Initiation Of Antituberculous Treatment Research Articles

Extrapulmonary Tuberculosis: An Otorhinolaryngologist's Perspective.

The study aimed to determine the clinical manifestations and epidemiology of extrapulmonary tuberculosis (EPTB) of the head and neck in the otorhinolaryngeal regions. There is an increase in the incidence of EPTB in recent years because of increase in immunocompromised states and development of resistant bacteria. The clinical symptoms and signs of EPTB of the otorhinolaryngeal regions overlap with that of malignancies and other diseases in otorhinolaryngology thereby requiring correct early diagnosis so as to avoid unnecessary surgeries and procedures with initiation of appropriate anti tuberculous treatment under RNTCP. Our prospective study was done on 45 patients who attended the ENT OPD at a tertiary care centre in Southern India over a period of 18months with diagnosed EPTB of the otorhinolaryngeal regions. The study included 29 (64.4%) patients who presented with cervical lymphadenopathy, 11 (24.4%) patients with tuberculous laryngitis, 3 (6.6%) patients with tuberculous otitis media and 1 each with nasal and oral cavity tuberculosis. In our study 6 (13.3%) patients had co-existing pulmonary tuberculosis, 8 (18%) had diabetes, 5 (11%) had past history of tuberculosis and 7 (16%) had contact with patient with tuberculosis. A high index of suspicion of EPTB must be kept among patients where (i) the clinical symptoms are out of proportion to the signs, (ii) common treatment fails or (iii) there is persistence or recurrence of symptoms despite therapy. The challenge is in confirming diagnosis which requires histopathological examination (HPE) of the tissue specimen. The timely diagnosis and initiation of anti tuberculous treatment (ATT) as per RNTCP helps in complete recovery thereby reducing morbidity.

Clinical characteristics and Outcome of Tuberculous Meningitis in the pediatric population- a cross sectional study at the Aga Khan University hospital

Aims and Objectives: The aim of this retrospective chart review was to determine the clinical characteristics and treatment outcome of the patients diagnosed with Tuberculous Meningitis (TBM) at a tertiary care hospital setting. Methods: This was a cross sectional study included children of either gender aged 1-18 years treated for suspected or confirmed diagnosis of TBM at the pediatric unit of Aga Khan University Hospital. The patients enrolled from January 2015 to June 2020 were identified through electronic medical record system. The data was collected on a predesigned paper-based questionnaire and results are presented as mean, standard deviation and interquartile ranges for continuous variables. Whereas, the qualitative variables presented as frequency and percentages. Results: There were 52 children included in the study with a mean age of 10.66 ± 6.21 years. Of these 27 (52%) were males and 25 (48%) females. Most of the patients 33 (63.5%) presented within ≤14 days of the onset of symptoms. Median length of stay at hospital was 10 days. The median time from admission to initiation of anti-tuberculous treatment (ATT) was 5 days however, the ATT was initiated before admission to hospital in 11 (21%). In 19 (35%) of patients. Cerebrospinal fluid (CSF) culture was positive for TBM in 5 (9%) patients. GeneXpert test performed on CSF sample in 40 (77%) children. Treatment was completed in half of the patients, seven each lost to follow up and died during treatment. A significant number of patients 33 (63%) developed mild to moderate disability in the initial phase followed by full recovery. Conclusion: The findings revealed that TBM is highly associated with morbidity and disability. Early initiation of treatment and diagnosis likely to play pivot role in outcomes.

