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Background Since the roll-out of the Xpert MTB/RIF assay, continuous surveillance can provide an estimate of rifampicin-resistant TB (RR-TB) prevalence, provided high drug susceptibility testing (DST) coverage is achieved. We use national data from Rwanda to describe rifampicin DST coverage, estimate the prevalence of RR-TB and assess its predictors. Methods Routinely collected DST data were entered into an electronic TB case-based surveillance system. DST coverage was calculated among all bacteriologically confirmed pulmonary TB patients notified from 1 July 2019 to 30 June 2020 in Rwanda. The prevalence of RR-TB was estimated among those with DST results. Univariable and multivariable analysis was performed to explore predictors for RR TB. Results Among 4066 patients with bacteriologically confirmed pulmonary TB, rifampicin DST coverage was 95.6% (4066/4251). RR-TB was diagnosed in 73 patients. The prevalence of RR-TB was 1.4% (53/3659; 95% CI 1.09 to 1.89%) and 4.9% (20/406; 95% CI 3.03 to 7.51%) in new and previously treated TB cases, respectively. Predictors of RR-TB were: (1) living in Kigali City (adjusted OR [aOR] 1.65, 95% CI 1.03 to 2.65); (2) previous TB treatment (aOR 3.64, 95% CI 2.14 to 6.19); and (3) close contact with a known RR-TB patient (aOR 11.37, 95% CI 4.19 to 30.82). Conclusions High rifampicin DST coverage for routine reporting allowed Rwanda to estimate the RR-TB prevalence among new and previously treated patients. [ABSTRACT FROM AUTHOR]

Background: A recently published Ugandan study on tuberculosis (TB) diagnosis in HIV-positive patients with presumptive smear-negative TB, which showed that out of 90 patients who started TB treatment, 20% (18/90) had a positive Xpert MTB/RIF (Xpert) test, 24% (22/90) had a negative Xpert test, and 56% (50/90) were started without Xpert testing. Although Xpert testing was available, clinicians did not use it systematically. Here we aim to show more objectively the process of clinical decision-making. First, we estimated that pre-test probability of TB, or the prevalence of TB in smear-negative HIV infected patients with signs of presumptive TB in Uganda, was 17%. Second, we argue that the treatment threshold, the probability of disease at which the utility of treating and not treating is the same, and above which treatment should be started, should be determined. In Uganda, the treatment threshold was not yet formally established. In Rwanda, the calculated treatment threshold was 12%. Hence, one could argue that the threshold was reached without even considering additional tests. Still, Xpert testing can be useful when the probability of disease is above the treatment threshold, but only when a negative Xpert result can lower the probability of disease enough to cross the treatment threshold. This occurs when the pre-test probability is lower than the test-treat threshold, the probability of disease at which the utility of testing and the utility of treating without testing is the same. We estimated that the test-treatment threshold was 28%. Finally, to show the effect of the presence or absence of arguments on the probability of TB, we use confirming and excluding power, and a log10 odds scale to combine arguments.Conclusion: If the pre-test probability is above the test-treat threshold, empirical treatment is justified, because even a negative Xpert will not lower the post-test probability below the treatment threshold. However, Xpert testing for the diagnosis of TB should be performed in patients for whom the probability of TB was lower than the test-treat threshold. Especially in resource constrained settings clinicians should be encouraged to take clinical decisions and use scarce resources rationally. [ABSTRACT FROM AUTHOR]

