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American Journal of Infectious Diseases 2 (4): 210-218, 2006
ISSN 1553-6203
© 2006 Science Publications
Corresponding Author: Sarder Nasir Uddin, Assistant Professor, Biotechnology and Genetic Engineering Discipline,
Khulna University, Bangladesh
210
Consequence on Treatment of TB Patients Affected by HIV/AIDS
A Conceptual Research
1Sarder Nasir Uddin, 1S.J.Hossain, 1Md. N. Huda, 1M.H. Rahman and 2Md Eunus Ali
1Biotechnology and Genetic Engineering Discipline, Khulna University, Bangladesh
2Pharmacy Discipline, Khulna University, Bangladesh
Abstract: Mycobacterium tuberculosis is an ancient malady, which is one of the world’s most wide
spread infectious bacterial agents. Fully one-third of the world’s population is already infected with
Mycobacterium tuberculosis, with the greatest burden of disease and infection borne by people in
developing countries. Tuberculosis disease is still out of control. Alarming spread of Human
Immunodeficiency Virus (HIV) and emergence of drug resistance is now further complicating the
major problem. HIV not only makes the diagnosis of TB more difficult; it contributes to an increase in
TB incidence. The rate of breakdown to clinical TB in individuals infected both with HIV and
tuberculosis is many times higher than in those without HIV. The present vaccine is not sufficient to
reduce the death rate by eradicating TB with HIV/AIDS. The present review is based on the prevention
and treatment of TB patient and co-infected with HIV/AIDS and effect of HIV/AIDS on the treatment
and prevention of TB. It will help assuming idea about future steps in prevention and treatment of TB
among HIV/AIDS patients.
Key words: TB, HIV, AIDS, patients
INTRODUCTION
Tuberculosis is an increasing and major worldwide
problem, especially in Africa where AIDS facilitates
the spread. It is estimated that nearly 1 billion people
will become newly, over 150 million will become sick
and 36 million will die worldwide between now and
2020 if control is not further strengthened. Each year
there are more than 8.7 million cases and close to 2
million deaths attributed to TB; 100,000 of those 2
million deaths occur among children. In the 1940s,
scientists discovered the first of several drugs now used
to treat TB. As a result, TB slowly began to disappear
in the United States. But TB has come back between
1985 and 1992, the number of TB cases increased. The
country became complacent about TB and funding to
TB problems was decreased. However, with increased
funding and attention to the TB problem, we have had a
steady decline in the number of persons with TB. But
TB is still a problem; more than 16,000 cases were
reported in 2000 in the United States[1,2].
Projections of the future toll of the global TB
pandemic are even more frightening. Currently, it is
estimated that less than halves of all TB cases
worldwide are diagnosed and fewer than 60 percent of
diagnosed cases are cured[3] Without unprecedented
efforts to improve TB control in regions hardest hit by
the disease, incidence is expected to climb steadily[4].
Tuberculosis will remain one of the world’s top ten
causes of adult mortality in the year 2020[5].
Since AIDS was first described in the United
States, this country has majority of this reported cases
and now a day it has been reported from more than 163
countries around the world and the pool of HIV-
infected person in Africa and Asia is large and
expanding[6]. There are some encouraging data which
suggests that rapid increase in HIV prevalence have
been observed in India, Vietnam, Myanmar (Burma)
and South Africa and it is predicted that South Africa
will experience one of the worst epidemics in Africa.
The World Health Organization (WHO) estimated that,
at the end of 1997; 30.6 million people worldwide were
living with HIV/AIDS of which over 90% were in
developing countries, two thirds in sub-Saharan
Africa[7].
From the United States, the epidemiological data
suggest that the adults developing AIDS may be
classified into five groups[6].
* Homosexual or bisexual males constitute by far the
largest group, accounting for 60% of the reported
cases. This also includes the 5% who were
intravenous drug abuser.
* Intravenous abusers with no previous history of
homosexuality compose the next largest group,
which represents about 23% of all the patients.
This group represents the majority of all cases
among heterosexuals.
