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transported through the lymphatics to establish secondary sites (lymphohematogenous spread).
The development of an immune response, heralded by a delayed-type hypersensitivity reaction
over the next 4 weeks, leads to granuloma formation, with a subsequent decrease in the number
of bacilli. Some of them remain viable, or dormant, for many years. This stage is called latent TB
infection (LTBI), which is generally an asymptomatic, radiologically undetected process in
humans. Sometimes, a primary complex (Ghon complex) can be seen radiographically, mostly in
the lower and middle lobes, and comprises the primary lesion, hilar lymphadenopathy, with or
without a lymphangitic track. Later, the primary lesion tends to become calcified and can be
identified on chest radiographs for decades. Most commonly, a positive tuberculin test result
remains the only proof of LTBI, and therefore does not signify active disease.
Under certain conditions of immature or disregulated immunity, alveolar macrophagesand the subsequent biologic cascade could fail in limiting the mycobacterial proliferation,
leading to primary progressive tuberculosis; this is seen mostly in children younger than 5 years
or in HIV-positive or profoundly immunosuppressed individuals. Factors known to influence this
unfavorable course are patient's age, nutritional status, host immunity, and bacterial infective
load.
Once infected withM. tuberculosis, 3% to 5% of immunocompetent persons develop
active disease (i.e., secondary progressive tuberculosis) within 2 years and an additional 3% to
5% later on during their lifetime. Overall, there is a lifetime risk of re-activation of 10%, with
one half occurring during the first 2 years after infectionhence, the necessity to treat all
tuberculin skin test converters. The lifetime re-activation rate is approximately 20% for most
persons with purified protein derivative (PPD) induration of more than 10 mm and either HIV
infection or evidence of old, healed tuberculosis; it is between 10% and 20% for recent PPD skin
test converters, adults younger than 35 years with an induration of more than 15 mm or on
therapy with infliximab (a tumor necrosis factor [TNF-] receptor blocker), and children
younger than 5 years and a skin induration of more than 10 mm.
Studies performed in New York City and San Francisco using DNA fingerprinting have
indicated that recent transmission (exogenous reinfection), especially among HIV patients, could
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account for up to 40% of new TB cases. This is significantly different from older studies, which
have shown that approximately 90% of new TB cases are the result of endogenous re-activation.
After inhalation, the pathogenic bacilli start to replicate slowly and continuously and lead
to the development of a cellular immunity in about 4 to 6 weeks. T lymphocytes and local
(pulmonary and lymphatic node) macrophages represent key players in limiting further spread of
bacilli in the host. This can be seen at the pathologic level, where the bacilli are in the center of
necrotizing (caseating) and non-necrotizing (noncaseating) granulomas, surrounded by
lymphocytes and macrophages. The infected macrophages release interleukins 12 and 18 (IL-12
and IL-18), which stimulate CD4-positive T lymphocytes to secrete IFN-(interferon gamma),
which in turn activate the macrophage phagocytosis ofM. tuberculosis and the release of TNF-.
TNF-has an important role in granuloma formation and the control of infection.
Genetic defects are illustrated by different polymorphisms of theNRAMP-1gene (natural
resistance-associated macrophage protein-1); vitamin D receptors, and interleukin-1 have also
been shown to be involved in TB pathogenesis. It can be difficult to differentiate between genetic
predisposition and overwhelming bacteriologic load, as often seen in countries with a high
prevalence of TB.
HIV coinfection is the greatest risk factor for progression to active disease in adults. Therelation between HIV and TB has augmented the deadly potential of each disease. Other risk
factors include diabetes mellitus, renal failure, coexistent malignancies, malnutrition, silicosis,
immunosuppressive therapies (including steroids and anti-TNF drugs), and TNF-receptor, IFN-
receptor, or IL-12 1receptor defects (Ioachimescu and Tomford, 2010).
2.2 Risk Factors
Tuberculosis is associated with a wide range of comorbidities. Globally, about 15% of
people with this disease are infected with HIV (WHO, 2009). About 50% of patients with
tuberculosis in high-burden countries are undernourished; in adults, about 50% are smokers,
about 20% misuse alcohol, and about 15% have diabetes, with much higher numbers in some
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countries than in others. Services for these diseases are often underdeveloped in low-income and
middle-income countries and, as a result, they are often not diagnosed (Harries et al, 2009).
