Is having sex with other men a risk factor for transfusion-transmissible infections in male blood donors in Western countries?: a systematic review

Background : Although increased prevalence of transfusion transmissible infections (TTI) among “men who have sex with men” (MSM) has been well documented, the exclusion of MSM as blood donors is contested. The aim of this systematic review is to find studies that describe the risk of TTI in MSM blood donors. Methods : We searched MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, Cinahl, and Web of Science, and used GRADE for determining evidence quality. We included studies comparing MSM and non-MSM blood donors (or people eligible to give blood), living in areas most relevant for our Blood Service. Results : Out of 18 987 articles, 14 observational studies were included. Two studies directly compared MSM with non-MSM donors showing that MSM donors have a statistically significant higher risk of HIV-1 infections. In one of these studies it was shown that this was related to recent (< 12 months) MSM contact. In two additional studies no evidence was shown in favour of a certain deferral period for MSM. Ten studies, applying permanent deferral for MSM, compared infected versus non-infected donors. One study found that MSM is a statistically significant risk factor for HIV-1 infection in blood donors. For other TTI such as HBV or HCV, an increased risk of infection could not be demonstrated, because the precision of the results was affected by the low numbers of donors with MSM as risk factor, or because of risk of bias in the included studies. All studies included low level evidence, because of risk of bias and imprecision of the results. Conclusions : High-quality studies investigating the risk of TTI in MSM who donate blood are scarce. The available evidence suggests a link between MSM blood donors and HIV-1 infection, but is too limited to be able to unambiguously/clearly recommend a certain deferral policy

Identification of Mimotopes with Diagnostic Potential for Trypanosoma brucei gambiense Variant Surface Glycoproteins Using Human Antibody Fractions

Background: At present, screening of the population at risk for gambiense human African trypanosomiasis (HAT) is based on detection of antibodies against native variant surface glycoproteins (VSGs) of Trypanosoma brucei (T.b.) gambiense. Drawbacks of these native VSGs include culture of infective T.b. gambiense trypanosomes in laboratory rodents, necessary for production, and the exposure of non-specific epitopes that may cause cross-reactions. We therefore aimed at identifying peptides that mimic epitopes, hence called “mimotopes,” specific to T.b. gambiense VSGs and that may replace the native proteins in antibody detection tests. Methodology/Principal Findings A Ph.D.-12 peptide phage display library was screened with polyclonal antibodies from patient sera, previously affinity purified on VSG LiTat 1.3 or LiTat 1.5. The peptide sequences were derived from the DNA sequence of the selected phages and synthesised as biotinylated peptides. Respectively, eighteen and twenty different mimotopes were identified for VSG LiTat 1.3 and LiTat 1.5, of which six and five were retained for assessment of their diagnostic performance. Based on alignment of the peptide sequences on the original protein sequence of VSG LiTat 1.3 and 1.5, three additional peptides were synthesised. We evaluated the diagnostic performance of the synthetic peptides in indirect ELISA with 102 sera from HAT patients and 102 endemic negative controls. All mimotopes had areas under the curve (AUCs) of ≥0.85, indicating their diagnostic potential. One peptide corresponding to the VSG LiTat 1.3 protein sequence also had an AUC of ≥0.85, while the peptide based on the sequence of VSG LiTat 1.5 had an AUC of only 0.79. Conclusions/Significance: We delivered the proof of principle that mimotopes for T.b. gambiense VSGs, with diagnostic potential, can be selected by phage display using polyclonal human antibodies

Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies

<p>Abstract</p> <p>Background</p> <p>A minority of HIV-1 infected individuals develop broad cross-neutralizing (BCN) plasma antibodies that are capable of neutralizing a spectrum of virus variants belonging to different HIV-1 clades. The aim of this study was to identify the targeted epitopes of an individual with BCN plasma antibodies, referred to as ITM4, using peptide phage display. This study also aimed to use the selected mimotopes as tools to unravel the evolution of the antibody landscape and the viral envelope escape which may provide us with new insights for vaccine design.</p> <p>Results</p> <p>This study led us to identify ITM4 plasma antibodies directed to the 4E10 epitope located in the gp41 membrane-proximal external region (MPER). Analysis of antibody specificities revealed unusual immunogenic properties of the ITM4 viral envelope, as not only the V3 loop and the gp41 MPER but also the C1 and lentivirus lytic peptide 2 (LLP2) region seem to be targets of the immune system. The 4E10-like antibodies are consistently elicited during the 6-year follow up period. HIV-1 ITM4 pseudoviruses showed an increasing resistance over time to MPER monoclonal antibodies 4E10 and 2F5, although no changes are found in the critical positions of the epitope. Neutralization of COT6.15 (subtype C; 4E10-sensitive) pseudoviruses with alanine substitutions in the MPER region indicated an overlapping specificity of the 4E10 monoclonal antibody and the ITM4 follow up plasma. Moreover the 4E10-like antibodies of ITM4 contribute to the BCN capacity of the plasma.</p> <p>Conclusions</p> <p>Using ITM4 BCN plasma and peptide phage display technology, we have identified a patient with 4E10-like BCN antibodies. Our results indicate that the elicited 4E10-like antibodies play a role in virus neutralization. The viral RNA was isolated at different time points and the ITM4 envelope sequence analysis of both early (4E10-sensitive) and late (4E10-resistant) viruses suggest that other regions in the envelope, outside the MPER region, contribute to the accessibility and sensitivity of the 4E10 epitope. Including ITM4 specific HIV-1 Env properties in vaccine strategies may be a promising approach.</p

