Months Of Tuberculosis Treatment Research Articles

Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial.

Children living with HIV(CLWH) are at high risk of tuberculosis(TB) and face poor outcomes, despite antiretroviral treatment(ART). We evaluated outcomes in CLWH and HIV-uninfected children treated for non-severe TB in the SHINE trial. SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, non-severe TB who were randomized to receive 4 vs 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CLWH. Of 1204 enrolled, 127(11%) were CLWH, of similar age (median(IQR) 3.6(1.2, 10.3) vs. 3.5(1.5, 6.9)years, p= 0.07), but more underweight (WAZ; -2.3(-3.3, -0.8) vs -1.0(-1.8, -0.2), p<0.01) and anemic (hemoglobin 9.5(8.7, 10.9) vs 11.5(10.4, 12.3)g/dl, p<0.01) compared to HIV-uninfected children. 68(54%) CLWH were ART-naïve; baseline median CD4 count 719(241-1134) cells/mm3, CD4% 16(10-26)%). CLWH were more likely to be hospitalized (aOR=2.4(1.3-4.6)) and die (aHR(95%CI) 2.6(1.2,5.8)). HIV status, age <3 years (aHR 6.3(1.5,27.3)), malnutrition (aHR 6.2(2.4,15.9)) and hemoglobin <7g/dl(aHR 3.8(1.3,11.5) independently predicted mortality. Among children with available VL, 45% and 61% CLWH had VL<1000copies/ml at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 vs 6 months) on TB treatment outcomes by HIV status (p for interaction=0.42). We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CLWH treated for non-severe TB. Irrespective of TB treatment duration, CLWH had higher rates of mortality and hospitalization than HIV-uninfected counterparts.

Safety and immunogenicity of the H56:IC31 tuberculosis vaccine candidate in adults successfully treated for drug-susceptible pulmonary TB: a phase 1 randomized trial.

H56:IC31 is a candidate vaccine against tuberculosis (TB) with the potential to reduce TB recurrence rate. It is thus important for future clinical trials to demonstrate safety and immunogenicity of H56:IC31 in individuals treated for TB. 22 adults confirmed to be Mtb negative (by 2 GeneXpert tests or 2 sputum cultures) after four-five months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive two doses of H56:IC31 (5 mg H56:500 nmol IC31; N=16) or placebo (N=6) 56 days apart. Participants were followed for 420 days for safety and immunogenicity. H56:IC31 vaccination was associated with an acceptable safety profile, consisting mostly of mild self-limited injection site reactions. No serious adverse events, and no vaccine-related severe adverse events, were reported. H56:IC31 induced a CD4+ T-cell response for Ag85B and ESAT-6, with ESAT-6 being immunodominant, which persisted through six months after the last vaccination. There was some evidence of CD8+ T-cell responses for both Ag85B and ESAT-6, but to a lesser extent than CD4+ responses. H56:IC31 was associated with an acceptable safety profile, and induced a predominant CD4+ T-cell response, in adults recently treated for drug-susceptible, uncomplicated pulmonary TB. ClinicalTrials.gov, NCT02375698.

Otoprotective and antioxidant activity of cytoflavin in pulmonary tuberculosis patients receiving amikacin

