Slower response to treatment of iron-deficiency anaemia in pregnant women infected with HIV: a prospective cohort study.

OBJECTIVE: Antenatal anaemia is associated with increased peripartum transfusion requirement in South Africa. We studied whether HIV was associated with the response to treatment of iron-deficiency anaemia. DESIGN: Prospective cohort study. SETTING: Hospital-based antenatal anaemia clinic in South Africa. SAMPLE: Equal-sized cohorts of pregnant women testing positive for HIV (HIV+) and testing negative for HIV (HIV-) with iron-deficiency anaemia. METHODS: Haemoglobin trajectories of women with confirmed iron-deficiency anaemia (ferritin < 50 ng/ml) were estimated from the initiation of iron supplementation using mixed-effects modelling, adjusted for baseline HIV status, ferritin level, maternal and gestational ages and time-varying iron supplementation. MAIN OUTCOME MEASURES: Haemoglobin trajectories. RESULTS: Of 469 women enrolled, 51% were HIV+, 90% of whom were on antiretroviral therapy (with a mean CD4+ lymphocyte count of 403 cells/mm3 ). Anaemia diagnoses did not differ by HIV status. A total of 400 women with iron-deficiency anaemia were followed during treatment with oral or intravenous (6%) iron therapy. In multivariable analysis, haemoglobin recovery was 0.10 g/dl per week slower on average in women who were HIV+ versus women who were HIV- (P = 0.001), 0.01 g/dl per week slower in women with higher baseline ferritin (P < 0.001) and 0.06 g/dl per week faster in women who were compliant with oral iron therapy (P = 0.002). CONCLUSIONS: Compared with women who were HIV-, women who were HIV+ with iron-deficiency anaemia had slower but successful haemoglobin recovery with iron therapy. Earlier effective management of iron deficiency could reduce the incidence of peripartum blood transfusion. TWEETABLE ABSTRACT: Among pregnant women with iron-deficiency anaemia in South Africa, HIV slows haemoglobin recovery in response to oral iron therapy.

Building capacities in research for blood services in Africa.

BACKGROUND: Capacity building of African based blood services researchers has been identified as key in developing a sustainable programme of generation local evidence to support sound decision making. There are a number of research training programmes that have been instituted targeted at blood services in Africa. The article shares programme experiences of building research capacities for blood services in Africa. METHODOLOGY: The Francophone Africa Transfusion Medicine Research Training network, the NIH REDS-III and NIH Fogarty South Africa programmes and T-REC (Building transfusion research capacity in Africa) have been the key research capacity programmes targeting blood services in Africa over the last decade. To understand their experiences on the implementation of the capacity building programmes, data were drawn from research outputs, publications and end of programme reports. The success, challenges and the main research outputs from their initiatives were highlighted. RESULTS: The Francophone research network achievements included more than 135 trainees and in excess of 30 publications. The NIH REDS study the achievements included more than 12 research publications with South Africa junior investigators as lead authors. The NIH Fogarty program currently includes 56 short course trainees, 5 Masters and 6 PhD candidates. The four year (2011-2015, funding period) T-REC programme produced more than 20 publications, 4 PhDs, 42 in-service Diploma in Project Design and Management (DPDM), and supported bursaries for 60 Masters/undergraduate research. The main common challenges in the running of the research programmes include shortages of in-country mentoring and identified needs in high quality research grants writing. DISCUSSION AND CONCLUSION: The key achievements for the blood services research capacity building include a mix of short courses, medium-term (epidemiology & biostats) and MS/PhD degree training. Also, having a "train the trainers' programme to develop in-country mentors has been instrumental. Overall, the key recommendations for blood services research capacity building include the need for research collaborations with high-income countries which can jump-start research,and for more in-country grant-writing capacity building, which would help sustainability.

A multicentre study investigating vital sign changes occurring in complicated and uncomplicated transfusions.

