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1.  Effect of age on presentation with diabetes: Comparison of nondiabetic patients with new smear-positive pulmonary tuberculosis patients 
Diabetes mellitus (DM) has been reported to modify the presenting features of pulmonary tuberculosis (PTB), but data regarding the effect of diabetes on the presentation of PTB are highly variable.
To determine whether DM alters the demographic, clinical, and radiological manifestations of tuberculosis and whether the effect of diabetes varies with the age group of PTB patients.
Materials and Methods :
This prospective observational study was conducted on new smear-positive PTB patients with DM (PTB-DM group) and non-diabetic PTB patients (PTB group). Patients of both groups were again divided into six age groups (15–29, 30–39, 40–49, 50–59, 60–69, and >70 rears) to analyze and compare the impact of age on clinicoradiological presentations of PTB.
Patients in the PTB-DM group were significantly older (53.34 ± 14.06 year) in comparison to their nondiabetic counterparts (PTB group) (44.35 ± 18.14 year) (P < 0.001). The former group also had a lower male:female ratio, although the difference was not statistically significant (1.16:1 vs. 2.05:1, P = 0.101). Tuberculin positivity was significantly higher in the PTB group, compared with patients in the PTB-DM group (P < 0.004). The proportion of patients with lower lung field involvement (P = 0.003) and cavitations (P = 0.005) was also higher in the former group compared with the latter.
Diabetic patients with tuberculosis were relatively older, had lower tuberculin positivity, and higher proportion of lower lung field involvement and cavitation in comparison to nondiabetic patients.
PMCID: PMC3162756  PMID: 21886953
Comparative study; diabetes mellitus; pulmonary tuberculosis; radiology
2.  Are pulmonary opacities a marker of pulmonary tuberculosis? 
On most occasions treatment of pulmonary tuberculosis is started by physicians based predominantly on radiological opacities. Since these opacities may not be suggestive of active pulmonary tuberculosis and most of these opacities may even remain unchanged after complete treatment, starting treatment solely on the basis of these opacities may lead to ambiguous end points of cure. In view of this, study of misdiagnosis of radiological opacities as active pulmonary tuberculosis by physicians was undertaken in one of the respiratory centers of Armed Forces hospitals.
This was a prospective study of patients referred to our center for confirmation of active disease and institutional therapy. All patients who were diagnosed as pulmonary tuberculosis predominantly on radiological basis by physicians were evaluated for active pulmonary tuberculosis clinically, radiologically and microbiologically. Patients found to have inactive disease were followed for one year. At three monthly review, history, clinical examination, sputum AFB and chest radiographs were done.
There were 36 patients [all males, mean age: 36.9 years (range: 22–46 years)]. The most common initial presentation was of asymptomatic persons (33.3%) reporting for routine medical examination. The commonest radiological pattern was localized reticular opacities (52.8%)On follow up, only one patient was diagnosed to have pulmonary tuberculosis. The final diagnosis was consolidation in 6, bronchiectasis in 8, pulmonary tuberculosis in 1 and localized pulmonary fibrosis in 21 patients.
Diagnosing and treating tuberculosis predominantly on radiological basis is not appropriate and sputum microscopy and culture remains the cornerstone of diagnosing pulmonary tuberculosis.
PMCID: PMC3946516  PMID: 24623942
Pulmonary opacities; Radiological misdiagnosis; Pulmonary tuberculosis
3.  Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus 
Concept of Diabetes Mellitus:
Diabetes mellitus is a group of diseases associated with various metabolic disorders, the main feature of which is chronic hyperglycemia due to insufficient insulin action. Its pathogenesis involves both genetic and environmental factors. The long‐term persistence of metabolic disorders can cause susceptibility to specific complications and also foster arteriosclerosis. Diabetes mellitus is associated with a broad range of clinical presentations, from being asymptomatic to ketoacidosis or coma, depending on the degree of metabolic disorder.
Classification (Tables 1 and 2, and Figure 1):
 Etiological classification of diabetes mellitus and glucose metabolism disorders
Note: Those that cannot at present be classified as any of the above are called unclassifiable.
The occurrence of diabetes‐specific complications has not been confirmed in some of these conditions.
 Diabetes mellitus and glucose metabolism disorders due to other specific mechanisms and diseases
The occurrence of diabetes‐specific complications has not been confirmed in some of these conditions.
 A scheme of the relationship between etiology (mechanism) and patho‐physiological stages (states) of diabetes mellitus. Arrows pointing right represent worsening of glucose metabolism disorders (including onset of diabetes mellitus). Among the arrow lines, indicates the condition classified as ‘diabetes mellitus’. Arrows pointing left represent improvement in the glucose metabolism disorder. The broken lines indicate events of low frequency. For example, in type 2 diabetes mellitus, infection can lead to ketoacidosis and require temporary insulin treatment for survival. Also, once diabetes mellitus has developed, it is treated as diabetes mellitus regardless of improvement in glucose metabolism, therefore, the arrow lines pointing left are filled in black. In such cases, a broken line is used, because complete normalization of glucose metabolism is rare.
The classification of glucose metabolism disorders is principally derived from etiology, and includes staging of pathophysiology based on the degree of deficiency of insulin action. These disorders are classified into four groups: (i) type 1 diabetes mellitus; (ii) type 2 diabetes mellitus; (iii) diabetes mellitus due to other specific mechanisms or diseases; and (iv) gestational diabetes mellitus. Type 1 diabetes is characterized by destruction of pancreatic β‐cells. Type 2 diabetes is characterized by combinations of decreased insulin secretion and decreased insulin sensitivity (insulin resistance). Glucose metabolism disorders in category (iii) are divided into two subgroups; subgroup A is diabetes in which a genetic abnormality has been identified, and subgroup B is diabetes associated with other pathologic disorders or clinical conditions. The staging of glucose metabolism includes normal, borderline and diabetic stages depending on the degree of hyperglycemia occurring as a result of the lack of insulin action or clinical condition. The diabetic stage is then subdivided into three substages: non‐insulin‐ requiring, insulin‐requiring for glycemic control, and insulin‐dependent for survival. The two former conditions are called non‐insulin‐dependent diabetes and the latter is known as insulin‐dependent diabetes. In each individual, these stages may vary according to the deterioration or the improvement of the metabolic state, either spontaneously or by treatment.
Diagnosis (Tables 3–7 and Figure 2):
 Criteria of fasting plasma glucose levels and 75 g oral glucose tolerance test 2‐h value
*Casual plasma glucose ≥200 mg/dL (≥11.1 mmol/L) and HbA1c≥6.5% are also regarded as to indicate diabetic type.
Even for normal type, if 1‐h value is 180 mg/dL (10.0 mmol/L), the risk of progression to diabetes mellitus is greater than for <180 mg/dL (10.0 mmol/L) and should be treated as with borderline type (follow‐up observation, etc.). Fasting plasma glucose level of 100–109 mg/dL (5.5–6.0 mmol/L) is called ‘high‐normal’: within the range of normal fasting plasma glucose.
Plasma glucose level after glucose load in oral glucose tolerance test (OGTT) is not included in casual plasma glucose levels. The value for HbA1c (%) is indicated with 0.4% added to HbA1c (JDS) (%).
 Procedures for diagnosing diabetes mellitus
*The value for HbA1c (%) is indicated with 0.4% added to HbA1c (JDS) (%). **Hyperglycemia must be confirmed in a non‐stressful condition. OGTT, oral glucose tolerance test.
