Programmatic management of rifampicin-resistant tuberculosis with standard regimen in Cameroon: a retrospective cohort study.

OBJECTIVES: To describe treatment outcomes for rifampicin-resistant tuberculosis (Rr-TB) started on standard regimen and the frequency of acquired drug resistance in patients treated using the standard treatment regimen (STR) in Cameroon between 2015-2019. METHODS: This is a retrospective cohort study. Rr-TB patients were initiated on the STR, including a fluoroquinolone (FQ), a second-line injectable drug (SLI), and companion drugs. In case of resistance to fluoroquinolones (FQr) at baseline, FQ, SLI and ethionamide were replaced by bedaquiline, delamanid, and linezolid in a modified treatment regimen (mTR), FQr-mTR. In case of resistance to SLI (SLIr) at baseline, SLI was replaced by linezolid (LZD), SLIr-mTR. Logistic regression and competing risk regression were used to estimate predictors of early (first eight weeks) mortality and overall mortality, respectively. RESULTS: Of 709 patients started on a standard regimen, treatment success occurred in 84.7% (587/693), 72.7% (8/11) and 100% (10/10) of patients treated with STR, FQr-mTR and SLIr-mTR as final regimens, respectively. Three (0.6%) patients acquired FQr during treatment. Early mortality occurred in 4.1% (29/709) and was associated with being HIV positive, male sex and being underweight. Overall mortality was associated with missing drug-susceptibility testing results at baseline, being HIV positive, age>40 and male sex. CONCLUSION: Programmatic management of Rr-TB, with additional second-line drug resistance treated with mTR, resulted in excellent treatment outcomes.

Tuberculosis-loop-mediated isothermal amplification implementation in Cameroon: Challenges, lessons learned and recommendations.

Background: Until 2016, microscopy was the main tool for the early detection of pulmonary tuberculosis in Cameroon, especially in remote settings. Due to the poor sensitivity of microscopy, there was a need to implement a molecular assay in order to improve tuberculosis case detection. Intervention: In 2017, tuberculosis loop-mediated isothermal amplification (TB-LAMP), a molecular rapid diagnostic test recommended by the World Health Organization, was implemented in Cameroon as a replacement test of microscopy for initial diagnosis of pulmonary tuberculosis and also as a follow-on test to microscopy for smear-negative sputum specimens. A roll out plan for TB-LAMP implementation in Cameroon had been developed from January 2017 to April 2017, followed by initial implementation at four sites in May 2017. Additional sites were added progressively. Lessons learnt: The use of TB-LAMP as a follow-on test to microscopy for smear-negative sputum specimens helped in the detection of tuberculosis in 14.77% of those who were sputum-smear negative in 2019. Tuberculosis-loop-mediated isothermal amplification usage as an initial test, followed by testing with Xpert MTB/RIF for rapid tuberculosis and rifampicin resistance detection during tuberculosis mass screening campaigns, reduced the turn-around time by 73.23% as compared to when the Gene Xpert instrument was used alone. Recommendations: The implementation and scaling up of TB-LAMP in Cameroon contributed to increase access to tuberculosis molecular diagnosis in remote settings and as such improved tuberculosis case notification. However, to better enhance this notification and optimise the use of a TB-LAMP instrument, a suitable sample transport system is recommended.

Diagnostic Accuracy of the Truenat MTB Plus Assay and Comparison with the Xpert MTB/RIF Assay to Detect Tuberculosis among Hospital Outpatients in Cameroon.

The Truenat MTB Plus assay is a rapid molecular test that has been recommended by the World Health Organization since 2020 as an initial test to detect tuberculosis (TB). The WHO highlighted the need to further evaluate assay performance to inform future recommendations, including in people living with HIV and compared to the Xpert MTB/RIF assay. We conducted a prospective evaluation of the diagnostic accuracy of the Truenat assay in Cameroon, a country with a high burden of HIV/TB. Adult outpatients were recruited at four hospitals; demographic information and medical history were collected, and participants produced two sputum specimens. Truenat and Xpert testing was performed on the same specimen, and performance was compared to TB culture as the reference standard. From November 2019 to December 2020, 945 participants were enrolled and included in the analysis. Among 251 participants with culture-positive TB, the sensitivity of Truenat MTB Plus was 91% (95% confidence interval [CI], 86 to 94%), similar to Xpert (90%; 95% CI, 86 to 93%). Among 74 HIV-positive participants with culture-positive TB, the sensitivity of Truenat MTB Plus was 85% (95% CI, 75 to 92%) compared to 81% for Xpert (95% CI, 70 to 89%). Among 47 participants with smear-negative TB, the sensitivity of Truenat MTB Plus was 55% (95% CI, 40 to 70%), similar to Xpert (53%; 95% CI, 38 to 68%). The specificity of Truenat MTB Plus was 96% (95% CI, 94 to 97%) compared to 99% (95% CI, 97 to 99%) for Xpert. For TB detection compared to the reference standard of TB culture, the performance of the Truenat MTB Plus assay was similar to that of Xpert in this population, including among people living with HIV.