* Hemophiliacs, especially those, who received large
amount of factor VIII concentrates before 1985,
make up 1% of all cases.
Am. J. Infect. Dis., 2 (4): 210-218, 2006
211
* Recipients of blood and blood components who are
not hemophiliacs but who received transfusions of
HIV-infected whole or components; for example
platelets, plasma account for 2% of the patients. On
the contrary, organs obtained from HIV-infected
donors can also transmit AIDS.
* Heterosexuals’ contacts members of other high-risk
groups (chiefly intravenous drug abusers)
constitute 6% of the patient population.
In approximately 6% of cases, risk factors cannot
be determined. The pediatric population comprises 2%
of all AIDS cases. The remaining 20% are
hemophiliacs and others who have a history of
reception of bloods or blood products before 1985[6].
At least one in every three HIV-positive adults
worldwide is latently infected with the TB bacillus, but
not actively sick with TB and not infectious to others.
TB-prevalence therapy is aimed at preventing
progression from latent disease to active TB. The
World Health Organization supports the introduction of
TB-preventive therapy, specifically, six months of
isoniazid daily for the benefit of people co-infected
with HIV and the TB bacillus in countries where
national HIV/AIDS programs are able to supply
adequate HIV counseling and testing facilities and
those that have well-functioning DOTS program[8].
TB and HIV/AIDS
Evidence for an association between TB and HIV[9]:
Studies show that there is a close association between
HIV and tuberculosis, one potentiating the impact of
the other. The evidence for this interaction includes the
following observations:
i. The areas that have been most affected by the HIV
epidemic also report the greatest increases in TB
cases;
ii. The largest increase in TB cases has occurred
among people aged 25-44 years, the age group
most affected by AIDS;
iii. TB is a common opportunistic infection among
AIDS patients (between 60% -75% of AIDS
patients in the Region will develop TB) and
iv. HIV prevalence among TB patients is higher than
that in the general population. For example, rates
of up to 40% have been seen among TB patients
compared to 8% among antenatal clinic attendees
in Northern Thailand[10].
Capathogenicity of TB and HIV disease: Human
immunodeficiency virus type 1 (HIV-1) and M.
tuberculosis are two intracellular pathogens that interact
at the population, clinical and cellular levels. Initial
studies of HIV-1 and TB emphasized the impact of
HIV-1 on the natural progression of TB, but mounting
immunologic and virologic evidence now indicates that
the host immune response to M. tuberculosis enhances
HIV replication and might accelerate the natural
progression of HIV infection[11]. Therefore, the
interaction between these two pathogens has important
implications for the prevention and treatment of TB
among HIV-infected persons. Studies of the immune
response in persons with TB disease support the
biologic plausibility of copathogenesis in dually
infected persons. The initial interaction between the
host immune system and M. tuberculosis occurs in the
alveolar macrophages that present mycobacterial
antigens to antigen-specific CD4+ T cells[12]. These T
cells release interferon-gamma, a cytokine that acts at
the cellular level to activate macrophages and enhance
their ability to contain mycobacterial infection. The
activated macrophages also release proinflammatory
cytokines, such as tumor necrosis factor and
interleukin-1, cytokines that enhance viral replication in
monocyte cell lines in vitro[13]. The mycobacteria and
their products also enhance viral replication by
inducing nuclear factor kappa-B, the cellular factor that
binds to promoter regions of HIV[14].
When TB disease develops in an HIV-infected
person, the prognosis is often poor, though it depends
on the person's degree of immunosuppression and
response to appropriate antituberculosis therapy[15]. The
1-year mortality rate for treated, HIV-related
tuberculosis ranges from 20% to 35% and shows little
variation between cohorts from industrialized and
developing countries[16]. The observed mortality rate for
HIV-infected persons with TB is approximately four
times greater than the rate for TB patients not infected
with HIV[16]. Although the cause of death in the initial
period of therapy can be TB[17]. Death after the
induction phase of anti-tuberculosis therapy usually is
attributed to complications of HIV other than TB[18].
