Sensitive Diagnostic Test Research Articles

Utility of surveillance data for planning for dengue elimination in Yogyakarta, Indonesia: a scenario-tree modelling approach

IntroductionField trials and modelling studies suggest that elimination of dengue transmission may be possible through widespread release of Aedes aegypti mosquitoes infected with the insect bacterium Wolbachia pipientis (wMel strain),...

Sensitivity and specificity of a syphilis rapid diagnostic test in blood donors’ samples

Rapid Diagnostic Tests (RDT) are useful to identify syphilis cases, particularly for hard-to-reach populations and if laboratory services are scarce. However, RDT performance may be suboptimal. We aimed to assess the sensitivity and specificity of a syphilis RDT using well-characterized blood donors’ samples. We categorized samples from 811 blood donors into five groups: 1 - Samples with reactive Chemiluminescence (QML), FTA-Abs, and VDRL; 2 - Samples with reactive QML and FTA-Abs, and nonreactive VDRL; 3 - Samples with reactive QML, and nonreactive for other markers (false-positives); 4 - Controls with nonreactive QML; and 5 - Samples reactive for HIV, with nonreactive QML. Sensitivity was tested in groups 1 (overall and according to VDRL titers) and 2; specificity was tested in groups 3‒5. The RDT had high specificity, even in samples reactive for HIV. The sensitivity was high (91.9%) in samples with reactive VDRL but varied between 75.0%‒100% according to VDRL titers. The overall sensitivity was lower (81.3%) in samples with reactive FTA-Abs and nonreactive VDRL. The RDT is a useful tool to detect active syphilis but may be more limited for cases with very early or remote infection, or those with prior treatment. When higher sensitivity is needed, additional strategies including recurrent testing or laboratory-based tests may be required.

Clinical and Metagenomic Characterization of Neurological Infections of People With Human Immunodeficiency Virus in the Peruvian Amazon.

Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose. One hundred forty people with HIV with acute neurological symptoms from Iquitos, Peru, were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF) and for cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples was evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses. Twenty-seven participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow Coma Scale score (P = .05), unilateral focal motor signs (P = .01), positive Babinski reflex (P = .01), and multiple lesions on head computed tomography (CT) (P = .002) were associated with cerebral toxoplasmosis. Photophobia (P = .03) and absence of lesions on head CT (P = .02) were associated with cryptococcal meningitis. mNGS of 42 samples identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, 5 possible cases of tuberculous meningitis, and incidental detections of hepatitis B virus (n = 1) and pegivirus (n = 1). mNGS had a positive percentage agreement of 71% and a negative percentage agreement of 91% with qPCR for T gondii. mNGS had a sensitivity of 78% and specificity of 100% for Cryptococcus diagnosis. An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for central nervous system infections.

Converging Epidemics: A Narrative Review of Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) Coinfection.

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (MTB), remains a leading cause of mortality in individuals living with human immunodeficiency virus (HIV) infection, posing a significant strain on healthcare systems. Coinfection of HIV and TB results in a mutually advantageous relationship that accelerates the progression of both diseases. TB is a major contributor to mortality in individuals with HIV. However, diagnosing coinfected individuals is challenging due to the prevalence of extrapulmonary TB and smear-negative disease. Overthe past decade, significant progress has been made in the fight against TB, thanks to advances in molecular techniques. Yet, these molecular diagnostic assays remain inaccessible to many individuals coinfected with HIV and TB due to their high cost. To expedite treatment and reduce transmission, it is crucial to integrate HIV and TB control programs more closely, thereby minimizing diagnostic delays and enhancing early case detection. This review aims to provide a comprehensive overview of the current state of knowledge regarding the interplay between HIV and TB. It highlights recent developments in sensitive and rapid TB diagnostic tests, cutting-edge preventive strategies, and the screening of individuals coinfected with both HIV and TB. The objectives of this review are to shed light on the complex relationship between these two diseases and to emphasize the importance of integrated efforts in combating their impact on public health.

