The next step from intensified case finding is to implement activities which provide isoniazid preventive therapy for prevention of tuberculosis.
Dr Mohammed Yassin of the Global Fund spoke at the 2011 STOP TB symposium
about the operational challenges implementing contact investigation and IPT in
children, and shared the experience in Hawassa, southern Ethiopia
following a cohort of children who were contacts of smear-positive TB cases. He
also described the TB REACH-Ethiopia-LSTM's innovative programme to implement community-based
TB diagnosis, prevention and treatment, and described some of its early results,
focusing on how the programme addressed contact tracing in children and IPT.
Children in contact with infectious TB cases
are at a higher risk of infection and progression to disease. But it has been well
established that IPT is effective in preventing TB progression.6 Consequently, WHO and most
NTPs recommend contact screening and provision of IPT for asymptomatic children
under 5 years of age.7
But in practice, Dr Yassin said, “contact
screening and IPT provision are often overlooked and many programmes don’t do
it.8 The gap between policy
and practice related to contact screening and IPT is significant, especially in
developing countries."9
Dr Yassin described the many challenges to
implementing contact investigation and IPT, starting with contact screening.
"NTPs
recommend contact screening — it’s usually included in their guidelines or manuals
— but most don’t implement it, or those who do implement it, usually just ask
index cases to bring their contacts to the facilities, adopting a “passive”
approach,” he said, adding that often staff don’t even inform index cases about
the need to bring in their contacts, possible due to lack of awareness of the
policy. The majority of index cases who are
told to bring their contact in, don’t, because they haven’t been made
adequately aware, as parents or relatives, about the advantages of screening
their children and the potential benefit of preventive therapy.
In fact, if the health care staff have not
convinced the TB patient of the utter necessity of bringing their children in
for screening, it is really unreasonable to expect him or her to do so, if one stops
to think about the ordeal it could be to gather together all the children in
the household, particularly more than one, corral or carry them to the health
facility, and probably endure half the day struggling with them in a crowded waiting
room filled with sick and injured people.10
As for the challenges related to
implementing IPT? Firstly, no one is going to provide IPT if there
hasn’t been a concerted effort to put an IPT programme in place, or if the
resources and tools to support successful implementation are not available.
“IPT related recording and
reporting systems often do not exist in most national programmes. There are no dedicated registers or
patient contact cards,” said Dr Yassin. In
addition, without training, health care workers are often reluctant to initiate
IPT in a young child because they are not confident in their ability to exclude
active TB in a child, and fear that if they provide IPT and the child does have
TB, it might lead to drug resistance.
Moreover, the drug may not even be in stock — because no one has made it a priority to
plan for it, established a supply system nor has the programme allocated
resources for this purpose.
Consequently
only a very few children initiate IPT and there is evidence that even active
tracing may not improve IPT uptake significantly.11
If someone does prescribe it for a child contact, that is probably all that is done — so adherence
is probably very poor and whether it is prescribed or not, is not documented in
the registers – assuming they exist.
In short, in most resource limited settings, there is very little if any access to
services providing IPT to children exposed to TB, especially in rural
communities.
The child contact tracing to IPT completion cascade
Dr Yassin presented a graph on
child contact tracing and IPT that was very similar to the notorious ‘PMTCT Cascade’
— which showed that there were multiple step/events, a critical pathway, that
had to be followed for an HIV-positive pregnant woman and her child to actually
take the antiretrovirals to prevent vertical transmission of HIV, and for each
step along that path, fewer and fewer women were retained in the programme, so
that by the time of delivery, very few infants of pregnant women were actually
receiving the benefits that the programme had been set up to deliver.
Something similar happens between contact
tracing and completion of IPT.
“Only a
fraction of children end up completing IPT, whereas you can start with a very
large number of contacts, but not all contacts are informed or visited at home.
