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.

Blood transfusion safety in sub-Saharan Africa: A literature review of changes and challenges in the 21st century.

BACKGROUND: Access to a safe, adequate blood supply has proven challenging in sub-Saharan Africa, where systemic deficiencies spanning policy, collections, testing, and posttransfusion surveillance have long been recognized. Progress in transfusion safety in the early 2000s was in large part due to intervention by the World Health Organization and other foreign governmental bodies, coupled with an influx of external funding. STUDY DESIGN AND METHODS: A review of the literature was conducted to identify articles pertaining to blood safety in sub-Saharan Africa from January 2009 to March 2018. The search was directed toward addressing the major elements of the blood safety chain, in the countries comprising the World Health Organization African region. Of 1380 articles, 531 met inclusion criteria and 136 articles were reviewed. RESULTS: External support has been associated with increased recruitment of voluntary donors and expanded testing for the major transfusion-transmitted infections (TTIs). However, the rates of TTIs among donors remain high. Regional education and training initiatives have been implemented, and a tiered accreditation process has been adopted. However, a general decline in funding for transfusion safety (2009 onwards) has strained the ability to maintain or improve transfusion-related services. Critical areas of need include data collection and dissemination, epidemiological surveillance for TTIs, donor recruitment, quality assurance and oversight (notably laboratory testing), and hemovigilance. CONCLUSION: Diminishing external support has been challenging for regional transfusion services. Critical areas of deficiency in regional blood transfusion safety remain. Nonetheless, substantive gains in education, training, and accreditation suggest durable gains in regional capacity.

Real-time determination of enantiomeric and isomeric content using photoelectron elliptical dichroism.

The fast and accurate analysis of chiral chemical mixtures is crucial for many applications but remains challenging. Here we use elliptically-polarized femtosecond laser pulses at high repetition rates to photoionize chiral molecules. The 3D photoelectron angular distribution produced provides molecular fingerprints, showing a strong forward-backward asymmetry which depends sensitively on the molecular structure and degree of ellipticity. Continuously scanning the laser ellipticity and analyzing the evolution of the rich, multi-dimensional molecular signatures allows us to observe real-time changes in the chemical and chiral content present with unprecedented speed and accuracy. We measure the enantiomeric excess of a compound with an accuracy of 0.4% in 10 min acquisition time, and follow the evolution of a mixture with an accuracy of 5% with a temporal resolution of 3 s. This method is even able to distinguish isomers, which cannot be easily distinguished by mass-spectrometry.

A pilot serosurvey of Babesia microti in Chinese blood donors.

BACKGROUND AND OBJECTIVES: Babesia spp. are tick-borne, intraerythrocytic protozoan parasites, several of which are transfusion-transmissible. Transfusion-transmitted babesiosis poses serious risk to a diverse patient population, including neonates, patients aged >50 years, the asplenic and the immunocompromised that are over-represented among transfusion recipients. Despite reports of B. microti and B. venatorum in People's Republic of China (PRC), no surveillance of blood donors for Babesia has previously been undertaken. We sought to determine the rates of B. microti seroreactivity in a sample of blood donors in the PRC. MATERIALS AND METHODS: A pilot serosurvey was conducted of community blood donors (n = 1000) who donated July-August 2016 at Mudanjiang Blood Center (Heilongjiang Province) using indirect fluorescent antibody testing for antibodies against B. microti. The slides were prepared using B. microti-infected hamster blood. Samples that were initially positive to a titre of 64 were subjected to repeat IFA testing. Final seroreactivity was based on repeat reactivity to ≥64. RESULTS: A total of 1000 individual donor samples were evaluated, comprising 888 whole blood and 112 platelet donations. Thirteen of 1000 (1·3%) donors were seroreactive for B. microti [8 (0·8%) and five (0·05%) at titres of 64 and 128, respectively]. CONCLUSION: Our preliminary findings support the need for expanded Babesia surveillance in Chinese blood donors, replete with molecular evaluation, to evaluate the risk to the blood supply.