Misled by the Xpert-Kikuchi’s disease masquerading as tuberculosis

Kikuchi-Fujimoto disease (KFD), also called histiocytic-necrotizing lymphadenitis is a rare, idiopathic and self-limiting cause of lymphadenitis. Clinical presentation of KFD closely resembles nodal tuberculosis (TB). Here we present a case of an adolescent female whose diagnosis of KFD was made despite being misled in the course. A 15-year-old female, previously treated for tuberculous lymphadenitis was brought with complaints of fever for 1 month. Various possibilities considered were TB reactivation, autoimmune disorders, lymphoma. Lymph node biopsy for gene Xpert showed TB bacilli detected but low with no RIF resistance. Despite anti tuberculous treatment initiation, there was no improvement in the clinical condition. Histopathology of cervical node showed features of Kikuchi lymphadenitis. Literature search revealed that gene Xpert can detect the intact DNA of Mycobacterium tuberculosis even years after the previous treatment. On stopping anti tuberculosis therapy (ATT) and starting IV steroid, she started improving dramatically. KFD should always be kept as a differential diagnosis in any individual with fever and lymphadenopathy. Diagnosis can be misled in any patient based on gene Xpert reports alone which often turns out to be positive if there is past history of TB as gene Xpert detects DNA from non-intact cells suggesting that dead bacilli contribute to the false positivity.

Predicting drug-induced liver injury from anti-tuberculous medications by early monitoring of liver tests

Tuberculosis Drug Induced Liver Injury (TB-DILI) is a common and potentially severe complication associated with anti-tuberculous treatment (ATT). Optimal liver test monitoring for standard TB medication has not been established. We describe the predictive value of pre-treatment liver tests (LTs) and at 2-weeks after initiation of ATT for the detection of TB-DILI. Patients initiating ATT were monitored with routine LTs pre-treatment and after 2-weeks. Logistic regression models were constructed to retrospectively identify pre-treatment variables associated with 'late' TB-DILI (>2 weeks after treatment initiation) and whether pre-treatment and 2-week alanine aminotransferase (ALT) levels could predict late TB-DILI. 1247 patients with active tuberculosis managed at 5 sites across north west London between January 2015 and December 2018 were monitored with routine LTs. 103 cases (8.3%) of ATT-associated DILI were diagnosed. 60 cases (58.3%) of TB-DILI occurred later than 2-weeks. The risk of late TB-DILI was 2.2-fold greater for every 30 U/L increment in ALT pre-treatment (OR 2.16, 95% CI 1.38-3.29 p<0.001) and 2.1-fold greater for every 30 U/L increment in ALT gradient at 2-weeks (OR 2.06, 95% CI 1.52-2.76 p<0.001). Routine 2-week LTs capture early TB-DILI and may be valuable in predicting late TB-DILI in patients on ATT.

Determination of cerebrospinal fluid adenosine deaminase activity cut-off for the diagnosis of tuberculous meningitis in Hong Kong

AimsTuberculous meningitis (TBM) is a severe infection which may lead to serious complication and mortality. Prompt diagnosis and treatment are essential. There is a need for a simple and fast...

Engagement of private healthcare providers for case finding of tuberculosis and diabetes mellitus in Pakistan

BackgroundThe rising co-epidemic of tuberculosis (TB) and diabetes mellitus (DM) is a challenge for constrained health systems in low and middle-income countries. Diabetes is a known risk factor for tuberculosis and associated with poor tuberculosis treatment outcomes, while tuberculosis is associated with worsening glycemic control. We investigated the performance of bi-directional TB and DM case finding approaches through a private-sector engagement model in Karachi, Pakistan.MethodsBetween July 2016 and July 2018, private health care providers were engaged to generate referrals for bi-directional TB and DM screening at private diagnostic and treatment centers in Karachi, Pakistan. Individuals diagnosed with TB underwent glycated hemoglobin (HbA1c) testing at the time of anti-tuberculous treatment initiation and at three -month follow up stage. All individuals with a history of diabetes or random blood sugar of greater than 200 mg/dl were screened for TB using a chest X-ray and Xpert MTB/RIF.ResultsA total of 6312 persons with tuberculosis were tested on HbA1c at treatment initiation, of whom 1516 (24%) were newly diagnosed with DM. About one third of those with HbA1c in the diabetic range (≥ 6.5%) at baseline were found to have a normal HbA1c (< 5.7%) result at 3-month follow-up. A total of 3824 individuals with DM, of whom 2396 (63%) were known cases and 1428 (37%) were newly identified with random blood sugar > 200 mg/dl, underwent chest x-ray and Xpert MTB/RIF testing, with 321 (13.4%) known and 54 (3.8%) new diabetics respectively identified with tuberculosis.ConclusionThis study demonstrates a high yield of TB and DM through bidirectional screening and the feasibility of engagement of private sector in finding missing cases of tuberculosis and diabetes. Given the high prevalence of undiagnosed DM in individuals with TB tuberculosis patients, there is a need to scale-up DM screening within TB programmes. Increased awareness of the high risk of TB among individuals with DM is needed among private health providers and screening for TB among diabetics should be strongly considered.

