Gaucher disease is a rare autosomal recessive glycosphingolipid storage disease that ultimately leads to reduced life expectancy. Management of Gaucher disease is challenging due to its wide ...genotypic and phenotypic variability and changing clinical manifestations due to effective treatment. Deliberation between experts is essential to discuss daily clinical practice and identify controversies regarding the management of Gaucher disease. The usefulness of methods like Delphi surveys is suitable for setting up consensus recommendations for different clinical scenarios. The goal of this study was to develop an expert consensus document for the management of type 1 Gaucher disease by local experts. A modified e-Delphi was carried out to develop an expert consensus document on the management goals of type 1 Gaucher disease in South Africa. Following a literature review and input from the steering committee, 205 management goals and best practice statements were e-mailed to an independent panel for consensus development using three rounds of voting. The panel consisted of five local healthcare practitioners with expertise in Gaucher disease. Each panelist provided independent evaluations of statements sent to them via a dedicated survey platform. Panelists indicated their level of agreement on a 9-point Likert scale (1 = absolute disagreement to 9 = absolute agreement) during each round of voting. The criteria to retain a statement in the final round were greater than or equal to80% high agreement (7-9). 193 statements met the consensus threshold after three rounds of voting and were included in the final guidance document. In general, the management goals presented in this paper are in line with existing literature on the subject. Additional management goals and general recommendations on sound clinical practice, obtained from more recent research and the panelists' own clinical experience, have been included to develop a comprehensive consensus document on the management goals of type 1 Gaucher disease. This paper provides high-level guidance with respect to management goals, and the use of current therapies and adjunctive interventions in type 1 Gaucher disease to assist clinicians in their decisions about the appropriate management of patients in everyday clinical practice. These management goals and best practice statements might be used to inform an update to future South African guidelines on the disease.
The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health ...care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and “flattening the curve” while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient’s own blood. This multinational and diverse group of authors issue this “Call to Action” underscoring “The Essential Role of Patient Blood Management in the Management of Pandemics” and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.
The WHO recently recommended the new Xpert MTB/RIF Ultra assay (Ultra) instead of the Xpert MTB/RIF assay because Ultra has improved sensitivity. We report the diagnostic accuracy of Ultra for ...tuberculous adenitis in a tuberculosis and HIV endemic setting.
We obtained fine-needle aspirates (FNA) and lymph node tissue by core-needle biopsy in adult patients with peripheral lymphadenopathy of >20 mm. Ultra and mycobacterial culture were performed on FNA and tissue specimens, with histological examination of tissue specimens. We assessed the diagnostic accuracy of Ultra against a composite reference standard of 'definite tuberculosis' (microbiological criteria) or 'probable tuberculosis' (histological and clinical criteria).
We prospectively evaluated 99 participants of whom 50 were HIV positive: 21 had 'definite tuberculosis', 15 'probable tuberculosis' and 63 did not have tuberculosis (of whom 38% had lymphoma and 19% disseminated malignancy). Using the composite reference standard the Ultra sensitivity on FNA was 70% (95% CI 51-85; 21 of 30), and on tissue was 67% (45-84; 16/24) these were far superior to the detection of acid-fast bacilli on an FNA (26%; 7/27); AFB on tissue (33%; 8/24); or tissue culture (39%; 9/23). The detection of granulomas on histology had high senstivity (83%) but the lowest specficity. When compared with culture the Ultra on FNA had a sensitvity of 78% (40-97; 7/9) and tissue 90% (55-100; 9/10).
Ultra performed on FNA or tissue of a lymph node had good sensitivity and high specificity. Ultra had a higher yield than culture and has the advantage of being a rapid test. Ultra on FNA would be an appropriate initial investigation for lymphadenopathy in tuberculosis endemic areas followed by a core biopsy for histopathology with a repeat Ultra on tissue if granulomas are present.
Background
Undisclosed antiretroviral drug (ARV) use among blood donors who tested HIV antibody positive, but RNA negative, was previously described by our group. Undisclosed ARV use represents a ...risk to blood transfusion safety. We assessed the prevalence of and associations with undisclosed ARV use among HIV‐positive donors who donated during 2017.
Study design and methods
South African National Blood Service (SANBS) blood donors are screened by self‐administered questionnaire, semi‐structured interview, and individual donation nucleic acid amplification testing for HIV. Stored samples from HIV‐positive donations were tested for ARV and characterized as recent/longstanding using lag avidity testing.
