Treatment Of Extrapulmonary Tuberculosis Research Articles

259. Long-term Transcriptomic Changes in the CD4 T cells Following Treatment of Extrapulmonary Tuberculosis

Abstract Background The adaptive immune system is known to be responsible for maintain long-term immune memory in an antigen-specific manner. However, recent studies have shown that in chronic infections such as CMV, HCV, and HIV, long-lasting modifications can occur in immune cells without antigen specificity. In the present study, we longitudinally investigated transcriptional characteristics of CD4+ T cells in extrapulmonary tuberculosis (EPTB) before, during and after anti-tuberculosis treatment. Methods Peripheral blood mononuclear cells were isolated from patients with EPTB at three time points: before treatment (0 months), during treatment (2 months), and after treatment (6-8 months). Single-cell libraries were generated using Chromium Single Cell 3’ Library & Gel Bead Kit v3 (10X Genomics), and sequenced. The sequencing data were aligned to the reference human genome (GRCh38). The analysis was performed using R (v4.2.1). Results We performed unsupervised clustering to classify a total of 49,317 cells into five major cell types, including T cells, B cells, NK cells, Monocytes, and Dendritic cells. Among 14,845 CD4+ T cells, we identified seven different subclusters according to highly variable genes. Comparison of the proportion of each CD4+ T cell cluster between healthy donors and patients with EPTB at different time points revealed an increased proportion of ‘Cluster 1’ in EPTB, even after anti-tuberculosis treatment. We calculated cluster-specific differentially expressed genes (DEGs) and found that ‘Cluster 1’ was characterized by up-regulation of FOS, JUN, FOSB, JUNB, NFKBIA, NFKBIZ, SOCS3, SGK1, AREG. Protein interaction network analysis of selected top 30 up-regulated genes in each cluster revealed the Activation protein 1 (AP-1) family genes were core genes of ‘Cluster 1’. Gene set enrichment analysis according to DEGs of CD4+ T cells revealed that AP-1 pathway gene sets in Pathway interaction database were down-regulated in healthy donor, while up-regulated in EPTB patients before, during, and after treatment. Single-cell transcriptomes of PBMCs from extrapulmonary tuberculosis. (A) Schematic representation of the experimental protocols. (B) Unbiased UMAP projection of 49,317 PBMCs colored by cell type information. (C) Dot plots showing the average normalized expression of marker genes in each cell cluster. (D) tSNE projection of 14,845 CD4+ T cells of healthy donor and patients with extrapulmonary tuberculosis. (E) Heatmap of cluster-specific differentially expressed genes for each CD4+ T cell cluster. (F) The proportion of cluster 1 cells in CD4+ T cells. (G) A network plot representing upregulated genes in cluster 1 CD4+ T cells. (H) Gene sets enrichment analysis of AP1 pathway in cluster 1 CD4+ T cells at different time points after anti-tuberculosis treatments. Conclusion Our study revealed that CD4+ T cell transcriptomic changes associated with the AP-1 pathway persisted in patients with EPTB even after treatment. Further research is required to determine the clinical implication of these transcriptomic changes. Disclosures All Authors: No reported disclosures

Synchronous anal mucinous adenocarcinoma and anal tuberculosis presenting as chronic anal fistula: Challenging management