 Disorders and conditions associated with low HbA1c values
 Situations where a 75‐g oral glucose tolerance test is recommended
*The value for HbA1c (%) is indicated with 0.4% added to HbA1c (JDS) (%).
 Definition and diagnostic criteria of gestational diabetes mellitus
(IADPSG Consensus Panel, Reference 42, partly modified with permission of Diabetes Care).
 Flow chart outlining steps in the clinical diagnosis of diabetes mellitus. *The value for HbA1c (%) is indicated with 0.4% added to HbA1c (JDS) (%).
Categories of the State of Glycemia:  Confirmation of chronic hyperglycemia is essential for the diagnosis of diabetes mellitus. When plasma glucose levels are used to determine the categories of glycemia, patients are classified as having a diabetic type if they meet one of the following criteria: (i) fasting plasma glucose level of ≥126 mg/dL (≥7.0 mmol/L); (ii) 2‐h value of ≥200 mg/dL (≥11.1 mmol/L) in 75 g oral glucose tolerance test (OGTT); or (iii) casual plasma glucose level of ≥200 mg/dL (≥11.1 mmol/L). Normal type is defined as fasting plasma glucose level of <110 mg/dL (<6.1 mmol/L) and 2‐h value of <140 mg/dL (<7.8 mmol/L) in OGTT. Borderline type (neither diabetic nor normal type) is defined as falling between the diabetic and normal values. According to the current revision, in addition to the earlier listed plasma glucose values, hemoglobin A1c (HbA1c) has been given a more prominent position as one of the diagnostic criteria. That is, (iv) HbA1c≥6.5% is now also considered to indicate diabetic type. The value of HbA1c, which is equivalent to the internationally used HbA1c (%) (HbA1c [NGSP]) defined by the NGSP (National Glycohemoglobin Standardization Program), is expressed by adding 0.4% to the HbA1c (JDS) (%) defined by the Japan Diabetes Society (JDS).
Subjects with borderline type have a high rate of developing diabetes mellitus, and correspond to the combination of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) noted by the American Diabetes Association (ADA) and WHO. Although borderline cases show few of the specific complications of diabetes mellitus, the risk of arteriosclerosis is higher than those of normal type. When HbA1c is 6.0–6.4%, suspected diabetes mellitus cannot be excluded, and when HbA1c of 5.6–5.9% is included, it forms a group with a high risk for developing diabetes mellitus in the future, even if they do not have it currently.
Clinical Diagnosis:  1 If any of the criteria for diabetic type (i) through to (iv) is observed at the initial examination, the patient is judged to be ‘diabetic type’. Re‐examination is conducted on another day, and if ‘diabetic type’ is reconfirmed, diabetes mellitus is diagnosed. However, a diagnosis cannot be made only by the re‐examination of HbA1c alone. Moreover, if the plasma glucose values (any of criteria [i], [ii], or [iii]) and the HbA1c (criterion [iv]) in the same blood sample both indicate diabetic type, diabetes mellitus is diagnosed based on the initial examination alone. If HbA1c is used, it is essential that the plasma glucose level (criteria [i], [ii] or [iii]) also indicates diabetic type for a diagnosis of diabetes mellitus. When diabetes mellitus is suspected, HbA1c should be measured at the same time as examination for plasma glucose.2 If the plasma glucose level indicates diabetic type (any of [i], [ii], or [iii]) and either of the following conditions exists, diabetes mellitus can be diagnosed immediately at the initial examination.• The presence of typical symptoms of diabetes mellitus (thirst, polydipsia, polyuria, weight loss)• The presence of definite diabetic retinopathy3 If it can be confirmed that the above conditions 1 or 2 existed in the past, diabetes mellitus can be diagnosed or suspected regardless of the current test results.4 If the diagnosis of diabetes cannot be established by these procedures, the patient is followed up and re‐examined after an appropriate interval.5 The physician should assess not only the presence or absence of diabetes, but also its etiology and glycemic stage, and the presence and absence of diabetic complications or associated conditions.
Epidemiological Study:  For the purpose of estimating the frequency of diabetes mellitus, ‘diabetes mellitus’ can be substituted for the determination of ‘diabetic type’ from a single examination. In this case, HbA1c≥6.5% alone can be defined as ‘diabetes mellitus’.
Health Screening:  It is important not to misdiagnose diabetes mellitus, and thus clinical information such as family history and obesity should be referred to at the time of screening in addition to an index for plasma glucose level.
Gestational Diabetes Mellitus:  There are two hyperglycemic disorders in pregnancy: (i) gestational diabetes mellitus (GDM); and (ii) diabetes mellitus. GDM is diagnosed if one or more of the following criteria is met in a 75 g OGTT during pregnancy:
1 Fasting plasma glucose level of ≥92 mg/dL (5.1 mmol/L)2 1‐h value of ≥180 mg/dL (10.0 mmol/L)3 2‐h value of ≥153 mg/dL (8.5 mmol/L)
However, diabetes mellitus that is diagnosed by the clinical diagnosis of diabetes mellitus defined earlier is excluded from GDM. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00074.x, 2010)
PMCID: PMC4020724  PMID: 24843435
Diabetes mellitus; Clinical diagnosis; HbA1c
4.  Glenohumeral tuberculous arthritis complicated with beta haemolytic streptococcus: An extraordinary rare association: A case report 
Septic arthritis of the glenohumeral joint is a rare entity and its diagnosis is difficult with a superadded infection in the presence of underlying tuberculosis. We report the first case of group B beta haemolytic streptococcal glenohumeral arthritis with underlying tuberculosis.
A 40 year old lady previously diagnosed to have poliomyelitis, rheumatoid arthritis, hepatitis C, and diabetes mellitus for the last 10 years, presented to the emergency room with diabetic ketoacidosis. Two weeks prior to presentation she developed fever along with pain and swelling in left shoulder with uncontrolled blood sugars. Local examination of the shoulder revealed global swelling with significant restricted range of motion. MRI showed a large multiloculated collection around the left shoulder joint extending into the axilla, and proximal arm. Urgent arthrotomy performed and about 120 ml thick pus was drained. The patient was started on clindamicin and antituberculous chemotherapy and her symptoms dramatically improved.
Bone and joint involvement accounts for approximately 2% of all reported cases of tuberculosis (TB), and it accounts for approximately 10% of the extra pulmonary cases of TB. Tuberculosis of the shoulder joint constitutes 1–10.5% of skeletal tuberculosis. Classical symptoms of fever, night sweats, and weight loss may be absent, and a concurrent pulmonary focus may not be evident in most cases.
Despite acute presentation of septic arthritis, in areas endemic for tuberculosis and particularly in an immunocompromised patient, workup for tuberculosis should be part of the routine evaluation.
PMCID: PMC3312055  PMID: 22382034
Glenohumeral tuberculous arthritis; Beta haemolytic streptococcus; Septic arthritis
5.  Overt diabetes mellitus among newly diagnosed Ugandan tuberculosis patients: a cross sectional study 
BMC Infectious Diseases  2013;13:122.
There is a documented increase of diabetes mellitus in Sub Saharan Africa, a region where tuberculosis is highly endemic. Currently, diabetes mellitus is one of the recognised risk factors of tuberculosis. No study has reported the magnitude of diabetes mellitus among tuberculosis patients in Uganda, one of the countries with a high burden of tuberculosis.
