CHAPTER ONE

INTRODUCTION

1.1 Background of the Study

Tuberculosis (TB) is a potentially serious infectious disease that mainly affects your

lungs. The bacteria that cause tuberculosis are spread from one person to another through tiny

droplets released into the air via coughs and sneezes.

Tuberculosis with the bacteria Tubercle bacillus, in the past also called phthisis, Phthisis

pulmonalis or consumption, is a wide spread and in many cases fatal infectious disease caused by

various strains of Mycobacterium, usually Mycobacterium tuberculosis (Raviglione et al., 2010).

Tuberculosis typically attacks the lungs, but can also affect other parts of the body. It spreads

through the air when people who have an active tuberculosis infection cough, sneezes or

otherwise transmits respiratory fluids through the air (Horsburgh & Rubin, 2011).

Most infections do not have symptoms, known as Latent Tuberculosis. About one in ten latent

infections eventually progresses to active disease which if left untreated, kills more than 50% of

those so infected.

1.1.1 Epidemiology of Tuberculosis

Roughly one-third of the world's population has been infected with M. tuberculosis (WHO,

2010), with new infections occurring in about 1% of the population each year (WHO, 2002).

However, most infections with M. tuberculosis do not cause tuberculosis disease (CDC, 2011),

and 90–95% of infections remain asymptomatic (Skolnik, 2011). In 2012, an estimated 8.6

million chronic cases were active (WHO, 2013). In 2010, 8.8 million new cases of tuberculosis

were diagnosed, and 1.20–1.45 million deaths occurred, most of these occurring in developing

1

countries (WHO, 2011 & Lozano, 2012). Of these 1.45 million deaths, about 0.35 million occur

in those also infected with HIV (WHO, 2011b).

Tuberculosis is the second-most common cause of death from infectious disease (after those due

to HIV/AIDS) (Gerald, et al., 2010). The total number of tuberculosis cases has been decreasing

since 2005, while new cases have decreased since 2002 (WHO, 2011). China has achieved

particularly dramatic progress, with about an 80% reduction in its tuberculosis mortality rate

between 1990 and 2010 (WHO, 2011c). The number of new cases has declined by 17% between

2004–2014 (Kielstra, 2014). Tuberculosis is more common in developing countries; about 80%

of the population in many Asian and African countries test positive in tuberculin tests, while only

5–10% of the US population test positive (Kumar, et al., 2007). Hopes of totally controlling the

disease have been dramatically dampened because of a number of factors, including the

difficulty of developing an effective vaccine, the expensive and time-consuming diagnostic

process, the necessity of many months of treatment, the increase in HIV-associated tuberculosis,

and the emergence of drug-resistant cases in the 1980s (Lawn, 2011).

In 2007, the country with the highest estimated incidence rate of tuberculosis was Swaziland,

with 1,200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0

million new cases (WHO, 2009). In developed countries, tuberculosis is less common and is

found mainly in urban areas. Rates per 100,000 people in different areas of the world were:

globally 178, Africa 332, the Americas 36, Eastern Mediterranean 173, Europe 63, Southeast

Asia 278, and Western Pacific 139 in 2010 (WHO, 2011b). In Canada and Australia, tuberculosis

is many times more common among the aboriginal peoples, especially in remote

areas(FitzGerald, et al., 2000 &Quah et al., 2009). In the United States Native Americans have a

2

fivefold greater mortality from tuberculosis (Birn, 2009), and racial and ethnic minorities

accounted for 84% of all reported tuberculosis cases (CDC, 2012).

The rate of tuberculosis varies with age. In Africa, it primarily affects adolescents and young

adults (WHO, 2006). However, in countries where incidence rates have declined dramatically

(such as the United States), tuberculosis is mainly a disease of older people and the

immunocompromised (risk factors are listed above) (Kumar, et al., 2007 & CDC, 2006).

Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well as

83% of deaths (Kielstra, 2014).

1.1.2 History of Tuberculosis

Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of

M. tuberculosis involves evidence of the disease in the remains of bison in Wyoming dated to

around 17,000 years ago. However, whether tuberculosis originated in bovines, then was

transferred to humans, or whether it diverged from a common ancestor, is currently unclear. A

comparison of the genes of M. tuberculosis complex (MTBC) in humans to MTBC in animals

suggests humans did not acquire MTBC from animals during animal domestication, as was

previously believed. Both strains of the tuberculosis bacteria share a common ancestor, which

could have infected humans as early as the Neolithic Revolution (Comas &Gagneux, 2009).

Skeletal remains show prehistoric humans (4000 BC) had tuberculosis, and researchers have

found tubercular decay in the spines of Egyptian mummies dating from 3000–2400 BC. Genetic

studies suggest tuberculosis was present in the Americas from about 100 AD (Konomi, et al.

2002).

3

Phthisis is a Greek word for consumption, an old term for pulmonary tuberculosis (Chambers

Dictionary, 1998); around 460 BC, Hippocrates identified phthisis as the most widespread

disease of the times. It was said to involve fever and the coughing up of blood, which was almost

always fatal (Hippocrates, 2006).

Before the Industrial Revolution, folklore often associated tuberculosis with vampires. When one

member of a family died from it, the other infected members would lose their health slowly.

People believed this was caused by the original person with tuberculosis draining the life from

the other family members (Sledzik & Bellantoni, 1994).

Although the pulmonary form associated with tubercles was established as a pathology

by Dr Richard Morton in 1689 (Trail, 1970), due to the variety of its symptoms, tuberculosis was

not identified as a single disease until the 1820s. It was not named "tuberculosis" until 1839, by

J. L. Schönlein. During 1838–1845, Dr. John Croghan, the owner of Mammoth Cave, brought a

number of people with tuberculosis into the cave in the hope of curing the disease with the

constant temperature and purity of the cave air; they died within a year (CNN, 2004). Hermann

Brehmer opened the first tuberculosis sanatorium in 1859 in Görbersdorf (now Sokołowsko),

Silesia (McCarthy, 2001).

The bacillus causing tuberculosis, M. tuberculosis, was identified and described on 24 March

1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this

discovery (Nobel Foundation, 2006). Koch did not believe the bovine (cattle) and human

tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of

infection. Later, the risk of transmission from this source was dramatically reduced by the

invention of the pasteurization process. Koch announced a glycerin extract of the tubercle bacilli

as a "remedy" for tuberculosis in 1890, calling it "tuberculin". While it was not effective, it was

4

later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis

(Waddington, 2004). Albert Calmette and Camille Guérin achieved the first genuine success in

immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was

called Bacille Calmette–Guérin (BCG). The BCG vaccine was first used on humans in 1921 in

France (Bonah, 2005), but received widespread acceptance in the US, Great Britain, and

Germany only after World War II (Comstock, 1994).

Tuberculosis caused the most widespread public concern in the 19th and early 20th centuries as

an endemic disease of the urban poor. In 1815, one in four deaths in England was due to

"consumption". By 1918, one in six deaths in France was still caused by tuberculosis. After

tuberculosis was determined to be contagious, in the 1880s, it was put on a notifiable disease list

in Britain; campaigns were started to stop people from spitting in public places, and the infected

poor were "encouraged" to enter sanatoria that resembled prisons (the sanatoria for the middle

and upper classes offered excellent care and constant medical attention). Whatever the

(purported) benefits of the "fresh air" and labor in the sanatoria, even under the best conditions,

50% of those who entered died within five years (circa 1916) (McCarthy, 2001).

In Europe, rates of tuberculosis began to rise in the early 1600s to a peak level in the 1800s,

when it caused nearly 25% of all deaths (Bloom, 1994). By the 1950s, mortality had decreased

nearly 90% (Persson, 2010). Improvements in public health began significantly reducing rates of

tuberculosis even before the arrival of streptomycin and other antibiotics, although the disease

remained a significant threat to public health such that when the Medical Research Council was

formed in Britain in 1913, its initial focus was tuberculosis research (Hannaway, 2008).

In 1946, the development of the antibiotic streptomycin made effective treatment and cure of

tuberculosis a reality. Prior to the introduction of this drug, the only treatment (except sanatoria)

5

was surgical intervention, including the "pneumothorax technique", which involved collapsing

an infected lung to "rest" it and allow tuberculous lesions to heal (Shields, 2009).

Because of the emergence of MDR-TB, surgery has been re-introduced as an option within the

generally accepted standard of care in treating tuberculosis infections. Current surgical

interventions involve removal of pathological chest cavities ("bullae") in the lungs to reduce the

number of bacteria and to increase the exposure of the remaining bacteria to drugs in the

bloodstream, thereby simultaneously reducing the total bacterial load and increasing the

effectiveness of systemic antibiotic therapy (Lalloo, et al., 2006).

Hopes of completely eliminating tuberculosis (cf.smallpox) from the population were dashed

after the rise of drug-resistant strains in the 1980s. The subsequent resurgence of tuberculosis

resulted in the declaration of a global health emergency by the World Health Organization in

1993(WHO, 2011).

1.1.3 Etiology of the Disease and Risk Factors

The causative agent responsible for tuberculosis is an acid-fast bacillus known as

Mycobacterium tuberculosis. Compared to other bacteria, this bacterium does not stain well with

Gram stain, but is able to take in the carbol-fuchsin dye upon Ziehl-Neelsen staining and displays

a red color resistant to acid-alcohol washes when seen under a microscope. The growth of this

mycobacterium occurs at a very slow rate, doubling about every 20 hours compared to every 20

minutes for most non mycobacterium. Primary infection occurs from inhaling airborne droplets

containing the bacterium. The number of organisms inhaled, their virulence, and the host’s

immune response determine whether the infection progresses to active tuberculosis or remains

latent (Mayo Clinic, 2015).

6

There are a variety of risk factors for tuberculosis. Patients who were recently infected or

those with close contact to individuals with tuberculosis, such as health care workers, are at

increased risk of acquiring the disease. Others include those who were born in or have emigrated

from countries with a high prevalence of tuberculosis and those who are homeless, incarcerated,

or IV drug users, or who live in unsanitary conditions. Race and ethnicity are important risk

factors. Hispanics, African Americans, and Asian Americans carry a greater risk of tuberculosis

when compared to whites. The percentage of foreign-born persons with tuberculosis is higher

than that of U.S.-born persons, and most cases of tuberculosis in the U.S. are found in the major

points of entry: California, Florida, New York, and Texas. Finally, patients with weakened

immune systems such as those with cancer, solid-organ transplants, and HIV have an increased

risk for tuberculosis (American Lung Association, 2012).