Metachronous anal tuberculosis to an anal adenocarcinoma is an exceptional condition. The aim of our study was to report management of the first case of synchronized anal canal adenocarcinoma and anal canal tuberculosis and report our multidisciplinary approach. A 71-year-old man was admitted for non-healing anal fistula. Rectal examination at supine position showed an ulcerative growth at the medio-superior quadrant on a radius of 2cm from the anal verge. Digital rectal examination assessed no tumor in the anorectum. Biopsy of fistulae confirmed diagnosis of anal mucinous adenocarcinoma with coexisting anal tuberculosis. Further exploration confirmed diagnosis with no distal metastasis, no active pulmonary tuberculosis and no immunodepression. Adjuvant anti-bacillary chemotherapy was initiated 1 month prior to adjuvant radio-chemotherapy. Patient was re-admitted at the 6th week following the last dose of radio-chemotherapy for surgery. On long-term evaluation at 10 months, the patient reported absence of symptoms with weight gain. Association of both entities is rare. Chronic inflammatory damage may possibly initiate a sequence of metaplasia and dysplasia, resulting in neoplastic transformation. Anal canal adenocarcinoma treatment follows same guidelines as rectal cancer. Extra-pulmonary tuberculosis treatment follows anti-bacillary protocol with consequent side effects. Therefore, our case is a unique clinical challenge for physicians. Management decision was multidisciplinary process. Their pathophysiology relationship is yet to be understood. Moreover, each entity has defined and individual therapeutic protocols and indications. All this taken into consideration, such case presents a clinical and therapeutic challenge for physicians.

Tuberculosis in adulthood - The Sk2-Guideline of the German Central Committee against Tuberculosis (DZK) and the German Respiratory Society (DGP) for the diagnosis and treatment of adult tuberculosis patients

In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany.

A 17-Year-old Boy With Nodular Lesions in the Thyroid and Lymphadenopathy.

A 17-Year-old Boy With Nodular Lesions in the Thyroid and Lymphadenopathy.

Predictors of extrapulmonary tuberculosis among diabetic patients at Debre Markos compressive specialized hospital, Ethiopia, 2021: A retrospective cohort study

BackgroundExtrapulmonary tuberculosis is an emerging public health problem among diabetic patients. Diabetes, which causes immunosuppression, is increasingly being recognized as an independent risk factor for tuberculosis, and the two often coexist and impact each other. Therefore, this study aimed to investigate the incidence and predictors of extra pulmonary tuberculosis among diabetic patients at Debre Markos referral hospital, Northwest Ethiopia. MethodsThis institutionally-based retrospective cohort study was undertaken among 433 diabetic patients of Debre Markos compressive specialized hospital between January 2016 to December 2020. All eligible diabetic patients who full filled the inclusion criteria were included in the study. Data were entered using Epi-data Version 3.1 and analyzed using STATA Version 14. The survival time of diabetic patients was estimated using the Kaplan-Meier survival curve, and the survival time between different categorical variables was compared using the log rank test. Both bi-variable and multivariable Cox-proportional hazard regression models were fitted to identify independent predictors of tuberculosis among diabetic patients. ResultsAmong a cohort of 433 diabetic patients at Debre Markos compressive specialized hospital, 17(3.9%) developed extra pulmonary tuberculosis during the follow-up time. The total time allotted to follow up the study participants was 1101.5 person-years (PY). The overall extra pulmonary tuberculosis incidence rate was 1.5 per 100 PY with 95% CI. Using the multivariable Cox-regression analysis, age (AIR 4.8 (95% CI (1.2–20.7), 0.03), diabetic medication (AIR 1.4 (95% CI(1.24–16), 0.03), having past history of PTB before diabetic follow up initiation (AID 1.5(95% CI (3.2–6.9),0.01) and having history of alcohol (AIR (95%CI (4(1.2–13),0.02) were significantly increased the risk of extra pulmonary tuberculosis while BMI (18.5–25) AIR(95% CI (0.22 (0.06–0.76), 0.02) was associated with a rate reduction for the incidence of extra pulmonary tuberculosis. ConclusionsIn this study, we found a high rate of extra pulmonary tuberculosis among diabetic patients. Factors significantly linked with increased risk of extra pulmonary tuberculosis included: age, using insulin as hypoglycemic medication, having past history of PTB before diabetic follow up initiation and alcoholic history while BMI was associated with a rate reduction of EPTB. Early screening and treatment for extra pulmonary tuberculosis is highly recommended at diabetes mellitus follow up for patients with the above risk factors.

