Sushmita Shivkumar

Supervised and unsupervised self-testing for HIV in high-and low-risk populations: a systematic review

By systematically reviewing the literature, Nitika Pant Pai and colleagues assess the evidence base for HIV self tests both with and without supervision.

Head-to-head comparison of accuracy of a rapid point-of-care HIV test with oral versus whole-blood specimens: a systematic review and meta-analysis.

BACKGROUND The focus on prevention strategies aimed at curbing the HIV epidemic is growing, and therefore screening for HIV has again taken centre stage. Our aim was to establish whether a convenient, non-invasive, HIV test that uses oral fluid was accurate by comparison with the same test with blood-based specimens. METHODS We did a systematic review and meta-analysis to compare the diagnostic accuracy of a rapid HIV-antibody-based point-of-care test (Oraquick advance rapid HIV-1/2, OraSure Technologies Inc, PA, USA) when used with oral versus blood-based specimens in adults. We searched five databases of published work and databases of five key HIV conferences. Studies we deemed eligible were those focused on adults at risk of HIV; we excluded studies in children, in co-infected populations, with self-reported inferior reference standards, and with incomplete reporting of key data items. We assessed the diagnostic accuracy of testing with oral and blood-based specimens with bivariate regression analysis. We computed positive predictive values (PPVs) in high-prevalence and low-prevalence settings with Bayesian methods. FINDINGS In a direct head-to-head comparison of studies, we identified a pooled sensitivity about 2% lower in oral (98·03%, 95% CI 95·85-99·08) than in blood-based specimens (99·68%, 97·31-99·96), but similar specificity (oral 99·74%, 99·47-99·88; blood 99·91%, 99·84-99·95). Negative likelihood ratios were small and similar (oral 0·019, 0.009-0·040; blood 0·003, 0·001-0·034), but positive likelihood ratios differed (oral 383·37, 183·87-799·31; blood 1105·16, 633·14-2004·37). Although in high-prevalence settings PPVs were similar (oral 98·65%, 95% credible interval 85·71-99·94; blood 98·50, 93·10-99·79), in low-prevalence settings PPVs were lower for oral (88·55%, 77·31-95·87) than blood (97·65%, 95·48-99·09) specimens. INTERPRETATION Although Oraquick had a high PPV in high-prevalence settings in oral specimens, the slightly lower sensitivity and PPV in low-prevalence settings in oral specimens should be carefully reviewed when planning worldwide expanded initiatives with this popular test.

Incidence of acute hepatitis C virus infection among men who have sex with men with and without HIV infection: a systematic review

Background A recent increase in reports of acute hepatitis C virus infection (HCV) in HIV-infected and HIV-uninfected men who have sex with men (MSM), with the sole risk factor being sexual exposure, has led to routine screening and targeted prevention requests for this population; current evidence for this necessity is unclear. Objective A systematic review was conducted to assess the incidence of HCV infection among studies conducted in HIV-positive and/or HIV-negative MSM to explore the implications for routine HCV screening. Data sources The MEDLINE, EMBASE and BIOSYS databases were searched for the period January 2000 to May 2012, yielding 21 studies. Six conferences were hand-searched for the same period yielding four abstracts. Study selection Only studies in English presenting incidence rates of HCV and specifying HIV status were included. Data abstraction Data were abstracted by two authors using predefined data fields. The STROBE checklist was used to assess study quality. Data synthesis Data were divided into HIV-negative MSM and HIV-positive MSM subgroups, and HCV incidence density measurements were pooled. Using a DerSimonian–Laird random effects model, pooled incidence was 1.48/1000 person-years (95% CI 0.75 to 2.21) for the HIV-negative MSM subgroup. The HIV-positive MSM subgroup was at 4.1 times higher risk of acquiring HCV at 6.08/1000 person-years (95% CI 5.18 to 6.99). Studies directly comparing subgroups estimated a pooled risk difference of 3.45/1000 person-years (95% CI 1.63 to 5.27). Conclusion HIV-positive MSM were at higher risk for acute HCV infection than HIV-negative MSM, substantiating the need for routine screening initiatives. Insufficient evidence exists to warrant routine screening of HIV-negative MSM, except on a case-by-case basis, such as high-risk sexual behaviour.