Treatment of ocular tuberculosis-an update

Tuberculous uveitis (TU) is initially usually not acute, accompanied by only slight visual disorders and affects otherwise healthy individuals so that the diagnosis is frequently primarily overlooked. This study was carried out to provide an update of the treatment options in suspected TU. APubMed search was undertaken using the key terms uveitis AND tuberculosis AND treatment for manuscripts published within the last decade. Cross-identified articles relevant to the topic were also evaluated regarding their evidence based on the authors' expertise. When the suspicion of a TU is not supported by further investigations, the decision has to weigh up the risks and benefits of treatment. Aresponse of the uveitis to antituberculous treatment (ATT) in 82% represents an important diagnostic indication. Based on this remarkably good response rate and an acceptable side effect profile of ATT, agenerous indication seems reasonable. Alack of response or aparadox worsening of uveitis under treatment for manifestations of extrapulmonary tuberculosis, probably represent ahypersensitivity reaction to mycobacterial antigens and require additional corticosteroid treatment. Eales' disease, an isolated retinal vasculitis, is associated with TU but does not respond to ATT and requires laser ablation of the ischemic area. TU typically affects otherwise healthy individuals without extraocular manifestations. Early consideration of TU and initiation of ATT ideally before the start of systemic corticosteroids is decisive for long-term functional recovery. Treatment success, defined as absence of new uveitic flares within 6 months of treatment cessation, is to be expected in at least 82%. In cases of paradox worsening or lack of response, additional anti-inflammatory treatment is required.

Host Determinants of Infectiousness in Smear-Positive Patients With Pulmonary Tuberculosis.

BackgroundEpidemiologic data suggests that only a minority of tuberculosis (TB) patients are infectious. Cough aerosol sampling is a novel quantitative method to measure TB infectiousness. MethodsWe analyzed data from three studies conducted in Uganda and Brazil over a 13-year period. We included sputum acid fast bacilli (AFB) and culture positive pulmonary TB patients and used a cough aerosol sampling system (CASS) to measure the number of colony-forming units (CFU) of Mycobacterium tuberculosis in cough-generated aerosols as a measure for infectiousness. Aerosol data was categorized as: aerosol negative (CFU = 0) and aerosol positive (CFU > 0). Logistic regression models were built to identify factors associated with aerosol positivity.ResultsM. tuberculosis was isolated by culture from cough aerosols in 100/233 (43%) TB patients. In an unadjusted analysis, aerosol positivity was associated with fewer days of antituberculous therapy before CASS sampling (p = .0001), higher sputum AFB smear grade (p = .01), shorter days to positivity in liquid culture media (p = .02), and larger sputum volume (p = .03). In an adjusted analysis, only fewer days of TB treatment (OR 1.47 per 1 day of therapy, 95% CI 1.16-1.89; p = .001) was associated with aerosol positivity.ConclusionCough generated aerosols containing viable M. tuberculosis, the infectious moiety in TB, are detected in a minority of TB patients and rapidly become non-culturable after initiation of antituberculous treatment. Mechanistic studies are needed to further elucidate these findings.

Clinical Spectrum of Central Nervous System Tuberculosis and the Efficacy of Revised National Tuberculosis Control Program in its Management.