This was a cross-sectional study conducted among 260 consenting adult patients with a confirmed diagnosis of tuberculosis admitted on the pulmonology wards of Mulago national referral and teaching hospital in Kampala, Uganda to determine the prevalence of diabetes mellitus and associated clinical factors. Laboratory findings as well as the socio-demographic and clinical data collected using a validated questionnaire was obtained. Point of care random blood sugar (RBS) testing was performed on all the patients prior to initiation of anti tuberculosis treatment. Diabetes mellitus was diagnosed if the RBS level was ≥ 200mg/dl in the presence of the classical symptoms of diabetes mellitus.
The prevalence of diabetes mellitus among the admitted patients with tuberculosis was 8.5%. Only 5 (1.9%) patients with TB had a known diagnosis of diabetes mellitus at enrolment. Majority of the study participants with TB-DM co-infection had type 2 diabetes mellitus (n=20, 90.9%).
At bivariate analysis, raised mean ALT concentrations of ≥80 U/L were associated with DM (OR-6.1, 95% CI 1.4-26.36, p=0.032) and paradoxically, HIV co-infection was protective of DM (OR-0.32, 95% CI 0.13-0.79, P=0.016). The relationship between DM and HIV as well as that with ALT remained statistically significant at multivariate analysis (HIV: OR- 0.17 95%CI 0.06-0.51, p=0.002 and ALT: OR-11.42 95%CI 2.15-60.59, p=0.004).
This study demonstrates that diabetes mellitus is common among hospitalized tuberculosis patients in Uganda. The significant clinical predictors associated with diabetes mellitus among tuberculosis patients were HIV co-infection and raised mean serum alanine transaminase concentrations.
PMCID: PMC3599954  PMID: 23497232
6.  Evaluation of the status of tuberculosis as part of the clinical case definition of AIDS in India 
Postgraduate Medical Journal  2005;81(956):404-408.
Aim: To assess HIV associated tuberculosis in a high tuberculosis prevalence setting and its status in the clinical case definition of AIDS.
Methods: All HIV patients attending the infectious disease clinic, Varanasi, India between January 2001 and December 2003 were included in the study. They were stratified into three distinct immunological categories depending on their CD4 levels in accordance to Centers for Disease Control (CDC) classification. Tuberculosis of different organs was defined as detailed below.
Results: Tuberculosis was the commonest opportunistic disease, seen in 163 patients. Of these, 68 had exclusively pulmonary tuberculosis, 55 extrapulmonary disease, and 40 the disseminated form. Pulmonary and extrapulmonary tuberculosis had low positive predictive value (PPV) (51% and 42%) for CD4 levels of <200 when compared with the disseminated form (specificity 87% and PPV 75%). Among 86 patients with radiological evidence of tuberculosis, typical radiological features of post-primary tuberculosis were present in 60 cases (70%). Other features such as effusion (14 patients, 16%) and miliary shadows (12 patients, 14%) were comparatively rare.
Conclusion: Keeping pulmonary and extrapulmonary forms of tuberculosis in AIDS defining illness should be reconsidered. In a similar way tuberculosis in HIV patients from areas endemic with tuberculosis occurs in patients with a wide range of immune status and has a better prognosis than other AIDS defining illnesses. Therefore the inclusion of tuberculosis in clinical case definition of AIDS is not justified.
PMCID: PMC1743281  PMID: 15937209
7.  Diabetes Mellitus Increases the Risk of Active Tuberculosis: A Systematic Review of 13 Observational Studies 
PLoS Medicine  2008;5(7):e152.
Several studies have suggested that diabetes mellitus (DM) increases the risk of active tuberculosis (TB). The rising prevalence of DM in TB-endemic areas may adversely affect TB control. We conducted a systematic review and a meta-analysis of observational studies assessing the association of DM and TB in order to summarize the existing evidence and to assess methodological quality of the studies.
Methods and Findings
We searched the PubMed and EMBASE databases to identify observational studies that had reported an age-adjusted quantitative estimate of the association between DM and active TB disease. The search yielded 13 observational studies (n = 1,786,212 participants) with 17,698 TB cases. Random effects meta-analysis of cohort studies showed that DM was associated with an increased risk of TB (relative risk = 3.11, 95% CI 2.27–4.26). Case-control studies were heterogeneous and odds ratios ranged from 1.16 to 7.83. Subgroup analyses showed that effect estimates were higher in non-North American studies.
DM was associated with an increased risk of TB regardless of study design and population. People with DM may be important targets for interventions such as active case finding and treatment of latent TB and efforts to diagnose, detect, and treat DM may have a beneficial impact on TB control.
In a systematic review and meta-analysis including more than 17,000 tuberculosis cases, Christie Jeon and Megan Murray find that diabetes mellitus is associated with an approximately 3-fold increased risk of tuberculosis.
Editors' Summary
Every year, 8.8 million people develop active tuberculosis and 1.6 million people die from this highly contagious infection that usually affects the lungs. Tuberculosis is caused by Mycobacterium tuberculosis, bacteria that are spread through the air when people with active tuberculosis cough or sneeze. Most infected people never become ill—a third of the world's population is actually infected with M. tuberculosis—because the human immune system usually contains the infection. However, the bacteria remain dormant within the body and can cause disease many years later if host immunity declines because of increasing age or because of other medical conditions such as HIV infection. Active tuberculosis can be cured by taking a combination of several antibiotics every day for at least six months, and current control efforts concentrate on prompt detection and carefully monitored treatment of people with active tuberculosis to prevent further transmission of the bacteria.
Why Was This Study Done?
Despite this control strategy, tuberculosis remains a major health problem in many countries. To reduce the annual number of new tuberculosis cases (incidence) and the number of people with tuberculosis (prevalence) in such countries, it may be necessary to identify and target factors that increase an individual's risk of developing active tuberculosis. One possible risk factor for tuberculosis is diabetes, a condition characterized by high blood sugar levels and long-term complications involving the circulation, eyes and kidneys, and the body's ability to fight infection. 180 million people currently have diabetes, but this number is expected to double by 2030. Low- to middle-income countries (for example, India and China) have the highest burden of tuberculosis and are experiencing the fastest increase in diabetes prevalence. If diabetes does increase the risk of developing active tuberculosis, this overlap between the diabetes and tuberculosis epidemics could adversely affect global tuberculosis control efforts. In this study, the researchers undertake a systematic review (a search using specific criteria to identify relevant research studies, which are then appraised) and a random effects meta-analysis (a type of statistical analysis that pools the results of several studies) to learn more about the association between diabetes and tuberculosis.
What Did the Researchers Do and Find?
From their search of electronic databases, the researchers found 13 observational studies (nonexperimental investigations that record individual characteristics and health outcomes without trying to influence them in any way) that had examined whether diabetes mellitus increases the risk of active tuberculosis. Diabetes was positively associated with tuberculosis in all but one study, but the estimates of how much diabetes increases the risk of developing active tuberculosis were highly variable, ranging from no effect to an increased risk of nearly 8-fold in one study. The variability may represent true differences between the study populations, as higher increases in risk due to diabetes was found in studies conducted outside of North America, including Central America, Europe, and Asia; or it may reflect differences in how well each study was done. This variability meant that the researchers could not include all of the studies in their meta-analysis. However, the three prospective cohort studies (studies that follow a group of individuals with potential risk factors for a disease over time to see if they develop that disease) that they had identified in their systematic review had more consistent effects estimates, and were included in the meta-analysis. This meta-analysis showed that, compared to people without diabetes, people with diabetes had a 3-fold increased risk of developing active tuberculosis.
What Do These Findings Mean?
