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 9095% 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 1.201.45 million deaths occurred, most of these occurring in developing
countries (WHO, 2011 & Lozano, 2012). Of these 1.45 million deaths, about 0.35 million occur
in those also infected with HIV (WHO, 2011b).
1

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
20042014 (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
510% 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
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 30002400 BC. Genetic
studies suggest tuberculosis was present in the Americas from about 100 AD (Konomi, et al.
2002).
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. Schnlein. During 18381845, 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 Grbersdorf (now Sokoowsko),
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
later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis
4

(Waddington, 2004). Albert Calmette and Camille Gurin achieved the first genuine success in
immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was
called Bacille CalmetteGurin (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 hosts

immune response determine whether the infection progresses to active tuberculosis or remains
latent (Mayo Clinic, 2015).
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).

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
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-Gurin (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

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
10

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.

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.

11

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).
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

12

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):

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
13

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
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
14

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 HIVnegative 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.
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 (MDRTB). 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
15

of anything that can reduce the persons 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 firstline 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 drugresistant 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

16

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

17

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

18

Since the BCG vaccine does not offer complete protection against TB, vaccines have been
designed to bolster BCGs 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 TBs association with the developing world. Progression of vaccine designs relies
heavily on outcomes in animal models. Appropriate animal models are scarce because it is

19

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 nonprimate 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 hosts 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 hosts copper attack (Wilmot, 2007).
An approach in a direction to design such compounds that disable the bacterium to fight against
the host bodys 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

20

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

21

is needed to address resistance issues, and an adherence plan that emphasizes DOT should be
implemented when possible (CDC, 2012).
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

22

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 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 HIVrelated 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

23

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
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& OBrien, 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:

24

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).

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 drugresistant 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.

25

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
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.

26

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 (MDRTB).

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 Pharmacists 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
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 ethambutolinduced optical neuritis are more serious, require further evaluation, and may necessitate
27

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
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
28

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 nonprescription, herbal and dietary supplements on a daily basis. This research hopes to make
known the significance and critical importance of community pharmacists 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

ii.

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

iii.

role.
To determine if the pharmacists higher qualification will affect their management
skill in patients with tuberculosis.

29

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

30

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 states capital, Asaba etc.
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

31

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 Nigerias
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.
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

32

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.

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
33

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.

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
34

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%).

Table: 3.1: Demographic Profile of Patients

Variable
Frequency
Gender
Male
44
Female

40

Percentage
52.4
47.6

35

Total

84

100

AGE
20-30 Years

67

79.8

31-40Years

14

16.7

41-50 Years

3.6

84

100

B.Pharm

Level of QUALIFICATION
50

59.5

PharmD

15

17.9

M.Pharm

15

17.9

Others

4.8

84

100

Total

Total

Years of Experience
1-5 Years
5-10 Years
Above 10 Years
Total
Hospital
Academia
Industry
Total

31
36
17
84
Other Experiences
74
6
4
84

36.9
42.9
20.2
100
88.1
7.1
4.8
100

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.
36

Table 3.2 Attendance of TB Workshop, Seminars and Trainings

Response
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 dont 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

6.0

Diarrheal

1.2

Do not know for certain

1.2

84

100.0

Total

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.

37

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

84

100

Total

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 TB
Response
Frequency
Percentage
<1 month

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

1.2

Total

84

100.0

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%)
38

said general antibiotics could be used while 48(57.1%) responded advocated the use of specific
antibiotics.
Table 3.6: Responses on TB curability
Response
Frequency

Percentage

TB cannot be cured, only

managed
Herbal Remedies

10

11.9

8.3

Bed rest without medicine

3.6

General Antibiotics

14

16.7

Specific anti-TB regimen

48

57.1

Do not know for certain

2.4

84

100

Total

Table 3.7 on the WHOs 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

39

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 case
Response
Frequency
Percentage
Patient who remained or
became smear positive
again near the end of the
treatment course
Patients whose treatment
was interrupted
Patients
who
are
previously treated and
cured, but once again
bacteriologic
ally
confirmed TB
Do not know
Total

