Tuberculosis has been a
major public health problem for centuries.
The implementation of effective public health
interventions for the prevention and control
of TB has significantly contributed to a
substantial reduction of the global disease
burden. However, the emergence of the HIV
epidemic has posed major challenges to TB
control efforts globally. In a country with
almost 40% of population already infected
with TB, an increasing prevalence of HIV
will jeopardize TB control efforts with
serious consequences.
In India,
there were an estimated 3.97 million people
living with HIV at the end of year 2001(TB
figures).
There exists a synergistic
relationship between tuberculosis and HIV.
Impact of HIV on TB
About a third of the HIV population,
world wide, is co-infected with M. TB.
HIV epidemic has the potential to worsen
the TB epidemic as has happened in certain
African countries. This is mainly because
HIV increases the risk of disease reactivation
in people with latent TB and because HIV-infected
persons are more susceptible to new TB
infection. These patients can then spread
TB to other people. HIV is the most powerful
risk factor for progression of TB infection
to TB disease.
An HIV positive person infected with
M.TB has a 50% lifetime risk of developing
TB whereas an HIV negative person infected
with M. tuberculosis has only a 10% risk
of developing TB. This is especially important
in India where it is estimated that 40%
of the adult population harbors M. tuberculosis.
HIV- infected persons who become newly
infected with M. tuberculosis rapidly
progress to active TB.
TB is the most common serious opportunistic
infection occurring among HIV-positive
persons and is the first manifestation
of AIDS in more than 50% of cases in developing
countries.
In developing countries, tuberculosis
is the major cause of mortality in PLWHA.
In a developing country like India,
the potential extra burden of new TB cases
attributable to HIV could overwhelm budgets
and support services, as has happened
in countries most heavily affected by
the HIV epidemic.
Impact of HIV on
TB control program
In populations where HIV/TB is common,
health services are struggling to cope with
the large and rising numbers of TB patients
with the following consequences:
Over- diagnosis of sputum smear-negative
PTB.
Under-diagnosis of sputum smear-positive
PTB.
Inadequate supervision of anti-TB chemotherapy.
High mortality rates during treatment.
High default rates because of adverse
drug reactions.
High rates of TB recurrence.
Increased emergence of drug resistance.
Impact of TB on
HIV
TB shortens the survival of patients
with HIV infection.
TB accelerates the progression of HIV
as observed by a six-to seven-fold increase
in the HIV viral load in TB patients.
TB is the cause of death for one out
of every three people with AIDS worldwide.
In order to contain the deadly duo of HIV-TB,
it is, therefore, essential that both HIV
and TB control programmes work together.
NACP-
RNTCP Co-ordination
In view of the fact that tuberculosis is one
of the commonest infectious disease seen in
HIV infected individuals, there is a clear
case for active collaboration between the
HIV and TB control programmes to ensure the
early diagnosis and successful treatment of
tuberculosis and extending adequate care and
support facilities to PLHA.
PATHOGENESIS
During the initial (primary)
infection of immunocompetent persons with
Mycobacterium tuberculosis (M. Tb), macrophages
ingest the organisms and process and present
the mycobacterial antigens to T cells. CD4+
T lymphocytes secrete lymphokines that enhance
the capacity of macrophages to ingest and
kill the mycobacteria. In most people, tuberculosis
infection is contained and tuberculosis
does not develop, although a small number
of dormant bacilli may remain in the body.
Clinically apparent TB develops in approximately
10% of infected patients, soon after primary
infection or years later (reactivation TB).
These consequences are thought to be due
to defects in T cell or macrophage function
(or both).
The hallmark of HIV infection
is a progressive depletion and dysfunction
of CD4+ T lymphocytes, coupled with defects
in the macrophage and monocyte function.
Because CD4+ T lymphocytes and macrophages
have a central role in anti-mycobacterial
defences, dysfunction of these cells places
patients with HIV infection at high risk
for primary or reactivation TB. Epidemiological
evidence indicates that HIV infection increases
the risk of reactivation of latent tuberculosis
infection.
DIAGNOSIS
Pulmonary tuberculosis
is the most common manifestation of tuberculosis
in adults infected with HIV. Tuberculosis
can occur at any point in the course of
progression of HIV infection. The clinical
pattern of tuberculosis correlates with
the patient’s immune status. If TB
occurs in the early stages of HIV infection
when immunity is only partially compromised,
the clinical features are more like typical
tuberculosis, commonly with upper lobe cavitation,
and the disease resembles that seen in pre-HIV
era. As immunodeficiency advances, HIV-infected
patients present with atypical pulmonary
disease resembling primary tuberculosis
or extra-pulmonary and disseminated disease.
The PTB in advanced HIV disease commonly
presents with hilar adenopathy and lower
lobe involvement. Pulmonary cavitation and
granuloma formation in tissues is less common
in presence of marked immunosuppression.
