Rate of Treatment Failure among Tuberculosis Patients

ABSTRACT

Treatment failure in patients with pulmonary tuberculosis (PTB) poses a great danger to the global effort in control of tuberculosis. This study evaluated prevalence of treatment failure among PTB patients at a tertiary care teaching hospital in Pakistan. Consecutive patients of smear positive PTB patients managed between February 2011 to October 2013 at the directly observed therapy (Tuberculosis) unit of our hospital were enrolled for the study. Sputum specimens were collected from each patient at entry for Acid Fast Bacilli microscopic examination and repeated at the end of 2nd (in category I cases only), 3rd (in category II cases only), 5th and 7th month of treatment. Of the 144 patients recruited, 124 patients consisting of 53 (42.74%) males and 71 (57.26%) females aged 14-85 years completed the study. Ninety three (75 %) of the patients were New (category I) at entry while 31 (25%) were Retreatment cases (category II). Among 124 smear positive patients at baseline, 22 (17.74%), 6(4.84%) and 6(4.84%) patients remained positive after 2nd (in category I patients only) and 3rd (in category II cases only), 5th and 7th month of treatment respectively. In conclusion, there is considerable treatment failure rate (4.84%) among our smear positive TB patients; and this poses a great danger to healthcare personnel and close contacts in the community.

Key words: Pulmonary tuberculosis, prevalence, treatment failure.

INTRODUCTION:

About two billion or nearly a third of the world’s population is infected with Mycobacterium tuberculosis.(1) The global prevalence of TB was an estimated 14 million, with 9.4 million incident cases and 1.3 million deaths among HIV-negative cases for the year 2009. (2) Eighty-five percent of the 9 million people infected with TB each year live in the developing countries. (2) Whereas more women of child bearing age die of Tuberculosis than from all causes of maternal mortality combined.(3) TB incidence has tripled in high HIV prevalence countries in the last two decades with a slight decline in 2009. Globally, in people living with AIDS, one out of every four deaths is due to TB; globally 380,000 people died of HIV associated TB in 2009. Persons co-infected with TB and HIV are 20-30 times more likely to develop active TB disease than persons without HIV. Globally, 440,000 MDR TB cases were estimated in 2009 (8). There are 27 high MDR TB burden countries contributing 86% of the MDR TB case burden. Pakistan falls on number 4 among these high MDR TB burden countries.(2) Currently Pakistan stands 5th amongst the 22 high TB burden countries which account for about 81 % of all estimated TB cases around the globe. (4) Pakistan contributes about 63% of tuberculosis burden in the Eastern Mediterranean Region. According to WHO, the incidence of sputum positive TB cases in Pakistan is 97/100,000 per year and for all types it is 231/100,000 or around 420,000 new cases each year. The prevalence of the disease is much higher and is estimated at 373/100,000 population or 670,000 cases.(5) TB is responsible for 5.1 percent of the total national disease burden in Pakistan. The impact of TB on socio economic status is substantial.(6) Sputum smear-positive patients are the most potent sources of infection and, without chemotherapy, have poor outcomes, as about two-thirds of them die within 2-3 years of developing disease. (Ten years case fatality rate of HIV negative untreated smear positive pulmonary tuberculosis is 70%, while that for smear negative cases is 20%). (7)

Non-completion of treatment has serious consequences, including ongoing infectiousness and development of drug-resistant Mycobacterium tuberculosis. The problem of resistance results from treatment that is inadequate, often because of an irregular drug supply, inappropriate regimens, or poor compliance. Drug resistance is a potential threat to tuberculosis-control programs throughout the world. (8)

Materials and methods

The study was carried out in a tertiary care teaching hospital in Pakistan. The research proposal was approved by the Ethics and Review Committee of the hospital. Informed consent was obtained from the patients. The hospital has a TB clinic which is supported by the National Tuberculosis Control Programme Pakistan. Laboratory services for sputum microscopy and the drug regimens are provided according to National Tuberculosis Control Programme protocol.

Consecutive patients who presented at the TB clinic of the hospital with smear positive pulmonary tuberculosis were enrolled. Sociodemographic data such as age, sex, marital status and occupation were recorded. Patients of age less than 5 years were excluded.

