Low Prevalence Settings Research Articles

QuantiFERON-TB Gold Plus Assay in Patients With Latent vs. Active Tuberculosis in a Low Incidence Setting: Level of IFN-γ, CD4/CD8 Responses, and Release of IL-2, IP-10, and MIG

ObjectivesWe analyzed the results of the QuantiFERON Glod Plus assay (QFT) and cytokine patterns associated with active tuberculosis (ATB) among patients with positive QFT.MethodsA total of 195 patients are QFT-positive, among which 24 had an ATB and 171 had a latent tuberculosis infection (LTBI). Interferon-gamma (IFN-γ) secretion was analyzed relative to interleukin-2 (IL-2), IFN-γ inducible protein or CXCL-10 (IP-10), and monokine induced by IFN-γ or CXCL-9 (MIG) secretion, and then compared between two sets of peptide antigens [tube 1 - cluster of differentiation 4 (CD4+) T cell stimulation; tube 2 - CD4+/CD8+ T cell response].ResultsHigher IFN-γ responses were measured in the ATB group (p = 0.0089). The results showed that there was a lower ratio of tube 1/tube 2 IFN-γ concentrations in the ATB group (p = 0.0009), and a median [interquartile ranges (IQR)] difference between the two sets at −0.82 IU/ml (−1.67 to 0.18) vs. −0.07 IU/ml (−0.035 to 0.11, p < 0.0001) in the ATB group compared to the LTBI group, respectively. In addition, patients with low ratios of IL-2/IFN-γ, IP-10/IFN-γ, and MIG/IFN-γ were much more likely to have ATB.ConclusionHigh levels of IFN-γ secretion, preferential IFN-γ response in tube 2, and lower secretion of IL-2, IP-10, and MIG release relative to IFN-γ secretion were more likely observed in subjects with ATB. These features of T cell response may be helpful in low prevalence settings to suspect ATB in patients tested positive for IFN-γ release assays (IGRA).

Meticillin-resistant Staphylococcus aureus Contact Screening Strategy in a Low Prevalence Setting; a Nested Case-Control Study

SummaryBackgroundThe optimal screening strategy in hospitals to identify secondary cases after contact with a meticillin-resistant Staphylococcus aureus (MRSA) index patient in a low prevalence setting is not well defined. We aimed at identifying factors associated with documented MRSA transmissions.MethodSingle center, retrospective, nested case-control study. We evaluated the screening strategy in our 950 bed tertiary care hospital from 2008 – 2014. Room and ward contacts of MRSA index patients present at time of MRSA identification were screened. We compared characteristics of Staphylococcus aureus Protein A (spa)-type matched contact patients (cases) to negative or spa-type mismatched contact patients (controls).ResultsAmong 270,000 inpatients from 2008 – 2014, 215 MRSA screenings yielded 3013 contact patients, and 6 (0.2%) spa-type matched pairs. We included 225 controls for the nested case-control study. The contact type for the cases was more frequently “same room” and less frequently “same ward” compared with the controls (P = 0.001). Also, exposure time was longer for cases (median of 6 days [IQR 3–9]) than for controls (1 day [0–3], P=0.016).ConclusionThe extensive MRSA screening strategy revealed only few index/contact matches based on spa-typing. Prolonged exposure time and a shared room were significantly associated with MRSA transmission. A targeted screening strategy may be more useful in a low prevalence setting than screening entire wards.

Estimating SARS-CoV-2 Seroprevalence in Canadian Blood Donors, April 2020 to March 2021: Improving Accuracy with Multiple Assays.

