End Of Tuberculosis Treatment Research Articles

Effectiveness of double-dose dolutegravir in people receiving rifampin-based tuberculosis treatment: an observational, cohort study of people with HIV from six countries.

Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50 mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV. Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment. We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000 copies/mL. In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

Whole blood RNA signatures in tuberculosis patients receiving H56:IC31 vaccine as adjunctive therapy.

Therapeutic vaccination in tuberculosis (TB) represents a Host Directed Therapy strategy which enhances immune responses in order to improve clinical outcomes and shorten TB treatment. Previously, we have shown that the subunit H56:IC31 vaccine induced both humoral and cellular immune responses when administered to TB patients adjunctive to standard TB treatment (TBCOX2 study, NCT02503839). Here we present the longitudinal whole blood gene expression patterns in H56:IC31 vaccinated TB patients compared to controls receiving standard TB treatment only. The H56:IC31 group (N=11) and Control group (N=7) underwent first-line TB treatment for 182 days. The H56:IC31 group received 5 micrograms of the H56:IC31 vaccine (Statens Serum Institut; SSI, Valneva Austria GmbH) intramuscularly at day 84 and day 140. Total RNA was extracted from whole blood samples collected in PAXgene tubes on days 0, 84, 98, 140, 154, 182 and 238. The expression level of 183 immune-related genes was measured by high-throughput microfluidic qPCR (Biomark HD system, Standard BioTools). The targeted gene expression profiling unveiled the upregulation of modules such as interferon (IFN) signalling genes, pattern recognition receptors and small nucleotide guanosine triphosphate (GTP)-ases in the vaccinated group compared to controls two weeks after administration of the first H56:IC31 vaccine. Additionally, the longitudinal analysis of the Adolescent Cohort Study-Correlation of Risk (ACS-COR) signature showed a progressive downregulation in both study arms towards the end of TB treatment, in congruence with reported treatment responses and clinical improvements. Still, two months after the end of TB treatment, vaccinated patients, and especially those developing both cellular and humoral vaccine responses, showed a lower expression of the ACS-COR genes compared to controls. Our data report gene expression patterns following H56:IC31 vaccination which might be interpreted as a lower risk of relapse in therapeutically vaccinated patients. Further studies are needed to conclude if these gene expression patterns could be used as prognostic biosignatures for therapeutic TB vaccine responses.

Managing Comorbidities, Determinants and Disability at Start and End of TB Treatment under Routine Program Conditions in China.

Many patients with tuberculosis (TB) have comorbidities, risk determinants and disability that co-exist at diagnosis, during and after TB treatment. We conducted an observational cohort study in 11 health facilities in China to assess under routine program conditions (i) the burden of these problems at the start and end of TB treatment and (ii) whether referral mechanisms for further care were functional. There were 603 patients registered with drug-susceptible TB who started TB treatment: 84% were symptomatic, 14% had diabetes, 14% had high blood pressure, 19% smoked cigarettes, 10% drank excess alcohol and in 45% the 6 min walking test (6MWT) was abnormal. Five patients were identified with mental health disorders. There were 586 (97%) patients who successfully completed TB treatment six months later. Of these, 18% were still symptomatic, 12% had diabetes (the remainder with diabetes failed to complete treatment), 5% had high blood pressure, 5% smoked cigarettes, 1% drank excess alcohol and 25% had an abnormal 6MWT. Referral mechanisms for the care of comorbidities and determinants worked well except for mental health and pulmonary rehabilitation for disability. There is need for more programmatic-related studies in other countries to build the evidence base for care of TB-related conditions and disability.

Comparing cardiac MRI and lung PET/CT after completion of tuberculosis treatment – preliminary findings of participants co-enrolled into the StatinTB trial and Cardiac Imaging After TB (CIA-TB) study

