Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

BACKGROUND: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. METHODS: We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. RESULTS: Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. CONCLUSIONS: Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

Dying in honour: experiences of end-of-life palliative care during the 2013-2016 Ebola outbreak in Guinea.

With no cure and a high mortality rate, Ebola virus disease (EVD) outbreaks require preparedness for the provision of end-of-life palliative care. This qualitative study is part of a larger project on palliative care in humanitarian contexts. Its goal was to document and deepen understanding of experiences and expectations related to end-of-life palliative care for patients infected with Ebola virus disease (EVD) in West African Ebola treatment centres (ETCs) during the 2013-2016 epidemic. It consisted of 15 in-depth semi-structured interviews with individuals impacted by EVD in a Guinean ETC: either as patients in an ETC, healthcare providers, healthcare providers who were also EVD patients at one point, family relations who visited patients who died in an ETC, or providers of spiritual support to patients and family. Analysis was team based and applied an interpretive descriptive approach. Healthcare delivery in humanitarian emergencies must remain respectful of patient preferences but also local and contextual values and norms. Of key importance in the Guinean context is the culturally valued experience of "dying in honour". This involves accompaniment to facilitate a peaceful death, the possibility of passing on final messages to family members, prayer, and particular practices to enact respect for the bodies of the deceased. Participants emphasized several challenges to such death in Ebola treatment centres (ETCs), as well as practices they deemed helpful to alleviating dying patients' suffering. An overarching message in participants' accounts was that ideally more would have been done for the dying in ETCs. Building on participants' accounts, we outline a number of considerations for optimizing end-of-life palliative care during current and future public health emergencies, including for COVID-19.

Impact of the Ebola virus disease outbreak (2014-2016) on tuberculosis surveillance activities by Guinea's National Tuberculosis Control Program: a time series analysis.

BACKGROUND: Most countries in Subsaharan Africa have well-established National Tuberculosis Control Programs with relatively stable routine performances. However, major epidemiological events may result in significant disruptions. In March 2014, the World Health Organization announced the outbreak of Ebola virus disease in Guinea, a country with a high incidence of TB and HIV. Our study aimed to assess the impact of the Ebola virus disease outbreak on TB notification, treatment, and surveillance, using main indicators. METHODS: This is a retrospective cohort study that compared TB trends using surveillance data from the periods before (2011-2013), during (2014-2016), and after (2017-2018) Ebola virus disease outbreak. A time-series analysis was conducted to investigate the linkages between the decline in TB notification and the Ebola virus disease outbreak through cross-correlation. The lag in the cross-correlation test was evaluated using ANCOVA type II delayed variable dependent model. The surveillance system was assessed using TB surveillance standards and benchmarks and vital registration systems recommended by WHO, compared with those of 2015 during the Ebola virus disease. RESULTS: The rate of reporting of TB declined from 120 cases per 100,000 in 2011 to 100 cases per 100,000 in 2014, at the peak of the Ebola virus disease outbreak. The time-series cross-correlation test of all notified cases of TB and Ebola showed a significant lag of - 0.4 (40%), reflecting a drop in the rate of notification (F-value = 5.7 [95% CI: 0.2-21.3]). The Ebola virus disease had no negative impact on patient treatment outcomes (F-value = 1.3 [95% CI: 0.0-8.8]). Regarding the surveillance system, five out of 13 WHO standards and benchmarks were met following their evaluation in 2019, after the Ebola virus disease outbreak, compared to three in 2015. CONCLUSION: Major epidemics such as the Ebola virus disease outbreak may have a significant impact on well-established TB control programs as shown in the example of Guinea. Sudden disruptions of routine performance may lead programs to improve their surveillance system. The experience acquired in the fight against EVD and the investments made should make it possible to prepare the health system in a coherent manner for the other probable episodes.

Different profiles of body mass index variation among patients with multidrug-resistant tuberculosis: a retrospective cohort study.

BACKGROUND: Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. METHODS: We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. RESULTS: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3-8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m2. Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m2; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m2; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0218). CONCLUSION: Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.