1.1.4 Types of Tuberculosis

From the symptoms of tuberculosis, it can be classified as follows:

i. Latent Tuberculosis. In this condition, you have a tuberculosis infection, but the

bacteria remain in your body in an inactive state and cause no symptoms. Latent

tuberculosis, also called inactive tuberculosis or tuberculosis infection, isn't

contagious. It can turn into active tuberculosis, so treatment is important for the

person with latent tuberculosis and to help control the spread of tuberculosis in

general. An estimated 2 billion people have latent tuberculosis.

ii. Active Tuberculosis. This condition makes you sick and can spread to others. It can

occur in the first few weeks after infection with the tuberculosis bacteria, or it might

occur years later (Skolnik, 2011).

7

1.1.5 Pathophysiology of Tuberculosis

Tuberculosis spreads from one person to another by coughing or sneezing and occurs when

droplets of M tuberculosis are suspended in the air and then inhaled into the lungs. Once in the

alveoli, macrophages attempt to ingest the bacilli. If the bacilli continue to multiply,

macrophages may rupture and release the bacilli, causing the spread of the bacteria to the lymph

nodes and possibly into the blood. Cell-mediated immunity begins with the presentation of

antigens to the T lymphocytes. Upon activation, T lymphocytes release interferon-gamma as well

as other cytokines, which causes the macrophages to become bactericidal. Delayed-type

hypersensitivity also occurs after activation and multiplication of T lymphocytes. A few weeks

after exposure, macrophages typically form granulomas to hold the bacilli and prevent the spread

of the infection. Bacilli contained within granulomas may become dormant, resulting in LTBI.

This is shown in most patients by a positive tuberculin skin test (TST) due to tissue

hypersensitivity. Patients with LTBI are not infectious and cannot spread the disease. In 10% of

infected patients, LTBI may progress to active tuberculosis. Patients with active tuberculosis are

infectious and can spread the disease (Skolnik, 2011).

1.1.6 Clinical Presentation and Diagnostic Considerations

A comprehensive patient history, including travel history and clinical presentation, is important

when evaluating a patient for tuberculosis. While LTBI is usually asymptomatic, patients with

active pulmonary tuberculosis may present with persistent productive cough, hemoptysis, fever,

dull or aching chest pain, night sweats, loss of appetite, weight loss, and/or fatigue. Moderate

leukocytosis particularly lymphocytosis may also be observed on hematology reports. Presence

of nodular infiltrates on a chest radiograph, especially in the upper lobe, as well as formation of

8

cavities, is usually consistent with tuberculosis, and the presence of acid-fast bacilli in the

sputum indicates a positive result (CDC, 2012).

The Mantoux test, also known as the purified protein derivative (PPD) test or TST, has been the

gold standard for tuberculosis testing for many years. Once an intradermal tuberculin injection is

given, individuals with prior exposure to tuberculosis will produce a delayed-type

hypersensitivity reaction characterized by an induration. The reaction peaks at 48 to 72 hours and

should be read within that time frame. Based on the maximum induration, a positive test is

confirmed according to patient-specific factors. A positive skin test requires further examination

to determine whether a person has LTBI or active tuberculosis. Many factors affect the result of

the tuberculin skin test, especially being infected with nontuberculous mycobacteria and being

immunized with the Bacilli Calmette-Guérin (BCG) vaccine. This vaccine is used in many parts

of the world, but is not routinely used in the U.S. New tests such as nucleic acid amplification

and interferon-gamma release assay are generally considered more sensitive and specific in

detecting M tuberculosis and may potentially replace the TST once more data become available

(Manzurek, et al., 2010).

1.1.7 Risk Factors

Anyone can get tuberculosis, but certain factors can increase your risk of the disease. These

factors include:

Weakened immune system

A healthy immune system often successfully fights tuberculosis bacteria, but your body can't

mount an effective defense if your resistance is low. A number of diseases and medications can

weaken your immune system, including:

HIV/AIDS

9

Diabetes

End-stage kidney disease

Certain cancers

Cancer treatment, such as chemotherapy

Drugs to prevent rejection of transplanted organs

Some drugs used to treat rheumatoid arthritis, Crohn's disease and psoriasis

Malnutrition

Very young or advanced age

Travelling or living in certain areas

The risk of contracting tuberculosis is higher for people who live in or travel to countries that

have high rates of tuberculosis and drug-resistant tuberculosis, such as:

Sub-Saharan Africa

India

China

Russia

Pakistan

Poverty and substance abuse

Lack of medical care. If you receive a low or fixed income, live in a remote area, have

recently immigrated to the United States, or are homeless, you may lack access to the

medical care needed to diagnose and treat tuberculosis.

Substance abuse. IV drug use or alcohol abuse weakens your immune system and makes

you more vulnerable to tuberculosis.

10

Tobacco use. Using tobacco greatly increases the risk of getting tuberculosis and dying

of it.

Where you work or live

Health care work. Regular contact with people who are ill increases your chances of

exposure to TB bacteria. Wearing a mask and frequent hand-washing greatly reduce your

risk.

Living or working in a residential care facility. People who live or work in prisons,

immigration centers or nursing homes are all at a higher risk of tuberculosis. That's

because the risk of the disease is higher anywhere there is overcrowding and poor

ventilation.

Living in a refugee camp or shelter. Weakened by poor nutrition and ill health and

living in crowded, unsanitary conditions, refugees are at especially high risk of

tuberculosis infection.

1.1.8 Treatments and Drugs

Medications are the cornerstone of tuberculosis treatment. But treating tuberculosis takes

much longer than treating other types of bacterial infections.

With tuberculosis, you must take antibiotics for at least six to nine months. The exact drugs and

length of treatment depend on your age, overall health, possible drug resistance, the form of

tuberculosis (latent or active) and the infection's location in the body.

Recent research suggests that a shorter term of treatment — four months instead of nine — with

combined medication may be effective in keeping latent tuberculosis from becoming active

tuberculosis. With the shorter course of treatment, people are more likely to take all their

medication and the risk of side effects is lessened. Studies are ongoing (Horsburgh, 2011).

11

Most Common Tuberculosis Drugs

If you have latent tuberculosis, you may need to take just one type of tuberculosis drug. Active

tuberculosis, particularly if it's a drug-resistant strain, will require several drugs at once. The

most common medications used to treat tuberculosis include:

Isoniazid

Rifampin (Rifadin, Rimactane)

Ethambutol (Myambutol)

Pyrazinamide

If you have drug-resistant tuberculosis, a combination of antibiotics called fluoroquinolones and

injectable medications, such as amikacin, kanamycin or capreomycin, are generally used for 20

to 30 months. Some types of tuberculosis are developing resistance to these medications as well.

A number of new drugs are being looked at as add-on therapy to the current drug-resistant

combination treatment including:

Bedaquiline

Delamanid

PA-824

Linezolid

Sutezolid

Medication Side Effects

Serious side effects of tuberculosis drugs aren't common but can be dangerous when they do

occur. All tuberculosis medications can be highly toxic to your liver. When taking these

medications, call your doctor immediately if you experience any of the following (Mahmoudi &

Iseman, 1993):

12

Nausea or vomiting

Loss of appetite

A yellow colour to your skin (jaundice)

Dark urine

A fever that lasts three or more days and has no obvious cause

Completing Treatment is Essential

After a few weeks, you won't be contagious and you may start to feel better. It might be

tempting to stop taking your tuberculosis drugs. But it is crucial that you finish the full course of

therapy and take the medications exactly as prescribed by your doctor. Stopping treatment too

soon or skipping doses can allow the bacteria that are still alive to become resistant to those

drugs, leading to tuberculosis that is much more dangerous and difficult to treat. To help people

stick with their treatment, a program called directly observed therapy (DOT) is recommended. In

this approach, a health care worker administers your medication so that you don't have to

remember to take it on your own.

Latent Tuberculosis Infection

The ATS and the CDC released guidelines for the treatment of LTBI in 2000.Since then,

several studies have been conducted to evaluate the efficacy and safety of various regimens in

reducing the likelihood of progression to active tuberculosis. The most commonly used

monotherapy is isoniazid 300 mg po daily for 6 to 9 months. This regimen is associated with

rash, hepatotoxicity, and peripheral neuropathy. Alcohol consumption increases the risk of

isoniazid-induced hepatitis and neuropathy. Pyridoxine 25 to 50 mg po daily decreases the risk

of neuropathy and should be administered to high-risk patients such as those with diabetes, HIV,

malnutrition, seizures, or uremia, and to pregnant women. Isoniazid 900 mg po twice weekly for

13

6 to 9 months is an alternative regimen but must be administered by directly observed therapy

(DOT), in which patients are observed to ingest each dose of anti-tuberculous agent to maximize

the likelihood of treatment completion and minimize the risk of resistance. Another commonly

used monotherapy is rifampin 600 mg po daily for 4 months. This regimen is associated with a

low risk of hepatotoxicity and hematologic toxicity, but a high risk of drug interactions, as

rifampin is a potent inducer of CYP450 3A4. Concerns regarding efficacy and lack of data limit

the use of this regimen (Fitzgerald et al., 2010). A commonly used combination therapy is

isoniazid 300 mg and rifampin 600 mg administered daily for 3 months. Although this regimen

can be administered for a relatively short duration of therapy, it is not well studied in the HIV-

negative population and is associated with rash, hepatotoxicity, peripheral neuropathy,

hematologic toxicity, and a high risk for drug interactions. The newest combination therapy is

isoniazid 900 mg and rifapentine 900 mg administered once weekly by DOT. Compared to

isoniazid monotherapy, this regimen is associated with a higher rate of treatment completion and

a lower rate of hepatotoxicity, but with a higher risk of hypersensitivity reactions and drug

interactions, as rifapentine is a potent inducer of CYP3A4. The combination rifampin and

pyrazinamide, whether administered daily for 2 months or twice weekly for 2 to 3 months by

DOT, is no longer recommended because of an unacceptably high rate of severe hepatotoxicity

(Fitzgerald et al., 2010).

1.1.9 Drug Resistance in Mycobacterium Tuberculosis

Drug resistance in M. tuberculosis arises due to the bacteria in ability to respond to the

activities of one or more drugs as a result of mutation or abuse of drug. These are discussed

under the following headlines.

14

Extensively drug-resistant tuberculosis (XDR-TB) is a form of tuberculosis caused by

bacteria that are resistant to some of the most effective anti-TB drugs. XDR-TB strains

have arisen after the mismanagement of individuals with multidrug-resistant TB (MDR-

TB). One in three people in the world is infected with TB bacteria. Only when the

bacteria become active do people become ill with TB. Bacteria become active as a result

of anything that can reduce the person’s immunity, such as HIV, advancing age, or some

medical conditions. TB can usually be treated with a course of four standard, or first-line,

anti-TB drugs (i.e., isoniazid, rifampin and any fluoroquinolone). If these drugs are

misused or mismanaged, multidrug-resistant TB (MDR-TB) can develop. MDR-TB takes

longer to treat with second-line drugs (i.e., amikacin, kanamycin, or capreomycin), which

are more expensive and have more side-effects. XDR-TB can develop when these

second-line drugs are also misused or mismanaged and therefore also become ineffective.