Results
Of the 1462 HIV‐positive donations in 2017, 1250 had plasma availability for testing of which 122 (9.8%) tested positive for ARV. Undisclosed ARV use did not differ by gender (p = .205) or ethnicity (p = .505) but did differ by age category (p < .0001), donor (p < .0001), clinic type (p = .012), home province (p = .01), and recency (p < .0001). Multivariable logistic regression found older age (adjusted odds ratio aOR 3.73, 95% confidence interval CI 1.98–7.04 for donors >40 compared with those <21), first‐time donation (aOR 5.24; 95% CI 2.48–11.11), and donation in a high HIV‐prevalence province (aOR 9.10; 95% CI 2.70–30.72) compared with Northern Rural provinces to be independently associated with undisclosed ARV use.
Discussion
Almost 1 in 10 HIV‐positive blood donors neglected to disclose their HIV status and ARV use. Demographic characteristics of donors with undisclosed ARV use differed from those noted in other study. Underlying motivations for nondisclosure among blood donors remain unclear and may differ from those in other populations with significant undisclosed ARV use.
Little is known about the pathway to diagnosis of lymphoma in Sub-Saharan Africa, despite the increased risk of lymphoma in people living with HIV (PLHIV). The challenges of diagnosis in this setting ...include diagnostic confusion with extrapulmonary tuberculosis (EPTB), which commonly causes lymphadenopathy in PLHIV.
We analysed the time to diagnosis and treatment in patients using predetermined time intervals. Univariate and multivariable analyses were performed to determine the relationship between patient and disease-specific variables with delays to diagnosis. We were particularly interested in the impact of HIV, empiric tuberculosis therapy and fine-needle aspirate for cytology (FNAC) in contributing to delay.
Patients (n = 163), 29% HIV-infected, waited a median of 4 weeks before seeking medical attention. It took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention, termed the healthcare practitioner interval. In multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease (OR 2.3, 95% CI 1.1-5.2) and Hodgkin lymphoma (HL) (OR 3.0, 95% CI 1.1-8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3-2.2). The median time to diagnosis was a median of 4 weeks longer for patients on tuberculous (TB) therapy (n = 16, p = 0.28) and patients who underwent an FNAC (n = 63, p = 0.04). Where FNAC was performed, it was diagnostic for lymphoma in only 11%. Diagnostic delay was not associated with overall survival.
Time-to-diagnosis of lymphoma in South Africa was similar to that reported from high-income countries and shows significant periods of delay between the onset of symptoms to diagnosis and treatment. The longest period of delay was in the health practitioner interval. Education regarding the significance of lymphadenopathy for both patients and health care practitioners and appropriate investigative steps preferably by best-practice algorithms specific to TB-endemic areas are needed to shorten the time-to-diagnosis of lymphoma.
Background and Objectives
Accurate HIV incidence estimates among blood donors are necessary to assess the effectiveness of programs aimed at limiting transfusion‐transmitted HIV. We assessed the ...impact of undisclosed HIV status and antiretroviral (ARV) use on HIV recency and incidence estimates using increasingly comprehensive recent infection testing algorithms.
Materials and Methods
Using 2017 donation data from first‐time and lapsed donors, we populated four HIV recency algorithms: (1) serology and limiting‐antigen avidity testing, (2) with individual donation nucleic amplification testing (ID‐NAT) added to Algorithm 1, (3) with viral load added to Algorithm 2 and (4) with ARV testing added to Algorithm 3. Algorithm‐specific mean durations of recent infection (MDRI) and false recency rates (FRR) were calculated and used to derive and compare incidence estimates.
Results
Compared with Algorithm 4, progressive algorithms misclassified fewer donors as recent: Algorithm 1: 61 (12.1%); Algorithm 2: 14 (2.8%) and Algorithm 3: 3 (0.6%). Algorithm‐specific MDRI and FRR values resulted in marginally lower incidence estimates: Algorithm 1: 0.19% per annum (p.a.) (95% confidence interval CI: 0.13%–0.26%); Algorithm 2: 0.18% p.a. (95% CI: 0.13%–0.22%); Algorithm 3: 0.17% p.a. (95% CI: 0.13%–0.22%) and Algorithm 4: 0.17% p.a. (95% CI: 0.13%–0.21%).
Conclusion
We confirmed significant misclassification of recent HIV cases when not including viral load and ARV testing. Context‐specific MDRI and FRR resulted in progressively lower incidence estimates but did not fully account for the context‐specific variability in incidence modelling. The inclusion of ARV testing, in addition to viral load and ID‐NAT testing, did not have a significant impact on incidence estimates.
After dental problems, iron deficiency (ID) is one of the most common health problems in the world, affecting one-third of the world’s population1,2. It is one of the leading health problems in South ...Africa, affecting ~45% of women and is the most common health problem in pregnancy3,4. Fifty percent of all anaemias are caused by iron deficiency. Iron metabolism involves the processes of iron intake, absorption, transport, utilisation, recycling, storage and iron loss5.