Accuracy of Rapid and Point-of-Care Screening Tests for Hepatitis C: A Systematic Review and Meta-analysis

BACKGROUND 170 million persons worldwide are infected with hepatitis C, many of whom are undiagnosed. Although rapid diagnostic tests (RDTs) and point-of-care tests (POCTs) provide a time- and cost-saving alternative to conventional laboratory tests, their global uptake partly depends on their performance. PURPOSE To meta-analyze the diagnostic accuracy of POCTs and RDTs to screen for hepatitis C. DATA SOURCES MEDLINE, EMBASE, BIOSIS, and Web of Science (1992 to 2012) and bibliographies of included articles. STUDY SELECTION All studies evaluating the diagnostic accuracy of POCTs and RDTs for hepatitis C in adults (aged ≥18 years). DATA EXTRACTION Two independent reviewers extracted data and critiqued study quality. DATA SYNTHESIS Of 19 studies reviewed, 18 were meta-analyzed and stratified by specimen type (whole blood, serum, plasma, or oral fluid) or test type (POCT or RDT). Sensitivity was similarly high in POCTs of whole blood (98.9% [95% CI, 94.5% to 99.8%]) and serum or plasma (98.9% [CI, 96.8% to 99.6%]), followed by RDTs of serum or plasma (98.4% [CI, 88.9% to 99.8%]) and POCTs of oral fluid (97.1% [CI, 94.7% to 98.4%]). Specificity was also high in POCTs of whole blood (99.5% [CI, 97.5% to 99.9%]) and serum or plasma (99.7% [CI, 99.3% to 99.9%]), followed by RDTs of serum or plasma (98.6% [CI, 94.9% to 99.6%]) and POCTs of oral fluid (98.2% [CI, 92.2% to 99.6%]). LIMITATION Lack of data prevented sensitivity analyses of specific tests. CONCLUSION Data suggest that POCTs of blood (serum, plasma, or whole blood) have the highest accuracy, followed by RDTs of serum or plasma and POCTs of oral fluids. Given their accuracy, convenience, and quick turnaround time, RDTs and POCTs may be useful in expanding first-line screening for hepatitis C. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research.

Are Treponema pallidum Specific Rapid and Point-of-Care Tests for Syphilis Accurate Enough for Screening in Resource Limited Settings? Evidence from a Meta-Analysis

Background Rapid and point-of-care (POC) tests for syphilis are an invaluable screening tool, yet inadequate evaluation of their diagnostic accuracy against best reference standards limits their widespread global uptake. To fill this gap, a systematic review and meta-analysis was conducted to evaluate the sensitivity and specificity of rapid and POC tests in blood and serum samples against Treponema pallidum (TP) specific reference standards. Methods Five electronic databases (1980–2012) were searched, data was extracted from 33 articles, and Bayesian hierarchical models were fit. Results In serum samples, against a TP specific reference standard point estimates with 95% credible intervals (CrI) for the sensitivities of popular tests were: i) Determine, 90.04% (80.45, 95.21), ii) SD Bioline, 87.06% (75.67, 94.50), iii) VisiTect, 85.13% (72.83, 92.57), and iv) Syphicheck, 74.48% (56.85, 88.44), while specificities were: i) Syphicheck, 99.14% (96.37, 100), ii) Visitect, 96.45% (91.92, 99.29), iii) SD Bioline, 95.85% (89.89, 99.53), and iv) Determine, 94.15% (89.26, 97.66). In whole blood samples, sensitivities were: i) Determine, 86.32% (77.26, 91.70), ii) SD Bioline, 84.50% (78.81, 92.61), iii) Syphicheck, 74.47% (63.94, 82.13), and iv) VisiTect, 74.26% (53.62, 83.68), while specificities were: i) Syphicheck, 99.58% (98.91, 99.96), ii) VisiTect, 99.43% (98.22, 99.98), iii) SD Bioline, 97.95%(92.54, 99.33), and iv) Determine, 95.85% (92.42, 97.74). Conclusions Rapid and POC treponemal tests reported sensitivity and specificity estimates comparable to laboratory-based treponemal tests. In resource limited settings, where access to screening is limited and where risk of patients lost to follow up is high, the introduction of these tests has already been shown to improve access to screening and treatment to prevent stillbirths and neonatal mortality due to congenital syphilis. Based on the evidence, it is concluded that rapid and POC tests are useful in resource limited settings with poor access to laboratories or screening for syphilis.

Will an unsupervised self-testing strategy for HIV work in health care workers of South Africa? A cross sectional pilot feasibility study.

