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Background: Most Chinese blood centers have implemented mini pool (MP) HBV nucleic acid testing (NAT) together with HBsAg ELISA in routine blood donor screening for HBV infection since 2015, and a few centers upgraded MP to individual donation (ID) NAT screening recently, raising urgent need for cost-benefit analysis of different screening strategies. In an effort to prevent transfusion-transmitted infections (TTIs) for HBV, cost-benefit analyses of three different screening strategies: HBsAg alone, HBsAg plus MP NAT and HBsAg plus ID NAT were performed in blood donors from southern China where HBV infection was endemic., Methods: MP-6 HBV NAT and ID NAT were adopted in parallel to screen blood donors for further comparative analysis. On the basis of screening data and the documented parameters, the number of window period (WP) infection, HBV acute infection, chronic hepatitis B infection (CHB) and occult hepatitis B infection (OBI) was evaluated, and the potential prevented HBV TTIs and benefits of these three strategies were predicted based on cost-benefit analysis by an estimation model., Results: Of 132,323 donations, the yield rate for HBsAg-/DNA + screened by ID NAT (0.12%) was significantly higher than that by MP NAT (0.058%, P < 0.05). Furthermore, the predicted transfusion-transmitted HBV cases prevented was 1.25 times more by ID NAT compared to MP-6 NAT. The cost-benefit ratio of the universal HBsAg screening, HBsAg plus ID NAT and HBsAg plus MP NAT were 1:58, 1:27 and 1:22, respectively., Conclusions: Universal HBsAg ELISA screening in combination with HBV ID NAT or MP-6 NAT strategies was highly cost effective in China. To further improve blood safety, HBsAg plus HBV DNA ID NAT screening should be considered in HBV endemic regions/countries., (© 2024. The Author(s).)

The rational laboratory use and implementation of test ordering procedures aim to reduce unnecessary test requests. This study aimed to determine the financial burden caused by inappropriate serological test requests for viral hepatitis and to investigate physicians' reasons for making unnecessary test requests. We performed a retrospective evaluation of inappropriate requests for hepatitis serology testing and the financial burden they caused at a tertiary care hospital over a 1-year period. The study found 2183 (3.84%) inappropriate test requests, costing $3309.00. Of these, 357 were same-day repeat requests and 1826 were requests not following diagnostic algorithms. In the logistic regression analysis of the factors affecting unnecessary test requests, a statistically significant difference was found between whether the unit was internal or surgical, whether the request came from inpatient services or outpatient clinics, and the professional titles (P < .05). Both types of inappropriate requests were more common among male physicians (P < .05). The highest rates of inappropriate test requesting were in physical therapy and rehabilitation, pediatrics, and adult emergency units. To identify the reasons behind unnecessary test requests, 135 physicians from 23 different departments participated in the survey. The main reasons for requesting tests were identified as protecting against malpractice and fears of misdiagnosis or overlooking a diagnosis. It has been observed that physicians often order tests routinely, without being fully familiar with standard test ordering procedures based on diagnostic algorithms, and lacking knowledge about rational laboratory use. The cost of tests is mostly unknown to clinicians. The study concludes that there are laboratory tests that incur much higher costs. When this assessment is applied to the entire laboratory, it becomes clear how significant a financial burden, unnecessary workload, and loss of time this situation can cause. Identifying the presence of unnecessary test requests is the first step in preventing them. Appropriate measures include highlighting these issues, providing necessary information, and offering in-service training., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives: Taiwan is among the few hepatitis B virus (HBV) high-endemic countries that implement universal mini-pool nucleic acid testing (MP-NAT) and hepatitis B surface antigen (HBsAg) testing together with confirmatory individual donor nucleic acid testing (ID-NAT) for its blood supply since 2013. The aim of this study was to reappraise the value of HBsAg test in Taiwan's HBV testing strategy., Materials and Methods: A Markov model was constructed, and cost-effectiveness analysis was conducted in order to reappraise the existing HBV screening strategy in Taiwan., Results: The incremental cost-effectiveness ratio (ICER) for the current testing strategy in Taiwan was estimated to be $US 443 154 per quality-adjusted life year (QALY) gained. This is almost six times the willingness-to-pay (WTP) threshold that reflects local preferences., Conclusion: Universal HBsAg and MP-8-NAT together with confirmatory ID-NAT testing prevents a significant amount of HBV infections from entering the Taiwan blood supply. However, this comes at a disproportionate increase in cost., (© 2020 International Society of Blood Transfusion.)

The control of brucellosis across sub-Saharan Africa is hampered by the lack of standardized testing and the use of tests with poor performance. This study evaluated the performance and costs of serological assays for human brucellosis in a pastoralist community in northern Tanzania. Serum collected from 218 febrile hospital patients was used to evaluate the performance of seven index tests, selected based on international recommendation or current use. We evaluated the Rose Bengal test (RBT) using two protocols, four commercial agglutination tests and a competitive enzyme-linked immunosorbent assay (cELISA). The sensitivity, specificity, positive predictive value, negative predictive value, Youden's index, diagnostic accuracy, and per-sample cost of each index test were estimated. The diagnostic accuracy estimates ranged from 95.9 to 97.7% for the RBT, 55.0 to 72.0% for the commercial plate tests, and 89.4% for the cELISA. The per-sample cost range was $0.69-$0.79 for the RBT, $1.03-$1.14 for the commercial plate tests, and $2.51 for the cELISA. The widely used commercial plate tests performed poorly and cost more than the RBT. These findings provide evidence for the public health value of discontinuing the use of commercial agglutination tests for human brucellosis in Tanzania.

Trypanosoma cruzi, the protozoan agent of Chagas' disease, displays a complex population structure made up of multiple strains showing a diverse ecoepidemiological distribution. Parasite genetic variability may be associated with disease outcome, hence stressing the need to develop methods for T. cruzi typing in vivo. Serological typing methods that exploit the presence of host antibodies raised against polymorphic parasite antigens emerge as an appealing approach to address this issue. These techniques are robust, simple, cost-effective, and are not curtailed by methodological/biological limitations intrinsic to available genotyping methods. Here, we critically assess the progress towards T. cruzi serotyping and discuss the opportunity provided by high-throughput immunomics to improve this field., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The opioid epidemic has been associated with an increase in hepatitis C virus (HCV) infections. Federally qualified health centers (FQHCs) have a high burden of hepatitis C disease and could serve as venues to enhance testing and treatment., Methods: We estimated clinical outcomes and the cost-effectiveness of hepatitis C testing and treatment at US FQHCs using individual-based simulation modeling. We used individual-level data from 57 FQHCs to model 9 strategies, including permutations of HCV antibody testing modality, person initiating testing, and testing approach. Outcomes included life expectancy, quality-adjusted life-years (QALY), hepatitis C cases identified, treated and cured; and incremental cost-effectiveness ratios., Results: Compared with current practice (risk-based with laboratory-based testing), routine rapid point-of-care testing initiated and performed by a counselor identified 68% more cases after (nonreflex) RNA testing in the first month of the intervention and led to a 17% reduction in cirrhosis cases and a 22% reduction in liver deaths among those with cirrhosis over a lifetime. Routine rapid testing initiated by a counselor or a clinician provided better outcomes at either lower total cost or at lower cost per QALY gained, when compared with all other strategies. Findings were most influenced by the proportion of patients informed of their anti-HCV test results., Conclusions: Routine anti-HCV testing followed by prompt RNA testing for positives is recommended at FQHCs to identify infections. If using dedicated staff or point-of-care testing is not feasible, then measures to improve immediate patient knowledge of antibody status should be considered., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Human visceral leishmaniasis (VL) is a severe and potentially fatal parasitic disease if not correctly diagnosed and treated. Brazil is one of the three countries most endemic for VL and, like most countries affected by this disease, has a large budget constraint for the incorporation of new health technologies. Although different diagnostic tests for VL are currently available in the country, economic studies evaluating diagnostic kits are scarce. The objective of this study was to conduct a cost-effectiveness analysis of the nine available diagnostic tests for human VL in HIV-infected and uninfected patients in Brazil. The perspective of analysis was the Brazilian public health system, and the outcome of interest was "cases diagnosed correctly". The costs of the tests were estimated using the microcosting technique, and comparisons were performed with decision trees. Sensitivity analyses were explored applying variations in cost and effectiveness values. For VL diagnosis among HIV-uninfected patients, using blood samples for the rapid tests (RDTs), the noncommercial direct agglutination test (DAT-LPC) and IT-LEISH were cost-effective tests compared with the baseline OnSite test, but they presented different incremental cost-effectiveness ratios (ICER) of US$7.04 and US$ 205.40, respectively. Among HIV-infected patients, DAT-LPC was the most cost-effective diagnostic test. Comparisons among the tests with the same methodology, based on the low ICER values, revealed that IT-LEISH was the most cost-effective test among the RDTs and the Ridascreen Leishmania Ab among the ELISA tests. These results confirm that cost-effectiveness analyses can provide useful information to support the incorporation of new health technologies within a known scenario and willingness to pay threshold. It was observed that tests based on the same methodologies presented different cost-effectiveness ratios for the same group of patients and that different tests should be recommended for different patient groups. DAT-LPC was an important cost-effective strategy for all patients, requiring minimum laboratorial infrastructure, and IT-LEISH was the cost-effective test for VL screening in HIV-uninfected patients. IT-LEISH and DAT-LPC have complementary profiles and should both be provided by the Brazilian health system., Competing Interests: The authors have declared that no competing interests exist.

