Background
Resistance to all first-line antibiotics necessitates the use of less effective or more toxic “reserve” agents Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic

Difficult-to-Treat Resistance in Gram-negative Bacteremia at 173 US Hospitals: Retrospective Cohort Analysis of Prevalence, Predictors, and Outcome of Resistance to All First-line Agents.

A critical component of laboratory surveillance for measles is the genetic characterization of circulating wild-type viruses. The World Health Organization (WHO) Measles and Rubella Laboratory Network (LabNet), provides for standardized testing in 183 countries and supports genetic characterization of currently circulating strains of measles viruses. The goal of this report is to describe the lessons learned from nearly 20 years of virologic surveillance for measles, to describe the global databases for measles sequences, and to provide regional updates about measles genotypes detected by recent surveillance activities. Virologic surveillance for measles is now well established in all of the WHO regions, and most countries have conducted at least some baseline surveillance. The WHO Global Genotype Database contains >7000 genotype reports, and the Measles Nucleotide Surveillance (MeaNS) contains >4000 entries. This sequence information has proven to be extremely useful for tracking global transmission patterns and for documenting the interruption of transmission in some countries. The future challenges will be to develop quality control programs for molecular methods and to continue to expand virologic surveillance activities in all regions.

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Global distribution of measles genotypes and measles molecular epidemiology.

Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure.

https://www.pnas.org/content/pnas/116/11/4834.full.pdf

Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities

Digital health facilitated by wearable/portable electronics and big data analytics holds great potential in empowering patients with real‐time diagnostics tools and information. The detection of a majority of biomarkers at trace levels in body fluids using mobile health (mHealth) devices requires bioaffinity sensors that rely on “bioreceptors” for specific recognition. Portable point‐of‐care testing (POCT) bioaffinity sensors have demonstrated their broad utility for diverse applications ranging from health monitoring to disease diagnosis and management. In addition, flexible and stretchable electronics‐enabled wearable platforms have emerged in the past decade as an interesting approach in the ambulatory collection of real‐time data. Herein, the technological advancements of mHealth bioaffinity sensors evolved from laboratory assays to portable POCT devices, and to wearable electronics, are synthesized. The involved recognition events in the mHealth affinity biosensors enabled by bioreceptors (e.g., antibodies, DNAs, aptamers, and molecularly imprinted polymers) are discussed along with their transduction mechanisms (e.g., electrochemical and optical) and system‐level integration technologies. Finally, an outlook of the field is provided and key technological bottlenecks to overcome identified, in order to achieve a new sensing paradigm in wearable bioaffinity platforms.

/pdf/the-era-of-digital-health-a-review-of-portable-and-wearable-tj8im9v8mn.pdf

The Era of Digital Health: A Review of Portable and Wearable Affinity Biosensors

Recent advances in lab-on-a-chip technologies for viral diagnosis.

Serosurveys are useful for assessing population susceptibility to vaccine-preventable disease outbreaks. Although at-risk populations in remote areas could benefit from this type of information, they face several logistical barriers to implementation, such as lack of access to centralized laboratories, cold storage, and transport of samples. We describe a potential solution: a compact and portable, field-deployable, point-of-care system relying on digital microfluidics that can rapidly test a small volume of capillary blood for disease-specific antibodies. This system uses inexpensive, inkjet-printed digital microfluidic cartridges together with an integrated instrument to perform enzyme-linked immunosorbent assays (ELISAs). We performed a field validation of the system’s analytical performance at Kakuma refugee camp, a remote setting in northwestern Kenya, where we tested children aged 9 to 59 months and caregivers for measles and rubella immunoglobulin G (IgG). The IgG assays were determined to have sensitivities of 86% [95% confidence interval (CI), 79 to 91% (measles)] and 81% [95% CI, 73 to 88% (rubella)] and specificities of 80% [95% CI, 49 to 94% (measles)] and 91% [95% CI, 76 to 97% (rubella)] (measles, n = 140; rubella, n = 135) compared with reference tests (measles IgG and rubella IgG ELISAs from Siemens Enzygnost) conducted in a centralized laboratory. These results demonstrate a potential role for this point-of-care system in global serological surveillance, particularly in remote areas with limited access to centralized laboratories.

A digital microfluidic system for serological immunoassays in remote settings

Surveillance of measles virus detected an epidemiologic link between a refugee from Kenya and a Dutch tourist in New Jersey, USA. Identical genotype B3 sequences from patients with contemporaneous cases in the United States, Canada, and Mexico in November and December 2005 indicate that Kenya was likely to have been the common source of virus.

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Paul M. Chege

Papers

A digital microfluidic system for serological immunoassays in remote settings

Identical genotype B3 sequences from measles patients in 4 countries, 2005.