Mycobacterium tuberculosis complex whole-genome sequencing in New York State: Implementation of a reduced phenotypic drug susceptibility testing algorithm.

Whole-genome sequencing (WGS) can predict drug resistance and antimicrobial susceptibility in Mycobacterium tuberculosis complex (MTBC) and has shown promise in partially replacing culture-based phenotypic drug susceptibility testing (pDST). We performed a two-year side by side study comparing the prediction of drug resistance and antimicrobial susceptibility by WGS molecular DST (mDST) to pDST to determine resistance at the critical concentration by Mycobacterial Growth Indicator Tube (MGIT) and agar proportion testing. Negative predictive values of WGS results were consistently high for the first-line drugs: rifampin (99.9%), isoniazid (99.0%), pyrazinamide (98.5%), and ethambutol (99.8%); the rates of resistance to these drugs, among strains in our population, are 2.9%, 10.4%, 46.3%, and 2.3%, respectively. WGS results were available an average 8 days earlier than first-line MGIT pDST. Based on these findings, we implemented a new testing algorithm with an updated WGS workflow in which strains predicted pan-susceptible were no longer tested by pDST. This algorithm was applied to 1177 isolates between October 2018 and September 2020, eliminating pDST for 66.6% of samples and reducing pDST for an additional 22.0%. This algorithm change resulted in faster turnaround times and decreased cost while maintaining comprehensive antimicrobial susceptibility profiles of all culture-positive MTBC cases in New York.

Measles infection in persons with secondary vaccine failure, New York City, 2018-19.

A large measles outbreak in New York City, which included cases among vaccinated persons and adults presumed to be immune, provided the opportunity to better understand vaccine failure and the potential impact on measles transmission. Immunoglobulin G (IgG) avidity can distinguish primary (low avidity IgG, indicating no evidence of prior immunity) versus secondary vaccine failure (high avidity IgG, indicating prior immune response and waning antibody). Measles IgG avidity was measured on samples from 62 persons: avidity was high in 53 (16 vaccinated and 37 with unknown vaccination history) and low in 9 (1 recently vaccinated and 8 with unknown vaccination history). Secondary transmission from 2 persons with high-avidity IgG results occurred. These findings illustrate that in settings of sustained measles elimination, measles infection and transmission can occur in persons with secondary vaccine failure, underscoring the need to maintain a high index of suspicion for measles during an outbreak despite prior or presumed prior vaccination.