Occasionally HIV- infected patients with
pulmonary TB may have a normal chest X-ray.
TB disease develops when
the CD4 count falls below 400/ul as compared
to other infections, which develop when
the CD4 counts falls much below 250/ul.
This means that tuberculosis is one of the
earlier opportunistic disease to occur in
a patient with HIV.
Diagnosis
of Pulmonary Tuberculosis
Clinical
Features: Generally
there is no difference in clinical features
between HIV positive and HIV negative patients.
However, among HIV- infected patients, cough
is reported less frequently, probably because
there is less cavitation, inflammation and
endobronchial irritation as a result of
decrease in cell mediated immunity. Similarly,
haemoptysis, which results from caseous
necrosis of the bronchial arteries, is less
common in HIV-infected patients.
Tuberculin
test: Though
useful for measuring the prevalence of tuberculous
infection in a community, it has limited
value for the diagnosis of TB infection
in adults in India; though it can be used
as an adjunct to diagnose childhood TB.
Furthermore, with progression of immunodeficiency
and decrease in CD4 counts, cutaneous anergy
to tuberculosis increases, compounding the
issue further.
Sputum
Microscopy: It
is the cornerstone of diagnosis of TB even
in high HIV-prevalence areas. Patients suspected
of having TB should have three sputum specimens
examined for AFB. HIV-infected, smear positive
patients tend to excrete significantly fewer
organisms per ml of sputum than HIV- negative
patients, which can lead to AFB being missed
if the appropriate number of sputum samples
as well as high power fields are not examined
by microscopy.
Chest
X-Ray: The
chest X-ray is indicated in persons suspected
of having TB who are sputum smear-negative
and who do not respond to 2 weeks of antibiotic
therapy. No radiographic pattern is pathognomonic
of TB, although the classical hallmarks
of the disease are cavitation, apical distribution,
pulmonary fibrosis, shrinkage and calcification.
HIV infected persons with a well preserved
immune function will show these typical
features. However, as immune suppression
worsens, chest X-rays more often show atypical
findings such as pulmonary infiltrates affecting
the lower lobes, intrathoracic lymphadenopathy
military tuberculosis and rarely a normal
chest radiograph. Disease other than TB
can cause both the classical and atypical
chest X-ray findings, and if sputum smears
are negative, other conditions have to be
considered in the differential diagnosis.
Important HIV-related pulmonary diseases,
which may be confused with pulmonary TB,
are bacterial pneumonias, Pneumocystic carini
pneumonia, Kaposi’s sarcoma, fungal
infections and nocardiosis. The following
table highlights the differences between
the PTB occurring in early and late stages
of HIV infection.
Table:
Showing differences in pulmonary tuberculosis
occurring in early & late stage of HIV
infection.
Features
Stage
of HIV infection
Early
Late
Clinical presentation
Often resembles Post-primary
TB
Often resembles Primary TB
Sputum Smear Result
Often Positive
Often Negative
Chest X-Ray Appearance
Often Cavities
Often Infiltrates, No Cavities
Extra-Pulmonary
Tuberculosis
Extra
–pulmonary disease has been reported
in up to 70% of HIV-related TB cases when
the CD4 lymphocyte count is less than 100.
The main types of extra-pulmonary TB seen
in HIV-infected patients are lymphadenopathy,
(peripheral mediastinal, abdominal),pericardial
effusion, and organ involvement especially
liver spleen and meningeal involvement.
The definitive diagnosis of extra-pulmonary
TB is often difficult because of the paucity
of diagnostic facilities, and at times difficulty
in accessing the affected tissue for intervention.
Presentation
of extra-pulmonary TB is generally no different
in HIV-infected when compared with HIV-negative
patients. However, HIV-related TB lymphadenopathy
can occasionally be acute and resemble an
acute pyogenic bacterial infection. Diagnosis
can be made by fine needle aspiration, cylology
of the lymph node and histological examination
inspection of biopsied lymph nodes for macroscopic
caseation, examination of direct smears
from the cut surface for AFB, In TB meningitis,
the examination of CSF is a useful tool,
however it may be normal in some HIV-infected
persons. The CSF must always be subjected
to an India-ink preparation to exclude cryptoccocal
meningitis. Disseminated TB may be difficult
to diagnose. Pericardial TB is not rare
and may be diagnosed presumptively on the
characteristic radiological appearance.
Evidence of tuberculosis elsewhere may provide
circumstantial evidence in favour of the
diagnosis. A pericardial tap and examination
of pericardial fluid may also provide very
useful information. However it should be
undertaken only in a appropriately well
equipped facility.
Childhood
Tuberculosis
Similar
to adults, pulmonary TB is the most common
manifestation of TB in HIV-positive children.
The diagnosis of pulmonary TB in children
less than 4 years old has always been difficult
and HIV-infection further compounds the
problem. Tuberculin test is often negative.
