Diagnostic accuracy of genetic markers and nucleic acid techniques for the detection of Leptospira in clinical samples: A meta-analysis.

BACKGROUND: Leptospirosis is often difficult to diagnose because of its nonspecific symptoms. The drawbacks of direct isolation and serological tests have led to the increased development of nucleic acid-based assays, which are more rapid and accurate. A meta-analysis was performed to evaluate the diagnostic accuracy of genetic markers for the detection of Leptospira in clinical samples. METHODOLOGY AND PRINCIPLE FINDINGS: A literature search was performed in Scopus, PubMed, MEDLINE and non-indexed citations (via Ovid) by using suitable keyword combinations. Studies evaluating the performance of nucleic acid assays targeting leptospire genes in human or animal clinical samples against a reference test were included. Of the 1645 articles identified, 42 eligible studies involving 7414 samples were included in the analysis. The diagnostic performance of nucleic acid assays targeting the rrs, lipL32, secY and flaB genes was pooled and analyzed. Among the genetic markers analyzed, the secY gene showed the highest diagnostic accuracy measures, with a pooled sensitivity of 0.56 (95% CI: 0.50-0.63), a specificity of 0.98 (95% CI: 0.97-0.98), a diagnostic odds ratio of 46.16 (95% CI: 6.20-343.49), and an area under the curve of summary receiver operating characteristics curves of 0.94. Nevertheless, a high degree of heterogeneity was observed in this meta-analysis. Therefore, the present findings here should be interpreted with caution. CONCLUSION: The diagnostic accuracies of the studies examined for each genetic marker showed a significant heterogeneity. The secY gene exhibited higher diagnostic accuracy measures compared with other genetic markers, such as lipL32, flaB, and rrs, but the difference was not significant. Thus, these genetic markers had no significant difference in diagnostic accuracy for leptospirosis. Further research into these genetic markers is warranted.

Diagnostic accuracy and predictive value in differentiating the severity of dengue infection.

OBJECTIVE: To review the diagnostic test accuracy and predictive value of statistical models in differentiating the severity of dengue infection. METHODS: Electronic searches were conducted in the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE (complete), PubMed and Scopus. Eligible studies to be included in this review were cohort studies with participants confirmed by laboratory test for dengue infection and comparison among the different severity of dengue infection by using statistical models. The methodological quality of the paper was assessed by independent reviewers using QUADAS-2. RESULTS: Twenty-six studies published from 1994 to 2017 were included. Most diagnostic models produced an accuracy of 75% to 80% except one with 86%. Two models predicting severe dengue according to the WHO 2009 classification have 86% accuracy. Both of these logistic regression models were applied during the first three days of illness, and their sensitivity and specificity were 91-100% and 79.3-86%, respectively. Another model which evaluated the 30-day mortality of dengue infection had an accuracy of 98.5%. CONCLUSION: Although there are several potential predictive or diagnostic models for dengue infection, their limitations could affect their validity. It is recommended that these models be revalidated in other clinical settings and their methods be improved and standardised in future.

OBJECTIF: Analyser la précision des tests de diagnostic et la valeur prédictive des modèles statistiques pour différencier la sévérité de l'infection par la dengue. MÉTHODES: Des recherches électroniques ont été effectuées dans la base de données de revues systématiques Cochrane, le registre central des essais contrôlés Cochrane, MEDLINE (complète), PUBMED et Scopus. Les études éligibles à inclure dans cette revue étaient des études de cohorte avec des participants confirmés par un test de laboratoire pour l'infection par la dengue et une comparaison entre les différentessévérités de l'infection par la dengue à l'aide de modèles statistiques. La qualité méthodologique des articles a été évaluée par des scientifiques indépendants à l'aide de QUADAS-2. RÉSULTATS: 26 études publiées de 1994 à 2017 ont été incluses. La plupart des modèles de diagnostic ont produit une précision de 75% à 80%, sauf un avec 86%. Selon la classification de l'OMS 2009, deux modèles prédisant la dengue sévère présentent une précision de 86%. Ces deux modèles de régression logistique ont été appliqués au cours des trois premiers jours de la maladie. Leur sensibilité et leur spécificité étaient respectivement de 91% à 100% et de 79,3% à 86%. Un autre modèle évaluant la mortalité à 30 jours de la dengue présentait une précision de 98,5%. CONCLUSION: Bien qu'il existe plusieurs modèles prédictifs ou diagnostiques potentiels de l'infection par la dengue, leurs limites pourraient affecter leur validité. Il est recommandé que ces modèles soient revalidées dans d'autres milieux cliniques et leurs méthodes améliorées et normalisées dans le futur.

Predictive and diagnostic test accuracy of ultrasonography in differentiating severe dengue from nonsevere dengue.

