Dataset Information

Diagnosing risk factors alongside mass drug administration using serial diagnostic tests-which test first?

ABSTRACT:

Background

When tests are used in series to determine individual risk factors and infection status in a mass drug administration (MDA), the diagnostics, test order and subsequent treatment decisions (the testing algorithm) affect population-level treatment coverage and cost, but there is no existing framework for evaluating which algorithm optimizes any given outcome.

Methods

We present a mathematical tool (with spreadsheet implementation) to analyse the effect of test ordering, illustrated using treatment for onchocerciasis in an area where high-burden Loa loa co-infections present a known risk factor.

Results

The prevalence of the infection and risk factor have a non-linear impact on the optimal ordering of tests. Testing for the MDA infection first always leaves more infected people untreated but fewer people with the risk factor being misclassified. The cost of the treatment given to infected individuals with the risk factor does not affect which algorithm is more cost effective.

Conclusions

For a given test and treat algorithm and its costs, the correct strategy depends on the expected prevalence. In most cases, when the apparent prevalence of the target infection is greater than the apparent prevalence of the risk factor, it is cheaper to do the risk factor test first, and vice versa.

SUBMITTER: Dyson L

PROVIDER: S-EPMC6063283 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Diagnosing risk factors alongside mass drug administration using serial diagnostic tests-which test first?

Dyson Louise L Hollingsworth T Déirdre TD

Transactions of the Royal Society of Tropical Medicine and Hygiene 20180701 7

<h4>Background</h4>When tests are used in series to determine individual risk factors and infection status in a mass drug administration (MDA), the diagnostics, test order and subsequent treatment decisions (the testing algorithm) affect population-level treatment coverage and cost, but there is no existing framework for evaluating which algorithm optimizes any given outcome.<h4>Methods</h4>We present a mathematical tool (with spreadsheet implementation) to analyse the effect of test ordering, i ...[more]

PMID: 30020529

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Project description:BackgroundMelioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic in many tropical developing countries and has a high mortality. Here we evaluated combinations of a lateral flow immunoassay (LFI) detecting B. pseudomallei capsular polysaccharide (CPS) and enzyme-linked immunosorbent assays (ELISA) detecting antibodies against hemolysin co-regulated protein (Hcp1) or O-polysaccharide (OPS) for diagnosing melioidosis.Methodology/principal findingsWe conducted a cohort-based case-control study. Both cases and controls were derived from a prospective observational study of patients presenting with community-acquired infections and sepsis in northeast Thailand (Ubon-sepsis). Cases included 192 patients with a clinical specimen culture positive for B. pseudomallei. Controls included 502 patients who were blood culture positive for Staphylococcus aureus, Escherichia coli or Klebsiella pneumoniae or were polymerase chain reaction assay positive for malaria or dengue. Serum samples collected within 24 hours of admission were stored and tested using a CPS-LFI, Hcp1-ELISA and OPS-ELISA. When assessing diagnostic tests in combination, results were considered positive if either test was positive. We selected ELISA cut-offs corresponding to a specificity of 95%. Using a positive cut-off OD of 2.912 for Hcp1-ELISA, the combination of the CPS-LFI and Hcp1-ELISA had a sensitivity of 67.7% (130/192 case patients) and a specificity of 95.0% (477/502 control patients). The sensitivity of the combination (67.7%) was higher than that of the CPS-LFI alone (31.3%, p<0.001) and that of Hcp1-ELISA alone (53.6%, p<0.001). A similar phenomenon was also observed for the combination of CPS-LFI and OPS-ELISA. In case patients, positivity of the CPS-LFI was associated with a short duration of symptoms, high modified Sequential (sepsis-related) Organ Failure Assessment (SOFA) score, bacteraemia and mortality outcome, while positivity of Hcp1-ELISA was associated with a longer duration of symptoms, low modified SOFA score, non-bacteraemia and survival outcome.Conclusions/significanceA combination of antigen-antibody diagnostic tests increased the sensitivity of melioidosis diagnosis over individual tests while preserving high specificity. Point-of-care tests for melioidosis based on the use of combination assays should be further developed and evaluated.

Project description:Identifying a child with pneumonia in the large group of children with acute respiratory tract infections can be challenging for primary care physicians. Knowledge on the diagnostic value of specific signs and symptoms may guide future decision rules and guidelines for clinicians. We aimed to identify and systematically review available evidence for the diagnostic value of signs, symptoms, and additional tests to diagnose pneumonia in children in an ambulatory setting in developed countries. We conducted a systematic review, searching in the electronic databases of PubMed and Embase. Quality assessment of studies was done using the QUADAS-2 criteria. After data extraction from selected studies, we calculated and summarized test characteristics (sensitivity, specificity, negative and positive predictive values) of all available signs, symptoms, additional laboratory tests, and chest ultrasonography. The original search yielded 4665 records, of which 17 articles were eligible for analysis: 12 studies on signs and symptoms, 4 on additional laboratory tests, and 6 on ultrasonography. All included studies were performed in a secondary care setting. Risk of bias was present in the majority of studies in the domain of patient selection. Prevalence of pneumonia varied from 3.4% to 71.7%. The diagnostic value of the available 27 individual signs and symptoms to identify pneumonia was low. In a low prevalence setting, (4 studies, pneumonia prevalence <10%) clinically ill appearance of the child and oxygen saturation <94% can aid a physician. In a high prevalence setting (10 studies, pneumonia >10%), additional diagnostic tests such as oxygen saturation, C-reactive protein, and white blood cell count are more promising. Chest ultrasonography showed high diagnostic value in settings with higher prevalence of pneumonia. Single signs and symptoms from medical history and physical examination or individual additional diagnostic tests are insufficient to diagnose pneumonia in ambulant children. Very few diagnostic studies are conducted in settings with low prevalence of pneumonia. Future research in low prevalence settings should focus on the diagnostic value of the combination of clinical features and additional testing possibly using meta-analysis of individual data.

Dataset Information

Diagnosing risk factors alongside mass drug administration using serial diagnostic tests-which test first?

Background

Methods

Results

Conclusions

Publications

Diagnosing risk factors alongside mass drug administration using serial diagnostic tests-which test first?

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