Endocarditis and the impact of intravenous drug use: a cohort study.

OBJECTIVES: This cohort study is a comparison of infective endocarditis in intravenous drug users (IDUs) and non-IDUs within a single tertiary centre. We aim to quantify and describe the factors that influence prognosis and microbiological characteristics. METHOD: All consecutive admissions to a tertiary referral hospital in the north of England with a diagnosis of endocarditis from April 2013 to January 2020 were identified. Outcomes were all-cause mortality at 30 days, 12 months and 3 years, length of stay and progression to surgery. RESULTS: A total of 303 cases were identified via clinical coding of which 287 cases of endocarditis were confirmed. First episode endocarditis was then confirmed in 263 episodes, 44 in IDUs and 219 in non-IDUs. Methicillin sensitive Staphylococcus aureus (MSSA) was the most common organism seen overall, significantly more so in IDU than non-IDU cases (29/44 [65.9%] vs. 51/219 [23.3%], p < .001). Overall progression to valve surgery was similar between the two groups (92/219 [42.0%] vs. 19/44[43.2%], p = .886). In IDUs 30-d survival was 93% (80-98) and 3-year survival 47% (30-63%). In non-IDU 30-d survival was 88% (83-92%) and 60% (53-67%) at 3 years. Of the 19 IDUs who underwent valve surgery 7 (37%) survived to study completion without reinfection and 8 (42%) died following recurrent endocarditis. CONCLUSIONS: We demonstrate that prognosis in IDUs is worse than previously described, particularly in those undergoing valve surgery. This is despite comparable receipt of inpatient treatment to non-IDUs as demonstrated by equal length of stay and rates of surgery. Clinicians should consider the role of addictions services on discharge to break the cycle of reinfection.

Utility of Routine Laboratory Biomarkers to Detect COVID-19: A Systematic Review and Meta-Analysis.

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work. A systematic literature review and meta-analysis were performed. The search included names of commonly used, routine laboratory tests in the UK NHS, and focused on research papers reporting laboratory results of patients diagnosed with COVID-19. A random effects meta-analysis of the standardized mean difference between COVID-19-positive and -negative groups was conducted for each biomarker. When comparing reported laboratory biomarker results, we identified decreased white blood cell, neutrophil, lymphocyte, eosinophil, and platelet counts; while lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were elevated in COVID-19-positive compared to COVID-19-negative patients. Differences were identified across a number of routine laboratory biomarkers between COVID-19-positive and -negative patients. Further research is required to identify whether routine laboratory biomarkers can be used in the development of a clinical scoring system to aid with triage of patients.

Active case detection of malaria in pregnancy using loop-mediated amplification (LAMP): a pilot outcomes study in South West Ethiopia.

BACKGROUND: 125 million women are pregnant each year in malaria endemic areas and are, therefore, at risk of Malaria in Pregnancy (MiP). MiP is the direct consequence of Plasmodium infection during pregnancy. The sequestration of Plasmodium falciparum parasites in the placenta adversely affects fetal development and impacts newborn birth weight. Importantly, women presenting with MiP commonly develop anaemia. In Ethiopia, the Ministry of Health recommends screening symptomatic women only at antenatal care visits with no formal intermittent preventive therapy. Since MiP can display low-level parasitaemia, current tests which include microscopy and RDT are challenged to detect these cases. Loop mediated isothermal Amplification (LAMP) technology is a highly sensitive technique for DNA detection and is field compatible. This study aims to evaluate the impact of active malaria case detection during pregnancy using LAMP technology in terms of birth outcomes. METHODS: A longitudinal study was conducted in two health centres of the Kafa zone, South West Ethiopia. Both symptomatic and asymptomatic pregnant women were enrolled in the first or second trimester and allocated to either Standard of Care (SOC-microscopy and RDT) or LAMP (LAMP, microscopy and RDT). Women completed at least three visits prior to delivery, and the patient was referred for treatment if Plasmodium infection was detected by any of the testing methods. The primary outcome was to measure absolute birth weight, proportion of low birth weight, and maternal/neonatal haemoglobin in each arm. Secondary outcomes were to assess the performance of microscopy and RDT versus LAMP conducted in the field. RESULTS: One hundred and ninety-nine women were included and assigned to either LAMP or SOC. Six were lost to follow up. In this cohort, 66.8% of women did not display any clinical symptoms and 70.9% were multi-parous. A reduced proportion of low birth weight newborns was observed in the LAMP group (0%) compared to standard of care (14%) (p <0.001). Improved neonatal haemoglobin was observed in the LAMP (13.1 g/dL) versus the SOC (12.8 g/dL) (p = 0.024) arm. RDT and microscopy had an analytical sensitivity of 66.7% and 55.6% compared to LAMP as a reference standard. CONCLUSIONS: These results support the use of highly sensitive tools for rapid on-site active case detection of MiP which may improve birth outcomes in the absence of IPT. However, further large-scale studies are required to confirm this finding.

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.

Asymptomatic malaria in the clinical and public health context.

Introduction: Historically, the global community has focused on the control of symptomatic malaria. However, interest in asymptomatic malaria has been growing, particularly in the context of malaria elimination.Areas covered: We undertook a comprehensive PubMed literature review on asymptomatic malaria as it relates to detection and elimination with emphasis between 2014 and 2019. Diagnostic tools with a low limit of detection (LOD) have allowed us to develop a more detailed understanding of asymptomatic malaria and its impact. These highly sensitive diagnostics have demonstrated that the prevalence of asymptomatic malaria is greater than previously thought. In addition, it is now possible to detect the malaria reservoir in the community, something that was previously not feasible. Asymptomatic malaria has previously not been treated, but research has begun to examine whether treating individuals with asymptomatic malaria may lead to health benefits. Finally, we have begun to understand the importance of asymptomatic malaria in ongoing transmission.Expert opinion: Therefore, with malaria elimination back on the agenda, asymptomatic malaria can no longer be ignored, especially in light of new ultra-sensitive diagnostic tools.

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.

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.

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.