Epidemiologic data suggest that active TB accelerates
the natural progression of HIV infection. In a
retrospective cohort study of HIV-infected women from
Zaire, investigators estimated the relative risk of death
to be 2.7 among women with active TB compared with
those without TB[19]. In a retrospective cohort study of
HIV-infected subjects from the United States, active TB
was associated with an increased risk for opportunistic
infections and death[15]. The risk of death, or hazard
rate, for persons with HIV-related TB follows a
bimodal distribution, peaking within the first 3 months
of antituberculosis therapy and then again after 1
year[11]; the reasons for this distribution are not clear but
might relate to the impact of TB on HIV disease
progression. The observation that active TB increases
deaths associated with HIV infection has been
corroborated in studies of three independent cohorts in
Europe[7].
Early in the HIV epidemic, researchers postulated
that the immune activation resulting from concurrent
infection with parasitic or bacterial pathogens might
alter the natural progression of HIV infection[20].
Subsequent observations have demonstrated that
immune activation from TB enhances both systemic
Am. J. Infect. Dis., 2 (4): 210-218, 2006
212
and local HIV replication. In some patients with active
TB, the plasma HIV RNA level rises substantially
before TB is diagnosed[14]. Moreover, TB treatment
alone leads to reductions in the viral load in these
dually infected patients. TB and HIV also interact in the
lungs, the site of primary infection with M.
tuberculosis. In a recently published study of HIV-
infected patients with TB, researchers found that the
viral load was higher in the bronchoalveolar lavage
fluid from the affected versus the unaffected lung and
was correlated with levels of tumor necrosis factor in
bronchoalveolar fluid[21]. Researchers used V3 loop
viral sequences to construct a phylogenetic tree and
observed that the HIV quasispecies from the affected
lung differed from those in the plasma within the same
patient. These data suggest that pulmonary TB might
act as a potent stimulus for the cellular-level replication
of HIV. In summary, recent research findings have
improved clinicians' understanding of how HIV affects
the natural progression of TB and how TB affects the
clinical course of HIV disease and these findings
support the recommendation for prevention, early
recognition and effective treatment for both diseases.
HIV and TB alter each other pathogenesis and
natural course: The pathogenesis of both tuberculosis
infection and the disease relates directly to cell-
mediated immunity (CMI). Especially CD4+ T-
lymphocytes. Not surprisingly, HIV infection which
induces CD4+ T-lymphocytes depletion, also leads to
defective immunological response to M. tuberculosis.
the pathogenesis of TB can be altered by HIV either
through reactivation of latent tuberculosis infection to
active disease (more common) or by causing rapid
progression from recent infection with M. tuberculosis
to tuberculosis disease[10]. Findings from several
studies suggest that active TB may accelerate HIV-
induced immunological deterioration. The evidence is
as follows:
* Active TB is associated with transient CD4+ T-
lymphocyte depletion;
* TB cause immune stimulation and increased
production of cytokines, such as tumour necrosis
factor (TNF) which increases HIV replication in
vitro and
* HIV-infected persons with TB appear to have a
higher risk of opportunistic infections and death
than do HIV-infected patients with similar CD4+
T-lymphocyte counts but without TB[10].
The clinical features of TB more commonly seen in
HIV-positive individuals:
* As HIV infection progresses, CD4+ lymphocytes
decline in number and function. Therefore, the
immune system is less able to prevent the growth
and local spread of M. tuberculosis. As a result,
disseminated and extra-pulmonary disease is more
commonly seen. Nevertheless, pulmonary TB is
still the most common from of TB even in HIV-
infected patients. Many studies reveal that
pulmonary involvement occurs in 70-90% of all
patients with TB.
Pulmonary TB: The presentation of pulmonary TB
depends on the degree of immune suppression. The
Table 1 shows how the clinical features, results of
sputum smears and chest X-ray appearance differs in
early and late HIV infection. In advanced HIV
infection, the presence of many opportunistic infectious
affecting the lungs may cause difficulties in the
diagnosis of TB. The occurrence of hilar and
mediastinal adenopathy by chest X-ray can also suggest
the diagnosis of TB in an HIV-infected patient[10].
