Evaluation of Diagnostic Accuracy, Feasibility and Client Preference for Rapid Oral Fluid-Based Diagnosis of HIV Infection in Rural India

BACKGROUND: Oral fluid-based rapid tests are promising for improving HIV diagnosis and screening. However, recent reports from the United States of false-positive results with the oral OraQuick® ADVANCE HIV1/2 test have raised concerns about their performance in routine practice. We report a field evaluation of the diagnostic accuracy, client preference, and feasibility for the oral fluid-based OraQuick® Rapid HIV1/2 test in a rural hospital in India. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional, hospital-based study was conducted in 450 consenting participants with suspected HIV infection in rural India. The objectives were to evaluate performance, client preference and feasibility of the OraQuick® Rapid HIV-1/2 tests. Two Oraquick® Rapid HIV1/2 tests (oral fluid and finger stick) were administered in parallel with confirmatory ELISA/Western Blot (reference standard). Pre- and post-test counseling and face to face interviews were conducted to determine client preference. Of the 450 participants, 146 were deemed to be HIV sero-positive using the reference standard (seropositivity rate of 32% (95% confidence interval [CI] 28%, 37%)). The OraQuick test on oral fluid specimens had better performance with a sensitivity of 100% (95% CI 98, 100) and a specificity of 100% (95% CI 99, 100), as compared to the OraQuick test on finger stick specimens with a sensitivity of 100% (95% CI 98, 100), and a specificity of 99.7% (95% CI 98.4, 99.9). The OraQuick oral fluid-based test was preferred by 87% of the participants for first time testing and 60% of the participants for repeat testing. CONCLUSION/SIGNIFICANCE: In a rural Indian hospital setting, the OraQuick® Rapid- HIV1/2 test was found to be highly accurate. The oral fluid-based test performed marginally better than the finger stick test. The oral OraQuick test was highly preferred by participants. In the context of global efforts to scale-up HIV testing, our data suggest that oral fluid-based rapid HIV testing may work well in rural, resource-limited settings

HIV Risk and Associations of HIV Infection among men who have sex with men in Peri-Urban Cape Town, South Africa

<p>Abstract</p> <p>Background</p> <p>The HIV epidemic in Sub Saharan Africa has been traditionally assumed to be driven by high risk heterosexual and vertical transmission. However, there is an increasing body of data highlighting the disproportionate burden of HIV infection among MSM in the generalized HIV epidemics across of Southern Africa. In South Africa specifically, there has been an increase in attention focused on the risk status and preventive needs of MSM both in urban centers and peri-urban townships. The study presented here represents the first evaluation of HIV prevalence and associations of HIV infection among MSM in the peri-urban townships of Cape Town.</p> <p>Methods</p> <p>The study consisted of an anonymous probe of 200 men, reporting ever having had sex with another man, recruited through venue-base sampling from January to February, 2009.</p> <p>Results</p> <p>Overall, HIV prevalence was 25.5% (n = 51/200). Of these prevalent HIV infections, only 6% of HIV-1 infected MSM were aware of their HIV status (3/50). 0% of men reported always having safe sex as defined by always wearing condoms during sex and using water-based lubricants. Independent associations with HIV infection included inconsistent condom use with male partners (aOR 2.3, 95% CI 1.0-5.4), having been blackmailed (aOR 4.4, 95% CI 1.6-20.2), age over 26 years (aOR 4.2, 95% CI 1.6-10.6), being unemployed (aOR 3.7, 95% CI 1.5-9.3), and rural origin (aOR 6.0, 95% CI 2.2-16.7). Bisexual activity was reported by 17.1% (34/199), and a total of 8% (16/200) reported having a regular female partner. Human rights violations were common with 10.5% (n = 21/200) reporting having been blackmailed and 21.0% (n = 42/200) reporting being afraid to seek health care.</p> <p>Conclusions</p> <p>The conclusions from this study include that a there is a high risk and underserved population of MSM in the townships surrounding Cape Town. The high HIV prevalence and high risk sexual practices suggest that prevalence will continue to increase among these men in the context of an otherwise slowing epidemic. These data further highlight the need to better characterize risk factors for HIV prevention and appropriate targeted combination packages of HIV interventions including biomedical, behavioural, and structural approaches to mitigate HIV risk among these men.</p

HIV Prevalence, Risks for HIV Infection, and Human Rights among Men Who Have Sex with Men (MSM) in Malawi, Namibia, and Botswana

