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Use of routine HIV testing data for early detection of emerging HIV epidemics in high-risk subpopulations: A concept demonstration study.

ABSTRACT: Introduction:HIV epidemics in hard-to-reach high-risk subpopulations are often discovered years after epidemic emergence in settings with poor surveillance infrastructure. Using hypothesis-generation modeling, we aimed to investigate and demonstrate the concept of using routine HIV testing data to identify and characterize hidden epidemics in high-risk subpopulations. We also compared this approach to surveillance based on AIDS case notifications. Methods:A deterministic mathematical model was developed to simulate an emerging HIV epidemic in a high-risk subpopulation. A stochastic Monte Carlo simulation was implemented on the total population to simulate the sampling process of generating routine HIV testing data. Epidemiological measures were estimated on the simulated epidemic and on the generated testing sample. Sensitivity analyses were conducted on the results. Results:In the simulated epidemic, HIV prevalence saturated at 32% in the high-risk subpopulation and at 0.33% in the total population. The epidemic started its emerging-epidemic phase 28 years after infection introduction, and saturated 67 years after infection introduction. In the simulated HIV testing sample, a significant time trend in prevalence was identified, and the generated metrics of epidemic emergence and saturation were similar to those of the simulated epidemic. The epidemic was identified 4.0 (95% CI 3.4-4.6) years after epidemic emergence using routine HIV testing, but 29.7 (95% CI 15.8-52.1) years after emergence using AIDS case notifications. In the sensitivity analyses, none of the sampling biases affected the conclusion of an emerging epidemic, but some affected the estimated epidemic growth rate. Conclusions:Routine HIV testing data provides a tool to identify and characterize hidden and emerging epidemics in high-risk subpopulations. This approach can be specially useful in resource-limited settings, and can be applied alone, or along with other complementary data, to provide a meaningful characterization of emerging but hidden epidemics.

SUBMITTER: Ayoub HH

PROVIDER: S-EPMC6326224 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Use of routine HIV testing data for early detection of emerging HIV epidemics in high-risk subpopulations: A concept demonstration study.

Ayoub Houssein H HH Awad Susanne F SF Abu-Raddad Laith J LJ

Infectious Disease Modelling 20181106

<h4>Introduction</h4>HIV epidemics in hard-to-reach high-risk subpopulations are often discovered years after epidemic emergence in settings with poor surveillance infrastructure. Using hypothesis-generation modeling, we aimed to investigate and demonstrate the concept of using routine HIV testing data to identify and characterize hidden epidemics in high-risk subpopulations. We also compared this approach to surveillance based on AIDS case notifications.<h4>Methods</h4>A deterministic mathemati ...[more]

PMID: 30839930

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Project description:ImportanceEarly-life epilepsies are often a consequence of numerous neurodevelopmental disorders, most of which are proving to have genetic origins. The role of genetic testing in the initial evaluation of these epilepsies is not established.ObjectiveTo provide a contemporary account of the patterns of use and diagnostic yield of genetic testing for early-life epilepsies.Design, setting, and participantsIn this prospective cohort, children with newly diagnosed epilepsy with an onset at less than 3 years of age were recruited from March 1, 2012, to April 30, 2015, from 17 US pediatric hospitals and followed up for 1 year. Of 795 families approached, 775 agreed to participate. Clinical diagnosis of the etiology of epilepsy were characterized based on information available before genetic testing was performed. Added contributions of cytogenetic and gene sequencing investigations were determined.ExposuresGenetic diagnostic testing.Main outcomes and measuresLaboratory-confirmed pathogenic variant.ResultsOf the 775 patients in the study (367 girls and 408 boys; median age of onset, 7.5 months [interquartile range, 4.2-16.5 months]), 95 (12.3%) had acquired brain injuries. Of the remaining 680 patients, 327 (48.1%) underwent various forms of genetic testing, which identified pathogenic variants in 132 of 327 children (40.4%; 95% CI, 37%-44%): 26 of 59 (44.1%) with karyotyping, 32 of 188 (17.0%) with microarrays, 31 of 114 (27.2%) with epilepsy panels, 11 of 33 (33.3%) with whole exomes, 4 of 20 (20.0%) with mitochondrial panels, and 28 of 94 (29.8%) with other tests. Forty-four variants were identified before initial epilepsy presentation. Apart from dysmorphic syndromes, pathogenic yields were highest for children with tuberous sclerosis complex (9 of 11 [81.8%]), metabolic diseases (11 of 14 [78.6%]), and brain malformations (20 of 61 [32.8%]). A total of 180 of 446 children (40.4%), whose etiology would have remained unknown without genetic testing, underwent some testing. Pathogenic variants were identified in 48 of 180 children (26.7%; 95% CI, 18%-34%). Diagnostic yields were greater than 15% regardless of delay, spasms, and young age. Yields were greater for epilepsy panels (28 of 96 [29.2%]; P < .001) and whole exomes (5 of 18 [27.8%]; P = .02) than for chromosomal microarray (8 of 101 [7.9%]).Conclusions and relevanceGenetic investigations, particularly broad sequencing methods, have high diagnostic yields in newly diagnosed early-life epilepsies regardless of key clinical features. Thorough genetic investigation emphasizing sequencing tests should be incorporated into the initial evaluation of newly presenting early-life epilepsies and not just reserved for those with severe presentations and poor outcomes.

Project description:BackgroundThe timely and accurate diagnosis of bloodstream infection (BSI) is critical for patient management. With longstanding challenges for routine blood culture, metagenomics is a promising approach to rapidly provide sequence-based detection and characterisation of bloodborne bacteria. Long-read sequencing technologies have successfully supported the use of clinical metagenomics for syndromes such as respiratory illness, and modified approaches may address two requisite factors for metagenomics to be used as a BSI diagnostic: depletion of the high level of host DNA to then detect the low abundance of microbes in blood.MethodsBlood samples from healthy donors were spiked with different concentrations of four prevalent causative species of BSI. All samples were then subjected to a modified saponin-based host DNA depletion protocol and optimised DNA extraction, whole genome amplification and debranching steps in preparation for sequencing, followed by bioinformatical analyses. Two related variants of the protocol are presented: 1mL of blood processed without bacterial enrichment, and 5mL of blood processed following a rapid bacterial enrichment protocol-SepsiPURE.ResultsAfter first identifying that a large proportion of host mitochondrial DNA remained, the host depletion process was optimised by increasing saponin concentration to 3% and scaling the reaction to allow more sample volume. Compared to non-depleted controls, the 3% saponin-based depletion protocol reduced the presence of host chromosomal and mitochondrial DNA < 106 and < 103 fold respectively. When the modified depletion method was further combined with a rapid bacterial enrichment method (SepsiPURE; with 5mL blood samples) the depletion of mitochondrial DNA improved by a further > 10X while also increasing detectable bacteria by > 10X. Parameters during DNA extraction, whole genome amplification and long-read sequencing were also adjusted, and subsequently amplicons were detected for each input bacterial species at each of the spiked concentrations, ranging from 50-100 colony forming units (CFU)/mL to 1-5 CFU/mL.ConclusionIn this proof-of-concept study, four prevalent BSI causative species were detected in under 12 h to species level (with antimicrobial resistance determinants) at concentrations relevant to clinical blood samples. The use of a rapid and precise metagenomic protocols has the potential to advance the diagnosis of BSI.

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Use of routine HIV testing data for early detection of emerging HIV epidemics in high-risk subpopulations: A concept demonstration study.

Publications

Use of routine HIV testing data for early detection of emerging HIV epidemics in high-risk subpopulations: A concept demonstration study.

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