Antituberculous Treatment Research Articles

Baseline HBV load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis.

Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV). Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of >3, 5, and 10 times the upper limit of normal (ULN) were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin (TBil) levels that were more than 10 times the ULN (>171 μmol/L) with or without decreased (<40%) prothrombin activity (PTA) were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8% (n=52) and 25.3% (n=22), respectively. The following variables were correlated with the severity of hepatotoxicity: albumin (ALB) levels, PTA, platelet counts (PLT), and the use of antiretroviral therapies (P<0.05). Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio (OR) of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Tubercular abdominal cocoon in children - a single centre study in remote area of northern India.

BackgroundAmongst the numerous causes of intestinal obstruction listed in the literature, sclerosing encapsulating peritonitis also called Abdominal Cocoon (AC) is one of the rarest entities. Its characteristic feature is a thick fibrotic membrane encasing varying lengths of the small and large gut in a cocoon. In India, there is an increasing incidence of tuberculosis, especially in the rural areas.Aims and objectivesThe aim of this study was to investigate the clinical presentation and evaluate the operative findings of tuberculous AC. We also evaluated the outcomes and response to anti tuberculous treatment (ATT) in all the patients diagnosed with this condition.Material and methodsThis study was carried out at M.M. Institute of Medical Sciences and Research, Mullana, Ambala, India between April 2013 – March 2016 in the Department of Pediatric Surgery. This is a prospective study. A total of 17 patients diagnosed with abdominal cocoon secondary to tuberculosis have been included in the study.ResultsA total of 17 patients presented to the emergency ward with features of acute intestinal obstruction. The average age was 15.3 years (range 9 years to 16 years). There were 14 females and 3 males. All patients presented with abdominal pain, bilious vomiting, constipation and abdominal distention. The patients were operated in our hospital and relieved of their obstruction. Based on their operative findings and after histopathological confirmation, patients were given ATT. In the follow-up, all patients did well, without recurrence of tuberculosis or intestinal obstruction.ConclusionTuberculosis as a cause of childhood AC is rather common in developing countries and is potentially a fatal condition. A strong clinical suspicion, sonographic and computed tomography scan findings help establish a pre-operative diagnosis. Tuberculous AC has a strong prevalence in females. Surgery is the mainstay of treatment followed by anti-tuberculous drugs.

Primary Nasal Tuberculosis: Resurgence or Coincidence - A Report of Four Cases with Review of Literature.

Background:Primary nasal tuberculosis (TB) is a rare form of TB even in areas with high TB incidence. It is timely diagnosis and proper management are often delayed due to its rarity and nonspecific clinical presentation.Aim:The aim of the study was to review histopathologically diagnosed cases of nasal TB over a period of 1 year and to describe its clinical presentation, diagnostic workup, the importance of histopathological diagnosis along with a brief review of the literature.Materials and Methods:This was a retrospective study done in the Department of Pathology of a Tertiary Care Hospital of Delhi over a period of 1 year where all the cases with histopathological diagnosis of nasal TB were reviewed. Patients' clinical details, investigations and treatment details along with follow-up were obtained from the medical records section. For each case, routine hematoxylin and eosin stain were studied along with Ziehl–Neelson staining.Results:A total of four patients were diagnosed with nasal TB histopathologically. Patients' age ranged from 5 to 34 with an equal male to female ratio. All patients were immunocompetent. Primary nasal TB was seen in all of the four cases. None of the cases, it was clinically suspected, and histopathology was the mainstay of diagnosis. All the cases were treated with antituberculous treatment and showed considerable improvement.Conclusions:Although nasal TB is rare, it should be considered in the differential diagnosis of chronic nasal symptoms and granulomatous lesions of the nose. Histopathology plays an important role in the diagnosis of these clinically unsuspecting cases of nasal TB.

