Low Prevalence Settings Research Articles

Safety and efficiency of modified HEART scores without troponin or electrocardiography: an analysis based on two European out-of-hours primary care cohorts

Abstract Background Differentiating between acute chest pain of cardiac versus non-cardiac origin poses a diagnostic challenge. Risk stratification tools, such as the HEART (History, ECG, Age, Risk and Troponin) score, have been developed to aid in decision-making. These scores typically rely on troponin or electrocardiography (ECG), often unavailable in (low-resource) community-based healthcare settings. Purpose We evaluated the diagnostic performance of the HEART score in a low-risk setting when one of its five metrics is missing Methods We relied on data from two cohorts, OUT-ACS (n=1,711; for analyses with and without troponin) and TRACE (n=664; for analyses without troponin) of consecutive patients evaluated at primary care emergency clinics in respectively Norway (2016-2018; 47.7% female, median age: 56, 25th-75th percentiles:45-68) and the Netherlands (2017, 56.9% female, median age: 48, 25th-75th percentiles:32-67). We evaluated the HEAR score (all elements except troponin) and the HART score (all elements except ECG). The primary outcome was the diagnostic performance for ruling out myocardial infarction (MI) at index presentation, with a secondary outcome consisting of the composite of all-cause death or MI at 90-day follow-up. Results Among study participants, 61 (3.6%) were diagnosed with an MI in the OUT-ACS and 20 (3.0%) in the TRACE cohort. The percentages of patients deemed at low risk by HEAR (<=3) were 925 (54.1%) and 527 (79.4%) in OUT-ACS and TRACE, respectively. Sensitivity and specificity were 70.5% (95 % confidence interval 57.4-81.5) and 55.0% (52.5-57.4), and 75.0% (50.9-91.3) and 81.1% (77.8-84.0) for HEAR in the two respective cohorts. For the HART score, low risk was found in 696 (40.7%) OUT-ACS participants, with a respective sensitivity and specificity of 96.7% (88.7-99.6) and 42.1% (39.7-44.5), Positive predictive values ranged from 5.5-15.3%, whilst negative predictive values were 98.1-99.1% for HEAR and 99.7% for HART. By comparison, the HEART score determined 639 (37.3%) patients as low risk, had a sensitivity and specificity of 98.4% (91.2-100) and 38.7% (36.3-41.1), and positive and negative predictive values of 5.6% (5.3-5.9) and 99.8% (98.9-100). Similar findings were found for analyses using the secondary outcome. Conclusion HEART score variants in which troponin or ECG are omitted have higher efficiency but at the cost of decreased safety, particularly when leaving out troponin. Therefore, these biomarkers are paramount for adequate safety, despite the overall high negative predictive values in this low-prevalence primary care setting.

Biomarkers suitable for early detection of intrathoracic cancers in primary care: a systematic review.

Intrathoracic cancers, including lung cancer, mesothelioma, and thymoma, present diagnostic challenges in primary care. Biomarkers could resolve some challenges. We synthesized evidence on biomarkers performance for intrathoracic cancer detection in low-prevalence settings. A search in EMBASE and MEDLINE included studies that recruited participants with suspected intrathoracic cancer and reported on at least one diagnostic measure for a validated, non-invasive biomarker. Studies were excluded if participants were recruited based on a pre-established diagnosis. Fifty-two studies were included, reporting on 108 individual biomarkers and panels. CEA, CYFRA 21.1, and VEGF were evaluated for lung cancer and mesothelioma. For lung cancer, CEA and CYFRA 21.1 were most studied, with AUCs of 0.48-0.90 and 0.48-0.83, respectively. Pro-GRP and NSE had the highest NPVs (98.2%, 96.9%), while Early-CDT and MSC panels showed NPVs of 99.3% and 99.0% in smokers. For mesothelioma, Fibrillin-3 and mesothelin plus osteopontin had AUCs of 0.93 and 0.91, respectively. Thymoma panels (Binding AcHR + StrAb) and (Binding AcHR + Modulating AcHR + StrAb) had 100% NPVs in myasthenia gravis patients. The review highlights the performance of some biomarkers. However, few were evaluated in low-prevalence settings. Further evaluation is necessary before implementing these biomarkers for intrathoracic cancers in primary care.

