Introduction A Why POC Diagnostics? B Time B Patient Responsibility and Compliance B Cost B Diagnostic Targets C Proteins C Metabolites and Other Small Molecules C Nucleic Acids C Human Cells D Microbes/Pathogens D Drugs and Food Safety D Current Context of POC Assays E POC Glucose Assays E Lateral Flow Assays E Limitations of “Traditional” POC Approaches F Enabling Technologies G Printing and Laminating G Microfluidic Technologies and Approaches: “Unit Operations” for POC Devices G Pumping and Valving H Mixing I Separation I Reagent Storage J Sample Preparation K Surface Chemistry and Device Substrates L Physical Adsorption L Bioaffinity Attachment L Covalent Attachment M Substrate Materials M Detection M Electrochemical Detection N Optical Detection N Magnetic Detection N Label-Free Methods O Enabling Multiplexed Assays O Recent Innovation O Lateral Flow Assay Technologies O Proteins P Antibodies P Protein Expression and Purification Q Nucleic Acids Q Aptamers R Infectious Diseases and Food/Water Safety R Blood Chemistry S Coagulation Markers S Whole Cells S Trends, Unmet Needs, Perspectives T Glucose T Global Health and the Developing World T Personalized Medicine and Home Testing U Technology Trends U Multiplexing V Author Information V Biographies V Acknowledgment W References W

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Point of care diagnostics: Status and future

Background Timely diagnosis of influenza can help clinical management. Purpose To examine the accuracy of rapid influenza diagnostic tests (RIDTs) in adults and children with influenza-like illness and evaluate factors associated with higher accuracy. Data sources PubMed and EMBASE through December 2011; BIOSIS and Web of Science through March 2010; and citations of articles, guidelines, reviews, and manufacturers. Study selection Studies that compared RIDTs with a reference standard of either reverse transcriptase polymerase chain reaction (first choice) or viral culture. Data extraction Reviewers abstracted study data by using a standardized form and assessed quality by using Quality Assessment of Diagnostic Accuracy Studies criteria. Data synthesis 159 studies evaluated 26 RIDTs, and 35% were conducted during the H1N1 pandemic. Failure to report whether results were assessed in a blinded manner and the basis for patient recruitment were important quality concerns. The pooled sensitivity and specificity were 62.3% (95% CI, 57.9% to 66.6%) and 98.2% (CI, 97.5% to 98.7%), respectively. The positive and negative likelihood ratios were 34.5 (CI, 23.8 to 45.2) and 0.38 (CI, 0.34 to 0.43), respectively. Sensitivity estimates were highly heterogeneous, which was partially explained by lower sensitivity in adults (53.9% [CI, 47.9% to 59.8%]) than in children (66.6% [CI, 61.6% to 71.7%]) and a higher sensitivity for influenza A (64.6% [CI, 59.0% to 70.1%) than for influenza B (52.2% [CI, 45.0% to 59.3%). Limitation Incomplete reporting limited the ability to assess the effect of important factors, such as specimen type and duration of influenza symptoms, on diagnostic accuracy. Conclusion Influenza can be ruled in but not ruled out through the use of RIDTs. Sensitivity varies across populations, but it is higher in children than in adults and for influenza A than for influenza B. Primary funding source Canadian Institutes of Health Research.

Accuracy of rapid influenza diagnostic tests: a meta-analysis.

SUMMARY Respiratory syncytial virus (RSV) infection is a significant cause of hospitalization of children in North America and one of the leading causes of death of infants less than 1 year of age worldwide, second only to malaria. Despite its global impact on human health, there are relatively few therapeutic options available to prevent or treat RSV infection. Paradoxically, there is a very large volume of information that is constantly being refined on RSV replication, the mechanisms of RSV-induced pathology, and community transmission. Compounding the burden of acute RSV infections is the exacerbation of preexisting chronic airway diseases and the chronic sequelae of RSV infection. A mechanistic link is even starting to emerge between asthma and those who suffer severe RSV infection early in childhood. In this article, we discuss developments in the understanding of RSV replication, pathogenesis, diagnostics, and therapeutics. We attempt to reconcile the large body of information on RSV and why after many clinical trials there is still no efficacious RSV vaccine and few therapeutics.

Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment

Conventional fluorescent-antibody (FA) methods were compared to real-time PCR assays for detection of respiratory syncytial virus (RSV), influenza virus type A (FluA), parainfluenza virus types 1, 2, and 3 (PIV1, PIV2, and PIV3), human metapneumovirus (MPV), and adenovirus (AdV) in 1,138 specimens from children with respiratory illnesses collected over a 1-year period. At least one virus was detected in 436 (38.3%) specimens by FA and in 608 (53.4%) specimens by PCR (P < 0.001). Specimen quality was inadequate for FA in 52 (4.6%) specimens; 13 of these (25%) were positive by PCR. In contrast, 18 (1.6%) specimens could not be analyzed by PCR; 1 of these was positive by FA. The number of specimens positive only by PCR among specimens positive by PCR and/or FA was 18 (7.0%) of 257 for RSV, 18 (13.4%) of 134 for FluA, 25 (64.1%) of 39 for PIV1, 8 (88.9%) of 9 for PIV2, 17 (30.1%) of 55 for PIV3, and 101 (76.5%) of 132 for AdV. MPV was detected in 6.6% of all specimens and in 9.5% of the 702 specimens negative by FA. The mean number of virus copies per milliliter in specimens positive by both PCR and FA was significantly higher, at 6.7 × 107, than that in specimens positive only by PCR, at 4.1 × 104 (P < 0.001). The PCR assays were significantly more sensitive than FA assays for detecting respiratory viruses, especially parainfluenza virus and adenovirus. Use of real-time PCR to identify viral respiratory pathogens in children will lead to improved diagnosis of respiratory illness.

Comparison of Real-Time PCR Assays with Fluorescent-Antibody Assays for Diagnosis of Respiratory Virus Infections in Children

Development of three multiplex RT-PCR assays for the detection of 12 respiratory RNA viruses

Background Information on the onset of epidemics of acute respiratory tract infections (ARIs) is useful in timing preventive strategies (eg, the passive immunization of high-risk infants against respiratory syncytial virus [RSV]). Aiming at better predictions of the seasonal activity of ARI pathogens, we investigated the influence of climate on hospitalizations for ARIs. Methods Samples obtained from 3044 children hospitalized with ARIs in Mainz, Germany, were tested for pathogens with a multiplex reverse-transcriptase polymerase chain reaction enzyme-linked immunosorbent assay from 2001 through 2006. Hospitalizations for ARIs were correlated with meteorological parameters recorded at the University of Mainz. The frequency of hospitalization for RSV infection was predicted on the basis of multiple time series analysis. Results Influenza A, RSV, and adenovirus were correlated with temperature and rhinovirus to relative humidity. In a time series model that included seasonal and climatic conditions, RSV-associated hospitalizations were predictable. Conclusions Seasonality of certain ARI pathogens can be explained by meteorological influences. The model presented herein is a first step toward predicting annual RSV epidemics using weather forecast data.

Are Meteorological Parameters Associated with Acute Respiratory Tract Infections

Evaluation of a multiplex reverse transcriptase PCR ELISA for the detection of nine respiratory tract pathogens

Comparison of the BD Directigen Flu A+B Kit and the Abbott TestPack RSV with a multiplex RT-PCR ELISA for rapid detection of influenza viruses and respiratory syncytial virus

Haemophilus influenzae type b (Hib) vaccination led to a significant decrease in invasive bacterial infections in children. The aim of this study was to assess a potential shift to more non-type b invasive infections in a population with high Hib vaccination coverage and to compare the burden of suffering between children with Hib, capsulated non-b and non-capsulated Hi infections. Cases with confirmed invasive Hi infections were ascertained through two independent nationwide active surveillance systems in 1998–2005. Information on possible predisposing conditions and clinical information was available from 2001 onwards. The total number of reported non-type b Hi cases varied between 10 cases in 1998, 27 in 2000 and 14 in 2005. In each year, non-capsulated serotypes outnumbered capsulated non-type b ones. 192 cases were detected in 2001–2005, more than one half was non-type b and 88% of the non-type b cases were non-capsulated. For cases with Hib/capsulated non-type b infections the most common clinical presentation was meningitis (67% each); 89%/78% had no potential predisposing condition, 75%/72% completely recovered from disease and 6% (each) died. In contrast, meningitis was diagnosed in 34% of the non-capsulated Hi infections, septicaemia in 28% and pneumonia 21%; 62% had no potential predisposing condition, 83% completely recovered and 3% died. There was no increase in non-type b Hi invasive infections during 8 years of active surveillance in Germany. Invasive disease due to non-type b Hi is not confined to children with risk factors. In patients with capsulated non-type b Hi infections the proportion of meningitis cases is similar to Hib, but double as high as in non-capsulated Hi.

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Britta Gröndahl

Papers

Are Meteorological Parameters Associated with Acute Respiratory Tract Infections

Evaluation of a multiplex reverse transcriptase PCR ELISA for the detection of nine respiratory tract pathogens

Comparison of the BD Directigen Flu A+B Kit and the Abbott TestPack RSV with a multiplex RT-PCR ELISA for rapid detection of influenza viruses and respiratory syncytial virus

Invasive Haemophilus influenzae infections in Germany: impact of non-type b serotypes in the post-vaccine era.

Effectiveness of hexavalent vaccines against invasive Haemophilus influenzae type b disease: Germany's experience after 5 years of licensure.