scholarly journals The impact of emerging Plasmodium knowlesi on accurate diagnosis by light microscopy: a systematic review and modelling analysis

Author(s):  
John H. Huber ◽  
Margaret Elliott ◽  
Cristian Koepfli ◽  
T. Alex Perkins

ABSTRACTBackgroundThe five Plasmodium spp. that cause human malaria appear similar under light microscopy, which raises the possibility that misdiagnosis could routinely occur in clinical settings. Assessing the extent of misdiagnosis is of particular importance for monitoring P. knowlesi, which co-circulates with the other Plasmodium spp.MethodsWe performed a systematic review and meta-analysis of studies comparing the performance of microscopy and PCR for diagnosing malaria in settings with co-circulation of the five Plasmodium spp. We assessed the extent to which co-circulation of Plasmodium parasites affects diagnostic outcomes. We fit a Bayesian hierarchical latent class model to estimate variation in microscopy sensitivity and specificity.ResultsMean sensitivity of microscopy was low, yet highly variable across Plasmodium spp., ranging from 41.7% (95% CI: 22.8 – 64.1%) for P. falciparum and 40.3% (22.0 – 61.5%) for P. vivax to 0.119% (0.0121 – 0.640%) for P. knowlesi, 7.57% (2.66 – 22.0%) for P. malariae, and 0.180% (0.00491 – 1.21%) for P. ovale. Observed PCR prevalence was positively correlated with estimated microscopic sensitivity and negatively correlated with estimated microscopic specificity, though the strength of the associations varied by species.ConclusionsOur analysis suggests that co-circulation of Plasmodium spp. undermines the accuracy of microscopy. Sensitivity was considerably lower for P. knowlesi, P. malariae, and P. ovale. The negative association between specificity and PCR prevalence imply that less frequently encountered species may be misdiagnosed as more frequently encountered species. Together, these results suggest that the burden of P. knowlesi, P. malariae, and P. ovale may be underappreciated in a clinical setting.SummaryCo-circulation of Plasmodium species parasites may limit the accuracy of malaria diagnosis by light microscopy. Variation in performance of light microscopy is highly correlated with the prevalence of the parasites in the epidemiological setting.

Author(s):  
J Neves Briard ◽  
R Nitulescu ◽  
É Lemoine ◽  
S English ◽  
L McIntyre ◽  
...  

Background: CT-angiography is an ancillary test used to diagnose death by neurological criteria (DNC), notably in cases of unreliable neurological examinations due to clinical confounders. We studied whether clinical confounders to the neurological examination modified CT-angiography diagnostic accuracy. Methods: Systematic review and meta-analysis of studies including deeply comatose patients undergoing DNC ancillary testing. We estimated pooled sensitivities and specificities using a Bayesian hierarchical model, including data on CT-angiography (4-point, 7-point, 10-point scales, and no intracranial flow), and performing a subgroup analysis on clinical confounders to the reference neurological examination. Results: Of 40 studies included in the meta-analysis, 7 involve CT-angiography (n=586). There was no difference between subgroups (Table). The degree of uncertainty involving sensitivity estimates was high in both subgroups. Conclusions: Statistical uncertainty in diagnostic accuracy estimates preclude any conclusion regarding the impact of clinical confounders on CT-angiography diagnostic accuracy. Further research is required to validate CT-angiography as an accurate ancillary test for DNC. Table. Pooled sensitivities and specificities of CT-angiography for death by neurological criteria


2019 ◽  
Vol 71 (3) ◽  
pp. 499-513 ◽  
Author(s):  
Hiroaki Ogawa ◽  
Georgios D Kitsios ◽  
Mitsunaga Iwata ◽  
Teruhiko Terasawa

Abstract Background The clinical role of sputum Gram stain (SGS) in community-acquired pneumonia (CAP) diagnosis remains controversial. A 1996 meta-analysis of the diagnostic accuracy of SGS reported heterogeneous results. To update the available evidence, we performed a systematic review and a Bayesian standard and latent-class model meta-analysis. Methods We searched Medline, Embase, and Cochrane Central by 23 August 2018 to identify studies reporting on the diagnostic accuracy, yield (percentage of patients with any pathogen[s] correctly identified by SGS), and clinical outcomes of SGS in adult patients with CAP. Two reviewers extracted the data. We quantitatively synthesized the diagnostic accuracy and yield, and descriptively analyzed other outcomes. Results Twenty-four studies with 4533 patients were included. The methodological and reporting quality of the included studies was limited. When good-quality sputum specimens were selected, SGS had a summary sensitivity of 0.69 (95% credible interval [CrI], .56–.80) and specificity of 0.91 (CrI, .83–.96) for detecting Streptococcus pneumoniae, and a sensitivity of 0.76 (CrI, .60–.87) and specificity of 0.97 (CrI, .91–.99) for Haemophilus influenzae. Adjusted analyses accounting for imperfect reference standards provided higher-specificity estimates than the unadjusted analyses. Bacterial pathogens were identified in 73% (CrI, 26%–96%) of good-quality specimens, and 36% (CrI, 22%–53%) of all specimens regardless of quality. Evidence on other bacteria was sparse. Conclusions SGS was highly specific to diagnose S. pneumoniae and H. influenzae infections in patients with CAP. With good-quality specimens, SGS can provide clinically actionable information for pathogen-directed antibiotic therapies.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e047283
Author(s):  
Rosalind Gittins ◽  
Louise Missen ◽  
Ian Maidment

IntroductionThere is a growing concern about the misuse of over the counter (OTC) and prescription only medication (POM) because of the impact on physical and mental health, drug interactions, overdoses and drug-related deaths. These medicines include opioid analgesics, anxiolytics such as pregabalin and diazepam and antidepressants. This protocol outlines how a systematic review will be undertaken (during June 2021), which aims to examine the literature on the pattern of OTC and POM misuse among adults who are accessing substance misuse treatment services. It will include the types of medication being taken, prevalence and demographic characteristics of people who access treatment services.Methods and analysisAn electronic search will be conducted on the Cochrane, OVID Medline, Pubmed, Scopus and Web of Science databases as well as grey literature. Two independent reviewers will conduct the initial title and abstract screenings, using predetermined criteria for inclusion and exclusion. If selected for inclusion, full-text data extraction will be conducted using a pilot-tested data extraction form. A third reviewer will resolve disagreements if consensus cannot be reached. Quality and risk of bias assessment will be conducted for all included studies. A qualitative synthesis and summary of the data will be provided. If possible, a meta-analysis with heterogeneity calculation will be conducted; otherwise, Synthesis Without Meta-analysis will be undertaken for quantitative data. The reporting of this protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Ethics and disseminationEthical approval is not required. Findings will be peer reviewed, published and shared verbally, electronically and in print, with interested clinicians and policymakers.PROSPERO registration numberCRD42020135216.


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