The objective: to study the potential otoprotective and antioxidant activity of cytoflavin in new pulmonary tuberculosis patients receiving aminoglycoside amikacin.Subjects and Methods. A randomized controlled trial was conducted and included 90 patients with new infiltrative pulmonary tuberculosis with decay, of both genders aged from 20 to 50 years old. Clinical, paraclinical and statistical methods were used in the study. Audiometric screening was carried out by Diagnostic Audiometer AD 226. The degree of antioxidant protection was determined by the oxidation reaction of ABTS in blood serum and plasma.Results. The study included 4 groups of tuberculosis patients and 1 group of healthy donors. Dissemination of pulmonary tuberculosis in 4 groups was approximately the same and was measured by scores. Prior to the start of treatment in all 4 groups (the group receiving standard chemotherapy (CTX) without amikacin, the group receiving «CTX+amikacin», the group receiving «CTX+cytofl avin», the group receiving «CTX+amikacin+cytofl avin») there was a decrease in blood antioxidant activity compared to Control Group. After 3 months of tuberculosis treatment in all 4 groups, the results improved, while in «CTX+Cytofl avin» Group they were similar to Control Group, and «CTX+Amikacin+Cytofl avin Group», they were only 4.8% less. The elevated level of leukocytes decreased by 10.6% in CTX Group, 16.9% in «CTX+Amikacin» Group, 38.3% in «CTX+Cytofl avin» Group, and 72.3% in «CTX+Amikacin+Cytofl avin» Group. In the study, manifestations of oto- and vestibulotoxicity were found only in the «CTX+Amikacin» Group (in 4/20 (5%)). There were no such cases in «Amikacin+Cytofl avin» Group consisting of 23 patients.

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity.

People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB-treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB-diabetes (TB-DM) co-morbidity have excessive inflammatory and reduced interferon responses at diagnosis. It is unknown whether this persists through treatment and contributes to the adverse outcomes. Pulmonary TB patients recruited in South Africa, Indonesia and Romania were classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or TB-only, based on glycated haemoglobin concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood at diagnosis and intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification. Transcriptomic data were analysed by longitudinal mixed-model regression to identify whether genes were differentially expressed between clinical groups through time. Predictive models of TB-treatment response across groups were developed and cross-tested. Gene expression differed between TB and TB-DM patients at diagnosis and was modulated by TB treatment in all clinical groups but to different extents, such that differences remained in TB-DM relative to TB-only throughout. Expression of some genes increased through TB treatment, whereas others decreased: some were persistently more highly expressed in TB-DM and others in TB-only patients. Genes involved in innate immune responses, anti-microbial immunity and inflammation were significantly upregulated in people with TB-DM throughout treatment. The overall pattern of change was similar across clinical groups irrespective of diabetes status, permitting models predictive of TB treatment to be developed. Exacerbated transcriptome changes in TB-DM take longer to resolve during TB treatment, meaning they remain different from those in uncomplicated TB after treatment completion. This may indicate a prolonged inflammatory response in TB-DM, requiring prolonged treatment or host-directed therapy for complete cure. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes for use across populations.

Prevalence and factors associated with sputum smear non-conversion after two months of tuberculosis treatment among smear-positive pulmonary tuberculosis patients in Rwanda: a cross-sectional study

BackgroundNon-conversion of sputum smear prolongs the infectivity of pulmonary tuberculosis patients and has been associated with unfavorable tuberculosis (TB) treatment outcomes. Nevertheless, there is a limited evidence on predictors of sputum smear non-conversion among smear-positive PTB (SPPTB) patients in Rwanda. Therefore, this study aimed to determine the factors associated with sputum smear non-conversion after two months of treatment among SPPTB patients in Rwanda.MethodsA cross-sectional study was conducted among SPPTB patients registered in the national electronic TB reporting system by all health facilities countrywide (Rwanda) from July 2019 to June 2021. Eligible patients who had completed the first two months of anti-TB treatment and with smear results at the end of the second month of treatment were included in the study. Bivariate and multivariate logistic regression analyses were done using STATA version 16 to determine the factors associated with sputum smear non-conversion. Adjusted odds ratio (OR), 95% confidence interval (CI), and p-value < 0.05 was considered statistically significant.ResultsThis study included 7,211 patients. Of them, 632 (9%) patients had sputum smear non-conversion at the end of the second month of treatment. In multivariate logistic regression analysis, age groups of 20–39 years (AOR = 1.7, 95% CI: 1.0-2.8) and 40–59 years (AOR:2, 95% CI: 1.1–3.3), history of first-line TB treatment failure (AOR = 2, 95% CI: 1.1–3.6), follow-up by community health workers(CHWs) (AOR = 1.2, 95% CI: 1.0-1.5), BMI < 18.5 at TB treatment initiation (AOR = 1.5, 95% CI: 1.2–1.8), and living in Northern Province of Rwanda (AOR = 1.4, 95% CI: 1.0–2.0), were found to be significantly associated with sputum smear non-conversion after two months of treatment.ConclusionSputum smear non-conversion among SPPTB patients remains low in Rwanda compared to countries of similar health care setting. Identified risk factors for sputum smear non-conversion among SPPTB patients in Rwanda were age (20–39 years, 40–59 years), history of first-line TB treatment failure, follow up by CHWs, BMI < 18.5 at TB treatment initiation and residence (Northern province).

