CHAPTER  ONE

INTRODUCTION

1.1     Background to the study

Tuberculosis (TB) is a chronic airborne infectious disease caused by the bacillus Mycobacterium tuberculosis (MTB). According to a World Health Organization (WHO) 2016 report, MTB remains a major public health problem, ranking above HIV/AIDS. It is one of the leading causes of morbidity and mortality among infectious diseases worldwide WHO, (2016). The best estimate of TB deaths in 2015 was 4 million, with an additional 0.4 million deaths resulting from TB disease among HIV-positive people. In terms of cases, there were 10.4 million new TB cases, of which 5.9 million were men, 3.5 million women, and 1 million children detected. Cases that remain undetected continue to suffer from TB disease and also transmit the disease to their contacts Morrisonet al., (2008).

Tuberculosis/Human immunodeficiency virus (TB/HIV) co-infection has been a common phenomenon for decades, causing a substantially high morbidity and mortality with Tuberculosis ranking as the most common opportunistic infection and the most common cause of mortality among people living with HIV/AIDS (PLWHA) especially in resource restricted countries Manosuthi W et al, (2008) Corbett EL et al., (2003). In the year 2013 alone about 1.1 million new cases of TB were reported in HIV positive patients glob-ally where Majority of them (up to 78%) occurred in Africa WHO, (2014). Tuberculosis occurs as the first manifestation of HIV/AIDS in more than 50% of HIV positive patients WHO, (2004) and deaths that are linked to TB are significantly high especially in sub-Saharan Africa where in some countries this rate is reported to be more than 50% WHO, (2011).

Early initiation of Antiretroviral therapy (ART) in the course of TB treatment has been shown to have a mortality benefit and WHO strongly recommends on co-treatment of HIV/TB co-infection, with a rapid scaling up of Anti-retroviral therapy programs especially in resource restricted countries, where tuberculosis is for the most part the widespread opportunistic disease. Lawn et al., (2011) In these areas thus ART is regularly initiated when patients are being treated for tuberculosis, with a goal line being to provide an effective and safe Antiretroviral therapy and anti-tuberculosis management which is efficient enough to cure and prevent recurrence and resistance Friedland  et al., (2006).

Despite this overall success, HIV and TB co-treatment faces several important challenges including induction of sub-therapeutic levels of both Non-Nucleotide Reverse Transcriptase Inhibitors (NNRTIs) and Protease Inhibitors (PIs). Rifampicin which is the most important component of anti-tuberculous medications is remarkable for its induction effect on CYT P450 isoenzymes which may adversely increase the metabolism and disposition of both NNRTIs and PIs which can potentially cause inadequate plasma levels of these drugs and severely limiting the treatment options for optimal Highly Active Antiretroviral Therapy (HAART) regimens especially in resource limited settings. Whereas it has been established from prior studies that Rifampicin may be a cause of significant suboptimal levels of both NNRTIs and PIs, sub-therapeutic ARV plasma levels.Consequently, have been demonstrated to be associated with inadequate virological suppression which may subsequently lead into selection of resistant strains and a long term inadequate immune recovery and overall poor clinical outcome Brinkhof  et al, (2007).

In developed countries this challenge is overcome using Therapeutic Drug Monitoring (TDM) that is readily available for routine practical use where the patients’ NNRTIs and PIs plasma levels are monitored for any adverse drug levels, and corrections of dosages are timely done to improve the therapeutic outcomes. TDM has been useful in several clinical settings including monitoring of ARV plasma levels in TB/HIV co-treatment. In this regard a better treatment outcome has been documented among patients whose treatment was TDM guided than those whose ARV plasma levels were not monitored. Even though TDM is not done in most of the resource limited countries, the available studies from these settings demonstrate that a significant proportion of HIV patients co-treated with Anti-Tuberculous drugs (Rifampicin) have sub-therapeutic NNRTIs and PIs plasma levels and some of the locations have reported even higher rates of sub-therapeutic ARV (NNRTIs and PIs) plasma levels than most of resource rich countries Boulle et al, (2008)

