM pilot projects. Regardless, according
to the recent Global TB report, non-public health providers typically
contribute 20-40% of the TB cases notified in areas where they exist. So clearly PPM is important to fully scale up
to maintain a high quality of service, and improve the reach of TB diagnosis
and effective TB treatment.
“We need to step out of the project thinking, and really
think of this as something that should be mainstreamed into all programme
planning and scaled up on a national scale” he said. He referred to one CIDA-funded
project on intensified case finding being conducted in five countries. One
significant element of the programme was the inclusion of both public and
private hospitals. This was “showing a dramatic contribution by the hospital
sector, and a significant increase in case notification when you do so. This
kind of intervention needs to be scaled up rapidly,” said Dr Lönnroth.
Community and civil society engagement
The thinking around community and civil society
engagement must also evolve. NGOs/CSOs are a critical vehicle to effectively
scale up community-based TB activities. Study after study at the conference
illustrated the benefits of this engagement, showing that CSOs/CBOs and expert
patients can dramatically increase the reach and quality of TB services
including diagnosis, linkage to treatment and retention in care.
“We are going to remain
stuck at our current levels of programme performance, unless we start scaling
up and engaging the civil society,” Dr Ditiu said in the talk early during the
conference.
WHO is currently holding a series of consultations to
develop normative guidance to facilitate this scale-up, with constructive engagement
between civil society organisations and the TB programme. This has already
identified a number of key issues such as the need for clarity and simplicity
in community-based TB activities. Quality indicators to measure engagement need
to be developed, and innovation and use of modern technology is required.
The process is being spearheaded by Dr Haileyesus Getahun of
the STOP TB Department of WHO, who moderated a conference symposium introducing
the issue, that sought input from CBOs and the government health sector to
better define the core elements that need to be addressed in the normative
guidance WHO is developing. Essentially,
the process seeks to make the interaction a little formal, so that the partnership between programme and
civil society organisations can move forward in a more structured and
productive way.
Transform the
health systems
Many lessons have been learned in the recent expansion of
health services, in resource-limited settings. To provide universal access, all
diagnosis and treatment, services must be free of charge, including new technologies, throughout the health system.
In addition, the implementation of HIV and TB collaboration
and integration of essential services have provided a model for exploiting
synergisms across other programmes (NCDs, Maternal and Child Health, etc), and
underscore the need for a strengthened PHC that can provide high quality
services close to where the patient lives.
“We need to more actively promote Full Universal Health
Coverage: including Social support and protection,” said Dr Lönnroth, “to make
health services more accessible, to make it easier to stay on treatment, and to
make it more attractive to come forward and seek healthcare.
Outreach campaigns and programmes may also benefit from
integration and collaboration to develop platforms addressing multiple diseases
and risk factor for screening, combined with broad health promotion.
“If we are thinking about scaling up mass community
screenings for TB, we cannot do this in a vertical manner, we need to link up
with other health programmes that are thinking about screening for other risk
factors, in particular non-communicable disease and HIV,” said Dr Lönnruth. In
additional to the financial and logistical benefits, some interventions may
amplify the effect of the other. For instance, in the Zamstar study results,
one of the strengths of the contact tracing intervention was that it provided
increased access to HIV counselling and testing while the enhanced case finding
intervention did not.
Transform our
thinking about early detection
All of these elements ultimately support strategies that improve early detection.
For example, decentralisation of TB diagnostic
services to points closer to the patient can reduce barriers that
delay access to diagnosis.
Novel approaches and innovative technologies could shorten
the time spent undiagnosed, such as innovations for outreach, campaigns, mobile
diagnostics, health education, and e-health innovations. The TB Reach portfolio
is rich with examples.
But the primary way to find cases earlier is through TB
screening (active, enhanced, intensified case finding and contact tracing),
especially when targetted at groups at risk of TB. Depending on the diagnostic
tools, when screening is aggressive, it may identify cases at an extremely
early stage in the course of disease, while they have no or vague symptoms.
These may make up the majority of those who go undiagnosed.
TB screening of groups at risk may be performed to reach
vulnerable groups with poor health access. Many face stigma and discrimination
and are afraid to go to health services, or as Dr Ditiu said, “may not understand
their rights.”