Diagnostic accuracy of signs and symptoms in acute coronary syndrome and acute myocardial infarction

Background Acute coronary syndrome (ACS) and acute myocardial infarction (AMI) account for a large portion of cardiovascular deaths. Signs and symptoms for these syndromes, such as chest pain, are non-specific and can be caused by a variety of non-cardiac conditions, especially in low-prevalence settings such as general practice. The diagnostic value of these signs and symptoms can be assessed using diagnostic meta-analyses, but the last one dates from 2012. Methods We performed a diagnostic meta-analysis in accordance with PRISMA guidelines. We searched PubMed, Embase and CENTRAL from 2006 to 2024. We included studies that assessed the diagnostic accuracy of thirteen different signs and symptoms. We divided patients into two subgroups (AMI and ACS) on which analysis was performed independently. Results We selected 24 articles for inclusion. Our analysis indicates that signs and symptoms have a limited role in the diagnosis of AMI or ACS. The most useful (highest diagnostic odds ratios, DOR) in the diagnosis of AMI were pain radiating to both arms (DOR 2.95 (95%CI 1.57–5.06)), absence of chest wall tenderness (DOR 3.51 (95%CI 1.64–6.61)), pain radiating to the right arm (DOR 5.17 (95%CI 1.77–11.9)) and sweating (DOR 5.75 (95%CI 2.51–11.4)). For ACS these were pain radiating to the right arm (DOR 3.9 (95%CI 0.7–12.6)) and absence of chest wall tenderness (DOR 7.73 (95%CI 2.19–19.8)). Conclusion We report the accuracy of thirteen signs and symptoms in the diagnosis of AMI and ACS. These can be useful to calibrate general practitioners’ diagnostic assessment of chest pain in primary care settings.

Index-linked Assisted HIV Self-Testing for Children 2-14 Years: Results of a Pilot Evaluation in Ethiopia.

Case identification remains a challenge to reaching the United Nations 95-95-95 targets for children with HIV. While the World Health Organization approved oral mucosal HIV self-testing (HIVST) for children over 2 years in 2019, there is little information on HIVST for pediatric case identification in Ethiopia. Nine health facilities across Ethiopia. We implemented a pilot program from November 2021-April 2022 to assess acceptability and feasibility of using HIVST to screen children 2-14 years of adult index clients, (i.e., parents/caregivers living with HIV and on antiretroviral therapy). HIV-positive adults who had children with unknown HIV status were given HIVST kits (OraQuick®) to screen their children at home. Parents/caregivers were asked to report results telephonically and bring children screening positive to the health facility for confirmatory HIV testing. We defined HIVST acceptability as ≥50% of parents/caregivers accepting testing and ≥50% reporting results within seven days of receiving a test kit. Feasibility was defined as ≥60% of children with a reactive HIVST receiving confirmatory testing and <5 serious social harms reported per 1000 kits distributed. Overall, 1496 of 1651 (91%) parents/caregivers accepted HIVST kits to test their children at home and 1204 (71%) reported results within seven days. Of 17 children (1%) with reactive results, 13 (76%) received confirmatory testing; of which 7 (54%) were confirmed to be HIV-positive. One serious social harm was reported. Providing adult parents/caregivers with HIVST kits to screen their children at home is an acceptable and feasible strategy to reach untested children and improve pediatric case finding in a low prevalence setting.