ABSTRACTWe have previously used composite reference standards and latent class analysis (LCA) to evaluate the performance of laboratory assays in the presence of tarnished gold standards. Here, we apply these techniques to repeated, cross-sectional study of Canadian blood donors, whose sera underwent parallel testing with four separate SARS-CoV-2 antibody assays. We designed a repeated cross-sectional design with random cross-sectional sampling of all available retention samples (n = 1500/month) for a 12 -month period from April 2020 until March 2021. Each sample was evaluated for SARS-CoV-2 IgG antibodies using four assays an Abbott Architect assay targeting the nucleocapsid antigen (Abbott-NP, Abbott, Chicago IL) and three in-house IgG ELISAs recognizing distinct recombinant viral antigens: full-length spike glycoprotein (Spike), spike glycoprotein receptor binding domain (RBD) and nucleocapsid (NP). We used two analytic approaches to estimate SAR-CoV-2 seroprevalence: a composite reference standard and LCA. Using LCA to estimate true seropositivity status based on the results of the four antibody tests, we estimated that seroprevalence increased from 0.8% (95% CI: 0.5–1.4%) in April 2020 to 6.3% (95% CI: 5.1–7.6%) in March 2021. Our study provides further support for the use of LCA in upcoming public health crises, epidemics, and pandemics when a gold standard assay may not be available or identifiable.IMPORTANCE Here, we describe an approach to estimating seroprevalence in a low prevalence setting when multiple assays are available and yet no known gold standard exists. Because serological studies identify cases through both diagnostic testing and surveillance, and otherwise silent, unrecognized infections, serological data can be used to estimate the true infection fatality ratio of a disease. However, seroprevalence studies rely on assays with imperfect sensitivity and specificity. Seroreversion (loss of antibody response) also occurs over time, and with the advent of vaccination, distinction of antibody response resulting from vaccination as opposed to antibody response due to infection has posed an additional challenge. Our approach indicates that seroprevalence on Canadian blood donors by the end of March 2021was less than 10%. Our study supports the use of latent class analysis in upcoming public health crises, epidemics, and pandemics when a gold standard assay may not be available or identifiable.

Detecting asymptomatic carriage of Plasmodium falciparum in southern Ghana: utility of molecular and serological diagnostic tools

BackgroundAsymptomatic malaria infections can serve as potential reservoirs for malaria transmission. The density of parasites contained in these infections range from microscopic to submicroscopic densities, making the accurate detection of asymptomatic parasite carriage highly dependent on the sensitivity of the tools used for the diagnosis. This study sought to evaluate the sensitivities of a variety of molecular and serological diagnostic tools at determining the prevalence of asymptomatic Plasmodium falciparum parasite infections in two communities with varying malaria parasite prevalence.MethodsWhole blood was collected from 194 afebrile participants aged between 6 and 70 years old living in a high (Obom) and a low (Asutsuare) malaria transmission setting of Ghana. Thick and thin blood smears, HRP2 based malaria rapid diagnostic test (RDT) and filter paper dried blood spots (DBS) were prepared from each blood sample. Genomic DNA was extracted from the remaining blood and used in Plasmodium specific photo-induced electron transfer polymerase chain reaction (PET-PCR) and Nested PCR, whilst the HRP2 antigen content of the DBS was estimated using a bead immunoassay. A comparison of malaria parasite prevalence as determined by each method was performed.ResultsParasite prevalence in the high transmission site of Obom was estimated at 71.4%, 61.9%, 60%, 37.8% and 19.1% by Nested PCR, the HRP2 bead assay, PET-PCR, HRP2-RDT and microscopy respectively. Parasite prevalence in the low transmission site of Asutsuare was estimated at 50.1%, 11.2%, 5.6%, 0% and 2.2% by Nested PCR, the HRP2 bead assay, PET-PCR, RDT and microscopy, respectively. The diagnostic performance of Nested PCR, PET-PCR and the HRP2 bead assay was similar in Obom but in Asutsuare, Nested PCR had a significantly higher sensitivity than PET-PCR and the HRP2 bead assay, which had similar sensitivity.ConclusionsNested PCR exhibited the highest sensitivity by identifying the highest prevalence of asymptomatic P. falciparum in both the high and low parasite prevalence settings. However, parasite prevalence estimated by the HRP2 bead assay and PET-PCR had the highest level of inter-rater agreement relative to all the other tools tested and have the advantage of requiring fewer processing steps relative to Nested PCR and producing quantitative results.

