Diagnosis Of Extrapulmonary Tuberculosis Research Articles

Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.

BackgroundIdentifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB.MethodsArchived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility.ResultsHemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses.ConclusionsEvidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia and iron redistribution are likely due to viral and/or bacteria-driven processes and the host immune response to infection. As a result, iron supplementation may not be efficacious or safe under these circumstances. Clinical and nutritional management of HIV and Mycobacterium tuberculosis co-infected individuals, especially in regions where food insecurity and malnutrition co-exist, may be further improved when the iron-related TB risk factors identified here are better understood and managed to favor host rather than pathogen outcomes.

Determination of Sites Involved, HIV Co–Infection & Utility of Diagnostic Modalities in EPTB

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. 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. 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. 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.

Mapping the pattern and trends of extrapulmonary tuberculosis

Background and Objectives:There has been a rapid expansion of the directly observed treatment short-term (DOTS) under the revised national tuberculosis control program throughout India in the last decade. Few reports exist detailing individual DOTS centers’ experiences with regard to extrapulmonary tuberculosis (EPTB) in a medical college hospital setting.Materials and Methods:This is a retrospective, record-based study of patients with the diagnosis of EPTB, in all age groups. Data on all consecutive EPTB cases diagnosed at the K. S. Hegde Medical College and Hospital, Deralakatte, Mangalore from 1 January 2005 to 31 December 2011 at the DOTS centre attached to this hospital were collected, analyzed by Mantel-Haenszel Chi square for linear trend and described in proportion or percentages.Results:Among 1267 cases registered for treatment of all forms of tuberculosis, 528 (41.67%) had EPTB. Around half of the cases of EPTB (269, 51%) were among adult age groups and the majority of cases (342, 64.77%) received Category-I treatment. Pleural TB was the commonest type of EPTB (n = 148, 28.03%), followed by lymph node TB (n = 131, 24.81%). Involvement of lymph nodes was the commonest manifestation among the less than 14 years’ age group (27, 58.7%), while involvement of pleura was more common among > 65 years’ age group (23, 45.1%). The difference in the occurrence of EPTB by site between males and females is statistically significant with a P value of <0.005. There is a significant increase in the number of cases of tuberculosis affecting bones and joints, and other forms of tuberculosis over the years.Conclusion:The burden of EPTB is more among the productive age group. Increase in the trend of bone and joint tuberculosis, and other rare forms of EPTB is a point of concern highlighting the importance of strengthening the services towards this group.

Extra-pulmonary tuberculosis infection in the dialysis patients with end stage renal diseases: case reports and literature review

The diagnosis of extra-pulmonary tuberculosis (TB) seems relatively difficult due to the absence of specific symptoms and signs in patients on peritoneal dialysis or hemodialysis. We report four cases of extra-pulmonary tuberculosis on dialysis, with two cases on peritoneal dialysis and two cases on hemodialysis. The presentations, therapy, and outcomes of TB infection in these patients were reviewed. Otherwise, the English literature published in the PubMed database associating extra-pulmonary tuberculosis on dialysis over the last three decades is reviewed. A total of 61 studies containing 70 cases were included. The most common primary disease was diabetic nephropathy (22.86%, 16/70). The peritoneum (31.42%, 22/70), bone (21.42%, 15/70), and lymph node (20%, 14/70) were the most frequently infected. Single organ infection was common (90%, 63/70). Fever (58.57%, 41/70), pain (35.71%, 25/70), and enlarged lymph node (20%, 14/70) were the most common symptoms. Biopsy (67.14%, 47/70) and culture (40%, 28/70) provided most reliable methods for clear diagnosis of tuberculosis. The combined treatment of isoniazid, rifampicin, pyrazinamide, and ethambutol (44.29%, 31/70) was the most common therapy. The majority of patients improved (82.86%, 58/70); however, 12 cases got worse (17.14%), with 10 of them dying (14.29%). Physicians should be aware of the non-specific symptoms and location of infection, and consider tuberculosis in their differential diagnoses in dialysis patients presenting with symptoms such as fever, pain, and weight loss.