Thyroid Profile of Childhood Tuberculosis Treated with Anti Tuberculosis Drug During Intensive Phase

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The incidence is 10 % in children. Tuberculosis has high morbidity and mortality which needs adequate treatment. The side effects of FDC is thyroid hormone dysfunction which can interfere children's quality of life. However, research about the effect of FDC therapy on thyroid hormone profile in children with TB are very limited. Objective: To determine the effect of anti-tuberculosis drug treatment on thyroid hormone profile in paediatric tuberculosis. Methods: A one group pretest-posttest design study of 50 patients was conducted at the Semarang Health Center for the period January 2021-June 2021. Thyroid function tests of TSH, FT4 and T3, in TB children were measured before FDC therapy and 2 months after administration. The data were analysed descriptively and a comparative test was performed using SPSS 25.Results: There were no significant differences in TSH, FT4 and T3 serum levels before FDC therapy and 2 months of FDC administration. Thyroid hormone levels before treatment and 2 months after administration of FDC, respectively, euthyroid in 44 vs 42 patients.Conclusion: Two months of tuberculosis treatment in children decreased the serum FT4 and T3 level but no changes in the serum TSH level before and after the treatment.

Patients’ Perceptions on the Factors Contributing to Non-conversion after Two Months of Tuberculosis Treatment at Selected Primary Healthcare Facilities in the Ekurhuleni Health District, South Africa

Background: Tuberculosis patients’ non-conversion is one of the factors impeding the ‘End TB’ strategies in South Africa. Several reasons have been recognised as contributing to patients with TB non-conversion, including TB illiteracy, denial of TB infection, reluctance to honour follow-up visits, and an unwillingness to take prescribed treatment for six months. Objective: In light of this, this study aimed at exploring and describing factors contributing to patients with pulmonary TB non-conversion at two and three months of treatment at selected primary healthcare facilities in the Ekurhuleni Health District, Gauteng province. Methods: A qualitative, explorative and descriptive research design was adopted with eight purposively sampled patients receiving TB care from five selected primary healthcare facilities. Semi-structured interviews were utilised to collect data from eight purposively sampled participants, who were interviewed on what they perceived to be factors contributing to patients with TB non-conversion at two and three months of treatment. Results: The study found that patients with TB attending the selected primary healthcare facilities experience psychosocial problems, such as shortage of food and lack of family support, as well as insufficient patient healthcare literacy. Conclusion: The study recommends that enhanced patient education be given from the time a patient starts TB treatment. The involvement of multi-disciplinary teams and other stakeholders is important in the management of patients with TB. Furthermore, the outreach team must provide health education to patients with TB family members, so that they can support the patients with TB to comply with treatment. Family support must be emphasised because it encourages patients with TB to comply with the course of treatment.

Impact of early diagnosis of impaired glucose regulation in tuberculosis: Comparison of clinical outcomes in people with tuberculosis in Tanzania

Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. A prospective cohort study recruited TB participants receiving anti-TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre-existing DM or pre-treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6months of TB treatment. Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co-infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR (p> 0.05). Time to death for participants with and without IGR was 18 versus 28 days (p= 0.870), respectively. Age ≥ 40 years (p= 0.038), bacteriological positive (p= 0.039), HIV (p= 0.009), or recurrent TB (p= 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co-management of multi-morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.