1.2     Statement of the problem

The diagnosis, treatment and prevention of TB has become more complicated because of HIV-associated TB and multidrug resistant (MDR) TB. Many people die of TB owing to delayed diagnosis, which makes people, mainly in the sub-Saharan region, unable to reduce transmission significantly, and thus the epidemic continues. A global TB report estimated that there were about 322/100,000 population incidence for all forms of TB in Nigeria, 330/100,000 populationprevalence for all forms of TB. In the same report, there were about 97/100,000 population deathsdue to TB, (excludingHIV+TB), Mortality rate (HIV+TB only) for all forms of TB is 44/100,000 population related deaths during the same period. Nigeria ranks fourth among the world’s 30 high-TB-burden countries, second in sub-Saharan Africa. Globally in 2015 an estimated 480,000 people developed Multi resistant TB (MDR-TB) WHO, (2015).

Worldwide emergence of MDR-MTB has been reported in both developed and developing countries Sethi et al., (2004). Smear microscopy is widely used for the rapid diagnosis of TB, but it does not detect DR-MTB or sensitivity.In individuals who are coinfected with HIV, the detection rate varies between 20% and 50%. Results of mycobacterial culture turnaround require about 2–8 weeks, though this is not widely available in developing countries, including Nigeria.Getahunet al., (2006) This creates a diagnostic delay that hinders disease control, enhances transmission, and increases health-care costs. However, in 2010 WHO recommended the use of GeneXpert platform for the initial diagnosis test in all individuals presumed to have all forms of TB and paediatric TB. The test simultaneously detects MTBC and resistance to rifampicin (RIF) in less than 2 hours.In comparison, standard cultures can take 2 to 6weeks for MTBC to grow and conventional drug drug resistance test can add more weeks.

Despite the recommendation by WHO to use GeneXpert for routine TB test, continuous surveillance of the primary and acquired DR patterns of MTB is vital in assessing the efficacy of treatment regimens, as well as in detecting problems related to previous TB treatments. However, in developing countries, TB-culture and DR testing are not routinely carried out as part of the laboratory workup, owing to extreme economic disparities, low literacy, and impaired basic health-service delivery. Determining the prevalence of rifampicin-resistant MTBis critical to prevent drug resistance, like MDR-TB and extensively DR-TB.

As far as the literature is concerned, little work has been done to document information systematically on the prevalence of rifampicin-resistant among TB and HIV co-infected patients in Benue State of Nigeria.

1.5            Significance of the Study

The results from this study will be useful to assist the overall optimization of management of patients on ARV/anti-TB co-treatment especially in resource limited settings.

Also, the results from this study will provide a base for further studies on the subject and add to the existing body of knowledge regarding rifampicin resistance especially in resource limited countries.

1.4            Research Questions

1. What is the proportion of TB/HIV co-infected diagnosed with RIF resistance Pulmonary TB (PTB)
2. What is the distribution of RIF resistance PTB among Different age groups
3. What is the proportion of RIF resistance PTB in male and female gender

1.3     Objectives of the Study

The main objective of the study is to determine the prevalence of Rifampicin resistance TB among TB HIV Co-infected patients in Benue State of Nigeria while the specific objectives are to:

1. To determine the distribution of cases of RIF resistance bygender among TB/ HIV co-infected patients in Benue State.   
2. To determine prevalence of rifampicin resistance among TB-HIV positive patients in Benue State
3. To determine distribution of cases of RIF resistance by age among TB/HIV co-infected in Benue.

1.6     Scope of the Study/Limitation of the Study

The scope the study was delimited to prevalence of Rifampicin resistance TB among TB / HIV Co-infected patients in Benue State of Nigeria.

In every research work, it is likely that the researcher may encounter some limitations. The researcher encountered some challenges during the period of carrying out this research. Some of these challenges include the dearth of materials for a proper and effective research work constituted a major limitation. Again, how to get the true and required information from the health personnel on duty and medical record units as well as the Laboratorians also constituted a little constraint in the study.