Clinical SMN1 and SMN2 Gene-Specific Sequencing to Enhance the Clinical Sensitivity of Spinal Muscular Atrophy Diagnostic Testing

Purpose. Therapeutic advances in the treatment of spinal muscular atrophy (SMA) prompt the need for robust and efficient molecular diagnosis of this disease. Approximately five percent of SMA cases are attributable to one copy of SMN1 with a hypomorphic or inactivating variant in trans with a deleted or converted allele. These intragenic variants are challenging to definitively localize to SMN1 due to its sequence homology with the SMN2 gene. To enhance the clinical sensitivity of SMA diagnostic testing, we present an optimized gene-specific sequencing assay to localize variants to either SMN1 or SMN2. Methods. SMN1 and SMN2 genes are independently amplified by long-range allele-specific PCR. Long-range products are used in subsequent nested PCR reactions to amplify the coding exons of SMN1 and SMN2. The resulting products are sequenced using standard Sanger-based methodologies and analyzed for disease-associated alterations. Results. 83 probands suspicious for a clinical diagnosis of SMA with a nondiagnostic SMN dosage result were sequenced for intragenic variants in the SMN1 gene. Gene-specific sequencing revealed likely disease-associated variants in SMN1 in 42 cases (50.6%). Of the 42 variants, 27 are unique including 16 loss-of-function variants, 9 missense variants, 1 in-frame deletion variant, and 1 splice site variant. Conclusions. Herein, we describe an optimized assay for clinical sequencing of the full coding region of SMN1 and SMN2. This assay uses standard techniques and equipment readily available to most molecular diagnostic laboratories.

Clinical research progress of spinal epidural lipomatosis

To review the clinical research progress of spinal epidural lipomatosis (SEL). The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed. SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients. SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.

A clinical pilot study for the detection of sphingomyelinase in leptospirosis patient's urine at tertiary care hospital

PurposeLeptospirosis is a perplexing mystification for many clinicians. Clinically often underdiagnosed due to lack of a rapid, sensitive, and specific diagnostic test. Currently available diagnostic tests have their own limitations; therefore, monitoring biomarkers that contribute an essential role in pathogenesis is crucial. Herein, a pilot study was conducted to detect the presence of sphingomyelinase in urine of leptospirosis patients. MethodsBlood and urine samples were collected from 140 patients having febrile illness. Samples were analyzed through culturing, dark-field microscopy, detecting anti-leptospiral antibodies by MAT, IgM ELISA, Leptocheck-WB and screening for sphingomyelinase using a sphingomyelinase assay kit. ResultsOut of 140 febrile illness patients, 22.14 % were tested leptospirosis, 33.57 % were dengue, 25 % scrub typhus, 18.57 % malaria and 0.71 % co-infection (dengue-leptospirosis). MAT seropositivity of 19.28 % (27/140) was confirmed with the highest agglutinant determined against serovar Icterohaemorrhagiae RGA followed by Autumnalis, Australis, and Pyrogens. IgM ELISA and Leptocheck-WB positivity was 16.42 % and 13.57 % respectively. Whereas culture and dark-field microscopy showed a sensitivity of 4.28 % and 2.1 %, respectively. Out of 31 confirmed cases of leptospirosis, sphingomyelinase was detected in the urine of 25 (80.64 %) patients, MAT positivity was seen in 87.09 % and culture positivity was seen in 12.90 % of cases. ConclusionDetection of sphingomyelinase in the urine of a leptospirosis patient and its absence in other febrile illnesses like dengue, malaria and scrub typhus establish evidence of secretion of sphingomyelinase in urine during leptospiral infection. Hence, sphingomyelinase could be used as a potential diagnostic biomarker to detect leptospirosis in a non-invasive way.

Development of an artificial intelligence system for the forecasting of infectious diseases

Aim. Here, we provided an overview of artificial intelligence (AI) approaches for developing a system for prediction of infectious diseases and designed a respective step-by-step protocol.Materials and Methods. Literature search in PubMed and Google Scholar and PubMed.Key Points. Infectious diseases impose a heavy burden on a healthcare, demanding the development of novel and efficient approaches to prevention as well as sensitive and specific diagnostic tests. Evolution of data science have led to the emergence of promising artificial intelligence (AI) algorithms and tools for the forecasting of infectious diseases. Employing machine learning algorithms, AI systems can rapidly analyze a large amount of data, extract specific disease patterns, and screen for the most efficient AI instruments in relation to specific tasks, thus contributing to prevention, diagnostics, and treatment of infectious diseases in the context of personalized medicine. Importantly, such AI-based systems can determine specific human motor patterns from videos and/or photographs in order to assist physicians in primary diagnosis. Integration of AI tools into the existing healthcare algorithms can be especially useful for public health.

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023.

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.

