PATTERN OF FIRST-LINE ANTI-TUBERCULOSIS DRUG RESISTANCE AND ASSOCIATED FACTORS IN PATIENTS ATTENDING NATIONAL TUBERCULOSIS AND LEPROSY TRAINING CENTRE AND REFERRAL HOSPITAL ZARIA


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TABLE OF CONTENTS

Title page
Table of contents
List of acronyms
Summary

Chapter One - Introduction
1.1       Background
1.2       Problem Statement
1.3       Justification
1.4       Research questions
1.5       General and specific Objectives
1.5.1    General objectives
1.5.2    Specific objectives

Chapter Two - Literature Review
2.1       History of Tuberculosis
2.2       Causative Organism
2.3       Epidemiology of TB
2.4       Pathogenesis of the infection
2.5       Molecular techniques for TB diagnosis
2.6       TB drugs and development of resistance
2.7       Mechanisms of TB drug resistance
2.8       Global burden of TB
2.9       Pattern of anti-TB drug resistance
2.10     Factors associated with anti-TB drug resistance

Chapter Three – Methodology
3.1       Study area
3.2       Study design
3.3       Study population
3.3.1    Inclusion criteria
3.3.2    Exclusion criteria
3.4       Samples size determination
3.5       Sampling technique
3.6       Study instruments
3.6.1    Data Collection
3.6.2    Laboratory analysis
3.7       Data Collection methods
3.7.1    Sample collection and processing
3.8       Data management
3.8.1    Quality assurance and quality control
3.8.2    Statistical analysis
3.9       Ethical considerations
3.10     Limitations

Chapter Four – Results
4.1       Socio-demographic characteristics of participants
4.2       Identification of MTB and drug resistance
4.3       Bivariate analysis
4.4       Unconditional logistic regression analysis

Chapter Five – Discussion
5.1       Discussion

Chapter Six – Conclusions and Recommendations
6.1       Conclusions
6.2       Recommendations
References



SUMMARY

Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis.

Despite the availability of Short-course regimens of first-line drugs that can cure around 90% of cases, TB remains a major global health problem causing ill-health among millions of people each year. It ranks as the second leading cause of death from an infectious disease worldwide. In 2012, nearly 8.6 million people developed TB and 1.3 million died from the disease worldwide. Among these deaths, there was an estimated 450,000 who developed multi-drug resistant TB (MDR-TB) with an estimated 170,000 deaths. The African Region has 24% of the world’s cases and the highest rates of cases and deaths per capita. This study was therefore carried out to determine the pattern of first-line anti-Tb drug resistance and associated factors in patients attending National Tuberculosis and Leprosy Training Centre/Referral Hospital Zaria.

Sputum samples were collected from 200 DR-TB suspects median age 32 years (range 15 – 75 years) of which 138 (69%) were males. Among these, 156 (78%) and 44(22%) were new and retreatment cases respectively. Also, 59.5 % of the patients were in the age group 21-40 years and 90.6% of them were either unemployed or self employed, and 68.9% either have no formal education or terminated at secondary school level. The sputum samples were first screened for

M. Tuberculosis complex and rifampicin resistance using GeneXpert(MTB/Rif) and confirmed with Hain line probe aassay(LPA).

Of the 200 samples, 81(40.5%) were positive for Mycobacterium tuberculosis, out of which 55(67.9%) were rifampicin (RIF) resistant. More males (74.1%) were positive for MTBC and for MDR-TB (76.2%) than females. The highest resistance to any one drug alone and in combination with other drugs was found in rifampicin (67.9%). However, rifampicin mono resistance was 13.6%, Isoniazid mono resistance was 1.2% while mono resistance to streptomycin and ethambutol were not seen. Furthermore, 6 (7.4%) were resistant to all the 4 first line drugs while MDR-TB was (51.8%). On bivariate analysis, six factors were found to be associated with development of MDR-TB, 4 of which are patient related while 2 are health care related. Among these, being a retreatment case was the only statistically significant factor (OR=8.2, P-value <0 -="" .01="" a="" admitted="" against="" and="" associated="" at="" be="" being="" case="" development="" during="" factor="" factors="" found="" hospital="" however="" logistic="" male="" mdr-tb.="" mdr-tb="" of="" on="" only="" protective="" regression="" remained="" retreatment="" sex="" span="" study="" tb="" the="" to="" treatment="" two="" with="">



The study concluded that there was a high rate of rifampicin resistance and MDR-TB among patients attending NTBLTC/Referral Hospital Zaria and recommends that health care providers should adequately educate TB patients on the need for treatment adherence in order to prevent development of anti-TB drug resistance. The TB-DOTS strategy should also be reinforced to ensure patient compliance. Availability of drugs should also be ensured at all times and non-fixed drug combinations should be discouraged.




CHAPTER ONE – INTRODUCTION


1.1        Background

Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis.

Despite the availability of Short-course regimens of first-line drugs that can cure around 90% of cases since the 1980s, TB remains a major global health problem causing ill-health among millions of people each year. It ranks as the second leading cause of death from an infectious disease worldwide.(1) In 2012 for example, nearly 8.6 million people developed TB and 1.3 million died from the disease worldwide. Among these deaths, there was an estimated 450,000 people reported to have developed multi-drug resistant TB(MDR-TB) with an estimated 170,000 deaths due to MDR-TB.(2)

Geographically, the burden of TB is highest in Asia and Africa, India and China together account for almost 40% of the world’s TB cases, while about 60% of cases are in the South-

East Asia and Western Pacific regions. The African Region has 24% of the world’s cases, and the highest rates of cases and deaths per capita.(1) Although there has been considerable progress in reducing TB cases and deaths globally, the emergence of anti-Tuberculosis drug resistance has become a major problem confronting the global control of tuberculosis.(2) For this reason, knowledge of the estimate and pattern of drug resistance is extremely important in the epidemiology and control of TB.(3)

Recently, anti-TB drug resistance, particularly multi-drug resistant TB has received increased attention worldwide and it is said to occur in the majority of cases due to failure or inadequacy of TB control programs,(4) and in some cases due to inadequate treatment regimens prescribed by providers, nosocomial transmission as well as non-compliance by patients.....

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