BACKGROUND: In the generalized epidemics of HIV in southern Sub-Saharan Africa, men who have sex with men have been largely excluded from HIV surveillance and research. Epidemiologic data for MSM in southern Africa are among the sparsest globally, and HIV risk among these men has yet to be characterized in the majority of countries. METHODOLOGY: A cross-sectional anonymous probe of 537 men recruited with non-probability sampling among men who reported ever having had sex with another man in Malawi, Namibia, and Botswana using a structured survey instrument and HIV screening with the OraQuick(c) rapid test kit. PRINCIPAL FINDINGS: The HIV prevalence among those between the ages of 18 and 23 was 8.3% (20/241); 20.0% (42/210) among those 24-29; and 35.7% (30/84) among those older than 30 for an overall prevalence of 17.4% (95% CI 14.4-20.8). In multivariate logistic regressions, being older than 25 (aOR 4.0, 95% CI 2.0-8.0), and not always wearing condoms during sex (aOR 2.6, 95% CI 1.3-4.9) were significantly associated with being HIV-positive. Sexual concurrency was common with 16.6% having ongoing concurrent stable relationships with a man and a woman and 53.7% had both male and female sexual partners in proceeding 6 months. Unprotected anal intercourse was common and the use of petroleum-based lubricants was also common when using condoms. Human rights abuses, including blackmail and denial of housing and health care was prevalent with 42.1% (222/527) reporting at least one abuse. CONCLUSIONS: MSM are a high-risk group for HIV infection and human rights abuses in Malawi, Namibia, and Botswana. Concurrency of sexual partnerships with partners of both genders may play important roles in HIV spread in these populations. Further epidemiologic and evaluative research is needed to assess the contribution of MSM to southern Africa's HIV epidemics and how best to mitigate this. These countries should initiate and adequately fund evidence-based and targeted HIV prevention programs for MSM

Field Evaluation of Calypte’s AWARE™ Blood Serum Plasma (BSP) and Oral Mucosal Transudate (OMT) Rapid Tests for Detecting Antibodies to HIV-1 and 2 in Plasma and Oral Fluid

As programs to prevent and care for HIV-infected persons are scaled-up in Africa, there is the need for continuous evaluation of the performance of test kits that could best support these programs. The present study evaluated the sensitivity, specificity, ease of use, and cost of AWARE ™ Blood Serum Plasma (BSP) and Oral Mucosal Transudate (OMT) Rapid HIV-1/2 test kits using real-time and archived samples of HIV-infected persons from Cameroon. Matched whole blood and OMT specimens were collected prospectively from HIV-positive and HIV-negative persons from different regions of Cameroon and tested using the AWARE ™ BSP and OMT test kits, respectively. These results were compared to the gold standard that included a combination of Determine HIV-1/2 and Enzygnost HIV-1/2. The BSP Rapid test kit was further evaluated using well characterized panels of HIV-2 and HIV-1 group O samples. Cost and end-user analysis of the OMT test kit was done by comparing its actual cost, consumables, safety, bench time and manipulation with other test kits. Of the 732 matched samples, 412 (56.3%) and 320 (43.7%) were from females and males, respectively. Of these samples, 23 (3.1%) gave discordant results between Determine HIV-1/2 and Enzygnost HIV1/2 and were excluded from the analysis. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the AWARE™ BSP were 100%. The AWARE™ OMT had 98.8% sensitivity, 98.9% specificity, 98.0% PPV and 99.4% NPV. The results of a well-characterized archived panel of HIV-2 (n=7) and HIV-1 group O (n=3) samples using the AWARE™ BSP Rapid test kit gave 100% concordance. Total per patient cost of the AWARE OMT rapid test kit was US$4.72 compared to a mean cost of US$7.33 ± 0.11 for the other test kits. Both the AWARE™ BSP and OMT Rapid test kits demonstrated high sensitivities and specificities on all samples tested and were well adapted for use in resource-constrained settings with high HIV heterogeneity such as Cameroon. The AWARE ™ HIV-1/2 OMT Rapid test kit appears to be the cheapest, safest and easiest to use compared with other available test kits

Sensitivity of Five Rapid HIV Tests on Oral Fluid or Finger-Stick Whole Blood: A Real-Time Comparison in a Healthcare Setting

BACKGROUND: Health authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known. METHODS AND FINDINGS: 200 adults with documented HIV-1 (n=194) or HIV-2 infection (n=6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2 was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2, Determine HIV 1-2, Determine HIV-1/2 Ag/Ab Combo and INSTI HIV-1/HIV-2. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (p<0.0001). OraQuick was less sensitive on OF than on FSB (p=0.008). Among the six patients with three or more negative tests, two had recent HIV infection and four patients on antiretroviral therapy had undetectable plasma viral load. When patients positive in all the tests were compared with patients who had at least one negative test, only a plasma HIV RNA level<200 cp/ml was significantly associated with a false-negative result (p=0.009). When the 33 rapid tests negative on FSB were repeated on serum, all but six (5 negative with OraQuick, 1 with INSTI) were positive. The sensitivity of OraQuick, Determine and Determine Ag/Ab Combo was significantly better on serum than on FSB (97.5%, p=0.04; 100%, p=0.004; and 100%, p=0.02, respectively). CONCLUSION: When evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum

A Polyadenylation Factor Subunit Implicated in Regulating Oxidative Signaling in Arabidopsis thaliana