Background: This study compares venepuncture versus point-of-care (POC) HBsAg tests on screening cost and linkage to care in prospective outreach screenings in an Asian population in three major cities in Belgium between 10/2014 and 5/2018., Methods: Two community outreach screening programs were organised between 10/2014 and 5/2018. The first screening program used venepuncture and serologic testing for HBsAg. In the second program, HBsAg was tested in finger stick blood POC tests. Positive results were confirmed during outpatient visits with serologic testing. Linkage to care was defined as having received specialist care follow-up with at least one abdominal ultrasound within three months of screening., Results: For 575 participating individuals, 571 valid results were obtained, 456 with venepuncture, and 115 using POC testing. Overall HBsAg seroprevalence was 6.8%. Linkage to care was higher when using POC testing compared to venepuncture (86% or n = 6/7 versus 34% or n = 11/32; p = 0.020). The POC screening program was economically more attractive with a total cost of € 1,461.8 or € 12.7 per person screened compared to € 24,819 or € 54.0 per person screened when using venepuncture testing. Results and an appointment for specialist care follow-up were given onsite with POC testing, while with venepuncture testing; results were sent within 20-45 days., Conclusion: In an Asian migrant population in Belgium with an HBsAg seroprevalence of 6.8%, HBV screening based on POC tests resulted in lower costs per person screened (76.5% lower), and higher linkage to care (2.5 times)., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Background: Despite potentially severe and fatal outcomes, recent studies of solid organ transplant (SOT) recipients in Europe suggest that hepatitis E virus (HEV) infection is underdiagnosed, with a prevalence of active infection of up to 4.4%., Objectives: To determine the cost-effectiveness of introducing routine screening for HEV infection in SOT recipients in the UK., Methods: A Markov cohort model was developed to evaluate the cost-utility of 4 HEV screening options over the lifetime of 1000 SOT recipients. The current baseline of nonsystematic testing was compared with annual screening of all patients by polymerase chain reaction (PCR; strategy A) or HEV-antigen (HEV-Ag) detection (strategy B) and selective screening of patients who have a raised alanine aminotransferase (ALT) value by PCR (strategy C) or HEV-Ag (strategy D). The primary outcome was the incremental cost per quality-adjusted life-year (QALY). We adopted the National Health Service (NHS) perspective and discounted future costs and benefits at 3.5%., Results: At a willingness-to-pay of £20 000/QALY gained, systematic screening of SOT patients by any method (strategy A-D) had a high probability (77.9%) of being cost-effective. Among screening strategies, strategy D is optimal and expected to be cost-saving to the NHS; if only PCR testing strategies are considered, then strategy C becomes cost-effective (£660/QALY). These findings were robust against a wide range of sensitivity and scenario analyses., Conclusions: Our model showed that routine screening for HEV in SOT patients is very likely to be cost-effective in the UK, particularly in patients presenting with an abnormal alanine aminotransferase., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: In the UK, few employers offer general health checks for employees, and opt-in HIV testing is rarely included. There is a need to provide evidence-based guidance and support for employers around health checks and HIV testing in the workplace. An Agile approach was used to develop and evaluate a digital toolkit to facilitate employers' understanding about workplace health screening., Methods: The Test@Work toolkit development included an online survey (STAGE 1: n = 201), stakeholder consultation (STAGE 2: n = 19), expert peer review (STAGE 3: n = 24), and pilot testing (STAGE 4: n = 20). The toolkit includes employer guidance on workplace health promotion, workplace health screening, and confidential opt-in HIV testing with signposting to resources. Pilot testing included assessment of fidelity (delivery and engagement) and implementation qualities (attitudes, resources, practicality, acceptability, usability and cost)., Results: STAGE 1: The vast majority of respondents would consider offering general health checks in the workplace that included confidential opt-in HIV testing, and this view was broadly comparable across organisation types ( n = 201; public: 87.8%; private: 89.7%; third: 87.1%). STAGES 2 and 3: Stakeholders highlighted essential content considerations: (1) inclusion of the business case for workplace health initiatives, (2) clear pathways to employer responsibilities, and (3) presenting HIV-related information alongside other areas of health. With regards presentation, stakeholders proposed that the toolkit should be concise, with clear signposting and be hosted on a trusted portal. STAGE 4: Employers were satisfied with the toolkit content, usability and utility. The toolkit had high fidelity with regards to delivery and employer engagement. Assessment of implementation qualities showed high usability and practicality, with low perceived burden for completion and acceptable cost implications. Very few resource challenges were reported, and the toolkit was considered to be appropriate for any type of organisation, irrespective of size or resources., Conclusions: Employers perceived the Test@Work toolkit to be useful, meaningful and appropriate for their needs. This digital resource could be used to support employers to engage with health screening and opt-in HIV testing within the context of workplace health promotion.