A case of tuberculous peritonitis diagnosed by way of laparoscopy

Objective: Tuberculous peritonitis (TBP) is a rare form of extrapulmonary tuberculosis. The diagnosis of TBP is particularly challenging in children. Herein, we present a child who had been admitted with ascites and diagnosed as TBP by way of laparoscopy. Case report: A previously healthy 3-year-old girl was presented with newly onset fever and abdominal pain. She had abdominal distention and generalized tenderness on palpation. Abdominal percussion revealed dullness on nonspesific locations. Abdominal ultrasonography showed diffuse ascites with multiple septations, and paracenthesis performed detected exudative material with plenty of polmorphonuclear leukocytes. She was started on antibiotherapy. Lymphocytic pleocytosis persisted on control peritoneal lavage sample. Acid- resistant bacteria were not seen in the peritoneal fluid, tuberculous polymerase chain reaction test and tuberculous cultures were negative. Cytopathologic examination was not suggestive of malignancy. Diagnostic laparoscopy was compatible with TBP. Adenosine deaminase (ADA) level in peritoneal fluid was increased. She was started on quadruple antituberculous treatment including isoniazid (INH), rifampicin (RIF), pyrazinamide and ethambutol. On the 2nd month of antituberculous therapy, abdominal circumference showed obvious regression. She continued on INH-RIF therapy and is still being followedup in our outpatient clinic. Conclusion: Explorative laparoscopy and peritoneal fluid ADA level are very helpful in the diagnosis of TBP

Acute Generalized Exanthematous Pustulosis Due to Pyrazinamide in a Patient Receiving Antituberculous Treatment: A Case Report

Acute Generalized Exanthematous Pustulosis Due to Pyrazinamide in a Patient Receiving Antituberculous Treatment: A Case Report

Bacillus Calmette–Guérin Infection and Cytotoxicity in the Retinal Pigment Epithelium

ABSTRACTPurpose: To investigate bacillus Calmette–Guérin (BCG) infective capability and cytotoxicity in ARPE-19 cells.Methods: BCG inoculum was dispensed at a MOI 100:1 for 3 h in 90% confluent ARPE-19 cells. Infection rates at different time points were determined by colony forming units (CFU) count and, in parallel, by the number of microscopically infected cells. WST-1 reagent was used for cytotoxicity assays.Results: A 67-year-old man previously treated with intravesical BCG for bladder carcinoma presented with chronic, refractory, bilateral uveitis with macular edema. Quiescence was achieved only after commencing antituberculous treatment. BCG infection rate by two methods peaked at 48 h (16 ± 5.7% by CFU count and 40 ± 7.7% by microscopy; p = 0.058). BCG adhesion, phagocytosis, intracellular proliferation and cytolysis was observed. Cytotoxicity was minimal and did not differ from uninfected cells.Conclusions: BCG can infect at low rates and proliferate in ARPE-19 cells without toxicity in the surrounding monolayer.

An unusual cause of refractory ascites with cirrhosis

Reports of chronic constrictive pericarditis presenting with hepatomegaly, cirrhosis and ascites but no cardiac symptoms are rare. A 10 year old child presented with refractory ascites and firm hepatomegaly of 2 years duration which partially responded to diuretics. Doppler study showed dilated hepatic veins and inferior vena cava and ruled out hepatic venous outflow tract obstruction. Chest X ray showed pericardial calcification and 2D Echo was suggestive of chronic constrictive pericarditis. A diagnosis of chronic calcified constrictive pericarditis with cirrhosis and refractory ascites was made. Based on previous series which showed that tuberculosis is the most common cause of constrictive pericarditis, tuberculosis as the cause of constrictive pericarditis was kept. Anti tuberculous treatment as per Revised National Tuberculosis Control Program guidelines was started along with oral steroids and diuretics. Child showed response to the treatment and was later referred to cardiac surgery department for further management (pericardectomy).

Clinical profile of children presenting with acute abdomen in a tertiary care centre of South Tamilnadu: a retrospective observational study

Background: Acute abdominal pain is a common presentation in both outpatient visits and emergency room. It can be organic or functional, medical or surgical. We did an observational study to evaluate the clinical profile of children presenting with acute abdominal pain &lt;7 days duration and analyse the various medical and surgical causes for this clinical presentation.Methods: Children &lt;15 years presenting with acute onset pain abdomen &lt;7 days with or without fever, vomiting, loose stools or urinary symptoms and admitted in pediatric ward were included in the study. Out of the 205 children enrolled in the study, 120 were males and 85 were females.Results: Only 15.6% of cases were of surgical etiology requiring elective or emergency surgical interventions. Among the 173 children diagnosed with variety of medical conditions, the most common condition presenting with pain abdomen was acid peptic disease (16%) followed by acute gastro enteritis(14%) and Urolithiasis(13%). Increasing prevalence of acute pancreatitis and type 1 diabetes mellitus (13 cases each) in children were observed.Conclusions: Long term follow up of children presenting with mesenteric adenopathy without other significant pathology is warranted to avoid unnecessary empirical antituberculous treatment. Our study helped us to identify the different spectrum of etiologies across the three age groups (1-5 years, 6-10 years, 11-15 years) and some diseases were showing male or female predilection.