Diagnosis of extrapulmonary tuberculosis by polymerase chain reaction for mpb64 gene: An evaluation in a hospital based study

Diagnosis of extrapulmonary tuberculosis by polymerase chain reaction for mpb64 gene: An evaluation in a hospital based study

Diagnostic Performance of Commercially Available Enzyme-Linked Immunosorbent Assay Kit in the Diagnosis of Extrapulmonary Tuberculosis

Objectives:Antibody based serodiagnosis tests for tuberculosis (TB) was used widely in developed and developing countries. Pathozyme Myco® immunoglobulin (Ig) M, IgA, and IgG were evaluated in pulmonary TB in many studies.Materials and Methods:In this study we assessed this commercially available kit in detecting extrapulmonary TB (EPTB).Results:A total of 354 subjects were recruited for the study, of which 217 (61.2%) were EPTB patients and 137 (38.7%) were subjects with no suggestive TB. The mean age was 29.7 ± 13.7 and 31.2 ± 15.2 years, respectively for two groups. Serum samples were tested for IgM, IgA, and IgG using Pathozyme Myco® IgM, IgA, and IgG kit. The individual specificity rates of IgM, IgA, and IgG were 70.8% (95% confidence interval (CI): 62.7-77.7), 77.3% (95% CI: 68.6-83.5), and 68.6%. (95% CI: 60.4-75.7); while their sensitivity was 29% (95% CI: 23.4-35.4), 24.4% (95% CI: 19.1-30.5), and 34.5% (95% CI: 28.5-41.1); respectively.Conclusion:The serological tests either singly or in combination failed or performed poorly to diagnose EPTB.

PCR as a Diagnostic Tool for Extra-Pulmonary Tuberculosis

Extra-Pulmonary Tuberculosis (EPTB) accounts for approximately 40% of the tuberculosis cases. Though it is not communicable, it is a significant cause of morbidity. This study was conducted to know the efficacy of the Polymerase Chain Reaction (PCR) as an additional tool, along with the conventional methods, in the diagnosis of EPTB. Clinical samples were collected from suspected cases of EPTB. The Ziehl-Neelsen staining (ZNS), culture on the Lowenstein-Jensen medium (LJM) and PCR testing with the use of a commercial kit were performed on the homogenized samples. A total of 182 samples which were received for the molecular diagnosis of EPTB were also tested by ZNS and culture on LJM for the presence of Mycobacterium tuberculosis. Of these, 22 were positive by at least one of the tests which were used. PCR detected the maximum number of cases of EPTB, followed by culture. The results of PCR and the conventional tests were analyzed by using McNemar's test for the correlated proportions-the exact method of 'IBM SPSS Statistics 20'. The analysis showed a statistical significance. Whenever they are feasible, using all the available tests in combination increases the laboratory detection rates of M. tuberculosis from clinical samples. PCR must be included in the diagnostic panel of EPTB.

Is diagnostic protocol a cause of overestimation of extra-pulmonary tuberculosis in Himachal Pradesh? A report from a high-prevalence tuberculosis unit