Pathogen reduction and blood transfusion safety in Africa: strengths, limitations and challenges of implementation in low-resource settings.

Transfusion-transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion-transmitted infections (TTIs), dependence on high-risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource-constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high-income countries, primarily given the high costs of use. Logistical considerations, particularly in low-resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future.

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.

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.

Functionalization of Zr-based MOFs with alkyl and perfluoroalkyl groups: the effect on the water sorption behavior.

Stability and sorption of Metal-Organic Frameworks (MOFs) towards water are critical in many applications, and can a priori be modulated through the introduction of suitable organic functional groups on their backbone. We report here the preparation of a series of Zr(iv)-based MOFs functionalized with alkyl and perfluoroalkyl groups and their characterization by X-ray powder diffraction, multi-nuclei ((1)H, (13)C, (19)F) solid state nuclear magnetic resonance analyses, and nitrogen sorption measurements at 77 K. Their water sorption behavior was evaluated at 298 K and related to their physico-chemical features, highlighting both the effect of the confinement and the nature of the functional groups on the hydrophilic/hydrophobic balance.

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.

Positive hepatitis B virus core antibody in HIV infection--false positive or evidence of previous infection?

Isolated HBV core antibody (anti-HBc) is defined as the presence of anti-HBc with a negative HBV surface antigen (HBsAg) and HBV surface antibody (anti-HBs <10 IU/l). In patients infected with HIV with isolated anti-HBc, the aim was to determine: The prevalence of isolated positive anti-HBc; The most effective method of identifying which patients have had previous Hepatitis B Virus (HBV) infection; The prevalence of false positive anti-HBc. HBV serology results were identified from 539 patients infected with HIV sampled between January 2010 and December 2012. In those with an isolated anti-HBc and negative anti-HBe, a second anti-HBc test was carried out using a different assay. Samples were also screened for HBV DNA. The anti-retroviral regimens at time of screening were documented. 101/539 had an isolated anti-HBc. Of these, 32 (32%) had a positive anti-HBe (including 1 equivocal) and 69(68%) were anti-HBe negative. Of those negative for anti-HBe, 32 were tested for both DNA and a second anti-HBc. Of these 26 (81%) were on cART at time of HBV testing, with 25 (78%) on ART with anti-HBV activity. The prevalence of isolated anti-HBc was 19%. Only 32% were also anti-HBe positive, whereas 97% of those anti-HBe negative were positive on a second anti-HBc assay suggesting lack of utility of anti-HBe in resolving serological quandaries. One subject (3%) had a false positive anti-HBc. There was no evidence of chronic HBV but 78% patients were on HBV-suppressive combination anti-retroviral therapy.

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.

Microchimerism in the transfused obstetric population.

Microchimerism (MC), the coexistence of allogeneic populations of cells within a host, is well described in pregnancy and blood transfusion. To date, transfusion-associated MC (TA-MC) appears unique to patients transfused after severe traumatic injury. We sought to determine whether transfusion in the peripartum period results in enduring, high-level TA-MC. We conducted a prospective cohort study of 22 women who were newly transfused within 48 h of delivery. Two subjects showed evidence of transient TA-MC; however, MC was not detected at 6 weeks and 6 months. The negative findings suggest that enduring TA-MC does not occur in this population.

Mediastinal radiotherapy after multidrug chemotherapy and prophylactic cranial irradiation in patients with SCLC--treatment results after long-term follow-up and literature overview.