Evaluation of host biomarkers for monitoring treatment response in spinal tuberculosis: A 12-month cohort study

BackgroundMonitoring treatment response is an important precaution in spinal tuberculosis (TB), particularly when the condition was clinically diagnosed rather than bacteriologically confirmed and when drug susceptibility testing was not performed. Conventional monitoring measures have limitations and there is a need for favourable alternatives. Therefore, this study aimed to investigate changes in immune biomarkers over the course of treatment for spinal TB and to compare these responses to the conventional monitoring measure, erythrocyte sedimentation rate (ESR). MethodsPatients with spinal TB were recruited from a tertiary hospital in the Western Cape, South Africa, and provided blood samples at 0, 3, 6, 9 and 12 months of TB treatment. Blood samples were analysed for ESR, using standard techniques, and for 19 cytokines, using a multiplex platform. Changes in ESR and cytokine levels were investigated using a mixed model ANOVA and Least Significant Difference post-hoc testing. ResultsTwenty-six patients with spinal TB were included in the study although only fifteen remained in follow-up at 12 months. Seven biomarkers changed significantly over the course of treatment (CRP, Fibrinogen, IFN-γ, Ferritin, VEGF-A, ApoA1 and NCAM, p < 0.01) with a further three showing a strong trend towards change (CCL1, CXCL9 and GDF-15, 0.05 ≥ p ≤ 0.06). Responsive biomarkers could be approximately grouped according to patterns of progressive, initial or delayed change. ESR performed similarly to CRP, Fibrinogen and IFN-γ with all showing significant decreases between 0, 6 and 12- months of treatment. Individual ESR responses were variable. DiscussionIndividual ESR responses may be unreliable and support the investigation of multi-marker approaches to evaluating treatment response in spinal TB. Biomarkers of treatment response identified in the current study require validation in a larger study, which may also incorporate aspects such as evaluating biomarkers within the first week of treatment and the inclusion of a healthy control group.

Association Between Breast Carcinoma and Homolateral Axillary Lymph Node Tuberculosis: A Case Report.

Introduction: The association between axillary tuberculosis and breast cancer is rare, and only about thirty cases have been described in the literature. This entity must be mentioned in an endemic country faced with the notion of tuberculosis contagion. Case presentation: We report the case of a patient in whom the association between breast carcinoma and axillary tuberculosis discovery was fortuitous postoperatively. But retrospectivly her husband contracted the tuberculosis 30 years ago. She had mastectomy with axillary lymph node dissection because the tumour was multifocal. The carcinoma was classified as pT2N0M0 (stage IIA classification TNM) and she was only put on hormone therapy. After 5 years of follow-up, no recurrence was noted despite the therapeutic insufficiency. Conclusion: Mammary lymph node tuberculosis is rare; it must be mentioned in the context of tuberculosis contagion or in front of the the presence of calcifications in the axillary area on the x-ray. At the slightest suspicion of this diagnosis, the operating parts should not be fixed but sent in the fresh state for a ZIEHL-NELSEN staining for the detection of Koch's bacillus or for a culture. The anti-tuberculosis treatment should be immediately started after the surgery. If the cancer target is indicated, it should not be started until after 1 month of tuberculosis treatment, given the risk of tuberculosis outbreak.

Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis.

Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture–positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542–9188] vs 698 [218–4060] pg/mL, respectively; P = .004) and after (3650 [1214–3888] vs 720 [551–1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity.

