The impact of non-disclosure of HIV status and antiretroviral therapy on HIV recency testing and incidence algorithms.

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.

A case-control study of risk factors for incident hepatitis B virus infection in South African blood donors.

OBJECTIVES: Hepatitis B virus (HBV) infection remains a global health problem. Risk factors for HBV infection are usually assessed in prevalent rather than incident infections. To identify demographic and behavioral risks associated with incident HBV among South African blood donors. METHODS: A case-control study was performed between November 2014 and January 2018. Cases were blood donors testing positive for HBV DNA with or without hepatitis B surface antigen but negative for antibody to hepatitis B core antigen. Participants completed an audio computer-assisted structured interview on exposures during the previous 6 months. Sex-specific multivariable logistic regression yielded independent associations between risks and HBV infection. RESULTS: 56 females and 37 males with incident HBV were compared to 438 female and 439 male controls, respectively. For females, risk factors were accepting money or goods for sex, using agents to prepare one's anus prior to anal sex, penetrating injury, non-Black race, and lower educational status. Men reporting homosexual or bisexual orientation or sex with other men, previous injury, referral for HBV testing, or lack of medical insurance were at increased risk. For both sexes, having more than two male sexual partners increased risk. CONCLUSIONS: Sexual behaviors predominated over parenteral exposures as risks for incident HBV in both female and male blood donors.

The evolution and interpretation of seroprevalence of SARS-CoV-2 antibodies among South African blood donors from the Beta to Omicron variant-driven waves.

BACKGROUND AND OBJECTIVES: Confirmed COVID-19 diagnoses underestimate the total number of infections. Blood donors can provide representative seroprevalence estimates, which can be leveraged into reasonable estimates of total infection counts and infection fatality rate (IFR). MATERIALS AND METHODS: Blood donors who donated after each of three epidemic waves (Beta, Delta and first Omicron waves) were tested for anti-SARS-CoV-2 nucleocapsid antibodies using the Roche Elecsys anti-SARS-CoV-2 total immunoglobulin assay. Roche Elecsys anti-spike antibody testing was done for the post-Omicron sampling. Prevalence of antibodies was estimated by age, sex, race and province and compared to official case reporting. Province and age group-specific IFRs were estimated using external excess mortality estimates. RESULTS: The nationally weighted anti-nucleocapsid seroprevalence estimates after the Beta, Delta and Omicron waves were 47% (46.2%-48.6%), 71% (68.8%-73.5%) and 87% (85.5%-88.4%), respectively. There was no variation by age and sex, but there were statistically and epidemiologically significant differences by province (except at the latest time point) and race. There was a 13-fold higher seroprevalence than confirmed case counts at the first time point. Age-dependent IFR roughly doubled for every 10 years of age increase over 6 decades from 0.014% in children to 6.793% in octogenarians. CONCLUSION: Discrepancies were found between seroprevalence and confirmed case counts. High seroprevalence rates found among Black African donors can be ascribed to historical inequities. Our IFR estimates were useful in refining previous large disagreements about the severity of the epidemic in South Africa. Blood donor-based serosurveys provided a valuable and efficient way to provide near real-time monitoring of the ongoing SARS-CoV-2 outbreak.

Emotional and non-emotional mental imagery and auditory verbal hallucinations (hearing voices): A systematic review of imagery assessment tools.

It is unknown to what extent mental imagery and auditory verbal hallucinations (AVHs) are related. Trials evaluating this issue used both emotional and non-emotional mental imagery tools, thereby complicating outcomes comparisons. Therefore, the present study aimed to systematically review the literature on mental imagery in individuals with AVHs to (1) inventory imagery assessment tools used in this population, (2) to collect information on the relation between emotional and non-emotional mental imagery in all sensory domains and AVHs and (3) to integrate the outcomes of this systematic review in a model of different mental imagery domains and related assessment tools. We conducted a systematic literature search in the PubMed Database. After full-text screening, 17 papers were included. Findings showed that a variety of assessment methods have been used to assess various aspects of mental imagery in people with AVHs, suggesting that there is a lack of agreed theoretical conceptualization of mental imagery and AVHs. In addition, the studies confirmed as was expected that non-emotional mental imagery seemed unrelated to AVHs whereas emotional mental imagery was related to AVHs. Lastly, we proposed a model of mental imagery domains and corresponding assessment methods distinguishing between emotional and non-emotional mental imagery.

Association of ABO and RhD blood groups with the risk of HIV infection.

