1.1. BACKGROUND OF THE STUDY
Pulmonary tuberculosis (TB) is a contagious bacterial infection that mainly involves the lungs, but may spread to other organs and is caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis) (Sauders, 2007). One can get TB by breathing in air droplets from a cough or sneeze of an infected person. This is called primary tuberculosis.
In Ghana, most people will recover from primary TB infection without further evidence of the disease. The infection may stay asleep or inactive (dormant) for years. However, in some people it can reactivate (Ghana Health Service (GHS) publications, 2000). Most people who develop symptoms of a TB infection first became infected in the past (Southwick, 2007). However in some cases the disease may become active in some few weeks after primary infection. In Ghana, there are approximately 10 cases of TB per 100,000 people. However, rates vary dramatically by area of residence and socioeconomic class (G.H.S publications, 2000).
The following people are at high risk for active tuberculosis: elderly, infants and people with weaken immune system, for instance, AIDS. The risk for contracting TB increases if one is in frequent contact with people living with the disease, poor nutrition and living in crowded or unsanitary living condition (Southwick, 2007).
The following factors may increase the rate of TB infection in a population: Increase in HIV infections, increase in number of homeless people (poor environment and nutrition), and the appearance of drug-resistant strains of TB (Southwick, 2007).
The primary stage of the disease usually doesn't cause symptoms. When symptoms of pulmonary TB occur, they may include: cough (sometimes producing phlegm), coughing up blood, excessive sweating, especially at night, fatigue, fever, unintentional weight loss. Other symptoms that may occur with this disease are breathing difficulty, chest pain, wheezing. Examination may show clubbing of the fingers or toes (in people with advanced disease), enlarged or tender lymph nodes in the neck or other areas, fluid around a lung, unusual breath sounds (crackles) (Southwick, 2007).
Tests that may be used in the diagnosis of this disease include biopsy of the affected tissue (rare), bronchoscopy, chest CT scan, chest x-ray, sputum examination and cultures, tuberculin skin test. Tuberculosis prevention and control takes two parallel approaches. In the first, people with tuberculosis and their contacts are identified and then treated. Identification of infections often involves testing high-risk groups for tuberculosis. In the second approach, children are vaccinated to protect them from tuberculosis. No vaccine is available that provides reliable protection for adults. However, in tropical areas where the levels of other species of mycobacterium are high, exposure to nontuberculous mycobacterium gives some protection against tuberculosis (Fine et al., 2001). Many countries use Bacillus Calmette-Guérin (BCG) vaccine as part of their TB control program, especially for infants. According to the WHO in 1993, this is the most often used vaccine worldwide, with 85% of infants in 172 countries immunized in 1993. This was the first vaccine for TB and developed at the Pasteur Institute in France between 1905 and 1921. However, mass vaccination with BCG did not start until after World War II. The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is greater than 80%; its protective efficacy for preventing pulmonary TB in adolescents and adults is variable, ranging from 0 to 80%. In South Africa, the country with the highest prevalence of TB, BCG is given to all children under age three. However, BCG is less effective in areas where mycobacterium is less prevalent; therefore BCG is not given to the entire population in these countries. In the USA, for example, BCG vaccine is not recommended except for people who meet specific criteria (W.HO, 2000).
The World Health Organization (WHO) declared tuberculosis a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between 2006 and 2015. Since humans are the only host of Mycobacterium tuberculosis, eradication would be possible. This goal would be helped greatly by an effective vaccine.
BCG provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB, which accounts for most of the disease burden worldwide. Currently, there are more cases of TB on the planet than at any other time in history and most agree there is an urgent need for a newer, more effective vaccine that would prevent all forms of TB—including drug resistant strains—in all age groups and among people with HIV (Southwick, 2007). Several new vaccines to prevent TB infection are being developed. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in the United States in 2004, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice; it may take four to five years to be available in humans (W.H.O, 2005). A very promising TB vaccine, MVA85A, is currently in phase II trials in South Africa by a group led by Oxford University, and is based on a genetically modified vaccinia virus (W.H.O, 2005). In treatment, the goal is to cure the infection with drugs that fight the TB bacteria. Treatment of active pulmonary TB will always involve a combination of many drugs (usually four drugs). All of the drugs are continued until lab tests show which medicines work best. The most commonly used drugs include Isoniazid, Rifampin, Pyrazinamide, and Ethambutol (Southwick, 2007).
In other concept, haematological profile are those parameters of the blood forms (red blood cells, white blood cells and platelets) with normal range or value as reference for any value to know whether or not they are normal (Hoffbrand et al., 2005).Therefore there is the need to know those parameters of the blood which are abnormal in patients living with pulmonary tuberculosis. The erythrocyte sedimentation rate and few of red and white cell indices would be considered. It is true that when one gets infected with pulmonary tuberculosis there is some level of changes which occurs in the blood because it is a bacterial infection. These changes need to be looked at and the extent considered.
In the final concept, the setting for this study is the District Hospital in Cape Coast which is the Cape Coast Metropolitan Hospital. Patients with pulmonary tuberculosis visiting this hospital and those admitted in the hospital are the objects for this study. This means the study is based on patients identified already as pulmonary T.B patients.
1.2 PROBLEM STATEMENT
Pulmonary tuberculosis is a major public health concern in Ghana. In Ghana, there are approximately 10 cases of TB per 100,000 people. However, rates vary dramatically by area of residence and socioeconomic class (G.H.S publications, 2000). The continuous spread of TB, requires effort to know: what the haematological profile of the people living with pulmonary tuberculosis are, what abnormal changes occur in these haematological parameters, what effect age and sex have on these haematological parameters of the patients.
1.3 JUSTIFICATION OF RESEARCH
Looking at the continuous spread and mode of transmission of this disease resulting into haematological changes in the patient, there is therefore the need to check the haematological profile of patients in order to treat underlining haematological changes as a result of pulmonary T.B alongside the treatment of the disease itself.
People living with pulmonary tuberculosis may have abnormal changes in their haematological parameters. It is expected that these changes may be identified in this research in order to be treated alongside the treatment of the Mycobacterium tuberculosis.
1.5.1 GENERAL OBJECTIVE
To analyze the haematological profile of people living with pulmonary tuberculosis attending the district hospital, Cape Coast.
1.5.2 SPECIFIC OBJECTIVES
1. To determine the abnormal changes that occurs in the haematological parameters (FBC indices, erythrocyte sedimentation rates, ESR) of pulmonary tuberculosis patients.
2. To know the effect of age and sex on the haematological indices of pulmonary tuberculosis patients.
2.1 TUBERCULOSIS (T.B)
Tuberculosis or TB (short for tubercles bacillus) is a common and often deadly infectious disease caused by various strains of mycobacterium, usually Mycobacterium tuberculosis in humans (Kumar et al., 2007).Tuberculosis usually attacks the lungs but can also affect other parts of the body. It is spread through the air when people who have the disease cough, sneeze, or spit (Konstantinos, 2010). Most infections in humans result in an asymptomatic, latent infection, and about one in ten latent infections eventually progresses to active disease which, if left untreated, kills more than 50% of its victims.