Risk Factors for COVID-19 Positivity in Hospitalized Patients in a Low Prevalence Setting

Risk Factors for COVID-19 Positivity in Hospitalized Patients in a Low Prevalence Setting

In Situ Calibration of Passive Samplers for Viruses in Wastewater

Wastewater surveillance for SARS-CoV-2 RNAhas rapidly developed worldwide. In low-prevalence settings, sampling in sewage networks is proposed to monitor community transmission. Passive samplers are cost-effective and suitable for catchments where autosamplers cannot be operated. This resulted in their pioneering applications in some countries, even though their sampling kinetics for viruses remains unclear. We conducted in situ calibration of passive sampling materials (membranes, swabs, gauzes, and tampons) for the uptake of pepper mild mottle virus (PMMoV), enterovirus, and human adenovirus 40/41. Passive samplers were deployed in wastewater influent and retrieved sequentially over 48 h. Membranes performed continuous sampling over 48 h with estimated linear sampling rates of 1 mL h–1 for PMMoV, 0.3 mL h–1 for enterovirus, and 33.1 mL h–1 for adenovirus. Tampons and swabs showed a rapid initial uptake of viruses and reached equilibrium after 8 h, while gauze uptake rates were potentially confounded by either inhibitors or viral losses during extended exposure. Additionally, monitoring SARS-CoV-2 at 17 sewer manholes showed that the detection ratio of membranes (14 of 17) was higher than that of tampons (8 of 17). This study demonstrated the ability of passive samplers to retain viral fragments, making them a practical tool for wastewater surveillance for the detection of disease outbreaks in communities.

Effect of chronic kidney disease on all-cause mortality in tuberculosis disease: an Australian cohort study

BackgroundWhile there has been a recent epidemiological and clinical focus on the interaction between diabetes and tuberculosis, the interaction between chronic kidney disease and tuberculosis has been less studied. In particular, little is known of the effect of eGFR levels well above that seen in end stage kidney disease on mortality.MethodsWe conducted a retrospective cohort study of 653 adults from a large Australian hospital network, using data from a state-wide registry of reported tuberculosis cases between 2010 and 2018, with ascertainment of diabetes status and renal function data from hospital medical records and laboratory data. Cox proportional hazards regression models were used to calculate hazard ratios for all-cause mortality associated with categories of chronic kidney disease in adults with tuberculosis disease.ResultsTotal number of deaths was 25 (3.8%). Compared to tuberculosis cases with eGFR ≥ 60 ml/min, all-cause mortality was higher for those with chronic kidney disease from an eGFR level of 45 ml/min. The association was independent of sex, age and diabetes status with adjusted hazard ratio of 4.6 (95% CI: 1.5, 14.4) for eGFR 30–44 ml/min and 8.3 (95% CI: 2.9, 23.7) for eGFR < 30 ml/min.ConclusionsOur results suggest a notably increased risk of all-cause mortality even in those with more moderate degrees of renal impairment, in a low tuberculosis prevalence setting. The impact of these findings on a population basis are at least as significant as that found with diabetes and warrant further investigation in populations with higher tuberculosis prevalence.

Diagnostic Accuracy of Abbreviated Bi-Parametric MRI (a-bpMRI) for Prostate Cancer Detection and Screening: A Multi-Reader Study.

(1) Background: There is currently limited evidence on the diagnostic accuracy of abbreviated biparametric MRI (a-bpMRI) protocols for prostate cancer (PCa) detection and screening. In the present study, we aim to investigate the performance of a-bpMRI among multiple readers and its potential application to an imaging-based screening setting. (2) Methods: A total of 151 men who underwent 3T multiparametric MRI (mpMRI) of the prostate and transperineal template prostate mapping biopsies were retrospectively selected. Corresponding bpMRI (multiplanar T2WI, DWI, ADC maps) and a-bpMRI (axial T2WI and b 2000 s/mm2 DWI only) dataset were derived from mpMRI. Three experienced radiologists scored a-bpMRI, standard biparametric MRI (bpMRI) and mpMRI in separate sessions. Diagnostic accuracy and interreader agreement of a-bpMRI was tested for different positivity thresholds and compared to bpMRI and mpMRI. Predictive values of a-bpMRI were computed for lower levels of PCa prevalence to simulate a screening setting. The primary definition of clinically significant PCa (csPCa) was Gleason ≥ 4 + 3, or cancer core length ≥ 6 mm. (3) Results: The median age was 62 years, the median PSA was 6.8 ng/mL, and the csPCa prevalence was 40%. Using a cut off of MRI score ≥ 3, the sensitivity and specificity of a-bpMRI were 92% and 48%, respectively. There was no significant difference in sensitivity compared to bpMRI and mpMRI. Interreader agreement of a-bpMRI was moderate (AC1 0.58). For a low prevalence of csPCa (e.g., <10%), higher cut offs (MRI score ≥ 4) yield a more favourable balance between the predictive values and positivity rate of MRI. (4) Conclusion: Abbreviated bpMRI protocols could match the diagnostic accuracy of bpMRI and mpMRI for the detection of csPCa. If a-bpMRI is used in low-prevalence settings, higher cut-offs for MRI positivity should be prioritised.