INTRODUCTION: Curative therapy for patients with small-cell lung cancer (SCLC) is based on multidrug chemotherapy combinations and radiotherapy. After a long time follow-up, the aim of the study was to evaluate the efficacy and toxicity of sequential chemo-radiotherapy and the effect of prophylactic cranial irradiation (PCI). METHODS: From 1995-2005, 96 patients with SCLC (64 limited-disease [LD], 32 extensive-disease [ED]; median age 61 years [range 39-79]) were treated at our department with varying chemotherapy regimens and sequential mediastinal radiotherapy (50 Gy + 10 Gy boost in case of residual disease after chemotherapy). Afterwards, 15 patients with LD, good general condition and at least partial response after local treatment received PCI (30 Gy). RESULTS: After a median follow-up of 78.6 months, 20 patients remained alive (20.8%, median survival time 18.2 months). The 2-/5-year overall survival rates were 33.8% and 12.6%, the 2-/5-year loco-regional control rates were 30.3% and 24.5%, respectively. Distant metastases occurred in 43 patients (24 cerebral). Cerebral metastasis occurred in 6.7% and 27.2% of the patients with PCI and without PCI respectively. Only tumor stage showed a statistically significant impact on overall survival and loco-regional control in multivariate analysis. Radiotherapy was well tolerated. Grade 3/4 toxicity occurred in seven patients. Prognosis of patients with SCLC remains poor. Administration of PCI in selected patients bears a decrease in the incidence of cerebral metastases. Alternative chemotherapy schemes as well as irradiation schemes and techniques should be the substance of future randomized trials.

Differential processing and secretion of Abeta peptides and sAPPalpha in human platelets is regulated by thrombin and prostaglandine 2.

Metabolic and functional studies of the amyloid precursor protein (APP) in platelets have advanced our understanding of Alzheimer's disease (AD). Here we report that human platelets contain Abeta peptides, process and secrete them constitutively. Platelets generate formerly unkown Abeta-species by differential processing of APP. Release of Abeta peptides were also increased by platelet activation with thrombin, indicating the existence of a regulated exocytotic pathway. We showed that Abeta-levels, Abeta-processing patterns and Abeta-release kinetics were regulated by thrombin. In controls, release of Abeta peptide species (Abeta 1-40/42 and 1-37/38/39/) continued for more than 4 h, while thrombin activated cells ceased secretion after 1 h at large. Treatment of platelets with prostaglandine 2 slowed this process down. Intracellular Abeta peptide concentrations decreased steadily until no peptides could be detected after 20 h (control) or after 4 h (thrombin) in cultured platelets.

[Neonatal seizures, our experience]. / Convulsiones neonatales, experiencia en la unidad.

AIM: To study retrospectively all newborns admitted between 1992 and 1998 in our Neonatology Unit with convulsions before 30 days of life. PATIENTS AND METHODS: 77 patients, 63.6% male, with an average gestational age of 36.42 weeks, and an average birth weight of 2,653 g. Apgar score at five minutes was below 4 in 4 newborns. RESULTS: In 35 patients the first convulsion occurred in the first 48 hours of life, 7 patients showed status epilepticus. There was a single type of seizure in 49 newborns (65.3%), specially tonic and clonic (multifocal and focal). Head ultrasound was abnormal in 33 newborn, CT scan and/or MRI abnormal in 24, EEG was pathologic in 55. Phenobarbital was the initial treatment in 81.8%, half of them required a therapeutical change. 34 patients (55.7%) still received treatment at hospital discharge. The etiology was hypoxic ischaemic encephalopathy (39%), though less important than in previous studies, intracranial hemorrhage (13%), central nervous system malformations (9%), among other. 16 patients died, 35 showed an abnormal outcome (45.4%): cognitive delay in 24, epilepsy in 19, motor abnormalities in 12. CONCLUSION: The worst outcome was found in malformations, meningitis, intracranial hemorrhages, metabolic diseases and hypoxic ischaemic encephalopathy, while the best in hypoglycemia and in benign idiopathic neonatal seizures.