Background In South Africa, stigma, discrimination, social visibility and fear of loss of confidentiality impede health facility-based HIV testing. With 50% of adults having ever tested for HIV in their lifetime, private, alternative testing options are urgently needed. Non-invasive, oral self-tests offer a potential for a confidential, unsupervised HIV self-testing option, but global data are limited. Methods A pilot cross-sectional study was conducted from January to June 2012 in health care workers based at the University of Cape Town, South Africa. An innovative, unsupervised, self-testing strategy was evaluated for feasibility; defined as completion of self-testing process (i.e., self test conduct, interpretation and linkage). An oral point-of-care HIV test, an Internet and paper-based self-test HIV applications, and mobile phones were synergized to create an unsupervised strategy. Self-tests were additionally confirmed with rapid tests on site and laboratory tests. Of 270 health care workers (18 years and above, of unknown HIV status approached), 251 consented for participation. Findings Overall, about 91% participants rated a positive experience with the strategy. Of 251 participants, 126 evaluated the Internet and 125 the paper-based application successfully; completion rate of 99.2%. All sero-positives were linked to treatment (completion rate:100% (95% CI, 66.0–100). About half of sero-negatives were offered counselling on mobile phones; completion rate: 44.6% (95% CI, 38.0–51.0). A majority of participants (78.1%) were females, aged 18–24 years (61.4%). Nine participants were found sero-positive after confirmatory tests (prevalence 3.6% 95% CI, 1.8–6.9). Six of nine positive self-tests were accurately interpreted; sensitivity: 66.7% (95% CI, 30.9–91.0); specificity:100% (95% CI, 98.1–100). Interpretation Our unsupervised self-testing strategy was feasible to operationalize in health care workers in South Africa. Linkages were successfully operationalized with mobile phones in all sero-positives and about half of the sero-negatives sought post-test counselling. Controlled trials and implementation research studies are needed before a scale-up is considered.

Rapid point-of-care first-line screening tests for hepatitis B infection: a meta-analysis of diagnostic accuracy (1980-2010).

OBJECTIVES:Three-hundred fifty million people worldwide are chronically infected with Hepatitis B, with four million acute infections annually. With infection concentrated in hard-to-reach populations and low resource settings, rapid point-of-care (POC) tests offer an efficient screening alternative to laboratory tests. We conducted a meta-analysis to evaluate accuracy of rapid POC tests screening for Hepatitis B.METHODS:Two reviewers searched four databases, critiqued quality. A hierarchical Bayesian meta-analysis correcting for imperfect reference standards was used. Based on components of the antigen–antibody response, 17 studies were stratified into three subgroups: (i) Hepatitis B surface antigen (HBsAg) tests; (ii) anti-HBsAg tests, and (iii) HBs+eAg tests. Further, we pooled estimates on individual tests with sufficient data.RESULTS:In subgroup 1, the pooled sensitivity (Sn) was 94.76% (95% credible interval (CrI): 90.08–98.23%) and specificity (Sp) was 99.54% (95% CrI: 99.03–99.95%). The Determine test reported a pooled Sn 98.2% (95% CrI: 94.7, 99.9) and Sp 99.9% (95% CrI: 99.3, 100); in subgroup 2, Sn 93.2% (95% CrI: 85.1, 98.5), Sp 93.1% (95% CrI: 81.9, 99.9); and in subgroup 3, the Binax test showed Sn 95.5% (95% CrI: 88.9, 99.4), Sp 99.8% (95% CrI: 99.3, 100).CONCLUSIONS:HBsAg tests, including Determine, and the HBs+eAg test, Binax showed high accuracy. Improvements in sensitivity of antibody-based tests will enhance their potential for global first-line screening.

An ultrasound-based fetal weight reference for twins

OBJECTIVE The objective of the study was to construct an ultrasound-based estimated fetal weight-for-gestational-age reference for twin fetuses, stratified by chorionicity. STUDY DESIGN We performed a retrospective cohort study of live-born nonanomalous twins delivered longer than 34 weeks at the Royal Victoria Hospital (Montreal, Canada). Fetal weight was estimated using ultrasound biometric measurements combined using Hadlocks formula. Multilevel linear regression models were used to adjust for clustering by twin pregnancy and to account for the serial ultrasound measurements taken on each fetus. Based on this model, smoothed estimates of fetal weight were made for the third, 10th, 50th, 90th, and 97th percentiles of the fetal weight distribution. Fetal weight references were stratified by fetal chorionicity. RESULTS A total of 642 twin fetuses with a total of 3078 ultrasound observations were included. Sixteen percent of the cohort was monochorionic. Fetal growth accelerated in the second trimester and continued in a linear pattern in the third trimester until term. As expected, the median weight for monochorionic twins was lighter than the median weight for dichorionic twins throughout pregnancy. CONCLUSION The reference values created in this study address serious methodological limitations of existing reference charts and thus provide an improved tool for assessing fetal growth in twin pregnancies. Importantly, dichorionic twins deviated from singleton reference charts at approximately 32 weeks, whereas monochorionic twins deviated at 28 weeks.