Introduction:Tuberculosis (TB) is a major global problem and poses a threat which is of considerable magnitude, with an estimated one-third of the population infected with TB bacillus.Aim:The aim of this study is to study the treatment outcomes in patients with various forms of neurological TB treated with the standardized Revised National TB Control Program (RNTCP), directly observed treatment short-course (DOTS).Materials and Methods:Patients diagnosed to have TBM, tuberculoma with or without spinal arachnoiditis (central nervous system tuberculosis-TB [CNS-TB]) were categorized as per the RNTCP guidelines and received DOTS Category I or Category II thrice-weekly intermittent treatment as deemed appropriate.Results:The outcome of management with the standard RNTCP DOTS regimen was that a success rate (treatment completed) of 75%, the default rate of 6.6%, and a mortality of 3.3%. The target fixed by the RNTCP is to achieve a cure rate of 85%. We were able to document successful completion of treatment in 75% which is close to the target fixed by RNTCP. The default rate is 6.6% which quite negligible when compared to the unsupervised therapy which has a default rate of 50%.Conclusion:The most important factor in predicting the outcome of treatment in CNS-TB is early diagnosis and the timing of initiation of antituberculous treatment. Early initiation of treatment is associated with better treatment outcomes.

Impact of radiology reports on timely tuberculosis diagnosis

PurposeAs tuberculosis becomes less common in higher income countries, clinician familiarity with the disease is declining. Little is known about how chest radiograph interpretations affect tuberculosis care. We sought to...

Utilization and Clinical Value of Diagnostic Modalities for Tuberculosis in a High HIV Prevalence Setting.

Human immunodeficiency virus (HIV) infection is a major risk factor for the development of active tuberculosis (TB), one of the deadliest infectious diseases globally. The high mortality associated with the disease can be reduced by early diagnosis and prompt antituberculous treatment initiation. Facilities in TB-endemic regions are increasing the use of nucleic acid amplification (e.g., GeneXpert), which provides rapid results but may have suboptimal sensitivity in HIV-associated TB. Our objective was to evaluate the current practices for TB diagnosis at Edendale Hospital, a large regional hospital in KwaZulu-Natal, South Africa-a TB-endemic region with high HIV prevalence. In this cross-sectional study, all adult inpatients newly started on TB treatment at Edendale were identified over a 6-week period. Demographics, clinical information, diagnostic test results, and outcomes were documented. Pulmonary TB (PTB), extrapulmonary TB (EXTB), and PTB + EXTB were defined as disease evidence in the lungs, other organs, or both, respectively. Ninety-four cases were identified, of which 83% were HIV-associated. Only 30% of all TB patients were microbiologically confirmed, consisting of 7/16 (44%) HIV-uninfected and 21/78 (27%) HIV-infected TB patients. Smear microscopy and mycobacterial culture were seldom ordered. Ultrasound was performed in about one-third of suspected EXTB cases and was valuable in identifying abdominal TB. In this clinical setting with a high incidence of HIV-associated TB, TB diagnosis was more commonly based on clinical assessment and imaging results than on mycobacterial gold standard test confirmation.

Concordance of Cytomorphological Features of Cervical Lymphadenitis Suspected for Mycobacterium Tuberculosis on Fine Needle Aspiration Biopsy with GeneXpert for Mycobacterium Tuberculosis on Aspirated Material