Convulsiones neonatales, experiencia en la unidad / Neonatal seizures, our experience

Objetivo. Estudio retrospectivo de los pacientes atendidos en nuestra Unidad de Neonatología, en el período 1992-1998, con convulsiones neonatales iniciadas antes de los 30 días. Pacientes y métodos. 77 pacientes (63,6 por ciento sexo masculino), edad gestacional media 36,42 semanas, peso medio de nacimiento 2.653 g. Test de Apgar a los 5 minutos inferior a 4 en cuatro casos. Resultados. En 35 pacientes (47,3 por ciento) la primera crisis se manifestó en las primeras 48 horas de vida, siete pacientes presentaron estado de mal convulsivo. Se describió un único tipo de crisis en 49 neonatos (65,3 por ciento), especialmente tónicas, y clónicas (multifocales y focales). Ecografía craneal transfontanelar anormal en 33 casos, TAC o RM alteradas en 24, EEG patológico en 55. Se inició tratamiento con fenobarbital en el 81,8 por ciento, la mitad requirió una modificación terapéutica; 34 pacientes (55,7 por ciento) prosiguieron tratamiento anticonvulsionante al alta. Diagnóstico de encefalopatía hipoxicoisquémica (39 por ciento), aunque con menor incidencia respecto a series previas, hemorragia intracraneal (13 por ciento), y malformaciones del sistema nervioso central (9 por ciento). 16 pacientes fallecieron, manifestaron secuelas 35 (45,4 por ciento): afectación cognitiva 24, epilepsia 19, afectación motora 12. Conclusión. Se observa peor evolución en malformaciones del sistema nervioso central, meningitis, hemorragias intracraneales, metabolopatías y encefalopatía hipoxicoisquémica, mientras que en hipoglucemias y en las convulsiones neonatales idiopáticas benignas el pronóstico es mejor (AU)

Aim. To study retrospectively all newborns admitted between 1992 and 1998 in our Neonatology Unit with convulsions before 30 days of life. Patients and methods. 77 patients, 63,6% male, with an average gestational age of 36.42 weeks, and an average birth weight of 2,653 g. Apgar score at five minutes was below 4 in 4 newborns. Results. In 35 patients the first convulsion occurred in the firsts 48 hours of life, 7 patients showed status epilepticus. There was a single type of seizure in 49 newborns (65.3%), specially tonic and clonic (multifocal and focal). Head ultrasound was abnormal in 33 newborn, CT scan or MRI abnormal in 24, EEG was pathologic in 55. Phenobarbital was the initial treatment in 81.8%, half of them required a therapeutical change. 34 patients (55.7%) still received treatment at hospital discharge. The etiology was hypoxic ischaemic encephalopathy (39%), though less important than in previous studies, intracranial hemorrhage (13%), central nervous system malformations (9%), among other. 16 patients died, 35 showed an abnormal outcome (45.4%): cognitive delay in 24, epilepsy in 19, motor abnormalities in 12. Conclusion. The worst outcome was found in malformations, meningitis, intracranial hemorrhages, metabolic diseases and hypoxic ischaemic encephalopathy, while the best in hypoglycemia and in benign idiopathic neonatal seizures (AU)

Kinetics of plasma cytokine levels in children hyposensitized with wasp venom.

Specific immunotherapy shifts immune responses towards a Th0/Th1 response. Production of chemokines is also decreased early after the initiation of rush venom immunotherapy. We aimed to investigate in vivo whether cytokine plasma levels reflect the shift towards a Th0-Th1 pattern of immune response as seen in vitro in lymphocytes from patients undergoing venom immunotherapy. Therefore, we studied plasma levels of various cytokines before (day 1), during (day 2), and after (day 4) rush immunotherapy in nine wasp-allergic children. The levels of interleukin-5 and IFN-gamma were below the detection threshold. No variations were observed in levels of interleukin-4, interleukin-10, and TNF-alpha. In contrast, mean levels of RANTES transiently increased at day 2, and decreased below the pretreatment levels at day 4. Those alterations were significant in five children with high levels of RANTES at day 1, and reporting severe anaphylaxis. In the four other children, the levels of RANTES were not significantly increased at day 4. These results suggest that RANTES plasma levels are positively correlated with the severity of the reaction to hymenoptera venom, and that a significant decrease in the levels of RANTES occurs only in children with high pretreatment levels. However, the kinetics of RANTES plasma levels correlated neither with the results of allergological tests, nor with the outcome of venom immunotherapy.