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Rapid Diagnostic Testing of Hospitalized Malawian Children Reveals Opportunities for Improved HIV Diagnosis and Treatment.

ABSTRACT: Recent World Health Organization (WHO) guidelines recommend antiretroviral therapy (ART) for all HIV-infected people; previously CD4+ T lymphocyte quantification (CD4 count) or clinical staging determined eligibility for children ? 5 years old in low- and middle-income countries. We examined positive predictive value (PPV) of a rapid diagnostic test (RDT) algorithm and ART eligibility for hospitalized children with newly diagnosed HIV infection. We enrolled 363 hospitalized Malawian children age 2 months to 16 years with two serial positive HIV RDT from 2013 to 2015. Children aged ? 18 months whose nucleic acid testing was negative or unavailable were later excluded from the analysis (N = 16). If RNA PCR was undetectable, human immunodeficiency virus (HIV) enzyme immunoassay (EIA) and western blot (WB) were performed. Those with negative or discordant EIA and WB were considered HIV negative and excluded from further analysis (N = 6). ART eligibility was assessed using age, CD4 count, and clinical HIV stage. Among 150 patients with HIV RNA PCR results, 15 had undetectable HIV RNA. Of those, EIA and WB were positive in nine patients and negative or discordant in six patients. PPV of serial RDT was 90% versus RNA PCR alone and 96% versus combined RNA PCR, EIA, and WB. Of all patients aged ? 5 years, 8.9% were ineligible for ART under previous WHO guidelines. Improved HIV testing algorithms are needed for accurate diagnosis of HIV infection in children as prevalence of pediatric HIV declines. Universal treatment will significantly increase the numbers of older children who qualify for ART.

SUBMITTER: Madaline TF

PROVIDER: S-EPMC5805032 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Rapid Diagnostic Testing of Hospitalized Malawian Children Reveals Opportunities for Improved HIV Diagnosis and Treatment.

Madaline Theresa F TF Hochman Sarah E SE Seydel Karl B KB Liomba Alice A Saidi Alex A Matebule Grace G Mowrey Wenzhu B WB O'Hare Bernadette B Milner Danny A DA Kim Kami K

The American journal of tropical medicine and hygiene 20171012 6

Recent World Health Organization (WHO) guidelines recommend antiretroviral therapy (ART) for all HIV-infected people; previously CD4+ T lymphocyte quantification (CD4 count) or clinical staging determined eligibility for children ≥ 5 years old in low- and middle-income countries. We examined positive predictive value (PPV) of a rapid diagnostic test (RDT) algorithm and ART eligibility for hospitalized children with newly diagnosed HIV infection. We enrolled 363 hospitalized Malawian children age ...[more]

PMID: 29141709

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Project description:BackgroundCurrent WHO testing guidelines for resource limited settings diagnose HIV on the basis of screening tests without a confirmation test due to cost constraints. This leads to a potential risk of false positive HIV diagnosis. In this paper, we evaluate the dilution test, a novel method for confirmation testing, which is simple, rapid, and low cost. The principle of the dilution test is to alter the sensitivity of a rapid diagnostic test (RDT) by dilution of the sample, in order to screen out the cross reacting antibodies responsible for falsely positive RDT results.MethodsParticipants were recruited from two testing centres in Ethiopia where a tiebreaker algorithm using 3 different RDTs in series is used to diagnose HIV. All samples positive on the initial screening RDT and every 10th negative sample underwent testing with the gold standard and dilution test. Dilution testing was performed using Determine™ rapid diagnostic test at 6 different dilutions. Results were compared to the gold standard of Western Blot; where Western Blot was indeterminate, PCR testing determined the final result.Results2895 samples were recruited to the study. 247 were positive for a prevalence of 8.5 % (247/2895). A total of 495 samples underwent dilution testing. The RDT diagnostic algorithm misclassified 18 samples as positive. Dilution at the level of 1/160 was able to correctly identify all these 18 false positives, but at a cost of a single false negative result (sensitivity 99.6 %, 95 % CI 97.8-100; specificity 100 %, 95 % CI: 98.5-100). Concordance between the gold standard and the 1/160 dilution strength was 99.8 %.ConclusionThis study provides proof of concept for a new, low cost method of confirming HIV diagnosis in resource-limited settings. It has potential for use as a supplementary test in a confirmatory algorithm, whereby double positive RDT results undergo dilution testing, with positive results confirming HIV infection. Negative results require nucleic acid testing to rule out false negative results due to seroconversion or misclassification by the lower sensitivity dilution test. Further research is needed to determine if these results can be replicated in other settings.Trial registrationClinicalTrials.gov, NCT01716299 .