Comparison of multi-parallel quantitative real-time PCRs targeting different DNA regions and detecting soil-transmitted helminths in stool

BackgroundSoil-transmitted helminths infect an estimated 18% of the world’s population, causing a significant health burden. Microscopy has been the primary tool for diagnosing eggs from fecal samples, but its sensitivity drops in low-prevalence settings. Quantitative real-time polymerase chain reaction (qPCR) is slowly increasing in research and clinical settings. However, there is still no consensus on preferred qPCR targets.MethodsWe aimed to compare soil-transmitted helminth (STH) DNA detection methods by testing naïve stool samples spiked with known quantities of STH eggs and larvae. DNA extracts from spiked samples were tested using independent quantitative realtime PCR (qPCR) assays targeting ribosomal or putative non-protein coding satellite sequences.ResultsFor Trichuris trichiura, there was a strong correlation between egg/larvae counts and qPCR results using either qPCR method (0.86 and 0.87, respectively). Strong correlations also existed for A. lumbricoides (0.60 and 0.63, respectively), but weaker correlations were found for Ancylostoma duodenale (0.41 for both assays) and Strongyloides stercoralis (0.48 and 0.65, respectively). No correlation for Necator americanus was observed when testing with either qPCR assay. Both assays had fair-to-moderate agreement across targets when using field-collected stool samples (0.28–0.45, for all STHs), except for S. stercoralis (0.12) with slight agreement.ConclusionsThere is a strong correlation between qPCR results and egg/larvae counts. Our study confirms that qPCR is an effective diagnostic tool, even with low-intensity infections, regardless of the DNA-based diagnostic marker used. However, the moderate agreement between the two different qPCR assays when testing field samples highlights the need to understand the role of these targets in the genome so that the parasite burden can be quantified more accurately and consistently by qPCR.Graphical abstract

Implementation of routine HIV testing policy in medical admissions in the sultanate of Oman: An experience from the Middle East.

To tackle the issue of late HIV diagnosis in the country, the Ministry of Health (MOH) in Oman introduced a national policy of routine opt-out HIV in medical admission units in September 2022. We hereby report the implementation and outcomes of this policy. All patients aged 16-65years admitted to a medical ward in secondary and local hospitals were offered an HIV test regardless of their symptoms by medical doctors, with training and support from HIV teams. A retrospective review for the period from September 2022 to September 2023 was conducted to determine the HIV testing rate and outcomes of those testing HIV seropositive. Over 12months, there were 23,399 admissions; 6889 had HIV tests. Thirty-two patients (0.46 %) were diagnosed with HIV; all of them were new diagnoses. Two cases were diagnosed during seroconversion. 12 cases had AIDS-defining illnesses. Four contacts were tested HIV positive. Twenty-five out of 28 alive patients are on ART. This is the first national policy of a routine opt-out HIV in medical admission units in the MENA region. Our experience showed that, even in low HIV prevalence and high HIV stigma settings, this policy is feasible, acceptable, and effective.

Molecular xenomonitoring as an indicator of microfilaraemia prevalence for lymphatic filariasis in Samoa in 2019

BackgroundLymphatic filariasis (LF) is a globally significant, vector-borne, neglected tropical disease that can result in severe morbidity and disability. As the World Health Organization (WHO) Global Programme to Eliminate Lymphatic Filariasis makes progress towards LF elimination, there is greater need to develop sensitive strategies for post-intervention surveillance. Molecular xenomonitoring (MX), the detection of pathogen DNA in vectors, may provide a sensitive complement to traditional human-based surveillance techniques, including detection of circulating filarial antigen and microfilaraemia (Mf). This study aims to explore the relationship between human Mf prevalence and the prevalence of polymerase chain reaction (PCR)-positive mosquitoes using MX.MethodsThis study compared Mf and MX results from a 2019 community-based survey conducted in 35 primary sampling units (PSUs) in Samoa. This study also investigated concordance between presence and absence of PCR-positive mosquitoes and Mf-positive participants at the PSU level, and calculated sensitivity and negative predictive values for each indicator using presence of any Mf-positive infection in humans or PCR-positive mosquitoes as a reference. Correlation between prevalence of filarial DNA in mosquitoes and Mf in humans was estimated at the PSU and household/trap level using mixed-effect Bayesian multilevel regression analysis.ResultsMf-positive individuals were identified in less than half of PSUs in which PCR-positive mosquito pools were present (13 of 28 PSUs). Prevalence of PCR-positive mosquitoes (each species separately) was positively correlated with Mf prevalence in humans at the PSU level. Analysed at the species level, only Aedes polynesiensis demonstrated strong evidence of positive correlation (r) with human Mf prevalence at both PSU (r: 0.5, 95% CrI 0.1–0.8) and trap/household levels (r: 0.6, 95% CrI 0.2–0.9).ConclusionsFindings from this study demonstrate that MX can be a sensitive surveillance method for identifying residual infection in low Mf prevalence settings. MX identified more locations with signals of transmission than Mf-testing. Strong correlation between estimated PCR-positive mosquitoes in the primary vector species and Mf in humans at small spatial scales demonstrates the utility of MX as an indicator for LF prevalence in Samoa and similar settings. Further investigation is needed to develop MX guidelines to strengthen the ability of MX to inform operational decisions.Graphical abstract