Aims and Objectives: To study the diagnostic practices for diagnosis of extra-pulmonary tuberculosis (EPTB) in a high-prevalence tuberculosis unit (TU). Material and Methods: It was a cross-sectional study using a pre-designed and pre-tested structured questionnaire. The information was collected from new EPTB cases registered in Rampur TU between 1 July 2007 and 31 March 2008. Diagnostic practices of the medical practitioners for establishing the diagnosis of different types of EPTB were studied. Results: For the diagnosis of pleural TB the main tools used were X-ray chest (37 cases; 100.0%) and aspiration of pleural fluid (pleural tap) for color of pleural fluid (35 cases; 94.6%). For establishing the diagnosis of lymph node TB, eight (66.6%) cases were subjected to fine needle aspiration cytology (FNAC) examination of involved lymph nodes. Excision biopsy of lymph nodes was undertaken in the remaining four (33.3%) cases. The diagnosis of abdominal TB was primarily established on the basis of X-ray (six cases; 85.7%) and ultrasonography (USG) of abdomen for the presence of ascites in five (71.4%) cases. The patients of tubercular meningitis were diagnosed predominantly on clinical grounds whereas in bone and genitourinary TB, all appropriate investigations were performed for confirmation of EPTB of these organs. Conclusions: Except for lymph node TB and the patients in whom the diagnosis had been established in tertiary care institutions of the state, patients were being diagnosed on clinical grounds.

Evaluation of Nested Polymerase Chain Reaction for Rapid Diagnosis of Clinically Suspected Tuberculous Pleurisy

Early diagnosis of tuberculosis is important in its control. The conventional techniques like smear microscopy and culture suffer from low sensitivity for diagnosis of extra-pulmonary tuberculosis like Pleural Tuberculosis (PTB) due to paucibacillary nature of the fluid. Polymerase Chain Reaction (PCR) is presently seen as a promising alternative to conventional techniques. In this study we have evaluated IS6110 sequence based nested PCR (nPCR) for the detection of Mycobacterium tuberculosis (MTB) DNA directly from clinical samples. The results of PCR were compared with the results of conventional methods like smear, culture and Adenosine Deaminase (ADA) activity. A total of 50 pleural fluid samples from the patients with history suggestive of tuberculosis were taken. All the samples were processed for Ziehl-Neelsan (ZN) staining for Acid Fast Bacilli (AFB), culture ADA activity and PCR with primers targeting 123bp fragment of IS6110 of MTB complex. A significant difference was seen in the sensitivities of conventional methods and PCR (p<0.05). Out of these 50 samples 3 were positive by smear, culture was positive in 5 samples, 21 samples showed high ADA activity and 29 were positive by PCR with overall 100% sensitivity of PCR using culture on LJ media as gold standard. The combined analysis of nPCR, ADA activity and other lab investigations can be very useful in the rapid diagnosis in cases of PTB.

Comparisons among the diagnostic methods used for the detection of extra-pulmonary tuberculosis in Bangladesh

The present study was an attempt to establish a suitable method for the effective diagnosis of extra-pulmonary tuberculosis in Bangladesh. In this regard, detection of Mycobacterium tuberculosis from 390 different extra-pulmonary specimens was performed by Bright-Field microscopy, light-emitting diode fluorescence microscopy and Lowenstein–Jensen culture methods, followed by an extensive comparison among these methods. M. tuberculosis was detected in 53 cases through the conventional Lowenstein–Jensen culture method; 49 cases were detected under Bright-Field microscope, whereas the light-emitting diode fluorescence microscopy detected 64 cases. Out of 53 culture-positive isolates, 12 were found to be multi-drug resistant. Light-emitting diode fluorescence microscopy was found to be more sensitive and effective than both the Bright-Field microscopy and the Lowenstein–Jensen culture methods. Incidentally, light-emitting diode fluorescence microscopy appeared imperative to detecting the multi-drug resistant tuberculosis.

Extrapulmonary mycobacterial infections in a cohort of HIV-positive patients: ultrasound experience from Vicenza, Italy