Introduction: HIV testing is an essential prerequisite for accessing treatment with antiretroviral therapy or prevention using pre-exposure prophylaxis. Internet distribution of HIV self-tests is a novel approach, and data on the programmatic cost of this approach are limited. We analyse the costs and cost-effectiveness of a self-testing programme., Methods: Men who have sex with men (MSM) reporting unknown or negative HIV status were enrolled from March to August 2015 into a 12-month trial of HIV self-testing in the United States. Participants were randomly assigned either to the self-testing arm or the control arm. All participants received information on HIV testing services and locations in their community. Self-testing participants received up to four self-tests each quarter, which they could use themselves or distribute to their social network associates. Quarterly follow-up surveys collected testing outcomes, including number of tests used and new HIV diagnoses. Using trial expenditure data, we estimated the cost of implementing a self-testing programme. Primary outcomes of this analysis included total programme implementation costs, cost per self-test completed, cost per person tested, cost per new HIV diagnosis among those self-tested and cost per quality adjusted life year (QALY) saved., Results: A total of 2665 men were assigned either to the self-testing arm (n = 1325) or the control arm (n = 1340). HIV testing was reported by 971 self-testing participants who completed a total of 5368 tests. In the control arm, 619 participants completed 1463 HIV tests. The self-testing participants additionally distributed 2864 self-tests to 2152 social network associates. Testing during the trial identified 59 participants and social network associates with newly diagnosed HIV infection in the self-testing arm; 11 control participants were newly diagnosed with HIV. The implementation cost of the HIV self-testing programme was $449,510. The cost per self-test completed, cost per person tested at least once, and incremental cost per new HIV diagnosis was $61, $145 and $9365 respectively. We estimated that self-testing programme potentially averted 3.34 transmissions, saved 14.86 QALYs and nearly $1.6 million lifetime HIV treatment costs., Conclusions: The HIV self-testing programme identified persons with newly diagnosed HIV infection at low cost, and the programme is cost saving., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Primary care may be an avenue to increase coverage of HIV testing but it is unclear what challenges primary healthcare professionals in low- and middle-income countries face. We describe the HIV testing practices in community health centres (CHCs) and explore the staff's attitude towards further development of HIV testing services at the primary care level in China., Methods: We conducted a national, cross-sectional survey using a stratified random sample of CHCs in 20 cities in 2015. Questionnaires were completed by primary care doctors and nurses in CHCs, and included questions regarding their demographics, clinical experience and their views on the facilitators and barriers to offering HIV testing in their CHC. Multivariate logistic regression was conducted to examine the association between staff who would offer HIV testing and their sociodemographic characteristics., Results: A total of 3580 staff from 158 CHCs participated. Despite the majority (81%) agreeing that HIV testing was an important part of healthcare, only 25% would provide HIV testing when requested by a patient. The majority (71%) were concerned about reimbursement, and half (47%) cited lack of training as a major barrier. Almost half (44%) believed that treating people belonging to high-risk populations would scare other patients away, and 6% openly expressed their dislike of people belonging to high-risk populations. Staff who would offer HIV testing were younger (adjusted odds ratio (aOR) 0.97 per year increase in age, 95% confidence interval (CI):0.97-0.98); trained as a doctor compared to a nurse (aOR 1.79, 95%CI:1.46-2.15); held a bachelor degree or above (aOR 1.34, 95%CI:1.11-1.62); and had previous HIV training (aOR 1.55, 95%CI:1.27-1.89)., Conclusions: Improving HIV training of CHC staff, including addressing stigmatizing attitudes, and improving financial reimbursement may help increase HIV testing coverage in China.

Enteric fever is one of the leading causes of infection and subsequent fatality (greater than 1.8 million) (WHO 2018), especially in the developing countries due to contaminated water and food inter twinned with unhygienic practices. Clinical gold standard technique of culture-based method followed by biochemical tests demand 72+ hours for diagnosis while newly developed techniques (like PCR, RT-PCR, DNA microarray etc.) suffer from high limit of detection or involve high-cost infrastructure or both. In this work, a quick and highly specific method, SMOL was established for simultaneous detection of Salmonella paratyphi A and Salmonella typhi in clinical blood samples. SMOL consists of (i) pre-concentration of S. typhi and S. paratyphi A cells using magnetic nanoparticles followed by (ii) cell lysis and DNA extraction (iii) amplification of select nucleic acids by LAMP technique and (iv) detection of amplified nucleic acids using an affordable portable device (costs less than $70). To identify the viability of target cells at lower concentrations, the samples were processed at two different time periods of t = 0 and t = 4 h. Primers specific for the SPA2539 gene in S. paratyphi A and STY2879 gene in S. typhi were used for LAMP. Within 6 h SMOL was able to detect positive and negative samples from 55 human clinical blood culture samples and detect the viability of the cells. The results were concordant with culture and biochemical tests as well as by qPCR. Statistical power analysis yielded 100%. SMOL results were concordant with culture and biochemical tests as well as by qPCR. The sensitive and affordable system SMOL will be effective for poor resource settings.

Background: Prevention of new HIV infections is a critical public health issue. The highest HIV testing gaps are in men, adolescents 15-19 years old, and adults 40 years and older. Community-based HIV testing services (HTS) can contribute to increased testing coverage and early HIV diagnosis, with HIV self-testing (HIVST) strategies showing promise. Community-based strategies, however, are resource intensive, costly and not widely implemented. A community-led approach to health interventions involves supporting communities to plan and implement solutions to improve their health. This trial aims to determine if community-led delivery of HIVST can improve HIV testing uptake, ART initiation, and broader social outcomes in rural Malawi., Methods: The trial uses a parallel arm, cluster-randomised design with group village heads (GVH) and their defined catchment areas randomised (1:1) to community-led HIVST or continue with the standard of the care (SOC). As part of the intervention, informal community health cadres are supported to plan and implement a seven-day HIVST campaign linked to HIV treatment and prevention. Approximately 12 months after the initial campaign, intervention GVHs are randomised to lead a repeat HIVST campaign. The primary outcome includes the proportion of adolescents 15-19 years old who have tested for HIV in their lifetime. Secondary outcomes include recent testing in adults 40 years and older and men; ART initiation; knowledge of HIV prevention; and HIV testing stigma. Outcomes will be measured through cross-sectional surveys and clinic registers. Economic evaluation will determine the cost per person tested, cost per person diagnosed, and incremental cost effectiveness ratio., Discussion: To the best of our knowledge, this is the first trial to assess the effectiveness of community-led HTS, which has only recently been enabled by the introduction of HIVST. Community-led delivery of HIVST is a promising new strategy for providing periodic HIV testing to support HIV prevention in rural communities. Further, introduction of HIVST through a community-led framework seems particularly apt, with control over healthcare concurrently devolved to individuals and communities., Trial Registration: Clinicaltrials.gov registry ( NCT03541382 ) registered 30 May 2018.

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloantibodies against fetal human platelet antigens (HPAs), mostly caused by anti-HPA-1a. Population-based screening for FNAIT is still a topic of debate. Logistically and financially, the major challenge for implementation is the typing of pregnant women to recognize the 2% HPA-1a-negative women. Therefore, there is need for a high-throughput and low-cost HPA-1a-typing assay., Study Design and Methods: A sandwich ELISA was developed, using a monoclonal anti-GPIIIa as coating antibody and horseradish-peroxidase-conjugated recombinant anti-HPA-1a, as detecting antibody. The ELISA results were compared to an allelic discrimination PCR-assay. In phase I, samples from unselected consecutive pregnant women were tested with both assays. Phase II was part of a prospective screening study in pregnancy and genotyping was restricted to samples with an arbitrary set, OD < 0.500., Results: The ELISA was optimized to require no additional handling (swirling or spinning) of stored tubes. During phase I, 506 samples were tested. In phase II, another 62,171 consecutive samples were phenotyped, with supportive genotyping in 1,902. In total 1,585 HPA-1a negative and 823 HPA-1a positive women were genotyped. The assay reached 100% sensitivity with a cut-off OD from 0.160, corresponding with a 99.9% specificity and a false-HPA-1a negative rate of 0.03., Conclusion: A high-throughput, low-cost, and reliable HPA-1a phenotyping assay was developed which can be used in population-based screening to select samples for testing of presence of anti-HPA-1a. Because plasma from tubes of 3- to 6-days-old samples can be used, this assay is applicable to settings with suboptimal conditions., (© 2019 AABB.)

The tetravalent dengue vaccine CYD-TDV (Dengvaxia) is the first licensed vaccine against dengue, but recent findings indicate an elevated risk of severe disease among vaccinees without prior dengue virus (DENV) exposure. The World Health Organization currently recommends CYD-TDV only for individuals with serological confirmation of past DENV exposure. Our objective was to evaluate the potential health impact and cost-effectiveness of vaccination following serological screening. To do so, we used an agent-based model to simulate DENV transmission with and without vaccination over a 10-year timeframe. Across a range of values for the proportion of vaccinees with prior DENV exposure, we projected the proportion of symptomatic and hospitalized cases averted as a function of the sensitivity and specificity of serological screening. Scenarios about the cost-effectiveness of screening and vaccination were chosen to be representative of Brazil and the Philippines. We found that public health impact depended primarily on sensitivity in high-transmission settings and on specificity in low-transmission settings. Cost-effectiveness could be achievable from the perspective of a public payer provided that sensitivity and the value of a disability-adjusted life-year were both high, but only in high-transmission settings. Requirements for reducing relative risk and achieving cost-effectiveness from an individual perspective were more restricted, due to the fact that those who test negative pay for screening but receive no benefit. Our results predict that cost-effectiveness could be achieved only in high-transmission areas of dengue-endemic countries with a relatively high per capita GDP, such as Panamá (13,680 USD), Brazil (8,649 USD), México (8,201 USD), or Thailand (5,807 USD). In conclusion, vaccination with CYD-TDV following serological screening could have a positive impact in some high-transmission settings, provided that screening is highly specific (to minimize individual harm), at least moderately sensitive (to maximize population benefit), and sufficiently inexpensive (depending on the setting)., Competing Interests: GE and TAP have received research support from GlaxoSmithKline for unrelated work on dengue vaccines. AWS is a consultant on vaccines for arboviral diseases for the World Health Organization (WHO). The author alone is responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of WHO. The authors declare no conflicts of interest.

