Social and Economic Impact of Tuberculosis

Published Date: 20 Feb 2018

Introduction

Overview

Tuberculosis is a common and infectious communicable disease that is caused by mycobacterium tuberculosis. It is of two principle kinds: pulmonary TB, which usually attacks the lungs, and extra-pulmonary TB, which attacks any part of the body, such as: the lymphatic, pleural, bone and/or joint, genitourinary, miliary, peritoneal, meninges and/or central nervous system (CNS), and all other sites combined. Pulmonary TB sometimes combined with extra pulmonary tuberculosis (Parimon, 2008; Sreeramareddy et al., 2008; Friedman, 2001).

Tuberculosis is spread in form of droplets which are expelled when the infected persons cough, sneeze, speak, or sing. Close, prolonged, frequent, or intense contacts are the main ways that leads to 22% of the infection rate. Other resources include: foreign-born from areas where TB is common, residents and employees living in plagued congregate settings, health care workers who serve severely infected clients, low-income populations, highly inflicted racial or ethnic minority populations, children exposed to severely infected adults, and persons who inject illicit drugs.

Extra pulmonary TB that occurs outside the lungs may spread through lymphatic or hematogenous dissemination to any tract or through coughing and swallowing to the gastrointestinal tract. Such a type of bacteria may remain dormant for years at a particular site before causing the disease. Since extra pulmonary TB can affect virtually all organs, it has a wide variety of clinical manifestations. A matter which causes difficulty and delay in its diagnosis (Mehta, 1991; Gonzalez et al., 2003). Though, it is said to be more often diagnosed in women and young patients (Rieder et al., 1990; Gonzalez et al., 2003; Yang et al., 2004; Noertjojo et al., 2002; Cowie and Sharpe, 1997; Antony et al., 1995; Chan-Yeung et al.,2002). In the United States, extra pulmonary TB is associated with ethnic minorities and with those born in other countries (Rieder et al., 1990) while in Asia, lymphatic TB occupies the front position of the risky infectious diseases (Cowie and Sharpe, 1997, 1998; Moudgil and Leitch, 1994; Nisar et al., 1991; Ormerod, et al., 1991). A study of Somali TB patients in Minnesota showed frequent lymphatic TB as well (Kempainen, et al., 2001). In HIV-infected patients, the frequency of extra pulmonary TB depends on the degree of decrease in cellular immunity (Huebner and Castro, 1995; Barnes, et.al., 1991). While in patients with <100 CD4 cells/mL, extra pulmonary and disseminated TB counts for 70% of all forms of TB (Jones, et al., 1993). The materials needed for culture confirmation of extra pulmonary TB is much more difficult than that for culture confirmation of pulmonary TB (Gonzalez, et al., 2003).

Economic and Social Effect of Tuberculosis

Statistically speaking, Mycobacterium tuberculosis infects one-third of the world's population and is the most common single death causing agent in young adults (WHO, 2008). Globally, it accounts for 2.5% of the other diseases. However, the consequences of tuberculosis (TB) on society are huge. Worldwide, one person out of three is infected with Mycobacterium tuberculosis, i.e. two billion people in total. Currently, it holds the seventh place in the global ranking of the causes of death. (Dye, 1999; Smith, 2004).

Economically speaking, TB hinders socioeconomic development for the high percentage of the disease, 75%, afflict the productive age group that ranges between 15-54 years. Furthermore, ninety-five per cent of all cases and 99% of deaths occur in developing countries, with the greatest burden in sub- Saharan Africa and South East Asia (Dye, 2006; World Health Organization, 2006a).

Despite the availability of Effective drugs for more than 50 years, every 15 seconds, someone dies from TB. Besides, the percentage of TB infection is every second of every day (Dye, 2005; WHO, 2000). In light of this, Dye (1999) and Smith (2004) add that unless intensive efforts are made, it is likely to maintain that position through to 2020 and it is likely for a person with active TB to infect an average of 10 to 15 other people every year.

The total Budget for TB control in 22 severely-infected countries in 2006 equals US$ 1.6 billion, taking into consideration the cost of the health system staff, the infrastructure used for TB control, in addition to the requirements of the National Tuberculosis Control Programme which is less than that of 2002 which soared to US$ 876 million. However, the Russian Federation and South Africa occupy the front position as far as TB costs are concerned, where their costs amounted US$ 810 million. However, even though the health systems managed to control the growing number of TB patients in 2006, TB financial costs in 2006 would have been the same as for the National Tuberculosis Control Programme budgets, i.e. US$ 141 million. Furthermore, such costs and such funding gaps are liable to be increased to US$ 2.0 billion, and US$ 180 million, respectively when all 74 infected countries are included. Globally, these 74 countries represent 89 % of TB cases (Dye, 2006; World Health Organization, 2006a). On the other hand, WHO estimates that 9.27 million new cases of TB occurred in 2007 (139 per 100 000 population), compared with 9.24 million new cases (140 per 100 000 population) in 2006 and with 44% or 4.1 million (61 per 100 000 population), were new smear positive cases.

As far as the expected cost for diagnosing and curing this disease is concerned, it is of three kinds: the direct, indirect and the intangible costs, and as stated below:

Direct Costs

Direct or immediate costs for diagnosing and treating are of importance for poor families. (Lubeck, 2003; Verstappen, 2004; Drummond et al., 2005) state, in this respect, that direct costs include the costs of medical care and related items, such as: the expenses of visiting doctors, laboratory and radiological examinations, hospital costs, medications, transportation to and from the doctors, and special aids.

Indirect Costs

A great economic loss occurs as a result of "indirect" costs, which involve the cost stemming from losing employees, traveling to health facilities, selling assets to afford TB treatment, and in particular, losing productivity due to illness and premature death (Smith, 2004; Floyd, 2003; World Health Organization, 2005a). In light of this, Johannesson (1996) indicates that indirect costs are "those resulting from the loss of function in one's usual activity, including work disability, sick-leave or reduced productivity".

In calculating the loss of productivity, the two commonly used methods are the human capital and the friction cost approach. The human capital approach evaluates the individual's productivity by the market price; that is the potential gross salary of the individual, including all of the employer's contributions. While in case of self-employed persons, the gross personal income includes the statutory insurance expenses or as Lofland et al. (2001) puts it, it takes a societal approach. The friction cost approach assumes that the disabled person is replaced by a currently unemployed person during the friction period, where the latter is the time during which the sick person is replaced. Hence, friction costs include all the expenses related to replacing that worker (ibid.).

The estimated cost of TB treatment in patients with susceptible tuberculosis in developed countries ranges from US$ 276 to US$ 1546 and for multi-drug resistant tuberculosis (MDR-TB) ranges from USD 1000 to 10000. (Wyss & Lorenz, 2001, and WHO 2000). Determining the approximate costs for effective tuberculosis control is an important factor in specifying the actual expenditures required for treating tuberculosis. A matter that could be achieved by taking into consideration both the direct and indirect costs of tuberculosis.