Extrapulmonary tuberculosis (EPTB) is frequently seen in human immunodeficiency virus (HIV)-infected individuals in Sub-Saharan Africa and recent work has shown point-of-care (POC) ultrasound to be a diagnostic aid in the resource-limited, highly endemic setting. Its role in industrialized countries, however, has rarely been studied. With international migration, EPTB is increasingly seen in European hospitals. This study reports ultrasound findings and discusses the diagnostic relevance of EPTB in an industrialized country setting. In this retrospective study, we describe a cohort of 27 patients with a predominantly immigrant background diagnosed with HIV and EPTB in Northern Italy and evaluate the role of ultrasound in their clinical management. All inpatient files of HIV-positive individuals admitted to our hospital with culture-proven diagnosis of EPTB were reviewed, along with chest X-rays and ultrasound studies. The outcome and results of long-term follow-up were extracted. A total of 243 HIV-positive inpatients were identified between January 2005 and November 2011. Twenty-seven of the patients [11.1 %, 95 % confidence interval (CI) 7.4-15.7] were diagnosed with EPTB. Ultrasound showed a typical pattern of enlarged abdominal lymph nodes and focal lesions in the spleen and liver in 22 patients (81.5 %, 95 % CI 7.4-15.7) and, thus, helped to raise the suspicion of mycobacterial infection. As disseminated mycobacterial infections in HIV-positive patients can be treated effectively if diagnosed early, and typical sonographic findings are seen in the majority of these patients, we suggest that POC ultrasound should be integrated in diagnostic and screening algorithms for EPTB in developed countries.

Interferon-gamma release assays for the diagnosis of extrapulmonary tuberculosis: a systematic review and meta-analysis

Interferon -gamma release assays (IGRAs) provide a new diagnostic method for Mycobacterium tuberculosis (TB) infection. However, the diagnostic value of IGRAs for extrapulmonary TB (EPTB) has not been clarified. We searched several databases and selected papers with strict inclusion criteria, evaluated the evidence of commercially available IGRAs (QuantiFERON(®) -TB Gold QFT-G or QFT-GIT and T-SPOT(®) .TB) on blood and the tuberculin skin test (TST) using random effects models. Twenty studies with 1711 patients were included. After excluding indeterminate results, pooled sensitivity for the diagnosis of EPTB was 72% [95% confidence interval (CI) 65-79%] for QFT-G or GIT and 90% (95% CI, 86-93%) for T-SPOT; in high-income countries the sensitivity of QFT-G or GIT (79%, 95% CI 72-86%) was much higher than that (29%, 95% CI 14-48%) in low/middle-income countries. Pooled specificity for EPTB was 82% (95% CI 78-87%) for QFT-G or GIT and 68% (95% CI 64-73%) for T-SPOT. Pooled sensitivity of TST from four studies in high-income countries was lower than that of IGRAs. T-SPOT was more sensitive in detecting EPTB than QFT-G or GIT and TST. However, both IGRAs and TST have similar specificity for EPTB. IGRAs have limited value as diagnostic tools to screen and rule out EPTB, especially in low/middle-income countries. The immune status of patients does not affect the diagnostic accuracy of IGRAs for EPTB.

Diagnosis of extrapulmonary tuberculosis by PCR

During the last two decades, the resurgence of tuberculosis (TB) has been documented in both developed and developing nations, and much of this increase in TB burden coincided with human immunodeficiency virus (HIV) epidemics. Since then, the disease pattern has changed with a higher incidence of extrapulmonary tuberculosis (EPTB) as well as disseminated TB. EPTB cases include TB lymphadenitis, pleural TB, TB meningitis, osteoarticular TB, genitourinary TB, abdominal TB, cutaneous TB, ocular TB, TB pericarditis and breast TB, although any organ can be involved. Diagnosis of EPTB can be baffling, compelling a high index of suspicion owing to paucibacillary load in the biological specimens. A negative smear for acid-fast bacilli, lack of granulomas on histopathology and failure to culture Mycobacterium tuberculosis do not exclude the diagnosis of EPTB. Novel diagnostic modalities such as nucleic acid amplification (NAA) can be useful in varied forms of EPTB. This review is primarily focused on the diagnosis of several clinical forms of EPTB by polymerase chain reaction (PCR) using different gene targets.