Optimal strategies to screen health care workers for COVID-19 in the US: a cost-effectiveness analysis

BackgroundTransmission of SARS-CoV-2 in health care facilities poses a challenge against pandemic control. Health care workers (HCWs) have frequent and high-risk interactions with COVID-19 patients. We undertook a cost-effectiveness analysis to determine optimal testing strategies for screening HCWs to inform strategic decision-making in health care settings.MethodsWe modeled the number of new infections, quality-adjusted life years lost, and net costs related to six testing strategies including no test. We applied our model to four strata of HCWs, defined by the presence and timing of symptoms. We conducted sensitivity analyses to account for uncertainty in inputs.ResultsWhen screening recently symptomatic HCWs, conducting only a PCR test is preferable; it saves costs and improves health outcomes in the first week post-symptom onset, and costs $83,000 per quality-adjusted life year gained in the second week post-symptom onset. When screening HCWs in the late clinical disease stage, none of the testing approaches is cost-effective and thus no testing is preferable, yielding $11 and 0.003 new infections per 10 HCWs. For screening asymptomatic HCWs, antigen testing is preferable to PCR testing due to its lower cost.ConclusionsBoth PCR and antigen testing are beneficial strategies to identify infected HCWs and reduce transmission of SARS-CoV-2 in health care settings. IgG tests’ value depends on test timing and immunity characteristics, however it is not cost-effective in a low prevalence setting. As the context of the pandemic evolves, our study provides insight to health-care decision makers to keep the health care workforce safe and transmissions low.

Western Australian adolescent emotional wellbeing during the COVID-19 pandemic in 2020

BackgroundThe impacts of the COVID-19 pandemic have been vast and are not limited to physical health. Many adolescents have experienced disruptions to daily life, including changes in their school routine and family’s financial or emotional security, potentially impacting their emotional wellbeing. In low COVID-19 prevalence settings, the impact of isolation has been mitigated for most young people through continued face-to-face schooling, yet there may still be significant impacts on their wellbeing that could be attributed to the pandemic.MethodsWe report on data from 32,849 surveys from Year 7–12 students in 40 schools over two 2020 survey cycles (June/July: 19,240; October: 13,609), drawn from a study of 79 primary and secondary schools across Western Australia, Australia. The Child Health Utility Index (CHU9D) was used to measure difficulties and distress in responding secondary school students only. Using comparable Australian data collected six years prior to the pandemic, the CHU9D was calibrated against the Kessler-10 to establish a reliable threshold for CHU9D-rated distress.ResultsCompared to 14% of responding 12–18-year-olds in 2013/2014, in both 2020 survey cycles almost 40% of secondary students returned a CHU9D score above a threshold indicative of elevated difficulties and distress. Student distress increased significantly between June and October 2020. Female students, those in older Grades, those with few friendships or perceived poor quality friendships, and those with poor connectedness to school were more likely to score above the threshold.ConclusionsIn a large dataset collected during the first year of the COVID-19 pandemic, the proportion of secondary school students with scores indicative of difficulties and distress was substantially higher than a 2013/2014 benchmark, and distress increased as the pandemic progressed, despite the low local prevalence of COVID-19. This may indicate a general decline in social and emotional wellbeing exacerbated by the events of the pandemic.Trial registration: ANZCTRN (ACTRN12620000922976). Retrospectively registered 17/08/2020. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380429&isReview=true.