Intangible Costs

Lubeck (2003) and Xie et al. (2008) maintain that intangible costs can be defined as the pain and suffering of a patient because of the disease. It includes a reduction in the physical function, an increased psychological distress, and a reduced social function. Intangible costs can be measured either by HRQoL questionnaires or alternatively by a contingent evaluation method which is based on "eliciting the levels of willingness in paying".

Lienhardt et al. (2001) add that tuberculosis has a severe impact on the impoverishment of patients and their households. The major factors which lead to impoverishment involve the following: the inability to work due to illness, the direct and indirect costs of accessing diagnosis and treatment, and the repeated visits to different care providers, which are associated with providers and patient's delays.

DOTS have the potentiality to reduce the economic and social effect of TB for patients and their households. However, few studies have explicitly examined this issue. The study in Uganda by Saunderson (1995) found that under DOTS, patient costs were reduced and they were able to start working again quickly.

In South India, Muniyandi et al. (2008) conducted a comparative study to calculate the costs of treating TB patients, using DOTS programme with those who were treated without using such a programme. The total number of patients was 896, divided as such (455 for DOTS and 441 for non-DOTS). Throughout the study, it was found that the direct cost for patients registered in DOTS areas, and for the mean pre-treatment was significantly lower than that in non-DOTS areas (Rs 874 vs. Rs 1,064) and that the mean direct costs during the treatment were also lower than that of the former (Rs 227 vs. Rs 250).

Pre-treatment indirect costs were nil in Rs 951 in the DOTS area compared to Rs 1,895 in the non-DOTS area. Throughout treatment, the indirect costs were significantly less in DOTS than in those of the non-DOTS (Rs 825 DOTS vs. Rs 1,821 non DOTS). As for the total mean cost of pre-treatment direct cost, it was lower in DOTS, Rs 1,762 than in non-DOTS area, Rs 2,903. The total mean of the direct costs during the treatment was also lower in DOTS, Rs 1,014, in comparison to Rs 2,069 in non-DOTS. Generally speaking, the indirect costs were significantly lower in the DOTS area than in non-DOTs ones.

Sreeramareddy et.al. (2008) conducted a retrospective study for about 474 patients in a tertiary care hospital that lies in Western Nepal for the purpose of comparing demographic, life-style and clinical characteristics between EPTB and PTB patients. The study found that the ratio of males to females was 1.07 (119/111) in EPTB and 2.29 in PTB (170/74), and that the median age of EPTB patients (29.5 years) is much lower than that of PTB patients, (47.5 years). Further, the study stated that, in the past, smoking and immunosuppressive drugs like steroids or anti-cancer drugs, diabetes and TB were mostly and directly related to PTB.

Studies from a number of developing-countries revealed that the poor have much less access to TB and DOTS programmes than the non-poor, to the extent that they can be excluded from TB care (Singh et al., 2002; Balasubramanian et al., 2004). Cohen et al. (1999) carried out three studies to examine the association of several markers of social status (unemployment, perceived and observed social status) with the host resistance to upper respiratory infections. The study found that unemployment and lower social status were associated with the increased susceptibility to infection. Such an association proves the fact that the grave impact of this disease occurs in the lowest social status groups. Thus, the further the increase in social status, the more decreases in susceptibility.

Portero, et al. (2002) noticed that there is a relationship between being healthily uneducated and the percentage of TB infection among the general population of Metro Manila, Philippines. That is, a lower score was found to represent the general knowledge about TB while a higher score was independently associated with college education. On the other hand, the low monthly-paid persons were characterized by having no TB knowledge; no intention of seeking health care and by no self-treatment of TB. Schoeman et al. (1991) studied the relationship between the socioeconomic factors and pulmonary TB. By measuring variables, like: demographic details, general living conditions, household ownership of luxury items, and weekly consumption of four proteins (meat, fish, chicken and cheese). They concluded that no significant differences were found between cases and controls on most of the variables, and that the overall significant differences were on the pattern of language groups, employment and meat and chicken consumption. Such a tendency was observed for more employed cases than for the controls, who are of primary school education. However, no conclusive evidence was found on the association between socioeconomic factors and the risk of developing TB.

Gustafson et al. (2004) studied the impact of demographic, socioeconomic and cultural risk factors on active TB in Guinea, Bissau. They found that Bissau has a very high incidence of intra-thoracic TB. Factors as the human immunodeficiency virus (HIV), increasing age, male sex, ethnicity, adult crowding, family structure, and poor housing conditions were independent risk factors for TB. Apart from HIV prevention, TB control programmes need to emphasize risk factors, such as: the socioeconomic inequality, ethnic differences, crowding, and gender.

Souza et al. (2000) identified that socio-demographic risk factors are statistically associated with TB in Brazil, within "defined population bases" (i.e. populations living in areas with well-defined boundaries). A matter which makes it possible to construct different levels of aggregation, including census tracts, neighborhoods, and sanitary districts. The results, further, showed that the distribution of such a disease at the census-tract level is not aggregated randomly. The results also involved the need for additional ways of stratifying this population and expressing different collective levels TB risks. The results, furthermore, indicated that there were high percentages of households without satisfactory sanitary installations and without regular garbage collection, in addition to noticeable percentages of illiteracy among persons aged between 10–14 years and among extremely limited schooling heads of family.

Floyd et al. (1997) conducted a study in rural South Africa to compare the cost-effectiveness of (DOT) with conventionally delivered treatment for tuberculosis. Conventionally, the patients were stayed in the hospital for the first two months of treatment to ensure compliance with treatment during the intensive phase. But, throughout their study, they found that the directly observed treatment was 2.8 times cheaper to deliver than that of the conventional treatment (US 4740.90 compared with US$ 2047.70) and that it was more cost-effective, costing US$ 890.50 per cured patient compared with either US$2095.60 (best case) or US$3700.40 (worst case) of the conventional treatment.

The analytical study of Cost-effectiveness was done by Sanderson (1995) in Uganda to estimate the total costs borne by the patient and the health service for different treatment program designs. The study concentrated on two regimens (designs) of treatment: the first one is currently used and consists of two monthly hospitalized initial phase then four to ten months continuation phase. The other regimen consists of four non-hospitalized months, weekly supervision and of blister usage in the initial phase while the continuation phase is as the current used regimen.

The study found that the design based on an ambulatory treatment of patients without hospitalization is costlier than that depending on hospitalization during the initial phase (current regimen) which equals ? 115.23 and ? 190.09, respectively. The study also measured the cost for patients to be approximately 70% of the cost of the current used regimen (i.e., before diagnosing, during hospital stay, the lost work time and the social cost).