Objective: The objective of the study was to correlate different cytomorphological presentations of cervical lymphadenitis suspected for Mycobacterium Tuberculosis (MTB) on Fine Needle Aspiration Cytology (FNAC) with MTB detection by geneXpert on aspirated material.Study Design: Comparative, cross sectional study.Place and Duration of Study: Department of Histopathology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan, from January 2017 through November 2018.Methodology: Fine needle aspirates of total 100 patients with cervical lymphadenitis suspected for MTB were included in the study and the cytology was compared with geneXpert, keeping geneXpert as gold standard. After obtaining FNA aspirates from cervical lymph nodes, the smears were evaluated for various patterns of granulomatous inflammation. The aspirate was sent to the microbiology department for confirmation of presence of MTB by PCR (geneXpert), results of which were then compared. Data was analyzed using SPSS version 23. Descriptive statistics, frequencies and percentages were calculated.Results: A total of 100 samples of cervical lymphadenitis, in which MTB was suspected, were evaluated out of which 53 were males and 47 were females. The male to female ratio was 1.12:1. Mean age of population in study was 31 ± 15 years. Minimum age at presentation was 4 years and maximum age was 72 years. Maximum incidence of disease was seen in young patients between 15 and 40 years. On FNAC smears, a total of 61% (n=61) cases showed granulomas with caseous necrosis, 14% (n=14) cases showed abscess only, 10% cases (n=10) showed granulomas only, 10% (n=10) cases showed granulomas with abscess while 5% (n=5) cases showed caseous necrosis only. A total of 78 cases were positive for MTB while 22 cases were negative when compared with molecular analysis on aspirated material. Positivity for MTB by geneXpert was seen in 93% (n=57) cases with both caseous necrosis and granulomas, 80% (n=4) cases with caseous necrosis only, 80% (n=10) cases having granulomas along with neutrophilic abscess, 70% (n=7) cases showing only granulomas and 14% (n=2) cases with neutrophilic abscess only (p value<0.05). The sensitivity of FNAC was 97% and specificity was 54.Positive predictive value (PPV) was 88% and Negative predictive value (NPV) was 85%.Conclusion: MTB was detected by GeneXpert in a significant percentage of the FNAC samples included in our study. FNAC is a rapid, safe, inexpensive, easily available, minimally invasive, outpatient procedure and GeneXpert can be performed on the aspirated material for the diagnosis of cervical lymphadenitis suspected for MTB infection. This can aid the clinicians in timely initiation of Anti Tuberculous Treatment (ATT) in our country where tuberculosis is rampant and advanced diagnostic facilities are not easily accessible.

Réaction paradoxale à la fin du traitement antituberculeux chez le sujet immunocompétent

The features of paradoxical reactions (PR) that occurred in non-HIV infected patients are rare and not well known. The authors reported the case of a 21years old, non-immunocompromised, and HIV negative patient treated for disseminated tuberculosis. PR occurred after 8months after initiation of antituberculous treatment. PR presented as left cervical lymphadenopathy, pulmonary, pleural, costal and spinal location of the tuberculosis. The antituberculous drugs were prolonged. Patient's clinical symptoms improved initially. However, left inguinal lymphadenopathy appeared after 20months of antituberculous therapy. Inguinal lymph node biopsy revealed tuberculous lymphadenitis. The patient has a good compliance to the treatment. The patient was continued on same antituberculous treatment for a total of 28months. The cervical and inguinal lymphadenopathy disappeared and CT scan showed regression of thoracic, abdominal, costal and spinal lesions. PR during antituberculous treatment must be considered after exclusion of other causes. No consensus on the therapeutic management of this entity has been developed to date.

Paradoxical Deterioration During Anti-Tuberculous Therapy in Non-HIV-Infected Patients with Pleural Tuberculosis: A Pragmatic Approach.

We report a case of paradoxical deterioration. A male patient diagnosed with pleural tuberculosis, but who was not infected with human immunodeficiency virus (HIV), experienced clinical deterioration 3 weeks after the initiation of anti-tuberculous treatment. After other diagnoses were ruled out, a paradoxical response to treatment was established and the patient was started on systemic corticosteroids. Paradoxical response to treatment should be considered in patients with clinical deterioration after they start on anti-tuberculous treatment.LEARNING POINTSThe deterioration of patients with pleural tuberculosis during anti-tuberculous treatment should raise the suspicion of paradoxical response to treatment.Despite the clinical deterioration, patients should be kept on anti-tuberculosis treatment.There is no clear evidence concerning the benefits and harms of systemic corticosteroids or pleural drainage as additional treatment to control the patient’s symptoms in this scenario.