Effectiveness and safety of co-administration of moxifloxacin with netilmicin in drug-resistant tuberculosis patients, and its impact on inflammatory factors and immune function

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To study the effectiveness and safety of co-administration of moxifloxacin with netilmicin in drug-resistant tuberculosis (TB) patients, and its impact on levels of inflammatory factors and immune function.&#x0D; Methods: We enrolled 100 patients with drug-resistant TB admitted to People’s Hospital of Rizhao between May 2017 and October 2019. The patients were randomly allocated to control group and study group, with 50 patients per group. The control group received moxifloxacin at a dose of 0.2 g t.i.d. for 6 months and the study group received netilmicin at a dose of 0.1 g t.i.d. plus. The response, incidence of adverse reactions, expression levels of inflammatory factors, immune function, and sputum-negative status after 2, 4 and 6 months of TB treatment were compared.&#x0D; Results: The study group showed markedly higher response than the control group (p &lt; 0.05). Moreover, there were lower incidence of adverse effects in the study group than in the control group (p &lt; 0.05). The expression levels of inflammatory factors were significantly lower in the study group, while the concentrations of CD3+, CD4+, and CD8+ were markedly higher (p &lt; 0.05). After 2, 4 and 6 months of TB treatment, cases of sputum-negative conversion were significantly higher in the study group than in the control group (p &lt; 0.05).&#x0D; Conclusion: Co-administration of moxifloxacin with netilmicin produces much higher effectiveness and safety than moxifloxacin monotherapy, decreases inflammatory factor levels and improves immune function in patients with drug-resistant TB.&#x0D; &#x0D; &#x0D; &#x0D;

Efficacy of smoking cessation intervention delivered through mobile tele-counseling among smokers with tuberculosis in a Revised National Tuberculosis Control Program

BackgroundIndia has high burden of tuberculosis and smokers. Prevalence of tuberculosis is three times higher in smokers than non-smokers. Active smoking causes severe disease, delay in seeking treatment, lost to treatment follow up, delayed sputum conversion and drug resistance. WHO advocates mobile phone technology to improve health outcomes (mHealth). We used mobile tele-counseling as a smoking cessation intervention in smokers with tuberculosis (TB) receiving treatment under tuberculosis control program. AimTo determine smoking quit rate at six months of TB treatment among smokers receiving mobile tele-counseling versus brief advice and to estimate smoking quit rates and relapse rates during the tele-counseling period. MethodsOpen label randomized controlled trial. Newly detected pulmonary tuberculosis or pleural effusion patients received brief advice on smoking cessation as per The UNION's guiding framework. Subjects were then randomly allocated to intervention or control group. Intervention group was contacted telephonically at 2,3,4,5 and 6 months to assess smoking quit rates and provide continued smoking cessation advice. ResultsIntervention group had 80 and 82 in the control group, mean (SD) age was 40.6(12.6), 43.5(12.7) p = 0.53. Quit rate at six months was 54 (67.5%) in intervention group versus 34 (42%) in control group; RR 1.60 (95% CI 1.19, 2.16) p = 0.001. Trend in smoking quit rates in intervention group was 81.3%, 61.3%, 55%, 73.8% at 2,3,4 and 5 months respectively. Smoking relapse rate was 43.1%, 53.1%, 20.5%,15.3% at 3,4,5 and 6 months respectively. 27.5%, 43.8% were abstinent for last three, two months. ConclusionsMobile tele-counseling is an effective strategy for smoking cessation among TB patients.

Effect of quitting smoking on health outcomes during treatment for tuberculosis: secondary analysis of the TB & Tobacco Trial

BackgroundDespite treatment, patients with tuberculosis (TB) who smoke have poorer outcomes compared with non-smokers. It is unknown, however, if quitting smoking during the 6 months of TB treatment improves TB...

#95: Clinical Profile and Outcome of Pediatric Acute Lymphoblastic Leukemia Patients with Tuberculosis at the Philippine General Hospital