BACKGROUND AND OBJECTIVES: Many hospitals require transfusions to be discontinued when vital signs stray from predetermined ranges, regardless of clinical symptoms. Variations in vital signs may be unrelated to transfusion, however, and needlessly stopping a transfusion may delay medical care while increasing donor exposures and healthcare costs. We hypothesized that a detailed study of vital sign changes associated with transfusion of blood product by component, including those associated with potential reactions (complicated) and those deemed to be uncomplicated, would establish a useful framework of reference for treating clinicians and transfusion services alike. MATERIALS AND METHODS: A retrospective electronic record review of transfusion service and transfusion recipient data was completed on 3852 inpatient transfusion episodes over a 6-month period at four academic tertiary care hospitals across the United States. Vital signs pre- and post-transfusion were recorded by trained clinical research nurses. Serious reactions were adjudicated by a panel of transfusion medicine experts. RESULTS: In both uncomplicated transfusions (n = 3765) and those including an adverse reaction (n = 87), vital sign fluctuations were generally modest. Compared to uncomplicated transfusions, transfusions complicated by febrile reactions were associated with higher pretransfusion temperature and higher pretransfusion pulse rates. Episodes of transfusion circulatory overload were associated with higher pretransfusion respiration rates compared to uncomplicated transfusions. CONCLUSION: Most transfusions are associated with only modest changes in vital signs. Pretransfusion vital signs may be an important yet previously understudied predictor of vital sign changes during transfusion. The optimal role of vital sign assessment during blood transfusion deserves further study.

[Role of quality control for improvement of blood components in the Regional Blood Centre of Ouagadougou in Burkina Faso, 2014]. / Apports du contrôle qualité produits finis dans l'amélioration de la qualité des produits sanguins labiles au Centre régional de transfusion sanguine de Ouagadougou (Burkina Faso), 2014.

OBJECTIVES: In Burkina Faso, blood components must comply with national standards. Then, all Transfusion services must implement a quality control process to ensure compliance. Our study aims to establish the main characteristics of blood components of the regional transfusion center of Ouagadougou, and evaluate the capability of this center to improve its manufacturing process. METHODS: We conducted from marsh to December 2014 a pre-post study, assessing blood components' characteristics before and after the implementation of a six months' improvement plan. The assessed parameters were: volume, hematocrit (Ht) and hemoglobin (Hb) levels in RBCs; volume and the number of platelets in PPCs; and volume and concentration of clotting factor VIII in fresh frozen plasma (FFP), respectively. Three hundred and twelve RBCs and 280 PCs were randomly selected for the first series of controls, and 215 RBCs, 54 PCs and 60 FFP were selected for the second series of controls. We compared the mean values of the components parameters and the overall non-compliance rates for each series. RESULTS: The average Hb level of RBCs was respectively 47.8±8.9g and 54.7±7.2g in the first and second series compare to a standard of≥40g. Non-compliance rates of Hb level decreased significantly from 17.6% to 1.4%. For PCs units, the mean number of platelets was 0.14±0.10×1011 and 0.30±0.15×1011 in the first and second period compare to a standard of 0.5×1011. Non-compliance rates for platelets number were high 97.1% and 72.2%. CONCLUSION: The study demonstrates that only RBCs complied with national standards. The study also demonstrates the capability of CRTSO to improve blood components' processing even if for PCs and FFP, NC rates remain high. QC must be maintained and expanded to the others regional blood centers of the country.

Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections.

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r2=0.98-1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml-1 of IL-18 after adjusting for covariates (rs80011693; rs111311302 ß=-0.06, P-value=2.7 × 10-4). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections.

Incidence and clinical characteristics of transfusion-associated circulatory overload using an active surveillance algorithm.

BACKGROUND: The concordance of haemovigilance criteria developed for surveillance of transfusion-associated circulatory overload (TACO) with its clinical diagnosis has not been assessed. In a pilot study to evaluate an electronic screening algorithm, we sought to examine TACO incidence and application of haemovigilance criteria in patients with post-transfusion pulmonary oedema. STUDY DESIGN AND METHODS: From June to September 2014, all transfused adult inpatients at four academic hospitals were screened with an algorithm identifying chest radiographs ordered within 12 h of blood component release. Patients with post-transfusion pulmonary oedema underwent case adjudication by an expert panel. TACO incidence was calculated, and clinical characteristics were compared with other causes of post-transfusion pulmonary oedema. RESULTS: Among 4932 transfused patients, there were 3412 algorithm alerts, 50 cases of TACO and 47 other causes of pulmonary oedema. TACO incidence was 1 case per 100 patients transfused. TACO classification based on two sets of haemovigilance criteria (National Healthcare Safety Network and proposed revised International Society for Blood Transfusion) was concordant with expert panel diagnosis in 57% and 54% of reviewed cases, respectively. Although the majority of clinical parameters did not differentiate expert panel adjudicated TACO from other cases, improved oxygenation within 24 h of transfusion did (P = 0·01). CONCLUSIONS: The incidence of TACO was similar to that observed in prior studies utilizing active surveillance. Case classification by haemovigilance criteria was frequently discordant with clinical diagnoses of TACO in patients with post-transfusion pulmonary oedema. Improvements in oxygenation within 24 h of transfusion merit further evaluation in the diagnosis of TACO.