Six months therapy for tuberculous meningitis.

Tuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Most international guidelines recommend longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis disease to prevent relapse. However, longer regimens are associated with poor adherence, which could contribute to increased relapse, development of drug resistance, and increased costs to patients and healthcare systems. To compare the effects of short-course (six months) regimens versus prolonged-course regimens for people with tuberculous meningitis (TBM). We searched the following databases up to 31 March 2016: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS; INDMED; and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists and contacted researchers in the field. We included randomized controlled trials (RCTs) and prospective cohort studies of adults and children with TBM treated with antituberculous regimens that included rifampicin for six months or longer than six months. The primary outcome was relapse, and included studies required a minimum of six months follow-up after completion of treatment. Two review authors (SJ and HR) independently assessed the literature search results for eligibility, and performed data extraction and 'Risk of bias' assessments of the included studies. We contacted study authors for additional information when necessary. Most data came from single arm cohort studies without a direct comparison so we pooled the findings for each group of cohorts and presented them separately using a complete-case analysis. We assessed the quality of the evidence narratively, as using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was inappropriate with no direct comparisons between short- and prolonged-course regimens. Four RCTs and 12 prospective cohort studies met our inclusion criteria, and included a total of 1881 participants with TBM. None of the included RCTs directly compared six months versus longer regimens, so we analysed all data as individual cohorts to obtain relapse rates in each set of cohorts.We included seven cohorts of participants treated for six months, with a total of 458 participants. Three studies were conducted in Thailand, two in South Africa, and one each in Ecuador and Papua New Guinea between the 1980s and 2009. We included 12 cohorts of participants treated for longer than six months (ranging from eight to 16 months), with a total of 1423 participants. Four studies were conducted in India, three in Thailand and one each in China, South Africa, Romania, Turkey and Vietnam, between the late 1970s and 2011.The proportion of participants classified as having stage III disease (severe) was higher in the cohorts treated for six months (33.2% versus 16.9%), but the proportion with known concurrent HIV was higher in the cohorts treated for longer (0/458 versus 122/1423). Although there were variations in the treatment regimens, most cohorts received isoniazid, rifampicin, and pyrazinamide during the intensive phase.Investigators achieved follow-up beyond 18 months after completing treatment in three out of the seven cohorts treated for six months, and five out of the 12 cohorts treated for eight to 16 months. All studies had potential sources of bias in their estimation of the relapse rate, and comparisons between the cohorts could be confounded.Relapse was an uncommon event across both groups of cohorts (3/369 (0.8%) with six months treatment versus 7/915 (0.8%) with longer), with only one death attributed to relapse in each group.Overall, the proportion of participants who died was higher in the cohorts treated for longer than six months (447/1423 (31.4%) versus 58/458 (12.7%)). However, most deaths occurred during the first six months in both treatment cohorts, which suggested that the difference in death rate was not directly related to duration of ATT but was due to confounding. Clinical cure was higher in the group of cohorts treated for six months (408/458 (89.1%) versus longer than six months (984/1336 (73.7%)), consistent with the observations for deaths.Few participants defaulted from treatment with six months treatment (4/370 (1.1%)) versus longer treatment (8/355 (2.3%)), and adherence was not well reported. In all cohorts most deaths occurred in the first six months; and relapse was uncommon in all participants irrespective of the regimen. Further inferences are probably inappropriate given this is observational data and confounding is likely. These data are almost all from participants who are HIV-negative, and thus the inferences will not apply to the efficacy and safety of the six months regimens in HIV-positive people. Well-designed RCTs, or large prospective cohort studies, comparing six months with longer treatment regimens with long follow-up periods established at initiation of ATT are needed to resolve the uncertainty regarding the safety and efficacy of six months regimens for TBM.

