Tuberculous Disease Research Articles

Tuberculous gallbladder - A rare presentation of tuberculosis

Tuberculosis is one of the most widespread diseases worldwide but gallbladder tuberculosis (GT) is an extremely rare disease, and very few cases have been reported in the literature. The first case of GT was described in 1870 by Gaucher. The unusual case reported here showed features highly indicative of cholilitheasis with tuberculous disease of the gallbladder – as evidenced by the clinical, laboratory and ultrasonographic and CT scan findings, and confirmed by histopathological examination.

Clinical and ethical issue regarding cesarean section in HIV young woman with severe tuberculous disease

Clinical and ethical issue regarding cesarean section in HIV young woman with severe tuberculous disease

Study of the diagnostic value of a polymerase chain reaction for early diagnosis of experimental tuberculosis of bones and joints

The purpose of the present work was to study the diagnostic value of a polymerase chain reaction (PCR) in a new experimental model of tuberculous gonitis, created by the authors, and examine peculiarities in the clinical-pathomorphological course of tuberculosis of bones and joints (TBJ). Features of the clinical-pathomorphological course of tuberculous disease of joints were studied as result of an experiment, conducted on guinea pigs with use of an original procedure. The analysis of results of the above research made it possible to reveal that the diagnostic sensitivity of PCR was 80 % at the prearthritic stage of the disease development and 100 % at its arthritic one. At the same time, the specificity of the chosen technique was 100 %, thereby enabling us to draw a conclusion that the use of PCR of synovial fluid in the arsenal of diagnostic methods for patients with TBJ is reasonable.

AB 85. Presentation of cases of non tuberculous mycobacteria lung disease in immunocompetent patients

Background Nontuberculous mycobacteria (NTM) are acid-fast microorganisms that commonly cause lung disease in immunocompromised patients and patients with preexisting structural lung disease. Four cases of NTM infection in immunocompetent patients are presented.

Tuberculous Cold Abscess in the Axillary Lymph Nodes

A 56-year-old woman was admitted to the regional medical center suffering from dyspnea.She was diagnosed with tuberculous pericarditis and was treated with antituberculous drugs(INH,RFP, EB,and PZA).One month later,her cardiac condition was ameliorated and she was discharged.Subsequently EB and PZA were stopped.Two months later,she started to suffer from painful swelling of the left axillary lymph nodes.Although her cardiac condition was stable, the size of the lymph nodes was gradually enlarged (Fig. 1 A). CT and FDGPET showed a few translucent lymph nodes (Fig.2 A) and there was no sign of other malignancy. Because the swelling of the lymph nodes progressed in spite of the amelioration of pericarditis, the etiology was assumed to be neoplastic or autoimmune in nature.She was therefore referred to our hospital.On admission,she was afebrile and had no symptoms except for the swelling of a left axillary lymph node, which was approximately 4 cm in diameter,elastic and partially reddish.Blood examination revealed a slight inflammatory reaction (CRP 0.14 mg/dl, ESR 13 mm/hr). Contrast enhanced CT showed a consistent low density area surrounded by a ring-enhancing lesion (Fig.2 B).The tumor’s elasticity and CT findings suggested that the swelling was an abscess and EB was resumed. The abscess was located next to the skin and was on the verge of collapse.In case of collapse, there was the risk of nosocomial transmission, so we selected needle aspiration.Aspirated fluid revealed yellow pus (Fig. 3 A) which contained acid-fast bacteria (Fig. 3 B), though the subsequent culture revealed no growth of those.A diagnosis of tuberculous cold abscess was made.Two weeks after the aspiration,the abscess swelled and collapsed.It was surgically resected and she received an additional antituberculous medication(SM)because the lesions seemed to extend into neighboring lymph nodes in spite of medication with INH,RFP and EB.Three months after the surgical procedure, the abscess swelled again and broke forming a fistula(Fig.1 B), with the histology typical of a granuloma(Fig.3 C). With daily lavage through the fistula and continuous use of antituberculous drugs,her tuberculous lymph node lesions were completely cured 6 months after the last collapse.Although the lymph nodes are the most common sites of extrapulmonary tuberculosis ,tuberculous cold abscess in lymph nodes is less frequent in Japan .This case suggests that tuberculous lymphadenitis is an important differential diagnosis in examining lymph node swelling and that its progression is not always parallel to the exacerbation of other tuberculous disease conditions.