Diagnosis is made, most often, on clinical
and radiological criteria.
Once
the patient is diagnosed as having TB, the
next step is to classify the patient, determine
the type of case and the severity of illness
in order to decide the correct combination
of drugs and duration of treatment.
CLASSIFICATION
OF TUBERCULOSIS CASES:
Patients with tuberculosis are classified
into Pulmonary tuberculosis & Extra
pulmonary tuberculosis. PTB patients are
further divided into sputum positive pulmonary
TB and sputum negative pulmonary TB.
Criteria for the diagnosis
of smear positive, pulmonary tuberculosis
Two or three sputum smears positive
for Acid Fast Bacilli (AFB)
One sputum smear positive for AFB, with
radiographic abnormalities consistent
with active TB as determined by the Medical
Officer
One sputum smear positive for AFB, with
culture positive for AFB
Criteria for the diagnosis
of smear negative, pulmonary tuberculosis
Three sputum smears negative for AFB,
with radiographic abnormalities consistent
with active pulmonary TB which have persisted
after 2 weeks of antibiotic treatment.
Three sputum smears negative for AFB,
but culture positive
Three sputum smears negative, atypical
radiological presentation not responding
to appropriate antibiotic therapy with
strong clinical suspicion of active tuberculosis
in an HIV positive patient.
Criteria for the diagnosis
of extra-pulmonary tuberculosis
Clinical evidence of involvement of
particular affected organ.
Bacteriological confirmation on culture
from the aspirate from the extra-pulmonary
site or histological/cytological evidence
of TB the biopsy / fine needle aspiration
respectively from the affected organ.
TYPES
OF CASES
New case:
A patient who has never taken antituberculosis
treatment or has taken it for less than
one month.
Relapse case:
A patient declared cured of TB by a physician
but who reports back to the health service
and is found to be bacteriologically positive.
Transferred in
case: A patient who has been received
into a Tuberculosis Unit/District hospital
after starting treatment in another unit
where he has been recorded.
Default case:
A patient who has received antituberculosis
treatment for one month from any source
and who has interrupted treatment for more
than two months.
Failure case:
An initial smear positive patient who remains
smear positive at five months or more after
starting treatment OR an initial smear negative
patient who becomes smear positive during
the course of treatment.
Chronic case:
A patient who remains smear positive after
completing a re-treatment regimen.
Other:
A patient who does not fit into any of the
above categories, e.g. a relapse patient
may be smear negative or an extra-pulmonary
TB patient who has not responded to treatment.
Such patients are categorized as others
and receive category II treatment.
SEVERITY
OF ILLNESS
Seriously
ill / Not seriously ill smear negative pulmonary
TB:
Smear negative pulmonary TB cases should
be clinically ascertained for the severity
of illness.
Seriously
ill / Not seriously ill extra-pulmonary
TB:
Seriously ill extra-pulmonary TB includes
meningitis, disseminated TB, tuberculosis
pericarditis, peritonitis, bilateral or
extensive pleurisy, spinal disease with
neurological complications, intestinal and
genitourinary TB. Depending on the classification
of TB, type of TB, severity of illness,
history of treatment in the past, history
of interruptions in the treatment, the patient
will receive category I, category II or
category III treatment. The drugs are to
be taken on alternate days under direct
observation (DOTS-Directly Observed Treatment,
Short- course)
Implications
of diagnostic difficulties:
The advent of HIV has made the diagnosis
of TB more difficult because of its atypical
presentation, many HIV related illness may
be mistaken for tuberculosis and a false
diagnosis of TB may be made. However, they
account for a small proportion of all forms
of notified TB, and thus do not negate the
documented increases in TB notifications
in HIV-endemic areas.
Diagnosis
of HIV infection in TB patients
In a patient with tuberculosis,
if any of the following conditions are present,
HIV co-infection should be excluded:
1.Oral/ oesophageal candidiasis
2.Chronic diarrhea for more than one month
3.Herpes- zoster, especially multidermatomal
4.Recurrent pneumonia
5. Pneumocystis carinii pneumonia (PCP)
6.Oral hairy leukoplakia
7.Present or past genital ulcerations
8.Kaposi’s sarcoma
9.Weight loss more than 10% within the past
6 months period
10.Generalized dermatitis
Detection of HIV infection
in tuberculosis patients can be done by
referring the patients to the nearest VCTC.
TREATMENT
Early diagnosis and effective
treatment of TB among HIV-infected patients
are critical for curing TB, minimizing the
negative effects of TB on the course of
HIV and interrupting the transmission of
Mycobacterium tuberculosis to other persons
in the community. Even in the absence of
highly active anti-retroviral therapy, proper
case management of TB can significantly
prolong the lives of HIV positive persons
with tuberculosis.