Meeting the medical-care needs of patients with tuberculosis therefore requires access to basic
primary health-care services, beyond good tuberculosis care. Within national health plans, NTPs
should strengthen collaboration with other public health programs to contribute to the
prevention, treatment, and management of these conditions. Frameworks for such work are
already well established for HIV, and are being developed for smoking-related diseases (WHO,
2008). Finally, the challenge of inadequate information about tuberculosis morbidity and
mortality needs to be addressed in the context of broad efforts to tackle general deficiencies in
health-information systems. Experience in China has shown how improvements in the general
disease-notification system, combined with increased public health funding and regulatory
interventions, improved both the quality of tuberculosis statistics and program performance
(Wang, 2007).
The positive effects of improved living conditions and nutritional status in industrialized
countries over the past century, the negative effects of the economic downturn in countries of
eastern Europe and the former Soviet Union in the 1990s (Shilova and Die, 2001) and the clear
association between broad development indicators and tuberculosis incidence trends in the past
century and in recent years (Oxlade et al, 2009) are examples of how socioeconomic factors can
affect tuberculosis epidemics. Most of the proximate risk factors for tuberculosis are associated
with social conditions. People from low socioeconomic status groups typically have more
frequent contact with people with active disease, a higher likelihood of crowded living and
working conditions, greater food insecurity, lower levels of health awareness or less power to act
on existing knowledge concerning healthy\behaviour, and less access to quality health care than
do those from high socioeconomic groups (Lonroth et al, 2009). Malnutrition, crowding, and
exposure to indoor air pollution are direct markers of poverty. The prevalence of smoking is
consistently highest in low socioeconomic groups in all regions worldwide. For HIV, alcohol
misuse, and diabetes, the trend is not straightforward, but in middle-income and high-income
countries these factors are more prevalent in low socioeconomic groups (Blas and Sivasankara,
2010).
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Improved wealth, education, and social protection would greatly benefit tuberculosis
control. However, some aspects of economic development might have a negative effect. Rapid
industrialization, urbanization, and migrationdominant occurrences in most developing
countriescan create ideal conditions for tuberculosis epidemics to flourish, unless
accompanied by good urban planning, social reforms, environmental protection, and a strong and
well coordinated health system. The incidence in urban areas is generally higher than in rural
areas, possibly because of a combination of high population density and lifestyle changes
associated with urban living. Exposure to some tuberculosis risk factors such as smoking,
alcohol misuse, and unhealthy diet can increase when absolute poverty falls at the same time as
rapid sociocultural transition leads to changed patterns in health behavior (Kjellstrom, 2007).
2.2.1 Silicosis
People with silicosis have an approximately 30-fold greater risk for developing TB. Silica
particles irritate the respiratory system, causing immunogenic responses such as phagocytosis,
which results in high lymphatic vessel deposits. It is probably this interference and blockage
of macrophage function that increases the risk of tuberculosis. Persons with chronic renal failure
and also on hemodialysis have an increased risk (Segall and Covick, 2010). 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 sources of silica
include 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. Some drugs, including rheumatoid arthritis drugs that work by
blocking tumor necrosis factor-alpha (an inflammation-causingcytokine), 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).
2.2.2 HIV
HIV is a major risk factor for tuberculosis. The risk of developing TB is estimated to be
between 20-37 times greater in people living with HIV than among those without HIV infection.
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TB is a leading cause of morbidity and mortality among people living with HIV. In 2009, there
were 9.4 million new cases of TB, of which 1.2 (13%) million were among people living with
HIV. Of the 1.7 million people who died of TB, 400,000 (24%) were living with HIV (Reuben,
2010).
2.2.3 Nutrition
There is strong evidence that primary malnutrition raises the incidence and exacerbates
clinical manifestations of tuberculosis. In a World War II study, Leyton studied hard-working
prisoners of war in a German camp. Soviet prisoners had a daily caloric intake of about 1350
kcal, whereas UK prisoners received additional Red-Cross food supplies, which doubled their
daily caloric intake. The rate of radiologically and microscopically confirmed pulmonary\
tuberculosis was 158-fold higher in the Soviet prisoners than in the UK prisoners (190 vs
12%). Leyton concluded that the lack of food, not poor natural immunity, was the main cause of
this difference in rate.
