Evaluation of the accuracy of the Asanté assay as a point-of-care rapid test for HIV-1 recent infections using serum bank specimens from blood donors in South Africa, July 2018 - August 2021.

BACKGROUND: Point-of-care (POC) rapid recency testing can be used as a cost-effective tool to identify recently infected individuals (i.e. infected within the last 12 months) in near-real time, support epidemic control and identify hotspots for transmission as part of recent infection surveillance. OBJECTIVE: To evaluate the performance of the Asanté (HIV-1) rapid recency assay as a POC rapid test among blood donors in South Africa (SA). METHODS: The study was a cross-sectional and validity study of the Asanté HIV-1 Rapid Recency Assay performed on 715 consecutively archived plasma donor specimens from the SA National Blood Services to determine their recency and established HIV infection status. ELISA and rapid assays for HIV antibody detection were used as the reference-testing standard for confirming an infection, while the Maxim HIV-1 limiting antigen (LAg) avidity assay was used as a reference for comparing HIV recency status. Validity tests (sensitivity, specificity, negative and positive predictive values) and Cohen-Kappa tests of the agreement were conducted to compare the Asanté HIV-1 rapid recency assay results with the reference tests. RESULTS: Of the 715 studied blood samples, 63.1% (n=451/715) were confirmed to be HIV-positive based on the reference standard. The sensitivity and specificity of the Asanté HIV-1 rapid recency assay in diagnosing established HIV infection compared to the ELISA were 98.4% (95% CI 96.7 - 99.3) and 99.6% (95% CI 97.6 - 100), respectively. Compared with HIV rapid assay, the sensitivity and specificity of the Asanté HIV-1 rapid recency assay was 98.7% (95% CI 97.0 - 99.4) and 99.2% (95% CI 97.1 - 100), respectively. Of the 451 HIV-positive blood samples, 43% were confirmed as recent HIV infections by the Maxim HIV-1 LAg avidity assay. There was high agreement between the Asanté HIV-1 rapid recency assay and the Maxim HIV-1 LAg avidity assay (94.1%, k=0.879, p<0.0001). The sensitivity and specificity of the Asante HIV-1 assay was 89.4% (95% CI 84.0 - 93.0) and 97.7% (95% CI 94.8 - 99.0), respectively. CONCLUSION: The Asanté HIV-1 rapid recency assay test results demonstrated high accuracy (>90%) compared with the HIV ELISA and rapid assays for determining established infection and the Maxim HIV-1 LAg avidity assay for classifying recent HIV-1 infections. The assay's sensitivity for established infections was below the World Health Organization criteria (<99%) for POC devices. The Asanté HIV-1 rapid recency assay can be used to distinguish between recent and long-term infections, but may not be considered a POC test for determining HIV infection.

Recency of HIV infection, antiretroviral therapy use and viral loads among symptomatic sexually transmitted infection service attendees in South Africa.

BACKGROUND: Better integration of HIV and sexually transmitted infection (STI) prevention and treatment services is needed to accelerate progress towards the goal of zero new HIV infections. OBJECTIVES: To describe HIV positivity, antiretroviral therapy (ART) use, viral suppression and recency of HIV infection among symptomatic STI service attendees at two primary care clinics in South Africa. METHODS: In a cross-sectional study, male and female STI service attendees presenting with symptoms consistent with STI syndromes were enrolled following informed consent. An interviewer-administered questionnaire was completed and appropriate genital and blood specimens were collected for STI testing and HIV biomarker measurements including recency of infection and antiretroviral (ARV) drug levels. Descriptive statistics were used to describe enrolled attendees, and to determine the proportion of attendees who were HIV-positive, recently infected, taking ART and virally suppressed. HIV-positive attendees with detectable ARVs were considered to be on ART, while those with viral loads (VLs) ≤200 copies/mL were considered virally suppressed. RESULTS: Of 451 symptomatic attendees whose data were analysed, 93 (20.6%) were HIV-positive, with 15/93 (16.1%) being recently infected. Recent infection was independently associated with genital ulcer disease at presentation, especially ulcers with no detectable STI pathogens. Among the 78 (83.9%) with long-term infection, only 30 (38.5%) were on ART, with 23/30 (76.7%) virally suppressed. CONCLUSIONS: In a population at risk of HIV transmission, there was a high burden of recent infection and unsuppressed VLs. Incorporating pre-exposure prophylaxis, ART initiation and adherence support into STI services will be necessary for progress towards eliminating HIV transmission.

