Project: Evaluation of alternative bacteriological measures of response to therapy during the initial 16-weeks of MDR-TB treatment

Acronym	MDRTBTx-Monitor (Reference Number: TMA2018CDF-2351)
Duration	01/11/2019 - 31/10/2022
Project Topic	Background: Effective treatment monitoring is vital not only for proper patient management but also for preventing the unnecessary continuation of failing treatment and emergence of more drug-resistant M. tuberculosis (Mtb). Therefore, the urgent need for better treatment monitoring methods cannot be more emphasized. These methods will protect the currently effective drugs and streamline the development of new drugs for multi-drug resistant tuberculosis (MDR-TB). Treatment monitoring by sputum culture is the gold standard for TB treatment, however, this method remains less accessible due to high operational cost, high skills demand, longer turnaround time and contamination. The proposed study aims to evaluate the effectiveness of alternative methods compared with culture colony forming units (CFUs) determination for measuring response to therapy during the initial 16 weeks of MDR-TB treatment. We will evaluate how these alternative methods may predict outcomes to shorter MDR-TB treatment regimen. The methods include; fluorescein-di-acetate (FDA) AFB vital smear microscopy, XpertMTB/RIF assay done using sputum pre-treated with propidium mono-azide (PMA), Mtb16sr RNA assays (Molecular Bacterial Load Assay; MBLA) and liquid culture Mtb time-to-positivity (TTP). Methods: A prospective study of patients’ ≥ 18 years of age with MDR-TB diagnosed according to local standards will be enrolled into the study. Two sputum samples, a spot, and an overnight will be taken at weeks 0, 1, 2, 3, 4, 5, 6, 7, 8 and once during month 3 and 4. Follow- up will be active during the intensive phase and passive during the continuation phase up to 18 months of MDR-TB treatment to document treatment outcomes. Samples will be pooled and homogenized and divided into three portions; one for; 1) FDA- treated AFB smear microscopy 2) PMAXpert/ULTRA assay 3) liquid culture for Mtb-TTP. Portion two for 16s rRNA detection in an MBLA assay. Portion three will be used for CFUs/mL determination. Data will be analyzed for correlation with the alternative methods results with reducing culture CFUs. The alternative methods will be analysed to determine how well they predict MDR-TB patient treatment outcome. Potential Impact: This study will inform the possible alternative methods for MDR-TB treatment response monitoring in resource-limited settings allowing a quick decision making. This will help in protecting the best available treatment regimens and novel TB drugs, improve the efficiency of phase II trials/treatment regimens and lead to reduced delayed results-associated costs in the development of novel MDR-TB drugs which will eventually lead to better MDR-TB control.
Network	EDCTP2
Call	Career Development Fellowships 2018

Project partner

Number	Name	Role	Country
1	Makerere University	Coordinator	Uganda