Frequency of Positive Results of Bacille Calmette Gurein and Mantoux Skin Tests in Suspected Cases of Childhood Pulmonary Tuberculosis

&lt;p&gt;&lt;strong&gt;Abstract&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective:&lt;/strong&gt; To determine the frequency of positive results of Bacille Calmette Gurein and Mantoux skin tests in suspected cases of childhood pulmonary tuberculosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and Methods:&lt;/strong&gt; This prospective interventional study was conducted on 160 children from out-patient and inpatient departments of Pediatrics in Services institute of medical sciences, Lahore. An informed consent was taken from their parents for using their data in research and to keep the results confidential. Cases were diagnosed on the basis of history, examination and investigations. Each patient was giv-en 0.1 ml BCG intradermally on left shoulder and 5 IU of PPD intradermally on volar aspect of right forearm. The results were observed after 48 hours of application in the form of induration (in mm). The diagnostic BCG &amp;gt;8 and Mantoux test &amp;gt;10 after 48hrs was taken&lt;/p&gt;&lt;p&gt;(45%) patients showed positive response to both man-toux test and BCG. While alone BCG test was positive in 56 (35%) patients. Both BCG and mantoux tests were negative in rest of 32 (20%) patients. 131(81.9%) patients had variable degree of malnutrition. Severe malnutrition was present in 54 patients; out of these, 50 (92.6%) patients were BCG positive while only 10 (18.5%) patients showed positive response to mantoux test.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; BCG is more reliable than the tuberculin test in the diagnosis of childhood pulmonary tubercu-losis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Keywords:&lt;/strong&gt; Bacilli calmette gurein (BCG), Mantoux test, Tuberculosis (TB), Tuberculous meningitis (TBM), Antituberculous treatment (ATT).&lt;/p&gt;&lt;p class="MsoNormal" style="text-align: justify; tab-stops: .25in;"&gt;&lt;span style="font-size: 19pt;" lang="IT"&gt; &lt;/span&gt;&lt;/p&gt;&lt;p class="MsoNormal" style="text-align: justify; tab-stops: .25in;"&gt;&lt;strong&gt;&lt;span style="font-size: 18.0pt; mso-bidi-font-size: 11.0pt; color: #1f497d;" lang="IT"&gt;Frequency of Positive Results of Bacille Calmette Gurein and Mantoux Skin Tests in Suspected Cases of Childhood Pulmonary Tuberculosis&lt;/span&gt;&lt;/strong&gt;&lt;/p&gt;

Six-month therapy for abdominal tuberculosis.

BackgroundTuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers.ObjectivesTo compare six‐month versus longer drug regimens to treat people that have abdominal TB.Search methodsWe searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists.Selection criteriaWe included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT.Data collection and analysisTwo review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach.Main resultsWe included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months.Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens (very low quality evidence). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence).Authors' conclusionsWe found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question.2 April 2019Up to dateAll studies incorporated from most recent searchAll eligible published studies found in the last search (2 Sep, 2016) were included

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.