Low body weight is associated with risk of tuberculosis. A body mass index (BMI) below
18.5 increases the risk by 2 to 3 times. An increase in body weight lowers the risk (Leung, 2007).
People with diabetes mellitus are at increased risk of contracting tuberculosis (Restrepo, 2007),
and they have a poorer response to treatment, possibly due to poorer drug absorption (Nijland,
2006). 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).
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. Although a causal link is not
proved by this data, this increased risk could be caused by micronutrient deficiencies: possibly
iron, vitamin B12 or vitamin D. Further studies have provided more evidence of a link between
vitamin D deficiency and an increased risk of contracting tuberculosis (Nnoaham and Clarke,
2008). Globally, the severe malnutrition common in parts of the developing world causes a large
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increase in the risk of developing active tuberculosis, due to its damaging effects on the immune
system (Lnnroth and Raviglione, 2008). Along with overcrowding, poor nutrition may
contribute to the strong link observed between tuberculosis and poverty (Davies, 2003).
Experimental data have since corroborated this observation. Mice with protein caloriemalnutrition infected intravenously with Mycobacterium tuberculosis expressed less interferon-
gamma, tumour necrosis factor, and inducible nitric oxide in their lungs than did control mice.
Malnourished mice also had decreased granulomatous reaction,higher lung bacillary load, and a
more fatal tuberculosis course than did well nourished mice, which could be reversed by
restoring a diet with normal protein content. In other studies, protein malnutrition has impaired
T-cell function, particularly the production of T-helper-1 cytokines and macrophage
antimycobacterial effector functions. The relation between malnutrition and tuberculosis should
be highlighted in the context of the highly prevalent southern African HIV-1 and tuberculosis co-
infection. HIV-1 infection devastates CD4 lymphocyte numbers but has similar immunological
consequences to malnutrition, by suppressing T-helper-1 and macrophage functions, which may
have an additive effect in raising tuberculosis incidence, morbidity, and mortality. Malnutrition
will also increase the incidence of tuberculosis in HIV-1-negative individuals. Finally, HIV-1
infection and tuberculosis impair the nutritional state, which can lead to slim disease and
consumption, respectively. Thus, a merciless vicious circle exists between these two major
infections and nutritional deficiency. Therefore, an effective approach to control HIV-1 and
tuberculosis infection in sub-Saharan Africa, and particularly southern Africa, needs to include
food security. World leaders at the G8 summit in July, 2000, decided to tackle the three priority
diseases of povertyHIV-1 infection, tuberculosis, and malariaand to reduce prevalence of
and death from tuberculosis by 50% by 2010. The way to achieve this ambitious task is paved by
medical difficulties and by societal issues, including provision.
2.2.4 Crowding
Prisoners are particularly vulnerable to infectious diseases such as HIV/AIDS and TB.
Imprisonment facilities provide conditions that allow TB to spread rapidly due to overcrowding,
poor nutrition, and a lack of health services. TB outbreaks have been reported in prisons and jails
throughout the world, and is particularly concerning in the United States, which incarcerates a
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larger proportion of its population than any other nation. The prevalence of TB in prisons is
much higher than among the general populationin some countries as much as 40 times higher
(Larouz, 2008).
2.2.5 Diabetes Mellitus
There is also a very high 3 fold increased risk of infection with TB for patients who
have diabetes mellitus. Higher associations have been found between diabetes mellitus and TB in
study populations from Central America, Europe, and Asia. Developing countries with
exponential economic growth such as India and China that account for 40% of incident TB cases
in 2010 and are estimated to have a 69% increase in people with diabetes mellitus are of concern
for the joint burden of disease between diabetes mellitus and tuberculosis. The correlation
between diabetes mellitus and TB concerns public health as it merges communicable and non-
communicable diseases (Harries et al, 2010).