Bayesian interpretation of likelihood ratios in clinical diagnosis and public health

Purpose of review This study provides a Bayesian interpretation of likelihood ratios and their role in updating the pretest probability of disease, typically represented by the prevalence, to a posttest probability. Recent findings We highlight the importance of likelihood ratios in this process, particularly in low prevalence settings. For example, we demonstrate that a high LR+ can significantly increase the posttest probability of disease, providing crucial information for clinical decision-making. Furthermore, we emphasize the significance of the fold increase in the probability of disease given a positive test result, particularly in low prevalence settings. Summary This study underscores the importance of considering likelihood ratios on our posttest updated probability of disease and highlights their implications for public health and individual diagnosis. Understanding these factors can enhance the accuracy and effectiveness of diagnostic decision-making, ultimately leading to improved public health outcomes and patient care.

Abbott realtime MTB assay for detecting Mycobacterium tuberculosis complex in respiratory specimens: a cost-benefit analysis.

Molecular screening for Mycobacterium tuberculosis (MTB) can lead to rapid empirical treatment inception and reduce hospitalization time and complementary diagnostic tests. However, in low-prevalence settings, the cost-benefit balance remains controversial due to the high cost. We used a Markov model to perform an economic analysis to evaluate the profit after implementing molecular MTB screening (Period B) compared with conventional culture testing (Period A) in respiratory samples from 7,452 consecutive subjects with presumed tuberculosis (TB). The proportion of positivity was comparable between both periods (P > 0.05), with a total of 2.16 and 1.78 samples/patient requested in periods A and B, respectively (P < 0.001). The mean length of hospital stay was 8.66 days (95%CI: 7.63-9.70) in Period B and 11.51 days (95%CI: 10.15-12.87) in Period A (P = 0.001). The healthcare costs associated with diagnosing patients with presumed TB were reduced by €717.95 per patient with PCR screening. The probability of remaining hospitalized and the need for a greater number of outpatient specialty care visits were the variables with the most weight in the model. Employing PCR as an MTB screening method in a low-prevalence setting may increase the profits to the system.

Second Time's the Charm? Assessing the Sensitivity and Yield of Inpatient Diagnostic Algorithms for Pulmonary Tuberculosis in a Low-Prevalence Setting.

For persons with suspected pulmonary tuberculosis, the guidelines of the Centers for Disease Control and Prevention recommend collecting 3 respiratory specimens 8 to 24 hours apart for acid-fast bacilli (AFB) smear and culture, in addition to 1 nucleic acid amplification test (NAAT). However, data supporting this approach are limited. Our objective was to estimate the performance of 1, 2, or 3 AFB smears with or without NAATs to detect pulmonary tuberculosis in a low-prevalence setting. We conducted a retrospective study of hospitalized persons at 8 Massachusetts acute care facilities who underwent mycobacterial culture on 1 or more respiratory specimens between July 2016 and December 2022. We evaluated percentage positivity and yield on serial AFB smears and NAATs among people with growth of Mycobacterium tuberculosis on mycobacterial cultures. Among 104 participants with culture-confirmed pulmonary tuberculosis, the first AFB smear was positive in 41 cases (39%). A second AFB smear was positive in 11 (22%) of the 49 cases in which it was performed. No third AFB smears were positive following 2 initial negative smears. Of 52 smear-negative cases, 36 had a NAAT performed, leading to 23 additional diagnoses. Overall sensitivity to detect tuberculosis prior to culture positivity was higher in any strategy involving 1 or 2 NAATs (74%-79%), even without AFB smears, as compared with 3 smears alone (60%). Tuberculosis diagnostic testing with 2 AFB smears offered the same yield as 3 AFB smears while potentially reducing laboratory burden and duration of airborne infection isolation. Use of 1 or 2 NAATs increased sensitivity to detect culture-positive pulmonary tuberculosis when added to AFB smear-based diagnostic testing alone.