The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss. Infection of other organs causes a wide range of symptoms. Diagnosis relies on radiology (commonly chest X-rays), a tuberculin skin test, blood tests, as well as microscopic examination and microbiological culture of bodily fluids. Treatment is difficult and requires long courses of multiple antibiotics. Contacts are also screened and treated if necessary (Kumar et al., 2007). Antibiotic resistance is a growing problem in (extensively) multi-drug-resistant tuberculosis. Prevention relies on screening programs and vaccination, usually with Bacillus Calmette-Guérin vaccine. A third of the world's populations are thought to be infected with M. tuberculosis, (Jasmer et al., 2002) and new infections occur at a rate of about one per second. The proportion of people who become sick with tuberculosis each year is stable or falling worldwide but, because of population growth, the absolute number of new cases is still increasing (W.H.O, 2007).
In 2007 there were an estimated 13.7 million chronic active cases, 9.3 million new cases, and 1.8 million deaths, mostly in developing countries (W.H.O, 2009). In addition, more people in the developed world are contracting tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or AIDS.
The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5-10% of the US population test positive.
2.1.1 ORIGIN OF TUBERCULOSIS
Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 18,000 years before the present (Rothschild et al., 2001).Whether tuberculosis originated in cattle and then transferred to humans, or diverged from a common ancestor infecting a different species, is currently unclear (Pearce-Duvet, 2006). However, it is clear that M. tuberculosis is not directly descended from M. bovis, which seems to have evolved relatively recently (Ernst et al., 2007).Skeletal remains from a Neolithic Settlement in the Eastern Mediterranean show prehistoric humans (7000 BC) had TB, (Hershkovitz et al., 2008) and tubercular decay has been found in the spines of mummies from 3000–2400 BC (Zink et al, 2003). Phthisis is a Greek term for tuberculosis; around 460 BC, Hippocrates identified phthisis as the most widespread disease of the times involving coughing up blood and fever, which was almost always fatal (Hippocrates, 2006)
In South America, the earliest evidence of tuberculosis is associated with the Paracas-Caverna culture (circa 750 BC to circa 100 AD) (Konomi et al., 2002). In the past, tuberculosis has been called consumption, because it seemed to consume people from within, with a bloody cough, fever, pallor, and long relentless wasting. Other names included phthisis (Greek for consumption) and phthisis pulmonalis; scrofula (in adults), affecting the lymphatic system and resulting in swollen neck glands; tabes mesenterica, TB of the abdomen and lupus vulgaris, TB of the skin; wasting disease; white plague, because sufferers appear markedly pale; king's evil, because it was believed that a king's touch would heal scrofula; and Pott's disease, or gibbus of the spine and joints. Miliary tuberculosis—now commonly known as disseminated TB—occurs when the infection invades the circulatory system, resulting in millet-like seeding of TB bacilli in the lungs as seen on an X-ray (Encyclopedia Britannica, 2006). TB is also called Koch's disease, after the scientist Robert Koch (Ernst et al., 2007).
Before the Industrial Revolution, tuberculosis may sometimes have been regarded as vampirism. When one member of a family died from it, the other members that were infected would lose their health slowly. People believed that this was caused by the original victim draining the life from the other family members. Furthermore, people who had TB exhibited symptoms similar to what people considered to be vampire traits. People with TB often have symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin, extremely low body heat, a weak heart and coughing blood, suggesting the idea that the only way for the afflicted to replenish this loss of blood was by sucking blood (Sledzik, 1994). Another folk belief told that the affected individual was being forced, nightly, to attend fairy revels, so that the victim wasted away owing to lack of rest; this belief was most common when a strong connection was seen between the fairies and the dead (Katharine, 1976).
Similarly, but less commonly, it was attributed to the victims being "hagridden"—being transformed into horses by witches (hags) to travel to their nightly meetings, again resulting in a lack of rest (Katharine, 1976). TB was romanticized in the nineteenth century. Many people believed TB produced feelings of euphoria referred to as Spes phthisica ("hope of the consumptive"). It was believed that TB sufferers who were artists had bursts of creativity as the disease progressed. It was also believed that TB sufferers acquired a final burst of energy just before they died that made women more beautiful and men more creative (Lawlor, 2003). In the early 20th century, some believed TB to be caused by masturbation (Laumann et al., 1994). The study of tuberculosis, sometimes known as phthisiatry, dates back to The Canon of Medicine written by Ibn Sina (Avicenna) in the 1020s. He was the first physician to identify pulmonary tuberculosis as a contagious disease, the first to recognize the association with diabetes, and the first to suggest that it could spread through contact with soil and water (Al-Sharrah, 2003).
He developed the method of quarantine in order to limit the spread of tuberculosis (Al-Sharrah, 2003). In ancient times, treatments focused on sufferers' diets. Pliny the Elder described several methods in his Natural History: "wolf's liver taken in thin wine, the lard of a sow that has been fed upon grass, or the flesh of a she-ass taken in broth" (Al-Sharrah, 2003).
Although it was established that the pulmonary form was associated with "tubercles" by Dr Richard Morton in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s and was not named "tuberculosis" until 1839 by J. L. Schönlein (Konomi et al., 2002). During the years 1838 – 1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of tuberculosis sufferers 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. The first TB sanatorium opened in 1854 in Görbersdorf, Germany (today Sokołowsko, Poland) by Hermann Brehmer (Konomi et al., 2002).
The bacillus causing tuberculosis, Mycobacterium 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. Koch did not believe that bovine (cattle) and human tuberculosis were similar, which delayed the recognition of infected milk as a source of infection. Later, this source was eliminated by the pasteurization process. Koch announced a glycerin extract of the tubercle bacilli as a remedy for tuberculosis in 1890, calling it "tuberculin". It was not effective, but was later adapted as a test for pre-symptomatic tuberculosis (Ernst et al., 2007). The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guérin in 1906. It was called "BCG" (Bacillus of Calmette and Guérin). The BCG vaccine was first used on humans in 1921 in France, but it was not until after World War II that BCG received widespread acceptance in the USA, Great Britain, and Germany (Comstock, 1994). Tuberculosis, or "consumption" as it was commonly known, 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 of consumption; by 1918 one in six deaths in France were still caused by TB. In the 20th century, tuberculosis killed an estimated 100 million people (Bannon et al., 1999). After the establishment in the 1880s that the disease was contagious, TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were pressured to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention (Comstock, 1994).
Whatever the purported benefits of the fresh air and labor in the sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916) (Comstock, 1994).
The promotion of Christmas Seals began in Denmark during 1904 as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907 – 1908 to help the National Tuberculosis Association (later called the American Lung Association).In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons. In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in public health were reducing tuberculosis even before the arrival of antibiotics. The disease remained such a significant threat to public health, that when the Medical Research Council was formed in Britain in 1913, its initial focus was tuberculosis research (Bannon et al., 1999). It was not until 1946 with the development of the antibiotic streptomycin that effective treatment and cure became possible. Prior to the introduction of this drug, the only treatment besides sanatoria were surgical interventions, including bronchoscopy and suction as well as the pneumothorax or plombage technique — collapsing an infected lung to "rest" it and allow lesions to heal — a technique that was of little benefit and was mostly discontinued by the 1950s (Bannon et al., 1999).