Abstract Introduction Mortality rates after successful tuberculosis (TB) treatment remain elevated and healthy survival is impaired by chronic pulmonary disease and persistent inflammation. Inflammation leads to a complex cascade of events and has been associated with cardiovascular disease (CVD). Recent epidemiological work described an increased risk of CVD in persons with history of TB. Aims and objectives In our ongoing StatinTB trial (NCT04147286), we evaluate safety and efficacy of 40 mg atorvastatin to reduce persistent lung inflammation (PLI) after TB treatment in HIV−/HIV+ adults measured by 18F-FDG-PET/CT. Participants are co-enrolled into the Cardiac Imaging After Tuberculosis (CIA-TB) study. Here we report preliminary findings of participants enrolled into the StatinTB trial and CIA-TB study with the aim to correlate PLI with cardiac magnetic resonance imaging (CMR) parameters. Methods Participants with clinical response to TB treatment and a negative sputum culture at 16 weeks were screened at the end of a 24-week course of treatment for drug-sensitive TB. PET/CT was performed on a Philips Gemini TF scanner and analysed using MIM®Software. PLI was defined as total lung glycolysis (TLG) ≥50 SUV·mL (Figure 1). CMR was performed using a 3T Siemens Magnetom Skyra scanner and parameters were derived from the following acquisitions: SSFP cine imaging of the short and long axes, T1 mapping (MOLLI, 5 (3) 3), T2 mapping and late gadolinium enhancement (LGE) imaging. StatinTB trial is conducted according to ICH-GCP. Results 26 participants (mean age 37.8±13.8 years, 38.5% women) underwent PET/CT and CMR. 23.1% were infected with HIV, 34.6% smokers, and 26.9% had a previous history of TB. Median BMI was 21.3 (IQR 19.7; 24.3). One participant reported hypertension. Common symptoms at enrollment were cough (26.9%), shortness of breath (11.5%), and chest pain (3.9%). On CT scan, 73.1% had pulmonary nodules, 57.7% scarring, 50.0% cavities, 42.3% bronchiectasis, 19.2% centrilobular disease, 19.2% distorted lung architecture, and 11.5% consolidations. On PET/CT, PLI was detected among 11 (42.3%) participants with a mean TLG of 216.0 (IQR 78.2; 384.0). In a multivariable regression analysis, left ventricular end systolic volume (LVESV) (−1.46; 95% CI: −2.89, −0.23; p=0.047) and distorted lung architecture (2.84; 95% CI: 1.17, 4.52; p=0.003) were significantly associated with TLG. Native T1 relaxation time showed a strong, but not significant association with TLG (15.01; 95% CI: −8.08, 38.10; p=184). Conclusion We present data of a young cohort at the end of TB treatment without significant cardiac risk factors. Structural lung disease is affecting at least half of participants, and many remain symptomatic. PLI is present in more than one-third of participants and our preliminary findings suggest an association with cardiac impairment. Further enrolment and ongoing laboratory studies will shed more light into post-TB cardio-pulmonary sequelae. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EDCTP

Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment.

SummaryBackgroundGlobally, the tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success is lower among people with diabetes mellitus (DM). Predicting treatment outcome early after diagnosis, especially in TB-DM patients, would allow early treatment adaptation for individuals and may improve global TB control.MethodsSamples were collected in a longitudinal cohort study of adult TB patients from South Africa (n = 94) and Indonesia (n = 81), who had concomitant DM (n = 59), intermediate hyperglycaemia (n = 79) or normal glycaemia/no DM (n = 37). Treatment outcome was monitored, and patients were categorized as having a good (cured) or poor (failed, recurrence, died) outcome during treatment and 12 months follow-up. Whole blood transcriptional profiles before, during and at the end of TB treatment were characterized using unbiased RNA-Seq and targeted gene dcRT-MLPA.FindingsWe report differences in whole blood transcriptome profiles, which were observed before initiation of treatment and throughout treatment, between patients with a good versus poor TB treatment outcome. An eight-gene and a 22-gene blood transcriptional signature distinguished patients with a good TB treatment outcome from patients with a poor TB treatment outcome at diagnosis (AUC = 0·815) or two weeks (AUC = 0·834) after initiation of TB treatment, respectively. High accuracy was obtained by cross-validating this signature in an external cohort (AUC = 0·749).InterpretationThese findings suggest that transcriptional profiles can be used as a prognostic biomarker for treatment failure and success, even in patients with concomitant DM.FundingThe research leading to these results, as part of the TANDEM Consortium, received funding from the European Community's Seventh Framework Programme (FP7/2007-2013 Grant Agreement No. 305279) and the Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038). The research leading to the results presented in the Indian validation cohort was supported by Research Council of Norway Global Health and Vaccination Research (GLOBVAC) projects: RCN 179342, 192534, and 248042, the University of Bergen (Norway).