Multi-Drug-Resistant Tuberculosis (MDR-TB) is defined as tuberculosis that is

resistant to at least isoniazid (INH) and rifampicin (RMP), the two most powerful first-

line treatment anti-TB drugs. Isolates that are multiply resistant to any other combination

of anti-TB drugs but not to INH and RMP are not classed as MDR-TB. MDR-TB

develops in otherwise treatable TB when the course of antibiotics is interrupted and the

levels of drug in the body are insufficient to kill 100% of bacteria. This can happen for a

number of reasons: Patients may feel better and halt their antibiotic course, drug supplies

may run out or become scarce, patients may forget to take their medication from time to

time or patients do not receive effective therapy.

Totally Drug-resistant Tuberculosis (TDR-TB) is a generic term for tuberculosis

strains that are resistant to a wider range of drugs than strains classified as extensively

15

drug-resistant tuberculosis. TDR-TB has been identified in three countries; India, Iran,

and Italy. TDR-TB has resulted from further mutations within the bacterial genome to

confer resistance, beyond those seen in XDR- and MDR-TB. Development of resistance

is associated with poor management of cases. Drug resistance testing occurs in only 9%

of TB cases worldwide. Without testing to determine drug resistance profiles, MDR- or

XDR-TB patients may develop resistance to additional drugs. TDR-TB is relatively

poorly documented, as many countries do not test patient samples against a broad enough

range of drugs to diagnose such a comprehensive array of resistance.

Mechanism of Drug Resistance

Some of the ways the tubercle bacillus acquires drug resistance are:

1. Cell Wall: The cell wall of M. tuberculosis consists of complex lipids, and it acts as a

permeability barrier from drugs.

2. Drug Modifying & Inactivating Enzymes: The M. tuberculosis genome codes for certain

enzymes that make it drug resistant. The enzymes usually phosphorylate, acetylate, or

adenylate the drug compounds.

3. Drug Efflux systems

4. Mutations: Spontaneous mutations in the M. tuberculosis genome can give rise to

proteins that make the bacterium drug resistant, depending on the drug action.

1.2 Vaccine Management of Tuberculosis

Tuberculosis (TB) vaccines are vaccinations intended for the prevention of tuberculosis.

Immunotherapy as a defense against TB was first proposed in 1890 by Robert Koch (Hussey, et

al., 2007). Today, there is only one tuberculosis vaccine available, Bacilli Calmetter-Guérin

16

(BCG), which has been around since 1921. Only three out of every 10,000 people who get the

vaccine experience side effects. Although BCG immunization provides optimal protection for

infants and young children (Oksanen, et al. 2013).

It poses unpredictable and inconsistent consequences in adults, with efficacy ranging

from 0%-80%. (Tameris, 2013; Hussey, et al., 2007) Several confounding variables are

considered responsible for varying outcomes. Demand for TB immunotherapy advancement

exists because the disease has become increasingly drug-resistant (Tameris, 2013).

Forecasting TB Vaccine Development

To promote successful and lasting management of the TB epidemic, effective vaccination

is absolutely required (White et al., 2013) Although the World Health Organization (WHO)

endorses a singular dose of BCG, revaccination with BCG has been standardized in most, but not

all countries (Verma, and Ajay, 2009) However, improved efficacy of multiple dosages has yet

to be demonstrated. It is unlikely that a single new vaccine will meet all or even most of the

requirements for an ideal replacement or alternatives. More than one vaccine will be needed as a

result:

1.2.1 Novel Approaches for Sub-Unit Vaccines

1. Booster to BCG

2. Post-infection

3. Therapeutic vaccine

17

Since the BCG vaccine does not offer complete protection against TB, vaccines have been

designed to bolster BCG’s effectiveness. The industry has now transitioned from developing new

alternatives, to selecting the best options currently available to advance into clinical testing.

MVA85A is characterized as the “most advanced ‘boost’ candidate” to date. (Tyne et al., 2013;

White, et al., 2013)

Vaccine Delivery Alternatives

BCG is currently administered intradermally to improve efficacy, research approaches

have been directed at modifying the delivery method of vaccinations. Patients can receive

MVA85A intradermally or as an oral aerosol this particular combination proved to be protective

against mycobacterial invasion in animals, and both modes are well tolerated. The design

incentive behind aerosol delivery is to target the lungs rapidly, easily and painlessly in contrast to

intradermal immunization. In murine studies, intradermal vaccination caused localized

inflammation at the site of injection whereas MVA85A did not cause unfavourable effects. A

correlation has been found between the mode of delivery and vaccine protection efficacy.

Research data suggests aerosol delivery has not only physiological and economic advantages, but

also the potential to supplement systemic vaccination.

Obstacles in Tb Vaccine Development

Treatment and prevention of TB has been delayed compared to the resources and

research efforts put into other diseases. Large pharmaceutical companies do not see profitable

investment because of TB’s association with the developing world. Progression of vaccine

designs relies heavily on outcomes in animal models. Appropriate animal models are scarce

18

because it is difficult to imitate TB in non-human species. It is also challenging finding a species

to test on a large-scale. Most animal testing for TB vaccines has been conducted on murine,

bovine and non-primate species. Recently, a study deemed zebra fish as a potentially suitable

model organism for preclinical vaccine development (Oksanen et al., 2013).

1.2.2 Hopes for Future Research

Researchers have now discovered a unique copper-repressing protein in the

mycobacterium that may pave the way for new anti-TB treatment. When the host’s immune cells

(macrophages) engulf the invading bacterium, they dump excessive amount of copper onto the

invader bacterium which leads to its cell death. Unfortunately, the invaders have developed their

own defence mechanism in the form of a unique copper repressor protein that blocks the

excessive copper and thereby protects the bacterium from host’s copper attack (Wilmot, 2007).

An approach in a direction to design such compounds that disable the bacterium to fight against

the host body’s defense mechanisms by inhibiting the bacterium copper repressor protein could

serve as a potential weapon against tuberculosis infection.

Genomics research has enabled crucial insights into the adaptive evolution of

Mycobacterium tuberculosis as an obligate human pathogen. As an obligate pathogen, M.

tuberculosis is distinguished from many other infectious organisms (bacterial, viral, and

parasitic) which have recourse to non-human reservoirs. Nevertheless, the application of modern

genomics techniques in these diverse systems reinforces the potential to elucidate functions and

properties that are essential to pathogenesis (Kafsack, et al., 2014), or which drive the rapid

emergence of outbreak strains (Fang, et al., 2012) and ensure their long-term circulation within

host populations (Gire, et al., 2014). High-resolution genotyping, in particular, has revealed that

19

the diversification of clonal infecting strains into ‘clouds of diversity’ (McAdam, et al., 2014) is

a feature of many different pathogenic organisms. Determining the extent to which intraspecific

diversity is crucial for pathogenesis therefore represents a key research question, and will require

the development of systems biology approaches to determine the emergent properties of

microdiverse infecting populations.

For TB, it will be useful to consider the immediate research priorities in the context of the

major lifecycle stages, active disease, clinical latency, and transmission and to prioritize

genomics applications that are most likely to inform future drug and vaccine development

programs In summary, genomics research will continue to drive efforts to understanding the

evolutionary processes that have enabled the adaptation of M. tuberculosis as a human pathogen.

Translating the exciting advances provided by genomics into new tools that can radically

transform TB control will require significant and sustained resourcing. It is incumbent upon the

TB research community to ensure that there is sufficient political will to make this happen.

1.2.3 Drug-Susceptible Pulmonary Tuberculosis

The ATS, CDC, and IDSA released guidelines for the treatment of tuberculosis in 2003.

The goals of therapy are to cure the individual patient, eradicate M tuberculosis, limit the

development of resistance, and prevent disease relapse. There are four recommended regimens

for the treatment of drug-susceptible tuberculosis, and each regimen has an initial phase of 2

months followed by a continuation phase of 4 to 7 months. The initial phase usually consists of

four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol), and the continuation phase

usually includes two agents (isoniazid and rifampin).The use of multiple antituberculous agents

is needed to address resistance issues, and an adherence plan that emphasizes DOT should be

implemented when possible (CDC, 2012).

20

1.2.4 Complications Of Tuberculosis

Without treatment, tuberculosis can be fatal. Untreated active disease typically affects your

lungs, but it can spread to other parts of the body through your bloodstream. Examples of

tuberculosis complications include:

Spinal pain. Back pain and stiffness are common complications of tuberculosis.

Joint damage. Tuberculosis arthritis usually affects the hips and knees.

Swelling of the membranes that cover your brain (meningitis). This can cause a

lasting or intermittent headache that occurs for weeks. Mental changes also are possible.

Liver or kidney problems. Your liver and kidneys help filter waste and impurities from

your bloodstream. These functions become impaired if the liver or kidneys are affected

by tuberculosis.

Heart disorders. Rarely, tuberculosis can infect the tissues that surround your heart,

causing inflammation and fluid collections that may interfere with your heart's ability to

pump effectively. This condition, called cardiac tamponade, can be fatal (Mayo clinic,

2015).

1.2.5 Special Populations

Patients with HIV: It is estimated that 8% of patients with TB in the U.S. are co-infected with

HIV, resulting in increased morbidity and mortality. Treating TB in patients with HIV is

complex and requires vigilant care. Recommendations are similar to those for adults without

HIV, with a few exceptions. Occasionally, HIV-infected patients who develop TB may

temporarily experience exacerbation of symptoms while on treatment due to immune

reconstitution. Guidelines for prevention and treatment of opportunistic infections in HIV-

infected individuals are available from the CDC, the National Institutes of Health, and the HIV

21

Medicine Association of IDSA. Since antiretroviral agents have the potential to interact with

antituberculous agents, it is important to follow the guidelines for managing drug interactions in

the treatment of HIV-related tuberculosis. In general, rifampin can be substituted with dose-

adjusted rifabutin since the latter is less likely to interact with antiretroviral agents, and

rifapentine should not be used because of an increased risk of rifamycin resistance.

Pregnant Women: If the probability of tuberculosis is moderate to high in a pregnant woman,

treatment should be initiated with isoniazid, rifampin, and ethambutol supplemented with

pyridoxine for a minimum of 9 months. Although isoniazid, rifampin, and ethambutol cross the

placenta, they have not been associated with teratogenic effects. There are insufficient data to use

pyrazinamide in pregnant women; thus, it is not recommended for general use.

