Completion of anti-tuberculosis (TB) treatment is of paramount importance for TB patients, as well as for the global efforts of TB control. However, there is neither a gold-standard measure to monitor adherence to TB treatment nor a widely used definition for different levels of adherence. Areas covered: in this review we aim to describe the different methods used to measure patients' adherence to anti-TB treatment, identifying their main strengths and limitations, with a focus on low resource settings. Expert commentary: there is a need for continuing the quest for a low cost, reliable and acceptable measure of adherence to TB treatment. We should harmonize treatment adherence measurement to allow adequate comparison of different interventions aimed at increasing adherence to TB treatment, although the way we ensure adherence can affect adherence endpoints themselves. The accuracy of adherence measurement is of importance in the context of drug clinical development.
Chagas disease is caused by infection with the parasite Trypanosoma cruzi, which might lead to a chronic disease state and drive to irreversible damage to the heart and/or digestive tract tissues. Endemic in 21 countries in the Americas, it is the neglected disease with a highest burden in the region. Current estimates point at ~6 million people infected, of which ~30% will progress onto the symptomatic tissue disruptive stage. There is no vaccine but there are two anti-parasitic drugs available: benznidazole and nifurtimox. However, their efficacy is variable at the chronic symptomatic stage and both have frequent adverse effects.Since there are no prognosis markers, drugs should be administered to all T. cruzi-infected individuals in the indeterminate and early symptomatic stages. Nowadays, there are no testsof-cure either, which greatly undermines patients´ follow-up and the search of safer and more efficacious drugs. Therefore, the identification and validation of biomarkers of disease progression and/or treatment response on which to develop tests of prognosis and/or cure is a major research priority. Both parasite-and host-derived markers have been investigated. In the present manuscript we present an updated outlook of the latter.
We present a field evaluation of the diagnostic accuracy of Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra), using two cohorts in a high TB/HIV burden setting in Southern Mozambique. Single respiratory specimens from symptomatic adults accessing health care services (passive case finding (PCF) cohort), and from household and community close contacts (active case finding (ACF) cohort), were tested by smear microscopy, culture, Xpert and Ultra. Liquid and solid culture served as a composite reference standard. We explored trace results’ impact on specificity via their recategorisation to negative (in all and just among those previously treated individuals) A total of 1419 and 252 participants were enrolled in the PCF and ACF cohorts, respectively. For the PCF cohort, Ultra showed higher sensitivity than Xpert overall (0.95 (95% CI: 0.90, 0.98) versus 0.88 (0.82, 0.93); p<0.001) and among smear negative patients (0.63 (0.48, 0.76) and 0.84 (0.71, 0.93). Ultra's specificity was lower than Xpert's (0.98 (0.97, 0.99) versus 0.96 (0.95, 0.97); p=0.008). For ACF, sensitivities were the same (0.67 (95% CI: 0.22,0.96) for both tests), although Ultra detected a higher number of microbiologically confirmed samples than Xpert (4.7% (12/252) versus 2.7% (7/252)). Conditional recategorisation of trace results among previously treated participants maintained differences in specificity in the PCF cohort. These results add evidence on the improved sensitivity of Ultra and support its use in different case finding scenarios.
In this retrospective cohort study, we aimed to assess whether introducing benznidazole at escalating doses reduces the probability of adverse events or treatment discontinuation compared with a full-dose scheme. We collected data from patients who had chronic Trypanosoma cruzi infection and underwent treatment from July 2008 to January 2017 in a referral center in Madrid. Dose was adjusted to body weight (5 mg/kg/day), with treatment introduction with full dose or escalating dose according to local consensus and protocols. Among the 62 patients treated, benznidazole was introduced at full dose in 28 patients and on escalating dose in the remaining 34. We found no statistical differences in the number of adverse events, treatment discontinuations, days of treatment, or sociodemographic profiles. There is insufficient evidence to support escalating dose as a strategy for reducing the adverse effects of benznidazole. Further research is needed to evaluate this approach.
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