Sensitivity of wastewater-based epidemiology for detection of SARS-CoV-2 RNA in a low prevalence setting

To assist public health responses to COVID-19, wastewater-based epidemiology (WBE) is being utilised internationally to monitor SARS-CoV-2 infections at the community level. However, questions remain regarding the sensitivity of WBE and its use in low prevalence settings. In this study, we estimated the total number of COVID-19 cases required for detection of SARS-CoV-2 RNA in wastewater. To do this, we leveraged a unique situation where, over a 4-month period, all symptomatic and asymptomatic cases, in a population of approximately 120,000, were precisely known and mainly located in a single managed isolation and quarantine facility (MIQF) building. From 9 July to 6 November 2020, 24-hr composite wastewater samples (n = 113) were collected daily from the sewer outside the MIQF, and from the municipal wastewater treatment plant (WWTP) located 5 km downstream. New daily COVID-19 cases at the MIQF ranged from 0 to 17, and for most of the study period there were no cases outside the MIQF identified. SARS-CoV-2 RNA was detected in 54.0% (61/113) at the WWTP, compared to 95.6% (108/113) at the MIQF. We used logistic regression to estimate the shedding of SARS-CoV-2 RNA into wastewater based on four infectious shedding models. With a total of 5 and 10 COVID-19 infectious cases per 100,000 population (0.005% and 0.01% prevalence) the predicated probability of SARS-CoV-2 RNA detection at the WWTP was estimated to be 28 and 41%, respectively. When a proportional shedding model was used, this increased to 58% and 87% for 5 and 10 cases, respectively. In other words, when 10 individuals were actively shedding SARS-CoV-2 RNA in a catchment of 100,000 individuals, there was a high likelihood of detecting viral RNA in wastewater. SARS-CoV-2 RNA detections at the WWTP were associated with increasing COVID-19 cases. Our results show that WBE provides a reliable and sensitive platform for detecting infections at the community scale, even when case prevalence is low, and can be of use as an early warning system for community outbreaks.

Coronavirus disease 2019 (COVID-19) polymerase chain reaction (PCR) screening of asymptomatic healthcare workers in a low-prevalence setting: A single-center UK cohort study.

In this cohort study of UK healthcare workers, we evaluated the use of fortnightly polymerase chain reaction (PCR) screening to facilitate the safe resumption of elective surgery in a low-prevalence setting. We found that adherence to serial testing was poor, and the resource required to identify 1 asymptomatic case was substantial.

Evaluation of a Two-Test Strategy for HIV Screening in a Low-Prevalence Setting and the Indications for Optimizing Clinical Management

Evaluation of a Two-Test Strategy for HIV Screening in a Low-Prevalence Setting and the Indications for Optimizing Clinical Management

Assessment of latent tuberculosis infection pre-immunomodulatory therapy; 5 year experience in a UK centre

• A 5 year retrospective review of 367 LTBI referrals to a UK TB service. • 51% were referred pre-immunomodulatory therapy with 25 different agents. • They were older and had more negative & indeterminate screening IGRAs than ‘traditional’ LTBI referrals. • 57% either didn’t initiate or couldn’t complete chemoprophylaxis. An ever greater variety of immunomodulatory agents with potential to reactivate latent TB infection are being used in clinical practice. We set out to describe the experience of assessing and mitigating TB reactivation risk for patients planning to start immunomodulatory biological or small molecule inhibitor (SMI) therapies referred to a TB service in a high income low TB prevalence setting. Retrospective clinical case note review of patients referred to the infectious diseases TB service of Sheffield Teaching Hospitals following LTBI screening between 1 September 2015 and 30 September 2020. 367 patients had been referred and assessed. 179 patients referred for new entrant or contact screening and 188 (51%) patients were being worked up pre-immunomodulatory therapy with 25 different biologic/SMIs for more than 20 conditions. This group were older (median age 56.2 vs 32.6 years, p < 0.0001), and more likely to have had a negative or indeterminate screening IGRA (25.5% vs 4.1%, p < 0.0001). 155/188 were diagnosed with LTBI, of whom 58% commenced chemoprophylaxis (50 isoniazid, 40 rifampicin/isoniazid) and they were significantly younger than those who did not (median age 48.7 vs 70.6 years, p = 0.0004). 75% completed chemoprophylaxis with 7% stopping early due to altered liver function tests and 10% due to other adverse effects. No differences were observed between isoniazid or rifampicin/isoniazid treated groups. Increased age, less reliable screening IGRAs and adverse effects of chemoprophylaxis in the face of a widening variety of agents make management of LTBI in patients pre-immunomodulatory therapy complex. Better tests and treatments are required.