Extra-pulmonary TB: The most common forms of
extra-pulmonary involvement include
lymphadenopathy, pleural effusion, pericardial disease,
military disease and meningitis, cervical,
supraclavicular and auxiliary lymphnodes are the most
common sites of peripheral lymphadenitis.
Percutanaous needle aspiration of the lymph nodes can
be useful in establishing the diagnosis[10].
HIV infection influences the diagnosis of TB: In most
cases, the clinical presentation of tuberculosis among
patients with HIV is indistinguishable from other cases.
However, some may show a bizarre pattern with a
higher proportion of cases tending to have a negative
sputum smear. In spite of that, sputum smear
examination remains an essential component in the
diagnosis of tuberculosis in countries where HIV
infection is common because of its ability to identify
infectious cases.
The diagnosis of TB in HIV-positive patients is more
difficult for three main reasons:
* Proportion of HIV-positive patients with
pulmonary TB will have positive sputum smears;
* X-ray abnormalities, which are not specific for TB
in HIV-negative patients, are even more non-
specific in HIV-infected with only minor
abnormalities on chest X-ray or with abnormalities
which do not look like classical TB and
* Patients infected with have frequent illnesses with
pulmonary involvement caused by agents other
than M. tuberculosis[10].
Treatment of TB patients affected by HIV/AIDS:
The response to anti-TB therapy is the same for HIV-
positive and HIV-negative TB patients. The only
exception is that thiacetazone is not recommended for
HIV-positive TB patients because it may increase the
risk of severe and sometimes fatal skin reactions;
Short-course treatment hastens cure and prolongs
survival in HIV-infected persons[22].
HIV-related immuno-suppression does not
interfere with the effectiveness of therapy for TB. Since
the management of TB and the response to standard
short course regimen is similar in patients with or
without HIV, there is no rationale for HIV tests in the
clinical settings from the patient management of view.
TB bacteria die very slowly.
Am. J. Infect. Dis., 2 (4): 210-218, 2006
213
Table 1: Clinical Features of Pulmonary TB in HIV- Siropositive Persons[10]
Features of Pulmonary TB Strategy of HIV Infection
----------------------------------------------------------------------------------------------------------------------
Early Late
Clinical picture Often resembles post-primary TB primary TB
Sputum smear result Often positive Often negative
Chest X-ray Often cavities are seen Often infiltrates with no cavity
Table 2: Possible alternative treatment regimens for each treatment category[10]
TB Treatment category Alternative TB Treatment Regimens
-------------------------------------------------------------------------------------------------------------------------
Initial Phase Continuation Phase
I 2 EHRZ (SHRZ)* 6HE*
2 EHRZ (SHRZ) 4 HR
2 EHRZ (SHRZ) 4 H3R3
II SHRZE/ 1 HRZE 5 H3R3E3
2 SHRZE/ 1 HRZE 5 HRE
III 2 HRZ 6 HE
2 HRZ 4 HR
2 HRZ 4 H3R3
IV Not applicable (Refer to WHO guidelines for use of second line drugs specialized centers)
* A standard code is used for each drug. For example, the regimens of 2 HRZE(S)/4 HR has two phases:
* The intensive phase (2HRZE) means daily treatment with a combination of four drugs for two months: isoniazid (H), rifampicin (R),
pyrazinamide (Z) and ethambutol (E). The last drug (E) and streptomycin (S) can be interchanged where either one or the other of two drugs
is available.
* The continuation phase (4HR) means daily treatment with isoniazid (H) and rifampicin (R) for four months.
For the regimen 2HRZE(S)/4H3R3, the abbreviation H3R3 means a treatment three times a week with both isoniazid and rifampicin.