Clinical validation of RCSMS: A rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva.

Peru's holds the highest COVID death rate per capita worldwide. Key to this outcome is the lack of robust, rapid, and accurate molecular tests to circumvent the elevated costs and logistics of SARS-CoV-2 detection via RT-qPCR. To facilitate massive and timely COVID-19 testing in rural and socioeconomically deprived contexts, we implemented and validated RCSMS, a rapid and sensitive CRISPR-Cas12a test for the molecular detection of SARS-CoV-2 from saliva. RCSMS uses the power of CRISPR-Cas technology and lateral flow strips to easily visualize the presence of SARS-CoV-2 even in laboratories with limited equipment. We show that a low-cost thermochemical treatment with TCEP/EDTA is sufficient to inactivate viral particles and cellular nucleases in saliva, eliminating the need to extract viral RNA with commercial kits, as well as the cumbersome nasopharyngeal swab procedure and the requirement of biosafety level 2 laboratories for molecular analyses. Notably, RCSMS performed outstandingly in a clinical validation done with 352 patients from two hospitals in Lima, detecting as low as 50 viral copies per 10 μl reaction in 40 min, with sensitivity and specificity of 96.5% and 99.0%, respectively, relative to RT-qPCR. The negative and positive predicted values obtained from this field validation indicate that RCSMS can be confidently deployed in both high and low prevalence settings. Like other CRISPR-Cas-based biosensors, RCSMS can be easily reprogrammed for the detection of new SARS-CoV-2 variants. We conclude that RCSMS is a fast, efficient and inexpensive alternative to RT-qPCR for expanding COVID-19 testing capacity in Peru and other low- and middle-income countries with precarious healthcare systems.

Fatigue and vigilance in medical experts detecting breast cancer

An abundance of laboratory-based experiments has described a vigilance decrement of reducing accuracy to detect targets with time on task, but there are few real-world studies, none of which have previously controlled the environment to control for bias. We describe accuracy in clinical practice for 360 experts who examined >1 million women's mammograms for signs of cancer, whilst controlling for potential biases. The vigilance decrement pattern was not observed. Instead, test accuracy improved over time, through a reduction in false alarms and an increase in speed, with no significant change in sensitivity. The multiple-decision model explains why experts miss targets in low prevalence settings through a change in decision threshold and search quit threshold and propose it should be adapted to explain these observed patterns of accuracy with time on task. What is typically thought of as standard and robust research findings in controlled laboratory settings may not directly apply to real-world environments and instead large, controlled studies in relevant environments are needed.

Towards global elimination of lymphatic filariasis: a systematic review of the application of spatial epidemiological methods to enhance surveillance and support elimination programmes

BackgroundIn recent decades, spatial epidemiology has increasingly been used to study neglected tropical diseases (NTDs). Spatial methods are particularly relevant when transmission is strongly driven by sociodemographic and environmental factors,...

Assessment of the clinical and analytical performance of three Seegene Allplex SARS-CoV-2 assays within the VALCOR framework.

