Antibiotic resistance genes of public health importance in livestock and humans in an informal urban community in Nepal

Abstract

Efforts to mitigate the increasing emergence of antimicrobial resistance (AMR) will benefit from a One Health perspective, as over half of animal antimicrobials are also considered medically important in humans, and AMR can be maintained in the environment. This is especially pertinent to low- and middle-income countries and in community settings, where an estimated 80% of all antibiotics are used. This study features AMR genes found among humans, animals, and water at an urban informal settlement in Nepal with intensifying livestock production. We sampled humans, chickens, ducks, swine, and water clustered by household, as well as rodents and shrews near dwellings, concurrently in time in July 2017 in southeastern Kathmandu along the Manohara river. Real-time qualitative PCR was performed to screen for 88 genes. Our results characterize the animal-human-environmental interfaces related to the occurrence of specific resistance genes (bla_SHV-1 (SHV(238G240E) strain), QnrS, ermC, tetA, tetB, aacC2, aadA1) associated with antibiotics of global health importance that comprise several drug classes, including aminoglycosides, beta-lactams, tetracyclines, macrolides, and fluoroquinolones. By characterizing risk factors across AMR genes of public health importance, this research highlights potential transmission pathways for further investigation and provides prioritization of community-based prevention and intervention efforts for disrupting AMR transmission of critically important antibiotics used in both humans and animals in Nepal.

Figure 1

Logistic regression output of predictors associated with the detection of antibiotic resistance genes of public health importance in an urban informal settlement in Kathmandu, Nepal, 2017. Odds ratios and 95% confidence intervals indicated by point and line for each variable across models; specific results can be found in SI Table 1. Asterisks denote p-values (*p < 0.05, **p < 0.001, ***p < 0.0001). Colors indicate a protective (red) or risk (blue) factor (OR < 1 vs. > 1). Odds ratio scales shown at the bottom of each graph and vary by model. Not all variables were assessed in each model; see “Methods” section for specifics. bla_SHV-1 and tetB were mixed effects models and only fixed effect output is shown. Fecal samples comprise rectal swabs (swine, rodents, shrews), cloacal swabs (ducks, chickens), and feces (humans). Total genes serves as a proxy for co-occurrence of genes in the sample, as measured by total number of genes (out of N = 88) positive in the sample.

Figure 2

(A–G) Flowcharts of positive specimens from an urban, informal settlement in Kathmandu, Nepal separated by sample type and source sampled across seven antibiotic resistance genes of public health importance. Alluvial diagrams of positive specimens across seven antibiotic resistance genes of public health importance. Flow diagram should be read from left to right, with total numbers of samples positive on the left, sample type (fecal only, fecal and oral, oral only, or water) in the middle, and source sampled (chicken, duck, human, shrew, swine, water, or rodent) on the right. Numbers indicate number of samples positive for the AMR gene specified.