Evaluation of Real Time PCR for the diagnosis of Extrapulmonary Tuberculosis and comparison with AFB Microscopy among Bangladeshi population

Tuberculosis is a global public health issue and a disease burden in Africa and Asia. Bangladesh is one of the high burden countries in Southeast Asian region. Mycobacterium tuberculosis the causative agent of tuberculosis, is a devastating bacterium because it spreads person to person, acquired multiple antibiotic resistance and most importantly has the limitation in rapid diagnosis, specially in case of extrapulmonary infection. Here we showed Real-Time PCR assay with the primers targeting IS6110 is a better method than conventional AFB microscopy for the diagnosis of extrapulmonary tuberculosis. For the comparative study 99 extrapulmonary specimens from 9 different parts of the body were collected from suspected patients. Among those only 10 samples were positive, where 50% them were scanty positive in AFB microscopy, on the other hand 33 samples were positive in Real–Time PCR assay. All samples positive in AFB microscopy were also positive in Real-Time PCR assay with an additional 23 positive. Higher percentage of positive results were found in Real-Time PCR analysis in all the samples except Percutaneous nephrostomy (PCN) fluid and Pus. The sharp differences in the result indicate the effectiveness and of the Real-Time PCR assay over the conventional AFB microscopy. High precision and accuracy make it better choice as a diagnostic method for the diagnosis of extrapulmonary tuberculosis. DOI: http://dx.doi.org/10.3329/ijns.v2i1.10880 International Journal of Natural Sciences (2012), 2(1): 26-32

Super-paramagnetic iron oxide nanoparticles for use in extrapulmonary tuberculosis diagnosis

The limited sensitivity of serological tests for mycobacterial antigens has encouraged the development of a nanoparticle probe specific for the extrapulmonary form of Mycobacterium tuberculosis (Mtb). We developed an innovative probe comprised of super-paramagnetic iron oxide (SPIO) nanoparticles conjugated with Mtb surface antibody (MtbsAb-nanoparticles) to provide ultrasensitive imaging of biomarkers involved in extrapulmonary Mtb infection. MtbsAb-nanoparticles were significantly conjugated with Mtb bacilli. The extent of contrast enhancement reduction on magnetic resonance imaging (MRI) for Mtb and human monocytic THP1 cells was proportional to the concentration of MtbsAb-nanoparticles. When MtbsAb-nanoparticles were intravenously injected into mice bearing Mtb granulomas, the granulomatous site showed a 14-fold greater reduction in signal intensity enhancement on T2-weighted MR images compared with an opposing site that received PBS injection. Mtb sAb-nanoparticles represent a new non-invasive technology for the diagnosis of extrapulmonary Mtb.

Diagnosis of extrapulmonary tuberculosis using the Xpert® MTB/RIF assay

Evaluation of: Tortoli E, Russo C, Piersimoni C et al. Clinical validation of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis. Eur. Respir. J. doi:10.1183/09031936.00176311 (2012) (Epub ahead of print).The Xpert® MTB/RIF assay has been CE-marked for rapid molecular diagnosis of TB in Europe and has been endorsed by the WHO as a replacement for sputum smear microscopy for diagnosis of pulmonary TB in low- and middle-income countries. However, few data are available to inform recommendations for use of the assay for testing nonsputum clinical samples when investigating suspected extrapulmonary TB (EPTB). We review and discuss the findings of Tortoli and colleagues, who evaluated the assay used for this purpose in a large study of adults and children in Italy. They provide a per-sample analysis of 268 diagnoses of EPTB at a range of anatomic sites (sensitivity: 81.3%; 95% CI: 76.2–85.8) and data for 1206 samples in which EPTB was excluded (specificity: 99.8%; 95% CI: 99.4–100). We discuss how this paper forms an important addition to the growing body of literature demonstrating the utility of Xpert MTB/RIF for EPTB diagnosis when applied to diverse types of clinical samples.