Patients With Hepatic Impairment: Patients with hepatic impairment are at high risk for

developing drug-induced hepatitis. Isoniazid, rifampin, and pyrazinamide are known to be

hepatotoxic. There are several options available in the setting of hepatic impairment. One option

is a treatment without isoniazid. It includes rifampin, pyrazinamide, and ethambutol for 6

months. Another option is a treatment without pyrazinamide. It includes isoniazid and rifampin

for a total of 9 months, with ethambutol for the initial 2 months or until drug susceptibility

results are obtained. In cases of advanced liver disease, rifampin should generally be used along

with ethambutol for a total of 12 to 18 months and an additional agent such as fluoroquinolone,

cycloserine, or an injectable agent for the first 2 months.

Patients With Renal Impairment: Isoniazid and rifampin are metabolized by the liver; thus, they

do not require dosing adjustment in patients with renal impairment. Pyrazinamide and

ethambutol are partially eliminated by the kidneys; thus, a longer interval involving thrice

weekly dosing is recommended. Levofloxacin, aminoglycosides, and cycloserine also require

22

dosing adjustment based on the degree of renal impairment. Measurement of serum

concentrations should be considered in certain cases to avoid toxicity. In patients undergoing

hemodialysis, antituberculous agents should be administered after dialysis to facilitate DOT and

avoid premature removal (American Lung Association, 2012; Raviglione& O’Brien, 2010).

1.2.6 Prevention of Tuberculosis

If you test positive for latent tuberculosis infection, your doctor may advise you to take

medications to reduce your risk of developing active tuberculosis. The only type of tuberculosis

that is contagious is the active variety, when it affects the lungs. So if you can prevent your latent

tuberculosis from becoming active, you won't transmit tuberculosis to anyone else.

Protect your family and friends

If you have active TB, keep your germs to yourself. It generally takes a few weeks of treatment

with TB medications before you're not contagious anymore. Follow these tips to help keep your

friends and family from getting sick:

Stay home. Don't go to work or school or sleep in a room with other people during the

first few weeks of treatment for active tuberculosis.

Ventilate the room. Tuberculosis germs spread more easily in small closed spaces where

air doesn't move. If it's not too cold outdoors, open the windows and use a fan to blow

indoor air outside.

Cover your mouth. Use a tissue to cover your mouth anytime you laugh, sneeze or

cough. Put the dirty tissue in a bag, seal it and throw it away.

Wear a mask. Wearing a surgical mask when you're around other people during the first

three weeks of treatment may help lessen the risk of transmission (Lawn & Zumla, 2011).

23

Finish your entire course of medication

This is the most important step you can take to protect yourself and others from tuberculosis.

When you stop treatment early or skip doses, tuberculosis bacteria have a chance to develop

mutations that allow them to survive the most potent tuberculosis drugs. The resulting drug-

resistant strains are much more deadly and difficult to treat.

Coping and Support

Treatment for tuberculosis is a complicated and lengthy process. But the only way to cure the

disease is to stick with your treatment. You may find it helpful to have your medication given by

a nurse or other health care professional so that you don't have to remember to take it on your

own. In addition, try to maintain your normal activities and hobbies and stay connected with

family and friends.

Keep in mind that your physical health can affect your mental health. Denial, anger and

frustration are normal when you must deal with something difficult and unexpected. At times,

you may need more tools to deal with these or other emotions. Professionals, such as therapists

or behavioral psychologists, can help you develop positive coping strategies.

1.2.7 Global Impact of Tuberculosis

TB occurs in every part of the world. In 2013, the largest number of new TB cases occurred in

the South-East Asia and Western Pacific Regions, accounting for 56% of new cases globally.

However, Africa carried the greatest proportion of new cases per population with 280 cases per

100 000 population in 2013.

In 2013, about 80% of reported TB cases occurred in 22 countries. Some countries are

experiencing a major decline in cases, while in others the numbers are dropping very slowly.

Brazil and China for example, are among the 22 countries that showed a sustained decline in TB

24

cases over the past 20 years. In the last decade, the TB prevalence in Cambodia fell by almost

50% (Mayo Clinic, 2015).

Key facts

Tuberculosis (TB) is second only to HIV/AIDS as the greatest killer worldwide due to a

single infectious agent.

In 2013, 9 million people fell ill with TB and 1.5 million died from the disease.

Over 95% of TB deaths occur in low- and middle-income countries, and it is among the

top 5 causes of death for women aged 15 to 44.

In 2013, an estimated 550 000 children became ill with TB and 80 000 HIV-negative

children died of TB.

TB is a leading killer of HIV-positive people causing one fourth of all HIV-related

deaths.

Globally in 2013, an estimated 480 000 people developed multidrug resistant TB (MDR-

TB).

The estimated number of people falling ill with TB each year is declining, although very

slowly, which means that the world is on track to achieve the Millennium Development

Goal to reverse the spread of TB by 2015.

The TB death rate dropped 45% between 1990 and 2013.

An estimated 37 million lives were saved through TB diagnosis and treatment between

2000 and 2013 (Mayo Clinic, 2015).

1.2.8 The Pharmacist’s Role in Tuberculosis Management

Pharmacists play a pivotal role in the management of patients with TB by providing their

expertise within an interdisciplinary team approach to patient care. They can assess the

25

appropriateness, efficacy, and safety of antituberculous therapy by monitoring patients and

ensuring medication adherence. They can educate patients and clinicians about the expected

therapy outcomes and the side effects as well as drug interactions associated with antituberculous

agents. Minor adverse events such as gastrointestinal disturbances are common in the first few

weeks of therapy and usually do not necessitate discontinuation of first-line agents. Patients may

choose to take their medications with food, although absorption may be delayed. Other adverse

events such as drug-induced hepatitis, pyrazinamide-induced hyperuricemia, and ethambutol-

induced optical neuritis are more serious, require further evaluation, and may necessitate

discontinuation of therapy. Pharmacists may recommend pyridoxine to decrease the risk of

isoniazid-induced neuropathy. They should screen patients with comorbid conditions such as

HIV infection for potential drug interactions, particularly those patients receiving rifamycins and

protease inhibitors. Pharmacists can also educate patients and clinicians about the importance of

adherence and DOT to ensure efficacy and minimize resistance. They should remain vigilant to

avoid the addition of a single agent to a failing regimen.

Studies have shown better outcomes and substantially improved rates of treatment completion

when pharmacists are directly involved in the management of patients with TB, including health

care workers. Institutions should explore the possibility of adding a pharmacist to their TB

management team (Clark, et al., 2007; Tavitian, et al., 2003; Last &Kozakiewicz, 2009).

1.3 Justification of The Study

Tuberculosis (TB) today remains an epidemic in much of the world, causing the deaths of

several million people each year, mostly in the developing countries. Twenty-two countries,

mostly in South East Asia and Africa, account for 80% of the tuberculosis cases in the world.

Moreover, tuberculosis cases are on the rise in many developed countries too, largely owing to

26

migration and social deprivation - a known predisposer to tuberculosis. If tuberculosis disease is

detected early and fully treated, people with the disease quickly become non-infectious and

usually cured. Resistance to antituberculous drugs - including multidrug-resistant

tuberculosis(MDR-TB) and extensively drug-resistant tuberculosis(XDR-TB) - HIV-associated

tuberculosis, and weak health systems are major challenges in healthcare.

In Nigeria, community pharmacists are often the first point of contact for patients with

health-related and medication questions. The 2007 Wilson Rx Pharmacy customer satisfaction

survey reports that the average pharmacy customer visits their pharmacy an average of two or

three times per month, which is greater than ten times the number of times they visit their

primary care physician in a year (Ginger L). Community Pharmacists are faced with the

challenge of identifying and resolving medication-related problems for prescription and non-

prescription, herbal and dietary supplements on a daily basis. This research hopes to make

known the significance and critical importance of community pharmacist’s role in the

management of tuberculosis in patients. Pharmacist being drug experts, with a sound knowledge,

attitude and practice on how to effectively manage tuberculosis patient will provide optimum

drug therapy to patients, determine the proportion of anti-tuberculosis treatment and improve

their quality of life.

1.4 Objectives of the Study

i. To determine the proportion of tuberculosis patients that are treated by community

pharmacists’.

ii. To assess the knowledge of pharmacists on tuberculosis as a disease and management

role.

27

iii. To determine if the pharmacists’ higher qualification will affect their management

skill in patients with tuberculosis.

28

CHAPTER TWO

METHODS

2.1 Study Design

This is a prospective study design that accesses Community Pharmacists’ knowledge, attitude

and practice towards Tuberculosis and related treatments.

2.2 Research Setting

This research was carried out towards all registered pharmacists’ in community setting in delta

state. Delta State, an oil and agricultural producing state of Nigeria situated in the region known

as the South-South geo-political zone with the recent slogan of the state The Finger of God

which was formerly The Big Heart. Delta state is ethnically diverse with people and seven major

languages and dialects spoken in the state. The state is divided into two regions on account of

state creation movement (between 1976 and 1996) which was a feature of the military

governance in Nigeria.

The first group are the Anioma (Igboid group) which consists of Aniocha/Oshimilli (Igbo

speaking), Ndokwa (Ukwuani speaking) and the Ika group.

The second group comprises Urhobo/Isoko (Ediod group) Itsekiri (Yoruboid group), and the

Ezon ethnic group. The state comprises of 25 Local governments areas which are in three

senatorial districts across the state which includes: Central Senatorial District with 8 local

government areas, Delta North senatorial districts with 9 local government areas, and finally the

Delta South senatorial district comprising of 8 local government headquarters. The state holds

major Cities such as Warri, Agbor, Sapele, Ughelli, the state’s capital, Asaba etc.

29

The name Warri province was once applicable to the part of an area now called Delta State under

the colony and protectorate of Southern Nigeria. Warri is one of the major hubs of petroleum

activities and businesses in the southern Nigeria. It is a commercial capital city of Delta State,

with a population of over 311,970 people according to the national population census figures for

2006. The city is one of the cosmopolitan city is one cities in southern Nigeria comprising

originally of Itsekiri, Urhobo and Ijaw people. Warri is predominantly Christian with mixture of

African traditional religions like most of the Southern Nigeria. The city is known nationwide for

its unique Pidgin English. Warri is regarded as a modern metropolitan area with expanded

infrastructural development in other local government areas such as Uvwie, Udu, Ughelli, Sapele

and Okpe in recent years, with various road networks linking these places into one.

Sapele is a city in Delta State. In 1891, the British government established a vice-consulate at

Sapele. The city holds 5 registered pharmacists’ in community setting. The population grew to

33,638 by 1952, including people from many Nigerian tribes. Today, the city has one of

Nigeria’s major ports. Its industries include the processing of timber, rubber and palm oil, as well

as furniture, tamarind balm and footwear manufacturing. As of 1995, its population was 135,800.