Recency of HIV infection, antiretroviral therapy use and viral loads among symptomatic sexually transmitted infection service attendees in South Africa

Background. Better integration of HIV and sexually transmitted infection (STI) prevention and treatment services is needed to accelerate progress towards the goal of zero new HIV infections. Objectives. To describe HIV positivity, antiretroviral therapy (ART) use, viral suppression and recency of HIV infection among symptomatic STI service attendees at two primary care clinics in South Africa. Methods. In a cross-sectional study, male and female STI service attendees presenting with symptoms consistent with STI syndromes were enrolled following informed consent. An interviewer-administered questionnaire was completed and appropriate genital and blood specimens were collected for STI testing and HIV biomarker measurements including recency of infection and antiretroviral (ARV) drug levels. Descriptive statistics were used to describe enrolled attendees, and to determine the proportion of attendees who were HIV-positive, recently infected, taking ART and virally suppressed. HIV-positive attendees with detectable ARVs were considered to be on ART, while those with viral loads (VLs) ≤200 copies/mL were considered virally suppressed. Results. Of 451 symptomatic attendees whose data were analysed, 93 (20.6%) were HIV-positive, with 15/93 (16.1%) being recently infected. Recent infection was independently associated with genital ulcer disease at presentation, especially ulcers with no detectable STI pathogens. Among the 78 (83.9%) with long-term infection, only 30 (38.5%) were on ART, with 23/30 (76.7%) virally suppressed. Conclusions. In a population at risk of HIV transmission, there was a high burden of recent infection and unsuppressed VLs. Incorporating pre-exposure prophylaxis, ART initiation and adherence support into STI services will be necessary for progress towards eliminating HIV transmission

Comparison of chlorine dioxide and dichloroisocyanurate disinfectants for use in the dental setting.

AIM: The aim of this study was to compare the antimicrobial properties of a slow release noncorrosive chlorine dioxide with those of sodium dichloroisocyanurate to establish their possible use in the dental settings. MATERIALS AND METHODS: Disinfectant solutions were prepared according to manufacturers' instructions and tested against Staphylococcus aureus ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Streptococcus mutans NCTC 1044, Candida albicans ATCC 90028, Bacillus subtilis ATCC 15244 spores, Mycobacterium tuberculosis ATCC 25177, Mycobacterium avium subsp. avium ATCC 25291 and Hepatitis B virus using the Standard quantitative suspension test. The shelf-lives of the disinfectants were also determined. RESULTS: Both disinfectants killed all the test organisms within 30 seconds. B. subtilis spores were killed in 2 and 2.5 minutes by chlorine dioxide and sodium dichloroisocya nurate respectively. When diluted solutions of these disinfectants were stored in screw cap bottles, they retained their activity for at least 30 days. CONCLUSIONS: Chlorine dioxide and sodium dichloroisocyanurate containing disinfectants can be used in the denta settings for surfaces and heat sensitive instruments. However, chlorine dioxide is advantageous because it is non-corrosive and the effective concentration is lower than that recommended for sodium dichloroisocyanurate.

Internal controls for quantitative polymerase chain reaction of swine mammary glands during pregnancy and lactation.

