Tuberculosis (TB) is among diseases of global health importance with Sub Saharan Africa (SSA) accounting for 25% of the global TB burden. TB prevalence among miners in SSA is estimated at ...3,000-7,000/100,000, which is about 3 to 10-times higher than in the general population. The study's objective was to determine the prevalence of TB and associated risk factors among mining communities in Mererani, northern Tanzania. This was a cross-sectional study conducted from April 2019 to November 2021 involving current Small Scale Miners (SSM) and the General Community (GC). A total of 660 participants, 330 SSM and 330 GC were evaluated for the presence of TB. Data were analysed using Statistical Package for the Social Sciences (SPSS) database (IBM SPSS Statistics Version 27.0.0.0). Binary logistic regression (Generalized Linear Mixed Model) was used to determine the association between TB and independent predictors. Prevalence of TB was 7%, about 24-times higher than the national prevalence of 0.295%. Participants from the general community had higher prevalence of TB 7.9% than SSM (6.1%). Both for SSM and the GC, TB was found to be associated with: lower education level (aOR = 3.62, 95%CI = 1.16-11.28), previous lung disease (aOR = 4.30, 95%CI = 1.48-12.53) and having symptoms of TB (aOR = 3.24, 95%CI = 1.38-7.64). Specifically for the SSM, TB was found to be associated with Human Immunodeficiency Virus (HIV) infection (aOR = 8.28, 95%CI = 1.21-56.66). Though significant progress has been attained in the control of the TB epidemic in Tanzania, still hot spots with significantly high burden of TB exists, including miners. More importantly, populations surrounding the mining areas, are equally affected, and needs more engagement in the control of TB so as to realize the Global End TB targets of 2035.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Antiretroviral therapy (ART) has been shown to reduce HIV-related morbidity and mortality amongst those living with HIV and reduce transmission of the virus to those who are yet to be infected. ...However, these outcomes depend on maximum ART adherence, and HIV programs around the world make efforts to ensure optimal adherence. Predictors of ART non-adherence vary considerably across populations and settings with respect to demographic, psychological, behavioral and economic factors. The objective of this study is to investigate risk factors that predict non-adherence to antiretroviral treatment among HIV-infected individuals in northern Tanzania.
At Kilimanjaro Christian Medical Centre (KCMC), a tertiary and referral hospital in northern Tanzania, we used an existing ART database to randomly select HIV-infected patients above 18 years of age who have been on triple ART for at least two years. We used interviewer administered structured questionnaires to cross-sectionally determine predictors of ART non-adherence. We determined non-adherence through retrospective review of pharmacy drug refill (PDR) records of the interviewed participants using a pharmacy database.
Non-adherence was defined as collecting less than 95% of expected monthly refills in the previous 2 years. Multivariable logistic regression model was used to determine the predictors of non-adherence. Of the 256 patients enrolled mean age was 44 years (SD ± 11) and median CD4 count was 499 cells per microliter (IQR 332-690). Median PDR adherence was 71% (IQR 58%-75%). Non-adherence was associated with younger age and unemployment.