A retrospective cohort study of 756 cases of abdominal tuberculosis: Two decades single centre experience

Aim/objectiveIndia accounts for the highest tuberculosis burden in the world, and abdominal tuberculosis has been an endemic surgical and gastroenterological problem. Aim of this study is to present our two decades experience on abdominal (gastrointestinal) tuberculosis. Method756 patients, who received standard antituberculous treatment with or without surgical treatment with the diagnosis of abdominal tuberculosis from January 1996 and May 2014, were reviewed retrospectively. On the basis of clinical presentation, four groups of clinical presentation were identified and various diagnostic measures used in different groups were studied. Numeric values were determined as percent or mean±standard deviation. Kruskal–Wallis test was used for quantitative results and chi-square test was used for qualitative results between groups. p value of less than 0.05 was considered to indicate the statistical significance. ResultsThe duration of symptoms was variable in this study. Out of 756 patients, 64 patients gave definite past history of tuberculosis. Most of the patients in the acute pain abdomen group required surgery while most patients in chronic pain group responded well to medical management. There was significant difference in mortality among the four groups (p=0.025). ConclusionPrognosis seems significantly related to the severity of disease, with graver prognosis and less symptomatic improvement in more seriously ill presentations.

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.

Tuberculous lymphadenitis of the head and neck in Canadian children: Experience from a low-burden region

BackgroundChildren are more likely than adults to develop extra-pulmonary tuberculosis (EPTB), which often presents as cervical lymphadenopathy. The role of surgery in management is uncertain. We reviewed all head and neck EPTB cases presenting to our tertiary care pediatric institution over a twelve-year period. MethodsAll children 18 years of age and younger with EPTB involving the head and neck were included. We recorded clinical data and age at diagnosis, birth country, BCG vaccination status, as well as radiographic, surgical, histological, and microbiological results. ResultsAll 16 patients presented with cervical lymphadenopathy. Fourteen were born outside of Canada in TB endemic areas and all had foreign-born parents. Diagnosis was confirmed microbiologically from lymph node biopsies in 14 cases. Multi-drug resistant TB was identified in two cases: both had previous excisional node biopsies that had not been cultured. Two patients had culture negative suppuration despite adequate anti-tuberculous treatment that required surgery for cure. ConclusionOngoing suppuration despite appropriate drug therapy is seen in a minority of patients. We found that excisional lymph node biopsy of diseased cervical lymph nodes is diagnostic, and also therapeutic in some cases with ongoing suppuration despite appropriate drug therapy. Mycobacterial culture of lymph nodes is important for diagnosis and determination of drug resistance patterns.

Utility of 18 F-FDG PET/CT scan to diagnose the etiology of fever of unknown origin in patients on dialysis.

Studies on fever of unknown origin (FUO) in patients of chronic kidney disease and end stage renal disease patients on dialysis were not many. In this study, we used 18 F-FDG PET/CT scan whole body survey for detection of hidden infection, in patients on dialysis, labelled as FUO. In this retrospective study, 20 patients of end stage renal disease on dialysis were investigated for the cause of FUO using 18F-FDG PET/CT scan. All these patients satisfied the definition of FUO as defined by Petersdorf and Beeson. Any focal abnormal site of increased FDG concentration detected by PET/CT, either a solitary or multiple lesions was documented and at least one of the detected abnormal sites of radio tracer concentration was further examined for histopathology. All patients were on renal replacement therapy. Of these, 18 were on hemodialysis and two were on peritoneal dialysis. 18F-FDG PET/CT scan showed metabolically active lesions in 15 patients and metabolically quiescent in five patients. After 18F-FDG PET/CT scan all, but one patient had a change in treatment for fever. Anti-tuberculous treatment was given in 15 patients, antibiotics in four patients and anti-malaria treatment in one patient. The present study is first study of 18F-FDG PET/CT scan in patients of end stage renal disease on dialysis with FUO. The study showed that the 18 F FDG PET/CT scan may present an opportunity to attain the diagnosis in end stage renal disease patients on dialysis with FUO.

Ewings Sarcoma of the Hand–A Case Report

Ewings sarcoma of the hand is relatively rare. Ewings sarcoma can present with minimal pain and swelling of the affected digit. The Erythrocyte sedimentation rate and C-reactive protein may be high. Radiologically, Ewings sarcoma can present with a plethora of features from permeative bone destruction to expansile lesions with or without periosteal reaction. Because of these features, this can be confused with Tuberculosis especially in a country like ours where Tuberculosis is endemic. This leads to starting of inappropriate treatment and delay in diagnosis. We report a case of an 18year old boy who was initially diagnosed as Tuberculous dactylytis of the proximal phalanx of the little finger. He was started on anti-tuberculous treatment and did not respond to it. Subsequent investigation in our centre which also included an open biopsy, confirmed the diagnosis of Ewings sarcoma. He was treated with ray excision, and chemotherapy. This case is being presented for its rarity and also to emphasize the fact that an open biopsy in suspected cases would be appropriate to confirm the diagnosis. This would prevent delay in diagnosis of rare conditions like Ewings sarcoma.

