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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


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
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 middleincome 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 tuberculosis 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 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 realizetion 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 tuberculosis Mycobacterium

*Corresponding author. E-mail: makram0451@gmail.com. Tel: 92-021-6440083. Fax: 92-021-6440079.

It is a slender, slightly curved rod, the waxy arabinogalactan cell wall layer (known as Wax D) is an active immunoadjuvant in complete Freuds 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. Mycobacterium tuberculosis is an acid-fast bacillus that retains the carbol fuchsin even when decolorized by acid alcohol


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(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).

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 reactivation 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, shortness of breath, chest pain. Screening (Vinay, 2007) Mantoux tuberculin skin test; interferon- release assays; QuantiFERON-TB Gold; T-SPOT.TB; chest photofluorography. 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

Risk factors (Vinay et al., 2007) Children younger than 5 years old; IV drug users; hospitalized 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

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).

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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, Paraaminosalicylic 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 drugresistant 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 smearnegative 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

Mycobacterium tuberculosis isolated from the same number of pulmonary tuberculosis cases (100 untreated cases, defined as patients either having no history of antituberculous 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 commonest. 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 interns 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 treatment. 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 treatment short course (DOTS) strategy (Khan et al., 2005). Prevalence of primary multidrug resistance to antituberculosis 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 streptomycin (10 g/ml) was found in 36 (5.4%) patients, isoniazid (INH) (1 g/ml) in 51 (7.6%), rifampicin (RMP) (5 g/ml) in 15 (2.2%), ethambutol (10 g/ml) in 12 (1.8%) and pyrazinamide in 22 (3.3%) samples. Forty-six


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(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 g/ml, RMP 5 g/ml). It was concluded 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, immediate action to improve undergraduate and continuing medical education is essential, with special emphasis on national guidelines.
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