High-throughput microarray analysis is an efficient means of obtaining a genome-wide view of transcript profiles across physiological states. However, quantitative PCR (qPCR) remains the chosen method for high-precision mRNA abundance analysis. Essential for reliability of qPCR data is normalization using appropriate internal control genes (ICG), which is now, more than ever before, a fundamental step for accurate gene expression profiling. We mined mammary tissue microarray data on >13,000 genes at -34, -14, 0, 7, 14, 21, and 28 d relative to parturition in 27 crossbred primiparous gilts to identify suitable ICG. Initial analysis revealed TBK1, PCSK2, PTBP1, API5, VAPB, QTRT1, TRIM41, TMEM24, PPP2R5B, and AP1S1 as the most stable genes (sample/reference = 1 +/- 0.2). We also included 9 genes previously identified as ICG in bovine mammary tissue. Gene network analysis of the 19 genes identified AP1S1, API5, MTG1, VAPB, TRIM41, MRPL39, and RPS15A as having no known co-regulation. In addition, UXT and ACTB were added to this list, and mRNA abundance of these 9 genes was measured by qPCR. Expression of all 9 of these genes was decreased markedly during lactation. In a previous study with bovine mammary tissue, mRNA of stably expressed genes decreased during lactation due to a dilution effect brought about by large increases in expression of highly abundant genes. To verify this effect, highly abundant mammary genes such as CSN1S2, SCD, FABP3, and LTF were evaluated by qPCR. The tested ICG had a negative correlation with these genes, demonstrating a dilution effect in the porcine mammary tissue. Gene stability analysis identified API5, VABP, and MRPL39 as the most stable ICG in porcine mammary tissue and indicated that the use of those 3 genes was most appropriate for calculating a normalization factor. Overall, results underscore the importance of proper validation of internal controls for qPCR and highlight the limitations of using absence of time effects as the criteria for selection of appropriate ICG. Further, we showed that use of the same ICG from one organism might not be suitable for qPCR normalization in other species.

Parental knowledge and attitudes of Minnesota laws concerning adolescent medical care.

OBJECTIVE: To determine parents' knowledge and attitudes of medicolegal issues affecting adolescent medical care. DESIGN: An anonymous, mailed survey with 16 questions concerning Minnesota consent and confidentiality laws that affect adolescents' medical care. SETTING: A community of >70 000 in rural, southeastern Minnesota. PARTICIPANTS: Parents of 600 randomly selected 7th- through 12th-grade public school students. RESULTS: Two hundred eighty-eight (48%) parents returned the surveys. Parents achieved a median score of 18.8% (range, 0%-93.8%) correct on a test of knowledge. Opinion was a median of +0.3 on a scale where -1 signified "a bad law," 0 signified "neither a good nor bad law," and +1 signified "a good law." Four questions, however, generated a more intense response. Seventy-seven percent of parents reported that, as a whole, the laws in the survey had no effect on them and/or their children. CONCLUSIONS: These results suggest that parents are not knowledgeable of Minnesota laws that affect adolescent medical care. Overall opinion of these laws was mildly positive, with notable exceptions. Parents also lack a sense of impact of laws affecting adolescent medical care. Lack of knowledge and the presence of certain attitudes allow for identification of issues that clinicians should address by incorporating medicolegal education into the care of adolescents and their families. These results are especially timely in light of the Parental Rights and Responsibilities Act under consideration in Congress, which would provide parents greater authority over their children's medical care.

On the culture of student abuse in medical school.

The abuse of students is ingrained in medical education, and has shown little amelioration despite numerous publications and righteous declarations by the academic community over the past decade. The culture of abuse conflicts with the renewed commitments of medical educators and practice professionals to imbue students with a higher degree of professionalism and cultural sensitivity. The authors describe the profiles of student abuse, drawn from recent national surveys of medical students using the AAMC Medical School Graduation Questionnaire, and focus on the most common forms of reported mistreatment--public belittlement and humiliation--that appear to be misguided efforts to reinforce learning. Along with others, the authors believe that the use of aversive methods to make students learn and behave is likely to foster insensitive and punitive behaviors that are passed down from teacher to learner, a "transgenerational legacy" that leads to future mistreatment of others by those who themselves have been mistreated. The undesirable result is compounded when these behaviors are adopted and directed toward patients and colleagues. The authors advocate more concerted action to curtail the abuse of medical students, citing current and proposed accreditation standards that will be employed more stringently by the LCME, and propose a series of more assertive actions that schools should take. The authors stress that the attitudes, behaviors, and values that students acquire in medical school are as much the products of their socialization as the outcomes of curricular design and pedagogy, and implore medical educators to tidy up the environment for learning.