In Botswana, 85% of persons living with HIV are aware of their status. We performed an economic analysis of HIV testing activities implemented during intensive campaigns, in 11 communities, between April 2015 and March 2016, through the Botswana Combination Prevention Project. The total cost was $1,098,312, or $99,847 per community, with 60% attributable to home-based testing and 40% attributable to mobile testing. The cost per person tested was $44, and $671 per person testing positive (2017 USD). Labor costs comprised 64% of total costs. In areas of high HIV prevalence and treatment coverage, the cost of untargeted home-based testing may be inflated by the efforts required to assess the testing eligibility of clients who are HIV-positive and on ART. Home-based and mobile testing delivered though an intensive community-based campaign allowed the identification of HIV positive persons, who may not access health facilities, at a cost comparable to other studies.

Introduction: HIV self-testing (HIVST) provides couples and individuals with a discreet, convenient and empowering testing option. As with all HIV testing, potential harms must be anticipated and mitigated to optimize individual and public health benefits. Here, we describe social harms (SHs) reported during HIVST implementation in Malawi, and propose a framework for grading and responding to harms, according to their severity., Methods: We report findings from six HIVST implementation studies in Malawi (2011 to 2017) that included substudies investigating SH reports. Qualitative methods included focus group discussions, in-depth interviews and critical incident interviews. Earlier studies used intensive quantitative methods (post-test questionnaires for intimate partner violence, household surveys, investigation of all deaths in HIVST communities). Later studies used post-marketing reporting with/without community engagement. Pharmacovigilance methodology (whereby potentially life-threatening/changing events are defined as "serious") was used to grade SH severity, assuming more complete passive reporting for serious events., Results: During distribution of 175,683 HIVST kits, predominantly under passive SH reporting, 25 serious SHs were reported from 19 (0.011%) self-testers, including 15 partners in eight couples with newly identified HIV discordancy, and one perinatally infected adolescent. There were no deaths or suicides. Marriage break-up was the most commonly reported serious SH (sixteen individuals; eight couples), particularly among serodiscordant couples. Among new concordant HIV-positive couples, blame and frustration was common but rarely (one episode) led to serious SHs. Among concordant HIV-negative couples, increased trust and stronger relationships were reported. Coercion to test or disclose was generally considered "well-intentioned" within established couples. Women felt empowered and were assertive when offering HIVST test kits to their partners. Some women who persuaded their partner to test, however, did report SHs, including verbal or physical abuse and economic hardship., Conclusions: After more than six years of large-scale HIVST implementation and in-depth investigation of SHs in Malawi, we identified approximately one serious reported SH per 10,000 HIVST kits distributed, predominantly break-up of married serodiscordant couples. Both "active" and "passive" reporting systems identified serious SH events, although with more complete capture by "active" systems. As HIVST is scaled-up, efforts to support and further optimize community-led SH monitoring should be prioritized alongside HIVST distribution., (© 2019 World Health Organization; licensed by IAS.)

Introduction: HIV self-testing (HIVST) is recommended by the World Health Organization in addition to other testing modalities to increase uptake of HIV testing, particularly among harder-to-reach populations. This study provides the first empirical evidence of the costs of door-to-door community-based HIVST distribution in Malawi, Zambia and Zimbabwe., Methods: HIVST kits were distributed door-to-door in 71 sites across Malawi, Zambia and Zimbabwe from June 2016 to May 2017. Programme expenditures, supplemented by on-site observation and monitoring and evaluation data were used to estimate total economic and unit costs of HIVST distribution, by input and site. Inputs were categorized into start-up, capital and recurrent costs. Sensitivity and scenario analyses were performed to assess the impact of key parameters on unit costs., Results: In total, 152,671, 103,589 and 93,459 HIVST kits were distributed in Malawi, Zambia and Zimbabwe over 12, 11 and 10 months respectively. Across these countries, 43% to 51% of HIVST kits were distributed to men. The average cost per HIVST kit distributed was US$8.15, US$16.42 and US$13.84 in Malawi, Zambia and Zimbabwe, respectively, with pronounced intersite variation within countries driven largely by site-level fixed costs. Site-level recurrent costs were 70% to 92% of full costs and 20% to 62% higher than routine HIV testing services (HTS) costs. Personnel costs contributed from 26% to 52% of total costs across countries reflecting differences in remuneration approaches and country GDP., Conclusions: These early door-to-door community HIVST distribution programmes show large potential, both for reaching untested populations and for substantial economies of scale as HIVST programmes scale-up and mature. From a societal perspective, the costs of HIVST appear similar to conventional HTS, with the higher providers' costs substantially offsetting user costs. Future approaches to minimizing cost and/or maximize testing coverage could include unpaid door-to-door community-led distribution to reach end-users and integrating HIVST into routine clinical services via direct or secondary distribution strategies with lower fixed costs., (© 2019 World Health Organization; licensed by IAS.)

Background and Objectives: Donor syphilis testing began in the 1940s amidst widespread transfusion-transmitted syphilis (TTS). Since then, the introduction of penicillin, pre-donation screening questionnaires and improved storage conditions have contributed to reducing transmission risk. Consequently, universal testing may no longer be cost-effective. This study analysed alternative options for donor syphilis testing to determine the optimal strategy., Materials and Methods: A model was developed using conservative parameter estimates for factors affecting TTS and 2009-2015 Australian donations to calculate risk outcomes (TTS infections, tertiary syphilis in recipients and transfusion-associated congenital syphilis) and cost-effectiveness of alternative testing strategies. The strategies modelled were as follows: universal testing, targeted-testing of high-risk groups (males ≤50 years old and first-time donors) and no testing., Results: The estimated risk of TTS is one in 49·5 million transfusions for universal testing, one in 6 million for targeted-testing of males ≤50 years old, one in 4 million for targeted-testing of first-time donors and one in 2·8 million for no testing. For all strategies, the risk of tertiary and congenital syphilis is <1 in 100 million. Universal testing is the least cost-effective strategy with an incremental cost-effectiveness ratio (ICER) estimated at $538·5 million per disability-adjusted life year averted., Conclusion: Universal testing is not required to maintain the risk of TTS within tolerable limits and is estimated to greatly exceed acceptable ICERs for blood safety interventions. However, despite a strong economic and risk-based rationale, given the epidemiology of syphilis in Australia is changing, feedback from critical stakeholders is not currently supportive of reducing testing., (© 2018 International Society of Blood Transfusion.)

HIV prevention efforts have contributed to a decline in annual HIV infections in the United States. However, progress has been uneven and certain groups and geographic areas continue to be disproportionately affected. Subsequent to implementation of CDC's high-impact HIV prevention approach to reducing new infections, we analyzed national-level CDC-funded HIV test data from 2016 to describe the population being reached in three urbanicity settings (metropolitan: ≥ 1,000,000 population; urban: 50,000-999,999; rural: < 50,000). Over 70% of CDC-funded HIV tests and almost 80% of persons newly diagnosed with HIV as a result of CDC-funded testing occurred in metropolitan areas. Nonetheless, CDC-funded testing efforts are reaching urban and rural areas, especially in the South, providing opportunities to identify persons unaware of their HIV status and link those with newly diagnosed HIV to medical care and prevention services. While CDC-funded testing efforts have continued to focus on population subgroups and geographic areas at greatest risk, efforts should also continue in rural areas and among groups in need with a low national burden.