Standard regimens of Revised
National Tuberculosis Control Programme
(RNTCP), particularly if supervised properly
are as effective in HIV positive as in HIV
negative patients. Further, treatment of
susceptible tuberculosis with first line
drugs is as effective to cure TB in people
infected with HIV as those not infected.
However, mortality under the TB treatment
will be higher for people living with HIV,
mainly due to other opportunistic infections.
Delays in the diagnosis of TB have been
associated with worse outcomes, so initiation
of treatment as soon as TB is suspected
is very important. Case fatality is lower
in HIV-infected TB patients treated with
short-course treatment than with the standard
12- month treatment regimens that do not
include rifampicin. This is partly because
short-course treatment is more effective,
but may also be related to the fact that
rifampicin has broad-spectrum antibacterial
activity. This may decrease deaths due to
HIV-related bacterial infections during
anti-TB treatment.
Direct observation of treatment is very
important for HIV- infected TB patients.
It has been reported that self-administration
of treatment is associated with higher case
fatality rates. Hence DOTS strategy that
promotes adherence to therapy should be
used for all patients with HIV- related
TB.
Relapse rate of TB is low in HIV-infected
TB patients who complete a full course of
directly observed rifampicin containing
short-course treatment regimen. The use
of non-rifampicin containing regimens and
treatment interruptions due to drug reactions
and inter-current opportunistic infections
are associated with an increased risk of
relapse of TB. The relapse rates tend to
be higher if they are treated with conventional
regimens or a short-course treatment regimen,
which uses isoniazid and ethambutol during
the continuation phase, or if the treatment
has not been directly observed.
Follow –
up of HIV – TB patients
Studies have shown high relapse rates
after completion of anti-TB treatment
in HIV/TB patients. In view of this,
it is advisable to have regular follow
up after completion of ATT to detect
relapse cases early and to reinstitute
appropriate anti-TB treatment.
Treatment Regimens for
Tuberculosis
Treatment
Category
Type of TB Patient
Regimen
IntensivePhase
ContinuationPhase
I
New smear positive pulmonary
TB
New smear negative, pulmonary
TB, seriously ill
New extra-pulmonary TB,
seriously ill
2(EHRZ)3(24 doses)
4(HR)3(54 doses)
II
Sputum smear positive relapses
Sputum smear positive treatment
failure cases
Sputum smear positive 'cases,
treatment after default
New smear negative, pulmonary
TB, not seriously ill
2(SEHRZ)3+I (EHRZ)3(24+
12 doses)
5(HRE)3(66 doses)
III
New smear negative, extra-pulmonary
TB, not seriously ill
2(HRZ)3(24 doses)
4(HR)3(54 doses)
Note: Prefix is number of months and
suffix is number of doses in a week H-Isoniazid
E-Ethambutol R-Rifampicin S-Streptomycin
Z-Pyrazinamide
The drugs are available in patient wise
boxes containing the full course of treatment
for the individual patient. Each box contains
two pouches -one for intensive phase and
the other for continuation phase. Drugs
are packed in blister pack; one blister
pack in intensive phase contains drugs for
a single day whereas for continuation phase,
each blister pack contains drugs for one
week. All the drugs are to be taken on alternate
days.
During the intensive phase all the doses
are to be swallowed under direct observation
(DOTS) whereas in continuation phase, the
patient takes the first weekly dose under
direct observation and the remaining drugs
for the week are to be consumed at home.
Follow up sputum examination is done at
the end of the intensive phase to decide
on the further course of treatment. If the
sputum remains positive for AFB, the intensive
phase drugs are continued for another one
month before starting the continuation phase.
Duration of therapy
Treatment-regimens recommended under RNTCP
are the same irrespective of patient's HIV-status.
The duration of therapy will be as per treatment
regimen and category. If required, duration
of therapy may be extended within the current
RNTCP guidelines.
Treatment in Special Situations
Hospitalization: Generally,
patients with PTB do not need hospitalization.
Those who are extremely ill can be hospitalized
during the initial phase of treatment.
In addition, all patients with significant
haemoptysis, pneumothorax or large accumulation
of pleural fluid leading to breathlessness
should be referred to the hospital.
Extra pulmonary TB: The
basic principles that support the treatment
of extra pulmonary TB in HIV uninfected
individuals also apply to HIV infected
patients. Most extra pulmonary forms of
TB (including TB meningitis, TB lymphadenitis,
pericardial TB, pleural TB, and disseminated
or miliary TB) are more common among persons
with advanced stage HIV disease than among
patients with asymptomatic HIV infection.
The drug regimens and treatment durations
that are recommended for treatment of
extra-pulmonary TB in HIV negative persons
are also recommended for treating HIV
positive patients. But if the clinical
or bacteriologic response is slow, treatment
may be prolonged as mentioned previously.
Also, in TB meningitis, a longer duration
of treatment is recommended as discussed
next.
Tuberculous meningitis: Tuberculous
meningitis is fatal if untreated. Patients
should generally be referred to the hospital,
and treatment should be started as soon
as possible.