The New Normal: Delayed Peak SARS-CoV-2 Viral Loads Relative to Symptom Onset and Implications for COVID-19 Testing Programs.

Early in the coronavirus disease 2019 (COVID-19) pandemic, peak viral loads coincided with symptom onset. We hypothesized that in a highly immune population, symptom onset might occur earlier in infection, coinciding with lower viral loads. We assessed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A viral loads relative to symptom duration in symptomatic adults (≥16 years) presenting for testing in Georgia (4/2022-4/2023; Omicron variant predominant). Participants provided symptom duration and recent testing history. Nasal swabs were tested by Xpert Xpress SARS-CoV-2/Flu/RSV assay and cycle threshold (Ct) values recorded. Nucleoprotein concentrations in SARS-CoV-2 polymerase chain reaction (PCR)-positive samples were measured by single molecule array. To estimate hypothetical antigen rapid diagnostic test (Ag RDT) sensitivity on each day after symptom onset, percentages of individuals with Ct value ≤30 or ≤25 were calculated. Of 348 newly-diagnosed SARS-CoV-2 PCR-positive individuals (65.5% women, median 39.2 years), 317/348 (91.1%) had a history of vaccination, natural infection, or both. By both Ct value and antigen concentration measurements, median viral loads rose from the day of symptom onset and peaked on the fourth/fifth day. Ag RDT sensitivity estimates were 30.0%-60.0% on the first day, 59.2%-74.8% on the third day, and 80.0%-93.3% on the fourth day of symptoms.In 74 influenza A PCR-positive individuals (55.4% women; median 35.0 years), median influenza viral loads peaked on the second day of symptoms. In a highly immune adult population, median SARS-CoV-2 viral loads peaked around the fourth day of symptoms. Influenza A viral loads peaked soon after symptom onset. These findings have implications for ongoing use of Ag RDTs for COVID-19 and influenza.

Development and Validation of Three Automated High-Throughput Molecular Tests to Detect Monkeypox Virus Infections.

The 2022 outbreak of the clade IIb monkeypox virus and subsequent global spread lead to an urgent need for the development of high-throughput, sensitive, and reproducible diagnostic tests. We developed 3 assays to detect monkeypox virus, 2 (MPXV+ and MPXV) for m2000 RealTime and 1 (MPXV) for Alinity m platforms. Dual targets in E9L and B6R (MPXV+) and J2L and B7R (MPXV) increased mutation resistance. In silico prediction indicates MPXV+ cross-reactivity with orthopox viruses and specific monkeypox virus detection with MPXV. m2000 RealTime MPXV+ and MPXV assay sensitivity was determined to be 3.2 plaque-forming units/mL using a reference virus culture diluted into universal transport medium (UTM). Alinity m MPXV lower limit of detection was 200 copies/mL using monkeypox virus plasmids in pooled UTM matrix. m2000 RealTime MPXV+ and MPXV assays were validated with lesion swabs in UTM and 1:1 saliva to UTM mixtures. Commercially available and remnant clinical lesion specimens in UTM were tested with RealTime MPXV+, RealTime MPXV and Alinity m MPXV assays and demonstrated high agreement to known mpox (MPX)-positive specimens. RealTime MPXV+, RealTime MPXV, and Alinity MPXV are high throughput and sensitive assays used for the detection of monkeypox virus. These assays maybe useful during MPX outbreaks.

Perceptions and drivers of healthcare provider and drug dispenser practices for the treatment of malaria in pregnancy in the context of multiple first-line therapies in western Kenya: a qualitative study