Naturally occurring antibodies against ABO antigens present in human sera have been shown to neutralize ABO-expressing HIV in vitro. We investigated associations between ABO and RhD blood groups and HIV infection among blood donors from all blood collection centers in eight of South Africa's nine provinces. Whole blood donations collected from first time donors between January 2012 and September 2016 were tested for HIV RNA by nucleic acid testing and HIV antibody using third generation serology assays. ABO and RhD blood types were determined using automated technology. Odds ratios for the association between HIV positivity and ABO and RhD phenotypes were calculated using multivariable logistic regression analysis. We analyzed 515,945 first time blood donors and the overall HIV prevalence was 1.12% (n = 5790). After multivariable adjustment, HIV infection was weakly associated with RhD positive phenotype (OR = 1.15, 95% CI 1.00-1.33) but not with ABO blood group. The observed association with RhD positive phenotype was marginal and likely due to residual confounding by racial group but could serve to generate hypotheses for further studies.

A linear programming based method for designing menus for controlled feeding trials.

BACKGROUND: Controlled feeding trials are an important method to determine cause-effect relationships between dietary intake and metabolic parameters, risk factors, or health outcomes. Participants of a controlled feeding trial receive full-day menus during a prespecified period of time. The menus have to comply with the nutritional and operational standards of the trial. Levels of nutrients under investigation should differ sufficiently between intervention groups, and be as similar as possible for all energy levels within intervention groups. Levels of other key nutrients should be as similar as possible for all participants. All menus have to be varied and manageable. Designing these menus is both a nutritional and a computational challenge that relies largely on the expertise of the research dietician. The process is very time consuming, and last-minute disruptions are very hard to manage. OBJECTIVE: This paper demonstrates a mixed integer linear programming model to support the design of menus for controlled feeding trials. METHODS: The model is demonstrated for a trial that involved consumption of individualized, isoenergetic menus with either a low or a high protein content. RESULTS: All menus generated by the model comply with all standards of the trial. The model allows for including tight ranges on nutrient composition, and complex design features. The model is very helpful in managing contrast and similarity of key nutrient intake levels between groups and energy levels, and in coping with many energy levels and nutrients. The model helps to propose several alternative menus and to manage last-minute disruptions. The model is flexible; it can easily be adapted to suit trials with other components or different nutritional requirements. CONCLUSIONS: The model helps to design menus in a fast, objective, transparent, and reproducible way. It greatly facilitates the design procedure for menus in controlled feeding trials and lowers development costs.

Motivations for blood donation by HIV-positive individuals on antiretrovirals in South Africa: A qualitative study.

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.

The potential contribution of house crickets to the dietary zinc content and nutrient adequacy in young Kenyan children: a linear programming analysis using Optifood.

Zn deficiency arising from inadequate dietary intake of bioavailable Zn is common in children in developing countries. Because house crickets are a rich source of Zn, their consumption could be an effective public health measure to combat Zn deficiency. This study used Optifood, a tool based on linear programming analysis, to develop food-based dietary recommendations (FBR) and predict whether dietary house crickets can improve both Zn and overall nutrient adequacy of children's diets. Two quantitative, multi-pass 24-h recalls from forty-seven children aged 2 and 3 years residing in rural Kenya were collected and used to derive model parameters, including a list of commonly consumed foods, median serving sizes and frequency of consumption. Two scenarios were modelled: (i) FBR based on local available foods and (ii) FBR based on local available foods with house crickets. Results revealed that Zn would cease to be a problem nutrient when including house crickets to children's diets (population reference intake coverage for Zn increased from 89 % to 121 % in the best-case scenario). FBR based on both scenarios could ensure nutrient adequacy for all nutrients except for fat, but energy percentage (E%) for fat was higher when house crickets were included in the diet (23 E% v. 19 E%). This manoeuvre, combined with realistic changes in dietary practices, could therefore improve dietary Zn content and ensure adequacy for twelve nutrients for Kenyan children. Further research is needed to render these theoretical recommendations, practical.

Management of blood transfusion services in low-resource countries.

BACKGROUND AND OBJECTIVES: Enabling universal access to safe blood components should be a key component of every country's national healthcare strategy. This study aimed to assess the current status of infrastructure and resources of blood transfusion services (BTS) in low- and middle-income countries. MATERIALS AND METHODS: A cross-sectional survey was designed to gather information on blood donations, components, redistribution, testing resources and quality management systems (QMSs). The survey was distributed to the International Society of Blood Transfusion members between October 2021 and November 2021. RESULTS: A total of 54 respondents from 20 countries responded to the survey. This included hospital-based BTS/blood centres (46%), national blood centres (11%)and national and regional blood services (11%). Voluntary non-remunerated, replacement and paid donors accounted for 94.2%, 84.6% and 21.1% of donations, respectively. Apheresis donation was available in 59.6% of institutions. National/regional criteria for redistribution of blood components were reported by 75.9% of respondents. Blood components incurred payment charges in 81.5% of respondents' institutions, and payments were borne by patients in 50% of them. Testing methods, such as manual (83%), semi-automated (68%) or fully automated (36.2%), were used either alone or in combination. QMSs were reported in 17 institutions, while accreditation and haemovigilance were reported in 12 and 8 countries, respectively. CONCLUSION: QMS was implemented in most of the countries despite the common use of paid donations and the lack of advanced testing. Efforts to overcome persistent challenges and wider implementation of patient blood management programmes are required.