In this setting, adherence strategies could be adapted to address issues facing young adults, and those with household challenges such as unemployment. Further research is required to better understand the potential roles of these factors in suboptimal adherence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Tuberculosis is the world's leading infectious disease killer. We aimed to identify shorter, safer drug regimens for the treatment of tuberculosis. Methods We did a randomised ...controlled, open-label trial with a multi-arm, multi-stage design. The trial was done in seven sites in South Africa and Tanzania, including hospitals, health centres, and clinical trial centres. Patients with newly diagnosed, rifampicin-sensitive, previously untreated pulmonary tuberculosis were randomly assigned in a 1:1:1:1:2 ratio to receive (all orally) either 35 mg/kg rifampicin per day with 15–20 mg/kg ethambutol, 20 mg/kg rifampicin per day with 400 mg moxifloxacin, 20 mg/kg rifampicin per day with 300 mg SQ109, 10 mg/kg rifampicin per day with 300 mg SQ109, or a daily standard control regimen (10 mg/kg rifampicin, 5 mg/kg isoniazid, 25 mg/kg pyrazinamide, and 15–20 mg/kg ethambutol). Experimental treatments were given with oral 5 mg/kg isoniazid and 25 mg/kg pyrazinamide per day for 12 weeks, followed by 14 weeks of 5 mg/kg isoniazid and 10 mg/kg rifampicin per day. Because of the orange discoloration of body fluids with higher doses of rifampicin it was not possible to mask patients and clinicians to treatment allocation. The primary endpoint was time to culture conversion in liquid media within 12 weeks. Patients without evidence of rifampicin resistance on phenotypic test who took at least one dose of study treatment and had one positive culture on liquid or solid media before or within the first 2 weeks of treatment were included in the primary analysis (modified intention to treat). Time-to-event data were analysed using a Cox proportional-hazards regression model and adjusted for minimisation variables. The proportional hazard assumption was tested using Schoelfeld residuals, with threshold p<0·05 for non-proportionality. The trial is registered with ClinicalTrials.gov ( NCT01785186 ). Findings Between May 7, 2013, and March 25, 2014, we enrolled and randomly assigned 365 patients to different treatment arms (63 to rifampicin 35 mg/kg, isoniazid, pyrazinamide, and ethambutol; 59 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, SQ109; 57 to rifampicin 20 mg/kg, isoniazid, pyrazinamide, and SQ109; 63 to rifampicin 10 mg/kg, isoniazid, pyrazinamide, and moxifloxacin; and 123 to the control arm). Recruitment was stopped early in the arms containing SQ109 since prespecified efficacy thresholds were not met at the planned interim analysis. Time to stable culture conversion in liquid media was faster in the 35 mg/kg rifampicin group than in the control group (median 48 days vs 62 days, adjusted hazard ratio 1·78; 95% CI 1·22–2·58, p=0·003), but not in other experimental arms. There was no difference in any of the groups in time to culture conversion on solid media. 11 patients had treatment failure or recurrent disease during post-treatment follow-up: one in the 35 mg/kg rifampicin arm and none in the moxifloxacin arm. 45 (12%) of 365 patients reported grade 3–5 adverse events, with similar proportions in each arm. Interpretation A dose of 35 mg/kg rifampicin was safe, reduced the time to culture conversion in liquid media, and could be a promising component of future, shorter regimens. Our adaptive trial design was successfully implemented in a multi-centre, high tuberculosis burden setting, and could speed regimen development at reduced cost. Funding The study was funded by the European and Developing Countries Clinical Trials partnership (EDCTP), the German Ministry for Education and Research (BmBF), and the Medical Research Council UK (MRC).
Abstract
Background
Diabetes mellitus (DM) is associated with poor TB treatment outcome. Previous studies examining the effect of DM on TB drug concentrations yielded conflicting results. No studies ...have been conducted to date in an African population.
Objectives
To compare exposure to TB drugs in Tanzanian TB patients with and without DM.
Patients and methods
A prospective pharmacokinetic study was performed among 20 diabetic and 20 non-diabetic Tanzanian TB patients during the intensive phase of TB treatment. Plasma pharmacokinetic parameters of isoniazid, rifampicin, pyrazinamide and ethambutol were compared using an independent-sample t-test on log-transformed data. Multiple linear regression analysis was performed to assess the effects of DM, gender, age, weight, HIV status and acetylator status on exposure to TB drugs.
Results
A trend was shown for 25% lower total exposure (AUC0–24) to rifampicin among diabetics versus non-diabetics (29.9 versus 39.9 mg·h/L, P=0.052). The AUC0–24 and peak concentration (Cmax) of isoniazid were also lower in diabetic TB patients (5.4 versus 10.6 mg·h/L, P=0.015 and 1.6 versus 2.8 mg/L, P=0.013). Pyrazinamide AUC0–24 and Cmax values were non-significantly lower among diabetics (P=0.08 and 0.09). In multivariate analyses, DM remained an independent predictor of exposure to isoniazid and rifampicin, next to acetylator status for isoniazid.
Conclusions
There is a need for individualized dosing of isoniazid and rifampicin based on plasma concentration measurements (therapeutic drug monitoring) and for clinical trials on higher doses of these TB drugs in patients with TB and DM.