10.7

33

39.3

22

26.2

20

23.8

84

100

Table 3.8 on the WHOs 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
40

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 cases
Response
Frequency
Percentage
Patient who remained or
became smear positive
again near the end of the
treatment course
Patients whose treatment
was interrupted
Patients
who
are
previously treated and
cured, but once again
bacteriologic
ally
confirmed TB
Do not know
Total

3.6

30

35.7

33

39.3

18

21.4

84

100

PRACTICES TOWARDS MANAGEMENT OF TUBERCULOSIS

41

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

1.2

Weekly

11

13.1

Monthly

4.8

Yearly

15

17.9

Never

53

63.1

84

100

Total

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 dont know.
Table 3.10: Responses on TB as a Public Health Threat in Delta State
Response
Frequency
Percentage
Yes

24

28.6

No

47

56

Do not know for certain

13

15.5

84

100

Total

42

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 Persons
Response
Frequency

Percentage

Homeless Person

4.8

Children Under 5years

12

14.3

People
living
with
HIV/AIDS
Health care worker treating a
confirmed case
Family members of a
confirmed case
Prison inmates

29

34.5

21

25.0

11

13.1

8.3

Total

84

100

43

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
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 Education
Response
Frequency

Percentage

World TB day

23

27.4

BCG Immunization

14

16.7

General health promotion/

education
messages
delivered
in
clinical
settings
With suspected/confirmed
cases only (i.e. no family
members)
With confirmed patient
and their family in a
community setting
Health education

8.3

24

28.6

10.7

8.3

84

100

Total

44

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
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

22

26.2

3.6

84

100

Sputum
Microscopy
Blood Culture
Total

Smear

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.

45

Table 3.13bImpact of Qualification on Preference of Diagnostic Test

DIAGNOSTIC TEST
Nasopha Chext Matoux Sputum
ryngeal
Xray
Test
Smear
Swab
Microsco
py
Qualific
B.
Count
6
10
14
19
ation
Phar
% within
12.0%
20.0%
28.0%
38.0%
m
Qualification
% of Total
7.1%
11.9%
16.7%
22.6%

Phar
mD

M.Ph
arm

Other
s

Total

Adjusted
Residual
Count
% within
Qualification
% of Total
Adjusted
Residual
Count
% within
Qualification
% of Total
Adjusted
Residual
Count
% within
Qualification
% of Total
Adjusted
Residual
Count
% within
Qualification
% of Total

Total
Blood
culture

1
2.0%
1.2%

-1.7

-1.8

.8

3.0

-.9

6
40.0%

8
53.3%

1
6.7%

0
.0%

0
.0%

7.1%

9.5%

1.2%

.0%

.0%

2.5

2.5

-1.8

-2.5

-.8

3
20.0%

3
20.0%

5
33.3%

2
13.3%

2
13.3%

3.6%

3.6%

6.0%

2.4%

2.4%

.2

-.7

.8

-1.2

2.2

0
.0%

2
50.0%

1
25.0%

1
25.0%

0
.0%

.0%
-1.0

2.4%
1.0

1.2%
.0

1.2%
.0

.0%
-.4

15
17.9%

23
27.4%

21
25.0%

22
26.2%

3
3.6%

17.9%

27.4%

25.0%

26.2%

3.6%

46

50
100.0
%
59.5
%

15
100.0
%
17.9
%

15
100.0
%
17.9
%

4
100.0
%
4.8%

84
100.0
%
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.
Table 3.13cChi-Square Tests of Significant effect of qualification on the preference of
Diagnostic test.
Value
DF
Assymp. Sig. (2Sided)
a
Pearson Chi-Square 26.742
12
0.008
Likelihood Ratio
29.363
12
0.003
Linear by Linear
1.517
1
0.218
Association
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

3.6

Total

84

100

47

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 TB
Response
Frequency
Percentage
Isoniazid

8.3

Rifampin

28

33.3

Ethambutol

11

13.1

Pyrazinamide

19

22.6

Combination Therapy

19

22.6

84

100

Total

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.