A case with multisystemic involved of Tuberculosis

Cases of tuberculosis with multisystemic involvement are rarely reported and these are often children and patients with AIDS whose and immune system is suppressed. Tuberculosis can mimic and present with various disorders. A 18-year-old Georgian male patient was admitted to the hospital with double vision, swelling and wound on the 3rd digit of the right hand. We defined the multisystemic tuberculous disease including orbital bone with soft tissue tuberculosis, tuberculosis spondylitis, tuberculosis dactylitis, scrofuloderma and pulmonary tuberculosis in these patient.

Evaluation of Adenosine Deaminase (Ada) in Tuberculous Pleurisy

Tuberculosis is a global health problem whose morbidity and mortality is increasing, as one-third of the world population is estimated to be infected with Mycobacterium tuberculosis and eight million new active cases occur annually commonest being pulmonary tuberculosis and is often associated with effusion. Delay in diagnosis and treatment results in poor prognosis. Adenosine deaminase estimation was done by Blake-Berman method. The purpose of this study is to find out the role of ADA levels in differentiation of tuberculous and non-tuberculous exudative pleural effusions of different etiologies. Adenosine deaminase values were compared between tuberculous and non-tuberculous groups and difference in these values was statistically significant (*p<0.01 for ADA). Adenosine deaminase estimation in pleural fluid has long been taken as a marker for tuberculous pleurisy. ADA levels in non-tuberculous exudative pleural effusions rarely exceeded the cutoff; set for tuberculous disease. The pleural fluid ADA levels were significantly higher in tuberculous exudative pleural effusions when compared with non-tuberculous exudative pleural effusions.

Epidemiologic surveillance to detect false-positive Mycobacterium tuberculosis cultures

This study was aimed to investigate the ability of potential indices from epidemiologic surveillance to detect false-positive cultures of Mycobacterium tuberculosis (MTB). All clinical specimens for mycobacterial culture from April 1 to August 31, 2010, were reviewed. Single-positive cultures without relevant clinical and pathologic information were categorized as suspected false-positive cultures. Genotyping methods were used to confirm false-positive cultures. The performance of epidemiologic surveillance indices to detect potential false-positive cultures was evaluated. A total of 14,462 specimens were sent to the laboratory and 214 batches were processed in 107 work days (average 67.6 specimens per batch, ranging from 21 to 130 specimens per batch). Seventy-one single-positive cultures were identified, among which 5 cultures of multidrug-resistant MTB in 1 batch were false-positive, confirmed by genotyping methods. Epidemiologic surveillance with statistical process control charts for single-positive cultures per day showed good performance in epidemiologic surveillance. The false-positive rate was 38.5% in the 13 potential false-positive cultures according to the statistical process control chart for single-positive cultures per day. Although the incidence of tuberculous disease is high in Taiwan, clustering of multidrug-resistant MTB in 1 batch or clustering of single-positive cultures still suggested the occurrence of false-positive MTB cultures. Therefore, epidemiologic surveillance for the clustering of single-positive cultures with the statistical process control chart could be used to monitor the occurrence of false-positive results.

Factors associated with severe tuberculous disease in children

Factors associated with severe tuberculous disease in children

Spondilodiscitis due to Mycobacterium tuberculosis in HIV and non-HIV-infected patients: Eleven years experience in a referent Hospital of infectious diseases in Argentina

Background: Tuberculosis (TB) is an emerging health problem despite the advances in the methods of diagnosis and treatment. The resurgence of tuberculous spondilodiscitis (TBSD) or Pott's disease can be expected to be associated with a concomitant increase in the incidence of extra-pulmonary TB. Aim: To describe the clinical features, imaging findings, and laboratory diagnosis in a group of patients with TBSD. Materials and Methods: From January 1 st 2000 to December 31 st 2010, we retrospectively reviewed 22 cases of spinal TB. Only those with positive culture results and/or characteristic clinical and pathological findings were enrolled. Demographic data, comorbilities, clinical manifestations, time up to the definitive diagnosis, outcome and sequelae were considered. Results : During the study period, 22 patients were diagnosed with TBSD; 14 were men and 8 women with a median of age of 34 years at the time of diagnosis. The median duration of symptoms before the TBSD diagnosis was 120 days (range 30 to 360 days). At the time of diagnosis, fever and back pain were the most common clinical symptoms; 7 patients (32%) had fever and 21 (95%) had spinal pain; eleven patients (50%) had constitutional symptoms; 6 (27%) had respiratory symptoms and 3 (13.6%) had neurological manifestations. Magnetic resonance imaging (MRI) was performed in 9 (40%) cases, computed tomography (CT) in 7 patients (32%), and abdominal ultrasound in 6 cases (27%). The lumbar spine was the most commonly involved site (14 patients, 64%); thoracic spine was involved in 2 patients (9%); dorsolumbar spine was compromised in 4 cases (18%). Cervical spine was only involved in one patient (4.5%) and the last patient (4.5%) presents a global spinal involvement (cervical-thoracic and lumbar spine). Conclusion: Insidious clinical course and ambiguous manifestations of TBSD often delay the accuracy of diagnosis. Spinal TB should be included in the differential diagnosis of patients with prolonged back pain and fever.