Incidence, risk factors and clinical characteristics of extra-pulmonary tuberculosis patients: a ten-year study in the North of Iran.

To determine the incidence of extra-pulmonary tuberculosis (EPTB) and examine the risk factors and the clinical features of the disease over a ten-year period. Retrospective study of records of patients who were followed and registered in the TB registry programme in the health district of Gorgan, Iran from January 1, 2008, through December 31, 2017. Among 2280TB records, 609 (26.71%) were EPTB. They were mostly female patients (53.7%) and residents in rural areas (56.5%) with a mean age of 40.55years [±16]. The average age of female patients (37.55years [±16.99]) was lower than of male patients (44.07years [±20.59]). The median of the incidence rate was 7.5 per 100000 inhabitants for EPTB; biopsy and pathology were the best methods for the detection of EPTB. The most frequent forms of EPTB were lymphatic TB (193/609=31.7%) and pleural TB (158/609=25.9%). In most cases (245/609=40.2%), one to three months elapsed between occurrence of symptoms and final confirmation of EPTB. The outcome of EPTB was weaker than of pulmonary TB (PTB). Our most important finding was the increasing incidence of EPTB, which shows the importance of attention to this disease. Lymph node and pleural tissue were the most commonly infected tissues. Skeletal TB presents a challenge in the diagnosis and treatment of EPTB.

Isoniazid Induced Toxic Epidermal Necrolysis in a HIV Positive Patient during Treatment for Extra Pulmonary Tuberculosis: A Case Report

Isoniazid Induced Toxic Epidermal Necrolysis in a HIV Positive Patient during Treatment for Extra Pulmonary Tuberculosis: A Case Report

Prospective Serial FDG PET/CT During Treatment of Extrapulmonary Tuberculosis in HIV-Infected Patients

The aim of this study was to prospectively describe evolution of F-FDG uptake of extrapulmonary tuberculosis (TB) throughout the course of TB treatment in HIV patients to evaluate F-FDG PET/CT as a monitoring tool of treatment response. We performed baseline FDG PET/CT, PET-2 after 2 months, and PET-3 at the end of TB treatment in 18 HIV/TB patients. We correlated evolution of FDG uptake with clinical outcome of patients. After 2 months of treatment, 78% of the patients had a significant metabolic response. Lymph node (LN) metabolic response was heterogeneous, with 57% of LN sites showing decreased SUVmax and 41% showing unchanged FDG uptake. Organs other than LNs showed more homogeneous response. The FDG PET/CT performed at the end of TB treatment showed a complete response of all infected organs and a drastic response in terms of active LNs in 95% of the patients (SUVmax mean decrease = 85%, median = 100%). A complete metabolic response after TB treatment was seen in only 47% of patients. In difficult-to-treat entities such as extrapulmonary TB in HIV patients, FDG PET/CT is a potential tool in monitoring TB treatment response and should be explored in larger studies.

Risk factors for extrapulmonary dissemination of tuberculosis and associated mortality during treatment for extrapulmonary tuberculosis

Many environmental, host, and microbial characteristics have been recognized as risk factors for dissemination of extrapulmonary tuberculosis (EPTB). However, there are few population-based studies investigating the association between the primary sites of tuberculosis (TB) infection and mortality during TB treatment. De-identified population-based surveillance data of confirmed TB patients reported from 2009 to 2015 in Texas, USA, were analyzed. Regression analyses were used to determine the risk factors for EPTB, as well as its subsite distribution and mortality. We analyzed 7007 patients with exclusively pulmonary TB, 1259 patients with exclusively EPTB, and 894 EPTB patients with reported concomitant pulmonary involvement. Age ≥45 years, female gender, human immunodeficiency virus (HIV)-positive status, and end-stage renal disease (ESRD) were associated with EPTB. ESRD was associated with the most clinical presentations of EPTB other than meningeal and genitourinary TB. Patients age ≥45 years had a disproportionately high rate of bone TB, while foreign-born patients had increased pleural TB and HIV+ patients had increased meningeal TB. Age ≥45 years, HIV+ status, excessive alcohol use within the past 12 months, ESRD, and abnormal chest radiographs were independent risk factors for EPTB mortality during TB treatment. The epidemiologic risk factors identified by multivariate analyses provide new information that may be useful to health professionals in managing patients with EPTB.