Treatment, therefore, has to be taken for at least six
months, once treatments begin, the patient will
probably start feeling well after only a few weeks. But
the TB bacteria will still be alive in the body. The
patient must therefore continue to take medicine until
all the TB bacteria are dead, even though he or she feels
better and has no more symptoms of TB disease. It can
be very dangerous if the TB patient does not continue
taking the medicines or is not taking medicine
regularly. The TB bacteria will continue to multiply
again and the patient will remain sick for a longer time
and continue to infect others. The bacteria may also
become resistant to drugs and the most effective drugs,
which normally kill the TB bacilli, may therefore no
longer work. Other types of drugs that may be needed
to treat such patients are often much less effective,
more expensive, have to be taken for a longer duration
and usually have serious side-effects. Many patients
who develop drug-resistant tuberculosis may therefore
die from the disease[10].
There are many possible anti-TB treatment
regimens. The World Health Organization (WHO) and
the International Union against Tuberculosis and Lung
Disease (IUATLD) recommend standardized TB
treatment regimens (when used in combination for
more than one drug, called a “regimen”) are: Isoniazid
(INH or H), Rifampicin (R), Pyrazinamide (Z),
Ethambutol (E), Streptomycin (S), Thiacetazone.
Based on case-definition, a TB patient may fall into
any one of the following four categories for treatment.
The categories are numbered in order to priority. The
highest priority for treatment is Category 1 patients and
the lowest priority is Category 4:
Category I: New cases who are smear-positive, or
seriously ill patients who are smear- positive, or
seriously ill patients who are smear-negative or who
have extra-Pulmonary disease.
Category II: Re-treatment cases including patients
with relapse, treatment failure and those who turn to
treatment after default. Such patients are generally
Sputum-positive.
Category III: Patients who are sputum-negative, or
who have extra-pulmonary TB and are not seriously ill.
Category IV: Chronic cases still sputum-positive after
supervised re-treatment.
Treatment regimens usually comprise two phases:
the intensive phase and the continuation phase. There
are several possible regimens for treating each category
TB. Suggested alternatives are given in Table 2.
However, it is important to stress that in a given
country, the regimen recommended by the National TB
Program, which is described in the NTP Manual, should
be followed[10].
The risk of TB disease can be reduced by
preventive therapy, although the efficacy is not 100%
Am. J. Infect. Dis., 2 (4): 210-218, 2006
214
(range from 60%-90%). However, it is still not clear as
to how preventive therapy must be given[10].
In Malawi, smear-negative pulmonary tuberculosis
and extra-pulmonary tuberculosis are more common in
TB patients with HIV infection; 75% of TB patients are
HIV-positive.
Treatment outcomes depend on the HIV status,
type of TB and age group. HIV-infected patients had a
higher death rate than HIV-negative TB patients (60%
vs 6%) and one third of all HIV-positive patients and
half of the new HIV-positive smear-negative pulmonary
patients died during treatment. The reason for high
death rates in smear-negative patients is probably due to
incorrect diagnosis, as three are many operational
difficulties in resource-poor settings in Sub-Saharan
Africa[23].
247 consecutive HIV-infective patients with smear-
positive pulmonary or clinically confirmed
extrapulmonary tuberculosis were compared with 312
HIV-negative TB patients. Mortality during treatment
was higher in HIV-infected patients (6% vs 0.4%) and
was even higher (10%) in HIV-infected patients with
low (<200/µL) CD4+ lymphocyte counts[24].
Tuberculosis and HIV can be effectively treated
concomitantly, as long as appropriate dose adjustments
are made to account for drug-drug interactions.
Treatment of both diseases simultaneously appears to
result in a substantial improvement in morbidity and
mortality compared to treatment of tuberculosis alone.
Persons with HIV infection and TB usually can be
treated with standard anti-TB regimens with good
results, although in some cases, prolonged therapy may
be warranted. Patients with TB and HIV may also have
more rapid resolution of their TB if the HIV infection is
treated concurrently[25]. Therefore, it is important for
clinicians to be aware of the HIV status of their patients
with TB. Testing of persons with TB for infection with
HIV is an important intervention point for counseling
and testing for HIV infection and for administration of
antiretroviral therapy and prophylaxis for opportunistic
infections. Since treatment of HIV may require protease
inhibitors or nonnucleoside reverse transcriptase
inhibitors and TB therapy for persons receiving these
drugs may preclude the use of rifampin, this may lead to
alteration of the anti-TB regimen[8].