Objectives: In the organ donation process, screening for serologic markers for a selection of agents is essential to prevent infection transmission. The screening of donors for specific potential infections can never absolutely exclude the risk of transmission. For reevaluation of serology tests, we analyzed results of tests requested for all brain-dead donors., Materials and Methods: Our study included all actual brain-dead donors who were seen from January 2017 to February 2018, received ancillary tests, and had final confirmation of brain death at our organ procurement unit., Results: Most candidates for organ and tissue donation were seronegative for intended agents. We found that 14.4% of the samples were suspicious for infectious and needed further evaluation; 12.2% of donors had positive results corresponding to hepatitis B, and only 1.9% were rejected from donation. Requisiteness to DNA detection for hepatitis B virus infection was mainly related to age over 50 years., Conclusions: The process of donor screening must systemically assess the donor. At the final stage, essential biomarkers must be investigated. Application of more caution in evaluation of older donors, including more screening tests before transfer to the operating room, remains mandatory.

Human herpesviruses (HHV) cause a variety of clinically relevant conditions upon primary infection of typically young and immunocompetent hosts. Both primary infection and reactivation after latency can lead to more severe disease, such as encephalitis, congenital defects and cancer. Infections with HHV are also associated with cardiovascular and neurodegenerative disease. However, most of the associations are based on retrospective case-control analyses and well-powered prospective cohort studies are needed for assessing temporality and causality. To enable comprehensive investigations of HHV-related disease etiology in large prospective population-based cohort studies, we developed HHV Multiplex Serology. This methodology represents a low-cost, high-throughput technology that allows simultaneous measurement of specific antibodies against five HHV species: Herpes simplex viruses 1 and 2, Varicella zoster virus, Epstein-Barr virus, and Cytomegalovirus. The newly developed HHV species-specific ('Monoplex') assays were validated against established gold-standard reference assays. The specificity and sensitivity of the HHV species-specific Monoplex Serology assays ranged from 92.3% to 100.0% (median 97.4%) and 91.8% to 98.7% (median 96.6%), respectively. Concordance with reference assays was very high with kappa values ranging from 0.86 to 0.96 (median kappa 0.93). Multiplexing the Monoplex Serology assays resulted in no loss of performance and allows simultaneous detection of antibodies against the 5 HHV species in a high-throughput manner., Competing Interests: The authors have declared that no competing interests exist.

Toxocariasis is a neglected zoonosis that affects children and adults. Recombinant proteins have been widely investigated for diagnosis, achieving high sensitivity and specificity in an overall population; however, little is known about age as a factor in its application. This study aims to investigate the diagnostic potential of Toxocara canis TES-30 and TES-120 recombinant proteins in humans, differentiating between its performance in children and adults. Serum samples collected from children and adults seropositive to Toxocara spp. were tested with indirect ELISA using T. canis TES-30 and TES-120 recombinant proteins produced in Escherichia coli. While rTES-30 sensitivity was not affected by age (81.8% in children and 87% in adults), rTES-120 sensitivity severely decreased in children to only 63.6%, down from 95.7% in adults. Furthermore, the sensitivity of rTES-30 increased to 97.8% after Western blotting confirmation. High specificity (>94%) against other geohelminths was reported for both recombinant proteins. Our study favors the use of rTES-30 with total IgG as the primary antibody in an indirect ELISA assay as a tool for epidemiological human studies., Competing Interests: The authors have declared that no competing interests exist.

The acceptability of financial incentives for pediatric HIV testing was evaluated in Kenya. Sixty HIV-positive women with children of unknown status were randomized to receive $5, $10 or $15 conditional upon HIV testing. Forty-four (73%) completed child testing, with similar rates across arms. Uptake was significantly higher than a cohort with similar procedures but no incentives (73% vs. 14%, P < 0.001).

IntroductionNeurocysticercosis (NCC) is one of the leading causes of epilepsy worldwide. The majority of cases in Europe are diagnosed in immigrants. Currently in Italy, routine serological screening for cysticercosis is recommended for internationally adopted children (IAC) coming from endemic countries. Methods: We retrospectively analyse the results of the serological screening for cysticercosis in IAC 16 years old or younger, attending two Italian third level paediatric clinics in 2001-16. Results: Of 2,973 children included in the study, 2,437 (82.0%) were screened by enzyme-linked immune electro transfer blot (EITB), 1,534 (51.6%) by ELISA, and 998 (33.6%) by both tests. The seroprevalence of cysticercosis ranged between 1.7% and 8.9% according to EITB and ELISA, respectively. Overall, 13 children were diagnosed with NCC accounting for a NCC frequency of 0.4% (95% confidence interval (CI): 0.2-0.6%). Among the 168 seropositive children, only seven (4.2%) were diagnosed with NCC. Of these children, three were asymptomatic and four presented epilepsy. Among seronegative children (n = 2,805), seven presented with neurological symptoms that lead to the diagnosis of NCC in six cases. The sensitivity, specificity, positive and negative predictive value for the diagnosis of NCC were 54.5%, 98.6%, 14.6%, 99.8% for EITB and 22.2%, 91.1%, 1.4%, 99.5% for ELISA. The yield of the screening programme was 437 NCC cases per 100,000. The number needed to screen to detect one NCC case was 228. The cost per NCC case detected was EUR 10,372. Conclusion: On the base of our findings we suggest the ongoing serological screening for cysticercosis to be discontinued, at least in Italy, until further evidence in support will be available.

Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Rima McLeod worked on a literature review for Sanofi Pasteur.

Background: Trypanosoma cruzi causes Chagas disease in the Americas. The outcome of infection ranges from lifelong asymptomatic status to severe disease. Relationship between T. cruzi lineage (TcI-TcVI) infection history and prognosis is not understood. We previously described peptide-based lineage-specific enzyme-linked immunosorbent assay (ELISA) with trypomastigote small surface antigen (TSSA)., Methods: A novel rapid diagnostic test (RDT; Chagas Sero K-SeT) that incorporates a peptide that corresponds to the TSSA II/V/VI common epitope was developed and validated by comparison with ELISA. Patients from Bolivia and Peru, including individuals with varying cardiac pathology, and matched mothers and neonates, were then tested using Chagas Sero K-SeT., Results: Chagas Sero K-SeT and ELISA results, with a Bolivian subset of cardiac patients, mothers, and neonates, were in accord. In adult chronic infections (n = 121), comparison of severity class A (no evidence of Chagas cardiomyopathy) with class B (electrocardiogram suggestive of Chagas cardiomyopathy) and class C/D (decreased left ventricular ejection fraction; moderate/severe Chagas cardiomyopathy) revealed a statistically significant increase in Chagas Sero K-SeT reactivity with increasing severity (χ2 for trend, 7.39; P = .007). In Peru, Chagas Sero K-SeT detected the sporadic TcII/V/VI infections., Conclusions: We developed a low cost RDT that can replace ELISA for identification of TSSA II/V/VI immunoglobulin G. Most importantly, we show that response to this RDT is associated with severity of Chagas cardiomyopathy and thus may have prognostic value. Repeated challenge with T. cruzi infection may both exacerbate disease progression and boost the immune response to the TSSApep-II/V/VI epitope.