The emergence of multidrug-resistant TB has again introduced surgery as part of the treatment for these infections. Here, surgical removal of chest cavities will reduce the number of bacteria in the lungs, as well as increasing the exposure of the remaining bacteria to drugs in the bloodstream. It is therefore thought to increase the effectiveness of the chemotherapy. Hopes that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, tuberculosis cases in Britain, numbering around 117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005 (Ernst et al., 2007).
Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence of TB in the late 1980s. The number of patients failing to complete their course of drugs is high. New York had to cope with more than 20,000 TB patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid).The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization (WHO) in 1993. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide (Al-Sharrah, 2003). Tuberculosis has co-evolved with humans for many thousands of years, and perhaps for several million years. The oldest known human remains showing signs of tuberculosis infection are 9,000 years old.
During this evolution, M. tuberculosis has lost numerous coding and non-coding regions in its genome, losses that can be used to distinguish between strains of the bacteria. The implication is that M. tuberculosis strains differ geographically, so their genetic differences can be used to track the origins and movement of each strain (Al-Sharrah, 2003).
The current clinical classification system for tuberculosis (TB) is based on the pathogenesis of the disease.
Classification System for TB
Class Type Description
0 No TB exposure No history of exposure
Not infected Negative reaction to tuberculin skin test
1 TB exposure History of exposure.
No evidence of infection Negative reaction to tuberculin skin test.
2 TB infection. No disease Positive reaction to tuberculin skin test
Negative bacteriologic studies (if done)
Fibrocaseous cavitary lesion (usually in
upper lobe of lungs)
3 TB, clinically active M. tuberculosis cultured (if done)
Clinical, bacteriologic, or radiographic
evidence of current disease
History of episode(s) of TB
4 TB Not clinically active or
Abnormal but stable radiographic
Positive reaction to the tuberculin skin
Negative bacteriologic studies (if done)
And No clinical or radiographic
evidence of current disease
5 TB suspect Diagnosis pending
TB disease should be ruled in or out
within 3 months
2.1.3 SIGNS AND SYMPTOMS
When the disease becomes active, 75% of the cases are pulmonary TB, that is, TB in the lungs. Symptoms include chest pain, coughing up blood, and a productive, prolonged cough for more than three weeks. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, pallor, and often a tendency to fatigue very easily (W.H.O, 2007). In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB, collectively denoted extra pulmonary tuberculosis. This occurs more commonly in immunosuppressed persons and young children. Extrapulmonary infection sites include the pleura in tuberculosis pleurisy, the central nervous system in meningitis, and the lymphatic system in scrofula of the neck, the genitourinary system in urogenital tuberculosis, and bones and joints in Pott's disease of the spine (W.H.O, 2007).
An especially serious form is disseminated TB, more commonly known as miliary tuberculosis. Extrapulmonary TB may co-exist with pulmonary TB as well (Madison, 2001).
The primary cause of TB, Mycobacterium tuberculosis, is a small aerobic non-motile bacillus. High lipid content of this pathogen accounts for many of its unique clinical characteristics (Cox, 2004).It divides every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour (Cox, 2004). (For example, one of the fastest-growing bacteria is a strain of E. coli that can divide roughly every 20 minutes). Since MTB has a cell wall but lacks a phospholipid outer membrane, it is classified as a Gram-positive bacterium. However, if a Gram stain is performed, MTB either stains very weakly Gram-positive or does not retain dye due to the high lipid & mycolic acid content of its cell wall (Madison, 2001). MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in vitro (Parish et al., 1999). Using histological stains on expectorate samples from phlegm (also called sputum); scientists can identify MTB under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified as an acid-fast bacillus (AFB) (Madison, 2001).The most common acid-fast staining technique, the Ziehl-Neelsen stain, dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an auramine-rhodamine stain and fluorescent microscopy.
The M. tuberculosis complex includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. Canetti and M. microti (van Soolingen et al., 1997). M. africanum is not widespread, but in parts of Africa it is a significant cause of tuberculosis (Niemann et al, 2002). M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public health problem in developed countries (Thoen et al., 2006). M. canetti is rare and seems to be limited to Africa, although a few cases have been seen in African emigrants (Pfyffer et al., 1998). M. microti is mostly seen in immunodeficient people, although it is possible that the prevalence of this pathogen has been underestimated (Niemann et al., 2000).
Other known pathogenic mycobacterium includes Mycobacterium leprae, Mycobacterium avium and M. kansasii. The last two are part of the nontuberculous mycobacterium (NTM) group. Nontuberculous mycobacterium cause neither TB nor leprosy, but they do cause pulmonary diseases resembling TB. Persons with silicosis have an approximately 30-fold greater risk for developing TB (Restrepo, 2007). Silica particles irritate the respiratory system, causing immunogenic responses such as phagocytosis which consequently results in high lymphatic vessel deposits (Restrepo, 2007). It is this interference and blockage of macrophage function which increases the risk of tuberculosis (Nijland et al., 2006). Persons with chronic renal failure who are on hemodialysis also have an increased risk: 10—25 times greater than the general population. Persons with diabetes mellitus have a risk for developing active TB that is two to four times greater than persons without diabetes mellitus, and this risk is likely greater in persons with insulin-dependent or poorly controlled diabetes. Other clinical conditions that have been associated with active TB include gastrectomy with attendant weight loss and malabsorption, jejunoileal bypass, renal and cardiac transplantation, carcinoma of the head or neck, and other neoplasms (e.g., lung cancer, lymphoma, and leukemia) (Restrepo, 2007).
Given that silicosis greatly increases the risk of tuberculosis, more research about the effect of various indoor or outdoor air pollutants on the disease would be necessary. Some possible indoor source of silica includes paint, concrete and Portland cement. Crystalline silica is found in concrete, masonry, sandstone, rock, paint, and other abrasives. The cutting, breaking, crushing, drilling, grinding, or abrasive blasting of these materials may produce fine silica dust. It can also be in soil, mortar, plaster, and shingles. When you wear dusty clothing at home or in your car, you may be carrying silica dust that your family will breathe.
Low body weight is associated with risk of tuberculosis as well. A body mass index (BMI) below 18.5 increases the risk by 2—3 times. On the other hand, an increase in body weight lowers the risk (Niobe-Eyangoh et al., 2003). Patients with diabetes mellitus are at increased risk of contracting tuberculosis, and they have a poorer response to treatment, possibly due to poorer drug absorption (Restrepo et al., 2007)
Other conditions that increase risk include IV drug abuse; recent TB infection or a history of inadequately treated TB; chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules; prolonged corticosteroid therapy and other immunosuppressive therapy; Immunocompromised patients (30-40% of AIDS patients in the world also have TB) hematologic and reticuloendothelial diseases, such as leukemia and Hodgkin's disease; end-stage kidney disease; intestinal bypass; chronic malabsorption syndromes; vitamin D deficiency (Nnoaham et al., 2008); and low body weight (Southwick et al., 2007). Twin studies in the 1940s showed that susceptibility to TB was heritable. If one of a pair of twins got TB, then the other was more likely to get TB if he was identical than if he was not (Jepson et al., 2001). These findings were more recently confirmed by a series of studies in South Africa (Jepson et al, 2001). Specific gene polymorphisms in IL12B have been linked to tuberculosis susceptibility (Tso et al., 2004). Some drugs, including rheumatoid arthritis drugs that work by blocking tumor necrosis factor-alpha (an inflammation-causing cytokine), raise the risk of activating a latent infection due to the importance of this cytokine in the immune defense against TB (Mutlu et al., 2006).
