Impact of diagnostic delays and short treatment regimens on outcomes of rifampicin-resistant tuberculosis patients in Cameroon

Rifampicin-resistant tuberculosis (RR-TB) remains a major health challenge in low- and middle-income countries despite availability of diagnostic platforms and treatment options. Despite, increasing, increasing use of rapid molecular tests (e.g., Xpert MTB/RIF or Ultra) for detection of RR-TB globally, there is still a major RR-TB diagnostic gap and low treatment success of those started on treatment. Short injectable-containing regimens which reached 80% treatment success in different settings, are now being widely replaced by bedaquiline-containing all oral regimen for RR-TB. It is yet unclear how treatment outcomes, including acquired resistance to core drugs, and safety will compare between the two main regimens. The use of short treatment regimens (STR) for RR-TB with additional fluoroquinolone resistance is poorly described. Cameroon is a high TB/HIV burden country with a RR-TB notification gap of almost 80% and limited data on treatment outcomes of short RR-TB regimens used in recent years.
To address the notification gap, I aim to first gather knowledge on the effect of Xpert MTB/RIF or Ultra on diagnostic delay and treatment outcomes of RR-TB patients using different interventions in high TB/HIV burden countries. Therefore, I will conduct a systematic literature review. These results will be complemented by a mixed-methods prospective patient pathway analysis in Cameroon to determine the first care seeking level of RR-TB patients and its alignment with TB service availability. The study will evaluate the effect of the level of care of the first visit on diagnostic and treatment delays and treatment outcomes. The qualitative component also addresses barriers and enablers perceived by patients and health care workers towards adequate and appropriate care for RR-TB.
In Cameroon, since 2012, RR-TB without proof of resistance to fluoroquinolones was treated using the injectable-based STR known as Bangladesh (Bdsh-)STR lasting 9-11 months. RR-TB with additional resistance to fluoroquinolones (FQr) was treated using a novel bedaquiline containing regimen known as FQr-Bdq-STR for 12-14 months while RR-TB with additional resistance to second-line injectable drugs (SLIr) was treated with a SLIr-STR for 9-11 months. In December 2019, due to the irreversible ototoxicity link to the use of injectables in the Bdsh-STR, the World Health Organization (WHO) recommend to countries to move towards using an all-oral short regimen with bedaquiline (Bdq-STR) lasting 9-11 months. This new regimen received approval by the Cameroon ministry of health for implementation in June 2021.
Two studies in this proposal address the limited data on treatment outcomes of short regimens used for RR-TB patients in Cameroon. I will retrospectively describe results of the Bdsh-STR used in the country during the past five years, including the two novel regimens used for RR-TB patients with additional resistance to second-line TB drugs (FQr-Bdq-STR; SLIr-STR). I will also prospectively compare treatment outcomes of the new Bdq-STR regimen to the Bdsh-STR to establish whether these regimens performed better that the Bdsh-STR. I will also determine the proportion of patients with acquired bedaquiline resistance (BDQr) using the Bdq-STR.
My PhD proposal therefore addresses two important issues which will serve as an evidence-based to the Cameroon national TB program for improving both the notification gap for RR-TB and better roll-out of future STR.