The coronavirus disease 2019 (COVID-19) pandemic demonstrated the need for accurate diagnostic testing for the early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the pandemic has ended, accurate assays are still needed to monitor viral spread at national levels and beyond through population and wastewater surveillance. To enhance early detection, SARS-CoV-2 assays should have high diagnostic accuracy and should be validated to assure accurate results. Three distinct SARS-CoV-2 assays were evaluated with clinical samples using the VALCOR (VALidation of SARS-CORona Virus-2 assays) framework, with the TaqPath COVID-19 assay (ThermoFisher Scientific, USA) as a comparator. We evaluated clinical sensitivity, specificity, limit of detection (LOD), and overall concordance between comparator and three index Allplex SARS-CoV-2 assays (Seegene, South Korea): Allplex-SC2, Allplex-SC2Fast (Fast PCR), and Allplex-SC2FabR (SARS-CoV-2/FluA/FluB/respiratory syncytial virus). Analytical performance and LOD of index assays were assessed using a dilution series of three synthetic SARS-CoV-2 sequence reference materials (RMs). Ninety SARS-CoV-2 positives and 90 SARS-CoV-2 negatives were tested. All Allplex assays had 100.0% sensitivity (95%CI = 95.9%-100.0%). Allplex-SC2 and Allplex-SC2Fast assays had 97.8% specificity (95%CI = 92.3%-99.7%) and 98.9% overall concordance [κ = 0.978 (95%CI = 0.947-1.000)]. Allplex-SC2FabR assay showed 100.0% specificity (95%CI = 95.9%-100.0%) and 100.0% overall concordance [κ = 1.000 (95%CI = 1.000-1.000)]. LOD assessment of index assays revealed detection down to 2.61 × 102 copies/mL in clinical samples, while the analytical LOD was 9.00 × 102 copies/mL. In conclusion, the evaluation of the three Seegene Allplex SARS-CoV-2 assays showed high sensitivity and specificity and an overall good assay concordance with the comparator. The assays showed low analytical LOD using RM and even a slightly lower LOD in clinical samples. Non-overlapping target gene sequences between SARS-CoV-2 assays and RMs emphasize the need for aligning targeted sequences of diagnostic assays and RMs.IMPORTANCEThe coronavirus disease 2019 pandemic has a significant impact on global public health, economies, and societies. As shown through the first phases of the pandemic, accurate and timely diagnosis is crucial for disease control, prevention, and monitoring. Though the pandemic phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has concluded, diagnostic assays remain in demand to monitor SARS-CoV-2 at the individual patient level, regionally, and nationally, as well as to remain an infectious disease preparedness instrument to monitor any new SARS-CoV-2 dissemination across borders using population and wastewater surveillance. The anticipation by WHO and central health care policy entities such as the Center for Disease Control, EMA, and multiple national health authorities is that SARS-CoV-2 will reside as an endemic respiratory disease for years to come. The key strategic consideration is hence shifting from combating a pandemic situation with a high number of patients to instead allowing precise diagnostics of suspected patients with the intention of correct management in a low-prevalence setting.

Performance of two SARS-CoV-2 rapid antigen detection tests in resource limited settings, the case of Mali.

While real-time reverse transcription PCR (RT-PCR) is the recommended laboratory method to diagnose severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection, its use in resource limited settings can be difficult to maintain due to high testing demand and shortage of reagents. The aim of this study was to evaluate the performances of Realy Tech™ and Standard Q™ in comparison to RT-PCR in a relatively low COVID-19 prevalence setting, Mali. We conducted a cross-sectional study between January and April 2021 in Bamako and Kati regions to evaluate both rapid tests during a large SARS-CoV-2 prevalence study in Mali. Of the 390 samples tested, the sensitivity and specificity of Realy Tech™ and Standard Q™ were 57.1% (95%CI: 44.1-69.2), 95.8% (95%CI: 93.1-97.5); 61.9% (95%CI: 46.8-75.0), and 94.1% (95%CI: 89.5-96.8) respectively. Using RT-PCR, the global prevalence of SARS-CoV-2 was 14.4% (56/390). In both rapid antigen tests, the performance was better when used in suspected patients compared to positive patients under treatment. Moreover, higher viral loads equivalent to Ct < 25 were associated with better detection rates. While waiting for more complete data, these preliminary studies suggest that Realy Tech™ and Standard Q™ should not be used alone for COVID-19 diagnosis in Mali.

The population structure of vancomycin-resistant and -susceptible Enterococcus faecium in a low-prevalence antimicrobial resistance setting is highly influenced by circulating global hospital-associated clones.

