African Journal of Microbiology Research Vol. 5(24), pp.

4029-4032, 30 October, 2011

Available online http://www.academicjournals.org/ajmr
DOI: 10.5897/AJMR11.167
ISSN 1996-0808 © 2011 Academic Journals

Review

Tuberculosis: A case study of Pakistan

H. M. Asif1, M. Akram2*, Saeed Ahmad Rao1, Irshad Ahmad1, Asim Awan2, Nadia Shamshad3,
Arham Shabbir4 and Qalb E. Saleem2
1
Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Pakistan.
2
Faculty of Eastern Medicine, Hamdard University Karachi, Pakistan.
3
School of Pharmacy, The University of Lahore, Islamabad Campus, Pakistan.
4
Department of Pharmaceutical Sciences, COMSATS Institute of Information Technology, Abbottabad, Pakistan.
Accepted 30 July, 2011

Tuberculosis (TB), an illness that mainly affects the respiratory system, is one of the world's most
pernicious diseases. TB currently infects one-third of the world's population and kills approximately 1.7
million people each year. Tuberculosis is a leading killer of young adults worldwide and the global
scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. This review highlights
the research done on different aspects of tuberculosis in Pakistan including, awareness of Pakistani
population about tuberculosis and drug resistant.

Key words: Tuberculosis, Pakistan, drug resistance, anti-tuberculosis drugs.

INTRODUCTION

Tuberculosis (TB) is a major contributor to the global
burden of disease and has received considerable
attention in recent years, particularly in low and middle-
income countries (Pio et al., 1999). Tuberculosis is a
specific infectious disease caused by M. Tuberculosis.
The disease primarily lungs and causes pulmonary
tuberculosis. It can also affects intestine, meninges,
bones, and joints, lymph glands, skin and other tissues of
the body. The disease is usually chronic with varying
clinical manifestations (Van, 2006). The disease also
affects animals like cattle; this is known as bovine tuber-
culosis which may sometimes be communicated to man
(Gleissberg et al., 2001). Tuberculosis (TB) is globally the
second most common cause of death from infectious
diseases, killing almost 2 million people annually. An
estimated 8 million new TB cases occur every year, of
which 80% are among people in the most economically
productive age groups (Dye, 1999), representing a major
economic burden for individuals and countries (Russell,
2004). Twenty-2 high-burden countries account for about
80% of the total TB disease burden worldwide. Although
sub-Saharan Africa has the highest incidence rate,
Bangladesh, China, India, Indonesia and Pakistan
*Corresponding author. E-mail: makram0451@gmail.com. Tel:
92-021-6440083. Fax: 92-021-6440079.
together account for half of the global TB burden (World
Health Organization, 2009). Pakistan ranks sixth in the
world in terms of tuberculosis (TB) burden, with a World
Health Organization estimated incidence of 181 per
100000, or 286000 new cases annually ((Javaid et al.,
2008). With the dawn of the era of drug resistance in
Tuberculosis the medical sciences have come to realize-
tion that not only the available knowledge is incomplete
but what ever is known is not well disseminated among
the medical professionals (Black, 1975). There are major
gaps of knowledge regarding the drug resistance in
Tuberculosis in health care providers highlighting the
urgent need to address this issue (Wajid et al., 2010).
General characteristics – Mycobacterium
tuberculosis
It is a slender, slightly curved rod, the waxy arabino-
galactan cell wall layer (known as Wax D) is an active
immunoadjuvant in complete Freud’s adjuvant.
Mycobacterium tuberculosis has a complex
peptidoglycan –arabinogalactan mycolate cell wall that is
approximately 60% lipid (Cole, 1998). Mycobacterium
tuberculosis stains poorly with gram stain but a highly
cross-linked peptidoglycan and no endotoxin. Myco-
bacterium tuberculosis is an acid-fast bacillus that retains
the carbol fuchsin even when decolorized by acid alcohol