Rapid diagnosis of extra pulmonary tuberculosis by automated Xpert MTB/RIF assay

Although extra pulmonary tuberculosis accounts for only 10-15% of tuberculosis in India, they have high morbidity and mortality because of lack of good diagnostic methods. One of the recent molecular methods namely the Xpert MTB/RIF is a fully automated real time PCR system that detects M. tuberculosis (Mtb) complex and rifampicin resistance directly from clinical samples. This assay has been extensively evaluated in the diagnosis of pulmonary tuberculosis. The purpose of this study was to test the efficiency of this assay for the rapid and reliable diagnosis of extra pulmonary tuberculosis (EPTB).

Detection of 123 bp fragment of insertion element IS6110 Mycobacterium tuberculosis for diagnosis of extrapulmonary tuberculosis

Purpose: Extrapulmonary tuberculosis (EPTB) is emerging problem in developing and developed countries. The diagnosis of EPTB in its different clinical presentations remains a true challenge. IS6110-based polymerase chain reaction (PCR) is used for rapid identification and positivity rate of the Mycobacterium tuberculosis complex in clinical isolates of different sites of EPTB. The present study was carried out to study the prevalence of M. tuberculosis complex in clinical isolates of EPTB at tertiary care centres in Lucknow. Materials and Methods: Seven hundred fifty-six specimens were collected from the suspected cases of EPTB which were processed for Mycobacteria by Ziehl Neelson (ZN) staining and BACTEC culture. All the specimens were also processed for IS6110-based PCR amplification with primers targeting 123 bp fragment of insertion element IS6110 of the M. tuberculosis complex. Results: Of these 756 specimens, 71(9.3%) were positive for acid fast bacilli (AFB) by ZN staining, 227(30.1%) were positive for mycobacteria by BACTEC culture and IS6110 PCR were positive for M. tuberculosis complex in 165 (20.7%) isolates. We found a significant difference in sensitivities of different tests (P<0.05). Conclusions: This study reveals the positivity of M. tuberculosis complex in clinical isolates of EPTB case in tertiary care hospitals in Northern India. 72.7% of M. tuberculosis complex was confirmed by IS6110-PCR in culture isolates from different sites of EPTB. The high prevalence of the M. tuberculosis complex was seen in lymph node aspirate and synovial fluid. However, utility of PCR may play a potentially significant role in strengthening the diagnosis of EPTB especially targeting IS6110.

Disseminated tuberculosis presenting as irido-ciliary granuloma in an immunocompetent patient