BackgroundEmergence of Plasmodium falciparum resistance to artemether-lumefantrine in Africa prompted the pilot introduction of multiple first-line therapies (MFT) against malaria in Kenya, potentially exposing women-of-childbearing-age (WOCBAs) to anti-malarials with unknown safety profiles in the first trimester. This qualitative study explored knowledge and perceptions among healthcare providers providing malaria treatment to WOCBAs and pregnant women.MethodsIn-depth interviews were conducted with purposively selected public and private health facility (HF) and drug outlet (DO) providers within and outside the pilot-MFT area. County health managers were interviewed about their knowledge of the national treatment guidelines. Transcripts were coded by content analysis using the World Health Organization health system building blocks (leadership/governance, financing, health workforce, health information systems, access to medicines, and service delivery).ResultsThirty providers (HF:21, DO:9) and three health managers were interviewed. Eighteen providers were from HFs in the pilot-MFT area; the remaining three and all nine DOs were outside the pilot-MFT area. The analysis revealed that providers had not been trained in malaria case management in the previous twelve months. DO providers were unfamiliar with national treatment guidelines in pregnancy and reported having no pregnancy tests. Health managers were unable to supervise DOs due to resource limitations. Providers from HFs and DOs noted poor sensitivity of malaria rapid diagnostic tests (RDTs) and hesitancy among patients who associated malaria-RDTs with HIV testing. Almost all providers reported anti-malarial stock-outs, with quinine most affected. Patient preference was a major factor in prescribing anti-malarials. Providers in HFs and DOs reported preferentially using artemether-lumefantrine in the first trimester due to the side effects and unavailability of quinine.ConclusionKnowledge of malaria case management in drug outlets and health facilities remains poor. Improved regulation of DO providers is warranted. Optimizing treatment of malaria in pregnancy requires training, availability of malaria commodities, and pregnancy tests.

Estimating the proportion of clinically suspected cholera cases that are true Vibrio cholerae infections: A systematic review and meta-analysis.

Cholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected cholera case definitions have high sensitivity but low specificity, challenging our ability to characterize cholera burden and epidemiology. Our objective was to estimate the proportion of clinically suspected cholera that are true Vibrio cholerae infections and identify factors that explain variation in positivity. We conducted a systematic review of studies that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR, and/or a rapid diagnostic test. We searched PubMed, Embase, Scopus, and Google Scholar for studies that sampled at least one suspected case between January 1, 2000 and April 19, 2023, to reflect contemporary patterns in V. cholerae positivity. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated V. cholerae positivity using a random-effects meta-analysis, adjusting for test performance. We included 119 studies from 30 countries. V. cholerae positivity was lower in studies with representative sampling and in studies that set minimum ages in suspected case definitions. After adjusting for test performance, on average, 52% (95% credible interval (CrI): 24%, 80%) of suspected cases represented true V. cholerae infections. After adjusting for test performance and study methodology, the odds of a suspected case having a true infection were 5.71 (odds ratio 95% CrI: 1.53, 15.43) times higher when surveillance was initiated in response to an outbreak than in non-outbreak settings. Variation across studies was high, and a limitation of our approach was that we were unable to explain all the heterogeneity with study-level attributes, including diagnostic test used, setting, and case definitions. In this study, we found that burden estimates based on suspected cases alone may overestimate the incidence of medically attended cholera by 2-fold. However, accounting for cases missed by traditional clinical surveillance is key to unbiased cholera burden estimates. Given the substantial variability in positivity between settings, extrapolations from suspected to confirmed cases, which is necessary to estimate cholera incidence rates without exhaustive testing, should be based on local data.

Challenges in the Management of Invasive Fungal Infections in the Middle East: Expert Opinion to Optimize Management Using a Multidisciplinary Approach.

Invasive fungal infection (IFI) is a significant global healthcare concern among critically ill and immunocompromised patients. In Middle Eastern countries, IFI has been steadily increasing among hospitalized patients in the past two decades. Diagnosis of IFI at an early stage is crucial for efficient management. Invasive fungal infection management is complex and requires the involvement of physicians from different specialties. There are several challenges associated with IFI management in the countries in the Middle East. This review aims to understand the key challenges associated with IFI management in the Middle East, encompassing epidemiology, diagnosis, therapeutic options, and optimizing a multidisciplinary approach. In addition, this review aims to incorporate expert opinions from multidisciplinary fields for optimizing IFI management in different Middle Eastern countries by addressing key decision points throughout the patient's journey. Lack of epidemiological data on fungal infections, slow and poorly sensitive conventional culture-based diagnostic tests, limited availability of biomarker testing, lack of awareness of clinical symptoms of the disease, limited knowledge on fungal infections, lack of local practice guidelines, and complicated disease management are the major challenges associated with IFI diagnosis and management in the Middle Eastern countries. Implementation of a multidisciplinary approach, antifungal stewardship, improved knowledge of fungal infections, the use of rapid diagnostic tests, and enhanced epidemiological research are warranted to lower the IFI burden in the Middle East.

Diagnostic Sensitivity and Specificity of Cognitive Tests for Mild Cognitive Impairment and Alzheimer's Disease in Patients with Down Syndrome: A Systematic Review and Meta-Analysis.

