We developed and validated a tNGS assay that was the first to target 22 whole genes instead of regions of drug resistance genes and comprehensively detected susceptibility to 14 anti-TB drugs, with great flexibility to include new or repurposed drugs. Notably, we demonstrated that our custom-designed Ion AmpliSeq TB research panel platform had high concordance with pDST and could significantly reduce turnaround time (by approximately 70%) to meet a clinically actionable time frame.

Bedaquiline (BDQ), which is recommended for the treatment of drug-resistant tuberculosis (DR-TB), was introduced in Taiwan in 2014. Due to the alarming emergence of BDQ resistance, we conducted BDQ resistance analyses to strengthen our DR-TB management program. This retrospective population-based study included initial Mycobacterium tuberculosis isolates from 898 rifampicin-resistant (RR) or multidrug-resistant (MDR) TB cases never exposed to BDQ during 2008–2019. We randomly selected 65 isolates and identified 28 isolates with BDQ MIC<0.25μg/ml and MIC≥0.25μg/ml as the control and study groups, respectively. BDQ drug susceptibility testing (DST) using the MGIT960 system and Sanger sequencing of the atpE, Rv0678, and pepQ genes was conducted. Notably, 18 isolates with BDQ MIC=0.25μg/ml, 38.9% (7/18), and 61.1% (11/18) isolates were MGIT-BDQ resistant and susceptible, respectively. Consequently, we recommended redefining MIC=0.25μg/ml as an intermediate-susceptible category to resolve discordance between different DST methods. Of the 93 isolates, 22 isolates were MGIT-BDQ-resistant and 77.3% (17/22) of MGIT-BDQ-resistant isolates harbored Rv0678 mutations. After excluding 2 MGIT-BDQ-resistant isolates with borderline resistance (GU400growth control-GU100BDQ≤1day), 100% (15/15) harbored Rv0678 gene mutations, including seven novel mutations [g-14a, Ile80Ser (N=2), Phe100Tyr, Ala102Val, Ins g 181–182 frameshift mutation (N=2), Del 11–63 frameshift mutation, and whole gene deletion (N=2)]. Since the other 22.7% (5/22) MGIT-BDQ-resistant isolates with borderline resistance (GU400growth control-GU100BDQ≤1day) had no mutation in three analyzed genes. For isolates with phenotypic MGIT-BDQ borderline resistance, checking for GU differences or conducting genotypic analyses are suggested for ruling out BDQ resistance. In addition, we observed favorable outcomes among patients with BDQ-resistant isolates who received BDQ-containing regimens regardless of Rv0678 mutations. We concluded that based on MIC≥0.25μg/ml, 3.1% (28/898) of drug-resistant TB cases without BDQ exposure showed BDQ resistance, Rv0678 was not a robust marker of BDQ resistance, and its mutations were not associated with treatment outcomes.

No abstract

Poli is one of the areas with high endemicity of onchocerciasis in Cameroon. Invermectin distribution campaign started there since 1993 but there has been no evaluation of the contribution of this measure to the decrease of the prevalence of the disease in the covered area. This study sort to determine the prevalence of onchocerciasis the microfilarial load and IgG3 levels of randomly chosen indigenous (112) who spent most of their lifetime in the Poli area. All persons retained for examination had either never taken ivermectin or had their last dose of ivermectin more than six months before the starting of the present study. The overall prevalence of human onchocerciasis in the eight villages studied was 65.18%. The prevalence was higher (68%) in males than females (59.45%). The microfilarial (mf) density was also higher in the male population (1.48 mf/mg of skin) than the females (1.34 mf/mg of skin). The prevalence of onchocerciasis for the four age groups: 5-20 years. 21-30 years. 31-50 years. >50 years 58.33%, 53.57%, 75.00%, 70.83% respectively while the microfilarial density for these same age groups (1.15 mf/mg of skin, 1.46 mf/mg of skin, 1.68 mf/mg of skin respectively. IgG3 response was higher in females than males and globally, IgG3 levels increased with age in onchocerciasis patients. Sex and age significantly influence the prevalence (P < 0.001 and P0.05). Only age significantly influence the microfilarial density (P 50 years. IgG3 levels did not however, show any correlation with microfilarial density (r = 0.006; P > 0.05). It is evident from this study that after close to a decade of onchocerciasis control in Poli, the disease is still highly endemic there. Health personal in Poli, high authorities of Cameroon Ministry of Public Health and the W.H.O are therefore alerted to visualise new strategies to reinforce control measures in view of the eradication of ''river blindness'' in Poli using the present epidemiological picture.