48

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

THERAPY
Qualificati
on
B. Pharm

PharmD

M.Pharm

Others

Total

Total
Combination

Isoniazid
Count

Rifampin

Ethanbutol Pyrazinamide

Therapy

18

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

Count

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

Count

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

Count

%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

Count

28

12

19

18

84

%within Qualification 8.3%

33.3%

14.3%

22.6%

21.4%

100.0%

% of Total

33.3%

14.3%

22.6%

21.4%

100.0%

8.3%

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.

49

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

Therapy
Value
df
Asymp. Sig. (2sided)
a
Pearson Chi-Square
6.537
12
.887
Likelihood Ratio
8.088
12
.778
Linear-by-Linear
.011
1
.916
Association
N of Valid Cases
84
a. 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
Development of drug
resistance
Death

10.7

50

59.5

18

21.4

There is no serious risk

8.3

Total

84

100

50

CHAPTER FOUR
4.1

Discussion
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
51

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
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.

52

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
53

skill level required to conduct DOTS with confirmed patients corresponds to that of self-efficacy,
the confidence in ones 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.

54

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.
55

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.

56

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, 19211933. Stud HistPhilosBiol Biomed Sci 36(4):696721.
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 tuberculosisUnited 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.
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.

57

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: Genomewide 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): 3515.
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 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.

58

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):147
Kafsack BF, Rovira-Graells N, Clark TG, Bancells C, Crowley VM, Campino SG, Williams AE,
Drought LG, Kwiatkowski DP, Baker DA, Corts A, Llins 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):473840.
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. 516522.
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): 17985.
Last JP, Kozakiewicz JM.Development of a pharmacist-managed latent tuberculosis clinic.Am J
Health Syst Pharm. 2009;66:1522-1523.
Lawn, SD; Zumla, AI (2011).Tuberculosis.Lancet 378 (9785): 5772.
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.
59

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 infectionUnited States, 2010.
MMWRRecomm Rep. 2010;59(RR-5):1-25.
Mayo

Clinic
(2015).Retrieved
from
http://www.mayoclinic.org/diseasesconditions/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): 4137. 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): 257266.
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., Hammarn, M.M., Ahava, M.J.,
Pajula, E.T., Lahtinen, M.J., Parikka, M. and Rmet, 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, OBrien RJ. Tuberculosis. In: Kasper DL, Fauci AS. Harrisons Infectious
Diseases. New York, NY: McGraw-Hill;2010:596-617.
Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat
latent Mycobacterium tuberculosis infection.MMWRRecomm Rep. 2011;60(48):16501653.
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.
60

Sledzik, Paul S.; Nicholas Bellantoni (1994). Bioarcheological and biocultural evidence for the
New England vampire folk belief. American Journal of Physical Anthropology94 (2):
269274.
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;60:18561861.
The Chambers Dictionary. New Delhi: Allied Chambers India Ltd. 1998. p. 352.
Trail, R.R. (1970). Richard Morton (16371698). Med Hist 14(2): 16674.
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 infectionUnited 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 Immunology20(5):663672
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. 633.
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 N104". November Retrieved 26
August, 2015.

61

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

62

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.
2.
3.
4.
5.
6.

Sex: Male ( ) Female ( )

Age: 20-30years ( ) 31-40 Years ( ) 41-50 years ( ) Above 50 Years ( )
Qualification: B.Pharm ( ) PharmD ( ) M. Pharm ( ) Others ( )
Years of Practice Intern ( ) 1-5 Years ( ) 5-10 Years ( ) Above 10 Years ( )
Other Practice Experiences: Hospital ( ) Academia ( ) Industry ( )
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? Cough3 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 ( )

63

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 ( )
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 ( )
64

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 ( )

65