The research shows that patients with DM and TB have more severe clinical
manifestations, delayed sputum conversion and a higher probability of treatment failure,
recurrence and relapse. Using molecular tools, we found that subsequent episodes among
patients with DM are due to bacteria with the same genotype or are caused by reinfection with
bacteria with a different genotype. It is therefore imperative to implement the collaborative
framework recommended by WHO and the Union broadly to prevent and control TB among
patients with DM (WHO, 2011).
2.2.6 Tobacco
As a risk factor of TB, tobacco smoking has increased substantially over the past three
decades, especially in developing countries (Lin et al, 2007). Globally, TB and smoking aresimultaneously increasing, both of which could damage the lungs, and interact at an
immunologic and cellular level. Studies investigating the association between smoking and TB
have been published since 1918 (Chiang et al, 2007). Both passive and active exposures to
tobacco smoke have been shown to be associated with TB infection and the transition from being
infected to developing TB disease. Moreover, cigarette smoking is also associated with the
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prognosis of TB. A cohort study conducted in Hong Kong found that significantly more current
smokers developed TB and subsequently died within the follow-up period than ex-smokers and
never-smokers. Thomas investigated predictors of recurrence among TB patients in South India
and showed that a higher relapse rate was independently associated with smoking (OR: 3.1, 95%
CI: 1.66.0) (Thomas et al, 2005).
However, the association between smoking and TB, which has been shown to exist in
different studies with different ethnic background, has not yet received sufficient attention in
terms of TB care standards and research. Though both smoking and TB are targeted by major
international prevention and control efforts, there has been little research on the measures and
effects of smoking cessation among TB patients.
Tobacco contains more than 4,500 compounds in the particulate and vapor phases whichcomprise five known human carcinogens and many toxic agents. Long-term inhalation of
tobacco smoke alters a wide range of immunological functions, resulting in significantly
increased risk of heart disease, lung cancer, microbial infections and delayed recovery from these
diseases. Though the underlying biological mechanism is unclear, strong associations between
tobacco smoking and TB have been proved in several areas (Slama et al, 2007). Furthermore, a
dose-response relationship between cigarette smoking and TB was also demonstrated in the
present study: with the increase of daily cigarettes consumption and duration of smoking, the risk
for TB also increased accordingly.
Why are diabetic females more likely to have TB than diabetic males? There are several
possibilities. First, male diabetic subjects with TB may be misclassified as non-diabetics more
frequently than women because of less than recommended chronic health care utilization (Asch
et al, 2006). Second, diabetic women may be more susceptible to TB than diabetic men.
Estrogens inhibit cytokines such as gamma interferon and alpha tumour necrosis factor (Salem,
2004). The potential for an immunosuppressive effect might be enhanced by diabetes. Finally,
observations could be due to increased environmental exposure to TB among women. Women
may be more likely to be at home as well as in a caregiving role. This could lead to increased
exposure to others with TB and pose a particular risk of infection for those with diabetes.
Whatever the underlying reason, the fact that higher rates of TB were found in both RI and
OSKP diabetic women aged 50-59, and that there is a reversal in the usual increased male to
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female ratio of TB in diabetic Mexicans (Perez-Guzman, 2003), supports the validity of this
observation. Diabetes should be considered a risk factor for TB in diabetic women aged 50-59
regardless of ethnicity and a possible predictor of TB in younger adult women as well.
An important finding is that diabetes usually preceded TB. Moreover, some oldersubjects in whom TB preceded diabetes may have been in a pre-diabetic state (or had
undiagnosed diabetes). These observations provide temporal evidence for a possible cause and
effect relationship. This is supported by a case control study that showed that T2DM is an
independent risk factor for TB in Hispanic subjects, and by observations that the precise defects
in cellular immunity and phagocytosis found with diabetes are those known to predispose to TB.
For example, a recent study reported a decrease in alveolar macrophage activity in diabetics with
TB.
2.2.7 Other
Other conditions that increase risk include the sharing of needles among IV drug users,
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, compromised immune system (3040% of people with AIDS
worldwide also have TB), hematologic andreticuloendothelial diseases, such
as leukemia and Hodgkin's disease, end-stage kidney disease, intestinal bypass, chronic
malabsorption syndromes, vitamin D deficiency, and low body weight (Nnoaham and Clark,
2008).