The continuation phase should be given
for 6-7 months (total treatment 8-9 months).
Steroids should be given initially to
reduce meningeal inflammation and reduced
gradually.
Pregnancy: HIV-infected
pregnant women who have tuberculosis or
are suspected of having TB disease should
be treated without delay. Streptomycin
should not be given during pregnancy because
of potential adverse effects on the foetus.
Other drugs used in the RNTCP are safe
during pregnancy. In patients on concomitant
ARV efavirenz should be avoided in view
of its teratogenicity.
DOTS
(Directly observed treatment, short course strategy)
can prevent emergence of MDR -TB and also will reverse
the trend of MDR- TB.
Failure to use DOTS can
lead to explosive spread of TB and rapid
increase in drug resistance. Tuberculosis
treatment following the DOTS strategy should
be initiated promptly in diagnosed HIV infected
cases of TB.
Treatment in the RNTCP
(Revised National TB Control Programme)
consists of 2 phases - an initial intensive
phase and a continuation
phase. The total duration of treatment is
6- 9 months. Sputum microscopy is done regularly
to monitor the response to treatment.
The intensive phase lasts
for 2-4 months. In this phase, a health
worker or some other trained person watches
as the patient swallows the drugs in his/her
presence. Treatment is given thrice a week
on alternate days and every dose is directly
observed.
The continuation phase lasts for 4-5 months
depending on the patient's response to treatment.
In this phase, the first dose of the medicine
every week is taken by the patient under
direct observation, while the other 2 doses
are taken by the patient himself. The patient
is requested to bring the previous week's
blister pack when coming to collect the
next week's blister pack.
It is important that the patient takes
regular and complete treatment in order
to ensure complete cure and prevent
development of drug-resistant TB. Treatment
of multi-drug resistant TB is extremely
difficult, expensive and often unsuccessful.
ANTI
TUBERCULOSIS THERAPY AND ANTI RETROVIRAL THERAPY
Till date no cure is available for HIV/AIDS.
However antiretroviral drugs are effective
in reducing viral replication and prolonging
life. These drugs fall into the following
three groups. (i) Nucleoside reverse transcriptase
inhibitors (NRTIs); (ii) Non-nucleoside
reverse transcriptase inhibitors (NNRTIs);
(iii) Protease inhibitors (PIs).
Some of the ARVs have adverse drug interactions
with ATT, therefore, appropriate drug choices
becomes imperative. Nucleoside reverse transcriptase
inhibitors like zidovudine, didanosine,
zalcitabine, stavudine, lamivudine and abacavir
can be safely co-administered with antituberculosis
drugs.
Co-administration of Rifampicin with protease
inhibitors (ritonavir, indinavir, nelfinavir)
or non-nucleoside reverse transcriptase
inhibitors (nevirapine, delavirdine, thioben)
is contraindicated. Protease inhibitors
and non-nucleoside reverse transcriptase
inhibitors may inhibit or induce cytochrome
P-450 isoenzymes and thus these drugs may
alter the serum concentration of rifamycins.
Rifamycins induce cytochrome P-450 and may
substantially decrease blood levels of the
antiretroviral drugs resulting in the potential
development of resistance. Rifabutin is
a less potent cytochrome-450 inducer than
rifampicin and thus can be used concurrently
with the NNRTIs (eg nevirapine, efavirenz)
or with certain protease inhibitors (eg
indinavir, nelfinavir). Rifabutin is at
present not available in India.
Isoniazid, Ethambutol, Pyrazinamide and
Streptomycin can be concurrently used with
protease inhibitors or non-nucleoside reverse
transcriptase inhibitors.
If a protease inhibitor or non-nucleoside
reverse transcriptase inhibitor is to be
started after giving Rifampicin, then at
least two weeks should elapse after the
last dose of Rifampicin. This time gap is
necessary for reduction of the enzyme inducing
activity of Rifampicin prior to commencement
of antiretroviral drugs.
ATT for patients
on ART
If patients already on ART develop active
TB then either the ART regimens should be
suitably modified to be compatible with
RNTCP regimens, or a non-rifampicin based
regimen should be used. However ART should
not be discontinued because of concerns
of development of drug resistance.
Investigations
for liver and renal functions together with
blood sugar and serum lipid levels would
have to be done at baseline and at periodic
intervals to detect drug induced toxicity
early. Pregnancy test would be done at baseline
and at periodic intervals for women who
are on efavirenz treatment and in the child
bearing age. Baseline CD4/CD8 counts and
if possible HIV viral load tests should
be done at baseline and at 6 monthly intervals
to monitor the response to anti-retroviral
therapy.
Immune Reconstitution
syndrome
For many opportunistic infections, including
TB, there can be a transient worsening of
symptom 2-3 weeks after the initiation of
ART. This is called the immune reconstitution
syndrome. For patients with TB, this syndrome
has been reported to occur in as many as
30% of cases on ART in the developed world.