And as of 2005/2006 the population of this advancing city is 142,652.

Abraka is a town in Ethiope East local government area of Delta State. Its headquarters are in the

town of Isiokolo and the town has just 1 registered pharmacist’ in community setting. It has an

area of 380kmsq and a population of 200,792 at the 2006 census with ninety percent of the

people being Urhobos. The people are mainly into subsistence farming, fishing, and animal

husbandry. Delta State University Abraka (DELSU) is situated in the hearts of Abraka which

makes the town a student environment.

30

Asaba is the capital of Delta State and has an estimated population of 149,603 at the 2006

census. Asaba as a capital of delta state has the highest number of licensed community pharmacy

(23) and this may greatly be due to its closeness to Onisha. Asaba was once the colonial capital

of the Southern Nigerian Protectorate, it was founded in 1884. The town of Asaba is located on a

hill at the Western edge of the majestic River Niger. The composition of Asaba is mainly Igbo

people, other groups in the city consists of Isekiri, Urhobo, Isoko, Ijaw, Hausa and Yoruba

People. One of the campuses of Delta State University is situated in Anwai, Asaba, which also

makes the town a student environment.

Agbor, also known as Ominije, is an Igbo town in Delta State Nigeria. The indigenes of Agbor

town are of Ika descendants and were founded by Omini from Aguleri. The people of Agbor

have traditionally relied on Farming and fishing for their food and commerce and have just 3

licensed pharmacists in community setting.

Obiaruku is an Ukwuani town in Ukwuani Local Government Area, Delta State Nigeria. The

population of Obiaruku was 68,731 in 2005With 33090 males and 35620 females. The town has

1 licensed pharmacist in community settings.

2.3 Study Population

A comprehensive current list of licensed pharmaceutical premises in Delta State was obtained

from the Pharmaceutical Society of Nigeria. The total number obtained was 85 and 84 was

retrieved after distribution.

31

2.4 Research Instrument

The research instrument used in collecting data for this study was a 21 item questionnaire which

was scrutinized by the supervising researcher to suit the research objectives. The validated 21

item questionnaire which was modified to suit the study, the was divided into three parts

(Sections A-C) being socio-demographics, knowledge, attitude and practice of the respondent on

Survey of the Role of Community pharmacist in the Management of Tuberculosis. Questionnaire

distribution was carried out from October to September 2015.

2.5 Data Collection Method

The researcher used a self administered questionnaire which was prepared in English Language

to thoroughly assess the respondents’ knowledge, attitude and practice on The Role of

Community Pharmacists in the Management of Tuberculosis.

2.6 Data Analysis

All sorted questionnaires were coded and fed into SPSS (Statistical Package for Social Science)

version 17 spread sheet for descriptive and inferential statistics. Simple percentage was

employed to compare various responses in awareness of tuberculosis and related treatments. The

chi-square statistics was used to test the level of significance of impact of qualification on

management skills of tuberculosis. Significance of the sub groups was determined using the

adjusted residual of the various items.

32

CHAPTER THREE

RESULTS

After collection of data from various community Pharmacists, the data collected were

sorted and coded. A total of 85 pretested questionnaires were distributed and only 84 were

retrieved and considered valid after sorting which led to a return rate of 99% retrieval rate. The

questionnaires so sorted were entered into the Statistical package of the Social Sciences version

17 (SPSS 17) and the descriptive statistics was determined. Inferential statistics was done using

the chi-square analysis and cross tabulation to determine the significance of pharmaceutical care

received by patients significant level of P<0.05.

Table 3.1 reveals the demographic profile of community pharmacists and indicates that 44 males

representing 52.4% of the respondents participated in the study while 40 females representing

47.6% of respondents. Likewise, 67 representing 79.8% of respondents fell within the 20-30

years age range, 14 representing 16.7% are 31-40 years and 3 representing 3.6%. The

qualification of respondents indicated 50 representing 59.5% had B.Pharm, 15 representing

17.9% had M.Pharm, and 4(4.8%) had other qualification. Relative to years of experience, 31

making up 36.9% had an experience of 1-5 years, 36 representing 42.9% have an experience

spanning 5-10 years while 17 representing 20.2% have an experience above 10 years. Relative

to Experiences, 74(88.1%) worked in hospital, Academia had 6(7.1%) and the industry had

4(4.8%).

33

Table: 3.1: Demographic Profile of PatientsVariable Frequency Percentage

GenderMale 44 52.4

Female 40 47.6

Total 84 100

AGE

20-30 Years 67 79.8

31-40Years 14 16.7

41-50 Years 3 3.6

Total 84 100

Level of QUALIFICATIONB.Pharm 50 59.5

PharmD 15 17.9

M.Pharm 15 17.9

Others 4 4.8

Total 84 100

Years of Experience

1-5 Years 31 36.95-10 Years 36 42.9Above 10 Years 17 20.2

Total 84 100

Other Experiences

Hospital 74 88.1

Academia 6 7.1

Industry 4 4.8

Total 84 100

34

Knowledge and Awareness of Tuberculosis

Table 3.2 revealed that 19 respondents making up 22.6% agreed attending a seminar/workshop

on tuberculosis while 65 comprising of 77.4% respondents disagreed.

Table 3.2 Attendance of TB Workshop, Seminars and TrainingsResponse Frequency Percentage

Yes 19 22.6

No 65 77.4

Total 84 100

Table 3.3 reveals that the symptoms of tuberculosis, 35(41.7%) respondents said cough and

blood was an indicator for TB, 42(50%) said it was fever, while 5(6%) said it was weight loss. 1

comprising of 1.2% said it was diarrheal and they don’t know respectively.

Table 3.3 Responses on Main Symptoms that are used as an indicator for infectious, active TB disease

Response Frequency Percentage

Cough with Blood 35 41.7

Fever 42 50.0

Weight loss 5 6.0

Diarrheal 1 1.2

Do not know for certain 1 1.2

Total 84 100.0

35

Table below shows that responses on whether someone can be infected with TB more than once,

40(47.6%) respondents agreed by saying yes, while 30(35.7%) said no, 14(16.7%) said they do

not know.

Table 3.4: Responses on whether someone can be infected with TB for more than once in their life time

Response Frequency Percentage

Yes 40 47.6

No 30 35.7

Do not know for certain 14 16.7

Total 84 100

Table 3.5 below revealed that 12(14.3%) respondents said the standard length for treatment of

newly diagnosed case of TB was 1-2 months, 30 comprising 35.7% said it was 3-4 months, 17

making up 20.2% claimed it was 5-6 months while 24(28.6%) noted it was >6 months and

1(1.2%) did not know.

Table 3.5 Responses on the standard length of treatment for a newly diagnosed case of TBResponse Frequency Percentage

<1 month 0 0

1-2Months 12 14.3

3-4 Months 30 35.7

5-6 Months 17 20.2

>6 Months 24 28.6

Do Not Know For Certain 1 1.2

Total 84 100.0

36

Table 3.6 on the cure for TB, 10(11.9%) noted TB cannot be cured but only managed, 7(8.3%)

advocated herbal management, 3(3.6%) noted bed rest without medicine was enough, 14(16.7%)

said general antibiotics could be used while 48(57.1%) responded advocated the use of specific

antibiotics.

Table 3.6: Responses on TB curabilityResponse Frequency Percentage

TB cannot be cured, only managed

10 11.9

Herbal Remedies 7 8.3

Bed rest without medicine 3 3.6

General Antibiotics 14 16.7

Specific anti-TB regimen 48 57.1

Do not know for certain 2 2.4

Total 84 100

37

Table 3.7 on the WHO’s criterion for relapse, 9(10.7%) respondents said patients who remained

positive towards the end of treatment course, 33(39.3%) noted they include patients whose

treatment was interrupted while 22(26.2) noted that they are patients who are previously treated

and cured, but once again bacteriologic ally confirmed TB while 20(23.8%) do not know.

Table 3.7: Responses on WHO Classification Criterion for a Relapse caseResponse Frequency Percentage

Patient who remained or became smear positive again near the end of the treatment course

9 10.7

Patients whose treatment was interrupted

33 39.3

Patients who are previously treated and cured, but once again bacteriologic ally confirmed TB

22 26.2

Do not know 20 23.8

Total 84 100

38

Table 3.8 on the WHO’s criterion for defauletrs,3 (3.6%) respondents said patients who

remained positive towards the end of treatment course, 30(35.7% noted they include patients

whose treatment was interrupted while 33(39.3) noted that they are patients who are previously

treated and cured, but once again bacteriologic ally confirmed TB while 18(21.4%) do not know.

Table 3.8: Responses on WHO classification criterion for a defaulter casesResponse Frequency Percentage

Patient who remained or became smear positive again near the end of the treatment course

3 3.6

Patients whose treatment was interrupted

30 35.7

Patients who are previously treated and cured, but once again bacteriologic ally confirmed TB

33 39.3

Do not know 18 21.4

Total 84 100

39

PRACTICES TOWARDS MANAGEMENT OF TUBERCULOSIS

Table 3.9 shows that only 1(1.2%) pharmacists had tuberculosis referred cases on daily bases,

11(13.1%) had it on weekly bases, 4(4.8%) claimed weekly while 15(17.9%); 53(63.1%)

claimed yearly and never respectively.

Table 3.9: Responses on TB Referral Cases amongst Community Pharmacists

Response Frequency Percentage

Daily 1 1.2

Weekly 11 13.1

Monthly 4 4.8

Yearly 15 17.9

Never 53 63.1

Total 84 100

Table 3.10 reveals that 24(28.6%) respondents claimed TB is a major public health problem in

Delta state while 47(56%) declined, 13(15.5%) respondents claimed they don’t know.

Table 3.10: Responses on TB as a Public Health Threat in Delta StateResponse Frequency Percentage

Yes 24 28.6

No 47 56

Do not know for certain 13 15.5

Total 84 100

40

Table 3.11 shows that responses relative to those who are most likely to become infected,

4(4.8%) respondents said Homeless persons, 12(14.3%) said children under 5 years, 29(34.5%

claimed people living with HIV/AIDS. On the other hand, 21(25.0%) of respondents claimed

health care workers treating a confirmed case stood a greater risk while 11(13.1%) respondents

identified family members of confirmed cases, 7(8.3%) said it was prison inmates.

Table 3.11: Responses on TB Risk PersonsResponse Frequency Percentage

Homeless Person 4 4.8

Children Under 5years 12 14.3

People living with HIV/AIDS

29 34.5

Health care worker treating a confirmed case

21 25.0

Family members of a confirmed case

11 13.1

Prison inmates 7 8.3

Total 84 100

Table 3.12 shows that data from respondents revealed that 23(27.4%) respondents admitted that

health education messages should be given on World TB day, while 7(8.3%) submitted that there

41

should be general health education in clinical settings, 24(28.6%) said with suspected/confirmed

cases only, 9(10.7%) submitted that it should include both confirmed cases and their family

members.