4030 Afr. J. Microbiol. Res.
(because of long-chain fatty acids called mycolic acids in
the cell wall). Mycobacterium tuberculosis is resistant to
acid and alkali, which allows treatment of sputum to
reduce normal contaminating bacteria before culture.
Mycobacterium tuberculosis is a slow grower because it
has single copies of ribosomal genes. It is resistant to
drying and to many disinfectants. It stimulates a strong
cell-mediated immune response in a healthy host (Lawn
et al., 2006).
The global epidemic of tuberculosis
It is estimated that 1.7 million people died of tuberculosis
in 2009. There were estimated 9.4 million new cases of
tuberculosis in 2009 of which the majority were in Asia
and Africa. It is thought that the rates of new tuberculosis
infections and deaths per capita have probably been
falling globally for several years now. However, the total
number of new tuberculosis cases is still slowly rising due
to population growth (Gleissberg et al., 2001).
Mode of transmission (Munro et al., 2007)
Droplet spread by the infectious pts by coughing
sneezing etc; dust droplets laden with tubercle bacilli
settled on ground may be inhaled after sweeping; food
handled by a tuberculosis pt or utensils used by him; files
may carry infection from sputum of food; common Huqqa
smoking; kissing by the tuberculous pt; contaminated
milk.
Incubation period
Three to six weeks (It may be weeks, months or years).
Risk factors (Vinay et al., 2007)
Children younger than 5 years old; IV drug users; hospi-
talized patients; prisoners; weakened immune systems;
HIV/AIDS; diabetes; kidney disease; organ transplant
recipients immunosuppressant drugs; pregnancy.
Pathogenesis of tuberculosis
Humans become infected with Mycobacterium
tuberculosis (MTB) most frequently by inhaling droplet
nuclei that contain tubercle bacilli. Droplet nuclei are
expelled by infected individuals, and, because of their
very small size (1 to 10 um in diameter) they remain
airborne for long periods of time. Infection may also result
from ingestion or rarely, through the skin (Armstrong,
1975).
Tuberculosis appears to be a highly infectious disease,
as manifested by the minor epidemics initiated by
infected schoolteachers, students, bus drivers, or others
who come into contact with large numbers of people.
Humans tend, however, to vary considerably in their
response to infection by tubercle bacilli, and active
disease can, in general, be thought of as resulting either
from a primary infection or from a subsequent reacti-
vation of a quiescent infection (Frieden et al., 2004).
Symptoms of active TB
Cough tiredness and weight loss, night sweats and a
fever, rapid heartbeat, lymph nodes enlargement, short-
ness of breath, chest pain.
Screening (Vinay, 2007)
Mantoux tuberculin skin test; interferon-γ release assays;
QuantiFERON-TB Gold; T-SPOT.TB; chest photofluoro-
graphy.
Physical exams
Clubbing; enlarged or tender lymph nodes; fluid around a
lung; unusual breath sounds (crackles).
Tests
Biopsy; bronchoscopy; chest CT scan; chest x-ray;
interferon-gamma blood test such as the QFT-Gold test
to test for TB infection.
Sputum examination and cultures
Thoracentesis; tuberculin skin test.
Treatment
Bed rest does not affect the outcome for the disease.
Some patients will require hospitalization for a brief
period; these include ill patients, those in whom the
diagnosis is uncertain and, most importantly, those
individuals from whom it is essential to gain cooperation.
The most important factor in the successful treatment of
tuberculosis lies in the continual self-administration of
drugs for 6 months: lack of patient compliance is a major
reason why 5% of patients do not respond to treatment
(Aziz et al., 2006). In vitroresistance to one or more of the
antituberculous drugs occurs in less than 1% of patients
in the UK (Nolan et al., 1999). Long stay in hospital is
now required for persistently uncooperative patients,
many of whom are homeless and abuse alcohol (Farmer
et al., 1998).