Delays in diagnosis and treatment of extrapulmonary tuberculosis in Guatemala

A 23-year-old indigenous Guatemalan man presented in 2016 to our clinic in Sololá, Guatemala, with 10 months of recurrent neck swelling, fevers, night sweats and weight loss. Previously, he had...

Cellular Architecture of Spinal Granulomas and the Immunological Response in Tuberculosis Patients Coinfected with HIV.

Mycobacterium tuberculosis (M.tb) and HIV are individually responsible for the most deaths worldwide among all infectious agents, and coinfection with M.tb and HIV is a significant public health challenge in the developing world. Although the lung is the primary target organ for tuberculosis (TB), M.tb can also cause extrapulmonary tuberculosis (EPTB) such as in the bones and joints. Treatment of EPTB is much more challenging than treatment of pulmonary TB. The hallmark of the host immune response against TB is the formation of organized structures called granulomas that are infiltrated with immune cells and are rich in cytokines and chemokines. Inside granulomas, the host confines the M.tb bacteria to a particular region of the organ and avoids dispersion. In this study, we analyzed immune cells in bone granulomas of patients with EPTB that are also coinfected with HIV. We found that HIV-infected TB patients have dispersed bone granulomas, with reduced T cell numbers and a concomitant increase in plasma cells. Additionally, HIV-infected patients exhibited dramatically increased serum levels of IgM and IgG1 antibodies, which is indicative of T-cell-independent B-cell activation and mucosal T-cell activation, respectively. Interestingly, we also observed that CD29+ stem cells are increased in HIV–TB coinfection, suggesting a link with HIV infection. Therefore, our work provides new insights into the architecture of spinal TB granulomas and the role of B-cells and humoral immunity against a highly infectious intracellular pathogen. We propose that our findings will inform biomarker identification for EPTB and possibly the development of related therapeutics and/or vaccines to protect HIV-infected patients against disseminated TB.

46-Year-Old Man With Lower Back Pain

46-Year-Old Man With Lower Back Pain

Analysis of infection and drug-resistance in 6 107 cases of extrapulmonary tuberculosis in Chengdu area

Objective: To analyze the infection and drug resistance of extrapulmonary tuberculosis, in order to provide useful references for prevention and treatment of tuberculosis (TB). Methods: A total of 6 107 suspected cases of extrapulmonary tuberculosis, including lymph node, pleural, peritoneal, meningeal, urinary tract, and bone tuberculosis, were collected retrospectively from January 2013 to December 2015 in Public Health Clinical Center of Chengdu. There were 4 033 male and 2 074 female patients, and the average age was 37 years.The epidemiological data, infection and drug resistance were analyzed statistically. Results: There were 21 036 cases of mycobacterial culture from January 2013 to December 2015, of which 7 119 were positive(33.8%). Extrapulmonary tuberculosis was found in 6 107 cases, of which 896 were positive, accounting for 12.6% of the positive cases(896/7 119). Culture-positive cases of extra-pulmonary tuberculosis showed a rising trend from 2013 to 2015 (n=174, 310, 421, respectively), and the annual average increasing rate was over 50%.Cases were distributed at younger ages (21-40 years), with an average age of 34 years.There were more male patients, with a male to female ratio of 2.1∶1. The most common site of extrapulmonary tuberculosis was the bone(62/243, 25.5%), followed by lymph node(283/1 297, 21.8%), pleural(289/1 840, 15.7%), urinary tract(63/452, 13.9%), peritoneum(41/303, 13.5%), meningeal(156/1 915, 8.1%)and other types of tuberculosis(2/57, 3.5%). Drug sensitivity test of 896 extrapulmonary tuberculosis strains showed that the resistance rate (from high to low) was in the order of isoniazid, rifampicin, streptomycin, ofloxacin, ciprofloxacin, amikacin, capreomycin and ethambutol. Multidrug-resistant(MDR)and extremely-drug resistant (XDR) rate was 9.7 %(87/896)and 2.0%(17/896)respectively. Conclusions: Cases of extrapulmonary tuberculosis sent for bacterial culture and the positive rate showed a rising trend by years in Chengdu area.The drug resistance level was higher than that reported both in China and abroad.The prevention and treatment of extrapulmonary tuberculosis should be strengthened in this area.

