Prevalence and Epidemiological Characteristics of Asymptomatic Malaria Based on Ultrasensitive Diagnostics: A Cross-sectional Study.

BACKGROUND: As the global public-health objectives for malaria evolve from malaria control towards malaria elimination, there is increasing interest in the significance of asymptomatic infections and the optimal diagnostic test to identify them. METHOD: We conducted a cross-sectional study of asymptomatic individuals (N = 562) to determine the epidemiological characteristics associated with asymptomatic malaria. Participants were tested by rapid diagnostic tests (CareStart, Standard Diagnostics [SD] Bioline, and Alere ultrasensitive RDT [uRDT]), loop-mediated isothermal amplification (LAMP), and quantitative reverse transcription polymerase chain reaction (qRT-PCR) to determine malaria positivity. Hemoglobin values were recorded, and anemia was defined as a binary variable, according to World Health Organization guidelines. RESULTS: Compared to reference qRT-PCR, LAMP had the highest sensitivity (92.6%, 95% confidence interval [CI] 86.4-96.5), followed by uRDT Alere Malaria (33.9%, 95% CI 25.5-43.1), CareStart Malaria (14.1%, 95% CI 8.4-21.5), microscopy (5.0%, 95% CI 1.8-10.5), and SD Bioline (5.0%, 95% CI 1.8-10.5). For Plasmodium falciparum specimens only, the sensitivity for uRDT Alere Malaria was 50.0% (95% CI 38.8-61.3) and SD Bioline was 7.3% (95% CI 2.7-15.3). Based on multivariate regression analysis with qRT-PCR as the gold standard, for every 3.2% increase in the prevalence of asymptomatic malaria, hemoglobin decreased by 1 gram per deciliter (prevalence ratio 0.968, 95% CI 0.940-0.997; P = .032). Deletions (4.8%) in hrp2 were noted. CONCLUSIONS: While uRDT Alere Malaria has superior sensitivity to rapid diagnostic tests and microscopy in detecting asymptomatic malaria, LAMP is superior still. Ultrasensitive diagnostics provide the accurate prevalence estimates of asymptomatic malaria required for elimination.

Low Use of Guideline-recommended Cardiorenal Protective Antihyperglycemic Agents in Primary Care: A Cross-sectional Study of Adults With Type 2 Diabetes.

OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown cardiorenal benefits independent of their glucose-lowering effects among persons living with type 2 diabetes mellitus (T2DM). In this study, we describe the proportion of persons with T2DM eligible to receive and currently receiving these agents based on their risk criteria for cardiorenal events. METHODS: This study was a cross-sectional analysis of primary care electronic medical records, in southern Alberta, of persons with T2DM who had at least 1 encounter with their primary care provider between December 31, 2018, to December 31, 2020. A descriptive and multivariate logistic regression analysis was conducted to examine clinical and demographic determinants of being prescribed one of the new treatments. RESULTS: Our study sample included 11,939 persons living with T2DM, among whom 66.3% had a cardiorenal indication for SGLT2i or GLP-1 RA use. In the secondary and primary prevention subsamples, 19.4% and 16.6% of persons were prescribed SGLT2i or GLP-1 RA, respectively, compared with 20.0% of those with no specific cardiorenal indication. Several person-level characteristics, such as age (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.96 to 0.97), male sex (OR, 1.37; 95% CI, 1.21 to 1.55) and glycated hemoglobin (OR, 1.29; 95% CI, 1.24 to 1.34), were associated with being prescribed SGLT2i or GLP-1 RA. CONCLUSIONS: Low rates of SGLT2i or GLP-1 RA use and minimal differences between high-risk and no cardiorenal indication subsamples suggest the presence of barriers to prescribing these medications in a primary care setting. Action to highlight the indications for, and improve access to agents with, cardiorenal benefits will be required to achieve better outcomes for people with T2DM in primary care.

Risk of malaria associated with travel to malaria-endemic areas to visit friends and relatives: a population-based case-control study.