Another study of cost effectiveness was carried out by David & Daniel (1999) in California during 1995 to compare between self-administration therapy (SAT) and directly observed treatment (DOT) for patients of less risky TB. They estimated that the rate of treatment default was 1.7%. The study found that SAT has more cost effectiveness than DOT. The total cost of SAT is less than DOT by US$ 1.83 million, excluding the cost of patients out of pocket money, the time of work lost, diagnosis and out of hospitalization.

Muniyandi et al. (2005) conducted another study to see the economic impact of TB in Tamilnadu, India during June and December 2000, to assess the expenditures incurred due to TB whether direct medical, non-medical, indirect and the total costs before and during the treatment and to specify the effect of such a disease on employment. The study arrived at the following fact that the median direct, indirect and total costs for 343 patients who completed their treatment successfully were Rs 340. During treatment, the direct costs, Rs 100, were more than 50% from patients who did not get any indirect costs in both pre treatment, and during treatment periods. Moreover, the total costs were Rs 1398. In other words, patients have lost about 12%, i.e. more than 60 workdays.

In (2009) Kik et al. conducted another comparative study to compare the direct and indirect costs of pulmonary and extra pulmonary 60 immigrant TB patients in Netherlands, and specifically, at the 14 Municipal Health Services (MHSs) and the two specialized TB hospitals from April 2007 to October 2007. In the course of the study, they did not observe any significant differences between the characteristics of the interviewed patients of PTB and ETB though ETB patients tended to be older than PTB patients. The expenditures of patients varied widely. For instance, the direct costs during the entire TB illness averaged €353 (median €190); the total direct costs of patients ranged from €0 to €3961; and the costs during the pre-diagnostic period were slightly higher for patients with ETB (mean €10, sd 18.8) than that with PTB (mean €3, sd 7.4, ). Most of the costs were incurred if patients were hospitalized, and in case of indirect costs, the average patients lose 81 days of their normal productivity due to TB infection (i.e. a median of 60 days) where ETB patients, on average, lose much time during the pre-diagnostic period than those of PTB patients.

Dejonghe et al. (1992) evaluated the direct cost effectiveness of standard and short-course treatments for the smear positive TB patient in Malawi, Mozambique and Tanzania and found that short-course chemotherapy with hospitalization is approximately 23% cheaper according to the heath services perspectives than the standard treatment and that by implementing the ambulatory short-course of treatment, the cost of treatment will be reduced to 35%, 65%, and 50%, in Malawi, Mozambique, and Tanzania, respectively.

Brown et al. (1991) estimated, in the united states, the total expenditures of health care for the patient, inpatient diagnosis and treatment, screening, preventive therapy, contact investigations, surveillance and for the outbreak investigations of tuberculosis. Throughout the study, which involved 26, 283 cases, they estimated that 90% of the patients were given an outpatient treatment (23,654 TB cases) and that the direct medical expenditure for TB was approximately US$ 703.1 million. From that, only US$ 423.8 million represented the cost of inpatient care whereas US$ 182.3 million represented the outpatient care. The study depended on estimation to count the total costs for drug resistant (10.7%) and for multi-drug resistant tuberculosis (3.5%) while the indirect cost of illness was excluded.

Wyse & Lorenz (2001) conducted a study, in Dar es Salaam, Tanzania, on the costs of tuberculosis for households and health care donors. This study included one hundred ninety-one patients with a treatment period ranging from 8-to-12 months. They found that the average costs to a patient range from US $ 186 to US $ 1457 (including costs such as the following: x-ray examinations, laboratory, consultation, drug, hospitalization, transportation and productive loss costs) and that the average costs to the health care donors per patient was only US $ 90 (including programme management, laboratory unite, drug and ambulatory care cost). The known major types of costs in the study were the costs of drugs, costs transportation and, in particular, the costs due to the loss of work force.

A cost effectiveness study, in Pakistan, was conducted by Khan et. al. (2001); the study lasted from Sep. 1996 until June 1998 for the purpose of finding out the most cost effective strategy for the implementation of direct observed treatment (DOT). Throughout the study, the patients were divided into three different groups according to the type of the DOT used strategy, such as: self administration of medication, DOT by family members or DOT by health care workers. The results illustrated that the type of self-administration DOT was themost cost-effective. Its costs soar high to US $ 164 per patient cured compared to the other strategies as DOT with family, and DOT with healthcare worker where their costs were US$ 172 and US$ 310, respectively.

A pharmacoeconmic evaluation of tuberculosis was conducted by Elamin et.al. (2008) in Penang, Malaysia. The number of patients was 202 with a treatment period ranging form 6-to-12 months. The study found that the average cost to the healthcare providers per patient was only US $ 189.5 (including x-ray examination, laboratory tests, consultation cost, drug and supplies, health staff time, hospitalization costs, stationary, and over head cost). Furthermore, the average costs to the patients was US $ 726.90 (including meals, transportation and the time away from work). The major types of costs documented in the study were drug and supplies, transportation and, in particular, the cost due to the loss of work forces

Further cost-effectiveness study was carried out by Islam et al. (2002) in Bangladesh to compare the cost-effectiveness of TB programme run by the Rural Advancement Committee (RAC), which used community health workers (CHWs), with that of the government TB programme which did not use CHWs. Such a study identified a total of 186 and 185 TB patients over one year to find that the application of CHWs was more cost-effective than government area, which obtained a cure rate at 84%, i.e. US$ 64 per patient compared with 82% cure rate, i.e. US$ 96 per patient in the governmental areas.

Rajeswari et al. (1999) conducted a study on the socioeconomic impact of TB on patients and families in India to assess the expenditures involved in tuberculosis diagnosis and treatment; the effect of tuberculosis on patient's family and to estimate the loss of income due to work disability. The study included that a total of 304 patients, who received their treatment from private practitioners, governmental and non-governmental hospitals. The expenditure cost included direct medical cost, such as: consultation fees and the money spent on investigation and drugs; direct non-medical cost, such as the money spent on transportation, loading, special food and on persons accompanying the patients; and indirect cost, as the loss of wage and the decreased earning ability due to illness. They found that the direct cost in the three different types of health facilities was US$ 38.5, US$ 48.5 and US$ 253.00, and that the total cost of TB treatment was US$ 147.50, US$ 169.50 and US$ 368.50 in the governmental hospital, non-governmental hospital and private practitioners, respectively.