Diagnosing severe dengue from those who do not develop complication is important to prevent death. The objective of this systematic review was to evaluate the diagnostic test accuracy of ultrasonography in differentiating severe dengue from nonsevere dengue; and to assess if ultrasonography/ultrasound can be used as a predictive (screening) and diagnostic tool in the course of dengue infection. An electronic search was conducted in different databases via OvidSP platform. The included studies were cohort studies between 1995 and 2016 wherein cases were confirmed by dengue blood test. Severity of dengue was assessed and compared using standard WHO references. The methodological quality of the paper was assessed by two independent reviewers by using QUADAS-2 tool. In total 12 studies were included in this review after suitable screening. Overall, the studies included had a low and unclear risk of bias. Seven out of nine studies that compared severe dengue and nonsevere dengue, performed an ultrasonography on gallbladder (wall thickness cutoff-3 mm) with a sensitivity of 24.2-100% and a specificity of 13.2-98.7%. Other parameters such as splenic subcapsular fluid collection, pericardial fluid and hepatic subcapsular fluid collection had a specificity of >90%, though the sensitivity was poor. There were insufficient evidence that ultrasonography is able to differentiate severe dengue from nonsevere dengue accurately. The predictive and diagnostic value of ultrasonography could not be concluded due to insufficient reporting on the temporality of the ultrasonography performed with regard to the diagnosis. However, it might serve as an adjunct investigation to support the clinical diagnosis.

The predictive and diagnostic accuracy of vascular endothelial growth factor and pentraxin-3 in severe dengue.

This study aimed to evaluate vascular endothelial growth factor (VEGF) and pentraxin 3 (PTX-3) as predictive and diagnostic markers in differentiating severe dengue from non-severe dengue. The study was conducted in Ampang Health Clinic, Ampang Hospital and Serdang Hospital. The plasma levels of VEGF and PTX-3 were compared between severe dengue and non-severe dengue by ELISA from the day of presentation until discharged. Multiple logistic regression was used to develop predictive and diagnostic models by incorporating other clinical parameters. The receiver operating characteristics (ROC) analysis was used to assess the accuracy of the biomarkers and the developed models. Eighty-two patients were recruited, 29 with severe dengue and four died. The Area Under the Curve (AUC) was statistically significant in VEGF as diagnostic marker at Day 2 and 3 of illness with sensitivity of 80.00%-100.00% and specificity of 76.47%-80.00%. The predictive model with AUC of 0.84 (p < 0.01) has a sensitivity of 100.00% and specificity of 79.25% for predicting severe dengue. The diagnostic model with AUC of 0.71 (p < 0.01) has a sensitivity of 76.19% and specificity of 73.58% for diagnosing severe dengue. The AUC for PTX-3 was not statistically significant. VEGF may be used in combination with other clinical parameters to predict the severity of the disease. As a single biomarker, it may be used as an adjunct investigation to support the diagnosis of severe dengue. PTX-3 was not able to differentiate severe dengue from non-severe dengue.

Clinical manifestations of dengue in relation to dengue serotype and genotype in Malaysia: A retrospective observational study.

BACKGROUND: Malaysia experienced an unprecedented dengue outbreak from the year 2014 to 2016 that resulted in an enormous increase in the number of cases and mortality as compared to previous years. The causes that attribute to a dengue outbreak can be multifactorial. Viral factors, such as dengue serotype and genotype, are the components of interest in this study. Although only a small number of studies investigated the association between the serotype of dengue virus and clinical manifestations, none of these studies included analyses on dengue genotypes. The present study aims to investigate dengue serotype and genotype-specific clinical characteristics among dengue fever and severe dengue cases from two Malaysian tertiary hospitals between 2014 and mid-2017. METHODOLOGY AND PRINCIPAL FINDINGS: A total of 120 retrospective dengue serum specimens were subjected to serotyping and genotyping by Taqman Real-Time RT-PCR, sequencing and phylogenetic analysis. Subsequently, the dengue serotype and genotype data were statistically analyzed for 101 of 120 corresponding patients' clinical manifestations to generate a descriptive relation between the genetic components and clinical outcomes of dengue infected patients. During the study period, predominant dengue serotype and genotype were found to be DENV 1 genotype I. Additionally, non-severe clinical manifestations were commonly observed in patients infected with DENV 1 and DENV 3. Meanwhile, patients with DENV 2 infection showed significant warning signs and developed severe dengue (p = 0.007). Cases infected with DENV 2 were also commonly presented with persistent vomiting (p = 0.010), epigastric pain (p = 0.018), plasma leakage (p = 0.004) and shock (p = 0.038). Moreover, myalgia and arthralgia were highly prevalent among DENV 3 infection (p = 0.015; p = 0.014). The comparison of genotype-specific clinical manifestations showed that DENV 2 Cosmopolitan was significantly common among severe dengue patients. An association was also found between genotype I of DENV 3 and myalgia. In a similar vein, genotype III of DENV 3 was significantly common among patients with arthralgia. CONCLUSION: The current data contended that different dengue serotype and genotype had caused distinct clinical characteristics in infected patients.