When people suffering from active pulmonary TB coughs, sneeze, speak, or spit, they expel infectious aerosol droplets 0.5 to 5 µm in diameter. A single sneeze can release up to 40,000 droplets. Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very low and inhaling less than ten bacteria may cause an infection (Nicas et al., 2005). People with prolonged, frequent, or intense contact are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10–15 other people per year. Others at risk include people in areas where TB is common, people who inject drugs using unsanitary needles, residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, patients immunocompromised by conditions such as HIV/AIDS, people who take immunosuppressant drugs, and health care workers serving these high-risk clients (Cole et al., 1998). Transmission can only occur from people with active — not latent — TB. The probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the virulence of the M. tuberculosis strain (Behr et al., 1999). The chain of transmission can, therefore, be broken by isolating patients with active disease and starting effective anti-tubercles therapy. After two weeks of such treatment, people with non-resistant active TB generally cease to be contagious. If someone does become infected, then it will take at least 21 days, or three to four weeks, before the newly infected person can transmit the disease to others (Jepson et al., 2001). TB can also be transmitted by eating meat infected with TB. Mycobacterium bovis causes TB in cattle. About 90% of those infected with Mycobacterium tuberculosis have asymptomatic, latent TB infection (sometimes called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease. However, if untreated, the death rate for these active TB cases is more than 50% (Sepulveda et al., 1994).
TB infection begins when the mycobacterium reach the pulmonary alveoli, where they invade and replicate within the endosomes of alveolar macrophages (Cobat et al., 2010). The primary site of infection in the lungs is called the Ghon focus, and is generally located in either the upper part of the lower lobe or the lower part of the upper lobe (Griffith et al., 1996). Bacteria are picked up by dendritic cells, which do not allow replication, although these cells can transport the bacilli to local (mediastinal) lymph nodes. Further spread is through the bloodstream to other tissues and organs where secondary TB lesions can develop in other parts of the lung (particularly the apex of the upper lobes), peripheral lymph nodes, kidneys, brain, and bone (Houben et al., 2006). All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid (Herrmann et al., 2005). Tuberculosis is classified as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B lymphocytes and fibroblasts are among the cells that aggregate to form a granulomatous, with lymphocytes surrounding the infected macrophages. The granulomatous functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected (Agarwal et al., 2005). Cytotoxic T cells can also directly kill infected cells, by secreting perforin and granulysin (Agarwal et al., 2005). Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of abnormal cell death, also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was termed caseous necrosis (Kaufmann, 2002).
If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most common in infants and the elderly and is called miliary tuberculosis. Patients with this disseminated TB have a fatality rate near 100% if untreated. However, if treated early, the fatality rate is reduced to near 10% (Kaufmann, 2002). In many patients the infection waxes and wanes (Grosset, 2003). Tissue destruction and necrosis are balanced by healing and fibrosis. Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are joined to the air passages bronchi and this material can be coughed up. It contains living bacteria and can therefore pass on infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.
If untreated, infection with Mycobacterium tuberculosis can become lobar pneumonia (Grosset, 2003).
Tuberculosis is diagnosed definitively by identifying the causative organism (Mycobacterium tuberculosis) in a clinical sample (for example, sputum or pus). When this is not possible, a probable - although sometimes inconclusive (Konstantinos, 2010) - diagnosis may be made using imaging (X-rays or scans) and/or a tuberculin skin test (Mantoux test). The main problem with tuberculosis diagnosis is the difficulty in culturing this slow-growing organism in the laboratory (it may take 4 to 12 weeks for blood or sputum culture). A complete medical evaluation for TB must include a medical history, a physical examination, a chest X-ray, microbiological smears, and cultures. It may also include a tuberculin skin test, a serological test. The interpretation of the tuberculin skin test depends upon the person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or immunosuppressant (Konstantinos, 2010). Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to an extract made from M. tuberculosis (Kumar et al., 2007). Those immunized for TB or with past-cleared infection will respond with delayed hypersensitivity parallel to those currently in a state of infection, so the test must be used with caution, particularly with regard to persons from countries where TB immunization is common(Cox, 2004). Tuberculin tests have the disadvantage of producing false negatives, especially when the patient is co-morbid with sarcoidosis, Hodgkin’s lymphoma, malnutrition, or most notably active tuberculosis disease. The newer interferon release assays (IGRAs) overcome many of these problems. IGRAs are in vitro blood tests that are more specific than the skin test. IGRAs detect the release of interferon gamma in response to mycobacterial proteins such as ESAT-6. These are not affected by immunization or environmental mycobacteria, so generate fewer false positive results (Pai et al., 2008). There is also evidence that the T-SPOT.TB IGRA is more sensitive than the skin test. Diagnosis of TB has also been done with use of various radiotracers using nuclear medicine methods, which not only detects but also locates tubercular infection (Lavani et al., 2005). New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These include polymerase chain reaction assays for the detection of bacterial DNA. The development of a rapid and inexpensive diagnostic test would be particularly valuable in the developing world (Reddy et al., 2002).
2.1.7 EPIDEMIOLOGY AND PROGNOSIS
Fig. (a) : The prevalence of TB per 100,000 people in sub – Saharan Africa in 2007.
In 2007, the prevalence of TB per 100,000 people was highest in sub-Saharan Africa, and was also relatively high in Asia (W.H.O, 2009).
Fig. (b): The annual number of new reported cases in the world.
Annual number of new reported TB cases. Data from W.H.O, 2007.
Roughly a third of the world's population has been infected with M. tuberculosis, and new infections occur at a rate of one per second (W.H.O, 2007). However, not all infections with M. tuberculosis cause TB disease and many infections are asymptomatic. In 2007, an estimated 13.7 million people had active TB disease, with 9.3 million new cases and 1.8 million deaths; the annual incidence rate varied from 363 per 100,000 in Africa to 32 per 100,000 in the Americas. Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS (W.H.O, 2007).
The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis (Iademarco et al., 2003). The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs (Lambert et al., 2003). The rate at which new TB cases occur varies widely, even in neighboring countries, apparently because of differences in health care systems (Sobero et al., 2006). In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases (W.H.O, 2009). The Philippines ranks fourth in the world for the number of cases of tuberculosis and has the highest number of cases per head in Southeast Asia. Almost two thirds of Filipinos have tuberculosis, and up to an additional five million people are infected yearly (Philippine Department of Health). In developed countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, the national average was 15 per 100,000 in 2007, and the highest incidence rates in Western Europe were 30 per 100,000 in Portugal and Spain. These rates compared with 98 per 100,000 in China and 48 per 100,000 in Brazil. In the United States, the overall tuberculosis case rate was 4 per 100,000 persons in 2007 (Sobero et al., 2006). In Canada tuberculosis is still endemic in some rural areas (Sobero et al., 2006).