Health Related Quality Of Life (HRQL)

Carr et al. (1996) stated that the broad-ranging concept, the quality of life (QoL), incorporates health states, satisfaction with work, leisure time, level of independence, social relationships, and environment. The World Health Organization (WHO) defined QOL as the ability of individuals to perceive their position in life within the cultural contextual and the valuable systems in which they live by in accordance with their goals, expectations, standards and concerns (Anonymous 1995). According to Khanna and Tsevat (2007), HRQoL is a multi-dimensional concept that associates the physical, emotional, and social components of an individual with his/her medical conditions or treatment).

In recent decades, the interest of measuring HRQoL has increased noticeably due to advances in medical science and technology and to the increased number of people who live contentedly with chronic diseases and disabilities. According to the patients' perspective, the change in the morbidity profile evoked the need of evaluating the outcome of different treatments.

Measuring HRQoL can be done either by disease-specific tools or generic measurement tools. The generic instruments allow comparisons between patient groups with different diagnoses, whereas the disease-specific instruments give information about only one certain disease and its effect on health. Disease-specific instruments are, however, more sensitive to the important differences in health status. They are; therefore, successfully used for measuring results of specific treatments. A well-known example of a disease-specific instrument is the questionnaire of Rheumatoid Arthritis Quality of Life (RaQoL). It is the first patient-completed instrument, especially designed to be used with RA patients (de Jong et al. 1997). Other example of a disease-specific instrument is the questionnaire of Tuberculosis Quality of Life (SF-12 Questionnaire by Dhingra and Rajpal 2003).

The generic instruments are divided into two kinds: profile and single index score measures, as illustrated below:

1. Profile measures describe the health state according to various physical and emotional dimensions, such as physical functioning, bodily pain, general health, social functioning, and other dimensions. A well-known example of it is the widely used a Health Status Survey Questionnaire resulted from a Medical Outcomes Study of a Short Form with 36 items, (SF-36).

Ware and Sherbourne (1992) mentioned that SF-36 is a well-validated generic health status measure used in health surveys of both general and various populations with different diseases. The 36 items in the questionnaire are grouped into 8 multi sub-scale items that measure the physical functioning; role limitations due to physical problems and bodily pains; general health perceptions; vitality; social functioning; mental health; and role limitations due to emotional problems. For each subscale, there is a score that calculates values from 0 to 100, where the low scores indicate poor health.

Chamla (2004) prospectively measured active TB patients' HRQL at the start point, middle, and at the end point of the treatment. During the treatment, role physical, vitality and mental health scores decreased after the initial 2 months, but showed an overall improvement at the end of the treatment while all the other subscale scores showed a gradual increase throughout the treatment. After the anti-TB treatment, the study observed a significant improvement in all physical health subscales of the SF-36 (physical problems and bodily pains; general health, p < 0.05), besides two mental health subscales role limitations due to emotional problems and social functioning (p < 0.05) improved significantly. The study also observed that, at the end of the treatment, active TB patients still significantly scored lower at role physical, vitality and mental health subscales compared to general population comparisons. Generally speaking, physical health subscales were more affected than mental ones. Furthermore they found that younger people tended to have better HRQL than older ones.

Two studies, in Canada at the Montreal Chest Institute, a TB clinic, were conducted by Dion et al. (2002, and 2004); the studies compared, in three consecutive interviews, between patients who had already begun treating active tuberculosis (three consecutive interviews during the intensive phase), people with LTBI and people had previously been treated from TB disease, the studies noticed that the active TB patients scored significantly lower in SF-36 physical Component Scores, but not in Mental Component Scores, when compared to people with LTBI and those with previously treated TB disease.

Wang et al. (1998) maintained that active TB patients reported lower scores (p < 0.01) across all SF-36 subscales than the healthy non-TB people, whose role of physical and role of mental are most affected. Guo et al. (2008, 1998) stated that, in comparison to those with LTBI, people with active TB scored significantly lower at all SF-36 subscales. In contrast, SF-36 scores among people with LTBI before taking the preventative therapy were very similar to that of U.S. norm references. In addition they found that older people tended to have poorer HRQL than younger ones.

Marra et al. (2008) identified areas of HRQL that are affected by LTBI and active TB disease, the study included the patients with recently diagnosed active TB (104) or LTBI (102)patients , the Short Form-36 (SF-36) at baseline, 3 months, and 6 months were administered. The study analyzed the differences in HRQoL of both Latent TB and Active TB infection and discovered that, in comparison to those with LTBI, people with active TB scored significantly lower at all SF-36 subscales, in the onset of treatment. In contrast, SF-36 scores among people with LTBI before the preventative therapy were very similar to that of U.S. and after 6 months of drug therapy, the study noted a significant HRQL improvement in active TB patients throughout the 6 months of treatment, using SF-36. Although anti-TB treatment was generally improved HRQL, active TB patients still had poorer HRQL in Physical Component Scores and Mental Component Scores at the end of the treatment, compared to the LTBI and general population. The study added that, after the preventive treatment, Mental Component Scores among people with LTBI declined significantly, while Physical Component Scores stayed unchanged.

Study in the Ankara, Turkey was conducted by Aydin and Ulusahin (2001); they compared the TB patients with COPD patients and the study found that TB patients had a lower prevalence of depression and anxiety and a lower level of disability. The study assumed that the chronic duration of COPD and the older age of the COPD patients may lead to a higher prevalence of psychological impairments, and that with multi-drug resistant, TB patients reported to have the worst disability level.

Yang et al. (2003) indicated that pulmonary TB patients showed more psychological symptoms and a lower degree of social support in comparison to healthy controls. Moreover they observed that males were more likely to have better health than females.

Duyan et al. (2005) found that the best HRQL correlated with variables like: the higher income, education, better housing conditions, better social security, and with closer family's and friends' relationships. Further addition the study found that there were no significant associations between gender, age and HRQL in TB patients

HRQoL assessment study for pulmonary TB and LTBI patients in Tarrant County in the United State was performed by Pasipanodya et al. (2007); they measured HRQL among pulmonary TB, who completed at least 20 weeks of the treatment period. They discovered that, in comparison to those with LTBI, treated TB patients had lower scores and that lung functions and/or those born in the United States (against foreign born) tended to have better HRQL outcomes. Moreover, no gender and smoking difference were noted.

Rekha et al. (2009) evaluated HRQoL of pulmonary TB in Chennai, India; the study noted that the HRQoL in TB patients in terms of symptom, activity and impact including the overall scores was worse in status when compared to that of the general population. Further, the study concluded that the females were the worst in status and that the male smokers had a low HRQoL.

Muniyandi et al. (2007) assessed HRQL of the previous sample of TB patients for one year after successfully treatment completion. They saw that 40% of these people reported persistent symptoms, such as breathlessness, cough, chest pain, and occasional fever. They further calculated three SF-36 component scores: the physical, mental, and the social well-being to arrive at the fact that there was no gender difference on physical well-being score. However, females scored much lower at mental and social well-being scores while younger people and older ones had only lower physical and mental well-being scores. They also offered U.S. general population norms for the three component scores and concluded that TB patients' HRQL came back to its normal level after one year achievement of the treatment.