Abstract Background The Philippines remains one of the countries on the WHO list of high-burden countries for tuberculosis (TB), and malignancy has long been recognized as a risk factor for this disease. This report describes the clinical profile and outcomes of pediatric patients with acute lymphoblastic leukemia (ALL) diagnosed with tuberculosis. Methods Medical records of pediatric patients with ALL consulting at the University of the Philippines – Philippines General Hospital diagnosed from January 2015 to December 2017 (excluding those with concomitant HIV infection) were reviewed. Those diagnosed with tuberculosis infection were further analyzed, obtaining demographic data, results of diagnostics, and treatment. Results Out of 102 patients, 5 were found to have tuberculosis, all of them being male, with an average age of 7.2 years old. All cases were pulmonary, with one patient having multi-drug-resistant TB. PPD was positive in 4 cases, with indurations measuring &amp;gt;10mm, while chest radiographs showed nonspecific findings for 3 patients. Of 3 patients who underwent sputum AFB testing, one had a positive result. While 1 patient was diagnosed with TB and ALL concurrently, majority of patients were diagnosed after entering remission. Three patients completed 6 months of TB treatment, while 1 patient is still on medication for multi-drug-resistant tuberculosis. One patient abandoned treatment. Conclusion In this group of ALL patients, malnutrition and corticosteroid use were not found to be independent risk factors for TB. As TB disease may be due to reactivation of latent TB infection (LTBI) during immunosuppression, screening for LTBI may be a worthwhile strategy to decrease morbidity. Transmission precautions are emphasized to reduce acquired TB infection in immunocompromised populations.

IP-10 as a Non Sputum Biomarker in TB Treatment Monitoring

There are currently still limitations in the diagnosis of tuberculosis (TB). Sputum collection as specimen for diagnosis is not only difficult but also has low sensitivity.In blood, IP-10/CXCL-10 chemokine plays a role in inducing the movements of chemotactic inflammatory cells towards the sites of inflammation. A high level of IP-10 is found in active pulmonary TB patients and significantly decline after the patients have completed the TB treatments. The aim of this study was to analyze the decline of the IP-10 level before and after 2 months of TB treatment. This study was conducted from March­ toJuni 2020. This was a comparative observational cohort study on active pulmonary TB patients who were &gt;18 years old at the DOTS Clinic of Dr. Hasan Sadikin General Hospital Bandung. Thirty patients who met the inclusion criteria were followed up until 2 months of TB treatment. Serum of these patients were collected and examined for the IP-10 level before and after 2 months of TB treatment. It was demonstrated that the median IP-10 level in new active pulmonary TB patients was 384.1 pg/mL (136.70–779.80) and dropped to 251.85 pg/mL (91.10–698.30) (p&lt;0l001) two months of TB treatment. Thus, the IP-10 level in the active pulmonary TB patients is significantly declined (p&lt;0.001) after 2 months of TB treatment and that serum IP-10 level could be considered as a non-sputum-based marker to monitor TB treatment.

Safety and immunogenicity of the adjunct therapeutic vaccine ID93 + GLA-SE in adults who have completed treatment for tuberculosis: a randomised, double-blind, placebo-controlled, phase 2a trial

