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.

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.

The outbreak of SARS-CoV-2 is posing serious global public health problems Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people The assay demonstrated high sensitivity and specificity, which is promising for the diagnosis and monitoring as well as control of SARS-CoV-2 worldwide

Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min.

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

Dadaab Refugee camp in Garissa County, Kenya, hosts nearly 340,000 refugees in five subcamps (Dagahaley, Hagadera, Ifo, Ifo2, and Kambioos) (1). On November 18 and 19, 2015, during an ongoing national cholera outbreak (2), two camp residents were evaluated for acute watery diarrhea (three or more stools in ≤24 hours); Vibrio cholerae serogroup O1 serotype Ogawa was isolated from stool specimens collected from both patients. Within 1 week of the report of index cases, an additional 45 cases of acute watery diarrhea were reported. The United Nations High Commissioner for Refugees and their health-sector partners coordinated the cholera response, community outreach and water, sanitation, and hygiene (WASH) activities; Medecins Sans Frontieres and the International Rescue Committee were involved in management of cholera treatment centers; CDC performed laboratory confirmation of cases and undertook GIS mapping and postoutbreak response assessment; and the Garissa County Government and the Kenya Ministry of Health conducted a case-control study. To prevent future cholera outbreaks, improvements to WASH and enhanced disease surveillance systems in Dadaab camp and the surrounding area are needed.

/pdf/cholera-outbreak-in-dadaab-refugee-camp-kenya-november-2015-wp7uyrqu4j.pdf

Cholera Outbreak in Dadaab Refugee Camp, Kenya - November 2015-June 2016.

Diabetes mellitus (DM) is increasing markedly in low- and middle-income countries where over three-quarters of global deaths occur due to non-communicable diseases. Unfortunately, these conditions are considered costly and often deprioritized in humanitarian settings with competing goals. Using a mixed methods approach, this study aimed to quantify the cost of outpatient treatment for uncomplicated type-1 (T1DM) and type-2 (T2DM) diabetes at a secondary care facility serving refugees in Kenya. A retrospective cost analysis combining micro- and gross-costings from a provider perspective was employed. The main outcomes included unit costs per health service activity to cover the total cost of labor, capital, medications and consumables, and overheads. A care pathway was mapped out for uncomplicated diabetes patients to identify direct and indirect medical costs. Interviews were conducted to determine inputs required for diabetes care and estimate staff time allocation. A total of 360 patients, predominantly Somali refugees, were treated for T2DM (92%, n = 331) and T1DM (8%, n = 29) in 2017. Of the 3,140 outpatient consultations identified in 2017; 48% (n = 1,522) were for males and 52% (n = 1,618) for females. A total of 56,144 tests were run in the setting, of which 9,512 (16.94%) were Random Blood Sugar (RBS) tests, and 90 (0.16%) HbA1c tests. Mean costs were estimated as: $2.58 per outpatient consultation, $1.37 per RBS test and $14.84 per HbA1c test. The annual pharmacotherapy regimens cost $91.93 for T1DM and $20.34 for T2DM. Investment in holistic and sustainable non-communicable disease management should be at the forefront of humanitarian response. It is expected to be beneficial with immediate implications on the COVID-19 response while also reducing the burden of care over time. Despite study limitations, essential services for the management of uncomplicated diabetes in a humanitarian setting can be modest and affordable. Therefore, integrating diabetes care into primary health care should be a fundamental pillar of long-term policy response by stakeholders.

/pdf/estimating-treatment-costs-for-uncomplicated-diabetes-at-a-7vvtag4u.pdf

John Kiogora

Papers

A digital microfluidic system for serological immunoassays in remote settings

Cholera Outbreak in Dadaab Refugee Camp, Kenya - November 2015-June 2016.

Estimating treatment costs for uncomplicated diabetes at a hospital serving refugees in Kenya