BACKGROUND: Plants respond to many unfavorable environmental conditions via signaling mediated by altered levels of various reactive oxygen species (ROS). To gain additional insight into oxidative signaling responses, Arabidopsis mutants that exhibited tolerance to oxidative stress were isolated. We describe herein the isolation and characterization of one such mutant, oxt6. METHODOLOGY/PRINCIPAL FINDINGS: The oxt6 mutation is due to the disruption of a complex gene (At1g30460) that encodes the Arabidopsis ortholog of the 30-kD subunit of the cleavage and polyadenylation specificity factor (CPSF30) as well as a larger, related 65-kD protein. Expression of mRNAs encoding Arabidopsis CPSF30 alone was able to restore wild-type growth and stress susceptibility to the oxt6 mutant. Transcriptional profiling and single gene expression studies show elevated constitutive expression of a subset of genes that encode proteins containing thioredoxin- and glutaredoxin-related domains in the oxt6 mutant, suggesting that stress can be ameliorated by these gene classes. Bulk poly(A) tail length was not seemingly affected in the oxt6 mutant, but poly(A) site selection was different, indicating a subtle effect on polyadenylation in the mutant. CONCLUSIONS/SIGNIFICANCE: These results implicate the Arabidopsis CPSF30 protein in the posttranscriptional control of the responses of plants to stress, and in particular to the expression of a set of genes that suffices to confer tolerance to oxidative stress

Mental health in the slums of Dhaka - a geoepidemiological study

Gruebner O, Khan MH, Lautenbach S, et al. Mental health in the slums of Dhaka - a geoepidemiological study. BMC Public Health. 2012;12(1): 177.Background: Urban health is of global concern because the majority of the world's population lives in urban areas. Although mental health problems (e.g. depression) in developing countries are highly prevalent, such issues are not yet adequately addressed in the rapidly urbanising megacities of these countries, where a growing number of residents live in slums. Little is known about the spectrum of mental well-being in urban slums and only poor knowledge exists on health promotive socio-physical environments in these areas. Using a geo-epidemiological approach, the present study identified factors that contribute to the mental well-being in the slums of Dhaka, which currently accommodates an estimated population of more than 14 million, including 3.4 million slum dwellers. Methods: The baseline data of a cohort study conducted in early 2009 in nine slums of Dhaka were used. Data were collected from 1,938 adults (>= 15 years). All respondents were geographically marked based on their households using global positioning systems (GPS). Very high-resolution land cover information was processed in a Geographic Information System (GIS) to obtain additional exposure information. We used a factor analysis to reduce the socio-physical explanatory variables to a fewer set of uncorrelated linear combinations of variables. We then regressed these factors on the WHO-5 Well-being Index that was used as a proxy for self-rated mental wellbeing. Results: Mental well-being was significantly associated with various factors such as selected features of the natural environment, flood risk, sanitation, housing quality, sufficiency and durability. We further identified associations with population density, job satisfaction, and income generation while controlling for individual factors such as age, gender, and diseases. Conclusions: Factors determining mental well-being were related to the socio-physical environment and individual level characteristics. Given that mental well-being is associated with physiological well-being, our study may provide crucial information for developing better health care and disease prevention programmes in slums of Dhaka and other comparable settings

Maternal Wnt/β-Catenin Signaling Coactivates Transcription through NF-κB Binding Sites during Xenopus Axis Formation

Maternal Wnt/β-Catenin signaling establishes a program of dorsal-specific gene expression required for axial patterning in Xenopus. We previously reported that a subset of dorsally expressed genes depends not only on Wnt/β-Catenin stimulation, but also on a MyD88-dependent Toll-like receptor/IL1-receptor (TLR/IL1-R) signaling pathway. Here we show that these two signal transduction cascades converge in the nucleus to coactivate gene transcription in blastulae through a direct interaction between β-Catenin and NF-κB proteins. A transdominant inhibitor of NF-κB, ΔNIκBα, phenocopies loss of MyD88 protein function, implicating Rel/NF-κB proteins as selective activators of dorsal-specific gene expression. Sensitive axis formation assays in the embryo demonstrate that dorsalization by Wnt/β-Catenin requires NF-κB protein activity, and vice versa. Xenopus nodal-related 3 (Xnr3) is one of the genes with dual β-Catenin/NF-κB input, and a proximal NF-κB consensus site contributes to the regional activity of its promoter. We demonstrate in vitro binding of Xenopus β-Catenin to several XRel proteins. This interaction is observed in vivo upon Wnt-stimulation. Finally, we show that a synthetic luciferase reporter gene responds to both endogenous and exogenous β-Catenin levels in an NF-κB motif dependent manner. These results suggest that β-Catenin acts as a transcriptional co-activator of NF-κB-dependent transcription in frog primary embryonic cells

Cervical epidural steroid injections in the management of cervical radiculitis: interlaminar versus transforaminal. A review

There has been recent concern regarding the safety of cervical epidural steroid injections. The decision to proceed with treatment requires balancing the risk and benefits. This article is an in depth review of the efficacy, complications, and technique of both interlaminar and transforaminal cervical epidural steroid injections in the management of cervical radiculitis