Letrait (1996) stated that apart from the physical symptoms, a patient with tuberculosis faces several physiological, psychological, financial and social problems. These problems impair the quality of his/her life and have a great impact on his/her well being. It has been recognized that the quality of life indices, which focus on patients' own perception of disease, provide additional information that cannot be found from conventional clinical and functional measurements.

1. The single index score instruments produce a single value (utility score) of 0-to- 1 scale that provides an overall picture of the level of HRQoL and that changes in it. Utility values are necessary for calculating the Quality-Adjusted Life Years (QALYs), developed to combine the quantity and quality of life into a single measure.

SF 12 (Short Form Health Survey)

Jenkinson (1997) said that Short Form Health Survey, SF-12, is an instrument of choice, where a short generic measure provides summary information on the physical and mental health status. Such a device is able to produce the two summary scales originally developed from the SF-36 with considerable accuracy and with far less respondent effect.

Study in New Delhi Tuberculosis Centre, India conducted by Dhingra and Rajpal (2003, 2005), by using Short Form (DR- 12) at baseline, four weeks and eight weeks of treatment, The study observed that there was a gradual improvement on DR- 12 scores in active TB patients over the course of the treatment. In general, the symptoms scores showed better improvement than socio-psychological and exercise adaptation scores. They added that there was a significant difference between the scores of pulmonary and extra-pulmonary tuberculosis patients (higher in extra-pulmonary cases) both in Symptom Scores and in Total HRQL Scores at the start point of treatment. Moreover, sputum negative patients showed a higher Symptom Score than the sputum positive patients.

In India, Singh et al. (2004) evaluated the impairment of HRQL for 100 patients (of 15 years & older) with tuberculosis during their treatment at 0 week, 4 weeks & 8 weeks by using a HRQL questionnaire. The Questionnaire was based on symptoms (score I), physiological, psychological & social interaction of the patients (score II). The study observed that there was a perceptible increase in the HRQL score at week 4 & 8 in all categories of patients and in patients, who did not convert sputum negative at the end of the intensive phase though the latter's increase was low as compared to those who turned sputum negative. Finally, an improvement was also noticed in both male & female patients with pulmonary or extra pulmonary disease.

Epidemiology of tuberculosis in Yemen

Tuberculosis is still one of the major problems in Yemen and Yemen was considering one of the high burden countries in the region for long time based on latest evaluation of TB which had done by National-Wide Survey of the Tuberculin Testing among school children (Annual report of NTCP 2007).

According to the report NTCP 2007, ARI= (0.86%) which is equivalent of occurring (43 NSS+)/100,000 Population each year. The annual expected incidence of NSS+ is =8480, and same number of other forms of Tuberculosis. The most recent estimated of tuberculosis in Yemen published by WHO (2007) shown that; the annual incidence of NSS+TB cases= (37/100,000 Population), which means =( 7297 NSS+TB cases/Year), and for all forms of TB cases=(82/100,000 Population ), while the prevalence is 136/ 100,000 Population, mortality (death /100,000 Population /Year =10), HIV+ among new adult TB cases= 0.8%) and the new cases of Multi-drug resistant/ 2004= (3.1%) and in previously treated cases= 9.4%.

The majority of tuberculosis patients in Yemen are in the period of 15-54 years of age as shown in figure 1.1 and the pulmonary tuberculosis represented 72 % while the extra pulmonary represented 28% most of them in Sana'a city 24%. (NTCP report 2007)

Transmission and Pathogenesis of Tuberculosis

As it stated earlier, the bacterial disease, tuberculosis (TB), is transmitted by particles, or droplet nuclei that are expelled when persons who have pulmonary TB sneeze, cough, speak or sing (Brewer and Heymann, 2004; Bjune, 2005; CDC, 2000; Gandy & Zumla, 2002; Feja, 1999).

Droplet nuclei which contain one to 10 bacilli whose diameter is roughly 10 ?m are expelled through coughing, and suspend in the air to be later transported by air currents. Normal air currents can keep them airborne for prolonged periods of time and spread them throughout rooms or buildings. Some of these droplet nuclei, usually those larger than 10 ?m, are inhaled and anchored in the upper respiratory tract (Wells, 1995).

The effective droplet nucleus is very small; measuring 5 ?m or less. Despite small, it is able to avoid the mucus and ciliary system action and produce the anchorage in bronchioles and respiratory alveoli. Being small in size allows them to remain suspended in the air for prolonged periods of time. (Friedman, 2001; CDC, 2000; WHO 1999).

TB transmission occurs with greater prevalence in poorly ven­tilated and crowded spaces (Hawker et al., 1999; Beggs et al., 2003; Elender et al., 1998 and Valin et al., 2005). A sputum smear-positive individual with pulmonary TB is four to six times more conta­gious than a smear-negative case (Menzies, 1999). However, sputum smear-negative, culture-positive patients with pulmonary TB are also infectious to others (Hernandez-Garduno, 2004; Behr, 1992). According to Jerant et al. (2000); White & Williman (2001); and WHO (1999), environmental factors that suit TB transmissions include the following:

1. The exposure of susceptible individuals to an infectious person in a relatively small, enclosed space
2. Inadequate ventilation that results in either insufficient dilution or in the removal of infectious droplet nuclei
3. The recirculation of air containing infectious droplet nuclei
4. The duration of exposure
5. The susceptibility of the exposed person.

Correa (1997), Starke (1996), and Vallejo (1994) all maintained that five to 200 inhaled bacilli are enough to be successfully infected. After inhalation, the bacilli are usually installed in the mid lung zone to move then to the distal and sub pleural respiratory bronchioles or alveoli. Subsequently, alveolar macrophages phagocytose the inhaled bacilli. However, these first macrophages are unable to kill mycobacteria; accordingly, the bacilli continue their replication inside these cells. As a result, logarithmic multiplications of the mycobacteria take place within the macrophage at the primary infection site. Then, the infected macrophages transport to the regional lymph nodes to disseminate the lymphohematogenous of the mycobacteria to other lymph nodes and organs, such as: kidneys, epiphyses of long bones, vertebral bodies, and juxtaependymal meninges that are adjacent to the subarachnoid space, and, occasionally, to the apical posterior areas of the lungs. In addition to whatever mentioned, chemotactic factors, released by the macrophages, attract the circulating monocytes to the infection site, and lead them to be mature macrophages with an increased capacity to ingest and kill free bacteria.