In the United States, 14% of persons with TB in
1993-1994 also were reported to have AIDS and in
some areas, HIV infection is seen in as many as 58% of
patients with TB[26]. While the rate of co infection
varies widely among different geographic areas,
clinicians are poor predictors of which patients are
likely to have HIV infection. Therefore, HIV testing is
recommended for and should be offered to all patients
with newly diagnosed TB. However, because not all
patients will accept HIV serologic testing, 80% rather
than 100% is the proposed performance indicator[27].
HIV-infected patients who received directly
observed, intermittent treatment were more likely to
complete treatment than were HIV infected patients
who received short-course chemotherapy without
directly observed treatment. HIV infected patients who
received directly observed treatment were also much
likely to survive (85% vs 57%, p=0.01). This improved
survival was found in multivariate as well as univariate
analysis[28].
The HIV epidemic caused an increase in the
notification rates of smear-positive tuberculosis in
adults. The study indicates that the presence of an
effective DOTS programme curtailed tuberculosis
transmission despite a substantial increase in TB due to
the HIV epidemic[29].
A study found that DOTS can prevent drug-
resistant TB in the context of a HIV epidemic in low-
income counties, but could not prevent the increase in
incidence of TB. This increase is likely due primarily to
reactivation of latent tuberculosis infection in HIV-
infected persons in this area where the prevalence of
HIV in the adult population exceeds 20%[27].
Directly observed treatment, short course (DOTS):
DOTS as the International Union against TB and Lung
Disease (IUTLD) pioneered a TB control strategy. The
DOTS strategy takes simple technology-the successful
components of TB control and packages it with good
management practices for widespread use. The strategy
can be easily integrated into general health services and
can therefore be widely used. How the DOTS strategy
is implemented varies from country to country and
within countries. The implementation of DOTS requires
flexibility in adapting the strategy according to local
circumstances. There are five key elements that are
considered essential for the implementation of the
DOTS strategy[10].
The principles of DOTS were first developed in the
national TB programme in Tanzania and subsequently
expanded to a further six countries in Africa and to
Nicaragua, with the assistance of IUTLD. The brand
name “DOTS” was born in 1994. Modifying the
commonly used DOT acronym to include another key
element of he strategy-the Short-course form “SCC”-
now gave meaning to “DOTS”[10].
The five major components of DOTS[10]:
i. Political commitment and resources: TB control is
a public health responsibility and top-down support is
crucial. This component must be the strongest link in
the chain.
Am. J. Infect. Dis., 2 (4): 210-218, 2006
215
ii. Microscopy: Accurate diagnosis using sputum-
smear microscopy among symptomatic patients is the
first step in early detection of active TB infection. It
sets the DOTS cure cycle in motion and protects others
from infection.
iii. Treatment: Standardized six-to eight-month
regimens for all patients with active TB, with Directly
observed treatment for at least the first two months, is
necessary. The Success of this phase is contingent upon
a sound, functional health-sector infrastructure and
trained personnel.
iv. Medicines: Regular, uninterrupted supplies of the
four to six most effective anti-TB drugs are essential.
Full compliance with the drug regimen results in nine
out of ten patients being cured.
v. Monitoring: A standardized recording and reporting
system allows assessment of each patient’s treatment
and progress. Rigorous overall record-keeping also acts
as early warning for emerging disease trends (such as
MDR-TB)[10].
Specialty about DOTS: DOTS cure active TB. It is
remarkably effective. Without treatment, seven in ten
people with infectious TB will die of he disease, on
average within four to five years of onset, even if they
are young when they contract the disease[30]. Though
non-DOTS considerably, such programs are usually
less successful at curing TB. Many sufferers remain
chronically ill and continue to unknowingly transmit
the disease to family, friends and even strangers.