A therapeutic vaccine that prevents recurrent tuberculosis would be a major advance in the development of shorter treatment regimens. We aimed to assess the safety and immunogenicity of the ID93 + GLA-SE vaccine at various doses and injection schedules in patients with previously treated tuberculosis. This randomised, double-blind, placebo-controlled, phase 2a trial was conducted at three clinical sites near Cape Town, South Africa. Patients were recruited at local clinics after receiving 4 months of tuberculosis treatment, and screened for eligibility after providing written informed consent. Participants were aged 18-60 years, BCG-vaccinated, HIV-uninfected, and diagnosed with drug-sensitive pulmonary tuberculosis. Eligible patients had completed standard treatment for pulmonary tuberculosis in the past 28 days. Participants were enrolled after completing standard treatment and randomly assigned sequentially to receive vaccine or placebo in three cohorts: 2 μg intramuscular ID93 + 2 μg GLA-SE on days 0 and 56 (cohort 1); 10 μg ID93 + 2 μg GLA-SE on days 0 and 56 (cohort 2); 2 μg ID93 + 5 μg GLA-SE on days 0 and 56 and placebo on day 28 (cohort 3); 2 μg ID93 + 5 μg GLA-SE on days 0, 28, and 56 (cohort 3); or placebo on days 0 and 56 (cohorts 1 and 2), with the placebo group for cohort 3 receiving an additional injection on day 28. Randomisation was in a ratio of 3:1 for ID93 + GLA-SE and saline placebo in cohorts 1 and 2, and in a ratio of 3:3:1 for (2 ×) ID93 + GLA-SE, (3 ×) ID93 + GLA-SE, and placebo in cohort 3. The primary outcomes were safety and immunogenicity (vaccine-specific antibody response and T-cell response). For the safety outcome, participants were observed for 30 min after each injection, injection site reactions and systemic adverse events were monitored until day 84, and serious adverse events and adverse events of special interest were monitored for 6 months after the last injection. Vaccine-specific antibody responses were measured by serum ELISA, and T-cell responses after stimulation with vaccine antigens were measured in cryopreserved peripheral blood mononuclear cells specimens using intracellular cytokine staining followed by flow cytometry. This study is registered with ClinicalTrials.gov, number NCT02465216. Between June 17, 2015, and May 30, 2016, we assessed 177 patients for inclusion. 61 eligible patients were randomly assigned to receive: saline placebo (n=5) or (2 ×) 2 μg ID93 + 2 μg GLA-SE (n=15) on days 0 and 56 (cohort 1); saline placebo (n=2) or (2 ×) 10 μg ID93 + 2 μg GLA-SE (n=5) on days 0 and 56 (cohort 2); saline placebo (n=5) on days 0, 28 and 56, or 2 μg ID93 + 5 μg GLA-SE (n=15) on days 0 and 56 and placebo injection on day 28, or (3 ×) 2 μg ID93 + 5 μg GLA-SE (n=14) on days 0, 28, and 56 (cohort 3). ID93 + GLA-SE induced robust and durable antibody responses and specific, polyfunctional CD4 T-cell responses to vaccine antigens. Two injections of the 2 μg ID93 + 5 μg GLA-SE dose induced antigen-specific IgG and CD4 T-cell responses that were significantly higher than those with placebo and persisted for the 6-month study duration. Mild to moderate injection site pain was reported after vaccination across all dose combinations, and induration and erythema in patients given 2 μg ID93 + 5 μg GLA-SE in two or three doses. One participant had grade 3 erythema and induration at the injection site. No vaccine-related serious adverse events were observed. Vaccination with ID93 + GLA-SE was safe and immunogenic for all tested regimens. These data support further evaluation of ID93 + GLA-SE in therapeutic vaccination strategies to improve tuberculosis treatment outcomes. Wellcome Trust (102028/Z/13/Z).

The Impact of Hypertension and Use of Calcium Channel Blockers on Tuberculosis Treatment Outcomes

Hypertension induces systemic inflammation, but its impact on the outcome of infectious diseases like tuberculosis (TB) is unknown. Calcium channel blockers (CCB) improve TB treatment outcomes in preclinical models, but their effect in patients with TB remain unclear. This retrospective cohort study, including all patients > 18 years receiving treatment for culture-confirmed, drug-sensitive TB from 2000 to 2016 at the National Taiwan University Hospital, assessed the association of hypertension and CCB use with all-cause and infection-related mortality during the first 9 months of TB treatment, as well as sputum smear microscopy and sputum culture positivity at 2 and 6 months. Of the 2894 patients, 1052 (36.4%) had hypertension. A multivariable analysis revealed that hypertension was associated with increased mortality due to all causes (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.23-1.99) and infections (HR, 1.87; 95% CI, 1.34-2.6), but there were no statistical differences in microbiological outcomes when stratified based on hypertensive group. Dihydropyridine-CCB (DHP-CCB) use was associated only with reduced all-cause mortality (HR, 0.67; 95% CI, .45-.98) by univariable Cox regression. There were no associations between DHP-CCB use and infection-related mortality (HR, 0.78; 95% CI, .46-1.34) or microbiological outcomes in univariable or multivariable regression analyses. Patients with hypertension have increased all-cause mortality and infection-related mortality during the 9 months following TB treatment initiation. DHP-CCB use may lower all-cause mortality in TB patients with hypertension. The presence of hypertension or the use of CCB did not result in a significant change in microbiological outcomes.