Correa (1997); Friedman (2001); and CDC (2000) noticed that two or three weeks after the initial M. tuberculosis infection, a cell-mediated immune response is fully established. While CD4+ T helper cells activate the macrophages to kill the intracellular bacteria and finally to motivate the formation of epithelioid granuloma, CD8+ suppressor T cells lyses of the infected macrophages, which resulted in the formation of caseous granulomas with central necrosis. Due to the fact that mycobacteria are not able to grow under the adverse conditions of the extracellular environment, most infections are controlled by the host immune system and the only evidence of a real and effective infection is a positive tuberculin skin test TST.

However, the initial pulmonary infection site, which denominates "primary complex or Ghon focus" and its adjacent lymph nodes, sometimes, reach a sufficient size that activates the development of radiographically demonstrable necrosis and calcification (Feja 2005, Schluger 1994).

Diagnosis of Tuberculosis

For proper and complete medical evaluation of TB diagnosis, the following steps have to be taken into consideration:

Determining the Medical History

One should obtain from the patient a complete history of the possible exposures to people with TB, Multidrug-Resistant TB (MDR-TB), past history of TB, previous positive tuberculin skin test, and previous history of treatment either for TB infection or any disease. An adequate clinical history should look for information about household, immigration from high prevalence area, and about the medical factors which motivate factors for TB disease (e.g. diabetes mellitus, HIV infection, injection drug users and homeless people). (American Thoracic Society (2000), American Thoracic Society/Centers for Disease Control and Prevention (2001), Correa (1997), Feja (2005), Jacobs (1993), Taylor (2005), Vallejo (1994).

Examining the Physical Symptoms

Physical examination is an essential part in evaluating, and obtaining the history of clinical signs and symptoms of pulmonary TB, which may include prolonged and productive coughs over two weeks duration, hoarseness, chest pain, or hemoptysis. Systemic symptoms of TB may involve unexplainable weight loss, fever, night sweats, appetite loss, easy fatigability, or chills.

Examining the Bacteriological Aspect

Such a step implies adopting the following examinations of:

Sputum Smear

Bacteriological examination of sputum is referred to as acid fast bacilli (AFB). Such an examination is considered the only way in which the diagnosis of pulmonary tuberculosis can be confirmed. Whenever tuberculosis is suspected, three specimens of sputum should, at least, be collected and examined by microscopy and the examined samples be preferably obtained within two days.

Sputum culture

Timothy (2006) stated that the culture of tubercle bacilli is a regarded as a confirmation step that is necessary for carrying out the sensitivity test that is in turn essential for monitoring the initial and acquired drug resistance to anti-tuberculosis drugs.

Examining TB Radiographically

Chest x-ray screening has been used for active case finding for the last seventy years Golub (2005). WHO (1994), CDC (2000) and Friedman (2001), mentioned that the x-ray diagnosis of tuberculosis is unreliable because other chest diseases may resemble tuberculosis on x-ray, and because pulmonary TB may show many forms of radiographic abnormalities.

Adopting Tuberculin Skin Test (TST)

A tuberculin skin test can be done by using the Mantoux method. Such a test is utilized to diagnose Latent TB Infection (LTBI) (Laura, 2007). Although this test is considered the best-studied test available to diagnose TB infection, it is not useful in diagnosing active TB disease, but rather in detecting the presence of TB infection. A positive TST does not necessarily signify active TB; it may be falsely negative in up to 20% of clients with active TB disease. Further, diagnostic tests (e.g. CXR, sputum for AFB smear, culture) should be carried out before diagnosing active TB. False positive reactions to the TST may result from the exposure to non tuberculosis mycobacteria (NTM). A negative reaction to the TST does not exclude the diagnosis of active TB disease or LTBI. Some persons may have a false negative reaction to the TST if they are tested too soon to TB exposure. In general, it takes 2 to 12 weeks after the initial infection of person's immune system to respond to the tuberculin antigen (delayed hypersensitivity reaction).

Treatment of Tuberculosis

History of TB Treatment

Before discovering specific antibiotics for TB treatment, the mortality of patients with pulmonary disease (disease of the lungs) was about 50%. The introduction of anti-tuberculosis drugs in the 1950s and the development of the various drug regimens meant that by 1980s, there was a 98% chance of cure. However, such a treatment has to be continued with good quality drugs for six months to ensure the completion of the therapy.

The present TB chemotherapy treatment is one of the most spectacular achievements in medicine. The first trials of Tuberculosis treatment began when Robert Koch (1882) discovered a staining technique that enabled him to see Mycobacterium tuberculosis. Since then, the scientist started to find drugs that are effective for such organisms. Below are the names of scientists with their invented drugs:

1. Cantan (1885) discovered that inhaling the cultures of nonpathogenic bacteria could diminish the quantity of Mycobacterium tuberculosis in patient sputum.
2. Babe (1888) found that the growth of bacteria bacilli could be inhibited by products of Gram-ve and Gram+ bacteria.
3. Streptomycin was discovered in USA in 1944, and was soon brought to clinic use. It was considered the first specific anti-tuberculosis drug, but after few months of treatments the bacteria developed a resistance to streptomycin.
4. Scientists in Europe continued working to find a cure for TB. They succeeded in developing para-aminosalycilic acid (PAS), which was brought into use in the late 1946s. By combining the two drugs, streptomycin and PAS in the regimen, the emergence of drug resistant bacteria was largely prevented and the cure became the norm.
5. In 1951, there discovered isoniazed, pyrazinamide (1954), cycloserine (1955), ethambutol (1962) and rifampicin (1963).

Treatment of Latent Tuberculosis Infection (LTBI)

The purpose of treating asymptomatic infection is to prevent the development of active disease in the future. Such a treatment has other nomenclatures, such as: preventive therapy, chemoprophylaxis or latent TB treatment. Treating latent TB with Isoniazid (10 mg/kg/day or, at most, 300 mg/day) for six to nine months is indicated in every adult person susceptible to develop an active disease (International Union Against Tuberculosis and Lung Disease, 1994; Horsburgh, 2004; Castelo-Filho, 2004; Hopewell, 2006).

Such a treatment reduces the risk of developing the disease from endogenous reactivation, but it does not protect the patient from exogenous exposure. Therefore, when there is a possibility for recent new exposures to the tubercle bacillus, the patient must extend the treatment of latent TB (when receiving Isoniazid) or the instauration of a new treatment (when the previous one has already been discontinued).

The candidates for treating latent TB infection are:

• household contacts of AFB smear-positive pulmonary TB patients, who have not recently been vaccinated with BCG, have TST in duration>10 mm; or and who have BCG vaccination within the previous two years with TST in duration > 15 mm;
• individuals with TST conversion (a positive test with >10 mm in duration after a previously negative test, which had been applied 12 months earlier)
• HIV-infected individuals with a reactive TST of > 5 mm;
• HIV-infected individuals that report close contact with a smear-positive TB patient, regardless of the TST response; and
• Individuals with a chest X-ray image consistent of residual TB, and without a history of previous anti-TB treatment.