Post-tuberculosis lung disease: a comparison of Brazilian, Italian, and Mexican cohorts.

ABSTRACTObjective:To evaluate lung function in a cohort of patients with a history of pulmonary tuberculosis in Brazil, as well as to evaluate the decline in lung function over time and compare it with that observed in similar cohorts in Mexico and Italy. Methods:The three cohorts were compared in terms of age, smoking status, pulmonary function test results, six-minute walk test results, and arterial blood gas results. In the Brazilian cohort, pulmonary function test results, six-minute walk test results, and arterial blood gas results right after the end of tuberculosis treatment were compared with those obtained at the end of the follow-up period. Results:The three cohorts were very different regarding pulmonary function test results. The most common ventilatory patterns in the Brazilian, Italian, and Mexican cohorts were an obstructive pattern, a mixed pattern, and a normal pattern (in 58 patients [50.9%], in 18 patients [41.9%], and in 26 patients [44.1%], respectively). Only 2 multidrug-resistant tuberculosis cases were included in the Brazilian cohort, whereas, in the Mexican cohort, 27 cases were included (45.8%). Mean PaO2 and mean SaO2 were lower in the Mexican cohort than in the Brazilian cohort (p < 0.0001 and p < 0.002 for PaO2 and SaO2, respectively). In the Brazilian cohort, almost all functional parameters deteriorated over time. Conclusions:This study reinforces the importance of early and effective treatment of drug-susceptible tuberculosis patients, because multidrug-resistant tuberculosis increases lung damage. When patients complete their tuberculosis treatment, they should be evaluated as early as possible, and, if post-tuberculosis lung disease is diagnosed, they should be managed and offered pulmonary rehabilitation because there is evidence that it is effective in these patients.

Peculiarities of persons who inject drugs among patients with HIV–tuberculosis coinfection registered in 4th District TB Unit Bucharest during 2009–2018

Abstract Introduction: Human immunodeficiency virus (HIV)–tuberculosis (TB) coinfection is a worldwide problem and a subject of concern, being associated with high mortality and risk of complications. Intravenous drug use is a way of getting infected with HIV that continues to rise, especially in the big cities. We aimed to study the peculiarities of persons with HIV–TB who inject drugs. Methods: We performed a retrospective, observational study, among patients treated for TB in the 4th District TB unit, Bucharest, during a 10-year period. A unique registry of patients with TB was used, and data of all patients with HIV–TB were noted ( demographics, medical, treatment outcome). A comparison between drug users (people who inject drugs [PWID]) and nondrug users (non-PWID) was assessed. Results: We identified 122 patients with HIV–TB: 60 PWID, 58 non-PWID, and 4 former users. The mean age was 36.4 ± 9.8 years, 75% were males, and 73% were using antiretroviral treatment (ART). After comparing PWID with non-PWID patients, the following differences were noted: age (33.0 ± 6.0 years in PWID vs 40.5 ± 11.3 in non-PWID, P &lt; 0.0001), gender (87% vs 66% males, P = 0.0034), presence of chronic hepatitis (97% vs 21%, P &lt; 0.0001), CD4 number (156.1 ± 204.5 cells/mm3 vs 260.8 ± 248.9 cells/mm3, P = 0.0409), ART (65% vs 84%, P = 0.0075), and evaluation at the end of TB treatment (P = 0.0373). Conclusions: PWID represent a vulnerable population of those with HIV–TB coinfection, whose outcome in TB treatment is significantly poorer and who are at risk of abandonment, death, and comorbidities. They should be included in dedicated programmes that are aimed at increasing adherence to treatment and care, additionally assessing the dependence problem.

Is It Feasible to Conduct Post-Tuberculosis Assessments at the End of Tuberculosis Treatment under Routine Programmatic Conditions in China?