On the importance and validity of medical accreditation standards.

In late 1997, the authors conducted a national survey of communities of interest about the importance and clarity of 44 accreditation standards applied to teaching, learning, and evaluation in medical schools by the Liaison Committee on Medical Education (LCME). Questionnaires were mailed to deans and educational administrators at U.S. medical schools; current LCME members and surveyors and those who had served during the preceding five years; a random selection of residency program directors drawn from both general practice and speciality disciplines; sample groups of medical students and residents; and a cohort of practicing physicians not affiliated with academic medical institutions. Altogether 1,659 questionnaires were mailed, and 701 responses were received (42%). The recipients were asked to use a five-point Likert scale to rate each of the 44 standards both for its perceived importance as an indicator of the quality of undergraduate medical education and for the clarity with which the standard's intent was conveyed. Although the mean ratings of importance all fell in the "moderately important" and "highly important" areas across the respondent groups, the ratings divided into three groups, semantically and statistically. At the high end for importance are standards dealing with fundamental qualities of students, instruction, and the structuring of resources. At the low end of the importance scale are standards dealing largely with matters of process. The ratings for clarity were systematically lower than the ratings for importance, and in some cases the rating for clarity were even more widely discrepant with the ratings for importance. Individual comments by respondents about certain standards were critical of their complicated construction and of confusion about their meaning and measures of compliance. One or more of these hallmarks--being rated of lower importance or clarity, and being the target of criticism by survey respondents--distinguished most of the standards that earlier study had shown are often neglected by surveyors. The predictive validity of each of a number of standards was examined by testing the association between the standard (or its derivative) and outcomes expressed in annual student and school questionnaires and compiled in databases of the Association of American Medical Colleges and the American Medical Association. The result was a mixed bag, confounded by the absence of specific dimensions of many accreditation standards (independent variables) and the lack of discriminating measures of outcome (dependent variables). Nevertheless, the LCME's accreditation standards are believed to be important by those most affected by them. And beyond validating that medical accreditation is guided by relevant standards for teaching, learning, and evaluation, the results of this study point to ways by which the process can be made more precise and useful.

The meaning and application of medical accreditation standards.

The authors examined the operational meaning of the 48 items that state the accreditation standards for teaching, learning, and evaluation in medical school, and determined the extent to which these standards were applied by schools and by on-site evaluators for 59 programs surveyed by the Liaison Committee on Medical Education (LCME) in 1994-1996. In this study, "application" meant that evidence was offered, not necessarily that it proved compliance with the standard. The data sources employed were the medical education databases and self-studies prepared by schools undergoing accreditation surveys, and the reports prepared by ad hoc teams of surveyors. The frequency with which evidence of compliance was offered by the schools and cited by evaluators was determined for each of the 48 accreditation requirements. In addition, the authors compared the patterns of surveyors' concerns about noncompliance at schools surveyed during 1984-1986 and at those visited during 1994-1996. In 1994-1996, schools addressed 42 of the 48 accreditation requirements in 90% of instances of more. The areas of particularly low attention dealt with the definition and communication of educational objectives (47% of schools provided evidence); faculty authority and control of academic programs in clinical affiliates (12%); and the faculty's commitment to being effective teachers and their understanding of pedagogy, curricular design, and methods of evaluation (8%). Survey teams, in contrast, accounted in their reports for only 26 (55%) of the standards during the same time period. Among those least frequently addressed were the definition and communication of educational objectives by schools (accounted for in 59% of the reports); assessment of students' problem-solving ability (51%); comparability of educational experiences and student evaluation across dispersed teaching sites (49%); faculty understanding of pedagogy, curriculum construction, and the evaluation of students (8%); faculty authority and control of academic programs in clinical affiliates (7%); and knowledge of the administration and faculty about methods for measuring student performance (2%). Over the past decade, surveyors' most frequently cited concerns about schools' noncompliance with accreditation standards dealt with student counseling and health services, institutional financial and space/facilities resources, faculty issues, and vacant decanal and department chair positions. Next in order were concerns about various aspects of the educational program leading to the MD degree. Among the high-profile concerns about the educational program that increased significantly over the decade were those about curriculum design, management, and evaluation; primary/ambulatory care experiences; and student advancement policies and due-process issues. Schools paid high attention to most of the 48 standards, in large part because they were prompted by the formatting of the medical education database and self-study guidelines. In those instances of lesser attention, the fault lies as much or more with ambiguities in the construction and meaning of the standards as with institutional laxity. The surveyors' inattention to accreditation standards is more troubling. In some cases it can be attributed to uncertainties about the meaning of the requirements and the quantities that need to be audited; or surveyors may be comfortable reaching a "substantial compliance" threshold without adducing all the evidence. The authors argue that many of the standards given scant attention on surveys are important to educational program development and quality control. The LCME will need to consider whether more prominent definition and highlighting should be given to neglected standards, or whether some of the requirements are at the margin as quality indicators. A planned survey of communities of interest-educators, practitioners, students, graduates, and residency program directors, among others-may help confirm