2.3. Manifestation
The fight against tuberculosis would always remain incomplete without addressing theissues related to the control of HIV/AIDS. This study clearly brings out the important message
that at least 34% of the HIV patients were found to have tuberculosis co-infection at the time of
detecting or confirming their HIV disease. Significantly, a lower number of women living with
HIV were found to attend the hospital, reflecting their current health remedy seeking behavior.
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Further, they need the support of their family members to travel long distances to attend the
health institutions providing care and support to people living with HIV.
While the usual pulmonary tuberculosis was detected only to the extent of 56% of HIV-
TB study population, disseminated TB and extra-pulmonary TB were witnessed in 14% and 30%of the patients respectively. Increasing frequency of dissemination of tuberculosis was observed
with extra-pulmonary manifestations in several developing countriesas the hallmark of
advanced HIV disease. This is the resultant of unrecognized and demonstrableMycobacteremia
in severely immunosuppressed patients.
Among all the HIV-TB patients, sputum smear positive detection rate was low (31%
only). Advanced HIV disease is often associated with sputum smear negative pulmonary
tubercuosis,
atypical radiographic pictures and extra-pulmonary spread. Unrecognizedtuberculosis in patients with HIV disease has far-reaching consequences, including delayed
diagnosis, unacceptable therapeutic delayand even rapid progression to 'untreatable TB.'
(Rajasekaran et al, 2007).
Manifestation TB to DM.
Research found that clinical and radiological manifestations are more severe among
patients with DM and TB (Tatar et al, 2009). Research also found higher independent risks of
recurrence and relapse among patients with DM. In contrast to the previous literature (Baker et
al, 2011), the use of M tuberculosis fingerprinting allowed researcher to document whether
patients with DM experiencing subsequent episodes had TB caused by the same bacteria as the
previous episode or reinfection with a different strain. Patients with DM are more likely to have
infections caused by the same bacteria as the previous episode. However, the occurrence of
exogenous reinfection in one-fifth of the cases merits further consideration. Exogenous TB
reinfection in patients with DM might be due to nosocomial TB transmission occurring as a
result of attending clinics where there is a high prevalence of diagnosed and undiagnosed TB, as
has been described for HIV-infected patients (Bock et al, 2007).
DM thus appears to have an aggravating effect on TB. Although the physiopathology of
the coexistence of these two diseases has yet to be elucidated, changes to the immune system of
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patients
alveolar
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2008).
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Vitamin D is a secosteroid that is either synthesised in the skin by the action of sunlight
or ingested in the diet; dietary intake accounts for a much smaller proportion of total vitamin D,
because it is scarce in foods (Holick, 2007). Vitamin D is generated by the action of ultraviolet B
radiation on the precursor, 7-dehydrocholesterol, in the skin, and subsequent hydroxylation in
other organs. The vitamin has pleiotropic effects on many organs, including the adaptive immune
system and the innate immune system. Vitamin D deficiency increases the risk of type 1 and type
2 diabetes mellitus, and supplementation is protective against both types (Holick, 2007).
Vitamin D is thought to affect pancreatic cell function (insulin synthesis and secretion)
and immune response; (Chiu et al, 2004) low concentrations of vitamin D are associated with
insulin resistance and glucose intolerance (Chiu et al, 2004). In chronic disease, vitamin D is
used to restore health in organ systems, the risk of deficiency is therefore increased. Because
vitamin D deficiency is associated with active tuberculosis (odds ratio 29, 95% CI 1365)
(Wilkinson et al, 2000), diabetes-related deficiency might lead to susceptibility to tuberculosis
infection and vice versa. In vitro, the actions of monocytes and macrophages onMycobacterium
tuberculosisare heavily dependent on vitamin D concentrations (Holick, 2007). If these
concentrations become too low, phagocytosis cannot occur. The strong association of vitamin D
concentrations with tuberculosis and diabetes mellitus means that vitamin D deficiency might
explain some of the association between these two diseases, thus, population-wide
supplementation measures to prevent both diseases should be considered.
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REFERENCES
1. Asch SM, Kerr EA, Keesey J, Adams JL, Setodji CM, Malik S, McGlynn EA. Who is atgreatest risk for receiving poor quality health care?N Engl J Med 2006;354:1147-56.