The syndrome is characterized by fever,
lymphadenopathy, worsening pulmonary lesions
and expanding lesions of the central nervous
system (CNS). These reactions are typically
self-limiting, although they may require
the use of a brief course of cortocosteroids
in order to reduce inflammation of CNS or
severe respiratory symptoms. The initiation
of ART can also unmask previously undiagnosed
infections by augmenting the inflammatory
response. In general, ART should not be
interrupted if the immune reconstitution
syndrome occurs.
WHO Recommendations
WHO recommends that people with TB/HIV complete
their TB therapy prior to beginning anti-retroviral
treatment unless there is a high risk of
HIV disease progression and death during
the period of TB treatment (i.e., a CD4
count <200/mm3 or the presence of disseminated
TB). In cases where a person needs TB and
HIV treatment concurrently, first line treatment
options include ZDV/ 3TC (lamivudine) or
d4T (Stavudine)/3TC plus either an NNRTI
or ABC (Abacavir). If an NNRTI-based regimen
is used, EFZ (Efavirenz) would be the preferred
drug as its potential to aggravate the hepatotoxicity
of TB treatment appears less than with NVP
(Nevirapine). Except for SQV/r (Saquinavir/low
dose ritonavir). PIs are not recommended
during TB treatment with rifampicin due
to their interactions with the latter drug.
Antiretroviral
Therapy for Individuals with Tuberculosis
(WHO Recommendations- June 2002)
Situation
Recommendations
Pulmonary
TB and CD4 count < 50/ mm3
or extrapulmonary TB
Start TB therapy. Start one
of these regimens as soon as
TB therapy is tolerated:
ZDV/3TC/EFZ**
ZDV/3TC/ABC
ZDV/3TC/SQV/r
ZDV/3TC/NVP*
Pulmonary
TB and CD4 50-200/ mm3 or total
lymphocyte count < 1200/mm3
Start TB therapy. Start one
of these regimens after 2 months
of TB therapy:
ZDV/3TC/EFZ**
ZDV/3TC/ABC
ZDV/3TC/SQV/r
ZDV/3TC/NVP*
Pulmonary
TB and CD4 > 200/mm3 or total
lymphocyte count > 1200/mm3
Treat TB. Monitor CD4 counts
if available. Start ART when indicated
after ATT is completed.
*NVP is advised only in patients without
other options because rifampicin reduces
drug exposure to nevirapine by 31% and dose
adjustments for NVP co-administered with
rifampicin has not been established.
**In HIV-infected pregnant women who have
tuberculosis, efavirenz is contraindicated
due to its teratogenicity.
HIV
AND TUBERCULOSIS IN PAEDIATRIC PATIENTS
The guidelines for management of TB in children
are the same as that in adults except that
ethambutol should not to be given in young
children, as they may not be able to report
any diminution of visual acuity.
Active tuberculosis should generally be treated
before ART is begun. CD4+ T cell measurements,
when available, should be performed after
resolution of acute infection. Tuberculosis
is often presumptively diagnosed in children
in resource poor countries because of general
difficulties of diagnosis in children. In
HIV infected children being treated for proven
or presumptive tuberculosis, ART should generally
be deferred until anti tuberculosis therapy
has been in progress for at least two months,
and if deemed safe, until the completion of
all anti-tuberculous therapy This is to avoid
interactions with rifampicin and possible
decreased adherence to ART and tuberculosis
medications because of the number of drugs
that have to be administered.
If an HIV infected child with tuberculosis
has significant HIV symptoms and/or severe
immunodeficiency and requires the initiation
of ART, the considerations about the choice
of regimen are similar to those for adults,
and include a triple NRTI regimen (AZT+3TC+ABC)
or a regimen of two NRTIs and efavirenz,
an NNRTI, in children over 3 years. There
are advantages in starting therapy using
triple NRTI consisting of ABC, ZDV and 3TC
because of the frequency of suspected, empirically
treated or proven tuberculosis disease in
HIV infected children in resource limited
settings and the lack of interactions of
this combination of ARVs with anti-tuberculous
medications. Efavirenz should be used only
for those aged over three years because
pharmacokinetic data for younger children
is not availlable.
INH Chemoprophylaxis for
TB & other issues
Preventive therapy for TB (i.e. treatment
of latent TB) reduces the risk of development
of active TB in HIV infected individuals,
although the durability of this effect may
be limited by high rates of re-infection
with TB in high TB burden countries like
India.
WHO recommends TB preventive therapy if
possible in areas where diagnostic testing,
such as chest X-rays, is available to exclude
active TB and where PPD skin testing is
feasible. In such situations, isoniazid
therapy (with pyridoxine supplementation)
for 6 months in tuberculin skin test reactors
could be given after exclusion of active
disease.