A cross-sectional study of peripartum blood transfusion in the Eastern Cape, South Africa.

BACKGROUND: Obstetric haemorrhage (OH) remains a major contributor to maternal morbidity and mortality. Blood transfusion is critical in OH management; yet, data on peripartum transfusion are lacking. A pilot study reported high rates of peripartum transfusion in a sample of South African (SA) hospitals, which was independently associated with HIV status. OBJECTIVES: To assess the incidence of peripartum transfusion in a sample of Eastern Cape, SA hospitals to evaluate generalisability of preceding study findings. METHODS: Hospital chart reviews were conducted of all deliveries at three large regional hospitals from February to June 2013. Additional clinical data were collected for patients who sustained OH and/or were transfused. RESULTS: A total of 7 234 women were enrolled in the study; 1 988 (27.5%) were HIV-positive. Of the 767 HIV-positive women with a CD4 count <350 cells/µL, 86.0% were on full antiretroviral therapy and 9.9% received drugs for prevention of mother-to-child transmission. The overall transfusion rate was 3.2%, with significant variability by hospital: Frere Hospital (1.5%), Dora Nginza Hospital (3.8%) and Cecilia Makiwane Hospital (4.6%). The number of red blood cell units per transfused patient and per delivery varied significantly by hospital. Bivariate analysis showed significant association between transfusion and HIV status. In a multivariate analysis, controlling for OH, age, mode of delivery, gestational age, parity and birthweight, this association (odds ratio 1.45; 95% confidence interval 0.78 - 2.71) was no longer significant. CONCLUSION: These findings confirm high rates of peripartum transfusion in SA. While this can be possibly ascribed to variability in practice and patient profile, variation in care and improvement in HIV treatment should be considered.

Infection with human T-lymphotropic virus types-1 and -2 (HTLV-1 and -2): Implications for blood transfusion safety.

Many countries currently perform antibody screening for HTLV-1 infection in blood donors, and this intervention is likely cost-effective in preventing HTLV-1 related diseases in high prevalence countries. However, a number of high-income countries with low prevalence of HTLV-1 infection also perform universal HTLV-1 screening and debate has arisen regarding the cost-effectiveness of these strategies. Filter-based leukoreduction is likely to substantially reduce HTLV-1 transmission by removing infected lymphocytes, but actual laboratory data on its efficacy is currently lacking. Similarly, cost-effectiveness research on HTLV-1 prevention strategies is limited by poor data on prevalence, transmission efficacy and the cost of treating HTLV1 diseases.

Screening for transfusion transmissible infections using rapid diagnostic tests in Africa: a potential hazard to blood safety?

Rapid diagnostic tests (RDTs) are routinely used in African blood centres. We analysed data from two cross-sectional studies representing 95 blood centres in 29 African countries. Standardized panels of sera containing varying concentrations of anti-human immunodeficiency virus (HIV) antibodies (Ab), hepatitis B virus antigen (HBsAg) and antihepatitis C virus (HCV) Ab were screened using routine operational testing procedures at the centres. Sensitivity of detection using RDTs was high for HIV Ab-positive samples, but low for intermediately HBsAg (51·5%) and HCV Ab (40·6%)-positive samples. These findings suggest that current RDT use in Africa could pose a hazard to blood safety.

Motivators and deterrents to blood donation among Black South Africans: a qualitative analysis of focus group data.