The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults (W.H.O, 2006). However, in countries where TB has gone from high to low incidence, such as the United States, TB is mainly a disease of older people, or of the immunocompromised (Centers for Disease Control and Prevention (CDC), 2006). There are a number of known factors that make people more susceptible to TB infection: worldwide the most important of these is HIV. Co-infection with HIV is a particular problem in Sub-Saharan Africa, due to the high incidence of HIV in these countries (Chaisson et al., 2008). Smoking more than 20 cigarettes a day also increases the risk of TB by two to four times (Davies et al., 2006), (Jha et al., 2008). Diabetes mellitus is also an important risk factor that is growing in importance in developing countries (Restrepo, 2007). Other disease states that increase the risk of developing tuberculosis are Hodgkin lymphoma, end-stage renal disease, chronic lung disease, malnutrition, and alcoholism (Kumar et al., 2007).
Diet may also modulate risk. For example, among immigrants in London from the Indian subcontinent, vegetarian Hindu Asians were found to have an 8.5 fold increased risk of tuberculosis, compared to Muslims who ate meat and fish daily (Strachan et al, 1995-02). Although a causal link is not proved by this data (Davis, 1995) this increased risk could be caused by micronutrient deficiencies: possibly iron, vitamin B12 or vitamin D (Strachan et al, 1995-02). Further studies have provided more evidence of a link between vitamin D deficiency and an increased risk of contracting tuberculosis (Ustianowski et al., 2005), (Nnoaham et al., 2008). Globally, the severe malnutrition common in parts of the developing world causes a large increase in the risk of developing active tuberculosis, due to its damaging effects on the immune system (Schaible et al., 2007), (Lönnroth et al., 2008). Along with overcrowding, poor nutrition may contribute to the strong link observed between tuberculosis and poverty (Davies, 2003).
Prisoners, especially in poor countries, are particularly vulnerable to infectious diseases such as HIV/AIDS and TB. Prisons provide a condition that allows TB to spread rapidly, due to overcrowding, poor nutrition and a lack of health services. Since the early 1990s, TB outbreaks have been reported in prisons in many countries in Eastern Europe. The prevalence of TB in prisons is much higher than among the general population – in some countries as much as 40 times higher (Larouzé et al., 2008).
2.1.8 TREATMENT AND PREVENTION
Treatment for TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which makes many antibiotics ineffective and hinders the entry of drugs. The two antibiotics most commonly used are rifampicin and Isoniazid (Webber et al., 2001). However, instead of the short course of antibiotics typically used to cure other bacterial infections, TB requires much longer periods of treatment (around 6 to 24 months) to entirely eliminate mycobacteria from the body. Latent TB treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing antibiotic resistance. People with latent infections are treated to prevent them from progressing to active TB disease later in life (Barder et al., 2006).
Drug resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons who are infected with a resistant strain of TB. A patient with fully susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low quality medication. Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. Multi-drug-resistant tuberculosis (MDR-TB) is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB (XDR-TB) is also resistant to three or more of the six classes of second-line drugs (C.D.C, 2006). The DOTS (Directly Observed Treatment Short-course) strategy of tuberculosis treatment recommended by WHO was based on clinical trials done in the 1970s by Tuberculosis Research Centre, Chennai, India. The country in which a person with TB lives can determine what treatment they receive. This is because multidrug-resistant tuberculosis is resistant to most first-line medications, the use of second-line antituberculosis medications is necessary to cure the patient. However, the price of these medications is high; thus poor people in the developing world have no or limited access to these treatments (Dietrich et al., 2006).
TB prevention and control takes two parallel approaches. In the first, people with TB and their contacts are identified and then treated. Identification of infections often involves testing high-risk groups for TB. In the second approach, children are vaccinated to protect them from TB. No vaccine is available that provides reliable protection for adults. However, in tropical areas where the levels of other species of mycobacteria are high, exposure to nontuberculous mycobacteria gives some protection against TB (Fine et al., 2001). The World Health Organization (WHO) declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between 2006 and 2015 (W.H.O, 2006). Since humans are the only host of Mycobacterium tuberculosis, eradication would be possible. This goal would be helped greatly by an effective vaccine (Martin, 2006).
2.2.0 HAEMATOLOGICAL INDICES
Haemoglobin is measured to detect anaemia and its severity and to monitor an anaemic patient’s response to treatment. Monitoring the haemoglobin level (or PCV) is also required when patients with HIV disease are being treated with drugs such as AZT. The test is also performed to check the haemoglobin level of a blood donor prior to donating blood (Cheesbrough, 2006).
The erythrocyte sedimentation rate (ESR) is a non-specific test. It is raised in a wide range of infectious, inflammatory, degenerative, and malignant conditions associated with changes in plasma proteins, particularly increases in fibrinogen, immunoglobulins, and C-reactive protein. The ESR is also affected by many other factors including anaemia, pregnancy, haemoglobinopathies, haemoconcentration and treatment with anti-inflammatory drugs. Moderately raised sedimentation rates can sometimes be found in healthy people, particularly those living in tropical countries and a ‘normal’ ESR cannot exclude disease. In many tropical countries, ESR measurements have been discontinued because they add little to diagnosing disease, assessing its progress and monitoring response to treatment. When performed, test results must be interpreted in conjunction with clinical findings and the results of other laboratory tests (Cheesbrough, 2006).
A white blood cell (WBC) count is used to investigate HIV/AIDS, infections and unexplained fever, and to monitor treatments which can cause leucopenia. In most situations when a total WBC count is requested it is usual to perform also a differential WBC count (Cheesbrough, 2006). The main causes of a raised WBC count (leukocytosis) are: Acute infections e.g. pneumonia, meningitis, abscess, whooping cough, tonsillitis, acute rheumatic fever, septicaemia, gonorrhoea, cholera, septic abortion; acute infections in children can cause a sharp rise in WBC count; Inflammation and tissue necrosis e.g. burns, gangrene, fractures and trauma, arthritis, tumours, acute myocardial infarction; metabolic disorders e.g. eclampsia, uraemia, diabetic coma and acidosis; poisoning e.g. chemicals, drugs, snake venoms; acute haemorrhage; leukaemias and myeloproliferative disorders; stress, menstruation, strenuous exercise (Cheesbrough, 2006). The main causes of a reduced WBC count are: Viral, bacterial, parasitic infections e.g. HIV/AIDS, viral hepatitis, measles, rubella, influenza, rickettsial infections, overwhelming bacterial infections such as miliary tuberculosis, relapsing fever, typhoid, paratyphoid, bucellosis, parasitic infections including leishmaniasis and malaria; drugs (e.g. cytotoxic) and reactions to chemicals; hypersplenism; aplastic anaemia Folate and vitamin B12 deficiencies (megaloblastic anaemia); bone marrow infiltration (e.g. lymphomas, myelofibrosis, myelomatosis); anaphylactic shock; ionizing radiation (Cheesbrough, 2006).