Gender differences in notification rates, clinical forms and treatment outcome of tuberculosis patients under the RNTCP

Introduction:An increased notification rate of tuberculosis (TB) in men is seen in the SAARC region. In India, the Revised National Tuberculosis Control Programme (RNTCP) detects nearly three times more male than female TB patients. Gender differences have also been reported in the clinical forms of tuberculous disease and in treatment adherence and cure rates in patients undergoing treatment for tuberculosis. The present study was undertaken to find out the sex differences in the notification rates and treatment outcomes of TB patients registered under the RNTCP in a rural tuberculosis unit (TU) in West Bengal.Materials and Methods:A retrospective record-based study was carried out among a total of 3605 cases registered under the RNTCP between January 1999 and June 2005. Notification rates of TB, clinical forms of TB and disease treatment outcomes recorded in the registers were analyzed based on genders. Outcomes were defined in accordance with the standard RNTCP definitions. The Z-test for proportion (for comparing differences in proportions), Student t-test (for comparing mean), and χ2 test (to see association) were performed for statistical analysis.Results:Among the total of 3605 patients, 2498 (69.3%) were male and 1107 (30.7%) were female with a male female ratio of 2.25:1. In patients less than 20 years of age, the notification rates among males and females were similar. In the other age groups, males were more likely to be notified compared to females and the difference was statistically significant. While new smear positive and retreatment cases were significantly more than in males, among females, new smear negative and new extrapulmonary cases were significantly higher. Among the new smear positive patients 89.4% of females were cured compared to 85.8% of males which was again significant statistically (Z=1.70, P<0.05). Male patients outnumbered females in all the unfavorable outcomes like death, failure, and default although none of the differences were statistically significant (P>0.05).Conclusion:The present study demonstrates a gender difference in the notification rates, clinical presentations and treatment outcomes of patients with tuberculosis. Integrated research is necessary to find the reasons for these differences. Such studies will be helpful in improving the efficacy of the RNTCP.

REVIEW ARTICLES Genitourinary tuberculosis: historical and basic science review: past and present

Genitourinary tuberculosis (GUTB) usually results from the reactivation of old, dormant tuberculous diseases by pathogens of the mycobacterium tuberculosis complex. GUTB is the second most common form of extrapulmonary tuberculosis, with more than 90% of cases occurring in developing countries. In GUTB, the kidneys are the most common sites of infection and are infected through hematogenous spread of the bacilli, which then spread through the renal and urinary tract. Patients with genital and urethral TB present with a superficial tuberculous ulcer on the penis or in the female genital tract develop mainly due to primary contact with mycobacterium exposure during intercourse or inoculation via goods or chattels contaminated with mycobacterium.The diagnosis of TB of the urinary tract is based on the case history, the finding of pyuria in the absence of infection as judged by culture on routine media, and by radiological imaging. However, a positive yellow egg culture and/or histological analysis of biopsy specimens, possibly combined with the polymerase chain reaction (PCR), is still required in most patients to establish a definitive diagnosis of GUTB.The standard antituberculous drug treatment should be administered initially for two months during the intensive phase with three or four drugs daily followed by dual continuation therapy for four months. Surgery as a treatment option in GUTB might be indicated in complicated urinary tuberculosis. After antituberculous treatment of GUTB, surveillance with regular follow-up visits over the next five years is recommended.In cases of drug resistance, additional drugs and prolonged treatment are required. Furthermore, increasing rates of drug-resistant cases and co-infection with HIV pose challenges in the treatment GUTB and other forms of TB.