BACKGROUND AND OBJECTIVES: South Africa has a markedly skewed representation where the majority of blood (62%) is presently collected from an ethnically White minority. This study seeks to identify culturally specific factors affecting motivation of donors in South Africa. MATERIALS AND METHODS: We performed a qualitative study to evaluate motivators and deterrents to blood donation among Black South Africans. A total of 13 focus groups, comprising a total of 97 Black South Africans, stratified by age and geographic location were conducted. Transcripts of the interviews were analysed using a coding framework by Bednall & Bove. RESULTS: Participants made 463 unique comments about motivators focusing primarily on promotional communications (28%), incentives (20%) and prosocial motivation (16%). Participants made 376 comments about deterrents which focused primarily on fear (41%), negative attitudes (14%) and lack of knowledge (10%). CONCLUSION: Although prosocial motivation (altruism) was the most frequently mentioned individual motivator, promotional communication elicited more overall comments by participants. As reported by many authors, fear and lack of awareness were strong deterrents, but scepticism engendered by perceived racial discrimination in blood collection were unique to the South African environment.

Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.

A pilot external quality assurance study of transfusion screening for HIV, HCV and HBsAG in 12 African countries.

BACKGROUND AND OBJECTIVES: Serologic screening for the major transfusion transmissible viruses (TTV) is critical to blood safety and has been widely implemented. However, actual performance as measured by proficiency testing has not been well studied in sub-Saharan Africa. Therefore, we conducted an external quality assessment of laboratories engaged in transfusion screening in the region. MATERIALS AND METHODS: Blinded test panels, each comprising 25 serum samples that were pedigreed for HIV, HBsAg, HCV and negative status, were sent to participating laboratories. The panels were tested using the laboratories' routine donor screening methods and conditions. Sensitivity and specificity were calculated, and multivariable analysis was used to compare performance against mode of testing, country and infrastructure. RESULTS: A total of 12 African countries and 44 laboratories participated in the study. The mean (range) sensitivities for HIV, HBsAg and HCV were 91·9% (14·3-100), 86·7% (42·9-100) and 90·1% (50-100), respectively. Mean specificities for HIV, HBsAg and HCV were 97·7%, 97% and 99·5%, respectively. After adjusting for country and infrastructure, rapid tests had significantly lower sensitivity than enzyme immunoassays for both HBsAg (P < 0·0001) and HCV (P < 0·05). Sensitivity also varied by country and selected infrastructure variables. CONCLUSION: While specificity was high, sensitivity was more variable and deficient in a substantial number of testing laboratories. These findings underscore the importance of proficiency testing and quality control, particularly in Africa where TTV prevalence is high.

Risk factors for human immunodeficiency virus infection among Brazilian blood donors: a multicentre case-control study using audio computer-assisted structured interviews.

BACKGROUND: Although risk factors for HIV infection are known, it is important for blood centres to understand local epidemiology and disease transmission patterns. Current risk factors for HIV infection in blood donors in Brazil were assessed. METHODS: A case-control study was conducted at large public blood centres located in four major cities between April 2009 and March 2011. Cases were persons whose donations were confirmed positive by enzyme immunoassays followed by Western blot confirmation. Audio computer-assisted structured interviews (ACASI) were completed by all cases and controls. Multivariable logistic regression was used to estimate adjusted odds ratios (AORs) and associated 95% confidence intervals (CIs). RESULTS: There were 341 cases, including 47 with recently acquired infection, and 791 controls. Disclosed risk factors for both females and males were sex with an HIV-positive person AOR 11.3, 95% CI (4.1, 31.7) and being an IVDU or sexual partner of an IVDU [AOR 4.65 (1.8, 11.7)]. For female blood donors, additional risk factors were having male sex partners who also are MSM [AOR 13.5 (3.1, 59.8)] and having unprotected sex with multiple sexual partners [AOR 5.19 (2.1, 12.9)]. The primary risk factor for male blood donors was MSM activity [AOR 21.6 (8.8, 52.9)]. Behaviours associated with recently acquired HIV were being a MSM or sex partner of MSM [13.82, (4.7, 40.3)] and IVDU [11.47, (3.0, 43.2)]. CONCLUSION: Risk factors in blood donors parallel those in the general population in Brazil. Identified risk factors suggest that donor compliance with selection procedures at the participating blood centres is inadequate.