In conclusion, pulmonary tuberculosis is a worldwide deadly disease which should be considered and tackled not forgetting other abnormal changes that it brings to the human body thereby tackling those changes too. Pulmonary tuberculosis is a major public health concern in Ghana. In Ghana, there are approximately 10 cases of TB per 100,000 people. However, rates vary dramatically by area of residence and socioeconomic class (G.H.S publications, 2000). The continues spread of TB, requires effort to know: what the haematological profile of the people living with pulmonary tuberculosis are, what abnormal changes occur in these haematological parameters, what effect age and sex have on these haematological parameters of the patients.
3.1.0 STUDY AREA AND WHERE RESEARCH WORK WAS UNDERTAKEN
Pulmonary tuberculosis patients who visited the district hospital (Cape Coast Metropolitan Hospital) in the Cape Coast Municipality in the Central Region of Ghana were the target population for the study. The research work was done in the laboratory within the same hospital.
3.1.1. STUDY PERIOD
The study was conducted between the months of December, 2010 and February, 2011. During this period the samples were taken weekly.
3.2.0 ETHICAL CONSIDERATION
The selection of subjects and the collection of specimens from the subjects was done after prior notice and approval from all protocols involved, was obtained.
3.3 SAMPLES, SAMPLING TECHNIQUE AND SIZE
A total number of one hundred (100) patients were sampled from the target population randomly. The blood samples only were taken into EDTA tubes using vacutainers for the venipuncture.
The vacutainer method of bloodletting into EDTA tubes was used in sampling the blood. Before the sampling all the necessary materials equipment (gloves, cotton wool, alcohol prep pad, tourniquet, plaster, needle and vacutainer holder) needed were prepared and set.
During the sampling, the patients name and age were taken. All specimen tubes were marked with the identification and pull on protective gloves to prevent contact with bodily fluids. Blood was drawn from the most common point--the median cubital vein--which runs on the inner part of the forearm. This is the optimum vein because it's close to the skin surface and there aren't a lot of nerves surrounding it. The chosen location was prepped by placing a tourniquet on the upper part of the arm, tight enough to make the vein bulge. The vein was gently patted and its size looked at. The best angle from which to draw the blood was then found. The needle was inserted into the vein with a smooth, fast motion. This technique lessened the pain. The vacutainer (blood specimen tube) was pushed into the holder, keeping the needle steady. The vacutainer automatically started filling with the right amount of blood needed for the specific specimen. The needle was pulled out at the same angle it was inserted once the specimen was collected. Immediately, after the needle was disposed off properly and cotton applied to the patient's wound, holding it to apply pressure and finally plastered it. The specimens were mixed thoroughly by gently swishing them around. Confirmation was made that each specimen was labeled correctly.
3.4.0 LABORATORY AND OR OTHER ACTIVITY
The laboratory activities that were carried out for the purpose of the study were the erythrocyte sedimentation rate, ESR (using the westergren method) and the full blood count, FBC (using the Sysmex XT- 20000i analyser).
Due to the lack of interest and state of some patients a large number of pulmonary tuberculosis patients were not sampled for the study.
The research involved only pulmonary tuberculosis patients who attended the district hospital in the municipality.
3.7.0 STATISTICAL TOOL AND ANALYSIS EMPLOYED
Pie charts and graphs percentages were used. Pie charts and graph where use to represent the values of the raw data taken and analysed using excel.
A total number of one hundred (100) patients were sampled from the target population randomly. The blood samples were taken into EDTA tubes using vacutainer method for the venipuncture.
4.1 The haemoglobin parameter studied in the study population.
Out of the 100 sampled, 62 (62%) had Hb below normal (<11.0g/dl) (anaemic), 38 (38%) had normal Hb (11.0g/dl-18.0g/dl) and none had Hb above normal (>18.0g/dl).
Fig 4.1 Haemoglobin parameter studied in the study population
4.2 The erythrocyte sedimentation rate (ESR) parameter studied in the study population
Out of the 100 sampled 6(6%) were within E.S.R value 0-20mm/hr (1), 1(1%) was within the E.S.R value 21-40mm/hr (2), 9(9%) were within the E.S.R value 41-60mm/hr (3), 7(7%) were within the E.S.R value 61-80mm/hr (4), 77(77%) were >80mm/hr (5).
Fig 4.2 Erythrocyte sedimentation rate (ESR) parameter studied in the study population
4.3 The total leucocyte count parameter studied in the study population
Out of the 100 sampled, 2(2%) had total leucocyte count below 4.0 * 10^3 / ul, 29 (29%) had normal total leucocyte count and 69 (69%) above 11.0 * 10^3 / ul.
Fig. 4.3 total leucocyte count parameter studied in the study population
4.4 The absolute neutrophil count (A.N.C) parameter studied in the study population
Out of the 100 sampled, 3(3%) had A.N.C below 2.5 * 10^3 / ul, 29 (29%) had normal A.N.C and 68 (68%) had A.N.C above 7.5 * 10^3 / ul.
Fig. 4.4 absolute neutrophil count (A.N.C) parameter studied in the study population
4.5 The absolute lymphocyte count parameter studied in the study population
Out of the 100 sampled, 17(17%) had absolute lymphocyte count below 1.5 * 10^3 / ul, 80 (80%) had normal absolute lymphocyte count and 3(3%) had absolute lymphocyte count above 3.5 * 10^3 / ul.
Fig. 4.5 absolute lymphocyte count parameter studied in the study population
4.6 The platelet count parameter studied in the study population
Out of the 100 sampled, 8(8%) had platelet count below 150 * 10^3 / ul, 49(49%) had normal platelet count and 43(43%) had platelet count above 150 * 10^3 / ul.
Fig. 4.6 platelet count parameter studied in the study population
4.7 The percentage of the study population’s sex
Out of the 100 sampled, 59(59%) were male and 41(41%) were female.
Fig. 4.7 Percentage of the Study Population’s Sex
4.8 The percentages of the study population’s age
Out of the 100 sampled 4(4%) were within the age range of 10 – 19, 55(55%) were within the age range of 20 – 29, 37(37%) were within the age range of 30 – 39, 4(4%) also were within the age range of 40 – 49, none of the patients were within the age ranges of 0 – 9 and 50 – 59.
Fig. 4.8 Percentages of the Study Population’s Age
5.0 DISCUSSION, CONCLUSION AND RECOMMENDATION
Based on the results obtained from the study carried out on 100 pulmonary T.B patients between the ages of 1 and 66 in the Cape Coast Metropolitan Hospital, of which 59 subjects were males and 41 females, the following assertions were made.