Objective: HIV testing rates in many sub-Saharan African countries have remained suboptimal, and there is an urgent need to explore strategic yet cost-effective approaches to increase the uptake of HIV testing, especially among high-risk populations., Methods: A costing analysis was conducted for a randomized controlled trial (RCT) with male truckers and female sex workers (FSWs) registered in the electronic health record system (EHRS) of the North Star Alliance, which offers healthcare services at major transit hubs in Southern and East Africa. The RCT selected a sample of truckers and FSWs who were irregular HIV testers, according to the EHRS, and evaluated the effect of SMSs promoting the availability of HIV self-testing (HIVST) kits in Kenyan clinics (intervention program) versus a general SMS reminding clients to test for HIV (enhanced and standard program) on HIV testing rates. In this paper, we calculated costs from a provider perspective using a mixed-methods approach to identify, measure, and value the resources utilized within the intervention and standard programs. The results of the analysis reflect the cost per client tested., Results: The cost of offering HIVST was calculated to be double that of routine facility-based testing (USD 10.13 versus USD 5.01 per client tested), primarily due to the high price of the self-test kit. In the two study arms that only offered provider-administered HIV testing in the clinic, only 1% of truckers and 6% of FSWs tested during the study period, while in the intervention arm, which also offered HST, approximately 4% of truckers and 11% of FSWs tested. These lower than expected outcomes resulted in relatively high cost per client estimates for all three study arms. Within the intervention arm, 65% of truckers and 72% of FSWs who tested chose the HIVST option. However, within the intervention arm, the cost per additional client tested was lower for FSWs than for truckers, at USD 0.15 per additional client tested versus USD 0.58 per additional client tested, driven primarily by the higher response rates., Conclusion: Whilst the availability of HIVST increased HIV testing among both truckers and FSWs, the cost of providing HIVST is higher than that of a routine health facility-based test, driven primarily by the price of the HIV self-test kit. Future research needs to identify strategies which increase demand for HIVST, and determine whether these strategies and the subsequent increased demand for HIVST are cost-effective in relation to the conventional facility based testing currently available., Competing Interests: The authors have declared that no competing interests exist.

The incidence of flavivirus infections has increased dramatically in recent decades in tropical and sub-tropical areas worldwide, affecting hundreds of millions of people each year. Dengue viruses are typically transmitted by mosquitoes and can cause a wide range of symptoms from flu-like fever to organ impairment and death. Although conventional diagnostic tests can provide early diagnosis of acute dengue infections, access to these tests is often limited in developing countries. Consequently, there is an urgent need to develop affordable, simple, rapid, and robust diagnostic tools that can be used at 'Point of Care' settings. Early diagnosis is crucial to improve patient management and reduce the risk of complications. In the present study, a novel laser-cut device made of glass-fiber paper was designed and tested for the detection of the dengue Non Structural 1 (NS1) viral protein and specific IgM in blood and plasma. The device, called PAD, was able to detect around 25 ng/mL of NS1 protein in various sample types in 8 minutes, following a few simple steps. The PAD was also able to detect specific IgM in human plasmas in less than 10 minutes. The PAD appears to have all the potential to assist health workers in early diagnosis of dengue fever or other tropical fevers caused by flaviviruses.

The aim of this work was to ascertain the usefulness of a new commercially-available single-assay chemiluminescence test (CHT) for the diagnosis of human tularemia (Tularaemia VIRCLIA IgG + IgM monotest, Vircell, Santa Fe, Granada, Spain). A total of 773 sera from 773 patients including 364 initial sera from patients with diagnosed tularemia, patients with suspected tularemia not confirmed (100), healthy people (152), patients with serology positive to Brucella (97), patients diagnosed with other infectious diseases (30), and patients diagnosed with autoimmune diseases (30) were included. All sera were tested by CHT, "in-house" microagglutination test (MAT), immunochromatographic test (ICT) (Virapid Tularaemia, Vircell, Santa Fe Granada, Spain), and "in-house" ELISA IgG, and ELISA IgM. Of the total initial sera, 334 (sensitivity 91.8%) were positive in the CHT, 332 (sensitivity 91.2%) in the MAT, 330 (sensitivity 90.7%) in the ICT, and 328 (sensitivity 90.1%) in the ELISA IgG and ELISA IgM tests. The specificity of the CHT was 96.7%; of the MAT, 100%; of the ICT, 98.7%; and of the ELISA IgG and ELISA IgM, 97.4%. In the group of patients with serology positive to Brucella, at least 12.4% of sera were positive in tularemia tests (12.4% in ELISA IgM, 13.4% in MAT, 14.4% in ICT, and 15.5% in CHT and ELISA IgG). In conclusion, CHT presents a sensitivity and specificity in early diagnosis of human tularemia, similar to MAT, ICT, and ELISA IgG and ELISA IgM. Its single assay design allows lower costs, especially in areas of low endemicity or inter-epidemic periods.

Background: Random duodenal biopsy to exclude coeliac disease during upper gastrointestinal endoscopy for the investigation of iron deficiency anaemia remains a common procedure, but is expensive and time-consuming. Serological investigation for coeliac disease is also recommended, having excellent accuracy with the added benefit of lower cost. This study sought to examine the utility of duodenal biopsy and coeliac serology in the diagnosis of coeliac disease., Methods: A prospectively maintained database was interrogated to identify all patients having upper gastrointestinal endoscopy for the investigation of anaemia between January 01, 2016, and December 31, 2016., Results: Of the 1131 patients having an endoscopy, coeliac serology was measured in only 412 (36%) and was positive in 9 cases (2%), leading to 6 histological diagnoses of coeliac disease and 3 false positives. Two-hundred and seventy-four patients with negative serology had biopsies taken which were all negative. Only 2/451 (0.4%) patients who had biopsies performed in the absence of a serology test were histologically positive for coeliac disease. The cost per diagnosis of a case of coeliac disease in those with either negative or absent coeliac serology was £18,839 (US$25,244, €21,196)., Conclusions: Random duodenal biopsy is not a cost-effective method of diagnosing coeliac disease and should be replaced with pre-endoscopy coeliac serology.

Background: Access to hepatitis B virus (HBV) and hepatitis C virus (HCV) diagnostics remains a key bottleneck in scale-up of access to HBV and HCV treatment, particularly in low- and middle-income countries (LMICs) that lack laboratory resources and skilled personnel. To inform the development of World Health Organization (WHO) testing guidelines on who to test and how to test, we performed a "values and preferences" survey of end users and implementers of hepatitis testing in LMICs on current hepatitis B and C testing practices and acceptability of diagnostic approaches, as well as preferences for the future., Methods: The survey consisted of a four-part, 28 question online survey tool using SurveyMonkey software. The invitation to participate was sent via email to a network of contacts in hepatitis clinical care, research, advocacy and industry., Results: The survey collected responses on current testing practices from 48 respondents in 23 LMICs. Only a small proportion of hepatitis testing is currently funded through government-supported programmes. Most limit their testing programmes to blood donor screening and although testing is recommended in several populations, this is not well implemented. Also, there is still very limited access to virological testing., Conclusions: The survey showed that HBV and HCV testing programmes in LMICs are inadequate and/or scarce. Lack of affordable diagnostic tests; lack of funding, public education and awareness; absence of national policies and guidelines; and a dearth of skilled health professionals are the most important barriers to scaling up HBV and HCV diagnosis and treatment.

As effective onchocerciasis control efforts in Africa transition to elimination efforts, different diagnostic tools are required to support country programs. Senegal, with its long standing, successful control program, is transitioning to using the SD BIOLINE Onchocerciasis IgG4 (Ov16) rapid test over traditional skin snip microscopy. The aim of this study is to demonstrate the feasibility of integrating the Ov16 rapid test into onchocerciasis surveillance activities in Senegal, based on the following attributes of acceptability, usability, and cost. A cross-sectional study was conducted in 13 villages in southeastern Senegal in May 2016. Individuals 5 years and older were invited to participate in a demographic questionnaire, an Ov16 rapid test, a skin snip biopsy, and an acceptability interview. Rapid test technicians were interviewed and a costing analysis was conducted. Of 1,173 participants, 1,169 (99.7%) agreed to the rapid test while 383 (32.7%) agreed to skin snip microscopy. The sero-positivity rate of the rapid test among those tested was 2.6% with zero positives 10 years and younger. None of the 383 skin snips were positive for Ov microfilaria. Community members appreciated that the rapid test was performed quickly, was not painful, and provided reliable results. The total costs for this surveillance activity was $22,272.83, with a cost per test conducted at $3.14 for rapid test, $7.58 for skin snip microscopy, and $13.43 for shared costs. If no participants had refused skin snip microscopy, the total cost per method with shared costs would have been around $16 per person tested. In this area with low onchocerciasis sero-positivity, there was high acceptability and perceived value of the rapid test by community members and technicians. This study provides evidence of the feasibility of implementing the Ov16 rapid test in Senegal and may be informative to other country programs transitioning to Ov16 serologic tools.