Between 2010 and 2015 the incidence of vancomycin-resistant Enterococcus faecium (VREfm) in Norway increased dramatically. Hence, we selected (1) a random subset of vancomycin-resistant enterococci (VRE) from the Norwegian Surveillance System for Communicable Diseases (2010-15; n=239) and (2) Norwegian vancomycin-susceptible E. faecium (VSEfm) bacteraemia isolates from the national surveillance system for antimicrobial resistance in microbes (2008 and 2014; n=261) for further analysis. Whole-genome sequences were collected for population structure, van gene cluster, mobile genetic element and virulome analysis, as well as antimicrobial susceptibility testing. Comparative genomic and phylogeographical analyses were performed with complete genomes of global E. faecium strains from the National Center for Biotechnology Information (NCBI) (1946-2022; n=272). All Norwegian VREfm and most of the VSEfm clustered with global hospital-associated sequence types (STs) in the phylogenetic subclade A1. The vanB2 subtype carried by chromosomal Tn1549 integrative conjugative elements was the dominant van type. The major Norwegian VREfm cluster types (CTs) were in accordance with concurrent European CTs. The dominant vanB-type VREfm CTs, ST192-CT3/26 and ST117-CT24, were mostly linked to a single hospital in Norway where the clones spread after independent chromosomal acquisition of Tn1549. The less prevalent vanA VRE were associated with more diverse CTs and vanA carrying Inc18 or RepA_N plasmids with toxin-antitoxin systems. Only 5 % of the Norwegian VRE were Enterococcus faecalis, all of which contained vanB. The Norwegian VREfm and VSEfm isolates harboured CT-specific virulence factor (VF) profiles supporting biofilm formation and colonization. The dominant VREfm CTs in general hosted more virulence determinants than VSEfm. The phylogenetic clade B VSEfm isolates (n=21), recently classified as Enterococcus lactis, harboured fewer VFs than E. faecium in general, and particularly subclade A1 isolates. In conclusion, the population structure of Norwegian E. faecium isolates mirrors the globally prevalent clones and particularly concurrent European VREfm/VSEfm CTs. Novel chromosomal acquisition of vanB2 on Tn1549 from the gut microbiota, however, formed a single major hospital VREfm outbreak. Dominant VREfm CTs contained more VFs than VSEfm.

Identification of dynamical changes of rabies transmission under quarantine: Community-based measures towards rabies elimination.

Quarantine has been long used as a public health response to emerging infectious diseases, particularly at the onset of an epidemic when the infected proportion of a population remains identifiable and logistically tractable. In theory, the same logic should apply to low-incidence infections; however, the application and impact of quarantine in low prevalence settings appears less common and lacks a formal analysis. Here, we present a quantitative framework using a series of progressively more biologically realistic models of canine rabies in domestic dogs and from dogs to humans, a suitable example system to characterize dynamical changes under varying levels of dog quarantine. We explicitly incorporate health-seeking behaviour data to inform the modelling of contact-tracing and exclusion of rabies suspect and probable dogs that can be identified through bite-histories of patients presenting at anti-rabies clinics. We find that a temporary quarantine of rabies suspect and probable dogs provides a powerful tool to curtail rabies transmission, especially in settings where optimal vaccination coverage is yet to be achieved, providing a critical stopgap to reduce the number of human and animal deaths due to rabid bites. We conclude that whilst comprehensive measures including sensitive surveillance and large-scale vaccination of dogs will be required to achieve disease elimination and sustained freedom given the persistent risk of rabies re-introductions, quarantine offers a low-cost community driven solution to intersectoral health burden.

Bovine cysticercosis epidemiology and the economic impact of the triceps brachii incision in a South African export abattoir.