Adverse drug reactions (ADRs) frequently occur in patients using second-line anti-tuberculosis medicine for treatment of multidrug resistant tuberculosis (MDR-TB). ADRs contribute to treatment ...interruptions which can compromise treatment response and risk acquired drug resistance to critical newer drugs such as bedaquiline, while severe ADRs carry considerable morbidity and mortality. N-acetylcysteine (NAC) has shown promise in reducing ADRs for medications related to TB in case series or randomized controlled trials in other medical conditions, yet evidence is lacking in MDR-TB patients. TB endemic settings have limited capacity to conduct clinical trials. We designed a proof-of-concept clinical trial primarily to explore the preliminary evidence on the protective effect of NAC among people treated for MDR-TB with second-line anti-TB medications.
This is a proof-of-concept randomized open label clinical trial with 3 treatment arms including a control arm, an interventional arm of NAC 900 mg daily, and an interventional arm of NAC 900 mg twice-daily administered during the intensive phase of MDR-TB treatment. Patients initiating MDR-TB treatment will be enrolled at Kibong'oto National Center of Excellence for MDR-TB in the Kilimanjaro region of Tanzania. The minimum anticipated sample size is 66; with 22 participants in each arm. ADR monitoring will be performed at baseline and daily follow-up over 24 weeks including blood and urine specimen collection for hepatic and renal function and electrolyte abnormalities, and electrocardiogram. Sputum will be collected at baseline and monthly thereafter and cultured for mycobacteria as well as assayed for other molecular targets of Mycobacterium tuberculosis. Adverse drug events will be analysed over time using mixed effect models. Mean differences between arms in change of the ADRs from baseline (with 95% confidence intervals) will be derived from the fitted model.
Given that NAC promotes synthesis of glutathione, an intracellular antioxidant that combats the impact of oxidative stress, it may protect against medication induced oxidative damage in organs such as liver, pancreas, kidney, and cells of the immune system. This randomized controlled trial will determine if NAC leads to fewer ADRs, and if this protection is dose dependent. Fewer ADRs among patients treated with MDR-TB may significantly improve treatment outcomes for multidrug regimens that necessitate prolonged treatment durations. Conduct of this trial will set the needed infrastructure for clinical trials.
PACTR202007736854169 Registered 03 July 2020.
Tuberculosis (TB) remains a major cause of morbidity and mortality, especially in sub-Saharan Africa. We qualitatively evaluated the implementation of an Evidence-Based Multiple Focus Integrated ...Intensified TB Screening package (EXIT-TB) in the East African region, aimed at increasing TB case detection and number of patients receiving care.
We present the accounts of participants from Tanzania, Kenya, Uganda, and Ethiopia regarding the implementation of EXIT-TB, and suggestions for scaling up.
A qualitative descriptive design was used to gather insights from purposefully selected healthcare workers, community health workers, and other stakeholders. A total of 27, 13, 14, and 19 in-depth interviews were conducted in Tanzania, Kenya, Uganda, and Ethiopia respectively. Data were transcribed and translated simultaneously and then thematically analysed.
The EXIT-TB project was described to contribute to increased TB case detection, improved detection of Multidrug-resistant TB patients, reduced delays and waiting time for diagnosis, raised the index of TB suspicion, and improved decision-making among HCWs. The attributes of TB case detection were: (i) free X-ray screening services; (ii) integrating TB case-finding activities in other clinics such as Reproductive and Child Health clinics (RCH), and diabetic clinics; (iii), engagement of CHWs, policymakers, and ministry level program managers; (iv) enhanced community awareness and linkage of clients; (v) cooperation between HCWs and CHWs, (vi) improved screening infrastructure, (vii) the adoption of the new simplified screening criteria and (viii) training of implementers. The supply-side challenges encountered ranged from disorganized care, limited space, the COVID-19 pandemic, inadequate human resources, inadequate knowledge and expertise, stock out of supplies, delayed maintenance of equipment, to absence of X-ray and GeneXpert machines in some facilities. The demand side challenges ranged from delayed care seeking, inadequate awareness, negative beliefs, fears towards screening, to financial challenges. Suggestions for scaling up ranged from improving service delivery, access to diagnostic equipment and supplies, and infrastructure, to addressing client fears and stigma.