In a research carried out on Haematological profile of patients with pulmonary tuberculosis in Ibadan, Nigeria, it was found that the haematological indices of sixty two pre-treatment, sputum-smear-AFB positive pulmonary tuberculosis patients were examined. Haematocrit, white cell count and differentials and erythrocyte sedimentation rates (ESR) were estimated by manual methods. Statistically significant heamatologic abnormalities found include high erythrocyte sedimentation rate (ESR), anaemia occurred in 93.6%, leucocytosis in 22.3%, neutrophilia in 45.2% and lymphopaenia in 4.8% of the patients. Thrombocytosis occurred in 12.9%, while 8% had thrombocytopaenia. None of the patients had leucopaenia and only 8.4% had lymphocytosis (Olaniyi et al., 2003).
Also another research carried out on the haematological abnormalities in pulmonary tuberculosis in Hungary revealed the extent and severity of haematological abnormalities which occurred in 380 patients with pulmonary tuberculosis. Full blood count, bone marrow aspiration smears, and bone marrow trephine biopsy was analyzed by authors. Anaemia was present in 32% of patients. Leucocytosis with neutrophilia occurred in 18%. Leucopenia with neutropenia, and lymphopaenia was observed in 16% in patients with very severe clinical tuberculosis. Elevated platelet count occurred in 8% with deep vein thrombosis in legs in 50%. There was a close correlation between the haematological abnormalities and the severity of clinical findings of pulmonary tuberculosis. This survey has revealed that haematological abnormalities are relatively common in severe pulmonary tuberculosis. It seems that body weight loss, white blood cell count, haemoglobin level and erythrocyte sedimentation rate are useful indices of severity of the tuberculosis. The return of these indices to a normal level is a good indication of disease control in that they correlate with sputum conversion to acid-fast bacilli negative (Bozóky et al., 1997).
Anaemia occurs when the Hb of an individual falls below normal (11.0g/dl). Anaemia occurs in different forms, with anaemia due to chronic disease such as tuberculosis (Cheesbrough, 2006) considered here. With this, leucocytes changes reflect the condition (Cheesbrough, 2006). Therefore, high leucocyte changes with low Hb reflect anaemia due to chronic condition such as tuberculosis. Increase in leucocytes count may also be as a result of increase in neutrophil count (Cheesbrough, 2006). In bacterial infections, neutrophil counts are increased (Cheesbrough, 2006). This may count for neutrophilia in most patients as Mycobacterium tuberculosis is a bacteria. Infection such as tuberculosis may lead to thrombocytosis as well as thrombocytopenia (Cheesbrough, 2006). Pulmonary tuberculosis (TB) is a contagious bacterial infection caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis) (Saunders, 2007). Significantly raised erythrocyte sedimentation rate can be caused by infection such as tuberculosis (Cheesbrough, 2006). The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults (W.H.O, 2006)
The figures (4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, and 4.8) above show the percentage of patients who fall below and above the normal ranges of each haematological profile (i.e., the percentage of patients with abnormal haematological changes) and also the percentages of the age and sex of the study population. In fig. 4.1, out of the 100 sampled, 62 (62%) had Hb below normal (anaemic), 38 (38%) had normal Hb and none had Hb above normal. This was because tuberculosis is one of the major causes of anaemia due to chronic infection (Cheesbrough, 2006). Also 94 out of the 100 patients had high erythrocyte sedimentation rate whereas only 6 of them where normal. People with infections such as pulmonary tuberculosis normally have high ESR. This was shown in fig. 4.2. Patients with high leucocytes count were 69 out of 100 patients making 69% of patients with leucocytosis. This was shown in fig4.3 as out of the 100 sampled, 2(2%) had total leucocytes count below 4.0 * 10^3 / ul, 29 (29%) had normal total leucocytes count and 69 (69%) above 11.0 * 10^3 / ul. Leucocytosis with low Hb reflects pulmonary tuberculosis (Cheesbrough, 2006). Also patients with high neutrophil count were 68 out of 100 patients making 68% of the patients with neutrophilia. Only a few (20) out of the 100 patients had abnormal values for lymphocyte count whereas 17 of the patients making 85% were below 1.5*103/ul (lymphopaenia) and 3 making 15% with lymphocytosis. A few of the patients (slightly above have of the total population (51)) also had abnormal platelet count with 43 of them making (43%) had thrombocytosis and 8 (8%) having thrombopenia and 49 (49%) were normal.
Fig.4.7 and 4.8 above shows the percentage of the study population (pulmonary TB patients) of various ranges of ages and sex (male and female). From fig. 4.8, 55% of the total population suffering from pulmonary tuberculosis was between the ages of 20 – 29 making up the largest age group suffering from pulmonary tuberculosis. The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults (W.H.O, 2006). This was followed by the age group 30 – 39 with 37%. The age groups 10 – 19 and 40 – 49 were the least suffering from pulmonary tuberculosis with 4% of the population each. No samples were taken for ages 0 – 9 and 50 – 59.
Comparing the results that were gotten from the research carried out in the District hospital, Cape Coast with that of the study done in Ibadan, Nigeria, it was found out that both had majority of the patients being anaemic, high erythrocyte sedimentation rate occurred in most of the patients. Leukocytosis with neutrophilia also occurred in most patients.
The study of the haematological profile of Pulmonary tuberculosis patients in the Cape Coast Metropolitan Hospital indicates a significant change in their haemoglobin (Hb) (very low Hb indicating anaemia), Erythrocyte Sedimentation Rate (ESR) (high ESR values), total leukocyte count (high leukocytes indicating leukocytosis), neutrophil count (high neutrophil count indicating neutrophilia), lymphocyte count and platelet count. A figure also indicated that the age group with the highest frequency of pulmonary tuberculosis was age group 20 to 29 and the age groups with the least number of pulmonary T.B subjects were age groups 10 to 19 and 40 to 49.
The study also pointed out that, males were infected with pulmonary tuberculosis than females.
Therefore, from the study, haematological changes occur in patients with pulmonary tuberculosis which are high erythrocyte sedimentation rate (ESR), anaemia, leukocytosis, neutrophilia occurring in most patients and lymphopaenia in some patients. Thrombocytosis occurred in some patients, thrombocytopaenia also occurred in some patient. A few of the patients had leucopaenia and lymphocytosis.
Based on this observation and the already stated conclusions, I therefore recommend that physicians treat patients suffering from pulmonary tuberculosis not only of pulmonary tuberculosis but underlining haematological disorders as a result of pulmonary tuberculosis. Further studies should also focus on finding the extent of damage caused by these abnormal changes as a co-infection with pulmonary tuberculosis. This will help establish whether these changes significantly affects the progress of pulmonary tuberculosis or the vice versa in pulmonary tuberculosis patients, or it will help establish the relation between pulmonary tuberculosis and abnormal haematological profile in pulmonary T.B patients.
Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D (2005). "Tuberculous dilated cardiomyopathy: an under-recognized entity?” BMC Infect Dis 5 (1): 29.
Al-Sharrah Y. A. (2003), "The Arab Tradition of Medical Education and its Relationship with the European Tradition", Prospects 33 (4), Springer.
Bozóky, Orv Hetil, Afr J Med Med Sci. 1997 Dec; 42(3):339-42
Cheesbrough M. (2006). “District Laboratory Practice in Tropical Countries” 2nd Edition, Cambridge press. Pages 299, 321 and313.