These findings support the idea that diabetes increases the risk of tuberculosis, a biologically plausible idea because, in experimental and clinical studies, diabetes was found to impair the immune responses needed to control bacterial infections. The 3-fold increased risk of tuberculosis associated with diabetes that the meta-analysis reveals suggests that diabetes may already be responsible for more than 10% of tuberculosis cases in countries such as India and China, a figure that will likely increase as diabetes becomes more common.
However, the estimate of this impact is based on three cohort studies from Asia; other studies suggest that the extent of the impact due to diabetes may vary by region and ethnicity. In populations where diabetes affects the risk of tuberculosis to a similar or greater extent, global tuberculosis control might benefit from active case finding and treatment of dormant tuberculosis in people with diabetes and from increased efforts to diagnose and treat diabetes.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Institute of Allergy and Infectious Diseases provides information on all aspects of tuberculosis
The US Centers for Disease Control and Prevention provide several fact sheets and other information resources about tuberculosis
The World Health Organization provides information (in several languages) on efforts to reduce the global burden of tuberculosis, including information on the Stop TB Strategy and the 2008 report Global Tuberculosis Control—Surveillance, Planning, Financing
The US Centers for Disease Control and Prevention provides information for the public and professionals on all aspects of diabetes
The US National Institute of Diabetes and Digestive and Kidney Diseases also provides information about diabetes (in English and Spanish)
PMCID: PMC2459204  PMID: 18630984
8.  Comparison of Epidemiological, Clinical, Laboratory and Radiological Features of Hospitalized Diabetic and Non-Diabetic Patients With Pulmonary Tuberculosis at Razi Hospital in Ahvaz 
Diabetes mellitus (DM) due to suppressive effect on cellular immunity can impact on progression of tuberculosis (TB).
The aim of this study was to investigate the impact of DM on the epidemiological, clinical and para clinical aspects of pulmonary TB.
Patients and Methods:
The information of 148 admitted pulmonary TB patients in infectious ward of Razi hospital in Ahvaz from 2009 to 2010 was extracted from their medical files. The patients were divided into two groups as TB with DM (n = 36) and TB without DM (n = 112). The related data on epidemiology, signs, symptoms, radiology and sputum smear examination in both groups were compared in SPSS 16 by using chi squared test.
The mean age of TB with DM patients was higher TB without DM patients (56.6 ± 12.7 vs. 44.8 ± 18.3; respectively, P = 0.006). Whereas cough, night sweating, fever and weigh loss was not statistically different, sputum, hemoptysis and dyspnea was more prominent in TB with DM (69.4%, 33.4%, 44.5% vs. 36.6%, 9.8%, 20.5%; P = 0.005, P = 0.001, P = 0.005, respectively). In chest x-ray, cavitation and reticulonodular pattern was more frequent in TB with DM (55.5%, 22.2% vs. 31.2%, 8% - P = 0.008, P = 0.02, respectively). The rate of sputum smear positivity in TB with DM and TB without DM was 66.6% and 47.3%, respectively (P = 0.03).
According to the results of this study, in approach to every DM cases suffering of respiratory symptoms such as productive cough, hemoptysis and dyspnea in association with cavitation or miliary mottling in chest x-ray, pulmonary TB should be considered at the top of the differential diagnosis list.
PMCID: PMC4255379  PMID: 25485064
Pulmonary tuberculosis; Diabetes Mellitus; Epidemiology; Clinical Features; Radiology
9.  Vitamin D status of patients with type 2 diabetes and sputum positive pulmonary tuberculosis 
Vitamin D deficiency is expected to be higher in patients with diabetes and pulmonary tuberculosis (TB). Studies estimating prevalence in the subset of patients with both diabetes and pulmonary TB are scarce.
Materials and Methods:
A total of 155 subjects were recruited; 46 patients with type 2 diabetes, 39 non-diabetic healthy controls, 30 patients of pulmonary TB and 40 patients with both pulmonary TB and type 2 diabetes. Vitamin D level (25 OH vitamin D) levels were done for all the 4 groups.
Mean vitamin D levels were not different between groups with TB, diabetes mellitus or combination of both, but the prevalence of severe vitamin D deficiency was higher in the group with both diabetes and TB (45%) as compared with the group with only TB (26.66%) and diabetes (17.39%) and healthy controls (7.69%).
The prevalence of patients with severe vitamin D deficiency is higher in patients with dual affection of TB and diabetes mellitus as compared with either disorder alone implying that patients with type 2 diabetes with the most severe vitamin D deficiency are the one of the most predisposed to pulmonary TB.
PMCID: PMC4046604  PMID: 24910835
Diabetes; pulmonary tuberculosis; vitamin D deficiency
10.  Tuberculosis and diabetes mellitus: convergence of two epidemics 
The Lancet infectious diseases  2009;9(12):737-746.
The link between diabetes mellitus and tuberculosis has been recognised for centuries. In recent decades, tuberculosis incidence has declined in high-income countries, but incidence remains high in countries that have high rates of infection with HIV, high prevalence of malnutrition and crowded living conditions, or poor tuberculosis control infrastructure. At the same time, diabetes mellitus prevalence is soaring globally, fuelled by obesity. There is growing evidence that diabetes mellitus is an important risk factor for tuberculosis and might affect disease presentation and treatment response. Furthermore, tuberculosis might induce glucose intolerance and worsen glycaemic control in people with diabetes. We review the epidemiology of the tuberculosis and diabetes epidemics, and provide a synopsis of the evidence for the role of diabetes mellitus in susceptibility to, clinical presentation of, and response to treatment for tuberculosis. In addition, we review potential mechanisms by which diabetes mellitus can cause tuberculosis, the effects of tuberculosis on diabetic control, and pharmacokinetic issues related to the co-management of diabetes and tuberculosis.
PMCID: PMC2945809  PMID: 19926034
11.  Progressive increase in cavitation with the evolution of fungus ball: A clue to the diagnosis of chronic necrotizing pulmonary aspergillosis 
Chronic necrotizing pulmonary aspergillosis (CNPA) is an uncommon pulmonary infection seen in the patients with chronic obstructive pulmonary disease, bronchiectasis, pneumoconiosis, diabetes mellitus, alcoholism, poor nutrition or low dose corticosteroid therapy. Here, we are presenting a case of CNPA with diabetes mellitus that was misdiagnosed as pulmonary tuberculosis.
PMCID: PMC2862516  PMID: 20442846
Aspergillus; diabetes; tuberculosis
12.  Tuberculosis risk factors among tuberculosis patients in Kampala, Uganda: implications for tuberculosis control 
BMC Public Health  2015;15:13.
Slow decline in the incidence of tuberculosis (TB) has been observed in most high TB burden countries. Knowledge of the prevalence of different TB risk factors can help expand TB control strategies. However with the exception of Human Immunodeficiency Virus (HIV) the prevalence of the other TB risk factors are poorly studied in Uganda. We aimed to determine the prevalence of different TB risk factors and TB disease presentation among TB patients in Kampala Uganda.
We assessed 365 adult TB patients and used descriptive statistics to summarize their socio-demographic, clinical, radiological, sputum mycobacteriology and TB risk factors (HIV, diabetes, TB contact, alcohol use, tobacco smoking, poverty and overcrowding) data.
A total of 158 (43.3%) patients were male and the median age was 29 (IQR 28–30). Majority of the patients (89.2%) had pulmonary TB, 86.9% were new and 13.2% were retreatment. Wasting (i.e. body mass index of <18.5 kg/m2) was found in 38.5% of the patients and 63% presented with cough. Constitutional symptoms (fever, anorexia, night sweats and weight loss) were reported by 32.1%. Most patients (78.6%) presented with non-cavity lung parenchyma disease (infiltrates, nodules, masses) but 35.2% had cavity disease. Pleural disease was detected in 19.3% of patients. Positive smear microscopy and culture (irrespective of month of treatment) was found in 52.7% and 36.5% of patients respectively. Any drug resistance was detected in 21.1% of patients while multidrug resistance (MDR) TB defined as resistance to rifampicin and isoniazid was detected in 6.3% of patients. All MDR patients were new patients.