But not all contacts are screened. But when we screen them, most of them will
be asymptomatic. One might assume that all these children then start IPT, but
not all children or their parents accept the offer of IPT, some refuse. And
several studies in Africa have shown that only a proportion of children who
start IPT actually complete the recommended six months prophylaxis,” said Dr
Yassin.
There could
be a number of other steps in this cascade. For instance, in the screening
process, TST (which involves at least two steps) and chest x-ray can be helpful
for screening wherever they are available, but their unavailability shouldn’t
preclude contact management, according to WHO’s Child TB
guidelines, which state that “clinical assessment is sufficient to decide
initiation of IPT for children with no symptoms.
Delivery of
IPT might also increase, Dr Yassin believes, if healthcare workers were made
aware that there are now a large body of data on IPT, including a review of thirteen
IPT trials with over 35,000 participants. that showed low risk of resistance
(RR 1.45, 95% CI 0.85-2.47).12
Cohort study in Hawassa, southern Ethiopia
Dr Yassin described a cohort study that
they conducted between 2007-2010 among child contacts of TB cases to determine
compliance to IPT and the risk of TB progression. This study also collected
data on TSTs, IGRAs, and other potential biological markers for progression of
TB.
Smear-positive
cases were identified in three health facilities and their houses were visited
and mapped by GPS. IPT started for children under five years old as recommended
by the NTP. The study included 184 children (82 under five years old, 102 five years
old and over) in contact with 83 index cases followed for a median period of 24
months. 46% of the children under five years of age, and 67% five years old and
over had TST ≥10mm, and 12% and 9% were HIV positive respectively. 82 children under
five years of age initiated IPT and were followed monthly.
Twenty-seven
took IPT for at least four months and only ten (12%) completed the 6-month course
— illustrating the child contact tracing to IPT completion cascade.
“The main
reason for interrupting IPT was that parents thought drugs were not necessary
for their healthy children,” said Dr Yassin, who added that they remained
difficult to convince even after a couple of interventions to change their
minds.
None of
those who initiated IPT developed active TB during follow-up. However, 11% (11)
children under the age of five who didn’t receive IPT developed active TB —none
of these children were HIV-positive.
“But we
learned that the risk of developing active TB among children in contact with
smear-positive TB is very high even without HIV infection and IPT reduces this
risk, though the numbers in our cohort were low,” Dr Yassin said.13
TB REACH Ethiopia-LSTM project
Dr Yassin also described the TB
REACH Ethiopia-LSTM project, a community-based intervention project to improve
TB control in Ethiopia. We previously reported another presentation Dr Yassin
gave during the Union World Conference in HATIP 184. The project almost
doubled TB case finding in the region of southern Ethiopia where it was implemented.
The
programme trained community health extension workers who are part of Ethiopia’s
health services, already embedded and providing comprehensive care within local
communities, to provide household contact tracing in the community.
Concurrently,
the project improved laboratory capacity and launched various advocacy, communication
and social mobilisation activities, including awareness creation workshops on
contact tracing and IPT targeting all levels of Ethiopian society, attended by
over 1,200 political, community, religious leaders, stakeholders, health
personnel and former TB patients.
In the
course of their routine daily work, health extension workers visited homes to
provide treatment and support, and screened for symptoms of TB. Health
extension workers identified TB “suspects,” collected their sputum samples, and
prepared the smears on slides for microscopy and phoned their supervisors to collect
the smears. (They all have mobile phones to keep in contact with the
supervisor). The supervisors would pick up the slides, take them to the lab
technicians, who examined the smears, and reported results to supervisors
(keeping slides for EDA). The supervisor would get the results, and make
certain that treatment was initiated by smear-positive cases in their
residences, screened household contacts and initiated IPT for children who were
asymptomatic. Treatment support was provided by health extension workers who reported
the outcomes and follows smear-negative cases within the communities.
In this
presentation, Dr Yassin described in more detail the child contact
investigation and IPT activities in the project. He said that that they only
received INH supplies in May 2011, months after the project had started, so health
extension workers received a refresher course of training in May-June.