High Mortality in Adults Hospitalized for Active Tuberculosis in a Low HIV Prevalence Setting

BackgroundThis study aims to evaluate the outcomes of adults hospitalized for tuberculosis in a higher-income region with low HIV prevalence.MethodsA retrospective cohort study was conducted on all adults hospitalized for pulmonary and/or extrapulmonary tuberculosis in an acute-care hospital in Hong Kong during a two-year period. Microscopy and solid-medium culture were routinely performed. The diagnosis of tuberculosis was made by: (1) positive culture of M. tuberculosis, (2) positive M. tuberculosis PCR result, (3) histology findings of tuberculosis infection, and/or (4) typical clinico-radiological manifestations of tuberculosis which resolved after anti-TB treatment, in the absence of alternative diagnoses. Time to treatment (‘early’, started during initial admission; ‘late’, subsequent periods), reasons for delay, and short- and long-term survival were analyzed.ResultsAltogether 349 patients were studied [median(IQR) age 62(48–77) years; non-HIV immunocompromised conditions 36.7%; HIV/AIDS 2.0%]. 57.9%, 16.3%, and 25.8% had pulmonary, extrapulmonary, and pulmonary-extrapulmonary tuberculosis respectively. 58.2% was smear-negative; 0.6% multidrug-resistant. 43.4% developed hypoxemia. Crude 90-day and 1-year all-cause mortality was 13.8% and 24.1% respectively. 57.6% and 35.8% received ‘early’ and ‘late’ treatment respectively, latter mostly culture-guided [median(IQR) intervals, 5(3–9) vs. 43(25–61) days]. Diagnosis was unknown before death in 6.6%. Smear-negativity, malignancy, chronic lung diseases, and prior exposure to fluoroquinolones (adjusted-OR 10.6, 95%CI 1.3–85.2) delayed diagnosis of tuberculosis. Failure to receive ‘early’ treatment independently predicted higher mortality (Cox-model, adjusted-HR 1.8, 95%CI 1.1–3.0).ConclusionsMortality of hospitalized tuberculosis patients is high. Newer approaches incorporating methods for rapid diagnosis and initiation of anti-tuberculous treatment are urgently required to improve outcomes.

Réactions paradoxales sous traitement antituberculeux chez des personnes non infectées par le VIH : quatre nouvelles observations et revue de la littérature

IntroductionThe features of paradoxical reactions (PR) that occurred in non-HIV infected patients treated with antituberculous drugs are diverse. We report four new cases of such PR and review the literature. Patients and methodsWere included all consecutive patients with PR that occurred in non-HIV infected patients who were treated for tuberculosis and followed-up in the department of internal medicine and infectious diseases between January 1st, 2009 and July 31st, 2010. ResultsThree of the patients were male. Their median age was 28.5years. Tuberculous locations were pulmonary (two instances) and extrapulmonary (three instances). Paradoxical reactions occurred after a median of 5.5weeks after initiation of antituberculous treatment. The PR presented as hypercalcemia (n=1), spondylitis of the 9th thoracic vertebra (n=1), intracerebral tuberculoma (n=1), pericardial effusion (n=1) and adenitis (n=3). Lymphopenia was present in three patients. Three out of the four patients received corticosteroid. Outcome was favorable in three patients. ConclusionPardoxical reactions are more common in patients who present with extrapulmonary tuberculosis. Intracerebral tuberculomas and spondylitis may be asymptomatic. Prescription of corticosteroids remains controversial except for intracerebral tuberculoma.