The objectives of medical education: reflections in the accreditation looking glass.

The authors explored the extent to which medical schools have established institutional and departmentalized educational objectives, by examining the accreditation databases, institutional self-studies, and site visit reports of 59 schools surveyed by the Liaison Committee on medical Education (LCME) in 1994-1996. In this study, the individual school was the unit of analysis, and the dependent variables were statements--in outcomes' terms--of institutional and departmental learning objectives. Objectives were classified as "robust" when they were expressed as measurable learning outcomes in the domains of knowledge and skills and behaviors. Departmental objectives were assessed separately for core basic science courses and clinical clerkships. A number of independent variables were studied for their association with the elaboration of outcomes-based educational objectives: centralized management of the curriculum, curricular reform, an office of education, an institutionalized faculty development program, problem-based learning, interdisciplinary teaching, systematized assessment of educational outcomes, and structured clinical skills assessment. Of the 59 schools, 15 (25%) had robust institutional objectives that identified items of measurable knowledge, skills, and behavior, while 44 (75%) had modest objectives, usually descriptions of the purpose of the curriculum, global statements about the knowledge and behavior qualities that students should acquire, and the subjects that instructors intended to tech. Schools with well-articulated learning outcomes were more likely to have centralized management of the curriculum, a record of curricular reform, a program of problem-based learning, rich basic science course and clerkship objectives, and structured assessment of students' clinical skills. Well-stated and diverse educational objectives were found for basic science courses in only 13 of the 59 schools (22%). Thirty of the schools (51%) had clerkships with robust learning objectives, more commonly in the generalist specialties of pediatrics, family medicine, and internal medicine. Clerkships with stout objectives more often employed structured assessments of students' clinical skills. Schools that paid attention to the explication of learning objectives were more likely to link specific institutional and departmentalized outcomes with methods of evaluating students, in turn guiding the content and methods of instruction. Schools with vapid objectives attracted 40% more accreditation citations for shortcomings in curricular management, course and clerkship quality, and the evaluation of student achievement, especially in the clinical skills domain. In the future, accreditors should focus more closely on this association.

The influence of accreditation on educational change in U.S. medical schools.