In every case, and before starting the preventive chemotherapy with Isoniazid, the physician should confirm the absence of active TB disease. A step can be done by noticing the following:

• the chest X-ray should be normal; and
• the individual should be asymptomatic and should before beginning with the preventive chemotherapy exclude active TB, either pulmonary or extra pulmonary, particularly, in patients with moderate/severe immunodeficiency. Moreover, appropriate follow-up for the patient is necessary to ensure the supplement of a regular drug and at least 70% adherence to the preventive treatment regimen.

Rose (1992); Jordan (2001) noticed that risk-benefit analyses demonstrated cost effective benefits for Isoniazid preventive therapy in low risk reactors, and a substantial cost effective benefits in higher risk reactors, in addition to another type of benefits, substantial long-term public health, that is mentioned by Salpeter (1993). However, the overall effectiveness of Isoniazid preventive therapy in low or middle income countries has not been well-established.

Treatment regimens

Isoniazid (H)

Isoniazid is the most widely used anti-tuberculosis drug. It is given in the dose of 5 mg per kg body weight per day up to maximum 300 mg per day. It can be safely in pregnant women. A major side effect, hepatitis, develop in about 0.5 % of cases, if hepatitis is suspected or jaundice is observed stop treatment.

Rifampicin

Rifampicin is very potent, relatively non toxic drug. The daily dose for children and adults is 10 mg per kg body weight up to 600 mg per day. It can be safely in pregnant women. When given in recommended dosage, rifampicin dose not cause any side effect with great frequency, particulary during continuous daily administration.

One of the major side effects of rifampicin is hepatitis, although this is rare. Alcoholism, pre-existing liver diseases or the simultaneous administration of other hepatotoxic agents seem to increase the risk. The development of jaundice requires discontinuation of the drug.

Pyrazinamide

Pyrazinamide is most active during 2(3) months of therapy. The daily dose for adult is 20- 30 mg per kg body weight and for children 30-40 mg per kg body weight up to maximum 2500 mg. it may be used safely in pregnant women. The most serious side effect of pyrazinamide is hepatitis. Joint pains and occasional attack of gout, due to the diminished execretion and accumulation of uric acid may occur less frequently.

Isoniazid/thioacetazone

Thioacetazone may help prevent the emergence of resistance to other drug such as isoniazid. And therefore administered in combination with isoniazid. The daily dose is 2.5 mg per kg body weight for adults and children up to maximum of 150 mg per day. Hepatitis the major side effect occurs as with isoniazid alone. Cutaneous reaction in patients treated with medication (due to thioacetazone) may be more serious than other drugs. Exfoliative dermatitis or Stevens-Johnson syndrome may occur and can be fatal.

Streptomycin

Streptomycin has strong effect on the elimination of tubercle bacilli in cavities of the lungs. The daily dose is 15 mg per kg body weight for adult 20 mg per kg body weight for children, up to maximum of one gram. The main toxic side effect of streptomycin is vestibular damage. The risk increases with the dose and age.

Ethambutol

The primary use of ethambutol is to prevent emergency of resistance to the drugs. The daily dose in the first two months of chemotherapy is 25 mg per kg body weight in adults and 15 mg per kg body weight in children. When administrated for more than two months, the dose should be reduced to 15 mg per kg body weight per day. Ethambutol may be produce impairment of vision; a decrease in visual acuity, blurring and red-green color blindness.

Regimens

Regimen for positive pulmonary

New cases of AFB smear positive pulmonary tuberculosis and other newly diagnosed seriously ill patients sever forms of tuberculosis. This regimen includes patients with tuberculosis meningitis, disseminated tuberculosis, tuberculosis pericarditis, peritonitis bilateral or extensive pleurisy, spinal disease with neurological complications, smear negative pulmonary tuberculosis with extensive parenchymal involvement, intestinal or genito-urinary tuberculosis.

The regimen consists of:

Initial (intensive) phase: 2HRZS(E); i.e., isoniazed, rifampicin, pyrazinamide and either streptomycin or ethambutol, given daily under strict direct observation for 2 months (8 weeks). When the patient has completed the Initial phase 2 months and the sputum smear is negative the continuous phase is started. If the sputum smear is positive at two months, the initial phase of 4 drugs daily is continued for other four week s under strict observation. After this the continuation phase is started, regardless of sputum smear examination results.

Continuation phase: 6HT, e.g. isoniazed and thioacetazone daily for six months. For the patients who have serious adverse reactions (such as Stevens-Johnson syndrome, exfoliative dermatitis) ethambutol may be substituted for thioacetazone. Patients should come to the health facility every four week to collect their drugs for self administration at home.

Regimen of extra pulmonary and negative pulmonary

Initial intensive phase: 2HTS (E), i.e., isoniazid, thioacetazone and either streptomycin or ethambutol, given daily for two months. Patients should come to healthy facility every month to collect their drugs for self administration at home.

Continuation phase: 10 HT i.e., isoniazid and thioacetazone daily for 10 months. Patients should come to healthy facility every month to collect their drugs for self administration at home.

Re-Treatment of TB

The regimen according to WHO (1997) should be given to patients afflicted with tuberculosis diseases after completing the standard regimen (2 months of isoniazed, rifampicin, pyrizanamide and streptomycin or ethambutol then 6 months of isoniazed and thioacetazone). Re-treating TB involves passing through two phases:

• Initial (Intensive Phase): this phase requires using 2HRZES/1HRZE, i.e. rifampicin, isoniazid, pyrazinamide and ethambutol, which is supplemented with streptomycin for the first two months. Then, the same drug is used again, but this time with no streptomycin. The dose should be taken daily for about one month and under direct strict observation. When the patient completes the initial phase which consists of 2 months and when the sputum smear is negative, the continuous phase is started. If the sputum smear is positive throughout the three months, the initial phase of treatment with four daily oral drugs lasts for other four weeks. If the patient is still smear- positive at the end of the fourth month, all drugs are stopped for 2-3 days, and a sputum specimen is sent to the laboratory for culture and for sensitivity testing. The patient should, then, start the continuation phase and refer to a specialist if possible.
• Continuation Phase: the second phase demands using 5HRE, i.e., 5 months of isoniazid, rifampicin and ethambutol, which are given daily under direct strict observation. If the patient remains positive after the completion of the continuation phase, s/he is no longer eligible for this regimen. That is to say, this patient will be considered as a chronic case and will be dealt with accordingly.

