Clinical trials

Multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to global public health. Globally, the World Health Organization (WHO) estimates the number at 400,000 patients with MDR-TB for 2023. Only 44% were diagnosed and put on treatment, the therapeutic success rate of the 2021 cohort is only 68%. In Guinea, the number of patients with MDR-TB is estimated at 450, and the treatment success rate is 74% for the 2021 cohort, primarily with the 9-months short oral regimen. Since 2022, the WHO has recommended the use of the 6-month short course of BPaL/BPaL-M for national tuberculosis control programs and Guinea began implementing this new regime within the programmatic framework starting in January 2025. Linezolid, a key component of new therapeutic regimens such as BPaL/BPaL-M, shows high bactericidal activity, although it is associated with serious adverse effects in a high percentage of patients, including myelosuppression, neuropathy and, in some cases, fatal lactic acidosis. In particular, peripheral neuropathy, an adverse event often irreversible that may lead to linezolid and the BPaL/BPaL-M regimen discontinuation, is reported in approximately 24% of patients receiving linezolid at 600 mg. A linezolid blood trough level of above 2 mg/l is associated with side effects, but its pharmacokinetics varies considerably between individuals and over time. There is little data on the role of therapeutic drug monitoring (TDM) in guiding its administration, some studies showing how the standard dose of 600 mg could exceed the toxicity target and the reduced dose of 300 mg might not achieve the target efficacy. The main objective of this study is to determine the role of TDM in the optimization of linezolid dosage in TB-MDR patients treated with the BPaL/BPaL-M regimen. The specific objectives aim to evaluate: * the variation in the occurrence of adverse events between patients who undergo a modification of the linezolid dose based on the TDM and patients taking linezolid standard dose * the treatment outcome in patients who undergo a modification of the linezolid dose based on TDM and patients taking linezolid standard dose * variations in the distribution of TDM throughout treatment in order to identify potential common trends.

This study has three primary objectives to address the public health challenges of the Mpox outbreak in Guinea, West Africa. Objective 1 (MOVIE-West Africa) focuses on understanding the kinetics of Monkeypox virus (MPXV) elimination from the human body in Mpox cases. Objective 2 (TRACE-West Africa) aims to determine the MPXV transmission dynamics between Mpox cases and their contacts. Objective 3 (VE-West Africa) examines the vaccine effectiveness of the MVA-BN vaccine in protection against MPXV infection and Mpox disease.

The LALGFA2019 Recommendations redefine the standard risk criteria and propose to introduce anthracycline induction in so-called high-risk forms (LAL line T and LAL line B with leukocytosis greater than or equal to 50 G/L or in children less than 1 year of age or more than 10 years of age) as well as Endoxan and Methotrexate in high dose consolidation.

EBO-PEP is a multicentre, multi-epidemic, phase III, comparative, controlled, randomised, strict superiority trial in two unblinded parallel arms. The trial will be open during EVD epidemics and will recruit asymptomatic participants at high risk of developing EVD. Participants will be randomized (1:1) into one of two trial arms: * Arm 1 (ERV): Ervebo D0 (72 million PFU IM) * Arm 2 (ERV+IMZ): Ervebo D0 (72 million PFU IM) + Inmazeb IV (150 mg/kg) D0 + Ervebo D56 (revaccination) Definition of high-risk: Direct contact with a person with EBOV PCR-confirmed EVD with diarrhea, vomiting or external bleeding ("wet symptoms"), or with their body fluids; Direct contact with the dead body of a person with confirmed or probable EVD; Needlestick with a syringe contaminated by the blood of a person with confirmed or probable EVD; Or a child born to or breastfed by an individual with EVD Trial follow-up All participants are monitored daily for a minimum of 21 days. Some visits are conducted in person at the investigation site, also called the Post-Exposure Prophylaxis (PEP) center: * at Day 5, Day 10, and Day 21 for the ERV arm, * at Day 5, Day 10, Day 21, and Day 56 for the ERV+IMZ arm. Other visits are conducted at home or by phone, in collaboration with the Ministry of Health's surveillance team. Participants in the ERV+IMZ arm have an in-person visit at Day 56 to be revaccinated with the Ervebo vaccine to compensate for potential inhibition of the vaccine response when Ervebo is administered simultaneously with Inmazeb. Participants in the ERV arm have a phone visit at Day 56. For all participants, a phone visit is scheduled at Day 60. It corresponds to the last visit for all trial participants. Follow-up in Case of Hospitalisation In case of clinical signs suggestive of EVD, participants enter the suspected case management pathway at the Ebola Treatment Center (ETC). If EVD is confirmed by EBOV PCR, participants are allowed at the ETC, and their study samples are discontinued. They continue to be followed by the research team, and daily data are collected throughout their stay at the ETC until they are discharged alive or deceased. The day of discharge from the ETC marks the end of follow-up in the study for these participants. Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56. Of note, participants in the ERV+IMZ arm who have confirmed EVD are not revaccinated at day 56. If EVD is not confirmed, participants continue to be followed up by the PEP center according to the protocol.

To date, the underlying causes of community-acquired fever, particularly non-malarial fever, are insufficiently documented in Guinea. Moreover, diagnostic capacity is limited, leading to inadequate prescription of antibiotics and antimalarials, as well as substantial delay in outbreak recognition. Thus, the investigators undertook a prospective observational multi-centric cohort study of febrile patients presenting at the emergency and outpatient department of selected health centers, districts and regional hospitals in four ecologically distinct sentinel health districts in Guinea.