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.

Associations between systemic inflammation, mycobacterial loads in sputum and radiological improvement after treatment initiation in pulmonary TB patients from Brazil: a prospective cohort study

BackgroundMycobacterium tuberculosis infection is known to cause inflammation and lung tissue damage in high-risk populations. Nevertheless, direct associations between mycobacterial loads, systemic inflammation and pulmonary lesions upon treatment initiation have not been fully characterized. In the present exploratory study, we prospectively depict the immune profile, microbial clearance and evolution of radiographic lesions in a pulmonary tuberculosis (PTB) patient cohort before and 60 days after anti-tuberculous treatment (ATT) initiation.MethodsCirculating levels of cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α) and C-reactive protein (CRP), as well as values of erythrocyte sedimentation rate (ESR) were measured in cryopreserved serum samples obtained from 73 PTB patients at pre-ATT and day 60 of treatment. Changes of the immune profile over time were compared with mycobacterial loads in sputum and culture conversion at day 60 of ATT. Additional analyses tested associations between improvement of chest radiographic lesions at day 60 and pre-treatment status of inflammation and mycobacterial loads.ResultsWithin the inflammatory parameters evaluated, values of CRP, IL-2, IL-4, TNF-α and ESR significantly decreased upon treatment initiation. On the converse, IL-10 levels substantially increased at day 60 of ATT, whereas concentrations of IL-6 and IFN-γ remained unchanged. Multidimensional analyses revealed that ESR, IL-2, IL-4 and CRP were the parameters with the highest power to discriminate individuals before and after treatment initiation. We further demonstrated that higher bacterial loads in sputum at pre-ATT were associated with increased systemic inflammation and higher risk for positive M. tuberculosis sputum cultures at day 60 of treatment. Furthermore, we found that pre-ATT mycobacterial loads in sputum and systemic inflammation synergistically associated with the status of radiographic lesions during treatment (Relative risk for chest X-ray improvement: 10.0, 95 % confidence interval: 2.4–40.0, P = 0.002).ConclusionsM. tuberculosis loads in sputum are directly associated to the status of systemic inflammation and potentially impact the immune profile, culture conversion and evolution of lung lesions upon ATT initiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1736-3) contains supplementary material, which is available to authorized users.

Lytic Lesions of Vertebrae Without Involvement of Intervertebral Disc- An Atypical Presentation of Spinal Tuberculosis

Tuberculosis is very common in our country. It can involve many organs and have broad spectrum of image presentation. It may resemble malignant diseases, especially in the elderly and thus confuse the judgement of the clinician. We report a case of a 58 year old gentleman presenting with chronic cough, low grade fever, weight loss for 16 months; features of progressive marrow failure for 8 months and severe low back pain without any neurological features for 2 months. The CT scan of spine revealed lytic lesions of vertebrae sparing the intervertebral discs, thus resembling metastatic lesions of bone. We approached this case as malignant disease initially, but found it to be a disseminated tuberculosis infection involving lungs, bone marrow and spine after a series of investigations. Though disseminated TB is not uncommon in our country, the purpose of presenting this case is to give emphasis that, clinicians should consider Pott’s disease (spinal tuberculosis) in the differential diagnosis of patients with back pain and destructive vertebral lesions. Proper diagnosis and anti-tuberculous treatment with or without surgery will result in cure of the patientBangladesh J Medicine Jul 2016; 27(2) : 81-85

Myelofibrosis with Tuberculosis: A Case Report

Myelofibrosis (MF), or fibrosis of the bone marrow, is an uncommon condition. Most cases arise secondary to other disease processes. However, whether tuberculosis can stimulate a secondary fibrotic reaction or develop in patients who have preexisting myeloproliferative disorders is not clear. Here we present a case of a 54-year-old man whose myelofibrosis disappeared completely after administration of antituberculous treatment. The purpose of reporting this case is to reconsider the relationship between tuberculosis and secondary myelofibrosis.