The prevalence of TB risk factors were as follows: HIV 41.4%, diabetes 5.4%, close contact 11.5%, family history 17.5%, smoking 26.37%, poverty 39.5%, overcrowding 57.3% and alcohol use 50.7%. Overcrowding increased smear positive rate, prevalence ratio 1.22, p = 0.09 but all the other studied risk factors did not affect clinical, radiological and mycobacteriological study patient characteristics.
Among TB patients in Kampala, Uganda, there is high prevalence of the known TB risk factors. Targeting reducing their prevalence may lead to better TB control in the country. Tuberculosis, risk factors, Uganda.
PMCID: PMC4311451  PMID: 25604986
13.  Tuberculosis and diabetes mellitus – an underappreciated association 
Archives of Medical Science : AMS  2014;10(5):1019-1027.
The current review presents up-to-date knowledge on tuberculosis (TB) in diabetic patients. On the basis of available literature, there is little doubt about the close relationship between these two conditions. Diabetes mellitus in this association may still contribute substantially to the burden of TB and negatively affect control of the latter. Chronic hyperglycemia at least to some extent may alter the clinical manifestation, radiological appearance, treatment outcome and prognosis of TB. Although the pathogenesis is not clear, diabetes may impair both innate and adaptive immune responses to Mycobacterium tuberculosis. Eventually, effective screening and dual management of the diseases have to be addressed both in low- and high-income countries in order to limit the negative effects of the forthcoming global diabetes epidemic.
PMCID: PMC4223145  PMID: 25395955
Mycobacterium tuberculosis; hyperglycemia; epidemic; screening
14.  Pulmonary Tuberculosis in Patients with HIV/AIDS in Iran 
Iranian Journal of Public Health  2011;40(1):100-106.
Pulmonary tuberculosis is still the most common form of tuberculosis in HIV infected patients having different presentations according to the degree of immunosuppression. This study appraised the impact of HIV infection on clinical, laboratory and radiological presentations of tuberculosis.
The clinical, laboratory and radiological presentations of pulmonary TB in 56 HIV-infected patients were compared with 56 individually sex and age matched HIV-seronegative ones, admitted to Imam Hospital in Tehran (1999–2006) using paired t-test in a case control study.
All cases and the controls were male. Fever was found in 83.9% of the HIV positive patients compared to 80% of the HIV negative ones. Cough was the most common clinical finding in the HIV negative group (89.3% vs. 82.1% in HIV positive group). Among radiological features, cavitary lesions, upper lobe and bilateral pulmonary involvement were observed significantly less often in the HIV-infected group. On the contrary, lymphadenopathy was just present in the HIV positive group in this series of patients (12%) and primary pattern tuberculosis was more common, as well (71% vs. 39%, P= 0.02). The Tuberculin test was reactive in 29% of the HIV/TB patients.
The coexistence of both infections alters the picture of tuberculosis in many aspects and should be taken into account when considering a diagnosis of HIV infection and its potential for TB co-infection, and vice-versa.
PMCID: PMC3481717  PMID: 23113062
Pulmonary Tuberculosis; HIV; TB and HIV; Iran
15.  Cytological and Transcript Analyses Reveal Fat and Lazy Persister-Like Bacilli in Tuberculous Sputum 
PLoS Medicine  2008;5(4):e75.
Tuberculous sputum provides a sample of bacilli that must be eliminated by chemotherapy and that may go on to transmit infection. A preliminary observation that Mycobacterium tuberculosis cells contain triacylglycerol lipid bodies in sputum, but not when growing in vitro, led us to investigate the extent of this phenomenon and its physiological basis.
Methods and Findings
Microscopy-positive sputum samples from the UK and The Gambia were investigated for their content of lipid body–positive mycobacteria by combined Nile red and auramine staining. All samples contained a lipid body–positive population varying from 3% to 86% of the acid-fast bacilli present. The recent finding that triacylglycerol synthase is expressed by mycobacteria when they enter in vitro nonreplicating persistence led us to investigate whether this state was also associated with lipid body formation. We found that, when placed in laboratory conditions inducing nonreplicating persistence, two M. tuberculosis strains had lipid body levels comparable to those found in sputum. We investigated these physiological findings further by comparing the M. tuberculosis transcriptome of growing and nonreplicating persistence cultures with that obtained directly from sputum samples. Although sputum has traditionally been thought to contain actively growing tubercle bacilli, our transcript analyses refute the hypothesis that these cells predominate. Rather, they reinforce the results of the lipid body analyses by revealing transcriptional signatures that can be clearly attributed to slowly replicating or nonreplicating mycobacteria. Finally, the lipid body count was highly correlated (R2 = 0.64, p < 0.03) with time to positivity in diagnostic liquid cultures, thereby establishing a direct link between this cytological feature and the size of a potential nonreplicating population.
As nonreplicating tubercle bacilli are tolerant to the cidal action of antibiotics and resistant to multiple stresses, identification of this persister-like population of tubercle bacilli in sputum presents exciting and tractable new opportunities to investigate both responses to chemotherapy and the transmission of tuberculosis.
Studying sputum from humans with pulmonary tuberculosis, Michael Barer and colleagues detect mycobacteria containing lipid bodies. Analyses linking this cytological feature to a slow-growing phenotype sheds light on persistence.
Editors' Summary
Every year, nearly nine million people develop tuberculosis—a contagious infection usually of the lungs—and about two million people die from the disease. Tuberculosis is caused by Mycobacterium tuberculosis, bacteria that are spread in airborne droplets when people with the disease cough or sneeze. The symptoms of tuberculosis include a persistent cough, weight loss, and night sweats. Diagnostic tests include chest X-rays, the tuberculin skin test, and sputum analysis. For the last of these tests, a sample of sputum (mucus and other matter brought up from the lungs by coughing) is collected and then taken to a laboratory where bacteriologists look for M. tuberculosis using special stains—tuberculosis-positive sputum contains “acid-fast bacilli”—and also try to grow bacteria from the sample. Tuberculosis can be cured by taking several powerful antibiotics for several months. It is very important that this treatment is completed to ensure that all the M. tuberculosis bacteria in the body are killed and to prevent the emergence of drug-resistant bacteria.
Why Was This Study Done?
Strenuous efforts are being made to reduce the global burden of tuberculosis but with limited success so far for many reasons. One barrier to success is the efficiency with which M. tuberculosis spreads from one person to another. Very little is known about this part of the bacteria's life cycle. If scientists could understand more about the transmission of M. tuberculosis between people, they might identify new therapeutic and preventative targets. In the study, therefore, the researchers examine the acid-fast bacilli in tuberculosis-positive sputum samples to get a snapshot of M. tuberculosis at the point of its transmission to a new person and ask how the characteristics of these bacilli compare with those of M. tuberculosis growing in the laboratory.
What Did the Researchers Do and Find?