Identification of Peptide Mimotopes of Trypanosoma brucei gambiense Variant Surface Glycoproteins

The control of human African trypanosomiasis or sleeping sickness, a deadly disease in sub-Saharan Africa, mainly depends on a correct diagnosis and treatment. The aim of our study was to identify mimotopic peptides (mimotopes) that may replace the native proteins in antibody detection tests for sleeping sickness and hereby improve the diagnostic sensitivity and specificity. We selected peptide expressing phages from the PhD.-12 and PhD.-C7C phage display libraries with mouse monoclonal antibodies specific to variant surface glycoprotein (VSG) LiTat 1.3 or LiTat 1.5 of Trypanosoma brucei gambiense. The peptide coding genes of the selected phages were sequenced and the corresponding peptides were synthesised. Several of the synthetic peptides were confirmed as mimotopes for VSG LiTat 1.3 or LiTat 1.5 since they were able to inhibit the binding of their homologous monoclonal to the corresponding VSG. These peptides were biotinylated and their diagnostic potential was assessed with human sera. We successfully demonstrated that human sleeping sickness sera recognise some of the mimotopes of VSG LiTat 1.3 and LiTat 1.5, indicating the diagnostic potential of such peptides

Is having sex with other men a risk factor for transfusion-transmissible infections in male blood donors in Western countries? A systematic review

Although increased prevalence of transfusion transmissible infections (TTI) among "men who have sex with men" (MSM) has been well documented, the exclusion of MSM as blood donors is contested. The aim of this systematic review is to find studies that describe the risk of TTI in MSM blood donors.status: publishe

Is blood of uncomplicated hemochromatosis patients safe and effective for blood transfusion? A systematic review

SummaryHemochromatosis is a disorder of the iron metabolism, characterized by high body iron content, necessitating frequent phlebotomies to remove excess iron. In some countries, this blood is discarded and not used for blood transfusion because of the non-voluntary character of this donation, and because a potential risk of microbial contamination of the donor blood is assumed.A systematic review was performed in order to collect and critically examine solid evidence with regard to the effectiveness and safety of blood for transfusion when derived from hemochromatosis patients who do not suffer from complications or organ damage. Using three databases (The Cochrane Library, MEDLINE, and Embase) we searched for studies from date of inception until January 2012.Out of 3470 articles, 80 references that were relevant to our question were selected, including many opinion pieces, comments, letters, and narrative reviews. Based on our selection criteria, we finally retained only six observational studies, so evidence on this subject is scarce and furthermore, the strength of the available evidence is low to very low, due to poor study designs. We found no evidence that red blood cell concentrates from hemochromatosis patients without complications of iron overload do not comply with the physiological quality requirements for transfusion, nor that their blood would present a greater risk to recipient safety than blood from non-hemochromatosis donors. However, in vitro findings from two studies suggest that iron-overloaded patients would be more susceptible to bacterial growth, but future in vivo studies are warranted to confirm this.Based on this, we call for harmonization of the blood donor selection policy among countries allowing hemochromatosis patients who do not suffer from complications of iron overload to donate blood, once iron levels are normalized

Methodologic quality assessment of red blood cell transfusion guidelines and the evidence base of more restrictive transfusion thresholds