Dr Lönnroth suggested that risk group screening should start
with the most feasible-to-reach groups with high TB prevalence — these include
all respiratory and obstructive pulmonary disease and in-patients where there
is a high prevalence of undetected TB, HIV, perhaps diabetics in high TB burden
settings, TB contacts (such as home-based, and prisoners). These are the low-hanging fruit where screening would be most cost-effective.
Of course, improving access to early diagnosis and
life-saving treatment for marginalised populations is its own justification —
however, if the goal of active case-finding is to reduce TB prevalence, other
factors, such as who is screened, and what proportion of the local cases are
due to recent infections are critical determinants of the epidemiological
impact of screening, according to Dr Corbett, so screening strategies must
weigh other considerations in addition to picking the low hanging fruit (see
below).
Fruit were the prevailing euphemism for TB cases in these
studies, probably because Prof. Golub and colleagues had chosen to display
the findings of the review, involving 30,000 abstracts on case finding, on the
branches of case-finding trees, with fruit representing cases from different
populations, hanging on different branches of the tree, depending on how easy
they are to reach, as well as what sort of tools (type of active case-finding
strategy) was best suited to harvest (or find) such cases.
He divided the studies by type (community, risk group,
contact tracing) and risk group, and using weighted study data, determined how
many people would have to be screened to detect one case in each group, in
different settings, and with which tools. For instance, when looking at HIV-positive
people, “what really stands out here is that when we look at and consider
culture in a diagnosis – when we’re screening for HIV-infected patients – we
see that the number needed to screen (to detect a TB case) drops down
considerably. This is really a reflection of the fact that many HIV-positive
patients are smear-negative, culture-positive. Culture is extremely important
in capturing the TB in that population,” he said.
“How we conceptualise a case-finding tree is looking at the
tree-tops: These are the populations that may be the hardest to reach, may
require a ladder and require more work to get to. In this population, to find
these cases requires community-wide, or door-to-door mobile units. The
mid-range branches are where we classify people known to be living with
HIV/AIDS. As we’ve mentioned, many of these are smear-negative and may need a
culture. So this adds a little bit of complexity to the accessibility and the
yield in these populations. Low-hanging
branches – diabetics –are populations that are relatively ripe for
screening and we need to get to them.
Low hanging fruit – we refer to as the ‘contacts’. The fallen fruit – those who
are just really waiting to be screened are the prison population and the
PMTCT clinics,” he said.
But Prof. Golub further explained that these risks shift
markedly based on whether someone lives in a low, medium or high incidence
country. For instance in South Africa case yields among people living with HIV
and general outpatient settings are particularly high (the fruit on the ground
or low hanging). In medium and high incidence countries, people who use drugs
or alcohol or the elderly are at higher risk.
Outreach to marginalised groups can yield significant rates
for case-finding. According to Dr Ditiu, “in
the TB Reach projects, after three quarters the number of cases detected and
treated increased by 20%, which shows that if you have people focusing on the
unreachable people with the tools you have, looking for the cases among the
poor and vulnerable or sex workers, we can increase case detection.”
Community population-wide screening is a much more ambitious
and expensive undertaking, though the total yield and total impact is large.
Reaching out to vulnerable communities where TB prevalence is high, such as
poor neighbourhoods, urban slums, requires more resources and is very difficult
to implement without involving others, including other healthcare providers (or
programmes, such as the HIV programme people) as well as communities, civil
societies and social services.
However, Dr Liz Corbett believes community screening
exercises are absolutely essential to interrupt the cycle of transmission.
“With case-finding, one has to recognise that most TB
disease is due to recent TB transmission, to casual contact. So, if you’re
doing profiling and trying to identify high-risk people, then you’re going to
miss most people with active disease in the community,” she said. “Many of these people don’t actually have
much by the way of symptoms. If you look in the facility, you see an
overwhelming predominance of sick HIV-positive people, but out in the
community, some of the HIV-negatives especially, can be very healthy with their
disease. So you find these people with your active case-finding intervention
and by doing so, prevent disease in the quite near future, in both
HIV-positives and negatives – that’s the principle of case finding.”