Laboratory-based testing for hepatitis C infection using dried blood spot samples: A systematic review and meta-analysis of diagnostic accuracy.

The use of dried blood spot (DBS) samples can facilitate the implementation of reflex testing by circumventing the need for centrifugation and freezing of venous blood samples. This systematic review assessed the accuracy of using DBS samples to diagnose chronic hepatitis C virus (HCV) infection. A comprehensive search was undertaken to identify articles published up to July 2020 evaluating the diagnostic accuracy of anti-HCV, HCV-RNA and HCV core antigen tests using DBS. Screening, data extraction, quality appraisal and Grading of Recommendations, Assessment, Development and Evaluations certainty of the evidence assessment were performed independently by two reviewers. Meta-analysis, meta-regression and sensitivity analyses were conducted. The evidence demonstrates that laboratory-based anti-HCV and HCV-RNA tests using DBS samples have high diagnostic accuracy. All comparisons were between DBS and venous samples. For the detection of anti-HCV, sensitivity was 95% (95% CI: 92%-97%) and specificity was 99% ([95% CI: 98%-99%]; n=25; I2 =81%; moderate certainty). For the detection of HCV-RNA, the sensitivity was 95% (95% CI: 93%-97%) and specificity was 97% ([95% CI: 94%-98%]; n=20; I2 =52%; moderate certainty). The sensitivity of HCV core antigen tests was 86% (95% CI: 79%-91%) and specificity was 98% ([95% CI: 94%-99%]; n=5; I2 =37%; low certainty) compared with HCV-RNA (the gold standard for detecting chronic HCV). DBS samples could facilitate diagnosis of chronic HCV infection as the necessary sequential tests (anti-HCV and then HCV-RNA or HCV core antigen) can be undertaken using the same blood sample. This could reduce loss of patient follow-up and support international efforts towards HCV elimination in both high and low prevalence settings.

Disease Prevalence Matters: Challenge for SARS-CoV-2 Testing.

While sensitivity and specificity are important characteristics for any diagnostic test, the influence of prevalence is equally, if not more, important when such tests are used in community screening. We review the concepts of positive/negative predictive values (PPV/NPV) and how disease prevalence affects false positive/negative rates. In low-prevalence situations, the PPV decreases drastically. We demonstrate how using two tests in an orthogonal fashion can be especially beneficial in low-prevalence settings and greatly improve the PPV of the diagnostic test results.

Performance evaluation and optimized reporting workflow for HIV diagnostic screening and confirmatory tests in a low prevalence setting.