Intestinal tuberculosis complicated with perforation during anti-tuberculous treatment in a 13-year-old girl with defective mitogen-induced IL-12 production

Interleukin-12 (IL-12) is a cytokine which is secreted by activated phagocytes and dendritic cells and promotes cell-mediated immunity to intracellular pathogens, by inducing type 1 helper T cell (TH1) responses and interferon- γ (IFN- γ) production. Defects in the IL-12 may cause selective susceptibility to intracellular pathogens, such as mycobacteria. We herein report on a 13-year-old girl with defective mitogen-induced IL-12 production, who developed intestinal tuberculosis with wide dissemination involving the lung and urinary tract. She improved gradually, but developed terminal ileal perforation approximately 6.1 months following initiation of anti-tuberculous treatment. The paradoxical response phenomenon was suspected. The girl subsequently underwent surgical resection of the affected bowel segment with a temporary double barrel stoma, and ileocolonic anastomosis was performed after the completion of the anti-tuberculous therapy. The patient remained well, with no evidence of recurrent tuberculosis in the past 5 years. This case illustrates the possibility of underlying primary immunodeficiency in a patient with disseminated tuberculosis; delayed tuberculous intestinal perforation can develop during chemotherapy for tuberculosis.

Delayed Suspicion, Treatment and Isolation of Tuberculosis Patients in Pulmonology/Infectious Diseases and Non-Pulmonology/Infectious Diseases Wards

Background/PurposeDelayed diagnosis and isolation increases the risk of nosocomial transmission of tuberculosis (TB). To assess the risk of delayed management of TB, we analyzed the risk factors of prolonged delay in isolation of smear-positive TB patients in pulmonology/infectious diseases and other wards in a tertiary teaching hospital.MethodsWe enrolled smear-positive TB patients aged > 16 years with delayed respiratory isolation following hospitalization. Medical records were reviewed retrospectively. Time intervals between admission, order of sputum acid-fast staining, initiation of anti-tuberculous treatment and isolation were compared between pulmonology/infectious diseases wards (PIWs) and other wards. Risk factors were analyzed in patients with prolonged isolation delay of > 7 days in individual groups.ResultsIsolation was delayed in 191 (73.7%) of 259 hospitalized smear-positive TB patients. Median suspicion, treatment and isolation delays were 0, 3 and 4 days in PIWs and 1, 5 and 7 days in other wards. For patients admitted to non-PIWs, atypical chest radiographs, symptoms without dyspnea or not being admitted from the emergency department (ED) were risk factors for prolonged isolation delay exceeding 7 days. The only risk factor for delayed isolation in patients admitted to PIWs was age ≥ 70 years.ConclusionDelays in suspicion, treatment and isolation of TB patients were longer in non-PIWs. Clinicians should be alert to those admitted to non-PIWs with atypical chest radiographs, atypical symptoms, or not admitted from the ED.

An unusual case of both upper and lower gastrointestinal bleeding in a kidney transplant recipient

Tuberculosis (TB) is an uncommon opportunistic infection in immunocompromised patients. Extrapulmonary infection involving the intestine is rare and poses diagnostic difficulties. A 49-year-old man with IgA nephropathy underwent a kidney transplantation in 1996 and was put on cyclosporine, azathioprine, and steroid. He suffered from a recurrence of his primary kidney disease and had a gradual deterioration of renal function since 1998. By 2005, he presented with an unusual gastrointestinal (GI) symptom with alternating signs of upper GI bleeding - melena - as well as lower GI bleeding with fresh rectal bleeding, resulting in severe anemia with hemoglobin level down to 5.0 g/dL. At the same time, his renal function further deteriorated and necessitated the initiation of dialysis while he was maintained on low-dose immunosuppressive drugs. Repeated upper and lower GI endoscopies were either unremarkable or revealed non-specific lesions. Symptoms persisted and exploratory laparotomy finally showed a 1 cm submucosal mass at the proximal jejunum and multiple inflammatory lesions at the terminal ileum. Segmental resection of the lesions was performed and confirmed TB infection. However, despite the initiation of anti-tuberculous treatment, the patient eventually died of complications. Diagnosing TB intestinal infection is a clinical challenge. A high index of suspicion in susceptible subjects is necessary, and early surgical intervention should always be considered when facing diagnostic uncertainties.