There is growing evidence that a substantial proportion of people who complete anti-tuberculosis treatment experience significant morbidity and mortality which can negatively affect their quality of life. It is suggested that national tuberculosis programs conduct end-of-treatment assessments, but whether this is feasible is currently not known. We therefore assessed whether tuberculosis program staff could assess functional and general health status of patients at the end of treatment in five TB clinics in four provinces in China. There were 115 patients, aged 14–82 years, who completed anti-tuberculosis treatment and a post-TB assessment. There were 54 (47%) patients who continued to have symptoms, the commonest being cough, dyspnea and fatigue. Symptom continuation was significantly more common in the 22 patients with diabetes (p = 0.027) and the 12 patients previously treated for TB (p = 0.008). There were 12 (10%) current smokers, an abnormal chest X-ray was found in 106 (92%) patients and distance walked in the 6-min walking test (6MWT) ranged from 30–750 m (mean 452 ± 120); 24 (21%) patients walked less than 400 m. Time taken to perform the post-TB assessment, including the 6MWT, ranged from 8–45 min (mean 21 ± 8 min). In 98% of the completed questionnaires, health workers stated that conducting post-TB assessments was feasible and useful. This study shows that post-TB assessments can be conducted under routine programmatic conditions and that there is significant morbidity that needs to be addressed.

Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study.

BackgroundNeutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.MethodsWe prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes.ResultsAmong 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]).ConclusionIncreased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted.

The Interaction of Diabetes and Tuberculosis: Translating Research to Policy and Practice.

Diabetes Mellitus increases the risk of developing Tuberculosis (TB) disease by about three times; it also doubles the risk of death during TB treatment and other poor TB treatment outcomes. Diabetes may increase the risk of latent infection with Mycobacterium tuberculosis (LTBI), but the magnitude of this effect is less clear. Whilst this syndemic has received considerable attention, most of the published research has focussed on screening for undiagnosed diabetes in TB patients or observational follow-up of TB treatment outcomes by diabetes status. There are thus substantial research and policy gaps, particularly with regard to prevention of TB disease in people with diabetes and management of patients with TB–diabetes, both during TB treatment and after successful completion of TB treatment, when they likely remain at high risk of TB recurrence, mortality from TB and cardiovascular disease. Potential strategies to prevent development of TB disease might include targeted vaccination programmes, screening for LTBI and preventive therapy among diabetes patients or, perhaps ideally, improved diabetes management and prevention. The cost-effectiveness of each of these, and in particular how each strategy might compare with targeted TB prevention among other population groups at higher risk of developing TB disease, is also unknown. Despite research gaps, clinicians urgently need practical management advice and more research evidence on the choice and dose of different anti-diabetes medication and effective medical therapies to reduce cardiovascular risks (statins, anti-hypertensives and aspirin). Substantial health system strengthening and integration may be needed to prevent these at risk patients being lost to care at the end of TB treatment.

The serum concentration of vitamin B12 as a biomarker of therapeutic response in tuberculosis patients with and without human immunodeficiency virus (HIV) infection.

BackgroundPrior to clinical trials of new tuberculosis (TB) drugs or therapeutic vaccines, it is necessary to develop monitoring tools to predict treatment outcomes in TB patients.MethodsMicronutrients concentration level was determined from a total of 262 study participants with five clinical groups: 57 TB patients coinfected with HIV (HIV+TB+), 87 active TB Patients (TB cases), 71 HIV infected without active and latent TB infection (HIV+TST-), 22 latent TB infection (TST+) and 25 healthy controls (TST-). Vitamin A concentration was measured using high-performance liquid chromatography (HPLC), whereas iron and vitamin B12 concentrations were measured using Cobas® 6000 analyzer.ResultThe serum concentration levels of iron, vitamin A and vitamin B12 had a significant difference between active TB and latent (LTBI) or healthy controls. Six months after treatment, the serum concentration levels of vitamin A, vitamin B12 and iron in tuberculosis became indistinguishable from the levels of LTBIs and healthy control individuals. The concentration levels of iron and vitamin B12 in HIV+TB+patients at the end of TB treatment were normalized to the levels observed in healthy controls (TST–) regardless of HAART treatment. However, the concentration level of vitamin A in HIV+TB+patients HAART untreated at the end of TB treatment was not normalized to the levels observed in healthy controls (TST–) or HAART untreated HIV+TST–.ConclusionDetecting serum concentration levels of vitamin B12 and vitamin A might be used as a biomarker of the diagnostic method of active TB regardless of HIV-infected individuals. Moreover, detecting serum concentration of vitamin B12 might also be used for TB treatment responses monitoring biomarker in TB-HIV-co-infected individuals regardless of HAART (in)eligibility and therapy.

