New research was presented at ASM Microbe 2019, the joint annual meeting of the American Society for Microbiology and the Interscience Conference on Antimicrobial Agents and Chemotherapy, from June 20-24 in San Francisco. The features below highlight some of the studies that emerged from the conference.
Outpatient Influenza A Cases Predict Hospital Influenza Activity
Influenza prevention control measures in the hospital are enacted after influenza activity has already increased, due to the cost and inability to accurately predict such activity in the emergency department. Outpatient influenza A-positive cases may be predictive indicator of hospital influenza activity. For a study, researchers continuously monitored such cases in nearly 50 UCLA-affiliated outpatient clinics spanning more than 300 square miles during the 2018-2019 influenza season. The clinics used the Influenza A + B Fluorescent Immunoassay test on a point-of-care platform, with de-identified results instantly transmitted through a global wireless surveillance and remote data management system, supporting a continuous monitoring of influenza testing and results based on geographic region. The total number of influenza tests and positive influenza cases at two UCLA-affiliated hospitals and emergency departments were recorded on a weekly basis. Based on more than 5,000 test results, influenza-positive cases were found to increase in the outpatient setting 1 week prior to the emergency department and inpatient units at both hospitals. “Our results suggest that outpatient influenza monitoring predicts [emergency department] and inpatient influenza, allowing for an earlier preventative infection control response,” concluded the study authors.
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Targeting a UTI Vaccine
With data indicating that urinary tract infection (UTI) is the second most common bacterial infection in humans, antibiotic resistance and morbidity of recurrent infection create an urgent need for a UTI vaccine. Using the knowledge that uropathogenic Escherichia coli (UPEC) is the primary cause of most UTIs in otherwise healthy individuals, researchers from the University of Michigan have developed an experimental vaccine targeting four UPEC outer membrane proteins to elicit protection against UTI. To better understand pre-existing antibody responses to UTI vaccine antigens in their target population, they obtained sera from 77 female cystitis patients and 20 healthy adult male donors. Total and antigen-specific immunoglobulin G (IgG) titers were measured for all patients. Although total IgG was consistent across all patients, antigen-specific IgG titers did not correlate with the presence or absence of the gene encoding the antigen in the infecting strain. Instead, titers were proportional to the prevalence of the genes encoding the antigen among all UPEC isolates. Similar results were seen upon testing sera from the males without a history of UTI. The researchers concluded that unvaccinated adults have non-protective levels of pre-existing antibodies to UTI vaccine antigens, establishing an important baseline for their target population and suggesting that a “UTI vaccine would need to boost pre-existing humoral responses beyond these background levels to offer protection from infection.”
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Risk Networks in HIV-Positive PWID
Applied to people who inject drugs (PWID), Seidman k-cores are network subsets whose members are each connected with k or more subset members or a larger network component, with previous research suggesting that HIV infection is very prevalent among 2-core network members. With other studies indicating that social norms on drug injection practices influence drug injection-related behavior, and therefore HIV transmission, study investigators sought to describe the prevalence of drug-related norms in a large component of a network of PWID in the context of an HIV outbreak during a serious economic crisis. Over 2 years, HIV-positive index “seeds” were recruited, as were members of the seeds’ risk networks and of network members’ risk networks, in a two-step process. Questionnaires including items on injection norms were administered to all. More than half (51.1%) of PWID were in the 2-core subset of a large network component, among whom HIV prevalence was significantly higher than among the rest of mostly isolated cases or very small connected groups (59.0% vs 28.2%). However, 48.3% of those in the latter group said that none of the people with whom they inject drugs at drug-using venues would object if someone tried to share syringes/needles, compared with 28.9% in the former. Also, in case of withdrawal, 61.2% of 2-core network participants said they would strongly agree that people they inject with would object to their use of a syringe that someone who looks dirty or very sick had just used, compared with 47.3% of non 2-core network members. “Successful interventions among PWID should focus on both parts of a risk network either to identify undiagnosed infections (as in a 2-core network subset given the high HIV prevalence in it) or to change norms (as among non 2-core network members),” write the study authors.
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Rapid Detection of Herpes Simplex Virus
Data indicate that disseminated neonatal herpes simplex virus (HSV) infection has high morbidity and mortality rates, with rapid diagnosis required for proper treatment. To evaluate the performance of a novel assay on whole blood specimens for the detection of HSV-1 and HSV-2, researchers tested whole blood specimens as a 1:1 dilution with peripheral blood samples (without magnesium and calcium) using the assay. Determination of limit of detection (LOD) was performed as a head-to-head comparison between spiked whole blood and cerebrospinal fluid (CSF) specimens. Patient correlation was performed with residual volume from patient specimens tested by a reference lab assay. The overall LOD for HSV-1 and HSV-2 in whole blood were comparable to performance in CSF. Both specimen types showed 100% detection at 2,000 copies/mL for both HSV-1 and HSV-2, with 10-fold dilutions below 2,000 copies/mL showing a rapid decline in detection until being completely undetectable at 20 copies/mL. The performance of the assay for detection of HSV-1 and HSV-2 in whole blood specimens was determined to be consistent and have a comparable LOD to HSV-1 and HSV-2 in CSF, the FDA-approved specimen type, suggesting that it can be used for detection of HSV-1 and HSV-2 in whole blood specimens.
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Curtailing Multiplex Respiratory Viral Testing
Although evidence suggests that multiplex screening platforms are widely used for identifying respiratory viral pathogens, guidelines defining optimal frequency for subsequent screening are lacking, possibly resulting in repeat screens obtained over short periods. Such overuse, combined with recent Medicare limitations on multiplex panel testing coverage, can place financial strain on clinical laboratories. To determine the optimal duration of between sample testing in which new actionable results can be expected, researchers analyzed multiplex viral panel results for 13 viruses from patients presenting at Cleveland Clinic over 5 years. During the study period, 40% of nearly 22,000 nasopharyngeal (NP) specimens were positive for at least one viral pathogen. More than 1,500 patients had more than one NP specimen tested within 90 days, producing 2,619 additional samples, with a median of 28 days between baseline and repeat sample. Among repeat specimens, only 29% had a different result than the initial, with changes in only 4% of repeats performed in 1 day and 36% of those done after 76-90 days and odds of change plateauing after 15 days. The odds of a change in result for tests repeated within 15 days were only 0.44 times the odds for 16-90 days, leading the researchers to conclude that “repeat screening of NP samples before 15 days demonstrates little benefit.”