BACKGROUND: Reports relying on population-based data and using epidemiologic methodologies such as case-control study designs for malaria in travellers and multivariable regression analysis of risk factors are rare. The aim of this study was to investigate the epidemiologic characteristics of travellers who tested positive for malaria after visiting friends and relatives in malaria-endemic areas to determine the risk of malaria associated with such travel. METHODS: Using routinely collected data from a population-based laboratory database, we conducted a case-control study of symptomatic people returning from travel to malaria-endemic areas who presented for malaria testing in Calgary from 2013 to 2017. We used a multivariable logistic regression to analyze the association between the presence of malaria and other risk factors. RESULTS: There were 251 confirmed malaria cases during the study period, of which 219 were matched to 1129 returning travellers without malaria. Based on the multivariable regression, the odds of a traveller who visited friends and relatives in malariaendemic areas being diagnosed with malaria was 2.82 (95% confidence interval [CI] 1.42-5.92) times greater than that of other travellers to these regions. Adults (odds ratio [OR] 3.62, 95% CI 1.66-8.84), males (OR 2.70, 95% CI 1.56-4.80), travellers to Africa (OR 11.52, 95% CI 6.33-22.05) and those who did not seek pretravel advice (OR 0.38, 95% CI 0.20-0.70) were more likely to be diagnosed with malaria. Although those travelling to visit friends and relatives tended to stay longer in endemic areas than other travellers, visit duration was not associated with an increased likelihood of malaria in the model. The annual incidence of malaria was highest (13.34 per 100 000) in metropolitan wards associated with lower socioeconomic status and immigrant communities. INTERPRETATION: Travellers who visited friends and relatives in malaria-endemic areas were less likely than other travellers to these regions to seek pretravel advice, take prophylaxis and have a visit duration less than 2 weeks; travelling to Africa and being male increased the odds of being diagnosed with malaria, independent of other factors. These data suggest that targeted strategies to provide pretravel care to travellers who visit friends and relatives in malaria-endemic areas may aid in reducing the burden of malaria in this population.

The Impact of Malaria on Liver Enzymes: A Retrospective Cohort Study (2010-2017).

BACKGROUND: It is unclear if malaria causes deranged liver enzymes. This has implications both in clinical practice and in research, particularly for antimalarial drug development. METHOD: We performed a retrospective cohort study of returning travelers (n = 4548) who underwent a malaria test and had enzymes measured within 31 days in Calgary, Canada, from 2010 to 2017. Odds ratios of having an abnormal alkaline phosphatase (ALP), alanine aminotransferases (ALT), aspartate aminotransferases (AST), and total bilirubin (TB) were calculated using multivariable longitudinal analysis with binomial response. RESULTS: After adjusting for gender, age, and use of hepatotoxic medications, returning travelers testing positive for malaria had higher odds of having an abnormal TB (odds ratio [OR], 12.64; 95% confidence interval [CI], 6.32-25.29; P < .001) but not ALP (OR, 0.32; 95% CI, 0.09-1.10; P = .072), ALT (OR, 1.01; 95% CI, 0.54-1.89; P = .978) or AST (OR, 1.26; 95% CI, 0.22-7.37; P = .794), compared with those who tested negative. TB was most likely to be abnormal in the "early" period (day 0-day 3) but then normalized in subsequent intervals. Returning travelers with severe malaria (OR, 2.56; 95% CI, 0.99-6.62; P = .052) had borderline increased odds of having an abnormal TB, but malaria species (OR, 0.70; 95% CI, 0.24-2.05; P = .511) did not. CONCLUSIONS: In malaria-exposed returning travelers, the TB is abnormal, especially in the early period, but no abnormalities are seen for ALT, AST, or ALP.

Clinical Validation of a Commercial LAMP Test for Ruling out Malaria in Returning Travelers: A Prospective Diagnostic Trial.

The mainstay of malaria diagnosis relies on rapid diagnostic tests (RDTs) and microscopy, both of which lack analytical sensitivity. This leads to repeat testing to rule out malaria. A prospective diagnostic trial of the Meridian illumigene Malaria assay (loop-mediated isothermal amplification [LAMP]) was conducted comparing it with reference microscopy and RDTs (BinaxNOW Malaria) in returning travelers between June 2017 and January 2018. Returning travelers with signs and symptoms of malaria were enrolled in the study. RDTs, microscopy, and LAMP assays were performed simultaneously. A total of 298 patients (50.7% male; mean age, 32.5 years) were enrolled, most visiting friends and relatives (43.3%), presenting with fever (88.9%), not taking prophylaxis (82.9%), and treated as outpatients (84.1%). In the prospective arm (n = 348), LAMP had a sensitivity of 98.1% (95% confidence interval [CI], 90.0%-100%) and a specificity of 97.6% (95% CI, 95.2%-99.1%) vs microscopy. After discrepant resolution with real-time polymerase chain reaction, LAMP had a sensitivity of 100% (95% CI, 93.7%-100%) and a specificity of 100% (95% CI, 98.7%-100%) vs microscopy. After discrepant resolution, RDTs had a sensitivity of 83.3% (95% CI, 58.6%-96.4%) and a specificity of 96.2% (95% CI, 93.2%-98.1%) vs microscopy. When including retrospective specimens (n = 377), LAMP had a sensitivity of 98.8% (95% CI, 93.2%-100%) and a specificity of 97.6% (95% CI, 95.2%-99.1%) vs microscopy, and after discrepant resolution of this set, LAMP had a sensitivity of 100% (95% CI, 95.8%-100%) and a specificity of 100% (95% CI, 98.7%-100%). A cost-benefit analysis of reagents and labor suggests savings of up to USD$13 per specimen using a novel algorithm with LAMP screening.