Knowledge about tuberculosis and infection prevention behavior: A nine city longitudinal study from India.

BackgroundImproving patients’ tuberculosis (TB) knowledge is a salient component of TB control strategies. Patient knowledge of TB may encourage infection prevention behaviors and improve treatment adherence. The purpose of this study is to examine how TB knowledge and infection prevention behaviors change over the course of treatment.MethodsA matched patient-health worker dataset (n = 6,031) of publicly treated TB patients with NGO-provided treatment support health workers was compiled in nine Indian cities from March 2013 to September 2014. At the beginning and end of TB treatment, patients were asked about their knowledge of TB symptoms, transmission, and treatment and infection prevention behaviors.ResultsPatients beginning TB treatment (n = 3,424) demonstrated moderate knowledge of TB; 52.5% (50.8%, 54.2%) knew that cough was a symptom of TB and 67.2% (65.6%, 68.7%) knew that TB was communicable. Overall patient knowledge was significantly associated with literacy, education, and income, and was higher at the end of treatment than at the beginning (3.7%, CI: 3.02%, 4.47%). Infection prevention behaviors like covering a cough (63.4%, CI: 61.2%, 65.0%) and sleeping separately (19.3%, CI: 18.0%, 20.7%) were less prevalent. The age difference between patient and health worker as well as a shared language significantly predicted patient knowledge and adherence to infection prevention behaviors.ConclusionsSocial proximity between health worker and patients predicted greater knowledge and adherence to infection prevention behaviors but the latter rate remains undesirably low.

Challenges Across the HIV Care Continuum for Patients With HIV/TB Co-infection in Atlanta, GA [corrected

BackgroundAntiretroviral therapy (ART) for persons with HIV infection prevents tuberculosis (TB) disease. Additionally, sequential ART after initiation of TB treatment improves outcomes. We examined ART use, retention in care, and viral suppression (VS) before, during, and 3 years following TB treatment for an inner-city cohort in the United States.MethodsRetrospective cohort study among persons treated for culture-confirmed TB between 2008 and 2015 at an inner-city hospital.ResultsAmong 274 persons with culture-confirmed TB, 96 (35%) had HIV co-infection, including 23 (24%) new HIV diagnoses and 73 (76%) previous diagnoses. Among those with known HIV prior to TB, the median time of known HIV was 6 years, and only 10 (14%) were on ART at the time of TB diagnosis. The median CD4 at TB diagnosis was 87 cells/uL. Seventy-four (81%) patients received ART during treatment for TB, and 47 (52%) has VS at the end of TB treatment. Only 32% of patients had continuous VS 3 years after completing TB treatment. There were 3 TB recurrences and 3 deaths post–TB treatment; none of these patients had retention or VS after TB treatment.ConclusionsAmong persons with active TB co-infected with HIV, we found that the majority had known HIV and were not on ART prior to TB diagnosis, and retention in care and VS post–TB treatment were very low. Strengthening the HIV care continuum is needed to improve HIV outcomes and further reduce rates of active TB/HIV co-infection in our and similar settings.

Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis

BackgroundThe incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. Recent evidence suggests that Chronic Pulmonary Aspergillosis and Aspergillus sensitisation might be responsible for significant mortality in patients treated for tuberculosis in Uganda.MethodsWe retrieved and tested paired serum aliquots for 101 HIV-TB co-infected patients at the beginning and week 24 of TB treatment. We tested samples for Aspergillus-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) using ImmunoCAP®; and Aspergillus-specific IgG and total serum IgE using Immulite® immunoassays. We compared antibody levels between baseline and week 24, relating them to selected baseline characteristics.Results10% of the patients had elevated Aspergillus-specific IgE (Aspergillus sensitization) and Aspergillus-specific IgG antibodies were elevated in 9% of the patients at the end of TB treatment. There was a significant fall in the Aspergillus-specific IgG antibody levels between baseline and week 24 (P = 0.02). Patients with cluster of differentiation 4 (CD4) T-cell count <100 cells/μl and those who were not on anti-retroviral therapy at baseline had more elevated Aspergillus-specific IgG antibodies (P = 0.01, P = 0.03). The ImmunoCAP® Aspergillus-specific IgG antibody titres were higher at week 24 than baseline with more positives at week 24; even though the difference in means was small. However, this difference was statistically significant (P = 0.02). Pulmonary infiltrates were the commonest x-ray abnormality and only 5% of the patients had pulmonary cavities on chest x-ray at week 24.ConclusionThese results suggest that Aspergillus infection may complicate active pulmonary TB and further studies including fungal culture and thoracic imaging may now be indicated to measure the prevalence of pulmonary aspergillosis complicating tuberculosis.Trial registrationThe SOUTH trial was registered prospectively. ClinicalTrials.gov Identifier: NCT01782950; Registration date: 4th February 2013; Last verified: 13th April 2015.