The researchers collected sputum samples from patients with tuberculosis in the UK and The Gambia before they received any treatment, and looked for the presence of acid-fast bacilli containing “lipid bodies.” These small structures contain a fat called triacylglycerol. M. tuberculosis accumulates triacylglycerol when it is exposed to several stresses present during infection (for example, reduced oxygen or hypoxia) and the researchers suggest that the presence of this fat may help the bacteria survive during transmission and establish a new infection. They found that all the samples contained some lipid body–positive acid-fast bacilli. Next, the researchers showed that M. tuberculosis grown in the laboratory under hypoxic conditions, which induce the bacteria to enter an antibiotic-tolerant condition called a “nonreplicating persistent” (NRP) state, also accumulated lipid bodies. This result suggests that the lipid body–positive acid-fast bacilli in sputum might be in an NRP state. To test this idea, the researchers compared the pattern of mRNAs (the templates from which proteins are produced; the pattern of mRNAs is called the transcriptome and gives an idea of which proteins a cell is making under given conditions) made by growing cultures of M. tuberculosis, by M. tuberculosis maintained in the NRP state, and by the acid-fast bacilli in several sputum samples. The transcriptome of the sputum sample revealed production of many proteins made in the NRP state. Finally, the researchers showed that the time needed to grow M. tuberculosis from sputum samples increased as the proportion of lipid body–positive acid-fast bacilli in the sputum increased, just as one would suspect if the presence of lipid bodies signifies nongrowing cells.
What Do These Findings Mean?
It has been generally assumed that the acid-fast bacilli in sputum collected from patients with tuberculosis are rapidly replicating M. tuberculosis released from infected areas of the lungs. By identifying a population of bacteria that contain lipid bodies and that are in an NRP-like state in all the samples of sputum examined from two geographical sites, this study strongly challenges this assumption. The characteristics of this population of bacteria, the researchers suggest, might help them survive the adverse conditions that M. tuberculosis encounters during transmission between people and might partly explain why complete clearance of M. tuberculosis requires extended treatment with antibiotics. To establish the clinical significance of these findings, future studies will need to examine whether antibiotic treatment affects the frequency of lipid body–positive M. tuberculosis bacteria in patients' sputum and whether there is any relationship between this measurement and infectiousness, or clinical response to treatment.
Additional Information.
Please access these Web sites via the online version of this summary at
The MedlinePlus encyclopedia contains pages on tuberculosis and on sputum culture (in English and Spanish)
The US National Institute of Allergy and Infectious Diseases provides information on all aspects of tuberculosis
The US Centers for Disease Control and Prevention Division of Tuberculosis Elimination provides several fact sheets and other information resources about tuberculosis
The World Health Organization provides information on efforts to reduce the global burden of tuberculosis
PMCID: PMC2276522  PMID: 18384229
16.  Clinico-epidemiological profile of HIV/TB coinfected patients in Vadodara, Gujarat 
The HIV epidemic has posed major, almost insurmountable, challenges to tuberculosis control efforts across the world. This study analyzes the prevalence and disease profile of HIV/AIDS coinfection in Vadodara, Gujarat, India.
Materials and Methods:
This study was conducted in the HIV Referral Clinic at Vadodara, India. Using convenience sampling method, 246 HIV-positive patients coinfected with tuberculosis were enrolled. A detailed history of every case was taken followed by a thorough physical examination. Baseline and follow up laboratory and radiological investigations were carried out as appropriately warranted.
Out of 500 HIV positive patients who presented to the clinic during the study period, 246 (49.2%) were coinfected with tuberculosis. Out of 246 coinfected cases, 35(14.2%) presented with demonstrable and documented tuberculosis whereas in 211(85.8%) cases, tuberculosis was extemporaneously detected by actively screening the patients. Sixty nine percent of patients were males, while 10.5% of cases were below fifteen years of age. The majority (68%) of patients had manifestations of extrapulmonary tuberculosis; but pulmonary tuberculosis, which is a more common presentation in HIV-negative cases, was present in only fifty five percent of this segment of the population. Abdominal tuberculosis was the most common site (74%) amongst extrapulmonary tuberculosis involvement, followed by clinically palpable lymph nodes (22%) and pleural effusion (17%).
The prevalence of tuberculosis in HIV-positive patients in this study (49%) was substantially higher than that reported in previous studies. However, this could be attributed to a selection and/or a diagnosis bias. This study used abdominal ultrasound for the diagnosis of tuberculosis which might have obviously increased the prevalence. Moreover, these cases were not confirmed by biopsy or other definitive TB diagnostic methods.
PMCID: PMC3168032  PMID: 21938107
Coinfection; HIV; HIV/AIDS; India; TB; tuberculosis
17.  Smear positive extra pulmonary tuberculosis disease at University of Gondar Hospital, Northwest Ethiopia 
BMC Research Notes  2013;6:21.
While pulmonary tuberculosis is the most common presentation, extra pulmonary tuberculosis is also an important clinical problem. However, no adequate information had been made available on the prevalence of smear positive extra pulmonary tuberculosis in Gondar. The aim of this study was to assess the prevalence and possible risk factors of smear positive extra pulmonary tuberculosis among suspected patients at University of Gondar Hospital.
A cross-sectional study on extra pulmonary tuberculosis suspected patients was conducted at University of Gondar Hospital from January 2012 to April, 2012. Specimens of patients suspected of extra pulmonary tuberculosis were obtained from fine needle aspiration and body fluid samples collected by pathologist. Demographic characteristics and other variables were collected using a pretested semi-structured questionnaire. Smears were prepared from each sample and stained by Ziehel Neelson and Wright stain. The result of the study was analyzed with bivariate and multivariate logistic regression.
A total of 344 extra pulmonary tuberculosis suspected clients were included in the study and specimens were taken from lymph node aspirates and body fluids. The overall prevalence of smear positive extra pulmonary tuberculosis was 34 (9.9%). Of these cases of extra pulmonary tuberculosis, lymph node tuberculosis constituted the largest proportion (82.4%). Among the 34 extra pulmonary tuberculosis patients, over half of them (52.9%) were positive for human immunodeficiency virus. The largest proportion of tuberculosis and human immunodeficiency virus cases occurred among persons with in the age group of 31–40 years. Previous history of tuberculosis (OR = 4.77, 95% CI 1.86-12.24), contact to a known tuberculosis cases (OR = 6.67 95% CI 2.78-16.90), history of underlying diseases (OR = 2.79 95% CI 1.15-6.78) and income (OR = 12.9 95% CI 2.25-68.02) were significantly associated with extra pulmonary tuberculosis infection.
The prevalence of smear positive extra pulmonary tuberculosis infection in Gondar is high. Screening of lymph node and other body fluid specimens for extra pulmonary tuberculosis could help for treatment, control and prevention of the disease.
PMCID: PMC3558382  PMID: 23331864
Extra pulmonary tuberculosis; Acid fast bacilli; Northwest Ethiopia
18.  A case of emphysematous cystitis complicated with miliary tuberculosis 
Emphysematous cystitis occurs mostly in diabetics with poor glycemic control or in immunocompromised patients. In most cases, diabetes mellitus correlates with the occurrence of emphysematous cystitis. The risk of relapse after tuberculosis cure or treatment completion is high among patients with diabetes mellitus.
Case Report:
A 64-year-old diabetic man suffering from high fever and lower abdominal pain was admitted to the emergency ward. Due to the results of radiographic examinations, he was diagnosed with an emphysematous cystitis. Although the emphysematous cystitis improved with urinary drainage and antibiotic therapy, the high fever recurred and respiratory symptoms appeared. This patient was diagnosed with a crisis of the pulmonary tuberculosis. He was started on the antituberculosis therapy, and he recovered.
This is the first report of a case of emphysematous cystitis that was complicated with pulmonary tuberculosis.