Implementation
of this aspect was purposely phased in. “This is a learning process as well, we
didn’t want to start IPT for everyone all at once,” said Dr Yassin. But the
numbers put on treatment increased dramatically in the last few months of
follow-up that Dr Yassin shared, so that 57% of the child contacts were
receiving IPT.
Dr Yassin concluded by giving his view of what
successful implementation and scale-up of IPT services depends on.
Planning and prioritising IPT
|
Proper planning and resource
allocation within the NTP
Ensuring availability of INH
(preferably in blister packs)
Separate
registers, contact cards and reporting formats need to be provided
Phased
implementation and scaling-up of activities
|
Capacity building
|
Training of staff about diagnosis and
the benefits of treatment for childhood TB, contact investigation and IPT
Improving communities’ awareness
about the risk of TB after exposure and the role of IPT in mitigating this
risk
Counselling of parents about the importance
of completing IPT
|
“Community-based
contact screening and IPT provision and follow-up would probably improve
access, uptake and compliance,” he concluded.
IPT in children in
Brazil
Dr Clemax Couto Sant´Anna, of the Universidade Federal do Rio de Janeiro described how Brazil, a high burden TB country
where BCG vaccination at birth is universal, has approached IPT in children.
Old Brazilian TB programme guidelines, which have now been
changed, emphasised that, due to widespread BCG vaccination, for a TST to be
considered suggestive of latent TB infection (LTBi), the reaction had to be
larger than in the current guidelines (see below). The policy was to give six
months of IPT to all child contacts (under 15 years of age) of TB cases,
provided they were asymptomatic with a normal chest X-ray, with the highest priority
given to children under five.
Brazil has experience and data from a number of
retrospective studies on thousands of children put on IPT. Despite the federal
policy, implementation varies between the states of Brazil (which have
different economic and culture situations) — some states seem to have put
different emphasis on the TST cut-off, for instance. Data from São Paolo in
2009 suggested the health system had been more successful giving IPT to
adolescents over the age of 15 compared to children under 5. Data also from São
Paolo in 2010, suggested that only 57.9% reported having completed their IPT.
There were only a small number of deaths, active disease or adverse events in
this cohort, and only 8% who were actually reported to be non-adherent, so the
problem seemed to be one of recording and reporting. Dr Sant’Anna noted a
recent prospective study in Rio, where 228
children with LTBi were put on IPT, andaround
17% were reported to be non-compliant. Unfortunately, he didn’t explain Brazil’s secret
for achieving such high adherence to IPT compared to the experience in other
settings.
Subsequently an online electronic data system for IPT has
been established to keep better track of the patient’s data.
In 2010, Brazil’s guidelines were updated so that now the
cut-off for TST is ≥ 5 mm in > 2 years BCG-vaccinated children; or non
BCG-vaccinated children or immunosuppressed patients, and ≥ 10 mm in < 2
years BCG-vaccinated children — which during the discussion, Dr Dráurio
Barreira, who heads Brazil’s NTP, emphasised is supported by the data the
programme has gathered. The priorities for both contact tracing and IPT (now
recommended for at least six months but ideally nine months) are 1) children
under 5 years of age and 2) children living with HIV. Asymptomatic HIV-infected
TB child contacts must start IPT independent of TST results, IF their chest
x-rays are normal.
As for HIV-infected patients in general (not specific to TB
contacts), IPT is recommended for people without the symptoms of TB and a
normal chest x-ray if their TST reaction is ≥ 5 mm — or if it ever has been ≥ 5
mm (unless they have subsequently been treated with a course of TB treatment or
IPT, since a smaller TST reaction might merely be a sign of anergy developing).
Again, TST results aren’t needed if the patient is a household or institutional
contact of a TB case, but in addition, any person living with HIV develops
signs of TB sequelae on their chest
x-ray should be put on IPT regardless of TST results (as long as active disease
has been ruled out).