Our institution utilizes an antigen/antibody screening test followed by a confirmatory antibody assay for preliminary positive results. Given the low prevalence for HIV infections in our institution's county, we suspect that a substantial portion of the reactive screens are false positives. We aimed to characterize the false positivity rate of the HIV screening test performed at Stanford Health Care. In parallel, we modified our reporting workflow to release both the screening and confirmatory results simultaneously to mitigate the stress of a presumptive positive test. We reviewed 45,296 eligible HIV screen specimens that underwent the Abbott ARCHITECT™ 4th generation HIV antigen/antibody combination assay between August 5, 2016 and March 16, 2021. Final sample signal/cutoff (S/CO) ratios ≥ 1 were deemed positive, which triggers a reflex order for the confirmatory Bio-Rad Geenius™ HIV 1/2 Supplemental Assay. Additional chart review was performed for positive screen cases with negative or indeterminate confirmatory results. Our institution demonstrated a 0.28% (128/45,296) positive screen rate, with 12.5% (16/128) of these samples confirmed as false positives based on a negative HIV-1 RNA test. Median S/CO ratios of true positive screens were significantly higher than those with negative or indeterminate confirmatory tests (602.27vs 2.98; p=0.0000323). We implemented a new synchronized reporting system for positive screens, which co-releases screen and confirmatory reports without compromise in the overall turnaround time. Our study demonstrates a relatively high percentage of false positive screens. Subsequently, by providing a more complete picture up front, our new reporting pipeline may reduce anxiety of a stand-alone positive screen and optimize downstream clinical decision-making.

Community-based point-of-care testing to identify new HIV infections: A cross-sectional study from Pune, India.

The World Health Organization recommends point-of-care testing (POCT) to detect human immunodeficiency virus (HIV) infected individuals in the community. This will help improve treatment coverage through detection of HIV infection among those who are unaware of their status.This study was planned with an objective to investigate the feasibility and acceptability of POCT for HIV in the community.A community-based cross-sectional study was conducted in rural and peri-urban areas of Pune, India. These sites were selected based on the distance from the nearest HIV testing center. Testing locations were identified in consultation with the local stakeholders and grass-root health workers to identify and capture the priority population. The POCT was performed on blood samples collected by the finger-prick method.The proportion of participants seeking HIV tests for the first time was 79.6% that signifies the feasibility of POCT. The acceptability in the peri-urban and rural areas was 70.2% and 69.7%, respectively. POCT was performed at construction sites (24.9%), nearby industries (16.1%) and parking areas of long-distance trucks (8.1%) in the peri-urban area. Three newly diagnosed HIV-infected participants (0.1%) were detected from the peri-urban areas but none from the rural areas. Two of the newly diagnosed participants and their spouses were linked to care.There was a high acceptability of POCT and wider coverage of priority population with a strategy of testing at places preferable to the study population. Therefore, we believe that community-based POCT is a promising tool for improving HIV testing coverage even in low prevalence settings with the concentrated HIV epidemic.

Diagnostics to support elimination of lymphatic filariasis-Development of two target product profiles.

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools.

Antibiotic resistance genes of emerging concern in municipal and hospital wastewater from a major Swedish city

The spread of antibiotic resistance among bacterial pathogens is to a large extent mediated by mobile antibiotic resistance genes (ARGs). The prevalence and geographic distribution of several newly discovered ARGs, as well as some clinically important ARGs conferring resistance to last resort antibiotics, are largely unknown. Targeted analysis of wastewater samples could allow estimations of carriage in the population connected to the sewers as well as release to the environment. Here we quantified ARGs conferring resistance to linezolid (optrA and cfr(A)) and colistin (mcr-1, -2, -3, -4 and -5) and the recently discovered gar (aminoglycoside ARG) and sul4 (sulphonamide ARG) in raw hospital and municipal wastewater as well as treated municipal wastewater during five years in a low antibiotic resistance prevalence setting (Gothenburg, Sweden). Additionally, variations in bacterial composition of the wastewaters characterized by 16S rRNA sequencing were related to the variations of the ARGs in an attempt to reveal if the presence of known or suspected bacterial host taxa could explain the presence of the ARGs in wastewater. The mcr-1, mcr-3, mcr-4, mcr-5, sul4 and gar genes were detected regularly in all types of wastewater samples while optrA and cfr(A) were detected only in hospital wastewater. The most abundant genes were mcr-3 and mcr-5, especially in municipal wastewater. The detection of optrA was restricted to a peak during one year. Most of the ARGs correlated with taxa previously described as bacterial hosts and associated with humans. Although some of the tentative hosts may include bacteria also thriving in wastewater environments, detection of the ARGs in the wastewaters could reflect their presence in the gut flora of the contributing populations. If so, they could already today or in the near future hinder treatment of bacterial infections in a setting where they currently are rarely targeted/detected during clinical surveillance.