P3-S5.04 The diagnostic accuracy of rapid point of care tests used to diagnose Hepatitis B: a Bayesian meta-analysis

Background More than 350 million people are infected with the Hepatitis B virus worldwide, with four million new cases every year. The prevalence of the Hepatitis B virus is highest in developing settings where laboratory equipment and diagnostic resources are limited. This creates a need for rapid point-of-care testing in order to screen blood donors and ensure timely diagnosis and treatment of infected individuals. Although studies have been conducted examining the accuracy of different tests, there has not been a synthesis of the available global evidence, or an assessment of the quality of evidence to date. Objective We conducted a systematic review of the global literature examining the sensitivity and specificity of rapid point-of-care tests used to diagnose Hepatitis B, and meta-analysed the data. Additionally, we conducted a critical appraisal of the quality of included studies. Methods Two reviewers conducted independent searches of five databases between the years of 1990 and 2010 for global evidence. Meta-analysis was performed grouping studies based on whether the index test identified HBsAg, both HBs and eAg, or antibody to HbsAg. We used Bayesian meta-analysis, accounting for the fact that all of the studies used imperfect reference standards (sensitivity and specificity assumed to range between 90% and 100%). The quality of all included full-text studies was assessed using the QUADAS and STARD checklists. Results A total of 17 studies were identified, of which 13 were from developing countries and which investigated 22 different index tests. When studies were pooled, the Determine HBsAg test showed a combined sensitivity of 98.76% and a specificity of 99.94%. Other HBsAg tests showed a lower combined sensitivity (96.77%) but comparable specificity (99.89%). The Amrad HBs+eAg test showed a combined sensitivity of 98.04% and a specificity of 99.04%, while the tests detecting antibody to HBsAg showed a combined sensitivity of 99.77% and a specificity of 96.08%. Studies were of poor-moderate quality with QUADAS scores ranging from 3 to 10/14 and STARD scores ranging from 7 to 14/25 see Abstract P3-S5.04 table 1. Abstract P3-S5.04 Table 1 Results from bayesian meta-analysis of diagnostic accuracy of hepatitis B point-of-care tests Program in R: Hierarchical model Assuming perfect reference standard (100%) Assuming imperfect reference standard (90%–100%) Subgroup Sensitivity (95% CI) Specificity (95% CI) Sensitivity (95% CI) Specificity (95% CI) HBsAg 94.76% (90.08 to 98.23%) 99.54% (99.03 to 99.953%) 96.77% (92.92 to 99.26%) 99.89% (99.55 to 100%) Determine–HBsAg 98.24% (94.74 to 99.98%) 99.96% (99.31 to 100%) 98.76% (94.67 to 99.99%) 99.94% (99.49 to 100%) Amrad–HBs+eAg 95.47% (88.88 to 99.44%) 99.81% (99.33 to 100%) 98.04% (93.39 to 99.83%) 99.95% (99.71 to 100%) Anti-HBs 93.15% (85.04 to 98.5%) 93.08% (81.9 to 99.99%) 99.77% (94.18 to 100%) 96.08% (86.38 to 100%) Conclusion The Amrad and Determine tests show the highest pooled accuracy. However, this could be explained by the fact that the other subgroups included studies examining different index tests with a wide range of accuracies. There is a need for more consistently designed studies, using ideal reference standards recommended by the CDC or Health Canada.

P1-S4.29 Synthesis of evidence on implementation research on point-of-care syphilis tests: a systematic review

Background With the increase in global prevalence of syphilis, synthesis of evidence of point-of-care (POC) assays is warranted. While a clear methodology exists to meta-analyse diagnostic performance, a clear rubric that incorporates implementation research outcomes (IRO) relevant for policy making is lacking. Recently, Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group called for a shift to emphasis on patient-centred outcomes for making policy recommendations. However, a lack of clarity in defining, elucidating, and reporting of these outcomes prevents their utilisation in practice. Within this context, we reviewed global evidence on IROs for syphilis POC tests. Method We systematically searched nine electronic databases for the period of January 1980 to September 2010. Articles that addressed IRO regarding POC syphilis tests were reviewed and data extracted. A second reviewer independently reviewed a subset of the articles. Outcomes were synthesised into a narrative review. Results 31 (48%) from 64 full text articles assessed were included in the narrative review. Twenty-four studies were cross-sectional, six were case-control, while one was a clustered randomised control trial (RCT). IROs were categorised into: Acceptability, Preference, Feasibility, Prevalence, Barriers and Challenges, and Economic Evaluations of POC tests. Three papers reported outcomes on acceptability, four on preference, ten on feasibility, seven on impact, six on prevalence, seven on barriers and challenges, and seven on economic evaluations. Overall, studies were concordant on findings of high acceptability and feasibility of POC tests as well as the testing strategy used. Preference was not well demonstrated in studies. Impact was particularly well demonstrated in antenatal clinic attendees by a clustered RCT. Barriers and challenges ranged from biotechnological limitations of the tests to lack of political will. Heterogeneous methodologies employed across studies to conduct economic evaluations made it difficult to draw conclusive statements. Conclusions Results were generally in agreement across studies, yet unsystematic methods of collecting and recording outcomes made it difficult to statistically combine outcomes. Weaknesses in the reporting of IROs limit our ability to form comprehensive context-specific policies. Further efforts in establishing a framework for conducting implementation research is required.