Improved health care for people with Down syndrome (DS) has resulted in an increase in their life expectancy therefore increasing comorbidities associated with age-related problems in this population, the most frequent being Alzheimer's disease (AD). To date, several cognitive tests have been developed to evaluate cognitive changes related to the development of mild cognitive impairment (MCI) and AD in people with DS. Identify and evaluate available cognitive tests for the diagnosis of MCI and AD in people with DS. A systematic search of the Pubmed and PsycInfo databases was performed to identify articles published from January 1, 2000 and July 1, 2022. Keysearch terms were DS, AD or MCI, cognition, and assessment. Relevant studies assessing the diagnostic accuracy of cognitive tests for AD or MCI with standard clinical evaluation were extracted. Risk of bias was assessed using the QUADAS 2. We identified 15 batteries, 2 intelligence scales, 14 memory tests, 11 executive, functioning tests, 11 motor and visuospatial functioning tests, 5 language tests, 3 attention tests, and 2 orientation tests. Analysis showed that the CAMCOG-DS present a fair to excellent diagnostic accuracy for detecting AD in patients with DS. However, for the diagnosis of MCI, this battery showed poor to good diagnostic accuracy. The findings highlight important limitations of the current assessment available for the screening of mild cognitive impairment and AD in patients with DS and support the need for more clinical trials to ensure better screening for this highly at-risk population.

DTAmetasa: An R shiny application for meta-analysis of diagnostic test accuracy and sensitivity analysis of publication bias.

Meta-analysis of diagnostic test accuracy (DTA) is a powerful statistical method for synthesizing and evaluating the diagnostic capacity of medical tests and has been extensively used by clinical physicians and healthcare decision-makers. However, publication bias (PB) threatens the validity of meta-analysis of DTA. Some statistical methods have been developed to deal with PB in meta-analysis of DTA, but implementing these methods requires high-level statistical knowledge and programming skill. To assist non-technical users in running most routines in meta-analysis of DTA and handling with PB, we developed an interactive application, DTAmetasa. DTAmetasa is developed as a web-based graphical user interface based on the R shiny framework. It allows users to upload data and conduct meta-analysis of DTA by "point and click" operations. Moreover, DTAmetasa provides the sensitivity analysis of PB and presents the graphical results to evaluate the magnitude of the PB under various publication mechanisms. In this study, we introduce the functionalities of DTAmetasa and use the real-world meta-analysis to show its capacity for dealing with PB.

Seroprevalence of HIV, Hepatitis B and C Viruses, and Treponema Pallidum among Blood Donors Attending the Garoua Regional Hospital Blood Bank, North Cameroon, a Cross-Sectional Study

Background. Human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C virus (HCV) are transfusion-transmittable infections (TTI). They currently constitute a major public health problem in Cameroon, like in other developing countries. Little is known about the seroprevalence of HIV, HBV, HCV, and syphilis among blood donors in northern region Cameroun. This study aims at filling the gap on the unknown sero-prevalence of those markers in blood donors. Methods. We conducted a cross-sectional study from June 04, to July 08, 2022 at the Garoua Regional Hospital Blood Bank (GRHBB). A total of 201donors were consecutively included and data on donor’s sociodemographic characteristics were obtained by the national program’s questionnaire. Serum samples from blood donors were tested using sensitive third generation Rapid diagnostic test (RDT) for presence of Hepatits B surface antigens (HBsAg), and antibodies to human immunodeficiency (HIV-1/2), Hepatits C (HCV) and Treponema pallidum; and quantitative enzyme-linked immunosorbent assays (ELISA) served for confirmation. Data were collected and entered into an Excel sheet and then exported to SPSS version 20.0 for analysis. Results. A total of 201 blood donors were identified and the sex ratio (male/female) was 7/1, with a mean age of 32.12 ± 8.4 years (range: 19 to 57 years). Of all blood donors, 35/201 (17.4%) were infested by at least one of the four TTIs. Among blood donors, HIV, HBV, HCV and syphilis were 5 (2.5%); 26 (12.9%); 1 (0.5%) and 5 (2.5%), respectively. Co-infection with HIV-Syphilis was 1 (0.5%); and HBV-HCV 1 (0.5%). Conclusions. This study has revealed the high prevalence of TTIs in blood donors who attended the Garoua Regional Hospital Blood Bank, identifying Hepatitis B as the greatest threat to blood safety in the North Region of Cameroon.