Project description:Bloodstream infections are associated with considerable morbidity and health care costs. Molecular rapid diagnostic tests (mRDTs) are a promising complement to conventional laboratory methods for the diagnosis of bloodstream infections and may reduce the time to effective therapy among patients with bloodstream infections. The concurrent implementation of antimicrobial stewardship programs (ASPs) may reinforce these benefits. The aim of this study was to evaluate the cost-effectivenesses of competing strategies for the diagnosis of bloodstream infection alone or combined with an ASP. To this effect, we constructed a decision-analytic model comparing 12 strategies for the diagnosis of bloodstream infection. The main arms compared the use of mRDT and conventional laboratory methods with or without an ASP. The baseline strategy used as the standard was the use of conventional laboratory methods without an ASP, and our decision-analytic model assessed the cost-effectivenesses of 5 principal strategies: mRDT (with and without an ASP), mRDT with an ASP, mRDT without an ASP, conventional laboratory methods with an ASP, and conventional laboratory methods without an ASP. Furthermore, based on the availability of data in the literature, we assessed the cost-effectivenesses of 7 mRDT subcategories, as follows: PCR with an ASP, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis with an ASP, peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with an ASP, a blood culture nanotechnology microarray system for Gram-negative bacteria (BC-GP) with an ASP, a blood culture nanotechnology microarray system for Gram-positive bacteria (BC-GN) with an ASP, PCR without an ASP, and PNA-FISH without an ASP. Our patient population consisted of adult inpatients in U.S. hospitals with suspected bloodstream infection. The time horizon of the model was the projected life expectancy of the patients. In a base-case analysis, cost-effectiveness was determined by calculating the numbers of bloodstream infection deaths averted, the numbers of quality-adjusted life years gained, and incremental cost-effectiveness ratios (ICERs). In a probabilistic analysis, uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. In the base-case analysis, MALDI-TOF analysis with an ASP was the most cost-effective strategy, resulting in savings of $29,205 per quality-adjusted life year and preventing 1 death per 14 patients with suspected bloodstream infection tested compared to conventional laboratory methods without an ASP (ICER, -$29,205/quality-adjusted life year). BC-GN with an ASP (ICER, -$23,587/quality-adjusted life year), PCR with an ASP (ICER, -$19,833/quality-adjusted life year), and PCR without an ASP (ICER, -$21,039/quality-adjusted life year) were other cost-effective options. In the probabilistic analysis, mRDT was dominant and cost-effective in 85.1% of simulations. Importantly, mRDT with an ASP had an 80.0% chance of being cost-effective, while mRDT without an ASP had only a 41.1% chance. In conclusion, our findings suggest that mRDTs are cost-effective for the diagnosis of patients with suspected bloodstream infection and can reduce health care expenditures. Notably, the combination of mRDT and an ASP can result in substantial health care savings.

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Rapid Diagnostic Testing of Hospitalized Malawian Children Reveals Opportunities for Improved HIV Diagnosis and Treatment.

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Rapid Diagnostic Testing of Hospitalized Malawian Children Reveals Opportunities for Improved HIV Diagnosis and Treatment.

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