Blood Center Testing Allows the Detection and Rapid Treatment of Acute and Recent HIV Infection.

Blood donations in South Africa are tested for HIV RNA using individual donation NAT (ID-NAT), allowing detection and rapid antiretroviral therapy (ART) of acute HIV infections. We enrolled a cohort of acute and recent HIV-infected blood donation candidates in South Africa in 2015-2018, measured HIV antibody, ID-NAT, and recency of infection <195 days (Sedia LAg) at enrollment and initiated early ART. A small cohort of HIV elite controllers was followed without treatment. HIV reservoir measurements included ultrasensitive plasma RNA, cell-associated HIV RNA, and total DNA. Enrollment of 18 Fiebig I-III and 45 Fiebig IV-VI HIV clade C subjects occurred a median of 18 days after index blood donation. ART was administered successfully and compliance with follow-up visits was excellent. There were only minimal differences in HIV reservoir between ART initiation in Fiebig stages I-III vs. IV-VI, but ART noncompliance increased HIV reservoir. In 11 untreated HIV elite controllers, HIV reservoir levels were similar to or higher than those seen in our early treated cohort. National blood services can identify acute HIV cohorts for subsequent HIV cure research studies. Among HIV clade C-infected donors, HIV reservoir differed little by Fiebig stage at treatment initiation, but was smaller than in chronically treated HIV and those with ART noncompliance.

Early and out-of-hospital use of COVID-19 convalescent plasma: An international assessment of utilization and feasibility.

BACKGROUND AND OBJECTIVES: The use of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) in the treatment of patients with severe acute respiratory syndrome-2 infection has been controversial. Early administration of CCP before hospital admission offers a potential advantage. This manuscript summarizes current trials of early use of CCP and explores the feasibility of this approach in different countries. MATERIALS AND METHODS: A questionnaire was distributed to the International Society of Blood Transfusion (ISBT) CCP working group. We recorded respondents' input on existing trials on early/outpatient CCP and out-of-hospital (OOH)/home transfusion (HT) practices in their countries and feedback on challenges in initiating home CCP infusion programmes. In addition, details of existing trials registered on clinicaltrials.gov were summarized. RESULTS: A total of 31 country representatives participated. Early/OOH CCP transfusion studies were reported in the United States, the Netherlands, Spain and Brazil. There were a total of six published and five ongoing trials on the prophylactic and therapeutic early use of CCP. HT was practised in Australia, the UK, Belgium, France, Japan, Nigeria, the Netherlands, Spain, Italy, Norway, the United States and some provinces in Canada. Thirty-four representatives indicated a lack of OOH CCP or HT in their institutions and countries. Barriers to implementation of OOH/HT included existing legislation, lack of policies pertaining to outpatient transfusion, and associated logistical challenges, including lack of staffing and resources. CONCLUSION: Early administration of CCP remains a potential option in COVID-19 management in countries with existing OOH/HT programmes. Legislation and regulatory bodies should consider OOH/HT practice for transfusion in future pandemics.

The Impact of Early Antiretroviral Treatment (ART) for HIV on the Sensitivity of the Latest Generation of Blood Screening and Point of Care Assays.

INTRODUCTION: Rapid initiation of antiretroviral therapy (ART) in early HIV infection is important to limit seeding of the viral reservoir. A number of studies have shown that if ART is commenced prior to seroconversion, the seroconversion may, or may not, occur. We aimed to assess whether seroreversion or no seroconversion occurs using samples collected during an early treatment study in South Africa. METHODS: We tested 10 longitudinal samples collected over three years from 70 blood donors who initiated ART after detection of acute or early HIV infection during donation screening on fourth- and fifth-generation HIV antibody and RNA assays, and three point of care (POC) rapid tests. Donors were allocated to three treatment groups: (1) very early, (2) early, and (3) later. Longitudinal samples were grouped into time bins post-treatment initiation. RESULTS: On all three high-throughput HIV antibody assays, no clear pattern of declining signal intensity was observed over time after ART initiation in any of the treatment initiation groups and 100% detection was obtained. The Abbott Determine POC assay showed 100% detection at all time points with no seroreversion. However, the Abbott ABON HIV1 and OraSure OraQuick POC assays showed lower proportions of detection in all time bins in the very early treated group, ranging from 50.0% (95% CI: 26.8-73.2%) to 83.1% (95% CI: 64.2-93.0%), and moderate detection rates in the early and later-treated groups. CONCLUSION: While our findings are generally reassuring for HIV detection when high-throughput serological screening assays are used, POC assays may have lower sensitivity for detection of HIV infection after early treatment. Findings are relevant for blood safety and other settings where POC assays are used.