Background: To achieve the ambitious 90-90-90 UNAIDS targets, access to routine viral load (VL) is critical. To measure VL, Rwanda has relied on a national reference laboratory for years. In 2014, a VL testing platform was implemented in a rural District in the Northern Province. Here we analyze the uptake of VL testing, identification of risks for detectable VL (≥1000 copies/ml), and the management of patients with a detectable VL.Methods: A retrospective cohort study of patients who started ART between July 2012 and June 2015 and followed until end December 2016. Using descriptive statistics, we describe the VL cascade, from VL uptake to the start of second-line ART in patients diagnosed with virological failure. We estimate predictors of having a detectable VL using logistic regression.Results: The uptake of VL testing increased progressively between 2013 and 2016, raising from 25.6% (39/152) in 2013 up to 93.2% (510/547) in 2016.In 2016, 88.5% (n = 451) of patients tested, had a suppressed VL. Predictors of having a detectable VL included being male (aOR 2.1; 95%CI 1.12-4.02; p = 0.02), being a sex worker (aOR 6.4; 95%CI 1.1-36.0; p = 0.04), having a WHO clinical stage IV when starting ART (aOR 8.8; 95%CI 1.8-43.0; p < 0.001), having had a previous detectable VL (aOR 7.2; 95%CI 3.5-14.5; p < 0.001), and having had no VL before 2016 (aOR 3.1; 95%CI 1.2-8.1; p = 0.02). Among patients with initial detectable VL between 2013 and 2016, 88% (n = 103) had a follow-up VL, of whom 60.2% (n = 62) suppressed their VL below 1000 copies/ml. The median time between the initial and follow-up VL was of 12.5 months (IQR: 8.7-19.0). Among patients with confirmed treatment failure, 63.4% (n = 26) started second-line ART within the study period.Conclusion: VL uptake increased after decentralizing VL testing in rural Rwanda. Virological suppression was high. An individualized follow up of patients at risk of non-suppression and a prompt management of patients with detectable VL may help to achieve and sustain the third global UNAIDS target: virological suppression in 90% of patients on ART. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization-endorsed phenotypic and genotypic drug-susceptibility testing (gDST/pDST) assays for the detection of rifampicin-resistant (RR) tuberculosis (TB), may miss some clinically relevant rpoB mutants, including borderline mutations and mutations outside the gDST-targeted hotspot region. Sequencing of the full rpoB gene is considered the reference standard for rifampicin DST but is rarely available in RR-TB endemic settings and when done indirectly on cultured isolates may not represent the full spectrum of mutations. Hence, in most such settings, the diversity and trends of rpoB mutations remain largely unknown., Methods: This retrospective study included rpoB sequence data from a longitudinal collection of RR-TB isolates in Rwanda across 30 years (1991-2021)., Results: Of 540 successfully sequenced isolates initially reported as RR-TB, 419 (77.6%) had a confirmed RR conferring mutation. The Ser450 Leu mutation was predominant throughout the study period. The Val170Phe mutation, not covered by rapid gDST assays, was observed in only four patients, three of whom were diagnosed by pDST. Along with the transition from pDST to rapid gDST, borderline RR-associated mutations, particularly Asp435Tyr, were detected more frequently. Borderline mutants were not associated with HIV status but presented lower odds of having rpoA-C compensatory mutations than other resistance-conferring mutations., Conclusion: Our analysis showed changes in the diversity of RR-TB conferring mutations throughout the study period that coincided with the switch of diagnostic tools to rapid gDST. The study highlights the importance of rapid molecular diagnostics reducing phenotypic bias in the detection of borderline rpoB mutations while vigilance for non-rifampicin resistance determinant region mutations is justified in any setting., Competing Interests: None

We report a case of acquired fluoroquinolone (FQ) resistance under short-course multidrug-resistant tuberculosis (MDR-TB) treatment. The patient was managed at Kabutare hospital, one of the two specialized MDR-TB clinics in Rwanda. A low dose of moxifloxacin was used in the first three critical months. Acquired resistance was identified at the ninth month of treatment, 3 months after stopping kanamycin in a strain initially susceptible only to FQs, kanamycin, and clofazimine. Fluoroquinolone resistance was detected in the same month by deep sequencing as routinely used second-line line probe assay and phenotypic drug susceptibility testing. High-dose FQ, preferably gatifloxacin, should be used to maximize effectiveness.