A high prevalence of multi-drug resistant Gram-negative bacilli in a Nepali tertiary care hospital and associated widespread distribution of Extended-Spectrum Beta-Lactamase (ESBL) and carbapenemase-encoding genes

Abstract: Background: Multi-drug resistance (MDR) and extensive-drug resistance (XDR) associated with extended-spectrum beta-lactamases (ESBLs) and carbapenemases in Gram-negative bacteria are global public health concerns. Data on circulating antimicrobial resistance (AMR) genes in Gram-negative bacteria and their correlation with MDR and ESBL phenotypes from Nepal is scarce. Methods: A retrospective study was performed investigating the distribution of ESBL and carbapenemase genes and their potential association with ESBL and MDR phenotypes in E. coli, Klebsiella spp., Enterobacter spp. and Acinetobacter spp. isolated in a major tertiary hospital in Kathmandu, Nepal, between 2012 and 2018. Results: During this period, the hospital isolated 719 E. coli, 532 Klebsiella spp., 520 Enterobacter spp. and 382 Acinetobacter spp.; 1955/2153 (90.1%) of isolates were MDR and half (1080/2153) were ESBL producers. Upon PCR amplification, blaTEM (1281/1771; 72%), blaCTXM-1 (930/1771; 53%) and blaCTXM-8 (419/1771; 24%) were the most prevalent ESBL genes in the enteric bacilli. BlaOXA and blaOXA-51 were the most common blaOXA family genes in the enteric bacilli (918/1771; 25%) and Acinetobacter spp. (218/382; 57%) respectively. Sixteen percent (342/2153) of all isolates and 20% (357/1771) of enteric bacilli harboured blaNDM-1 and blaKPC carbapenemase genes respectively. Of enteric bacilli, Enterobacter spp. was the most frequently positive for blaKPC gene (201/337; 60%). The presence of each blaCTX-M and blaOXA were significantly associated with non-susceptibility to third generation cephalosporins (OR 14.7, p < 0.001 and OR 2.3, p < 0.05, respectively).The presence of each blaTEM, blaCTXM and blaOXA family genes were significantly associated with ESBL positivity (OR 2.96, p < 0.001; OR 14.2, p < 0.001 and OR 1.3, p < 0.05 respectively) and being MDR (OR 1.96, p < 0.001; OR 5.9, p < 0.001 and OR 2.3, p < 0.001 respectively). Conclusions: This study documents an alarming level of AMR with high prevalence of MDR ESBL- and carbapenemase-positive ESKAPE microorganisms in our clinical setting. These data suggest a scenario where the clinical management of infected patients is increasingly difficult and requires the use of last-resort antimicrobials, which in turn is likely to intensify the magnitude of global AMR crisis

Social determinants and risk behaviors associated with prevalent Hepatitis C and HIV/HCV co-infection among male injection drug users in Nepal

Abstract Background Nepal is facing double burden of injecting drug use and HIV, yet the problem of Hepatitis C Virus (HCV) has not been so well addressed, where there is large population known to be at risk for HCV. This study assessed the prevalence of HCV infection and HIV/HCV co-infection among male injection drug users (IDUs) in Nepal and identified factors associated with infection. Methods Cross-sectional surveys in 2015 aimed to sample 1045 male IDUs in the Kathmandu valley, Pokhara Valley and Eastern Terai districts of Nepal. Information about socio demographic characteristics, injecting and sexual risk behaviours were obtained, and biological specimens tested for HCV and HIV. The logistic regression model was used to identify the determinants associated with HCV and HIV/HCV co-infection. Results HCV prevalence was 28.8% and HIV/HCV co-infection was 4%. Among the 6% of HIV positive male IDUs, 65% were found to be co-infected. The multivariate logistic analysis revealed that HCV prevalence was higher in Eastern Terai districts, longer duration of drug use and injecting drugs and presence of HIV. Similarly, HIV/HCV co-infection was associated with Eastern highway districts, older age and longer duration of injecting drugs. Conclusion The factors strongly contributing to HCV and HIV/HCV co-infection was longer duration of injecting drugs. Highest HCV and HIV/HCV co-infection was found in Eastern Terai districts. Target health interventions need to be focused in Eastern Terai districts and IDUs with longer duration of injecting drugs for the prevention of HCV and HIV/HCV transmission

Understanding Mycobacterium tuberculosis complex in elephants through a One Health approach: a systematic review

[Background]: Mycobacterium tuberculosis complex (MTC) that causes the chronic infectious disease- tuberculosis (TB), often presents with a complicated epidemiological pattern where the transmission chain may include humans, domestic animals and wildlife, including elephants. TB has been reported globally in both captive and wild elephants. The One Health approach might be the most effective way of understanding the shared MTC infection dynamics in captive and wild animals like Asian elephants. This systematic review accumulates evidence on occurrence, transmission pathways, and preventive measures of TB in elephants from a One Health perspective.[Results]: The prevalence of TB reported in elephant populations ranges from 0 to 23.33% and high prevalence's are reported for elephants that are in close proximity to infected humans. The risk of elephant to human infection transmission increased significantly with exposure duration and contact with infected elephants. Some studies described the plausible TB transmission to captive elephants from other animals (wild and domestic), suggesting inter- and intra-species transmission. The results of this systematic review based on 27 relevant published works, suggest three overarching interrelated transmission pathways for M. tuberculosis infections in Asian elephants- i) humans and elephants, ii) other animals (wild or domestic) and elephants and iii) unclear sources of infection.[Conclusions]: The progress made with new TB diagnostic tools provides multiple methods to choose from. However, lack of harmonization of TB testing in elephants and their human contacts remains a challenge to prevent TB in those animals. Routine TB screening among elephants and caretakers by setting up an occupational health program for early diagnosis of infection through combined efforts of public health, veterinary medicine, and occupational health experts is suggested. This implies the need for a One Health approach to elephant TB control. This review reveals the need for more research on Mycobacterium tuberculosis complex transmission pathways at the human-animal interface.Peer reviewe