Introduction: During year 2013, 5943 tests for antineutrophil cytoplasmic antibodies (ANCA) detection were performed in Bordeaux hospital, France. This seemed disproportionate, with regard to the low prevalence of ANCA-associated vasculitis (AAV). Our purpose was to evaluate the relevance of these requests., Methods: Requests for detection of ANCA during 2013 were recorded, with their results. A sample of 501 requests was secondarily established. Relevance of requests was assessed independently by two reviewers. During year 2014, we developed strategies of information, in order to reduce the number of requests and increase their relevance., Results: Only 17.8 % of the 5943 requests for detection of ANCA resulted in a positive test using indirect immunofluorescence (including 10.6 % of the requests with titles above 1/50). Using Luminex©, 9.7 % of the test of detection against antimyeloperoxidase or antiproteinase 3 antibodies were positive. Within the sample of 501 patients, only 28.7 % of the requests were relevant. A percentage of 40.2 of them weren't justified by a clinical affection typically associated with AAV. Exactly 15.9 of the requests were performed during systematic autoimmune screening. None of these requests could lead to the diagnosis of AAV. Combination of information procedures and use of a request form enabled a 19 % decrease of the number of requests. The percentage of requests without clinical justification also reduced from 40.2 % to 17.1 %. The reduction of the number of requests led to a 46,865 € saving., Conclusion: The majority of the requests for detection of ANCA was not relevant and could not lead to the diagnosis of AAV. Simple solutions enabled a partial but significant improvement of their relevance., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Background: Primary infection of Toxoplasma gondii during pregnancy can be transmitted to the unborn child and may have serious consequences, including retinochoroiditis, hydrocephaly, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Austria, a country with moderate seroprevalence, instituted mandatory prenatal screening for toxoplasma infection to minimize the effects of congenital transmission. This work compares the societal costs of congenital toxoplasmosis under the Austrian national prenatal screening program with the societal costs that would have occurred in a No-Screening scenario., Methodology/principal Findings: We retrospectively investigated data from the Austrian Toxoplasmosis Register for birth cohorts from 1992 to 2008, including pediatric long-term follow-up until May 2013. We constructed a decision-analytic model to compare lifetime societal costs of prenatal screening with lifetime societal costs estimated in a No-Screening scenario. We included costs of treatment, lifetime care, accommodation of injuries, loss of life, and lost earnings that would have occurred in a No-Screening scenario and compared them with the actual costs of screening, treatment, lifetime care, accommodation, loss of life, and lost earnings. We replicated that analysis excluding loss of life and lost earnings to estimate the budgetary impact alone. Our model calculated total lifetime costs of €103 per birth under prenatal screening as carried out in Austria, saving €323 per birth compared with No-Screening. Without screening and treatment, lifetime societal costs for all affected children would have been €35 million per year; the implementation costs of the Austrian program are less than €2 million per year. Calculating only the budgetary impact, the national program was still cost-saving by more than €15 million per year and saved €258 million in 17 years., Conclusions/significance: Cost savings under a national program of prenatal screening for toxoplasma infection and treatment are outstanding. Our results are of relevance for health care providers by supplying economic data based on a unique national dataset including long-term follow-up of affected infants.

A rapid test to identify patients with sickle cell disease could have important benefits in low-resource settings. Sickle cell anemia (SCA) affects about 300,000 newborns each year, the majority of whom are born in sub-Saharan Africa. Low-cost therapies are available to treat SCA, but most countries in sub-Saharan Africa lack robust neonatal screening programs needed to identify patients in need of treatment. To address this need, we developed and evaluated a competitive lateral flow assay that identifies patients with SCA (genotype HbSS) in 15 minutes using undiluted whole blood. A small volume of blood (0.5 μL- 3 μL) is mixed with antibody-coated blue latex beads in a tube and applied to the strip. Strips are then placed in a well of running buffer and allowed to run for 10 minutes. Laboratory evaluation with samples containing different proportions of hemoglobin A (HbA) and hemoglobin S (HbS) indicated that the test should enable identification of SCA patients but not persons with sickle cell trait (SCT). We evaluated the test using 41 samples from individuals with SCA, SCT, and normal blood. With visual inspection or quantitative analysis, we found a 98% accuracy when differentiating SCA from normal and SCT samples as a group (90% sensitivity and 100% specificity for identifying SCA). This work demonstrates important steps towards making a lateral flow test for hemoglobinopathies more appropriate for point-of-care use; further work is needed before the test is appropriate for clinical use.

Objectives: The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients., Methods: In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes)., Results: Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation., Conclusions: We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

We compared two community-based HIV testing models among fisherfolk in Lake Victoria, Uganda. From May to July 2015, 1364 fisherfolk residents of one island were offered (and 822 received) home-based testing, and 344 fisherfolk on another island were offered testing during eight community mobilization events (outreach event-based testing). Of 207 home-based testing clients identified as HIV-positive (15% of residents), 82 were newly diagnosed, of whom 31 (38%) linked to care within 3 months. Of 41 who screened positive during event-based testing (12% of those tested), 33 were newly diagnosed, of whom 24 (75%) linked to care within 3 months. Testing costs per capita were similar for home-based ($45.09) and event-based testing ($46.99). Compared to event-based testing, home-based testing uncovered a higher number of new HIV cases but was associated with lower linkage to care. Novel community-based test-and-treat programs are needed to ensure timely linkage to care for newly diagnosed fisherfolk., Competing Interests: COMPLIANCE WITH ETHICAL STANDARDS: There are no conflicts of interest to disclose. All human subjects procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

In light of the changing epidemiology of varicella, we sought to examine varicella antibody levels in the prenatal population in the Canadian province of Alberta. All prenatal varicella screening tests performed between August 1, 2002 and February 2, 2014 (454,592) were included in this study. Test results, demographics and vaccination status were examined to identify varicella seroprevalence and correlates for being seronegative. An overall seroprevalence for varicella of 95.8% was found across all pregnancy screenings. Significant independent correlates of seronegativity included younger age (AOR: 4.72 (95% CI: 3.87-5.77) for <20years of age vs. >40years of age) and having immigrated to Alberta from Africa or Asia (AOR: 4.55 (95% CI: 4.10-5.05) and AOR: 5.83 (95%CI; 5.48-6.19), respectively). Women who were initially seronegative for varicella antibodies and who received both postnatal vaccination and post-vaccination prenatal screening (2566) were examined to assess seroconversion. 66.3% of women who were tested up to six months post-vaccination were seropositive, however only 36.9% of women tested after 36months were seropositive. Finally, 40.9% of all prenatal varicella specimens tested were deemed redundant, i.e. women had either a history of (1) ⩾2 doses of varicella vaccine, (2) varicella infection, or (3) a previous positive varicella serology. Eliminating this redundant screening could provide an estimated $96,000 in savings annually in laboratory and Public Health follow-up costs alone. As the number of women with vaccine-derived immunity through universal childhood vaccination increase in the prenatal population, screening methods may need to adapt to ensure varicella immunity is accurately conducted and assessed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Acceptability and willingness to both take and pay for HIV self-tests (HIVSTs) in US neighbourhoods with high rates of HIV infection are not well understood., Methods: We surveyed 1,535 individuals about acceptability and willingness to take and pay for an HIVST in a predominately African American neighbourhood with 3% HIV seroprevalence. We recruited individuals presenting for HIV screening services in a community-based programme. Latent class analysis (LCA) grouped individuals with similar patterns of HIV-risk behaviours and determined which groups would be most willing to use and buy HIVSTs., Results: Nearly 90% of respondents were willing to use an HIVST; 55% were willing to buy HIVSTs, but only 23% were willing to pay the market price of US $40. Four distinct groups emerged and were characterized by risk behaviours: (1) low risk ( N  = 324); (2) concurrent partnerships ( N  = 346); (3) incarceration and substance use ( N  = 293); and (4) condomless sex/multiple partners ( N  = 538). Individuals in the low-risk class were less willing to self-test compared to concurrent sexual partners (OR = 0.39, p  = .003) and incarceration and substance use (OR = 0.46, p  = .011) classes. There were no significant differences across classes in the amount individuals were willing to pay for an HIVST., Conclusion: HIVSTs were overwhelmingly acceptable but cost prohibitive; most participants were unwilling to pay the market rate of US $40. Subsidizing and implementing HIVST programmes in communities with high rates of infection present a public health opportunity, particularly among individuals reporting condomless sex with multiple partners, concurrent sexual partnerships and those with incarceration and substance use histories.