Dear Editor,The diagnosis of extra-pulmonary tuberculosis can be chal-lenging, even in highly endemic countries. We report a caseof irido-ciliary granuloma, where initial screening for TBwas negative, but further investigations revealed multipleorgan involvement with acid-fast bacillus (AFB), confirmedas Mycobacterium tuberculosis (MTB) by polymerase chainreaction (PCR).Case report A17-year-oldboypresentedwithreducedvisionin the right eye for 2 months. Best corrected visual acuity(BCVA)wascountingfingers2mand6/6intherightandlefteyes, respectively. Intra-ocular pressures were in the right18 mmHg and left 16 mmHg. Slit lamp examination of theright eye showed mutton fat keratic precipitates and multipledensely vascularized granulomatous lesions on the anteriorsurface of iris that seemed to arise from angle of anteriorchamber (Fig. 1a). A vascularized scleral nodule, with sur-rounding ciliary congestion, was noted near the inferior lim-bus. The right fundus was not visible. The left eye showedoptic disc edema, but no other inflammatory signs. B scanultrasonography of the right eye showed disc edema, but notchoroidalthickeningorvitreousechoes.Ultrasoundbiomicro-scopy of the right eye showed the iris lesion extending intociliary body and then onto sclera (Fig. 1b).Systemic examination revealed left submandibular lymph-adenopathy(non-tender,matted,rubberyconsistency;Fig.1c).Based on the above findings, we diagnosed irido-ciliary gran-uloma with scleral extension in the right eye, associated withcervical lymphadenopathy of likely tubercular aetiology, andprobable raised intracranial pressure. However, the tuberculintest was negative (4 mm induration with 5TU) and chestradiogram was normal. Fine needle aspiration cytology of thesubmandibular lymphnodeshowed mixed population of reac-tivelymphoidcellswithscatteredhistiocytesandplasmacells.There was no evidence of epithelioid granulomas or caseousnecrotic material. Ziehl–Neelsen stain was negative for AFB.We therefore biopsied the scleral nodule that revealed well-formedgranulomascomposedofep ithelioidhistiocytes,chroniclymphomononuclear cells and plasma cells and on 20 % acid-fast staining showed scattered AFB in the tissue (Fig. 1d). PCRshowed positive for MTB with three different gene targets(IS6110, MPB64 and protein B).Subsequently,computedtomography(CT)ofheadshowedmultiple ring enhancing lesions in the brain parenchyma(Fig. 1e). CT thorax showed a small non-cavitatory lesionin the left lung (apical lobe, Fig. 1f). Sputum tested positivefor AFB. ELISA for HIV was negative. Based on neurolo-gist’s recommendation, we initially treated the patient withintravenous dexamethasone (to reduce risk of paradoxicalworsening of brain lesions) for 3 days, followed by five-drug ATT (anti-tubercular therapy —isoniazid, rifampicin,ethambutol,pyrazinamideandstreptomycin)andoralcortico-steroids(1mg/kg/day,tapered).Irido-ciliarygranuloma,opticdiscedema and cervicallymphadenopathy gradually resolvedover the next 2 months (Fig. 1g). BCVA of the right eyeimproved to 20/60. Thereafter, ATTwas changed to isoniazidandrifampicinforanother7months—rightBCVAwas20/50,andirislesionshadcompletelyresolvedwithminimalresidualfibrosis.Comment Disseminated TB refers to involvement of twoor more non-contiguous sites and is commonly associatedwith immune-compromised state [1]. This case illustrateswidespread dissemination of MTB (lung, eye, brain andlymph nodes) in animmunocompetent patient thatpresented

Site of Extrapulmonary Tuberculosis is Associated with HIV Infection

In the United States, the proportion of patients with extrapulmonary tuberculosis (EPTB) has increased relative to cases of pulmonary tuberculosis. Patients with central nervous system (CNS)/meningeal and disseminated EPTB and those with human immunodeficiency virus (HIV)/AIDS have increased mortality. The purpose of our study was to determine risk factors associated with particular types of EPTB. We retrospectively reviewed 320 cases of EPTB from 1995-2007 at a single urban US public hospital. Medical records were reviewed to determine site of EPTB and patient demographic and clinical characteristics. Multivariable logistic regression analyses were performed to determine independent associations between patient characteristics and site of disease. Patients were predominantly male (67%), African American (82%), and US-born (76%). Mean age was 40 years (range 18-89). The most common sites of EPTB were lymphatic (28%), disseminated (23%), and CNS/meningeal (22%) disease. One hundred fifty-four (48.1%) were HIV-infected, 40% had concomitant pulmonary tuberculosis, and 14.7% died within 12 months of EPTB diagnosis. Multivariable analysis demonstrated that HIV-infected patients were less likely to have pleural (adjusted odds ratio [AOR] 0.3; 95% confidence interval [CI] .2, .6) as site of EPTB disease than HIV-uninfected patients. Among patients with EPTB and HIV-infection, patients with CD4 lymphocyte cell count <100 were more likely to have severe forms of EPTB (CNS/meningeal and/or disseminated) (AOR 1.6; 95% CI, 1.0, 2.4). Among patients hospitalized with EPTB, patients coinfected with HIV and low CD4 counts were more likely to have CNS/meningeal and disseminated disease. Care for similar patients should include consideration of these forms of EPTB since they carry a high risk of death.