Reduction in extrapulmonary tuberculosis in context of antiretroviral therapy scale-up in rural South Africa

Scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has reduced the incidence of pulmonary tuberculosis (PTB) in South Africa. Despite the strong association of HIV infection with extrapulmonary tuberculosis (EPTB), the effect of ART on the epidemiology of EPTB remains undocumented. We conducted a retrospective record review of patients initiated on treatment for EPTB in 2009 (ART coverage <5%) and 2013 (ART coverage 41%) at four public hospitals in rural Mopani District, South Africa. Data were obtained from TB registers and patients' clinical records. There was a 13% decrease in overall number of TB cases, which was similar for cases registered as EPTB (n = 399 in 2009 vs. 336 in 2013; P < 0·01) and for PTB (1031 vs. 896; P < 0·01). Among EPTB cases, the proportion of miliary TB and disseminated TB decreased significantly (both P < 0·01), TB meningitis and TB of bones increased significantly (P < 0·01 and P = 0·02, respectively) and TB pleural effusion and lymphadenopathy remained the same. This study shows a reduction of EPTB cases that is similar to that of PTB in the context of the ART scale-up. The changing profile of EPTB warrants attention of healthcare workers.

Clinical Profile of Patients with Extrapulmonary Tuberculosis at a Tertiary Care Hospital, New Delhi

Background: Tuberculosis is a serious health problem worldwide and constitutes the main infectious cause of death. There are two types of clinical manifestation of tuberculosis are pulmonary tuberculosis and extrapulmonary tuberculosis. Apart of this, extra pulmonary tuberculosis, highly vascular areas such as lymph nodes, kidneys, spine, eyes, bones etc are commonly affected. Methods: The aim of the present study was carried out to determine the clinical profile of patients presenting with EPTB. The diagnosis of extrapulmonary tuberculosis relies on the detection of the causative organism after Staining technique for AFB ZealNeelsons method, Ultrasonography of abdomen, Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Results: Our study comprised of 151 individuals, out of whom EPTB showed similar preponderance in males and females. Maximum patients were in the age group 21-30years. Mean age of the study patients was 38.9 years with a standard deviation of 16.5 years. lymphadenitis as the most common form of EPTBin both males and females, followed by pleura, bones & joints, brain & Meninges, Miliary TB and TB abscess. Histopathology is the most commonly used method of diagnosis, followed by chest X ray. Past history of pulmonary TB and concurrent pulmonary TB are more chances to get the EPTB, 4(2.66%) patients had HIV seropositivity. DTB was found to be the commonest EPTB in HIV co-infected patients. Conclusions: In developing countries, the proportion of EPTB is relatively higher. Thus, based on our study there is a need to develop novel diagnostic techniques for appropriate treatment of extra pulmonary tuberculosis and to prevent its complications. Moreover, the treatment should be recommended by the WHO.