Conversely, good DOTS programs rapidly reduce
both death and disease, curing more than 85 percent of
patients. In human terms, DOTS gives young people
marked for premature TB death a chance to lead full
and productive lives, raise children to adulthood and
make contributions to their communities and society.
Additionally:
i. DOTS saves lives: TB deaths during the period 2001-
2005, in addition to the 4.2 million lives saved through
ongoing DOTS expansion program. Even today, in
China alone DOTS Modeling suggests that achievement
of WHO’s 2005 target would avert 15.5 million has
prevented 46 percent of deaths that would otherwise
have occurred in the provinces in which the program is
being applied. This translates into 30,000 lives saved
each year[23].
ii. DOTS stops the chain reaction of transmission:
Curing people with TB prevents them from infecting
others. For example, introducing DOTS in Peru have
accelerated the decline in notified TB incidence to
about 7 percent per year[31].
iii. DOTS prevents treatment failure and the
emergence of even more deadly strains of drug-
resistant TB: For example, the China Tuberculosis
Coalition (CTC) reported that the failure rate in
Previously treated patients fell from 17.6 percent to 6.2
percent following the Introduction of DOTS in World
Bank-assisted provinces in China.
iv. DOTS reduces TB recurrence rate: For example,
in the U.S. state of Texas, TB recurrence rates fell from
20.9 percent to 5.5 percent within six years when a
DOTS-based TB-control strategy was introduced[32].
v. DOTS indirectly alleviates poverty: Saving lives,
reducing periods of illness and prevention of new
infections means Fewer years of productive work lost.
vi. DOTS overcome TB’s stigma: Effective treatment,
combined with a positive approach, reduces the fear of
death and disability that has fuelled the profound stigma
often associated with TB. In Nepal, for example, the
introduction of DOTS has led to a general awareness
that TB is curable. As a result, TB is now less feared,
no longer “Khapate”-the disease that “dries you up”
before you die.
vii. DOTS provides a model for strengthening health
services: Remarkably successful in promoting the
development of peripheral health services, the DOTS
strategy can serve as a model for expanded use of HIV
antiretrovirals, as proposed in Malawi[33]. If adaptations
of the DOTS strategy were shown to be effective in
AIDS treatment, networks linked to DOTS TB-
treatment programmed could rapidly be set up, given
that up to one-third of all AIDS patients die of
tuberculosis.
viii. DOTS save taxpayer’s money and lives: The
World Bank has hailed DOTS as “one of he most cost-
effective interventions available”. Country studies in
the early 1990s from Malawi, Mozambique and
Tanzania showed the cost of TB interventions ranging
from $19-52 per life saved. But drugs cost up to four
times as much at that time. Today, the DOTS drug
package can be purchased for as little as $10[34]. This
means that investing in TB control will save lives,
immediately. Over time, TB control will also “turn a
profit” as it reduces the disease burden on society.
BCG vaccination: A Bacillus Calmette Guerin (BCG)
is a live vaccine derived from an attenuated strain of M.
Am. J. Infect. Dis., 2 (4): 210-218, 2006
216
bovis and is named after the two doctors Calmette and
Guerin (1920) who discovered it. BCG is effective in
preventing disseminated form of TB in children;
efficacy is debatable against adult forms of TB. It is a
major component of global TB-control efforts.
BCG cannot be expected to prevent TB in HIV-
positive individuals since young adults usually acquire
HIV infection. As BCG is mainly given at birth in
developing countries, the immunity from it wanes by
the age of young adult; BCG cannot against the
exogenous re-infection of TB adults.
BCG is not safe in individuals with AIDS because
of the risk of disseminated BCG disease. Presently,
WHO and UNICEF recommended that, for a
symptomatic HIV-infected children living in areas
where the risk of tuberculosis is high, BCG still be
given at birth or as soon as possible thereafter in
accordance with standard childhood immunization
policies, but that it be withheld in infants thought to
have symptomatic HIV-infection.
The effectiveness of BCG in general, particularly
in developing countries where it is given at birth or less
than one year of age, is limited to protection against the
severe forms of TB in children. The degree of
effectiveness varies between 0 and 80% but the vaccine
is unable to prevent most contagious forms of TB in
adults.