2. Baker MA, Harries AD, Jeon CY, et al. The impact of diabetes on tuberculosis treatmentoutcomes: a systematic review. BMC Med 2011;9:81.
3. Blas E, Sivasankara AK, eds. Priority public health conditions: from learning to action onsocial determinants of health. Geneva: World Health Organization, 2010.
4. Bock NN, Jensen PA, Miller B, et al. Tuberculosis infection control in resource-limitedsettings in the era of expanding HIV care and treatment. J Infect Dis 2007;196(Suppl
1):S10813.5. Chaisson, RE; Martinson, NA. 2008. "Tuberculosis in Africa--combating an HIV-driven
crisis.". The New England Journal of Medicine358(11): 108992.
6. Chiang CY, Slama K, Enarson DA: Associations between tobacco and tuberculosis. Int JTuberc Lung Dis2007, 11(3):258-262.
7. Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistanceand beta cell dysfunction.Am J Clin Nutr2004; 79: 820-905
8. Davies PD (2003). "The world-wide increase in tuberculosis: how demographic changes,HIV infection and increasing numbers in poverty are increasing tuberculosis".Annals of
medicine35(4): 23543.
9. Davies, PD; Yew, WW, Ganguly, D, Davidow, AL, Reichman, LB, Dheda, K, Rook, GA.2006. "Smoking and tuberculosis: the epidemiological association and
immunopathogenesis.".Transactions of the Royal Society of Tropical Medicine and
Hygiene100(4): 2918.
10.Harries, A. D., et al. 2010. "Defining the Research Agenda to Reduce the Joint Burden ofDisease from Diabetes Mellitus and Tuberculosis" Tropical medicine & international health :
TM & IH.
11.Harries AD, Billo N, Kapur A. Links between diabetes mellitus and tuberculosis: should weintegrate screening and care? Trans R Soc Trop Med Hyg 2009; 103: 12.
12.Holick MF. Vitamin D deficiency.N Engl J Med2007; 357: 266-281.
8/14/2019 2 (Autosaved) (Autosaved).pdf
15/17
13.Ioachimescu OC and Tomford JW. 2010. Tuberculosis. Available from :http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/infectious-
disease/tuberculosis/#s0030
14. Kjellstrom T, Mercado S, Sattherhwaite D, McGranaham G, Friel S, Havemann K. Ourcities, our health, our future: acting on social determinants for health equity in urban settings.
Report to the WHO Commission on Social Determinants of Health from the Knowledge
Network on Urban Settings. Kobe: World Health Organization Kobe Centre, 2007.
15.Kumar V, Abbas AK, Fausto N, Mitchell RN. 2007.Robbins Basic Pathology (8th ed.).Saunders Elsevier. pp. 516522.
16.Larouz B, Snchez A, Diuana V (2008). "Tuberculosis behind bars in developing countries:a hidden shame to public health". Trans. R. Soc. Trop. Med. Hyg.102(9): 8412.
17.Leung CC (June 2007). "Lower risk of tuberculosis in obesity".Arch. Intern. Med.167(12):1297304.
18.Lin HH, Ezzati M, Murray M: Tobacco smoke, indoor air pollution and tuberculosis: asystematic review and meta-analysis. PLoS medicine2007, 4(1):e20
19.Lonnroth K, Jaramillo E, Williams BG, Dye C, Raviglione M Drivers of tuberculosisepidemics: the role of risk factors and social determinants. Soc Sci Med 2009; 68: 224046
20.Mller, M; Hoal, EG. 2010. "Current findings, challenges and novel approaches in humangenetic susceptibility to tuberculosis.".Tuberculosis (Edinburgh, Scotland)90(2): 7183.
21.Mutlu G, Mutlu E, Bellmeyer A, Rubinstein I (2006). "Pulmonary adverse events of anti-tumor necrosis factor-alpha antibody therapy".Am J Med119(8): 63946.
22.Nijland HMJ et al. (2006). "Exposure to rifampicin is strongly reduced in patients withtuberculosis and type 2 diabetes". Clin Infect Dis43(7): 848854.
23.Nnoaham KE, Clarke A (2008). "Low serum vitamin D levels and tuberculosis: a systematicreview and meta-analysis".Int J Epidemiol37(1): 1139.