PATHOMORPHOSIS OF EXTRAPULMONARY TUBERCULOSIS IN CHILDREN

Aim. To study clinical and epidemiological aspects of pathomorphosis of extrapulmonary tuberculosis clinical forms. Materials and Methods. Retrospective analysis of 138 case histories in children aged to 15 years, obtaining extrapulmonary tuberculosis treatment in a specialized children's hospital during 1988-2015 was carried out. Among them, in 103 children, clinical forms of extrapulmonary tuberculosis combined with respiratory tuberculosis and in 35 children independent forms of extrapulmonary tuberculosis were found. Studied stage (1988-2015) was divided into 3 periods: I – 1988-1997, II – 1998-2007, III – 2008-2015. During 2008-2015, incomparison to previous periods, the number of cases of peripheral lymph node tuberculosis (PLN), meninges and central nervous system tuberculosis, bones and joints tuberculosis, and ocular tuberculosis decreased. In 2008-2015, the share of combined forms of meninges and central nervous system tuberculosis and ocular tuberculosis remained at 1998-2007 level. During 2008-2015, skin tuberculosis was not diagnosed. Nevertheless, in 2008-2015, in6.8±10.2 % of cases extrapulmonary tuberculosis combined with miliary tuberculosis, and in 5.8±10.4 % of cases the process characterized by lethal outcome, moreover 4.9±10.7% from them – in recent years. It is important that during period I, in 19.6±13.2 % of cases extrapulmonary tuberculosis combined with respiratory tuberculosis in reverse development phases, during period II – in 12.9±19.3 % of cases, during period III – in 23.8±21.2 % of cases. Conclusion. Despite the reduction, extrapulmonary tuberculosis combined with severe forms of respiratory tuberculosis, which led to lethal outcome in children in 5.8±10.4% of cases. Tuberculosis epidemiological situation worsening, reversion of severe forms of tuberculosis with the development of extrapulmonary one and several organs injuries in children shows the necessity of social, preventive and therapeutic measures intensification among children.

Factors associated with mortality in extrapulmonary tuberculosis patients at a teaching hospital in Ghana

Objectives : To investigate the clinical manifestations and factors associated with mortality in patients with extrapulmonary tuberculosis (EPTB) at the Korle-Bu Teaching Hospital Chest Clinic in Accra, Ghana. Design : We conducted a retrospective chart review of patients treated for EPTB at the Chest Clinic between January 1, 2009 and December 31, 2011. Patients with a new diagnosis of EPTB without concomitant pulmonary disease, aged 18 years or older, and who were treated at the Chest Clinic were eligible for participation in the study. Relevant data were abstracted from medical records and entered into a database. The factors associated with mortality were examined using bivariate and multivariate analysis. Results : Of the 157 patients in the study, the most affected age group was 25-34 years old (33.1%), 57.3% were male, and 71 (55.5%) of the 128 patients tested for HIV were sero-positive. Overall, 62 (39.5%) died during EPTB treatment. Mortality was associated with disseminated TB (AOR 149.85; P < 0.001), TB meningitis (AOR 79.14; P < 0.001), abdominal TB (AOR 23.59; P = 0.011), pleural effusion (AOR 12.6; P = 0.021) and age (AOR 1.05; P = 0.021). Among HIV co-infected patients, early initiation of ART reduced mortality rate. Conclusions : The site of EPTB was a key determinant of mortality. Given that death occurs soon after diagnosis, patients with suspected TB meningitis, disseminated, abdominal and pleural TB should be targeted for early diagnosis and treatment to reduce the high EPTB mortality in our setting. Key words: Extrapulmonary TB, HIV coinfection, Treatment outcomes, Mortality, Adults, Ghana

Recommendations Concerning the First-Line Treatment of Children with Tuberculosis.

This document describes the recommendations of a group of scientific societies concerning the first-line therapeutic approach to paediatric tuberculosis (TB). The treatment of pulmonary TB should be based on the existence of parenchymal involvement and the risk of antibiotic resistance. The treatment of extra-pulmonary TB is based on the regimens used for severe pulmonary TB. The administration of corticosteroids is recommended only in cases of miliary TB, tuberculous meningitis and tuberculous pericarditis. Vitamin B6 may be indicated in the case of isoniazid-treated TB in breastfeeding infants, severely malnourished subjects, or patients with other diseases at high risk of vitamin deficiency. Once having started treatment, children with TB should be carefully followed up in order to evaluate compliance, the response to treatment, the need for treatment changes, and the presence of drug-related adverse events. Primary care paediatricians can support reference centres in providing family healthcare education and encouraging treatment compliance.