Table 3.12: Responses on TB EducationResponse Frequency Percentage

World TB day 23 27.4

BCG Immunization 14 16.7

General health promotion/ education messages delivered in clinical settings

7 8.3

With suspected/confirmed cases only (i.e. no family members)

24 28.6

With confirmed patient and their family in a community setting

9 10.7

Health education 7 8.3

Total 84 100

Table 3.13a on the diagnostic test usually requested, 15(17.9%) of respondents noted the use of

Nasopharyngeal swab, 23(27.4%) said the use of Chest-Xray, 21(25%) said the use of Mantoux

42

test while 22(26.2%) identified the use of sputum smear microscopy and 3(3.6%) said the use of

blood culture.

Table 3.13a: Responses on Primary Diagnostic Test Response Frequency Percentage

Nasopharyngeal Swab 15 17.9

Chest X-ray 23 27.4

Matoux Test 21 25.0

Sputum Smear Microscopy

22 26.2

Blood Culture 3 3.6

Total 84 100

From data presented in table 3.13b, it was discovered that the qualification of pharmacists had an

impact on their choice of diagnostic test. It revealed that 12.0% B.Pharm holders preferred

nasopharyngeal swab, against 40.0% PharmD holders that preferred nasopharyngeal swab

likewise, 20.0% M.Pharm, and 0% others that preferred nasopharyngeal swab. On the use of

chest-xray, the trend of preference was 20% for B.Pharm, 53.3% for Pharm D., 20.0% for

M.Pharm and 50% for others. On mantoux test, the trend further showed disparity according to

qualification, revealing 28.0% for B.Pharm, 6.7% for PharmD, 33.3% for M.Pharm and 25% for

others. Blood microscopy showed the trend as 38.0% for B.Pharm, 0% for PharmD, 13.3% for

M.Pharm and 25.0% for others. The use of blood culture revealed 2.0% for B.Pharm, 0% for

PharmD, 1.3% for M.Pharm and 0% for others.

Table 3.13bImpact of Qualification on Preference of Diagnostic Test

DIAGNOSTIC TEST TotalNasopha Chext Matoux Sputum Blood

43

ryngeal Swab

Xray Test Smear Microsco

py

culture

Qualification

B. Phar

m

Count 6 10 14 19 1 50% within

Qualification12.0% 20.0% 28.0% 38.0% 2.0% 100.0

%% of Total 7.1% 11.9% 16.7% 22.6% 1.2% 59.5

%Adjusted Residual

-1.7 -1.8 .8 3.0 -.9

PharmD

Count 6 8 1 0 0 15% within

Qualification40.0% 53.3% 6.7% .0% .0% 100.0

%% of Total 7.1% 9.5% 1.2% .0% .0% 17.9

%Adjusted Residual

2.5 2.5 -1.8 -2.5 -.8

M.Pharm

Count 3 3 5 2 2 15% within

Qualification20.0% 20.0% 33.3% 13.3% 13.3% 100.0

%% of Total 3.6% 3.6% 6.0% 2.4% 2.4% 17.9

%Adjusted Residual

.2 -.7 .8 -1.2 2.2

Others

Count 0 2 1 1 0 4% within

Qualification.0% 50.0% 25.0% 25.0% .0% 100.0

%% of Total .0% 2.4% 1.2% 1.2% .0% 4.8%Adjusted Residual

-1.0 1.0 .0 .0 -.4

Total Count 15 23 21 22 3 84

% within Qualification

17.9% 27.4% 25.0% 26.2% 3.6% 100.0%

% of Total 17.9% 27.4% 25.0% 26.2% 3.6% 100.0%

Table 3.13 shows that from the calculated chi-square on the influence of qualification on

preference of diagnostic test revealed that qualification had an impact on the choice of diagnostic

test.

44

Table 3.13cChi-Square Tests of Significant effect of qualification on the preference of Diagnostic test.

Value DF Assymp. Sig. (2-Sided)

Pearson Chi-Square 26.742a 12 0.008Likelihood Ratio 29.363 12 0.003Linear by Linear Association

1.517 1 0.218

Valid Cases 84

Critical X2(4,5)= 21.026

Table 3.14 shows that responses on the qualification needed by community pharmacists to

effectively carry out directly observed treatment revealed that 24(28.6%) respondents said

B.Pharm, 16(19.0%) PharmD, 13(15.5%) claimed it was M.Pharm while 28(33.3%) said it was

FPC Pharm with only 3(3.6%) respondents saying other qualifications were needed.

Table 3.14: Responses on qualification needed by community pharmacists to effectively conduct directly observed treatment

Response Frequency Percentage

B.Pharm 24 28.6

Pharm.D 16 19.0

M.Pharm 13 15.5

FPC Pharm 28 33.3

Others 3 3.6

Total 84 100

45

Table 3.15a shows that responses on the most effective therapy for TB showed that 7(8.3%) said

it was Isoniazid, 28(33.3%) preferred Rifampin while 11(13.1%) preferred Ethambutol,

19(22.6%) preferred pyrazinamide and combination therapy respectively.

Table 3.15a: Responses on Most effective therapy for Patients with TBResponse Frequency Percentage

Isoniazid 7 8.3

Rifampin 28 33.3

Ethambutol 11 13.1

Pyrazinamide 19 22.6

Combination Therapy 19 22.6

Total 84 100

From data in table 3.15b, it was discovered that the qualification of pharmacists had no impact

on their choice of therapeutic drug used. It revealed that 10.0% B.Pharm holders preferred

Isoniazid, against 6.7% Pharm.D holders that preferred Isoniazid, likewise, 6.7% M.Pharm, and

0% others that preferred Isoniazid. On the use of Rifampin, the trend of preference was 36%for

B.Pharm, 13.3% for Pharm D., 40.0% for M.Pharm and 50% for others. On ethanbutol, the trend

further showed 12% for B.Pharm, 20% for PharmD, 13.3% for M.Pharm and 25% for others.

Pyrazinamide revealed the trend as 11% for B.Pharm, 33.3% for PharmD, 13.3% for M.Pharm

and 25.0% for others. The use of combination therapy 20% for B.Pharm, 26.7% for PharmD,

26.7% for M.Pharm and 0% for others.

46

Table 3.15b: Impact of Qualification on Most Effective Therapy Used

THERAPY

Total

Qualification

Isoniazid Rifampin Ethanbutol Pyrazinamide

Combination

Therapy

B. Pharm Count 5 18 6 11 10 50

%within Qualification 10.0% 36.0% 12.0% 22.0% 20.0% 100.0%

% of Total 6.0% 21.4% 7.1% 13.1% 11.9% 59.5%

Adjusted Residual .7 .6 -.7 -.2 -.4

PharmD Count 1 2 3 5 4 15

%within Qualification 6.7% 13.3% 20.0% 33.3% 26.7% 100.0%

% of Total 1.2% 2.4% 3.6% 6.0% 4.8% 17.9%

Adjusted Residual -.3 -1.8 .7 1.1 .5

M.Pharm Count 1 6 2 2 4 15

%within Qualification 6.7% 40.0% 13.3% 13.3% 26.7% 100.0%

% of Total 1.2% 7.1% 2.4% 2.4% 4.8% 17.9%

Adjusted Residual -.3 .6 -.1 -.9 .5

Others Count 0 2 1 1 0 4

%within Qualification .0% 50.0% 25.0% 25.0% .0% 100.0%

% of Total .0% 2.4% 1.2% 1.2% .0% 4.8%

Adjusted Residual -.6 .7 .6 .1 -1.1

Total Count 7 28 12 19 18 84

%within Qualification 8.3% 33.3% 14.3% 22.6% 21.4% 100.0%

% of Total 8.3% 33.3% 14.3% 22.6% 21.4% 100.0%

Table 3.15c shows that the calculated chi-square on the influence of qualification on difference

of therapeutic drug revealed that qualification had no impact on the choice of therapy.

Table 3.15c: Chi-Square Tests of Significance on the Impact of Qualification on Choice of Therapy

Value df Asymp. Sig. (2-

47

sided)Pearson Chi-Square 6.537a 12 .887Likelihood Ratio 8.088 12 .778Linear-by-Linear Association

.011 1 .916

N of Valid Cases 84a. 14 cells (70.0%) have expected count less than 5. The minimum expected count is .33.

Critical X2(4,5)= 21.026

Data in table 3.16 on the main risk associated with incomplete or interrupted treatment of TB, the

result revealed that 9(10.7%) indicated worsening symptoms and prolonged treatment course,

while 50(59.5%) said the development of drug resistance and 18(8.3%) attributed it to death,

7(8.3%) noted there is no serious risk.

Table 3.16: Responses on Main risk to the patient associated with incomplete or interrupted treatment course for TB

Response Frequency Percentage

Worsening of symptoms and prolonged treatment

course

9 10.7

Development of drug resistance

50 59.5

Death 18 21.4

There is no serious risk 7 8.3

Total 84 100

CHAPTER FOUR

4.1 Discussion

48

Assessment of Knowledge and Awareness Level on Tuberculosis Symptoms

Findings from this study revealed that the attendance of workshops on TB by community

pharmacists was low revealing that grossly high 77.5% respondents declined attending

workshops on TB in the last one year. On their knowledge level towards the symptoms of TB, it

revealed a high level of knowledge amongst community pharmacists on the symptoms of

tuberculosis as they were able to identify cough and blood and fever as symptoms of

tuberculosis. Likewise, findings revealed that 47.6% of community pharmacists in the study

agreed one could be infected more than once. It is important to note that the knowledge and

awareness level of pharmacists on the symptoms of TB is not in agreement with their level of

attendance of training/seminars on TB. According to the Health Belief Model, knowledge,

education and socio-demographic factors are considered modifying variables of behavior,

individual characteristics that influence personal perceptions. Although, there is limited study

that has investigated the awareness of pharmacists specifically on tuberculosis, the findings of

this study is in agreement with those of Zahra, (2014) who found no correlation amongst

attendance of TB trainings/seminars and their knowledge and awareness of TB symptoms

amongst public health workers in Jamaica. Likewise, the finding disagrees with the submissions

of Bhebhe, et al., (2014) who noted that the attitudes, knowledge and practice of health workers

in a hospital setting correlated with their level of attendance of trainings and seminars on

tuberculosis management.

