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ResearchTo cite: Prem K, Pheng SH, Teo AKJ, et al. Spatial and temporal projections of the prevalence of active tuberculosis in Cambodia.

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Background: Due to the emergence of Mycobacterium tuberculosis (M.tb) clinical isolates resistant to most potent first-line drugs (FLD), second-line drugs (SLD) are being prescribed more frequently. We explore the genetic characteristics and molecular mechanisms of M.tb isolates phenotypically resistant to SLD, including pre-extensively drug-resistant (pre-XDR) and extensively drug-resistant (XDR) isolates. Methods: Drug-resistant (DR) M.tb isolates collected from 2012 to 2017 were tested using sequencing and phenotypic drug susceptibility testing. Genotypes were determined to explore their links with SLD resistance patterns. Results: Of the 272 DR M.tb isolates, 6 non-multidrug resistant (non-MDR) isolates were fluoroquinolones (FQ)-resistant, 3 were XDR and 16 were pre-XDR (14 resistant to FQ and 2 to second-line injectable drugs). The most frequent mutations in FQ-resistant and secondline injectable drugs resistant isolates were gyrA D94G (15/23) and rrs a1401g (3/5), respectively. Seventy-five percent of pre-XDR isolates and 100% of XDR isolates harbored mutations conferring resistance to pyrazinamide. All XDR isolates belonged to the Beijing genotype, of which one, named XDR+, was resistant to all drugs tested. One cluster including pre-XDR and XDR isolates was observed. Conclusion: This is the first description of SLD resistance in Cambodia. The data suggest that the proportion of XDR and pre-XDR isolates remains low but is on the rise compared to previous reports. The characterization of the XDR+ isolate in a patient who refused treatment underlines the risk of transmission in the population. In addition, genotypic results show, as expected, that the Beijing family is the main involved in pre-XDR and XDR isolates and that the spread of the Beijing pre-XDR strain is capable of evolving into XDR strain. This study strongly indicates the need for rapid interventions in terms of diagnostic and treatment to prevent the spread of the pre-XDR and XDR strains and the emergence of more resistant ones.

Background The World Health Organization (WHO) estimated that 29% of global tuberculosis (TB) and almost 47% of childhood TB cases were not reported to national TB programs in 2019. In Cambodia, most childhood TB cases were reported from health facilities supported by the Global Fund to Fight AIDS, Tuberculosis, and Malaria in 2019. This study aimed to compare the healthcare providers' KAP on childhood TB case detection in ODs with high and low childhood TB case detection in Cambodia. Methods We conducted a cross-sectional study between November and December 2020 among healthcare providers in 10 purposively selected operational districts (ODs) with high childhood TB case detection and 10 ODs with low childhood TB case detection. A total of 110 healthcare providers from referral hospitals and 220 from health centers were interviewed. We collected information on socio-demographic characteristics, training, and KAP on childhood TB. Pearson's Chi-square or Fisher's exact and Student's t-tests were performed to explore the differences in KAP of healthcare providers from ODs with low vs. high childhood TB detection. Results Of the 330 respondents, 193 were from ODs with high childhood TB case detection, and 66.67% were from health centers. A significantly higher proportion (46.11%) of respondents from ODs with high childhood TB case detection received training on childhood TB within the past two years than those from low childhood TB case detection ODs (34.31%) (p=0.03). Key knowledge on childhood TB was not significantly different among respondents from ODs with high and low childhood TB case detection. A significantly higher proportion of respondents from ODs with high childhood TB case detection had a good attitude (98.96% v.s. 97.08%, p=0.002) and performed good practices (58.55% v.s. 45.26%, p=0.02) on contact investigation in the community than those from low childhood TB case detection ODs. Conclusions Healthcare providers from ODs with high childhood TB detection had better attitudes and practices towards childhood TB. The attitudes and practices need to be improved among healthcare providers in ODs with low case detection. Further investment in training and experience sharing on childhood TB case detection among healthcare providers is needed to improve childhood TB case detection.