In India however, the issue of INH prophylaxis
is complicated due to the following reasons:
Difficulty in excluding active TB disease
in those with HIV/TB co-infection
In a country like India where the burden
of TB is high, chemoprophylaxis may not
prevent the reinfection.
Widespread use of INH for chemoprophylaxis
may contribute to an increase in INH resistance.
PPD skin test may not be feasible and
is also not reliable in severely immuno-compromised
patients
BCG Vaccination
Vaccination with BCG in HIV patients is
effective in preventing the progression
of infection with M. tuberculosis to TB
disease provided it is given before infection.
But complications from vaccination have
been reported as mycobacterial meningitis,
cervical, axillary lymphadenopathy and disseminated
BCG disease. WHO does not recommend BCG
for children who show symptoms of HIV but
recommends vaccination of healthy infants
of HIV infected mothers. If some complication
does occur, it can be treated with anti-TB
treatment.
Operational Research
Research should form an important part of
the planning and implementation of collaborative
HIV and TB programme activities. An operational
research approach to the planning and management
of HIV/TB programme collaboration and/or
integration at central and district levels
should be an integral part of the work-plan
for collaborative HIV and TB activities.
Innovative approaches for HIV and TB are
needed, and wherever possible HIV and TB
programmes should work together with research
institutes to encourage relevant basic science
research and clinical trials to provide
much needed new HIV/TB diagnostic tools
and therapies.
Action Plan For
HIV-TB Programme Co-ordination
The basic purpose of HIV-TB coordination
is to ensure optimal synergy between the
two programmes for the prevention and control
of both diseases. Key areas include:
Commitment to HIV-TB coordination,
through sensitization;
Service delivery coordination and cross-referral,
through training, provision of additional
services, and coordination at the local
level;
Optimal and comprehensive use of the
community reach of both programmes through
the sensitisation and involvement of NGOs
and private practitioners who are involved
in both programmes;
Infection control to prevent spread
of TB in facilities caring for HIV-infected
persons, and to prevent spread of HIV
through safe injection practices in the
RNTCP;
Joint efforts at IEC particularly with
regard to de-stigmatisation, TB being
treatable; HIV being preventable; DOTS
prolongs life of HIV infected persons
and ensuring confidentiality of HIV- and
TB-related information.
Monitoring and evaluation at district,
State and National level to assess the
co-ordination between both these programmes.
In Phase I of the programme, coordination
was started initially in the six states
with high prevalence of HIV/AIDS i.e. Andhra
Pradesh, Tamil Nadu, Karnataka, Maharashtra,
Manipur and Nagaland.
Phase II of the
programme to extend to eight additional
States of Delhi, Gujarat, Himachal Pradesh,
Kerala , Orissa, Punjab, Rajasthan and West
Bengal.
Main Components
of the Action Plan
Sensitisation
of State key policy-makers to address
the importance of HIV-TB co-ordination
To present the facts about morbidity,
mortality and socio-economic consequences
of HIV, TB, and the interaction between
HIV and TB
To emphasize that HIV is preventable,
TB is curable, DOTS prolongs life of HIV-infected
persons and stops the spread of TB, and
that HIV prevention is essential to the
control of tuberculosis
Areas for coordination and commitment
and plan to coordination on the part of
both programmes.
Key policy makers at the State level may
include State Secretaries (Health, Medical
Education); Director Health Services; Representatives
from Professional Organizations, CII, FICCI;
State Project Directors NACP and State TB
Officers, NTCP; Municipal Corporation Representatives;
Director ESI Hospitals, Railways and; Key
NGOs of AIDS and RNTCP programme working
at state and regional level
2. Service Delivery
co-ordination and cross-referral:
through training, provision of additional
services, and coordination at the local
level.
2.a. Training Programme for service providers
involved in RNTCP and NACP
Staff of NACP to understand and be
able to apply principles of diagnosis,
treatment, monitoring, and reporting under
RNTCP;
Staff of RNTCP to understand and be
able to apply principles of HIV prevention
and AIDS control, and specific concerns
about diagnosis of TB in HIV-infected
persons (e.g., extra-pulmonary and atypical
presentations), about TB treatment in
HIV-infected persons, and about the need
for confidentiality;
Infection control to prevent further
spread of TB and HIV infection
Service providers under NACP to include:
District Nodal Officers-AIDS, medical officers
in charge of VCTCs and counselors. In those
VCTCs where facilities for sputum microscopy
do not exist within the same campus, the
VCTC laboratory technician to be trained
in sputum microscopy and the microscope
to be provided by the SACS.
Service providers under RNTCP to include:
District TB Officers, Medical Officer-District
TB Center and Tuberculosis unit, supervisory
staff under the RNTCP, medical and para-medical
staff of the CHC, PHC, TB sanatorium.