In tuberculosis (TB)-endemic areas, lymphadenopathy is frequently due to TB adenitis, but lymphoma and cancers are important differential diagnoses and critical to diagnose at the earliest ...opportunity. Key obstacles to lymphoma diagnosis include empiric TB treatment and difficulty accessing a biopsy. We report on a specialized clinic utilizing high-yield investigations for patients with lymphadenopathy.
This prospective interventional study investigated the utility of a core biopsy and the Xpert MTB/RIF Ultra (Ultra) on fine-needle aspirate (FNA) and tissue in a newly established lymph node biopsy clinic over 4 years. Electronic referral facilitated patient assessment within a week. Hematology fellows without specialist surgical or radiological expertise performed the biopsy on the first visit.
In 277 patients, including 43% people with HIV, TB was the most frequent diagnosis (34%), followed by lymphoma (27%) and other cancers (17%). Patients were seen a median of 5 days interquartile range (IQR) 2-8.5 days from referral. Core biopsy provided sufficient tissue for diagnosis in 96% of patients with lymphoma (72/75) and 94% of patients with cancer (44/47). FNA Ultra had a sensitivity of 73.9% 34/46; 95% confidence interval (CI) 58.9-85.7, and tissue Ultra 73% (46/63; 95% CI 60.3-83.4). There were six false-positive Ultra tests, highlighting the value of histology to either support TB or make an alternative diagnosis.
Core biopsies collected under the conditions described are safe and sensitive and can yield a rapid diagnosis. Combining Ultra and a core biopsy can accurately diagnose TB and cancer. This clinic provides an implementation model for resource-constrained and TB-endemic areas.
There is a need for effective therapy for COVID-19 pneumonia. Convalescent plasma has antiviral activity and early observational studies suggested benefit in reducing COVID-19 severity. We ...investigated the safety and efficacy of convalescent plasma in hospitalized patients with COVID-19 in a population with a high HIV prevalence and where few therapeutic options were available. We performed a double-blinded, multicenter, randomized controlled trial in one private and three public sector hospitals in South Africa. Adult participants with COVID-19 pneumonia requiring non-invasive oxygen were randomized 1:1 to receive a single transfusion of 200 mL of either convalescent plasma or 0.9% saline solution. The primary outcome measure was hospital discharge and/or improvement of ≥ 2 points on the World Health Organisation Blueprint Ordinal Scale for Clinical Improvement by day 28 of enrolment. The trial was stopped early for futility by the Data and Safety Monitoring Board. 103 participants, including 21 HIV positive individuals, were randomized at the time of premature trial termination: 52 in the convalescent plasma and 51 in the placebo group. The primary outcome occurred in 31 participants in the convalescent plasma group and and 32 participants in the placebo group (relative risk 1.03 (95% CI 0.77 to 1.38). Two grade 1 transfusion-related adverse events occurred. Participants who improved clinically received convalescent plasma with a higher median anti-SARS-CoV-2 neutralizing antibody titre compared with those who did not (298 versus 205 AU/mL). Our study contributes additional evidence for recommendations against the use of convalescent plasma for COVID-19 pneumonia. Safety and feasibility in this population supports future investigation for other indications.
Objectives
We performed a mixed‐methods study to explore the motivations associated with blood donation by donors with known, but undisclosed HIV‐positive status and ARV use (HIV+/ARV+), seeking ...potential strategies to reduce such donations and mitigate risk for blood recipients. Here, we report predominantly the qualitative component.
Background
A safe and sustainable blood supply is dependent in part, on effective pre‐donation donor assessment. We previously described failure by HIV+/ARV+ blood donors to disclose their status. Such donations may lead to transfusion‐transmitted HIV.
Methods
The social ecological model provided the conceptual framework for this study. Previously identified HIV+/ARV+ donors were invited to complete a survey (including a validated stigma scale) and qualitative interview, which underwent inductive and deductive thematic analysis.
Results
We uncovered two primary motivational paths to HIV+/ARV+ blood donations: privacy and altruism. The latter included a motivation not previously reported in the literature: donating specifically for other people living with HIV (PLWH). The other primary factor was a lack of privacy. These accounts often included donors encountering donation opportunities when accompanied by people to whom they had not and did not plan to disclose their HIV status. Most were highly confident their donations would be identified as HIV‐positive and discarded.
Conclusion
We demonstrated a complex interaction between individual, social, cultural, and structural/policy factors in blood donations by PLWH who take ARV. Recommendations to limit HIV + ARV+ donations include: (1) Targeted communication strategies to increase knowledge among PLWH of their deferral from blood donation—without increasing stigma, and (2) development of procedures to assist those who feel unable to opt‐out of donation due to privacy concerns.
PDF