Estimates of prevalence of anti-SARS-CoV-2 antibodies among blood donors in South Africa in March 2022.

In line with previous instalments of analysis from this ongoing study to monitor 'Covid Seroprevalence' among blood donors in South Africa, we report on an analysis of 3395 samples obtained in mid-March 2022 from all provinces of South Africa - a timepoint just after the fourth (primarily omicron) wave of infections. As in our previous analyses, we see no evidence of age and sex dependence of prevalence, but significant variation by race. Differences between provinces have largely disappeared, as prevalence appears to have saturated. In contrast to previous estimates from this study, which reported only prevalence of anti-nucleocapsid antibodies, this present work also reports results from testing for anti-spike antibodies. This addition allows us to categorise those donors whose only antibodies are from vaccination. Our race-weighted national extrapolation is that 98% of South Africans have some antibodies, noting that 10% have anti-spike antibodies but not anti-nucleocapsid antibodies - a reasonable proxy for having both 1) been vaccinated and 2) avoided infection.

Adherence to the Dutch healthy diet index and change in glycemic control and cardiometabolic markers in people with type 2 diabetes.

PURPOSE: To investigate whether adherence to the Dutch Healthy Diet index 2015 (DHD15-index) is associated with change in glycemic control and cardio-metabolic markers over two-year follow-up in people with type 2 diabetes (T2D). METHODS: This prospective cohort study included 1202 individuals with T2D (mean age 68.7 ± 9.0 years; 62.5% male; mean HbA1c 53.8 ± 11.7 mmol/mol) from the Diabetes Care System cohort. Baseline dietary intake was assessed using a validated food frequency questionnaire, and adherence to the DHD15-index was estimated (range 0-130). HbA1c, fasting glucose, blood lipids (HDL and LDL cholesterol, cholesterol ratio), blood pressure, estimated glomerular filtration rate (eGFR), and BMI were measured at baseline, and after one- and two-year follow-up. Linear mixed model analyses were conducted to examine the associations between adherence to the DHD15-index and glycemic control and the cardio-metabolic outcomes, adjusting for energy intake, sociodemographic and lifestyle characteristics, and medication. RESULTS: Highest adherence (T3) to the DHD15-index was not associated with change in HbA1c, compared to lowest adherence (T1) [ßT3vsT1: 0.62 mmol/mol (- 0.94; 2.19), Ptrend = 0.44]. There was a non-linear association with fasting glucose, where moderate adherence (T2) was associated with a decrease in fasting glucose [ßT2vsT1: - 0.29 mmol/L (- 0.55; - 0.03), Ptrend = 0.30]. Higher adherence to the DHD15-index was associated with a decrease in BMI [ß10point: - 0.41 kg/m2 (- 0.60; - 0.21), Ptrend < 0.001], but not with blood lipids, blood pressure or kidney function. CONCLUSION: In this well-controlled population of people with T2D, adherence to the DHD15-index was associated with a decrease in BMI, but not with change in glycemic control or other cardio-metabolic parameters.

International Society of Blood Transfusion survey of experiences of blood banks and transfusion services during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has impacted blood systems worldwide. Challenges included maintaining blood supplies and initiating the collection and use of COVID-19 convalescent plasma (CCP). Sharing information on the challenges can help improve blood collection and utilization. MATERIALS AND METHODS: A survey questionnaire was distributed to International Society of Blood Transfusion members in 95 countries. We recorded respondents' demographic information, impacts on the blood supply, CCP collection and use, transfusion demands and operational challenges. RESULTS: Eighty-two responses from 42 countries, including 24 low- and middle-income countries, were analysed. Participants worked in national (26.8%) and regional (26.8%) blood establishments and hospital-based (42.7%) institutions. CCP collection and transfusion were reported by 63% and 36.6% of respondents, respectively. Decreases in blood donations occurred in 70.6% of collecting facilities. Despite safety measures and recruitment strategies, donor fear and refusal of institutions to host blood drives were major contributing factors. Almost half of respondents working at transfusion medicine services were from large hospitals with over 10,000 red cell transfusions per year, and 76.8% of those hospitals experienced blood shortages. Practices varied in accepting donors for blood or CCP donations after a history of COVID-19 infection, CCP transfusion, or vaccination. Operational challenges included loss of staff, increased workloads and delays in reagent supplies. Almost half of the institutions modified their disaster plans during the pandemic. CONCLUSION: The challenges faced by blood systems during the COVID-19 pandemic highlight the need for guidance, harmonization, and strengthening of the preparedness and the capacity of blood systems against future infectious threats.