Taenia saginata is a zoonotic tapeworm of humans with bovines as its intermediate host (bovine cysticercosis). Traditional meat inspection is the main measure to identify the larval stage in carcasses and prevent human infection, but has a notoriously low sensitivity, especially in low prevalence settings. The legislation in multiple African countries mandates an incision in both triceps brachii muscles to detect the parasite as part of the normal post-mortem inspection, but this has an economic cost and is not universally mandated in other countries. The primary aim of this study was to investigate the epidemiology of bovine cysticercosis at an export abattoir in South Africa and determine the validity and cost of the triceps incision. Risk factors were investigated, and the effect of additional heart incisions on the current inspection. Four incisions were made into the heart in addition to the normal post-mortem inspection in 3353 carcasses. The proportion of positive animals with and without the cardiac and triceps incisions were compared using McNemar's chi-square tests, while risk factors were assessed using binary logistic regression. The economic impact of the triceps incision was estimated using a stochastic economic cost model. Thirty-three positive carcasses were identified for an apparent prevalence of 0.98 % (95 %CI, 0.69-1.36 %), while the true prevalence was estimated at 6.6 % (95 %CI, 4.3-8.8 %). All cysts were confirmed as T. saginata on histopathology with 70 % (95 %CI, 53-83 %) located in the heart. The additional cardiac incisions resulted in the detection of significantly more cases compared to the normal inspection method prevalence of 0.72 % (95 %CI, 0.47-1.05 %; P<0.001). The apparent prevalence of T. saginata when omitting the triceps incision was not significantly lower compared to the prevalence when included in the inspection(P=0.480). External feedlots (OR= 4.17, 95 %CI: 2.04-8.54, P<0.001) and older animals (OR=3.90, 95 %CI: 1.17-13.03, P=0.027) were associated with a positive detection. The current median annual financial cost to the food business operator from the triceps incision was estimated at $30387 (95 %CI: $0-$130696), with the proportion of deboned meat exported identified as the most important factor affecting cost (Spearman's rho=0.853). The identification of risk factors could aid in the development of a more effective risk-based inspection system. The current inspection should be modified to increase exposure of the heart and remove the triceps incisions. The latter should especially be considered given the minimal contribution to cysticercosis detection, the unsupported requirement for its inclusion specifically in Africa, and its economic impact, especially as beef exports increase.

Optimizing HIV case identification: investigating client characteristics predictive of HIV positivity from provider-initiated testing (PITC) in central Kenya

BackgroundRoutine program data indicates positivity rates under 2% from HIV testing services (HTS) at sites supported by Centre for Health Solutions-Kenya in Central Kenya. Achieving the UNAIDS 95:95:95 goals requires continuous identification of people living with HIV in an environment of diminishing resources. We assessed non-clinical and clinical characteristics of persons who tested HIV-positive aimed at improving the process of HTS through Provider-Initiated HIV Testing & Counseling (PITC).MethodsWe conducted a retrospective analysis of routine PITC program data collected between October 2018 and September 2019 from six health facilities located in three counties in central Kenya. Stratification was based on county and facility volume. A multivariable logistic regression model, clustered adjusted for facility using robust standard errors, was used to determine predictors of a positive HIV result.ResultsThe total sample was 80,693 with an overall positivity rate of 1.2%. Most, (65.5%), were female and 6.1% were < 15 years. Most clients, 55,464 (68.7%), had previously tested for HIV. Client characteristics associated with a higher odds of positivity on multivariable analysis included: being female (adjusted odds ratio [aOR] 1.27, 95% confidence interval [CI] (1.03–1.57); adults 15 years and above compared to children < 15 years, divorced and married polygamous compared to married monogamous [aOR 3.98, 95% CI (2.12–7.29) and aOR 2.41 95% CI (1.48–3.94) respectively]; clients testing for the first time compared to repeat testers in less than 12 months [aOR 1.39, 95% CI (1.27–1.51)]. Similarly, repeat testers in more than 12 months compared to repeat testers in less than 12 months [aOR 1.90, 95% CI (1.55–2.32)]; presumptive TB clients compared to those without signs of TB [aOR 16.25, 95% CI (10.63–24.84)]. Clients tested at inpatient departments (IPD) were more likely to get a positive HIV result compared to those tested at outpatient departments (OPD), and other departments.ConclusionsThe study findings highlight client characteristics such as age, marital status, HIV test entry point, first-time test, repeat test after 12 months, and TB status as factors that could influence PITC results and could be used to develop a screening tool to target eligible clients for HTS in low HIV prevalence settings.

Area-Based Sociodemographic Factors Associated with Latent Tuberculosis Infection in a Low-Prevalence Setting.

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.