In this issue

In this issue

Actinomycose pulmonaire disséminée avec atteinte hépatique : une forme trompeuse mimant un tableau polymétastatique

Thoracic actinomycosis, caused by bacteria of the Actinomyces genus, is a rare infection, with poor prognosis if untreated, whose clinical and radiological picture is misleading, which can simulate a tumoral or tuberculous disease. This is a case of generalised pseudotumoral pulmonary actinomycosis in a non-smoking, non-drinking 48-year-old man, who for one month has been presenting a cough with haemoptoic sputum, dyspnoea associated with fever and a deterioration in general condition. The clinical examination discovered weight loss, diffuse crackling rales and multiple dental caries. Biologically, he presented an inflammatory syndrome. The radiological imaging and lung and liver CT-scans discovered a peripheral lung mass right side associated with multiple nodular cannon-ball opacities, multiple liver lesions of metastatic appearance. The bacteriological examination of the bronchoalveolar lavage fluid (Gram stain and culture) and the transparietal biopsy of the lung mass confirmed the presence of Actinomyces. Progress under treatment with 10 million international units of parenteral penicillin G daily over a period of six weeks substituted by three grams of amoxicillin/clavulanic acid daily over a period of 12 months and following an oral preparatory procedure was favourable. The thoraco-abdominal scan carried out three months after the treatment showed that the lesions had completely disappeared. Our case illustrates the diagnostic difficulty of actinomycosis particularly faced with a picture of multiple lung and liver metastasis. Hence, the importance of a histological and bacteriological examination of samples. The prognosis of this complaint is generally good following well-managed, prolonged treatment; and the prognosis peculiar to disseminated forms is less certain.

Risk of tuberculosis among contacts of isoniazid-resistant and isoniazid-susceptible cases

To compare the risk to household contacts of isoniazid (INH) susceptible and INH-resistant cases of tuberculosis (TB) in a rural community in South India. In all, 5562 contacts of INH-susceptible and 779 contacts of INH-resistant patients and 246,845 persons with no TB case in the home were followed for 15 years, with surveys every 2.5 years comprising radiographic and sputum examination, selective follow-up of high-risk individuals and passive surveillance. If a new case developed, the household members were assigned to the 'INH-susceptible' (n = 7088) or 'INH-resistant' series (n = 526), whichever appropriate. Logistic regression and Cox's proportional hazards model were employed. The baseline prevalence of tuberculous infection was respectively 70% and 56% in contacts of INH-resistant and INH-susceptible patients (P < 0.001), compared to 46% in non-contacts. The incidence of culture-positive TB was respectively 295 and 311 per 100,000, compared to 162/100,000 in non-contacts. The adjusted hazard ratios were 2.4 and 2.0 for contacts of INH-resistant and INH-susceptible patients. The baseline prevalence of tuberculous infection was substantially higher in contacts of INH-resistant than INH-susceptible patients, but the incidence of tuberculous disease over a 15-year follow-up was similar in the two series, and twice as high as in non-contacts.

CT screening before treatment of latent tuberculous infection for the diagnosis of clinical TB among contacts

To evaluate the value of CT scan for the detection of tuberculous diseases among persons who are suspected to be infected at the contact examination. Fukujuji Hospital, Japan. Retrospective review of the medical records of 22 persons who were normal with plain chest X-ray at an outbreak at a private school, with which total 46 TB cases and 93 infected persons were detected by either symptomatic visits or contact examinations done mainly at public health centers. Among the 44 persons who visited Fukujuji Hospital, 4 persons were symptomatic visits, 3 persons were detected as TB cases by the contact examination at public health centers and 3 persons visited Fukujuji Hospital for the purpose of contact examination before examinations at the public health centers. Eight of these 10 persons were with abnormal chest plain Xray findings and the remaining two persons were normal with plain chest X-ray findings (group A). Among the 34 persons who were referred to Fukujuji Hospital from public health centers as the infected person without diseases, one person showed abnormal chest plain X-ray and 33 persons showed normal chest plain X-ray (group B). Group A persons were examined in June and Group B persons were examined in The 2 persons in the group A were with abnormal CT findings. They were not diagnosed as TB by the CT findings but followed up after sputum examinations. Both of them were diagnosed as TB by the positive TB culture. Among the 33 persons in the group B, 20 persons were tested with CT scan at the examination done before starting treatment of latent tuberuclous infection and six of these 20 persons were with abnormal findings and were judged as TB diseases. In the case of outbreak with many TB cases and infected persons, CT should be considered for the detection of TB cases among contacts.