Cole E, Cook C (1998). "Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies". Am J Infect Control 26 (4): 453–64.
Comstock G (1994). "The International Tuberculosis Campaign: a pioneering venture in mass vaccination and research". Clin Infect Dis 19 (3): 528–40
Davies PD (2003). "The world-wide increase in tuberculosis: how demographic changes, HIV infection and increasing numbers in poverty are increasing tuberculosis". Annals of medicine 35 (4): 235–43.
Davies PDO, Yew WW, Ganguly D, (2006). "Smoking and tuberculosis: the epidemiological association and pathogenesis". Trans R Soc Trop Med Hyg 100 (4): 291–8.
Ernst JD, Trevejo-Nuñez G, Banaiee N (July 2007). "Genomics and the evolution, pathogenesis, and diagnosis of tuberculosis". 4th edn. J. Clin. Invest. Page 117.
Ghana Health Service (G.H.S) publications, 2009.
Hippocrates, www.wikipedia.com, aphorisms. Accessed 7 October 2006.
Hoffbrand A.V & Petit J.E (2000) “Clinical Haematology”, 3rd Edn. Mosby, London. Pg. 56
Kaufmann S (2002). "Protection against tuberculosis: cytokines, T cells, and macrophages". Ann Rheum Dis 61 Suppl 2: ii54–8.
Keeffe E. B. (2004). “A treatment algorithm for the management of chronic infection in the United States.” Clin Gastroenterology Hepatol, 2:87-106.
Kent A Sepkowitz (2001). AIDS – The first 20 years.The new Eng. J. Med. 344( 23): 1764 – 1722.
Konstantinos E.T (2010), “Infectious Diseases: A Clinical Course” 2nd edition McGraw Hill Medical Publishing Division. Pg. 104.
Madison B (2001). "Application of stains in clinical microbiology". Biotech Histochem 76 (3): 119–25
Niemann S, Rüsch-Gerdes S, Joloba ML. (September 2002). "Mycobacterium africanum subtype II is associated with two distinct genotypes and is a major cause of human tuberculosis in Kampala, Uganda". J. Clin. Microbiol. 40 (9).
Ogun SA, Adelowo OO, Familoni OB, Adefuye BO, Alebiosu C, Jaiyesinmi EAE, Fakoya EAO, Odusan B, Odusoga OL, Ola OO, (2003). Spectrum and outcome of clinical disease in adults living with AIDS at the Ogun State University Teaching Hospital. East Afr. Med. J. 80 (10): 513-518.
Olaniyi JA, Aken'Ova YA, Afr J Med Med Sci. 2003 Sep; 32(3):239-42.
Parish T, Stoker N (2003). "Mycobacteria: bugs and bugbears (two steps forward and one step back)". Mol Biotechnology 13 (3): 191–200.
Sauders E. (2007) “Robbins Basic Pathology”, 8th Edition Cambridge Press, London. Pages 516 – 520.
Schaible UE, Kaufmann SH (May 2007). "Malnutrition and infection: complex mechanisms and global impacts". PLoS medicine 4 (5): e115.
Smith EM, Samadian S (1994). Use of the Erythrocyte sedimentation rate in the elderly. Br. J. Hosp. Med. 51: 394.
Sobero R, Peabody J (2006). "Tuberculosis control in Bolivia, Chile, Colombia and Peru: why does incidence vary so much between neighbors?” Int J Tuberc Lung Dis 10 (11): 1292–5. PMID 17131791.
Southwick L. (2007) “Testing Tuberculosis”, 4th Edition Australian Publishing. Pages 12 –18.
World Health Organization (2009). "EpidemiologyGlobal tuberculosis control: epidemiology, strategy, finances. pp. 6–33
World Health Organization (WHO) WHO report 2008: Global tuberculosis control Retrieved on 13 April 2009.
Www.wikipedia.com; retrieved 18-03-2011; 10:45 am.
LABORATORY TEST PROCEDURE FOR E.S.R AND FULL BLOOD COUNT
THE ERYTHROCYTE SEDIMENTATION RATE (ESR) TEST
The erythrocyte sedimentation rate (ESR) is a non-specific test. It is raised in a wide range of infectious (including pulmonary tuberculosis), inflammatory, degenerative, and malignant conditions associated with changes in plasma proteins, particularly increases in fibrinogen, immunoglobulin, and C-reactive protein. The ESR is also affected by many other factors including anaemia, pregnancy, haemoglobinopathies, haemoconcentration and treatment with anti-inflammatory drugs. Moderately raised sedimentation rates can sometimes be found in healthy people, particularly those living in tropical countries and a ‘normal’ ESR cannot exclude disease. In many tropical countries, ESR measurements have been discontinued because they add little to diagnosing disease, assessing its progress and monitoring response to treatment. When performed, test results were interpreted in conjunction with clinical findings and the results of other laboratory tests.
PRINCIPLE OF TEST
When citrated blood is vertically positioned and Westergren pipette is left undisturbed, red cells aggregate, stack together to form rouleaux, and sediment through the plasma. The ESR is the rate at which this sedimentation occurs in 1 hour as indicated by the length of the column of clear plasma above the red cells, measured in mm. Fibrinogen, immunoglobulin, and C reactive protein increase red cell aggregation. Sedimentation is increased when the ratio of red cells to plasma is altered, e.g. in anaemia. Sedimentation is reduced when the red cells are abnormally shaped, e.g. sickle cells. High temperatures (over 25 degrees Celsius) increase sedimentation.
EQUIPMENT USED FOR THE TEST
The following equipments were used for the test: westergren ESR pipette, westergren ESR stand with leveling device and timer capable of timing accurately 1 hour.
Tri-Sodium citrate, 32 g/l (3.2% W/v) anticoagulant, stored at 4-8 degrees Celsius.
1. 0.4 ml of sodium citrate anticoagulant was pipette into a small container for each patient.
2. 1.6 ml of the EDTA anticoagulated blood was added and mixed well. The cap of the container was removed and the sample placed in the ESR stand. A Westergren pipette was inserted and ensured it is positioned vertically.
3. Using a safe suction method, blood was drawn to the 0 mark of the Westergren pipette, avoiding air bubbles.
4. The ESR stand was checked if it was leveled by making sure that the bubble in the spirit level is central.
5. The timer was set for 1 hour. Ensuring that the ESR stand and pipette would not be exposed to direct sunlight.
6. After exactly 1 hour, the level at which the plasma meets the red cells in mm was read and recorded.
7. After reading the ESR, the blood was returned to its container; the pipette was carefully removed and soaked in sodium hypochlorite 2500 ppm av Cl (0.25%) disinfectant.
8. The blood was disposed off safely and decontaminated the container before washing it and also the ESR stand.
THE TEST FOR FULL BLOOD COUNT
The full blood count of the samples was done by using the Sysmex XT- 20000 I full count analyzer. The samples were mixed thoroughly before they were run on the analyzer. The sample then goes through some processes within the analyzer to produce results which come out printed on a sheet of paper.
The results of each sample are taken out and the necessary parameters needed to run the experiment was identified and recorded in a notebook.