Anaemia and blood transfusion in African children presenting to hospital with severe febrile illness

BACKGROUND: Severe anaemia in children is a leading cause of hospital admission and a major cause of mortality in sub-Saharan Africa, yet there are limited published data on blood transfusion in this vulnerable group. METHODS: We present data from a large controlled trial of fluid resuscitation (Fluid Expansion As Supportive Therapy (FEAST) trial) on the prevalence, clinical features, and transfusion management of anaemia in children presenting to hospitals in three East African countries with serious febrile illness (predominantly malaria and/or sepsis) and impaired peripheral perfusion. RESULTS: Of 3,170 children in the FEAST trial, 3,082 (97%) had baseline haemoglobin (Hb) measurement, 2,346/3,082 (76%) were anaemic (Hb <10 g/dL), and 33% severely anaemic (Hb <5 g/dL). Prevalence of severe anaemia varied from 12% in Kenya to 41% in eastern Uganda. 1,387/3,082 (45%) children were transfused (81% within 8 hours). Adherence to WHO transfusion guidelines was poor. Among severely anaemic children who were not transfused, 52% (54/103) died within 8 hours, and 90% of these deaths occurred within 2.5 hours of randomisation. By 24 hours, 128/1,002 (13%) severely anaemic children had died, compared to 36/501 (7%) and 71/843 (8%) of those with moderate and mild anaemia, respectively. Among children without severe hypotension who were randomised to receive fluid boluses of 0.9% saline or albumin, mortality was increased (10.6% and 10.5%, respectively) compared to controls (7.2%), regardless of admission Hb level. Repeat transfusion varied from ≤2% in Kenya/Tanzania to 6 to 13% at the four Ugandan centres. Adverse reactions to blood were rare (0.4%). CONCLUSIONS: Severe anaemia complicates one third of childhood admissions with serious febrile illness to hospitals in East Africa, and is associated with increased mortality. A high proportion of deaths occurred within 2.5 hours of admission, emphasizing the need for rapid recognition and prompt blood transfusion. Adherence to current WHO transfusion guidelines was poor. The high rates of re-transfusion suggest that 20 mL/kg whole blood or 10 mL/kg packed cells may undertreat a significant proportion of anaemic children. Future evaluation of the impact of a larger volume of transfused blood and optimum transfusion management of children with Hb of <6 g/dL is warranted. Please see related article: http://dx.doi.org/10.1186/s12916-014-0248-5. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-014-0246-7) contains supplementary material, which is available to authorized users

WHO guidelines on fluid resuscitation in children: missing the FEAST data.

The World Health Organization recommendations on management of common childhood illnesses affect the lives of millions of children admitted to hospital worldwide. Its latest guidelines,1 released in May 2013, continue to recommend rapid fluid resuscitation for septic shock, even though the only large controlled trial of this treatment (Fluid Expansion as a Supportive Treatment (FEAST) found that it increased the risk of death in African children.2 A subsequent systematic review of bolus resuscitation in children with shock resulting from severe infection also did not support its use.3 Failure to take this evidence into account is not consistent with WHO’s commitment to systematically and transparently assess evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) process when producing guidelines and could endanger the lives of children

Sustained reduction in vaccine-type invasive pneumococcal disease despite waning effects of a catch-up campaign in Kilifi, Kenya: A mathematical model based on pre-vaccination data.

BACKGROUND: In 2011, Kenya introduced the 10-valent pneumococcal conjugate vaccine together with a catch-up campaign for children aged <5years in Kilifi County. In a post-vaccination surveillance study based in Kilifi, there was a substantial decline in invasive pneumococcal disease (IPD). However, given the continued circulation of the vaccine serotypes it is possible that vaccine-serotype disease may re-emerge once the effects of the catch-up campaign wear off. METHODS: We developed a compartmental, age-structured dynamic model of pneumococcal carriage and invasive disease for three serotype groups: the 10-valent vaccine serotypes and two groups of non-vaccine serotypes based on their susceptibility to mutual competition. The model was calibrated to age- and serotype-specific data on carriage and IPD in the pre-vaccination era and used to predict carriage prevalence and IPD up to ten years post-vaccination in Kilifi. The model was validated against the observed carriage prevalence after vaccine introduction. RESULTS: The model predicts a sustained reduction in vaccine-type pneumococcal carriage prevalence from 33% to 8% in infants and from 30% to 8% in 1-5year olds over the 10-year period following vaccine introduction. The incidence of IPD is predicted to decline across all age groups resulting in an overall reduction of 56% in the population, corresponding to 10.4 cases per 100,000 per year. The vaccine-type IPD incidence is estimated to decline by 83% while non-vaccine-type IPD incidence is predicted to increase by 52%. The model's predictions of carriage prevalence agrees well with the observed data in the first five years post-vaccination. CONCLUSION: We predict a sustained and substantial decline in IPD through PCV vaccination and that the current regimen is insufficient to fully eliminate vaccine-serotype circulation in the model. We show that the observed impact is likely to be sustained despite waning effects of the catch-up campaign