The authors examined the influence of accreditation on educational change and reform in U.S. medical schools in the past decade, by reviewing the survey databases and site visit reports of 90 schools that had comprehensive accreditation surveys by the Liaison Committee on Medical Education (LCME) between July 1992 and June 1997. In this study, substantive change was defined as centralizing the design and management of the curriculum, as well as one or more of the following reforms: integrating basic and clinical science instruction and/or conversion to interdisciplinary courses; implementing methods of active, small-group, independent, and hypothesis-based learning; and substantially increasing students' exposure to ambulatory and primary care. Accreditation reports were reviewed to determine the extent to which the LCME previously had admonished schools for shortcomings in their educational programs and advised curricular changes. Notice was taken of grant support by national foundations promoting educational reform, in relation both to the correction of accreditation deficiencies and to curricular reform undertaken by schools on their own initiative. The study also scrutinized the evolution of accreditation standards promoting educational reform, and the LCME's support of initiatives for shortening the period of medical education and promoting performance-based teaching and the assessment of clinical skills. On entering the 1990s, the LCME toughened the standards for design and management of the medical curriculum and for the evaluation of educational program effectiveness that schools must conduct. The greater assessment rigor identified educational shortcomings in 61 of 90 medical schools coming up for accreditation surveys during 1992-1997. On those occasions, 34 of the 61 schools had instituted reforms or were on the verge of doing so. Twenty-five of the schools carrying out reforms (73%) had received major foundation grants, compared with ten of the 27 schools (37%) that had accomplished little. Fifteen schools that had not been reproached earlier were found on the 1992-1997 surveys to have undertaken substantial innovation on their own initiative, five with the help of major foundation awards. The study also shows that a number of schools implemented parts of more sweeping reforms with the help of smaller foundation grants for more discrete purposes. In some instances, it has not been possible to differentiate the influence of the LCME as a force for educational reform from the incentives for change created by national foundations. Overall, the LCME, through its standards and assessment practices, and in synergy with schools and kindred agencies promoting change, is now on the leading edge of improved education and evaluation in the nation's medical schools.

Defective monocyte chemotaxis in active lepromatous leprosy.

This study of monocyte chemotaxis in leprosy patients showed a significant inverse correlation (p less than 0.05) of chemotaxis and the bacterial index (BI) (N = 22). In addition, there was a significant inverse correlation (p less than 0.05) between chemotaxis and the serum levels of anti-phenolic glycolipid-I IgM antibodies (N = 20). Patients taking thalidomide who had a BI greater than or equal to 1 had a significantly greater (p less than 0.001) chemotaxis response than that of patients with the same BI who were not taking thalidomide. No significant decrease in chemotaxis of monocytes from healthy donors was observed when the cells were pre-incubated with serum from 18 leprosy patients. We conclude that monocytes from patients with active lepromatous leprosy not receiving thalidomide have an intrinsic abnormality when assessed by chemotaxis.

Successful spleno-renal shunt and splenectomy in two patients with alpha-1-antitrypsin deficiency.

Recent evidence suggests that the cirrhosis of alpha-1-antitrypsin deficiency is not invariably fatal as it was previously thought. Portal hypertension is often the major determinant of survival. The few reports of porta-systemic venous anastomosis in this disorder have shown poor results or uncertain outcome. Thus, doubts exist as to whether porta-systemic shunts should be performed in alpha-1-antitrypsin deficiency. Two patients with alpha-1-antitrypsin deficiency (PiZZ) and associated portal hypertension, cirrhosis, and hypersplenism underwent splenorenal shunt and splenectomy 8 yr ago, and both have done well. One of the patients has chronic severe headaches, diarrhea, exudative enteropathy, sinusitis, and hematuria, all uncommon in alpha-1-antitrypsin deficiency but possibly related to the antienzyme deficiency. She also has a higher trypsin inhibitory capacity than is generally reported in ZZ individuals. Based on the experience with these 2 patients, it appears that alpha-1-antitrypsin deficiency with cirrhosis is not a valid contraindication to the performance of a portasystemic shunt.

Cerebral gigantism and primary hypothyroidism: pleiotropy or incidental concurrence.

An 8.5-month-old baby girl had cerebral gigantism and primary hypothyroidism with generalized large muscles (the Kocher-Debré-Semelaigne syndrome). The significance of this association remains to be determined.

Hypocalcemic coma following two pediatric phosphate enemas.

Coma, tetany, dehydration, hypotension, tachycardia, and hyperpyrexia developed in a 2 1/2-year-old girl following two hypertonic phosphate pediatric enemas. She had marked hyperphosphatemia, hypocalcemia, hypernatremia, and acidosis. Hypocalcemia due to hyperphosphatemia can explain all of these findings. Calculations indicate that about one third of the phosphorus and sodium contents of the enema were absorbed. Physicians should be aware of the potentially lethal complication of this treatment, which is part of everyday practice.