According to Wright et al. (2004) the most commonly
used drugs include Isonizid, Rifampin, Pyrazinamide,
Ethambutol, while other drugs that may be used to treat
TB include Amikacin, Ethionamide, Moxifloxacin, Para-
aminosalicylic acid and Streptomycin.
Drug-resistant TB
MDR-TB is defined as resistance to the 2 most effective
first-line drugs, isoniazid and rifampin (CDC, 2009).
Another type of resistant TB, called extensively drug-
resistant TB (XDR-TB), is resistant to isoniazid, rifampin,
and second-line drugs used to treat MDR-TB. Mortality
rates for patients with XDR-TB are similar to those of
patients from the preantibiotic era. (Approximately 1 in 13
M tuberculosis isolates currently shows a form of drug
resistance) (CDC, 2009).
Clinical guidelines to diagnose smear-negative
pulmonary tuberculosis in Pakistan, a count
Study was done to develop and validate clinical
guidelines for diagnosis of smear-negative pulmonary
tuberculosis (TB) in developing countries with low-HIV
prevalence. In this study diagnostic guidelines for smear-
negative TB were undertaken. Clinical diagnoses based
on these guidelines were compared with sputum culture,
chest X-rays and reports of an expert panel. The
guidelines achieved a sensitivity of 0.59 [confidence
interval (CI) 0.46 to 0.66] and a specificity of 0.86 (CI
0.84 to 0.88) in diagnosing smear-negative TB. A total of
6.8% of patients who initially improved after a course of
antibiotics were later confirmed to have TB. Clinicians
detected an abnormal chest X-ray in 92% (CI 88 to 96%)
and radiological signs of pulmonary TB in 98% (CI 94 to
100%) of cases. Using radiological criteria for TB and
appropriate training can help in improving the diagnostic
skills of primary care clinicians working in low-HIV
settings with access to X-ray facilities. But a significant
number of apparently smear-negative TB cases may in
fact be smearing positive and TB programmes should
focus on improving the quality of direct acid-fast bacilli
microscopy. The value of an antibiotic trial is
questionable due to the relatively large number of false
negatives generated by this approach (Siddiqi K et al,
2006).
Some bacteriologic aspects of the epidemiology of
pulmonary and extra pulmonary tuberculosis
A study was carried out to investigate the drug resistance
patterns of the prevalent tubercle bacilli in pulmonary and
extra pulmonary tuberculosis in and about the city of
Lahore, Pakistan. This report includes 168 strains of
Asif et al. 4031
Mycobacterium tuberculosis isolated from the same
number of pulmonary tuberculosis cases (100 untreated
cases, defined as patients either having no history of anti-
tuberculous therapy or having had chemotherapy for not
more than 10 days; 68 treated, defined as having had
chemotherapy for more than 10 days), and 162 strains
from the same number of extra pulmonary tuberculosis
cases (77 untreated, 38 treated and 47 doubtful) (Siddiqi
et al., 1976). The proportion method of drug susceptibility
assay was employed. According to the procedures used
in this study and with 1% as the critical proportion for
resistance, bacterial resistance was found to be very
prevalent in pulmonary tuberculosis. Even among those
cases in which no history of previous treatment was
elicited, 46% were found to be excreting populations of
tubercle bacilli having some degree of resistance to one
or more of the primary drugs-isoniazid, streptomycin and
para-aminosalicylic acid. In treated cases, 86.8 were
found to have some resistance to one or more drugs.
Overall, resistance to streptomycin was found to be com-
monest. Drug resistance was observed to be somewhat
less common in extra pulmonary than in pulmonary
tuberculosis, with streptomycin resistance predominating.
Although both catalase - positive and catalase - negative
(Siddiqi et al., 1976).
Medical intern’s knowledge of TB in Pakistan
In this study out of 460 interns from five Pakistani
teaching hospitals surveyed, only 22% correctly identified
the estimated number of new TB cases in Pakistan. The
majority (96%) knew that droplet infection was the usual
mode of transmission. Only 38% considered sputum
smears for acid-fast bacilli as the best test for diagnosis
of pulmonary TB and 43.5% for follow-up during TB treat-
ment. The recommended four-drug anti-TB regimen was
prescribed by 56.5% in the initiation phase and the
recommended two-drug combination in the continuation
phase by 52%. Most interns (82%) were unable to
identify a single component of directly observed treat-
ment short course (DOTS) strategy (Khan et al., 2005).
Prevalence of primary multidrug resistance to anti-
tuberculosis drugs in Pakistan
In this cross-sectional study, sputum samples from 742
untreated newly diagnosed pulmonary TB patients from
all over the country were used. Objective was to assess
the prevalence of primary drug resistance in Pakistan.
Out of 672 culture-positive patients, 76 (11.3%) showed
resistance to one or more drugs. Resistance to strepto-
mycin (10 µg/ml) was found in 36 (5.4%) patients,
isoniazid (INH) (1 µg/ml) in 51 (7.6%), rifampicin (RMP)
(5 µg/ml) in 15 (2.2%), ethambutol (10 µg/ml) in 12
(1.8%) and pyrazinamide in 22 (3.3%) samples. Forty-six
4032 Afr. J. Microbiol. Res.
(6.8%) of the isolates tested were resistant to a single
drug, 10 (1.5%) to two drugs, 12 (1.8%) to three drugs,
and 6 (0.9%) to four drugs, while 2 (0.3%) isolates were
resistant to all five first-line agents. Primary MDR-TB was
1.8% (n = 12) (INH 1 µg/ml, RMP 5 µg/ml). It was con-
cluded that prevalence of primary MDR-TB in Pakistan is
< 2%, which needs to be addressed through an effective
DOTS strategy (Javaid et al., 2008).
Status of health professionals awareness about
resistant tuberculosis
An awareness survey was conducted with the view to
assess the basic knowledge of the various types of the
resistance pattern in tuberculosis amongst the medical
professionals. The definitions of the two types of drug
resistance namely multi drug resistant tuberculosis (MDR
TB) and Extreme (Extensively) drug resistant tuberculosis
(XDR TB) were asked and the medical professionals of
various levels of experience and seniority were asked to
give a spontaneous answer. Two hundred medical
doctors were included in this survey. One hundred and
twenty eight (69%) responses were finally included.
Remaining seventy two (31%) responses were classified
as regrets or incomplete responses. Fifty one (39.85%)
correct responses were recorded for definition of MDR
TB while seventy seven (60.15%) incorrect responses
were recorded. Only five (3%) correct responses were
recorded for definition of XDR TB while 103 (81%)
incorrect and 21 (16%) partially correct responses were
recorded in this category. Subset analysis of experience
and postgraduate qualifications was performed which
revealed that inadequacy of awareness was uniform in all
categories (Wajid et al., 2010).
CONCLUSION
Review of different studies reflects poor awareness of
and low compliance to the World Health Organization or
National Tuberculosis Programme guidelines among
Pakistan populations. For effective control of TB, imme-
diate action to improve undergraduate and continuing
medical education is essential, with special emphasis on
national guidelines.
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