PMCID: PMC3616067  PMID: 23569536
emphysematous cystitis; pulmonary tuberculosis
19.  Type 2 Diabetes Mellitus Coincident with Pulmonary Tuberculosis Is Associated with Heightened Systemic Type 1, Type 17, and Other Proinflammatory Cytokines 
Rationale: Type 2 diabetes mellitus is a major risk factor for the development of active tuberculosis, although the biological basis underlying this susceptibility remains poorly characterized.
Objectives and Methods: To identify the influence of coincident diabetes mellitus on cytokine levels in pulmonary tuberculosis, we examined circulating levels of a panel of cytokines and chemokines in the plasma of individuals with tuberculosis with diabetes and compared them with those of individuals without diabetes.
Measurements and Main Results: Tuberculosis with diabetes is characterized by elevated circulating levels of type 1 (IFN-γ, tumor necrosis factor-α, and IL-2), type 2 (IL-5), and type 17 (IL-17A) cytokines but decreased circulating levels of IL-22. This was associated with increased systemic levels of other proinflammatory cytokines (IL-1β, IL-6, and IL-18) and an antiinflammatory cytokine (IL-10) but not type 1 IFNs. Moreover, tuberculosis antigen–stimulated whole blood also showed increased levels of proinflammatory cytokines. Finally, type 1 and type 17 cytokines in plasma exhibit a significant positive correlation with hemoglobin A1C levels, indicating that impaired control of diabetes is associated with this proinflammatory milieu. Multivariate analysis revealed that the association of proinflammatory cytokines with diabetes mellitus was not influenced by age, sex, or other metabolic parameters.
Conclusions: Our data reveal that tuberculosis with diabetes is characterized by heightened cytokine responsiveness, indicating that chronic inflammation underlying type 2 diabetes potentially contributes to increased immune pathology and poor control in tuberculosis infection.
PMCID: PMC3960913  PMID: 23987505
bacterial; cytokines; chemokines; tuberculosis; diabetes mellitus
20.  Manifestations of tuberculosis in HIV/AIDS patients and its relationship with CD4 count 
HIV/AIDS pandemic is responsible for the resurgence of TB worldwide, resulting in increased morbidity and mortality. HIV and Mycobacterium tuberculosis have a synergistic interaction; each propagates progression of the other. Coinfection with HIV infection leads to difficulties in both the diagnosis and treatment of tuberculosis, increase risk of death, treatment failure and relapse.
The aim of the present study is to study the clinical, radiological profile of pulmonary and extrapulmonary tuberculosis (EPTB) in HIV-seropositive patients and their relationship to CD4 counts.
Materials and Methods:
It was a prospective study conducted over a period of 1 year in the department of medicine, Indira Gandhi Medical College, Shimla. We examined 87 HIV-infected patients with associated tuberculosis recruited from the department of medicine and antiretroviral center and were subjected to thorough clinical examination, X-ray chest, tuberculin testing and sputum examination for AFB and necessary relevant investigations for EPTB.
Most common affected age group was 31-40 years. EPTB is the commonest form of TB in our study detected in 65 patients. Commonest EPTB was CNS tuberculosis. Disseminated tuberculosis was only found in patient with CD4 count less than 200/cmm. Majority of lymph node TB was diagnosed by fine needle aspiration cytology (FNAC) examination. All patients with AFB-positive lymph node had CD4 count below 200/cum.
The results of this study provide information regarding the various forms of TB and their presentation in HIV-infected persons. Early diagnosis of tuberculosis and prompt institution of antitubercular treatment (ATT) reduces mortality and morbidity significantly. In resource-poor areas, the diagnosis can be established with cytological/biochemical analysis of fluid, histopathological examination and ZN staining of tissue coupled with radiological features and response to ATT. Therefore, adequate knowledge of the manifestations of tuberculosis in HIV-infected patients is absolutely necessary for optimal management and to reduce mortality and morbidity.
PMCID: PMC3213712  PMID: 22084539
AFB smear; CD4 count; extrapulmonary; HIV; pulmonary; tuberculosis
21.  Directly observed treatment short course in immunocompetent patients of tuberculous cervical lymphadenopathy treated in revised national tuberculosis control programme 
Prospective observation analysis to evaluate the cure in tuberculous cervical lymphadenopathy with directly observed treatment short course category III (DOTS CAT III) treatment as per revised national tuberculosis control program (RNTCP) at a tertiary care hospital in AP, India, from October 2007 to September 2009. These cases were followed up for period of 22 months.
Materials and Methods:
Total 1521 tuberculous cases were screened in KIMS both pulmonary and extra pulmonary cases out of which 146 cases were tuberculous lymphadenitis. Fifty cases of tuberculous cervical lymphadenopathy were included after diagnostic and treatment algorithm and fine needle biopsy or excision biopsy. Patients below 5 yrs, immunocompromised, having diabetes mellitus, pulmonary tuberculosis and with other co-morbid conditions were excluded from the study. All patients were put on DOTS CAT III as per RNTCP guidelines. Follow-up was done every 2 months till 6 months for 1) Constitution symptoms 2) Weight gain or loss 3) Appetite gain or loss 4) Regression of lymph nodes or increase 5) Compliance 6) Side effects 7) Failures by demonstration of organism by direct smear, culture or histopathological examination.
In this study, lymph node regression was found in 78% at the end of 2 months, 94% at the end of 4 months and 96% at the end of 6 months, 9 patients had regression in size though the nodes were palpable, 2 had no regression but fresh lymph nodes appeared on the same side and sinus discharge was present, culture was negative in these cases. Two cases had immune reconstitution syndrome, constitutional symptoms disappeared and showed clinical improvement. Four cases were subjected for surgical intervention.
DOTS CAT III is effective in the treatment of tuberculous cervical lymphadenopathy. Compliance was good with minimal, minor side effects, only two had immune reconstitution syndrome and two had sinus formation; they were referred for surgical intervention, and follow-up of 22 months did not show any relapses.
PMCID: PMC3354481  PMID: 22628922
Biopsy; cervical lymphadenopathy; DOTS; immune reconstitution syndrome; tuberculosis
22.  Prevalence of multidrug resistance in Mycobacterium tuberculosis isolates from HIV seropositive and seronegative patients with pulmonary tuberculosis in north India 
BMC Infectious Diseases  2013;13:137.
Multidrug resistant (MDR) and extensively-drug resistant (XDR) tuberculosis (TB) are a serious threat to the national TB control programs of developing countries, and the situation is further worsened by the human immunodeficiency virus (HIV) pandemic. The literature regarding MDR/XDR-TB is, however, scanty from most parts of India. We carried out this study to assess the prevalence of MDR/XDR-TB in new and previously treated cases of pulmonary TB and in HIV seropositive and seronegative patients.
Sputum and blood specimens were obtained from 2100 patients suspected of pulmonary tuberculosis and subjected to sputum microscopy and culture for TB, and HIV serology at our tertiary care centre in north India. The culture positive Mycobacterium tuberculosis isolates were subjected to drug susceptibility testing (DST) for first line anti-tuberculosis drugs, and the MDR isolates were further subjected to second line DST. Various parameters of the patients’ were analyzed viz. clinical presentation, radiology, previous treatment history, demographic and socioeconomic data and microbiology results.