Risk factors for mortality among tuberculosis patients on treatment at Bugando Medical Centre in north-western Tanzania: a retrospective cross-sectional study

Background: Tuberculosis (TB) is still an important cause of morbidity and mortality worldwide. Though it can effectively be treated, still a significant proportion of patients die on the course of their treatment. The objective of this study was to determine the outcome and risk factors of mortality among patients diagnosed with TB in a tertiary hospital in north-western Tanzania.Methods: A retrospective cross sectional study was done among all patients diagnosed with TB between January and December 2015 at Bugando Medical Centre. Information of demographic characteristics, smear positivity, haemoglobin concentration, HIV status, CD4 counts for HIV positive patients and treatment outcomes were collected and analysed. TB treatment outcomes as dead or alive were calculated and logistic regression was done to determine the factors associated with increased risk of death of patients on anti-TB treatment.Results: In total 701 patients were diagnosed with TB during the study period. Of these, 361 (51.5%) were males with a median age of 38 (IQR 27- 47) and 421 (60.06%) were younger than 40 years. Majority of the participants 409 (58.35%) had smear positive pulmonary tuberculosis and about half of patients (51.07%) tested positive for HIV. Of the enrolled patients 610 (87.02%) were alive at the end of TB treatment while 91 (12.98%) died in the course of treatment. The odds of deaths of patients on anti-TB treatment were strongly associated with male sex, HIV co infection and severe anaemia.Conclusion: The proportion of patients who die from TB treatment at BMC is high, with an increased risk of death among HIV co-infected, older than 40 years and severely anaemic patients. Improvement of strategies for early diagnosis and prompt treatment of TB patients will potentially improve treatment outcome.

Change in Health-Related Quality of Life among Pulmonary Tuberculosis Patients at Primary Health Care Settings in South Africa: A Prospective Cohort Study.

IntroductionPulmonary tuberculosis (TB) remains a major public health challenge in South Africa. However, little attention is paid to the impact of health related quality of life (HRQL) among TB patients at the beginning and at the end of TB treatment. This study assesses factors associated with HRQL among tuberculosis patients in three high risk provinces in South Africa.MethodsA prospective cohort study was conducted at primary health care settings. Patients completed the HRQL social functioning (SF)-12 health survey. Comparison of Physical Health Summary Score (PCS) and Mental Health Summary Score (MCS) was assessed at 6 months after treatment. Generalized estimating equations (GEEs) were used to examine the factors associated with changes in HRQL.ResultsIn all patients, after 6 months of treatment there was a significant improvement in HRQL with the biggest increase in the PCS. A higher educational qualification had a strong significant positive effect on the mental HRQL. Psychological distress showed a significant negative association with physical and mental HRQL after six months. Permanent residence showed a significant positive association with mental HRQL among TB patients compared to those living in shack/traditional dwellings. Rating ones health as being good and fair/poor was significantly associated with poor physical HRQL. Twenty drinks or more in the past month had a significant negative effect on the physical HRQL.ConclusionThe findings suggest that programmes targeted at improving TB treatment success should have specific interventions for patients with low educational background, impoverished households/communities and those with hazardous or harmful alcohol use.

Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis: A Systematic Review and Meta-analysis.

Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment remains challenging. To assess evidence from randomized, controlled trials of the timing of ART initiation in HIV-infected adults with newly diagnosed pulmonary TB. PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts, and ClinicalTrials.gov (from January 1980 to May 2015). Randomized, controlled trials evaluating early versus delayed ART initiation (1 to 4 weeks vs. 8 to 12 weeks after initiation of TB treatment) or deferred ART initiation (after the end of TB treatment). Three reviewers independently extracted data and assessed risk of bias. The main outcome measures were all-cause mortality and the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The 8 included trials (n= 4568) were conducted in Africa, Asia, and the United States and were generally at low risk of bias for the assessed domains. Overall, early ART reduced mortality compared with delayed ART (relative risk [RR], 0.81 [95% CI, 0.66 to 0.99]; I2= 0%). In a prespecified subgroup analysis, early ART reduced mortality compared with delayed ART among patients with baseline CD4+ T-cell counts less than 0.050×109 cells/L (RR, 0.71 [CI, 0.54 to 0.93]; I2= 0%). However, a mortality benefit from early ART was not found among those with CD4+ T-cell counts greater than 0.050×109 cells/L (RR, 1.05 [CI, 0.68 to 1.61]; I2= 56%). Early ART was associated with a higher incidence of TB-IRIS than delayed ART (RR, 2.31 [CI, 1.87 to 2.86]; I2= 19%). Few trials provided sufficient data for subgroup analysis. Early ART in HIV-infected adults with newly diagnosed TB improves survival in those with CD4+ T-cell counts less than 0.050×109 cells/L, although this is associated with a 2-fold higher frequency of TB-IRIS. In patients with CD4+ T-cell counts greater than 0.050×109 cells/L, evidence is insufficient to support or refute a survival benefit conferred by early versus delayed ART initiation. None. (PROSPERO registration: CRD42012001884).

Health-related quality of life as a predictor of tuberculosis treatment outcomes in Iraq

To determine how tuberculosis (TB) treatment affects the health-related quality of life (HRQL) of patients with pulmonary TB and to identify the predictors of favourable TB treatment outcomes in Baghdad, Iraq. The Functional Assessment of Chronic Illness Therapy-Tuberculosis (FACIT-TB), a new TB-specific quality of life instrument derived from the internationally recognized FACIT measurement system for the assessment of HRQL, was administered. The mean total and subscale scores of the FACIT-TB at baseline, end of the intensive phase, and end of TB treatment were compared. After the 2-month intensive phase, physical well-being, functional well-being, and the overall total scores were significantly increased (p<0.01). Furthermore, at completion of TB treatment, there were significant improvements in the overall HRQL as indicated by the FACIT-TB total score and all subscales, except social and economic well-being and spiritual well-being. In a direct logistic regression model, only the FACIT-TB total score made a statistically significant contribution towards predicting the likelihood that a patient would have a favourable TB treatment outcome. Therapeutic intervention had a positive impact on patient HRQL. We conclude that FACIT-TB is a reliable tool to monitor HRQL during the course of TB treatment.

Integration and Task Shifting for TB/HIV Care and Treatment in Highly Resource-Scarce Settings

A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4 count is 100-350 cells per cubic millimeter, and at the end of TB treatment after CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). ART uptake increased (17%-69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%, P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.

English

&nbsp; The aim of this study was to determine whether tuberculosis (TB) treatment normalizes the lipid profile strongly affected by pulmonary TB. Serum levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were determined in 83 patients with pulmonary TB before and after treatment, and compared to results obtained from 100 control subjects without TB. Before treatment, levels of TC (p&lt;0.005), HDL-C (p&lt;0.005) and LDL-C (p&lt;0.005) were significantly lower in pulmonary TB patients than normal subjects. Unlike TC and LDL-C, HDL-C decrease was correlated (r = 0.96, p&lt;0.05) with smear positivity extent (SPE). At the end of TB treatment, which lasted six months, TC (p&lt;0.01) and HDL-C (p&lt;0.005) levels were significantly increased than before treatment while LDL-C stayed relatively unchanged. The treatment significantly reduced the atherogenic indices TC/HDL-C (p&lt;0.001), LDL-C/HDL-C (p&lt;0.001) and log (TG/HDL-C) (p&lt;0.001) levels. Our results show that tuberculosis treatment increases TC levels and normalizes HDL while reducing atherogenic indices to below levels of controls. &nbsp; Key words:&nbsp;Pulmonary tuberculosis, lipid profile, treatment, atherogenic index.