Loss to follow-up among patients diagnosed with spinal tuberculosis at a tertiary hospital in Western Cape Province, South Africa: A retrospective cohort study.

Patients diagnosed with spinal tuberculosis (TB) at a major tertiary hospital in Western Cape Province, South Africa, are required to attend regular follow-up at the hospital's outpatient spine clinic and to remain on TB treatment for at least 9 months. This follow-up and lengthy treatment is intended to allow for specialist monitoring of TB treatment response and early identification of secondary complications, and to reduce the risk of recurrence. However, little is known about adherence to these recommendations. The main objectives were to describe (i) loss to spine clinic follow-up (LTFU), and (ii) TB treatment duration among patients diagnosed with spinal TB at the hospital. Secondary objectives were to investigate (i) the association between LTFU and treatment duration, and (ii) factors associated with LTFU. This retrospective cohort study included 173 adults diagnosed with spinal TB between 2012 and 2015 and investigated follow-up within 2 years from diagnosis. Clinical, demographic and appointment data were obtained from hospital records and a dataset provided by the provincial Department of Health. LTFU was presented as frequency (%) and as a survival analysis. TB treatment duration was reported as frequency &lt;9 months or ≥9 months, and the association between LTFU and &lt;9 months of treatment was investigated using relative risk (RR) with 95% confidence intervals (CIs). Univariate associations between explanatory variables and LTFU were investigated using simple logistic regression analysis. Patients had a median (interquartile range) age of 36 (29 - 48) years and included 98 females (57%) and 151 individuals (87%) residing &lt;50 km from the hospital. Primary outcomes were that 129 patients (75%) were LTFU within 2 years of diagnosis and 45 (30%) completed &lt;9 months of treatment. The RR of &lt;9 months of treatment was 1.62 (95% CI 1.39 - 1.88) among those LTFU compared with those retained in follow-up. LTFU was not associated with any of the clinical or demographic variables investigated. Three-quarters of the patients did not complete follow-up at the tertiary hospital spine clinic, and almost one in three received &lt;9 months of TB treatment. Remaining in spine clinic follow-up was significantly associated with receiving at least the minimum duration of TB treatment. However, LTFU could not be predicted from routine clinical and demographic information and is likely to be related to factors not accounted for in the current analysis.

Une histoire de fesse: cas d'une tuberculose gommeuse de la fesse chez un adulte immunocompétent

La tuberculose est une maladie endémique au Sénégal. Les formes cutanées sont rares et se caractérisent par leur polymorphisme clinique. Elles représentent 2% des localisations extra pulmonaires de la tuberculose. Nous rapportons l'observation d'une gomme tuberculeuse de la fesse révélant une localisation pulmonaire active chez un adulte immunocompétent. Un homme âgé de 47 ans fut admis pour une tuméfaction douloureuse de la fesse droite évoluant depuis quatre ans. L'examen physique notait un placard induré et polyfistulisé fait de nodules confluents avec une émission de pus jaunâtre, siégeant à la face inférointerne de la fesse droite, associé à des adénopathies inguinales bilatérales d'allure inflammatoire. Une tuberculose cutanée était retenue devant l'histologie qui montrait un granulome tuberculoïde et la recherche de BAAR dans le liquide de tubage gastrique qui était positif. La tomodensitométrie thoraco-abdominopelvienne avait montré de multiples micronodules pulmonaires acinaires basals bilatéraux. Les sérologies VIH et VHB étaient négatives. Une guérison était obtenue six mois après un traitement antituberculeux. La tuberculose cutanée se caractérise par son polymorphisme clinique en zone d'endémie. Elle doit aussi être cherchée devant tout placard d’abcès du périnée.