BACKGROUND: Recent literature suggests that more restrictive red blood cell (RBC) transfusion practices are equivalent or better than more liberal transfusion practices. The methodologic quality of guidelines recommending more restrictive transfusion thresholds and their underlying scientific evidence is unclear. Therefore, we aimed to evaluate the quality of the development process of RBC transfusion guidelines and to investigate the underlying evidence of guidelines recommending a more restrictive hemoglobin (Hb) threshold. STUDY DESIGN AND METHODS: Via systematic literature screening of relevant databases (NGC, GIN, Medline, and Embase), RBC transfusion guidelines recommending a more restrictive Hb level (<6, <7, or <8 g/dL) were included. Four assessors independently evaluated the methodologic quality by scoring the rigor of development domain (AGREE II checklist). The level of evidence served as a reference for the quality of the underlying evidence. RESULTS: The methodologic quality of 13 RBC transfusion guidelines was variable (18%-72%) but highest for those developed by Advancing Transfusion and Cellular Therapies Worldwide (72%), the Task Force of Advanced Bleeding Care in Trauma (70%), and the Dutch Institute for Healthcare Improvement (61%). A Hb level of less than 7 g/dL (intensive care unit patients) or less than 8 g/dL (postoperative patients) were the only thresholds based on high-quality evidence. Only four of 32 recommendations had a high-quality evidence base. CONCLUSION: Methodologic quality should be guaranteed in future RBC transfusion guideline development to ensure that the best available evidence is captured when recommending restrictive transfusion strategies. More high-quality trials are needed to provide a stronger scientific basis for RBC transfusion guidelines that recommend more restrictive transfusion thresholds

Characteristics of included studies.

<p>ALAT: alanine aminotransferase; EIA: enzyme immunoassay; ELISA: enzyme-linked immunosorbent assay; HBc: hepatitis B core antigen; HBs: hepatitis B surface antigen; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; IDU: intravenous drug use; MSM: men who have sex with men; RIBA: recombinant immunoblot assay; RNA: ribonucleic acid; RIP: radioimmunoprecipitation; (RT)-PCR: (reverse transcriptase) polymerase chain reaction; TTI: transfusion transmissible infections</p><p>Characteristics of included studies.</p

Quality assessment and summary of findings according to the GRADE approach.

<p>aOR: adjusted odds ratio; aRR: adjusted risk ratio; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; MSM: men who have sex with men; OR: odds ratio; RR: risk ratio; TTI: transfusion transmissible infections</p><p>1 Inappropriate eligibility criteria (random donors are a mix of male and female, while all homosexuals included are male); control for confounding unclear (not mentioned in article); other limitations: homosexuals were solicited via the press, other donors were random samples)</p><p>2 Random samples with young, minority and first-time donor oversampled; possible recall bias; the possible difference between respondents and non-respondents is not known</p><p>3 Control for confounding unclear (not mentioned in the article); no control group was included (e. g. states where no change in deferral policy was implemented): several blood safety-related interventions were implemented during the 10-year period covered by this study; there is a potential decline in the number of HIV-positive donors presenting to donate because of earlier HIV diagnosis in more recent times; before the implementation of the new policy, different states/territories had different policies (permanent deferral or 5 year deferral since last MSM contact) and the implementation of the new policy was not established at the same moment in each state/territory.</p><p>4 Control for confounding unclear (not mentioned in the article); no control group was included (e. g. states where no change in deferral policy was implemented)</p><p>5 First-time donations by infected persons (53.3%) were 1.7-fold higher than those among the control group (31.1%), which suggests that test-seeking donations may have been numerous.</p><p>6 Control for confounding unclear (not clear for which factors adjustment was made); questionnaire used to obtain information</p><p>7 Methods for exposure and outcome variables unclear (risk factors not determined in the same way for all cases); not controlled for confounding ((not clear if individuals with MSM as risk factor also have other risk factors)</p><p>8 Inappropriate eligibility criteria (all subjects had positive anti-HCV findings by enzyme immunoassay); not controlled for confounding</p><p>9 Inappropriate eligibility criteria (cases and controls not matched); not controlled for confounding (individuals with MSM as risk factor also have other risk factors); 5 out of 7 cases having homosexual contact also admitted personal drug use; questionnaire used</p><p>10 Control for confounding unclear (only adjusted for intravenous drug use, but unclear if this is sufficient)</p><p>11 Control for confounding unclear (only adjusted for intravenous drug use, but unclear if this is sufficient); questionnaire used to obtain information</p><p>12 Control for confounding unclear (only donors with no histories of transfusion or intravenous drug abuse, but unclear if this is sufficient); interview used to obtain information</p><p>13 Inappropriate eligibility criteria (cases and controls not matched; all subjects positive by ELISA); unclear if cases and controls received same questionnaire; control for confounding unclear (donors do not have former intravenous drug addiction, but unclear if this is sufficient); questionnaire used to obtain information</p><p>14 Inappropiate eligibility criteria (cases and controls not matched; all subjects positive by ELISA); not controlled for confounding (individuals with MSM as risk factor can also have other risk factors); interview used to obtain information</p><p>15 Low number of events</p><p>16 Calculations made by the reviewer(s) using Review Manager software</p><p>17 Not able to calculate confidence interval (data lacking)</p><p>18 Raw data calculated based on total number of participants and percentages</p><p>19 Raw data not available</p><p>20 Confidence interval of adjusted odds ratio not available, only p-value</p><p>Quality assessment and summary of findings according to the GRADE approach.</p