2.b. VCTC-RNTCP
Co-ordination
To provide facilities for diagnosis
and treatment of HIV-TB cases under the
same roof
To ensure that all VCTC staff are aware
of the importance of TB, know the need
to ask patients about cough, and refer
patients with cough for diagnosis and
treatment, preferably at the same place.
To ensure that RNTCP staff know where
to refer TB patients who desire HIV counseling
and testing.
To have a system in place whereby the
number of referrals made is monitored,
e.g., number of patients started on RNTCP
treatment as a result of referral from
VCTC.
3. Sensitization
of NGOs and private practitioners working
for NACP and RNTCP
To present the facts about morbidity,
mortality and socio-economic consequences
of HIV, TB, and the interaction between
HIV and TB
To emphasize that HIV is preventable,
TB is curable, that DOTS prolongs life
of HIV-infected persons and stops the
spread of TB, and that HIV prevention
is essential to the control of tuberculosis
Involve NGOs and private practitioners
participating in NACP in the RNTCP;
Involve NGOs and private practitioners
participating in RNTCP in the NACP.
4. Infection control
Prevent spread of TB in facilities
caring for HIV-infected persons: Issue
guidelines on prevention of spread of
TB in facilities caring for HIV-infected
persons;
Prevent spread of HIV through safe
injection practices in the RNTCP: Disseminate
guidelines on standard operating procedures
for hospital infection control to RNTCP
sites
5. Information, Education, and
Communication
Create greater awareness of means by
which HIV is and is not spread among health
providers and TB patients,
Create greater awareness of symptoms
of TB including extra-pulmonary TB cases
and about atypical presentations of TB
among staff and clients of NACP,
Generate awareness of the importance
of HIV/TB interaction and commitment to
greater coordination in staff of the two
programmes.
6. Monitoring and Evaluation of
co-ordination of both the programmes:
To assess the co-ordination between
these two national programmes
To disseminate the findings and observations
among the program managers and service
providers
To discuss the problems faced in the
field and to find out solutions
To further strengthen the co-ordination
District and State co-ordination committees
should be formed to review the programme
on a regular basis. National review of the
programme should take place at 6 monthly
intervals.
Operationalisation of treatment
services for HIV-TB patients
To reduce mortality in HIV/TB co-infection;
To prevent the further spread of infection;
To reduce relapses;
To prevent the development and spread
of drug resistant tuberculosis;
Thiacetazone never to be used in HIV-infected
tuberculosis patients or in those at risk
of HIV-infection;
In RNTCP areas, hospitalization to
be restricted to medically essential cases;
In RNTCP areas, where hospitalization
is done, length of stay should be kept
to a minimum, generally no more than 2
weeks and only more than 4 weeks when
medically crucial.
To be done:
a) For outdoor patients in RNTCP areas;
drug supply will be as per RNTCP policies,
with supply provided by the DTC so that
the patient can receive directly observed
treatment from the most conveniently located
DOTS centre
b) For indoor patients in RNTCP areas:
i. If patient is from TB Unit where the
facility is located, drug supply will be
via patient-wise box supplied by the DTC.
Upon discharge, it must be ensured that
the patient and the patient-wise box are
transferred to the appropriate DOTS centre
most convenient to the patient;
ii. If the patient is from another TB Unit
within the district, local arrangements
will be made to either provide treatment
via patient-wise box, or to provide SCC
treatment for 2 weeks or less and unless
medically crucial no more than 4 weeks,
then to transfer the patient to the concerned
TB unit. If SCC treatment has been used,
the concerned unit will start a fresh box
irrespective of previous SCC treatment while
hospitalization; if a patient-wise box was
opened, this must be transferred with the
patient. If the patient must remain indoors
for more than 1 month, then an RNTCP treatment
box should be opened and the patient and
the patient-wise box should be transferred
to the respective area when the patient
is discharged.
c) For outdoor patients in non-RNTCP, SCC
areas: the SCC regimen should be given.
Medicines will be provided from the District
Tuberculosis Centre. Whenever possible,
direct observation of treatment for the
first two months should be done, as this
has been shown to decrease mortality, drug
resistance, and relapse, particularly in
HIV-infected tuberculosis patients.
d) For outdoor patients in non-RNTCP, non-SCC
areas: NACO budget could be used to procure
drugs for this important opportunistic infection,
as per the regimen above. Whenever possible,
direct observation of treatment for the
first two months should be done, as this
has been shown to decrease mortality and
drug resistance, particularly in HIV-infected
tuberculosis patients.
e) For indoor patients in non-RNTCP areas:
Treatment should be with daily short-course
chemotherapy for 2 months followed by
6 months of isoniazid and ethambutol (2HRZE
/ 6HE).
Drug supply should be available with
the facility from usual sources. In case
drugs are not available, drug supply will
be via the DTC if this is an SCC district.
NACO budget could be used to procure drugs
for the important opportunistic infection,
as per the regimen above.