Various approaches are being taken to prevent
infection and also, more speculatively, to prevent re-
activation of patients already infected. These
approaches include DNA vaccines, recombinant BCG
and other live vectors, attenuated M. tuberculosis, lipid
antigens and relatively simple secreted antigens[34].
Adverse reactions are generally more common in
HIV-positive than in HIV-negative TB patients. Most
reactions occur in the first two months of treatment.
Skin rash and hepatitis are more common and most
often attributed to rifampicin. The usual drug
responsible for fatal skin reaction such as exfoliative
dermatitis, Steven-Johnson syndrome and toxic
epidermal necrolysis is thiacetazone. Therefore,
thiacetazone should never be given to HIV-positive TB
patients. From a programmatic point of view,
thiacetazone should not be prescribed in areas where
HIV prevalence is shown to be high[10].
CONCLUSION
Autopsy studies have shown that TB accounts for
up to one-third of AIDS deaths[35]. Controlling TB in
high HIV prevalence areas will require, first of all, a
highly effective DOTS program. The DOTS expansion
plans include cost estimates for building and sustaining
successful programs in all high-burden countries,
including countries with high HIV-infection rates. Once
DOTS programs are well established in high HIV-
prevalence countries, they will likely need to be
supplemented with active case-finding initiatives for
co-infected patients. The strategy has been successfully
demonstrated also among HIV-positive TB patients,
with increased completeness of therapy and improved
patient survival[8]. All HIV-infected persons at risk for
infection with M. tuberculosis must be carefully
evaluated and if indicated, administered therapy to
prevent the progression of latent infection to active TB
disease and avoid the complications associated with
HIV-related TB. All HIV-infected patients undergoing
treatment for TB should be evaluated for antiretroviral
therapy, because most patients with HIV-related TB are
candidates for concurrent administration of
antituberculosis and antiretroviral drug therapies.
However, the use of rifampin with protease inhibitors
or non-nucleoside reverse transcriptase inhibitors is
contraindicated[36].
Ideally, the management of TB among HIV-
infected patients taking antiretroviral drugs requires a)
directly observed therapy, b) availability of experienced
and coordinated TB/HIV care givers and in most
situations, c) use of a TB treatment regimen that
includes rifabutin instead of rifampin. Because
alternatives to the use of rifampin for antituberculosis
treatment are now available, the previously
recommended practice of stopping protease inhibitor
therapy to allow the use of rifampin for TB treatment is
no longer recommended for patients with HIV-related
TB. The use of rifabutin-containing antituberculosis
regimens should always include an assessment of the
patient's response to treatment to decide the appropriate
duration of therapy (i.e., 6 months or 9 months).
Physicians and patients also should be aware that
paradoxical reactions might occur during the course of
TB treatment when antiretroviral therapy restores
immune function[37].
One hundred eighteen years after Koch’s discovery
of the tuberculosis bacterium and 80 years after the
development of the BCG vaccine, the tuberculosis
pandemic is still out of control. The development of
new, stable, possibly DNA-based TB vaccine is the
hope of tomorrow, but the researchers involved made it
completely clear that we are still far from achieving
this. Hygienic measures and carefully monitored
follow-up and treatment (Directly Observed Treatment,
DOT) of TB cases is cost and environmentally effective
even today[38]. According to Hong Kong Chest
Service/Medical Research Council, (1976) the
tuberculosis has some side effects, which should be
considered to reduce as much as possible. This strategy
is now spreading with WHO help to many poor
countries. Future research can be including:
* Epidemiological research to assess the extent of the
spread of TB to HIV- negative & HIV- positive
people.
Am. J. Infect. Dis., 2 (4): 210-218, 2006
217
* The development of methods for early and accurate
diagnosis of M. tuberculosis infection in persons
coinfected with HIV.
* Basic research to define what host factors protect
persons from infection with M. tuberculosis and
HIV and from the development of TB and HIV
disease.
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