Awareness on Curability and WHO Standards

This study further revealed that community pharmacists had a low level of knowledge on

the standard duration of treating a newly diagnosed TB case showing less than 50% of them

49

knew it surrounds at about 5-6 months or more. A surprising trend also revealed that most

community pharmacists had a very low level of knowledge on specific anti TB regimen; it also

revealed that only few pharmacists’ 26.2% and 35.7% respondents are aware of the WHO

standard definition for relapse and defaulters. There is no doubt that this observation justifies the

earlier observation made on non attendance of TB training sessions/seminars while agreeing with

the submissions of Bhebhe, et al., (2014) that the attitudes, knowledge and practice of health

workers is correlated with their level of attendance of trainings and seminars on tuberculosis

management. On the same note, it further gives credence to the Health Belief Model of Janz, et

al., (1984) that behavior and practice of health workers is a product of the level of awareness,

knowledge and education gained.

Level of TB Referral Cases and TB Prevalence

Findings from this study revealed a very low level of referral cases of TB to pharmacist as 63.1%

of respondents claimed not to have had any case of referral while 1.2%, 13.1%, 4.8%, 17.9%

daily, weekly, monthly and yearly respectively. Relative to whether TB was a major public

health problem in Delta State, respondents submitted that most pharmacists declined to this

claim. On those who stood the highest risk of contracting the disease, it was submitted that those

having HIV/AIDs stood a higher risk. The implication of this observation is that most

community pharmacists are scarcely patronised relative to TB cases and that there may be a high

level of implementation of TB management and control guidelines in Delta stateas well as the

utilization of the state owned tuberculosis centre.

50

Level of Publicity Given to TB by Pharmacists

Results from this study revealed community Pharmacists believes that health education

on TB should be given more on world TB day while a few of them said it should be left to

general clinical setting, some others said it should be limted to only confirmed cases and their

families. The implication of this observation is that most community pharmacists are not

involved in the promotion of public health education on TB. It also gives credence to the earlier

claims of non involvement in training as they cannot offer what they do not have. These

submissions are not in consonance with the submissions of WHO (2011) who noted that the

current role of pharmacists in the fighting of the scourge of TB includes the proper provision of

education on TB management as well as acting as major sources of clinic referrals in suspected

TB cases. It further noted that the services of pharmacists in the control of TB have not been

sufficiently engaged.

Impact of Qualification on TB Diagnostic and Therapeutic Practices

Although community pharmacists had a high level of knowledge on the utilization of TB

diagnostics and therapeutics, the results revealed that the qualification of pharmacists only had

impact on their choice of diagnostic test while qualification had no impact on the therapeutic

drug used by the pharmacists. a p-value of 0.008 and 0.887 was observed for choice of

diagnostic test and therapeutic drug respectively. A careful observation of the choice of

diagnostic practice revealed that the use of chest-x-ray was more prevalent amongst all the

qualifications while the use of Rifampin was more prevalent amongst all the qualification of

community pharmacists. These submissions give credence to the submission that the minimum

skill level required to conduct DOTS with confirmed patients corresponds to that of self-efficacy,

51

the confidence in one’s ability to perform a specific function (Glanz, et al., 2002; Hayden, 2009).

The study of Zahra, (2014) also submits that the minimum level of expertise necessary to

conduct DOTS was a with clinical training, such as a registered nurse; followed by highly

qualified/ trained HCWs being the second most commonly noted skill level required.

52

CHAPTER FIVE

5.1 Conclusion

This study surveyed the role of community pharmacists in the management of

tuberculosis in Delta state. Findings from the study revealed quite a high level of awareness on

tuberculosis symptoms and a very low level of attendance in tuberculosis seminars, trainings and

workshops. Although they were aware of the symptoms, the study revealed a low level of

awareness on the curability and WHO standards relative to relapse and defaulters, while showing

a sharp contrast relative to their knowledge of diagnostic tests and therapeutic drugs, it was

revealed that most community pharmacists had little or no referral cases on TB, the study further

revealed that community pharmacists had a low level of participation in the promotion of

education on TB cases, qualification of the pharmacists had no impact on their choice of

diagnostic test and therapeutic drug for TB management.

Conclusively, the study wishes to make the following submissions as the major highlights

of the study;

Very little proportion of tuberculosis patients are treated by community pharmacists.

The knowledge level of community Pharmacists on Symptoms and signs of TB is high;

however, they have low level of management of the disease.

There is no significant relationship between qualification of Pharmacists and their

management skills of tuberculosis.

53

5.2 Recommendations

Based on the conclusion made above, the following are recommended

1. Community pharmacists as essential collaborators in the health care sector should always

make themselves available for trainings and seminars so as to keep up to date their

knowledge base and development in certain disease management.

2. The pharmaceutical council of Nigeria should at intervals promote development

workshops and seminars for practicing pharmacists on advances, new trends and

development in certain high risk factor diseases.

54

REFERENCES

American Lung Association. (2009). Tuberculosis.Symptoms, diagnosis, and treatment. www.lung.org/lung-disease/tuberculosis/symptoms-diagnosis.html. Accessed September, 9, 2015.

American Thoracic Society and CDC.Targeted tuberculin testing and treatment of latent tuberculosis infection.MMWRRecomm Rep. 2000; 49(RR-06):1-54.

American Thoracic Society, CDC, and Infectious Diseases Society of America.Treatment of tuberculosis.MMWRRecomm Rep. 2003;52(RR-11):1-77.

Bhebhe, L.T., Van Rooyen, C. and Steinberg, W.J. (2014). Attitudes, knowledge and practices of healthcare workers regarding occupational exposure of pulmonary tuberculosis. African Journal of Pharrmaceutical Healthcare Fam Med.6(1)

Birn, A. (2009). Textbook of International Health: Global Health in a Dynamic World. p. 261.

Bloom, editor, Barry R. (1994).Tuberculosis: pathogenesis, protection, and control. Washington, D.C.: ASM Press.

Bonah, C. (2005). The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921–1933. Stud HistPhilosBiol Biomed Sci 36(4):696–721.

CDC. Managing drug interactions in the treatment of HIV-related tuberculosis 2007. www.cdc.gov/tb/TB_HIV_Drugs/default.htm. Accessed September, 9, 2015.

CDC. Trends in tuberculosis–United States, 2011. MMWRRecomm Rep. 2012;61:181-185.

CDC. Tuberculosis.Basic TB facts.Risk factors. www.cdc.gov/tb/topic/basics/risk.htm. Accessed September, 9, 2015.

55

CDC. Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis.MMWRRecomm Rep. 2009;58:7-10.

Centers for Disease Control and Prevention (2006).Set Retrieved 13 October 2015.

Centers for Disease Control and Prevention (CDC).Tuberculosis.Data and statistics. www.cdc.gov/tb/statistics/default.htm. Accessed September, 9, 2015.

Centers for Disease Control and Prevention. CDC Surveillance Slides 2012 – TB

Centers for Disease Control. 20 June 2011.Fact Sheets: The Difference Between Latent TB Infection and Active TB Disease. Retrieved 26 July 2011.

Clark PM, Karagoz T, Apikoglu-Rabus S, et al. Effect of pharmacist-led patient education on adherence to tuberculosis treatment. Am J Health Syst Pharm. 2007;64:497-505.

CNN.Kentucky: Mammoth Cave long on history. 27 February 2004. Accessed September, 9, 2015.

Ena J, Valls V. Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis. Clin Infect Dis. 2005;40:670-676.

Fang G, Munera D, Friedman DI, Mandlik A, Chao MC, Banerjee O, Feng Z, Losic B, Mahajan MC, Jabado OJ, Deikus G, Clark TA, Luong K, Murray IA, Davis BM, Keren-Paz A, Chess A, Roberts RJ, Korlach J, Turner SW, Kumar V, Waldor MK, Schadt EE: Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing. Nature Biotechnology 30:1232-1239.

Fitzgerald DW, Sterling TR, Haas DW. Mycobacterium tuberculosis. In: Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2010:3129-3164.

FitzGerald, JM; Wang, L; Elwood, RK (8 February 2000). Tuberculosis: 13. Control of the disease among aboriginal people in Canada. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne162 (3): 351–5.

Gerald L. Mandell, John E. Bennett, Raphael (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases (7th ed.). Philadelphia, PA: Churchill Livingstone/Elsevier. pp. Chapter 250.

Gire SK, Goba A, Andersen KG, Sealfon RSG, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, Dudas G, Wohl S, Moses LM, Yozwiak NL, Winnicki S, Matranga CB, Malboeuf CM, Qu J, Gladden AD, Schaffner SF, Yang X, Jiang PP, Nekoui M, Colubri A, Coomber MR, Fonnie M, Moigboi A, Gbakie M, Kamara FK, Tucker V, Konuwa E, et

56

al. (2014). Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science 4 (345):1369-1372

Glanz, K., Rimer, B.K. & Lewis, F.M. (2002). Health Behavior and Health Education. Theory, Research and Practice. San Fransisco: Wiley & Sons.

Hannaway, C. (2008). Biomedicine in the twentieth century: practices, policies, and politics. Amsterdam: IOS Press. p. 233.

Hippocrates. Aphorisms, Classics, MIT, Accessed 7 October 2006.

Horsburgh CR Jr, Rubin EJ. Clinical practice.Latent tuberculosis infection in the United States.N Engl J Med. 2011; 364:1441-1448.

Hussey, G., Hawkridge, T. and Hanekom, W. (2007) Childhood Tuberculosis: Old And New Vaccines. Paediatric Respiratory Reviews 8(2):148-154.

Janz, Nancy K.; Marshall H. Becker (1984). The Health Belief Model: A Decade Later. Health Education Behavior 11(1):1–47

Kafsack BF, Rovira-Graells N, Clark TG, Bancells C, Crowley VM, Campino SG, Williams AE, Drought LG, Kwiatkowski DP, Baker DA, Cortés A, Llinás M: A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature 507:248-252.

Kaplan, J.E., Benson, C. and Holmes, K.K (2009). Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.MMWRRecomm Rep. 58(RR-4):1-216.

Kielstra, P. (2014). Zoe Tabary, ed. Ancient enemy, modern imperative – A time for greater action against tuberculosis. Economist Insights (The Economist Group).Retrieved 1 August 2014.

Konomi N, Lebwohl E, Mowbray K, Tattersall I and Zhang D (2002). Detection of Mycobacterial DNA in Andean Mummies J ClinMicrobiol 40(12):4738–40. doi:10.1128/JCM.40.12.4738-4740.2002

Kumar V, Abbas AK, Fausto N, Mitchell RN (2007).Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 516–522.

Lalloo, U.G., Naidoo, R, Ambaram A (2006). Recent advances in the medical and surgical treatment of multi-drug resistant tuberculosis. CurrOpinPulm Med, 12(3): 179–85.