P20 Rapid 15 min test to identify the three most common Gram-negative uropathogens in urinary tract infections

Abstract Background Every year, 6.2 million cases of urinary tract infection (UTI) are reported in England and Wales and have the second highest antibiotic prescription rate. The absence of fast and sensitive diagnostic tests has increased empirical antibiotic use and has contributed to the rise of antibiotic-resistant infections. To address this challenge, we have developed NANOPLEX™: a rapid 15 min test that uses glycan-functionalized-latex nanoparticles, microscopy and image-analysis software to identify and enumerate samples with bacteria. In this work, we show that NANOPLEX™ can correctly identify the three most common uropathogens using lab reference strains, clinical isolates and clinical urine samples. Materials and Methods The NANOPLEX™ assay was performed as per Vendeville et al. 2021.1 ACS Biomater 2022; 8, 1:242-252. Clinical isolates of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were obtained from an NHS clinical microbiology lab waste stream. N=30 isolates (per species) were tested via single-blind study protocols at concentrations of 10³–108 cfu/mL and compared with microbial culture to define performance metrics (sensitivity, specificity, PPV, NPV and accuracy) of each probe. Results A total of 90 isolates were tested against their target probes and demonstrated >90% accuracy (sensitivity 88%–90%, specificity 94%–98%, PPV 93%–98%, NPV 88%–90%, accuracy 91%–94%) for all probe-bacteria combinations at clinically significant concentrations (105 cfu/mL). Conclusions NANOPLEX™ was able to successfully detect the top three common Gram-negative pathogens in UTI at clinically relevant concentrations. A compact hardware and single-use cartridge system is under development to enable urologists to conduct rapid and accurate UTI testing in point-of-care environments. Larger clinical studies are planned to clinically validate these results.

Spatial Clustering and Risk Factors for Malaria Infections and Marker of Recent Exposure to Plasmodium falciparum from a Household Survey in Artibonite, Haiti.

Targeting malaria interventions in elimination settings where transmission is heterogeneous is essential to ensure the efficient use of resources. Identifying the most important risk factors among persons experiencing a range of exposure can facilitate such targeting. A cross-sectional household survey was conducted in Artibonite, Haiti, to identify and characterize spatial clustering of malaria infections. Household members (N = 21,813) from 6,962 households were surveyed and tested for malaria. An infection was defined as testing positive for Plasmodium falciparum by either a conventional or novel highly sensitive rapid diagnostic test. Seropositivity to the early transcribed membrane protein 5 antigen 1 represented recent exposure to P. falciparum. Clusters were identified using SaTScan. Associations among individual, household, and environmental risk factors for malaria, recent exposure, and living in spatial clusters of these outcomes were evaluated. Malaria infection was detected in 161 individuals (median age: 15 years). Weighted malaria prevalence was low (0.56%; 95% CI: 0.45-0.70%). Serological evidence of recent exposure was detected in 1,134 individuals. Bed net use, household wealth, and elevation were protective, whereas being febrile, over age 5 years, and living in either households with rudimentary wall material or farther from the road increased the odds of malaria. Two predominant overlapping spatial clusters of infection and recent exposure were identified. Individual, household, and environmental risk factors are associated with the odds of individual risk and recent exposure in Artibonite; spatial clusters are primarily associated with household-level risk factors. Findings from serology testing can further strengthen the targeting of interventions.

A 78-Year-Old Man with Weakness and Loss of Appetite for 2 Months

The incidence rate of tuberculosis (TB) in Korea has been consistently decreasing, but the proportion of extrapulmonary tuberculosis (EPTB) remains relatively stable at around 20%. Diagnosing EPTB remains a challenge because clinical samples obtained from relatively inaccessible sites may be paucibacillary, thus reducing the sensitivity of diagnostic tests. Delayed diagnosis and treatment some form of EPTB, such as tuberculous meningitis, can lead to fatal outcomes. Therefore, it is crucial to have a high index of suspicion and perform appropriate testing early on. Obtaining a specimen from the lesion and conducting microbiological tests (acid-fast bacilli smear, mycobacterial culture, and nucleic acid amplification test) along with histopathological examination is essential. When the specimen is limited for all testing, mycobacterial culture test should be prioritized as it has the highest diagnostic yield and allows for drug susceptibility testing. All patients with presumed EPTB should be assessed for pulmonary TB to assess infectiousness and potentially assist with diagnosis.