Mathematical modeling of pulmonary tuberculosis therapy: Insights from a prototype model with rifampin

There is a critical need for improved and shorter tuberculosis (TB) treatment. Current in vitro models of TB, while valuable, are poor predictors of the antibacterial effect of drugs in vivo. Mathematical models may be useful to overcome the limitations of traditional approaches in TB research. The objective of this study was to set up a prototype mathematical model of TB treatment by rifampin, based on pharmacokinetic, pharmacodynamic and disease submodels. The full mathematical model can simulate the time-course of tuberculous disease from the first day of infection to the last day of therapy. Therapeutic simulations were performed with the full model to study the antibacterial effect of various dosage regimens of rifampin in lungs. The model reproduced some qualitative and quantitative properties of the bactericidal activity of rifampin observed in clinical data. The kill curves simulated with the model showed a typical biphasic decline in the number of extracellular bacteria consistent with observations in TB patients. Simulations performed with more simple pharmacokinetic/pharmacodynamic models indicated a possible role of a protected intracellular bacterial compartment in such a biphasic decline. This modeling effort strongly suggests that current dosage regimens of RIF may be further optimized. In addition, it suggests a new hypothesis for bacterial persistence during TB treatment.

The role of gallium-67 scintigraphy in comparing inflammatory activity between tuberculous and nontuberculous mycobacterial pulmonary diseases

The purpose of this study was to compare the inflammatory activity of pulmonary lesions between active tuberculosis and nontuberculous mycobacterial (NTM) infection in acid-fast bacilli smear-positive non-HIV-infected patients using gallium-67 (Ga) scintigraphy. Twenty-four patients with culture-proven active pulmonary tuberculosis (PTB) and an additional 17 patients meeting the criteria of pulmonary NTM infection were enrolled into the retrospective study. The Ga uptake of the pulmonary lesion was assessed by visual scoring of uptake grade and semiquantitative region of interest analysis of the uptake ratio using the thoracic spine as a reference. Ga scans were positive in 23 of the 24 patients (95.8%) with PTB and in 12 of the 17 patients (70.6%) with pulmonary NTM infection. Twenty patients with active PTB had moderate or intense visual Ga uptake grade, whereas only three patients with pulmonary NTM infection had moderate visual Ga uptake grade. The semiquantitative pulmonary Ga uptake ratios in patients with active PTB and NTM infection were 1.17 ± 0.28 (range: 0.77-1.86) and 0.79 ± 0.12 (range: 0.60-1.03), respectively. The Ga uptake grade and ratio of active PTB were both significantly higher than NTM infection (both P < 0.001). In the receiver operating characteristic curve analysis for predicting active PTB, the area under the curves of Ga uptake grade and ratio were 0.90 ± 0.05 and 0.93 ± 0.04, respectively (both P < 0.001). The inflammatory activity of active PTB is significantly higher than that of pulmonary NTM infection in non-HIV-infected patients. Ga uptake grade and ratio could be used to predict active PTB in acid-fast bacilli smear-positive patients.

Germline CYBB mutations that selectively affect macrophages in kindreds with X-linked predisposition to tuberculous mycobacterial disease

Germline mutations in CYBB, the human gene encoding the gp91(phox) subunit of the phagocyte NADPH oxidase, impair the respiratory burst of all types of phagocytes and result in X-linked chronic granulomatous disease (CGD). We report here two kindreds in which otherwise healthy male adults developed X-linked recessive Mendelian susceptibility to mycobacterial disease (MSMD) syndromes. These patients had previously unknown mutations in CYBB that resulted in an impaired respiratory burst in monocyte-derived macrophages but not in monocytes or granulocytes. The macrophage-specific functional consequences of the germline mutation resulted from cell-specific impairment in the assembly of the NADPH oxidase. This 'experiment of nature' indicates that CYBB is associated with MSMD and demonstrates that the respiratory burst in human macrophages is a crucial mechanism for protective immunity to tuberculous mycobacteria.

A disarticulating spinal lesion

CT-guided aspiration of the spinal lesion yielded necrotic puslike material, an abscess. Tuberculous disease was considered but his risk factors for exposure were very low. The lesion destroyed the entire T10 vertebral body and resulted in a separation-distraction of the adjacent vertebrae by greater than 6 cm. The abscess and large mass-like infectious phlegmon capsule were drained and debrided and the spine stabilized and reconstructed with instrumentation. Cultures taken intra-operatively grew Corynebacterium. Blood and urine cultures taken at the time of admission did not grow any bacteria and we hypothesized that the patient’s spinal infection originated from his decubitus ulcers. The patient was treated with intravenous antibiotics for 6 weeks with resolution of abdominal pain, fever and leukocytosis. Abdominal pain is an unusual presentation for spinal infection, but may be the only sign in a patient with a complete thoracic sensory level. Spinal infection remains a highly morbid diagnosis and can occur in multiple anatomic locations including the vertebral body, intervertebral disc, epidural space and in the adjacent soft tissue.