A cost-benefit algorithm for rapid diagnosis of tuberculosis and rifampicin resistance detection during mass screening campaigns.

BACKGROUND: Active tuberculosis (TB) case finding is important as it helps detect pulmonary TB cases missed by the other active screening methods. It requires periodic mass screening in risk population groups such as prisoners and refugees. Unfortunately, in these risk population groups periodic mass screening can be challenging due to lengthy turnaround time (TAT), cost and implementation constraints. The aim of this study was to evaluate a diagnostic algorithm that can reduce the TAT and cost for TB and Rifampicin resistance (RR) detection. The algorithm involves testing with TB-LAMP followed by Xpert MTB/RIF for positive TB-LAMP cases to diagnose TB during mass campaigns in prisons and refugee camps. METHODS: The National Tuberculosis Control Program (NTCP) organized routine TB mass-screening campaigns in 34 prisons and 3 villages with refugees camps in Cameroon in 2019. TB LAMP was used for initial TB diagnosis and all TB-LAMP positive cases tested with the Xpert MTB/RIF assay to determine RR. TAT and cost benefits analysis of the combined use of TB-LAMP and Xpert MTB/RIF assays was determined and compared to the Xpert MTB/RIF assay when used only. RESULTS: A total of 4075 sputum samples were collected from TB presumptive, 3672 cases in 34 prisons and 403 samples in 3 villages. Of the 4,075 samples screened with TB-LAMP, 135 were TB positive (3.31%) and run on the Xpert MTB/RIF. Of the 135 positives cases, Xpert MTB/RIF revealed 3 were RR (2.22%). The use of TB-LAMP followed by testing with Xpert MTB/RIF for TB and RR detection reduced the TAT by 73.23% in prisons and 74.92% in villages. In addition to a reduced TAT, the two molecular tests used in synergy is cost benefit from year 2 onwards. CONCLUSION: This study demonstrates the advantages of a diagnostic algorithm based on an initial testing with TB-LAMP followed by testing with Xpert MTB/RIF for TB diagnosis. This approach improved early and rapid TB detection with an added advantage of providing RR status. The proposed algorithm is effective and less costly from the second year of implementation and should be used by TB control programs.

Impact of intensified tuberculosis case finding at health facilities on case notifications in Cameroon: A controlled interrupted time series analysis.

There is a large gap between the number of people who develop tuberculosis (TB) and those who are diagnosed, treated and notified, with only an estimated 71% of people with TB notified globally in 2019. Implementing better TB case finding strategies is necessary to close this gap. In Cameroon, 1,597 healthcare workers at 725 health facilities were trained and engaged to intensively screen and test people for TB, then follow-up to link people to appropriate care. Primary care centers were linked to TB testing through a locally-tailored specimen referral network. This intervention was implemented across 6 regions of the country, with a population of 16 million people, while the remaining 4 regions in the country, with 7.3 million people, served as a control area. Controlled interrupted time series analyses were used to compare routinely-collected programmatic TB case notification rates in the intervention versus control area for 12 quarters prior to (2016-2018) and for 8 quarters after the start of the intervention (2019-2020). In 2019-2020, a total of 167,508 people were tested for TB at intervention sites, including 52,980 people attending primary care facilities that did not previously provide organized TB services. The number of people tested for TB increased by 45% during the intervention as compared to prior to the intervention. The controlled interrupted time series analyses showed that after two years of the intervention, the all-forms TB case notification rate in the intervention population increased by 9% (ratio of case notification rate ratios = 1.09, 95% CI 1.06 to 1.12), as compared with the counterfactual estimated from pre-intervention trends. This increase was observed even during a negative national impact on case finding from the COVID-19 pandemic. These results support the use of this health-facility based intervention to improve access to TB testing and care in this setting.

Patient-Pathway Analysis of Tuberculosis Services in Cameroon.

In Cameroon, in 2019, tuberculosis (TB) treatment coverage was estimated at 53%, indicating that almost half of all people sick with TB were not diagnosed or linked to care. To inform strategies to improve access to TB services, we conducted an evaluation of the alignment between patient-initiated care-seeking behavior and spatial and institutional allocation of TB services. Data sources included the Cameroon Demographic and Health Survey (2018), the Health Facility List (2017), and routinely collected TB surveillance data. Data visualization was performed in Tableau and QGIS. The pathway analysis showed that only an estimated 9% of people attended a health facility providing TB services at initial care-seeking, with access varying from <3% to 16% across the ten regions of the country. While 72% of government and 56% of private hospitals (Level 2 facilities) provide TB services, most Cameroonians (87%) initially chose primary care (Level 1) or informal private sector sites (Level 0) without TB services. The gaps were greatest in regions with the highest prevalence of poverty, a significant determinant for TB. These results indicate that access may be improved by expanding TB services at both public and private facilities across the country, prioritizing regions with the greatest gaps.