A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice

While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy

Allelic variations in aroma gene in cultivated rice varieties

Germplasm is a valuable source of genetic diversity that supports crop improvement efforts in any breeding programme but it must first be fully characterised for economically valuable traits before it can be effectively utilised. In rice ( Oryza sativa ), the development of new varieties with improved aroma requires correct phenotyping and prior knowledge of the available genes and alleles governing the aroma trait in the gene pool. Correct phenotyping and genotyping can be achieved using sensory methods and functional markers associated with polymorphisms that define the aroma genes. The objective of this study was to evaluate the aroma status of rice accessions and to assess for the various alleles of badh2 gene using functional markers. A total of 56 rice accessions were evaluated at National Crops Resources Research Institute (NaCRRI) in Uganda for their aroma using sensory methods and a molecular marker to differentiate between aromatic and non- aromatic accessions. The aromatic accessions were then evaluated for variations within the betaine aldehyde dehydrogenase2 (badh2) gene responsible for aroma in rice using functional markers. Sensory evaluation of aroma identified 23 accessions to be aromatic; while 33 were non-aromatic. Molecular results identified 20 accessions as aromatic; while 36 accessions were non-aromatic. Functional marker analysis indicated the presence of badh2-E7 allele in 20 aromatic accessions within this collection that could be employed in the breeding programme for the rice aromatic trait.Le germoplasme est une source pr\ue9cieuse de diversit\ue9 g\ue9n\ue9tique qui soutient les efforts d\u2019am\ue9lioration des cultures dans tout programme de s\ue9lection, mais il doit d\u2019abord \ueatre enti\ue8rement caract\ue9ris\ue9 pour ses traits \ue9conomiquement pr\ue9cieux avant de pouvoir \ueatre utilis\ue9 efficacement. Dans le riz ( Oryza sativa ), le d\ue9veloppement de nouvelles vari\ue9t\ue9s avec un ar\uf4me am\ue9lior\ue9 n\ue9cessite un ph\ue9notypage correct et une connaissance pr\ue9alable des g\ue8nes et all\ue8les disponibles r\ue9gissant le caract\ue8re aromatique dans le pool g\ue9n\ue9tique. Un ph\ue9notypage et un g\ue9notypage corrects peuvent \ueatre obtenus en utilisant des m\ue9thodes sensorielles et des marqueurs fonctionnels associ\ue9s \ue0 des polymorphismes qui d\ue9finissent les g\ue8nes aromatiques. L\u2019objectif de cette \ue9tude \ue9tait d\u2019\ue9valuer le statut aromatique des accessions de riz et d\u2019\ue9valuer les diff\ue9rents all\ue8les du g\ue8ne badh2 \ue0 l\u2019aide de marqueurs fonctionnels. Un total de 56 accessions de riz ont \ue9t\ue9 \ue9valu\ue9es au National Crops Resources Research Institute (NaCRRI) en Ouganda pour leur ar\uf4me en utilisant des m\ue9thodes sensorielles et un marqueur mol\ue9culaire pour diff\ue9rencier les accessions aromatiques et non aromatiques. Les accessions aromatiques ont ensuite \ue9t\ue9 \ue9valu\ue9es pour les variations au sein du g\ue8ne de la b\ue9ta\uefne ald\ue9hyde d\ue9shydrog\ue9nase2 (badh2) responsable de l\u2019ar\uf4me du riz \ue0 l\u2019aide de marqueurs fonctionnels. L\u2019\ue9valuation sensorielle de l\u2019ar\uf4me a identifi\ue9 23 accessions comme aromatiques; tandis que 33 \ue9taient non aromatiques. Les r\ue9sultats mol\ue9culaires ont identifi\ue9 20 accessions comme aromatiques; tandis que 36 accessions n\u2019\ue9taient pas aromatiques. L\u2019analyse des marqueurs fonctionnels a indiqu\ue9 la pr\ue9sence d\u2019all\ue8les badh2-E7 dans 20 accessions aromatiques de cette collection qui pourraient \ueatre utilis\ue9es dans le programme de s\ue9lection pour le trait aromatique du riz

Population immunity to pneumococcal serotypes in Kilifi, Kenya, before and 6 years after the introduction of PCV10 with a catch-up campaign: an observational study of cross-sectional serosurveys

BACKGROUND: In Kilifi (Kenya), a pneumococcal conjugate vaccine (PCV10) was introduced in 2011 in infants (aged <1 year, 3 + 0 schedule) with a catch-up campaign in children aged 1-4 years. We aimed to measure the effect of PCV10 on population immunity. METHODS: In this observational study, repeated cross-sectional serosurveys were conducted in independent random samples of 500 children younger than 15 years every 2 years between 2009 and 2017. During these surveys, blood samples were collected by venesection. Concentrations of anti-capsular IgGs against vaccine serotypes (VTs) 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F, and against serotypes 6A and 19A, were assayed by ELISA. We plotted the geometric mean concentrations (GMCs) by birth year to visualise age-specific antibody profiles. In infants, IgG concentrations of 0·35 μg/mL or higher were considered protective. FINDINGS: Of 3673 volunteers approached, 2152 submitted samples for analysis across the five surveys. Vaccine introduction resulted in an increase in the proportion of young children with protective IgG concentrations, compared with before vaccine introduction (from 0-33% of infants with VT-specific levels over the correlate of protection in 2009, to 60-94% of infants in 2011). However, among those vaccinated in infancy, GMCs of all ten VTs had waned rapidly by the age of 1, but rose again later in childhood. GMCs among children aged 10-14 years were consistently high over time (eg, the range of GMCs across survey rounds were between 0·45 μg/mL and 1·00 μg/mL for VT 23F and between 2·00 μg/mL and 3·11 μg/mL for VT 19F). INTERPRETATION: PCV10 in a 3 + 0 schedule elicited protective IgG levels during infancy, when disease risk is high. The high antibody levels in children aged 10-14 years might indicate continued exposure to vaccine serotypes due to residual carriage or to memory responses to cross-reactive antigens. Despite rapid waning of IgG after vaccination, disease incidence among young children in this setting remains low, suggesting that lower thresholds of antibody, or other markers of immunity (eg, memory B cells), may be needed to assess population protection among children who have aged past infancy. FUNDING: Gavi, the Vaccine Alliance; Wellcome Trust