Global dengue death before and after the new World Health Organization 2009 case classification: A systematic review and meta-regression analysis.

BACKGROUND: Since the introduction of 2009 WHO dengue case classification, no literature was found regarding its effect on dengue death. This study was to evaluate the effect of 2009 WHO dengue case classification towards dengue case fatality rate. METHODS: Various databases were used to search relevant articles since 1995. Studies included were cohort and cross-sectional studies, all patients with dengue infection and must report the number of death or case fatality rate. The Joanna Briggs Institute appraisal checklist was used to evaluate the risk of bias of the full-texts. The studies were grouped according to the classification adopted: WHO 1997 and WHO 2009. Meta-regression was employed using a logistic transformation (log-odds) of the case fatality rate. The result of the meta-regression was the adjusted case fatality rate and odds ratio on the explanatory variables. RESULTS: A total of 77 studies were included in the meta-regression analysis. The case fatality rate for all studies combined was 1.14% with 95% confidence interval (CI) of 0.82-1.58%. The combined (unadjusted) case fatality rate for 69 studies which adopted WHO 1997 dengue case classification was 1.09% with 95% CI of 0.77-1.55%; and for eight studies with WHO 2009 was 1.62% with 95% CI of 0.64-4.02%. The unadjusted and adjusted odds ratio of case fatality using WHO 2009 dengue case classification was 1.49 (95% CI: 0.52, 4.24) and 0.83 (95% CI: 0.26, 2.63) respectively, compared to WHO 1997 dengue case classification. There was an apparent increase in trend of case fatality rate from the year 1992-2016. Neither was statistically significant. CONCLUSIONS: The WHO 2009 dengue case classification might have no effect towards the case fatality rate although the adjusted results indicated a lower case fatality rate. Future studies are required for an update in the meta-regression analysis to confirm the findings.

Risk factors associated with abdominal obesity in suburban adolescents from a Malaysian district.

INTRODUCTION: We aimed to determine the risk factors associated with abdominal obesity (AO) in suburban adolescents. METHODS: This cross-sectional study included adolescents aged 15-17 years from five randomly selected secondary schools in the Hulu Langat district of Selangor state, Malaysia. Waist circumference (WC) was measured at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest. Information on sociodemographic data, dietary habits, physical activity levels and duration of sleep was obtained via interviewer-administered questionnaires. Participants' habitual food intake was determined using a 73-item Food Frequency Questionnaire. RESULTS: Among 832 participants, 56.0% were girls; 48.4% were Malay, 40.5% Chinese, 10.2% Indian and 0.8% of other ethnic groups. Median age and WC were 16 (interquartile range [IQR] 15-16) years and 67.9 (IQR 63.0-74.6) cm, respectively. Overall prevalence of AO (> 90th percentile on the WC chart) was 11.3%. A higher proportion (22.4%) of Indian adolescents were found to have AO compared with Malay and Chinese adolescents. Logistic regression analysis showed that female gender (adjusted odds ratio [OR] 7.064, 95% confidence interval [CI] 2.087-23.913; p = 0.002), Indian ethnicity (adjusted OR 10.164, 95% CI 2.182-47.346; p = 0.003), irregular meals (adjusted OR 3.193, 95% CI 1.043-9.774; p = 0.042) and increasing body mass index (BMI) (adjusted OR 2.867, 95% CI 2.216-3.710; p < 0.001) were significantly associated with AO. CONCLUSION: AO was common among Malaysian adolescents. Female gender, Indian ethnicity, irregular meals and increasing BMI were significant risk factors.

Comparative assessment of students' performance and perceptions on objective structured practical models in undergraduate pathology teaching.

INTRODUCTION: Assessment is an important factor that drives student learning, as students tend to mainly focus on the material to be assessed. The current practice in teaching pathology extensively applies objective-structured practical examination for the assessment of students. As students will have to deal with real patients during clinical years, it is preferred that students learn and practise via potted specimens and slides instead of picture plates. This study aimed to assess the preferred assesment method of pathology practical exercises. METHODS: This was a cross-sectional survey carried out in two consecutive batches of Phase 2 medical students. Student competency was assessed using both the traditional (TD) (i.e. use of potted specimens and slides) and picture plate (PP) methods. To compare the two assessment methods, we compared the mean scores obtained by the students and examined student perception of the two methods. RESULTS: The mean scores obtained via the PP method were significantly higher than those obtained via the TD method for almost all the components tested. CONCLUSION: We found that students performed significantly better (p < 0.05) when assessed using the PP method instead of the TD method. PP preparations might provide better visuals, thus aiding understanding, than the TD method. The findings of this study are valuable in identifying and improving our current teaching and assessment methods of medical students, in line with advancements in information technology.