24.Oxlade O, Schwartzman K, Behr MA, et al. Global tuberculosis trends: a reflection ofchanges in tuberculosis control or in population health? Int J Tuberc Lung Dis 2009; 13:
123846.
25.Perez-Guzman C, Vargas MH, Torres-Cruz A, Perez-Padilla JR, Furuya ME, Villarreal-Velarde H. Diabetes modifies the male:female ratio in pulmonary tuberculosis. Int J Tuberc
Lung Dis 2003;7(4):354-58.
8/14/2019 2 (Autosaved) (Autosaved).pdf
16/17
26.Rajasekaran S, Mahilmaran A, Annadurai S, Kumar S , Raja K. 2007. Manifestation oftuberculosis in patients with human immunodeficiency virus: A large Indian study. Annals of
Thoracic Medicine 2007;2(2):58-60.
27.Restrepo, BI. 2007. "Convergence of the tuberculosis and diabetes epidemics: renewal of oldacquaintances.".Clinical infectious diseases : an official publication of the Infectious
Diseases Society of America45(4): 4368.
28.Restrepo BI, Fisher-Hoch SP, Pino PA, et al. Tuberculosis in poorly controlled type 2diabetes: altered cytokine expression in peripheral white blood cells. Clin Infect Dis
2008;47:63441.
29.Reuben Granich, Christopher Akolo, Christian Gunneberg, Haileyesus Getahun, PhoebeWilliams, and Brian Williams. 2010. Prevention of Tuberculosis in People Living with HIV.
Clin Infect Dis. 50(Supplement 3): S215-S222.doi: 10.1086/65149.
30.Salem ML. Estrogen, a double-edged sword: Modulation of TH1 and TH2 mediatedinflammations by differential regulation of TH1/TH2 cytokine population. Curr Drug
Targets Inflamm Allergy 2004;3:97-104.
31.Santo AH. Deaths attributed to multiple causes and involving tuberculosis in the state of Riode Janeiro Brazil between 1999 and 2001. J Bras Pneumol 2006;32:54452.
32.Segall L, Covic A (June 2010). "Diagnosis of tuberculosis in dialysis patients: currentstrategy". Clin J Am Soc Nephrol5(6): 111422.
33.Shilova MV, Dye C. The resurgence of tuberculosis in Russia. Philos Trans R Soc Lond BBiol Sci 2001; 356: 106975.
34.Slama K, Chiang CY, Enarson DA, Hassmiller K, Fanning A, Gupta P, Ray C: Tobacco andtuberculosis: a qualitative systematic review and meta-analysis. Int J Tuberc Lung
Dis2007, 11(10):1049-1061.
35.Tatar D, Senol G, Alptekin S, et al. Tuberculosis in diabetics: features in an endemic area.Jpn J Infect Dis 2009;62:4237.
36.Thomas A, Gopi PG, Santha T, Chandrasekaran V, Subramani R, Selvakumar N, Eusuff SI,Sadacharam K, Narayanan PR: Predictors of relapse among pulmonary tuberculosis
patients treated in a DOTS programme in South India. Int J Tuberc Lung
Dis2005, 9(5):556-561.
8/14/2019 2 (Autosaved) (Autosaved).pdf
17/17
37.Tsukaguchi K, Okamura H, Matsuzawa K, et al. (Longitudinal assessment of IFN-gammaproduction in patients with pulmonary tuberculosis complicated with diabetes mellitus).
Kekkaku: (Tuberculosis) 2002;77
38.van Exel E, Gussekloo J, de Craen AJ, et al. Low production capacity of interleukin-10associates with the metabolic syndrome and type 2 diabetes : the Leiden 85-Plus study.
Diabetes 2002;51:108892.
39.Wilkinson RJ, Llewelyn M, Toossi Z, et al. Influence of vitamin D deficiency and vitamin Dreceptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-
control study.Lancet2000; 355: 618-621.
40.World Health Organization. Collaborative framework for care and control of tuberculosis anddiabetes. http://www.who.int/diabetes/publications/tb_diabetes2011/en/index.html
41.World Health Organization. Global tuberculosis controla short update to the 2009 report.WHO/HTM/TB/2009.426. Geneva: World Health Organization, 2009.