Diagnosis and treatment of extrapulmonary tuberculosis.

Extrapulmonary tuberculosis (EPTB) constitutes about 20% of all cases of tuberculosis (TB) in Korea. Diagnosing EPTB remains challenging because clinical samples obtained from relatively inaccessible sites may be paucibacillary, thus decreasing the sensitivity of diagnostic tests. Whenever practical, every effort should be made to obtain appropriate specimens for both mycobacteriologic and histopathologic examinations. The measurement of biochemical markers in TB-affected serosal fluids (adenosine deaminase or gamma interferon) and molecular biology techniques such as polymerase chain reaction may be useful adjuncts in the diagnosis of EPTB. Although the disease usually responds to standard anti-TB drug therapy, the ideal regimen and duration of treatment have not yet been established. A paradoxical response frequently occurs during anti-TB therapy. It should be distinguished from other causes of clinical deterioration. Surgery is required mainly to obtain valid diagnostic specimens and to manage complications. Because smear microscopy or culture is not available to monitor patients with EPTB, clinical monitoring is the usual way to assess the response to treatment.

Difficulties in controlling HIV and TB infections in multi-experienced patients

The treatment of extra pulmonary tuberculosis in HIV infected patients experienced to antiretroviral therapy raises major issues of adherence, drug interactions, side effects and limited antiretroviral alternatives. This is the case of a 24 year old woman from countryside, most probably infected in 1989. She was diagnosed with HIV infection in 2000 after repeated admissions in hospital for pneumonia. She started ART when diagnosed with a favorable evolution: CD4 cell count increased from 200 to 674 cells/cmm, and HIV RNA levels became undetectable. She turned 18 in 2008 and refused to take her treatment for almost two years. She returned to the hospital in April 2010 with a CD4 cell count of 140 cells/cmm. She started again antiretroviral therapy with ABC+3TC+FPV/r. In April 2013 she is admitted with night sweats, chills and fever. At that time her CD4 cell count was 144 cells/cmm and had 461,000 copies/mL RNA-HIV. Her chest XR showed right pleural effusion, widened mediastinum and the CT revealed infiltrative-like lesion at subcarinal and retrocarinal level. Biopsy was performed and she was diagnosed with ganglionary tuberculosis. She started anti-TB treatment HRZE 7/7 and the ART was changed to ABC+RAL+T20. The anti-TB regimen is changed after three months to rifampicin and isoniazid 7/7 because she accused arthralgias, tingling of the extremities, blurred vision and decreased visual acuity. She was diagnosed with hyperuricemia (pyrazinamide) and optic and peripheral neuritis (ethambutol). New visit at the clinic for fatigability, after 7 months of antiretroviral therapy with ABV+RAL+T20. The CD4 cell count was 9 cells/cmm and RNA-HIV was 61,000 copies/mL. She admits taking 1 cp of Raltegravir BID, but denies any other adherence problem. The resistance test showed evidence of resistance to some NRTIs, to all NNRTIs, to RAL and no resistance to PIs. The tropism test showed that maraviroc can be used. We have excluded relapse of tuberculosis and other diseases associated. The ART was changed again to TDF+DRV/r+MRV and the anti-TB treatment is change to isoniazid and moxifloxacin. Adherence can be an important issue when treating patients for long periods of time. Other important issues are the drug-drug interactions (rifampicin – PIs) and the increased side effects which may lead to loss of good friends (Raltegravir). The poor outcome for this patient may be due to poor HIV and tuberculosis control.