Last JP, Kozakiewicz JM.Development of a pharmacist-managed latent tuberculosis clinic.Am J Health Syst Pharm. 2009;66:1522-1523.

57

Lawn, SD; Zumla, AI (2011).Tuberculosis.Lancet 378 (9785): 57–72.

Lexi-Comp Online [Internet database]. Hudson, OH: Lexi-Comp, Inc; 2011. www.lexi.com. Accessed February 29, 2012.

LoBue P, Sizemore C, Castro KG. Plan to combat extensively drug-resistant tuberculosis recommendations of the federal tuberculosis task force.MMWRRecomm Rep. 2009;58(RR-03);1-43.

Mahmoudi A, Iseman MD. Pitfalls in the care of patients with tuberculosis: common errors and their association with the acquisition of drug resistance. JAMA. 1993;270:65-68.

ManzurekGH, Jereb J, Vernon A, et al. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, 2010. MMWRRecomm Rep. 2010;59(RR-5):1-25.

Mayo Clinic (2015).Retrieved from http://www.mayoclinic.org/diseases-conditions/tuberculosis/basics/definition/con-20021761 on 14 April 2015.

McAdam PR, Richardson EJ, Fitzgerald JR (2014). High-throughput sequencing for the study of bacterial pathogen biology. Curentr Opinions in Microbiology 19C:106-113.

McCarthy, O.R. (2001). "The key to the sanatoria .J R Soc Med94 (8): 413–7. PMC 1281640

Menzies, D., Al Jahdali, H. and Al Otaibi, B (2011). Recent developments in treatment of latent tuberculosis infection. The Indian Journal of Medical Research 133(3): 257–266.

Nobel Foundation.The Nobel Prize in Physiology or Medicine 1905.Accessed 7 October 2006.

Oksanen, K.E., Halfpenny, N.J., Sherwood, E., Harjula, S.K., Hammarén, M.M., Ahava, M.J., Pajula, E.T., Lahtinen, M.J., Parikka, M. and Rämet, M. (2013). An adult zebrafish model for preclinical tuberculosis vaccine development. Vaccine, 31(45):5202-5209.

Peloquin CA, Namdar R. Tuberculosis. In: DiPiro JT, Talbert RL, Yee GC, et al. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011:1931-1949.

Persson, Sheryl (2010). Smallpox, Syphilis and Salvation: Medical Breakthroughs That Changed the World. ReadHowYouWant.com. p. 141.

Quah, Stella R.; Carrin, Guy; Buse, Kent; Kristian Heggenhougen (2009).Health Systems Policy, Finance, and Organization. Boston: Academic Press. p. 424.

Raviglione MC, O’Brien RJ. Tuberculosis. In: Kasper DL, Fauci AS. Harrison’s Infectious Diseases. New York, NY: McGraw-Hill;2010:596-617.

58

Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent Mycobacterium tuberculosis infection.MMWRRecomm Rep. 2011;60(48):1650-1653.

Shields, T. (2009).General thoracic surgery (7th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 792.

Skolnik, R. (2011). Global health 101 (2nd ed.). Burlington, MA: Jones & Bartlett Learning. p. 253.ISBN 978-0-7637-9751-5.

Skolnik, R. (2011). Global health 101 (2nd ed.). Burlington, MA: Jones & Bartlett Learning. p. 253.

Sledzik, Paul S.; Nicholas Bellantoni (1994). Bioarcheological and biocultural evidence for the New England vampire folk belief. American Journal of Physical Anthropology94 (2): 269–274.

Sterling TR, Villarino ME, Borisov AS, et al; TB Trials Consortium PREVENT TB Study Team. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365:2155-2166.

Tavitian SM, SpalekVH, Bailey RP. A pharmacist-managed clinic for treatment of latent tuberculosis infection in health care workers.Am J Health Syst Pharm. 2003;60:1856-1861.

The Chambers Dictionary. New Delhi: Allied Chambers India Ltd. 1998. p. 352.

Trail, R.R. (1970). Richard Morton (1637–1698). Med Hist 14(2): 166–74.

Tyne, A.S., Chan, J.G., Shanahan, E.R., Atmosukarto, I., Chan, H.K., Britton, W.J and West, N.P. (2013). TLR2-targeted secreted proteins from Mycobacterium tuberculosis are protective as powdered pulmonary vaccines. Vaccine, 31(40):4322-4329.

Update: Adverse event data and revised American Thoracic Society and Centers for Disease Control and Prevention recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection—United States, 2003. MMWRRecomm Rep. 2003;52(31):735-739.

Verma, Indu, and Ajay Grover (2009). Antituberculous Vaccine Development: A Perspective For The Endemic World. Expert Review of Vaccines 8(11) 1547-1553.

White, A. D., Sibley, L., Dennis, M. J., Gooch, K., Betts, G., Edwards, N. and Sharpe, S. A. (2013). Evaluation of the Safety and Immunogenicity of a Candidate Tuberculosis Vaccine, MVA85A, Delivered by Aerosol to the Lungs of Macaques. Clinical and Vaccine Immunology 20(5):663–672

59

WHO, (2011). The role of pharmacists in Tuberculosis care and control

Wilmot, C.M (2007) Fighting toxic copper in a bacterial pathogen. Nature Chemical Biology, 3:15-16.

World Health Organization (2009).Epidemiology.Global tuberculosis control: epidemiology, strategy, financing. pp. 6–33.

World Health Organization (2011). The sixteenth global report on tuberculosis

World Health Organization (2011b).Global Tuberculosis Control .Retrieved 15 Septembet 2015.

World Health Organization, (2010).Tuberculosis Fact sheet N°104". November Retrieved 26 August, 2015.

World Health Organization. (2006). Global Tuberculosis Control Report, 2006 – Annex 1 Profiles of high-burden countries. Retrieved 13 October 2015.

World Health Organization. (2011). Tuberculosis. Global tuberculosis control 2011. www.who.int/tb/publications/global_report/2011/gtbr11_executive_summary.pdf. Retrieved 5 October, 2015.

World Health Organization (2011). Global Tuberculosis Control.Retrieved 5 October, 2015.

World Health Organization (2013). Global tuberculosis report 2013, Retrieved 5 October, 2015.

Zahra N.W (2014). Survey on the knowledge, attitudes and practices on tuberculosis (TB) among health care workers in Kingston & St. Andrew, Jamaica, Unpublished M.Sc. Dissertation Department of Public Health, The University of Liverpool Accessed 2nd October, 2015 from www.support.liverpool-online.com

60

APPENDIX I: RESEARCH INSTRUMENT

A SURVEY OF THE ROLE OF COMMUNITY PHARMACISTS’ IN THE MANAGEMENT OF TUBERCULOSIS

Dear Respondent,

I am a final year student of Faculty of Pharmacy, Delta state University Abraka, undertaking a research work on the above topic. Please indicate appropriately your view regarding the statement or questions below. Information provided would be used strictly for research purposes and will be treated with utmost confidentiality. Thanks for your anticipated assistance and cooperation.

Yours Faithfully,Okungba Ogelenya Whitely (Researcher)

Section A: Demographics

1. Sex: Male ( ) Female ( )2. Age: 20-30years ( ) 31-40 Years ( ) 41-50 years ( ) Above 50 Years ( )3. Qualification: B.Pharm ( ) PharmD ( ) M. Pharm ( ) Others ( )4. Years of Practice Intern ( ) 1-5 Years ( ) 5-10 Years ( ) Above 10 Years ( )5. Other Practice Experiences: Hospital ( ) Academia ( ) Industry ( )

61

6. Location of practice;

Section B: Knowledge and Awareness

7. In the past 12 months have you attended a lecture, seminar or workshop on Tuberculosis? Yes ( ) No ( )

8. What is/are the main symptoms that are used as an indicator for infectious, active TB disease? Cough≥3 weeks ( ) cough with blood ( ) fever ( ) Weight loss ( ) Night Sweats ( ) Diarrheal ( ) Do not know for certain ( )

9. Can someone be infected with TB for more than once in their life time? Yes ( ) No ( ) Do not know for certain ( )

10. What is the standard length of treatment for a newly diagnosed case of TB? <1Month ( ) 1-2 Months ( ) 3-4 months ( ) 5-6 Months ( ) > 6 months ( ) Do not know for certain ( )

11. How can someone with TB be cured? TB cannot be cured, only managed ( ) Herbal remedies ( ) Bed rest without medicine ( ) General antibiotics ( ) Specific anti-TB regimen ( ) Do not know for certain ( )

12. What is WHO classification of a defaulter case?Patients who remained or became smear positive again near the end of the treatment ( )Patients whose treatment was interrupted for two months or more and returns to the treatment with bacteriologically confirmed TB ( )Patients who was previously treated and cured, but once again bacteriogically confirmed TB ( )Do not know for certain ( )

13. What is the WHO classification criterion for a relapse case?a. Patients who remained or became smear positive again near the end of the treatment

course ( )b. Patient whose treatment was interrupted for two (2) month or more and returns to the

treatment with bacteriological confirmed active TB ( )c. Patient who was previously treated and cured, but once again bacteriologically

confirmed TB ( )d. Do not know for certain ( )

Section C: Practices

14. How often do you get tuberculosis referred cases Daily ( ) Weekly ( ) Monthly ( ) Year ( ) Never ( )

15. In your opinion is TB a major public health threat in Delta State? Yes ( ) No ( ) Do not know for certain ( )

62

16. Who are the persons most likely to become infected in Delta state? Homeless person ( ) Children under 5 years ( ) People living with HIV/AIDS ( ) Health care worker treating a confirmed case ( ) Family members of a confirmed case ( ) Prison inmates ( )

17. Under what circumstances are health education messages on TB given to patients? World TB day ( ) BCG immunization ( ) General health promotion/education messages delivered in clinical settings ( ). With suspected/Confirmed cases only (i.e. no family members) ( ) Health Education on TB is generally not done with patients ( )

18. What is the primary diagnostic test that is usually requested in order to confirm or rule out a case active pulmonary TB? Nasopharyngeal swab ( ) Chest X-ray ( ) Mantoux test ( ) Sputum Smear microscopy ( ) Blood Culture ( )

19. What qualification is needed by community pharmacists to effectively conduct directly Observed treatment (DOT) with a patient with TB? B.Pharm ( ) Pharm.D ( M.Pharm ( ) FPC Pharm ( ) Others ( )

20. What is the most effective therapy for patients with TB? Isoniazid ( ) Rifampin ( ) Ethambutol ( ) Pyrazinamide ( ) Combination therapy ( )

21. What do you consider to be the main risk to patient associated with incomplete or interrupted treatment course for TB? Worsening symptoms and prolonged treatment course ( ) Development of drug resistance ( ) Death ( ) There is no serious risk ( )

63