Treatment of Drug-Resistant Tuberculosis

Tubercle bacteria developed resistance to the most effective drugs or at least to rifampicin and isoniazid, anti-TB drugs, or the so called Multi-drug-resistant TB. Such a process consists of two phases:

• Initial Phase: this phase involves taking the following for three months: streptomycin, kanamycin or mikacin, pyrzinamide, quinolones (ofloxacin or ciprofloxacin), ethambutol or cycloserine.
• Continuation Phase: in this phase three drugs should be used for 18-24 months, such as: ethionamide, quinolone, ethambutol or cycloserin:

Directly Observed Treatment (DOTS)

In 1994, the internationally recommended control strategy, later named DOTS, was launched. Hence, the abbreviation, DOTS, stands for Directly Observed Treatment, Short-course, and its key components include:

• government commitment;
• case detection by predominantly passive case finding;
• standardized short-course chemotherapy for, at least, all confirmed sputum;
• AFB smear-positive cases, provided under proper case management conditions;
• a system of regular drug supply; and
• a monitoring system for program supervision and evaluation.

Supplying drugs for 6 months for DOTS costs less than US$ 10 in some parts of the world. The World Bank ranked the strategy of DOTS as one of the "most cost-effective of all health interventions". Countries that employ DOTS are able to avoid an expected increase in drug resistance, such as the case in Cuba and Nepal, where levels of drug resistance showed a remarkable declination (World Health Organization 1994, World Health Organization 2002c). A total of 183 countries and territories implemented DOTS strategy in 2004. By the end of 2004, 83% of the world's population lived in DOTS-covered countries. DOTS programs notified 4.4 million new cases and relapsed TB cases in 2004, of which only 2.1 millions were new AFB smear-positive. In total, 21.5 million TB patients, and 10.7 million AFB smear-positive patients were treated in DOTS programs over 10 years ranging from 1995-2004 (Sharma 2006, World Health Organization 2006a).

Globally, the case detection rate by DOTS programs increased almost linearly from 11% in 1995 to 28% in 2000, and then were accelerated to 45% in 2003. If 7% of the global increase of detection between 2002 and 2003 was maintained, it would have reached approximately 60% by 2005, of which only 10% was below target. Comparing different parts of the world in 2003, it was found that case detection was the highest in Latin American (48%) and Western Pacific regions (50%), and the lowest was in Eastern Europe (22%). The recent acceleration has been mostly due to the rapid implementation in India, where case detection increased from 1.7% in 1998 to 47% in 2003. Whereas in China, case detection increased from 30% in 2002 to 43% in 2003. India and China together accounted for 63% of the increase in DOTS case-notification between 2002 and 2003. Hence, supporting agencies like: growing coverage, governments, donors, and others began asking for any piece of evidence that DOTS has on an expected epidemiologic impact (De Cock, 1999; World Health Organization, 2002b; World Health Organization, 2002c; Dye, 2005; Frieden, 2005; Sharma, 2006; World Health Organization, 2006a).

The global success rate of DOTS treatment has been high (77%) since the first observed cohort in 1994. In 1998, it remained above 80%, even though the cohort size increased 6 folds to 1.4 million patients. There is, however, much variation among regions. The success of treatment exceeded 85% in the Western Pacific region, largely because China reported a 93% success rate. Clearly, the biggest failure of DOTS was in Africa, where rates of TB continued to rise. In 2002, the African region registered less than 75% cure rates while death rates were as high as 8% in patients co-infected with M. tuberculosis and HIV. Whether this statistic indicates a failure of DOTS, or is the result of the rapid spread of the HIV epidemic is still debatable. Eastern Europe, another region plagued by poor health systems and by an expanding HIV epidemic, witnessed continuing increases in TB incidence rates throughout the 1990s, though the increase now seems to have peaked. Increases in the incidence rates of the disease are 274. A Global effect of TB was also noted in Central Asian countries, where death rates in DOTS recipients remained stable at 5%. However, both Eastern Europe and Central Asia represent hotspots of MDR-TB (Dye, 2005; Frieden, 2005; Sharma, 2006; and World Health Organization, 2006a).

Although the decline in TB has almost been avoided by good chemotherapy programs in countries such as Chile, Cuba, and Uruguay, there have only been few recent and unequivocal demonstrations of the impact of DOTS in severely plagued countries, as it happened in Peru and China. In Peru, the rate of pulmonary TB started decreasing annually by 6% with DOTS implementation in 1991. In 13 provinces of China that implemented DOTS, the prevalence rate of culture-positive TB was cut by 30% between 1990 and 2000 (Dye, 2005; World Health Organization, 2006a).

Although the substantial expansion and success with DOTS, most countries will probably not trespass the aspiration of the United Nations Millennium Development Goals in halving the prevalence of TB and its death rates between 1990 and 2015. Further, innovative steps should be taken into consideration when aspiring to control TB globally. The main objectives are: continuing DOTS expansion with more funding and oversight, building an existing DOTS programs to pursue DOTS-Plus, increasing funding on research to improve diagnosing, curing, and vaccining, re-visiting strategies of chemoprophylaxis and active case finding, and using DOTS to strengthen the infrastructure of public-sector and community- based health programs and insurance schemes (Sharma, 2006; World Health Organization, 2006a).

In Yemen, the government lined the policy of the National TB Control programme (NTP) with that of WHO TB control strategy of Direct Observed Treatment, short course (DOTS), where patients were observed by nurses when swallowing their medication in the initial phase of treatment, and when missing their clinic appointments, nurses will call them to come, otherwise, home visits will be done.

Adherence to TB Treatment

To ensure adherence and therapy completion, all patients must be treated under directly observed therapy (DOTS). Poor adherence to TB treatment can lead to relapse, transmission of the disease for more people and to the development of drug resistance. (Cabrera et.al., 2002; CDC, 1994 and Oza, 2000). Moreover, to insure following-up, patients should be healthily educated about TB diseases, methods of diagnosis, ways of transmission, treatment and prevention. (Cabrera et.al. 2002).

Study problem statement

In Yemen, no studies or even reports on the cost of tuberculosis treatment and HRQoL were conducted. So, the study will enable estimating the public health expenditures on tuberculosis treatments, investing its results by using an effective and accurate financial policy for the tuberculosis control, it also may help in the assessment of economic burden of tuberculosis in capital city Sana'a, allocation of resources and sets of priorities for tuberculosis control activities, give estimation for the total budget needed for National Tuberculosis Control Programme and encourage the health authorities to pay for prevention and early detection of tuberculosis infection before progression to disease in order to save large amount of money needed for treatment of tuberculosis diseases.

Another focus of our study was to assess the HRQoL of patients with pulmonary and extra pulmonary and to evaluate any change in HRQoL during treatment.

Aims of the Study

Objective General

1. Assessment economic burden of tuberculosis in Sana'a, Yemen, for the patient and the payer
2. Evaluate the health relat