The EXIT-TB package appears to have contributed towards increasing TB case detection and reducing delays in TB treatment in the study settings. Addressing the challenges identified is needed to maximize the impact of the EXIT-TB intervention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The analysis of phenotypic characteristics on
(MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied ...phenotypic changes on MTB-specific CD4 T cells upon anti-tuberculosis treatment initiation in relation to the treatment response as determined by sputum culture.
Peripheral blood mononuclear cells from subjects with latent MTB infection (
= 16) and aTB (
= 39) at baseline, weeks 9, 12, and 26 (end of treatment) were analyzed after intracellular interferon gamma staining and overnight stimulation with tuberculin. Liquid sputum cultures were performed weekly until week 12 and during 4 visits until week 26.
T cell activation marker expression on MTB-specific CD4 T cells differed significantly between subjects with aTB and latent MTB infection with no overlap for the frequencies of CD38
and Ki67
cells (both
< 0.0001). At 9 weeks after anti-TB treatment initiation the frequencies of activation marker (CD38, HLA-DR, Ki67) positive MTB-specific, but not total CD4 T cells, were significantly reduced (
< 0.0001). Treatment induced phenotypic changes from baseline until week 9 and until week 12 differed substantially between individual aTB patients and correlated with an individual's time to stable sputum culture conversion for expression of CD38 and HLA-DR (both
< 0.05). In contrast, the frequencies of maturation marker CD27 positive MTB-specific CD4 T cells remained largely unchanged until week 26 and significantly differed between subjects with treated TB disease and latent MTB infection (
= 0.0003).
Phenotypic changes of MTB-specific T cells are potential surrogate markers for tuberculosis treatment efficacy and can help to discriminate between aTB (profile: CD38
, CD27
), treated TB (CD38
, CD27
), and latent MTB infection (CD38
, CD27
).
Adherence to tuberculosis (TB) treatment is challenging because of many factors. The World Health Organization has recommended the use of digital adherence monitoring technologies in its End TB ...Strategy. However, evidence on improving adherence is limited. EvriMED is a real-time medication-monitoring device which was found to be feasible and acceptable in a few studies in Asia. In Tanzania, however, there may be challenges in implementing evriMED due to stigmatization, network and power access, accuracy, and cost effectiveness, which may have implications for treatment outcome. We propose a pragmatic cluster randomized trial to investigate the effectiveness of evriMED with reminder cues and tailored feedback on adherence to TB treatment in Kilimanjaro, Tanzania.
We will create clusters in Kilimanjaro based on level of health care facility. Clusters will be randomized in an intervention arm, where evriMED will be implemented, or a control arm, where standard practice directly observed treatment will be followed. TB patients in intervention clusters will take their medication from the evriMED pillbox and receive tailored feedback. We will use the 'Stages of Change' model, which assumes that a person has to go through the stages of pre-contemplation, contemplation, preparation, action, and evaluation to change behavior for tailored feedback on adherence reports from the device.
If the intervention shows a significant effect on adherence and the devices are accepted, accurate, and sustainable, the intervention can be scaled up within the National Tuberculosis Programmes.
Pan African Clinical Trials Registry, PACTR201811755733759 . Registered on 8 November 2018.
Coadministration of antituberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis (TB) is the most common opportunistic infection associated with ...HIV/AIDS. Concurrent use of rifampicin and many antiretroviral drugs is complicated by pharmacokinetic drug-drug interactions. Rifampicin is a very potent enzyme inducer, which can result in subtherapeutic antiretroviral drug concentrations. In addition, TB drugs and antiretroviral drugs have additive (pharmacodynamic) interactions as reflected in overlapping adverse effect profiles. This review provides an overview of the pharmacological interactions between rifampicin-based TB treatment and antiretroviral drugs in adults living in resource-limited settings. Major progress has been made to evaluate the interactions between TB drugs and antiretroviral therapy; however, burning questions remain concerning nevirapine and efavirenz effectiveness during rifampicin-based TB treatment, treatment options for TB-HIV-coinfected patients with nonnucleoside reverse transcriptase inhibitor resistance or intolerance, and exact treatment or dosing schedules for vulnerable patients including children and pregnant women. The current research priorities can be addressed by maximizing the use of already existing data, creating new data by conducting clinical trials and prospective observational studies and to engage a lobby to make currently unavailable drugs available to those most in need.
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