Of the 2100 patients, sputum specimens of 256 were smear positive for acid-fast bacilli (AFB), 271 (12.9%) grew Mycobacterium spp., and M. tuberculosis was isolated in 219 (10.42%). Of the 219 patients infected with M. tuberculosis, 20.1% (44/219) were found to be seropositive for HIV. Overall, MDR-TB was observed in 17.4% (39/219) isolates. There were 121 newly diagnosed and 98 previously treated patients, of which MDR-TB was found to be associated with 9.9% (12/121) and 27.6% (27/98) cases respectively. There was significantly higher association of MDR-TB (12/44, 27.3%) with HIV seropositive patients as compared to HIV seronegative patients (27/175, 15.4%) after controlling previous treatment status, age, and sex (odd’s ratio, 2.3 [95% CI, 1.000-5.350]; p-value, 0.05). No XDR-TB was found among the MDR-TB isolates.
The present study demonstrated a high prevalence of drug resistance amongst pulmonary TB isolates of M. tuberculosis from north India as compared to the WHO estimates for India in 2010, though this could possibly be attributed to the clustering of more serious or referred cases at our tertiary care centre. The prevalence of MDR-TB in HIV seropositive patients was significantly higher than seronegative individuals. The study emphasizes the need to monitor the trends of drug resistance in TB in various populations in order to timely implement appropriate interventions to curb the menace of MDR-TB.
PMCID: PMC3610146  PMID: 23497169
Mycobacterium tuberculosis; Multidrug resistant; Extensively-drug resistant; HIV; Socioeconomic status
23.  Efficacy of serum chitotriosidase activity in early treatment of patients with active tuberculosis and a negative sputum smear 
The results of sputum culture for Mycobacterium tuberculosis must be awaited in most cases, which delays the start of treatment in patients with sputum smear-negative pulmonary tuberculosis. We investigated whether plasma chitotriosidase activity is a strong marker for early diagnosis of tuberculosis in patients for whom a bacillus smear is negative and tuberculosis culture is positive.
Clinical, radiological, and laboratory features were evaluated in 75 patients, 17 of whom were diagnosed as having active tuberculosis by negative acid-fast bacillus smear and positive culture, 38 as having sequel tuberculosis which was radiologically and microbiologically negative, and 20 who served as healthy controls. Serum chitotriosidase activity levels were measured in both cases and controls.
The mean age of the cases with active pulmonary tuberculosis, cases with sequel lesions, and controls was 23 ± 2.4 years, 22 ± 1.7 years, and 24 ± 2.1 years, respectively. Serum chitotriosidase levels were 68.05 ± 72.61 nmol/hour/mL in smear-negative, culture-positive pulmonary tuberculosis cases (Group A) and 29.73 ± 20.55 nmol/hour/mL in smear-negative, culture-negative sequel pulmonary tuberculosis cases (Group B). Serum chitotriosidase levels from patients in Group A were significantly higher than in Group B and Group C. There was no statistically significant difference in serum chitotriosidase levels between cases with sequel pulmonary tuberculosis (Group B, smear-negative, culture-negative) and healthy controls (Group C).
In patients with active tuberculosis and a negative sputum smear for acid-fast bacillus, plasma chitotriosidase activity seems to be a strong marker for diagnosis of active disease which can be used while awaiting culture results.
PMCID: PMC3431959  PMID: 22956876
pulmonary tuberculosis; serum chitotriosidase; diagnosis; antituberculous treatment; disease activity
24.  Determination of Sites Involved, HIV Co–Infection & Utility of Diagnostic Modalities in EPTB 
Background: Tuberculosis remains a major global public health problem and an on-going epidemic. Though the chief objectives of the Revised National Tuberculosis Control Programme (RNTCP) in detecting and curing the infectious pulmonary cases is well taken, there has been a steady rise in the number of Extra Pulmonary Tuberculosis (EPTB) cases as documented in several studies. EPTB which usually constitutes around 15%-20% of the total TB cases is now being increasingly reported due to a combination of better diagnostic facilities, and the HIV pandemic. Though several studies have shown increasing prevalence of EPTB, only few studies are available, especially in the Indian scenario, that study the pattern and risk factors. Hence, this retrospective observational study was undertaken to determine the sites of the involvement, HIV co-infection and usefulness of various diagnostic modalities in EPTB affecting patients attending a medical college DOTS clinic.
Material and Methods: One hundred ten EPTB patients referred to the DOTS clinics of the TB & Chest department from the period Dec 2010– Mar 2012 were included in the study. The diagnosis of EPTB was established by combined clinical, microbiological, histopathological &/or imaging modalities. Their medical records were assessed to determine the age distribution, gender and anatomical sites of involvement. The presence of co-morbid conditions like smoking history, alcoholism, diabetic and HIV status were noted. BCG status and Mantoux test readings were recorded. The different diagnostic tests used in confirming EPTB at different sites were recorded. Chest x-ray was analysed for all patients to assess coexisting pulmonary involvement. All patients were followed to assess the outcome of treatment.
Results: The mean age of patients was 34.4. The male to female ratio was 58:52 showing a slight male predominance. The most common site of involvement was lymph node followed by pleural effusion and abdominal TB. The prevalence of lymph node TB was noted to be higher in female patients as compared to other sites of EPTB. Mantoux test was positive in 57 (51.8%) patients. HIV co-infection was noted in only 3 (2.7%) patients. Concomitant pulmonary involvement was seen in 19 (17.3%) patients.
Conclusions: Lymph node was the most common site involvement showing a significant female preponderance followed by pleural effusion and abdominal TB. The rates of HIV co-infection and diabetes mellitus were 2.7% and 20% respectively. The most useful diagnostic modality was tissue sampling followed by imaging. Mantoux test is not unequivocal for the diagnosis of EPTB.
PMCID: PMC3782920  PMID: 24086863
Extra–Pulmonary Tuberculosis; DOTS clinic; TB Lymphadenopathy; HIV co-infection; Mantoux test
25.  Empyema thoracis: A clinical study 
Annals of Thoracic Medicine  2007;2(1):14-17.
Empyema thoracis is a disease that, despite centuries of study, still causes significant morbidity and mortality.
The present study was undertaken to study the age-sex profile, symptomatology, microbiologic findings, etiology and the management and treatment outcome in a tertiary care hospital.
A prospective study of empyema thoracis was conducted on 40 consecutive patients with empyema thoracis admitted to the tuberculosis and chest diseases ward of a teaching hospital.
The demographic data, clinical presentation, microbiological findings, etiology, the clinical course and management were recorded as per a planned pro forma and analyzed.
The peak age was in the range of 21-40 years, the male-to-female ratio was 3.4:1.0 and the left pleura was more commonly affected than the right pleura. Risk factors include pulmonary tuberculosis, chronic obstructive pulmonary diseases, smoking, diabetes mellitus and pneumonia. Etiology of empyema was tubercular in 65% cases and nontubercular in 35% cases. Gram-negative organisms were cultured in 11 cases (27.5%). Two patients received antibiotics with repeated thoracentesis only, intercostal chest tube drainage was required in 38 cases (95%) and more aggressive surgery was performed on 2 patients. The average duration for which the chest tube was kept in the complete expansion cases was 22.3 days.
It was concluded that all cases of simple empyema with thin pus and only those cases of simple empyema with thick pus where size of empyema is small should be managed by aspiration/s. Cases failed by the above method, all cases of simple empyema with thick pus and with moderate to large size of empyema and all cases of empyema with bronchopleural fistula should be managed by intercostal drainage tube connected to water seal. It was also observed that all cases of empyema complicated by bronchopleural fistula were difficult to manage and needed major surgery.
PMCID: PMC2732064  PMID: 19724669
Closed tube thoracostomy; empyema; parapneumonic effusion

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