Therapeutic threshold for rifampicin-resistant tuberculosis: a case
report from Maputo, Mozambique
Abstract
Objectives Frequently used rapid rifampicin drug susceptibility tests
(RMP-DST) miss certain rifampicin resistance (RR)-conferring mutations,
leaving RR-tuberculosis undetected. Unknown for RR-TB is the therapeutic
threshold, the probability of disease at which there is equipoise
between treating and not treating. In Mozambique, in a patient not
responding to first-line treatment, clinicians decided to start RR-TB
treatment without bacteriological proof of RR-TB. We determined the
probability of RR-TB in this patient. Methods We converted probabilities
and odds ratios of clinical arguments for RR-TB from literature to
likelihood ratios. We then combined the associated confirming and
excluding power of those arguments to estimate the probability of RR-TB
when the patient was started on RR-TB treatment, and simulated its
variation. We used a log-odds scale to illustrate the effect of
confirming and excluding arguments. Results The starting point was the
prevalence of RR-TB in Mozambique. Positive HIV-status, treatment
failure after a first treatment and after retreatment were included as
confirming arguments, and RMP-DST showing rifampicin susceptibility as
excluding argument for RR-TB. In this patient, the probability of RR-TB
was 46.6% (95% uncertainty interval: 25.0%-72.0%) when RR-TB
treatment was started. Treatment failure and retreatment failure
provided strong confirming arguments, and the RMP-DST result a strong
excluding argument for RR-TB. Conclusions The therapeutic threshold to
start RR-TB-treatment is unknown but probably lower than 47%. The
uncertainty in our estimation reflects the clinical uncertainty in
low-resource settings. Determining the RR-TB therapeutic threshold is
needed to guide clinical decisions.