Risk factors for chronic hepatitis B virus infection among blood donors in Bangalore, India.

OBJECTIVES AND AIM: We performed a study of hepatitis B virus (HBV) risk factors among blood donors in Bangalore, India. BACKGROUND: HBV infection is prevalent in India and poses a potential risk of transmission by blood transfusion, but studies of risk factors for hepatitis B surface antigen (HBsAg) carriage among Indian blood donors are lacking. METHODS/MATERIALS: Using a case-cohort design, we enrolled 71 cases with repeatedly reactive HBsAg results and a cohort of 212 contemporaneous blood donors with unknown HBsAg status. Questionnaire data were analysed using multivariable logistic regression. RESULTS: In our multivariate analysis controlling for age, HBsAg positivity was associated with repeat donor status (OR = 0·34, 95% CI 0·17-0·71 vs first-time donor status), residence outside Bangalore and Hosur (rural areas) (OR = 15·66, 95% CI 3·60-68·07vs Bangalore residence), having been a customer at a local barber shop (OR = 4·07, 95% CI 2·06-8·03), close contact with a person who had jaundice (OR = 13·64, 95% CI 3·71-50·24) and cigarette smoking (OR = 3·25, 95% CI 1·39-7·60). CONCLUSION: In addition to recognised demographic risk factors, associations with patronage of local barbers and contact with jaundiced individuals suggest behavioural risk factors that could be adopted as exclusionary criteria for blood donation in India.

Lower numbers of circulating Natural Killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease.

Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. The majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.

Neurologic abnormalities in HTLV-I- and HTLV-II-infected individuals without overt myelopathy.

BACKGROUND: Human T-lymphotropic virus (HTLV) type I is the causative agent of HTLV-associated myelopathy (HAM)/tropical spastic paraparesis, and a number of HAM cases with HTLV-II infection have also been reported. However, despite some reports, it is unclear whether HTLV-I or -II infection is associated with other neurologic manifestations. METHODS: An analysis of medical histories and screening neurologic examinations from a prospective cohort of 153 HTLV-I, 388 HTLV-II, and 810 HTLV-seronegative individuals followed up for means of 11.5, 12.0, and 12.2 years was performed. Participants diagnosed with HAM were excluded. We calculated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, race or ethnicity, income, educational attainment, body mass index, alcohol and cigarette consumption, injection drug use, diabetes, and hepatitis C virus status, using generalized estimating equations for repeated measures. RESULTS: HTLV-I and -II participants were more likely than seronegative participants to have leg weakness (ORs 1.67 [95% CI 1.28-2.18] and 1.44 [1.16-1.78]), impaired tandem gait (ORs 1.25 [95% CI 1.07-1.47] and 1.45 [1.27-1.64]), Babinski sign (ORs 1.54 [95% CI 1.13-2.08] and 1.51 [1.18-1.93]), impaired vibration sense (ORs 1.16 [95% CI 1.01-1.33] and 1.27 [1.14-1.42]), and urinary incontinence (ORs 1.45 [95% CI 1.23-1.72] and 1.70 [1.50-1.93]). For both HTLV-I and -II participants, higher odds of sensory neuropathy by monofilament examination were no longer significant after adjustment for confounding. CONCLUSIONS: These results provide strong evidence that human T-lymphotropic virus (HTLV)-I and -II are associated with a spectrum of predominantly motor abnormalities in patients without overt HTLV-associated myelopathy. Further investigation of the clinical course and etiology of these abnormalities is warranted.

[Teaching transfusion medicine research in the francophone world]. / Une formation à la recherche en médecine transfusionnelle dans le monde francophone.

A two-week, French language, clinical research course in transfusion medicine has recently been created at the Pasteur Institute in Paris under the joint leadership of faculty members from the University of California San Francisco (UCSF), the Blood Systems Research Institute (BSRI) and the National Institute of Transfusion of Paris. The goal is to train transfusion professionals from the developing world to conduct clinical research that will contribute to improving the quality of care and safety in transfusion practices in their respective countries. The course provides training on clinical and epidemiological research methods and their potential applications in transfusion medicine. As part of the course, each student develops a study protocol that can be implemented in his/her blood center of hospital.