Before enrolling into the study, the patients were well informed about the consequences and potential predictors of treatment failure such as treatment compliance. Pretreatment sputum specimens were collected from each patient for acid fast bacilli (AFB) examination. Patients were categorized as New cases (category I) and Retreatment cases (category II) on the basis of history of previous anti TB treatment. All patients were followed up to completion of eight months TB treatment. Sputum examinations were repeated at 2^nd month (in case of category I only), 3^rd month (in case of category II only), 5^th month and 7^th month of treatment. Data were entered and analyzed using SPSS 16.0 version.

Results

A total of 144 patients were recruited during the study period (between February 2011 and October 2013). Twenty patients were either transferred out or lost to follow up. One hundred and twenty four patients who completed their treatment at the centre were evaluated. There were 93(75%) New cases (category I) and 31(25%) Retreatment cases (category II). There were 71 (57.26%) females and 53(42.74%) males aged between 14 and 85 years. Majority of the patients (47.58%) were aged above 45 years with 6 patients above 80 years. Table 2 shows the age group distribution of sputum positive pulmonary TB patients on entry.

Repeat sputum AFB results in study participants are presented in figure 1. Of the 124 patients who were sputum positive at baseline, 6 (4.84%) patients were AFB smear positive after 5 months therapy revealing the prevalence of treatment failure in these patients. Our study showed that TB affects mainly the middle and elderly age in our environment (47.58% of the patients managed were above age 45 years). This finding is also observed in some studies from the developed countries (9), While in developing countries it affects mainly the young age group. (10) One reason may be the changing circumstances in the less developed countries and further large scale studies may highlight the issue. Greater percentage of our study population was females which again is different from studies in our region. (10,11) Treatment failure rate among our patients was 4.84%. Though this is lower tthan reported in many studies we still need to further improve it (The cure rate of tuberculosis among Category I patients in our study was more than the cure rate reported by studies from Bangalore (65.7%) and Tamil Nadu (75%). (12,13) The World Health Organization guidelines have recommended achieving cure rate of 85%. The smear positive TB patients pose a significant risk to members of the public, close relatives, and health care staff who treat these patients. They are the focus for infection control measures, and contact investigations. This type of patient must be isolated because of risk of transmitting microbes. Treatment failure increases the risk further. These are the cases where there are much chances of drug resistance including multidrug resistance and extended drug resistance. ((((All 3 failure patients who underwent DST testing had MDR-TB, while 3 of 22 of relapse patients and 0 of 5 default patients tested did. While these DST results were only available for three failure patients and, therefore, not representative, these data and those from other studies suggest that MDR risk is not uniform among retreatment subgroups, with increased prevalence of MDR among patients with initial treatment failure. (14-16) Drug resistance is a global health concern and effective programmatic therapy of the smear positive cases is one of the cornerstones in its prevention. Facilities for rapid detection of rifampicin resistance are being made available throughout the country which can help in early detection of drug resistant cases. Physicians involved in TB management need to be involved in its programmatic management and timely referrals for testing resistance in appropriate cases. Taken together, these findings support use of DST in all retreatment patients, earlier DST testing in those with clinical and microbiological indications of impending treatment failure, and use of second-line drugs for retreatment of patients with initial treatment failure until DST results are known.(17) Recently, total drug-resistant tuberculosis has been described in which some patients with TB infection were completely unresponsive to all TB drugs. This is a big blow to the global effect in control of TB. On the other hand, additional burdens of isolation and stigmatization on the patients are enormous. (18) Noncompliance to treatment, deficient patient knowledge/health education, drug quality, and other comorbidities like diabetes mellitus and HIV infection had been identified as major predictors of treatment failure in patients with TB. These factors were not considered in our study participants. According to observations made in many countries, only directly observed therapy is capable of improving treatment outcomes. (19-22) The effectiveness of the DOTS strategy is also confirmed by our own studies.

In conclusion, there is still considerable treatment failure rate among TB patients managed in our tuberculosis clinic. There is need for provision of facility for sputum culture for detection of patients with drug resistant TB cases. Policies on the management of tuberculosis need to be reviewed and strengthened in order to reduce open TB cases in the community.