From December 2012 to March 2014, three randomized trials, each implementing a unique intervention in primary care settings (repeated mailing, an electronic health record best practice alert [BPA], and patient solicitation), evaluated hepatitis C virus (HCV) antibody testing, diagnosis, and costs for each of the interventions compared with standard-of-care testing. Multilevel multivariable models were used to estimate the adjusted risk ratio (aRR) for receiving an HCV antibody test, and costs were estimated using activity-based costing. The goal of this study was to estimate the effects of interventions conducted as part of the Birth-Cohort Evaluation to Advance Screening and Testing for Hepatitis C study on HCV testing and costs among persons of the 1945-1965 birth cohort (BC). Intervention resulted in substantially higher HCV testing rates compared with standard-of-care testing (26.9% versus 1.4% for repeated mailing, 30.9% versus 3.6% for BPA, and 63.5% versus 2.0% for patient solicitation) and significantly higher aRR for testing after controlling for sex, birth year, race, insurance type, and median household income (19.2 [95% confidence interval (CI), 9.7-38.2] for repeated mailing, 13.2 [95% CI, 3.6-48.6] for BPA, and 32.9 [95% CI, 19.3-56.1] for patient solicitation). The BPA intervention had the lowest incremental cost per completed test ($24 with fixed startup costs, $3 without) and also the lowest incremental cost per new case identified after omitting fixed startup costs ($1691)., Conclusion: HCV testing interventions resulted in an increase in BC testing compared with standard-of-care testing but also increased costs. The effect size and incremental costs of BPA intervention (excluding startup costs) support more widespread adoption compared with the other interventions. (Hepatology 2017;65:44-53)., (© 2016 by the American Association for the Study of Liver Diseases.)

Background: The aim of this study was to assess the cost effectiveness of introducing individual-donation nucleic acid testing (ID-NAT), in addition to serologic tests, compared with the exclusive use of serologic tests for the identification of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) I and II among blood donors in Zimbabwe., Study Design and Methods: The costs, health consequences, and cost effectiveness of adding ID-NAT to serologic tests, compared with serologic testing alone, were estimated from a health care perspective using a decision-analytic model., Results: The introduction of ID-NAT in addition to serologic tests would lower the risk of HBV, HCV, and HIV transmission to 46.9, 0.3, and 2.7 per 100,000 donations, respectively. ID-NAT would prevent an estimated 25, 6, and 9 HBV, HCV, and HIV transfusion-transmitted infections per 100,000 donations, respectively. The introduction of this intervention would result in an estimated 212 quality-adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio is estimated at US$17,774/QALY, a value far more than three times the gross national income per capita for Zimbabwe., Conclusion: Although the introduction of NAT could further improve the safety of the blood supply, current evidence suggests that it cannot be considered cost effective. Reducing the test costs for NAT through efficient donor recruitment, negotiating the price of reagents, and the efficient use of technology will improve cost effectiveness., (© 2016 AABB.)

Background: International guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance. We therefore assessed three key aspects to this hypothesis: 1) the availability of pre-endoscopy serology in anaemia; 2) the sensitivities and cost effectiveness of pre-endoscopy coeliac screening with Simtomax in anaemia; 3) whether other anaemia-related pathologies could be missed by this targeted-biopsy approach., Methods: Group 1: pre-endoscopy serology availability was retrospectively analysed in a multicentre cohort of 934 anaemic patients at 4 UK hospitals. Group 2: the sensitivities of Simtomax, endomysial and tissue-transglutaminase antibodies were compared in 133 prospectively recruited patients with iron deficiency anaemia attending for a gastroscopy. The sensitivities were measured against duodenal histology as the reference standard in all patients. The cost effectiveness of Simtomax was calculated based on the number of biopsies that could have been avoided compared to an all-biopsy approach. Group 3: the duodenal histology of 153 patients presenting to a separate iron deficiency anaemia clinic were retrospectively reviewed., Results: In group 1, serology was available in 361 (33.8 %) patients. In group 2, the sensitivity and negative predictive value (NPV) were 100 % and 100 % for Simtomax, 96.2 % and 98.9 % for IgA-TTG, and 84.6 % and 96.4 % for EMA respectively. In group 3, the duodenal histology found no causes for anaemia other than coeliac disease., Conclusion: Simtomax had excellent diagnostic accuracy in iron deficiency anaemia and was comparable to conventional serology. Duodenal biopsy did not identify any causes other than coeliac disease for iron deficiency anaemia, suggesting that biopsy avoidance in Simtomax negative anaemic patients is unlikely to miss other anaemia-related pathologies. Due to its 100 % NPV, Simtomax could reduce unnecessary biopsies by 66 % if only those with a positive Simtomax were biopsied, potentially saving £3690/100 gastroscopies., Trial Registration: The group 2 study was retrospectively registered with clinicaltrials.gov. Trial registration date: 13(th) July 2016;, Trial Registration Number: NCT02834429 .

Early diagnosis of patients with rheumatoid arthritis (RA) optimises therapeutic benefit and the probability of achieving disease remission. Notwithstanding clinical acumen, early diagnosis is dependent on access to reliable serodiagnostic procedures, as well as on the discerning application and interpretation of these. In the case of RA, however, no disease-specific serodiagnostic procedure is available due to the multi-factorial and polygenic nature of this autoimmune disorder. This has resulted in the development of an array of serodiagnostic procedures based on the detection of autoantibodies reactive with various putative autoantigens. Other procedures based on measurement of elevations in the concentrations of systemic biomarkers of inflammation, most commonly acute phase reactants and cytokines/chemokines, are used as objective indices of disease activity. Following a brief overview of RA research in African populations, the current review is focused on those autoantibodies/biomarkers, specifically rheumatoid factor, anti-citrullinated peptide antibodies and C-reactive protein, which are currently recognised as being the most reliable and cost-effective with respect to disease prediction and diagnosis, as well as in monitoring activity and outcome.

Quantitative point-of-care (POC) devices are the next generation for serological disease diagnosis. Whilst pathogen serology is typically performed by centralized laboratories using Enzyme-Linked ImmunoSorbent Assay (ELISA), faster on-site diagnosis would infer improved disease management and treatment decisions. Using the model pathogen Bovine Herpes Virus-1 (BHV-1) this study employs an extended-gate field-effect transistor (FET) for direct potentiometric serological diagnosis. BHV-1 is a major viral pathogen of Bovine Respiratory Disease (BRD), the leading cause of economic loss ($2 billion annually in the US only) to the cattle and dairy industry. To demonstrate the sensor capabilities as a diagnostic tool, BHV-1 viral protein gE was expressed and immobilized on the sensor surface to serve as a capture antigen for a BHV-1-specific antibody (anti-gE), produced in cattle in response to viral infection. The gE-coated immunosensor was shown to be highly sensitive and selective to anti-gE present in commercially available anti-BHV-1 antiserum and in real serum samples from cattle with results being in excellent agreement with Surface Plasmon Resonance (SPR) and ELISA. The FET sensor is significantly faster than ELISA (<10 min), a crucial factor for successful disease intervention. This sensor technology is versatile, amenable to multiplexing, easily integrated to POC devices, and has the potential to impact a wide range of human and animal diseases., (Copyright © 2015 Elsevier B.V. All rights reserved.)