Transfusion management of severe anaemia in African children: a consensus algorithm

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40–60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb 37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice

A monovalent chimpanzee adenovirus Ebola vaccine boosted with MVA

BACKGROUND The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. METHODS In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels — 1×1010 viral particles, 2.5×1010 viral particles, and 5×1010 viral particles — with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glyco- protein, in 30 of the 60 participants and evaluated a reduced prime–boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus–based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. RESULTS No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geo- metric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). CONCLUSIONS The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.

Ivermectin treatment of Loa loa hyper-microfilaraemic baboons (Papio anubis): Assessment of microfilarial loads, haematological and biochemical parameters and histopathological changes following treatment.

Individuals with high intensity of Loa loa are at risk of developing serious adverse events (SAEs) post treatment with ivermectin. These SAEs have remained unclear and a programmatic impediment to the advancement of community directed treatment with ivermectin. The pathogenesis of these SAEs following ivermectin has never been investigated experimentally. The Loa/baboon (Papio anubis) model can be used to investigate the pathogenesis of Loa-associated encephalopathy following ivermectin treatment in humans. 12 baboons with microfilarial loads > 8,000mf/mL of blood were randomised into four groups: Group 1 (control group receiving no drug), Group 2 receiving ivermectin (IVM) alone, Group 3 receiving ivermectin plus aspirin (IVM + ASA), and Group 4 receiving ivermectin plus prednisone (IVM + PSE). Blood samples collected before treatment and at Day 5, 7 or 10 post treatment, were analysed for parasitological, hematological and biochemical parameters using standard techniques. Clinical monitoring of animals for side effects took place every 6 hours post treatment until autopsy. At autopsy free fluids and a large number of standard organs were collected, examined and tissues fixed in 10% buffered formalin and processed for standard haematoxylin-eosin staining and specific immunocytochemical staining. Mf counts dropped significantly (p0.05). All animals became withdrawn 48 hours after IVM administration. All treated animals recorded clinical manifestations including rashes, itching, diarrhoea, conjunctival haemorrhages, lymph node enlargement, pinkish ears, swollen face and restlessness; one animal died 5 hours after IVM administration. Macroscopic changes in post-mortem tissues observed comprised haemorrhages in the brain, lungs, heart, which seen in all groups given ivermectin but not in the untreated animals. Microscopically, the major cellular changes seen, which were present in all the ivermectin treated animals included microfilariae in varying degrees of degeneration in small vessels. These were frequently associated with fibrin deposition, endothelial changes including damage to the integrity of the blood vessel and the presence of extravascular erythrocytes (haemorrhages). There was an increased presence of eosinophils and other chronic inflammatory types in certain tissues and organs, often in large numbers and associated with microfilarial destruction. Highly vascularized organs like the brain, heart, lungs and kidneys were observed to have more microfilariae in tissue sections. The number of mf seen in the brain and kidneys of animals administered IVM alone tripled that of control animals. Co-administration of IVM + PSE caused a greater increase in mf in the brain and kidneys while the reverse was noticed with the co-administration of IVM + ASA. The treatment of Loa hyper-microfilaraemic individuals with ivermectin produces a clinical spectrum that parallels that seen in Loa hyper-microfilaraemic humans treated with ivermectin. The utilization of this experimental model can contribute to the improved management of the adverse responses in humans

A Retrospective Study on The Prevalence of Fasciola Infection in Sheep and Goats at Slaughter and Associated Economic Losses from Condemnation of Infected Liver in Maiduguri Abattoir, Nigeria

A retrospective study on the prevalence of fasciolosis among small ruminants (sheep and goats) slaughtered at Maiduguri, metropolitan abattoir and the associated economic losses from condemnation of infected liver were estimated between January 2004 – December2009. Out of the 15, 113 sheep and 9, 617 goats examined during the period, 123(0.49%) and 70(0.28%) were infected with fasciolosis respectively. There was no statistical variation (P>0.05) on theprevalence of infection between the two species of ruminants. However, according to age, out of the 3, 959 young sheep and 4, 417 young goats (12 months) and goats examined, 103(0.68%) and 63(0.66%) were infected respectively. Among the sheep, the adults were found to be moreinfected than the young. Statistically, the difference was significant (p0.05) existed between age groups. According to sex, out of the 7, 097 male sheep and 4, 839 male goats examined, 56(0.37%) and 25(0.26%) were infected with fasciolosis respectively. Similarly, out of the 8, 016 female sheep and 4, 778 female goats examined, 67(0.44%) and 45(0.47%) were infected respectively. Among sheep, both male and female were equally infected (p>0.05). The difference was not significant. According to season, both sheep and goats were more infected during the rainy than the dry season. The difference was statistically significant (

Rapid purification of high activity Taq DNA polymerase expressed in transformed E. coli cells.

A simplified method is described here for the preparation of a thermostable Taq DNA polymerase enzyme from Escherichia coli (E. coli) strain DH5a carrying the pTTQ18 expression vector transformed with the Taq polymerase gene. Standard purifications were done with 1 litre batch cultures of E. coli cells and produced yields in excess of 100 000 units of Taq polymerase. Optimal induction times with isopropyl b-D-thiogalactopyranoside were determined at varying times of 11, 14 and 18 hours and found to be optimal at 11 hours. Induction times greater than 11 hours resulted in complete degradation of enzyme. The resulting enzyme preparation from 11 hour incubation of E. coli cells with IPTG gave a 94 kDa protein band on an 8% SDS-polyacrylamide gel consistent with the size of commercially available Taq polymerase. Transactions of the Zimbabwe Scientific AssociationVolume 72 1998, pp. 23-2

Development of an Isoelectric Focusing Technique for Characterising Isoenzyme Variability in Aphid Taxa

An isoelectric focusing (IEF) method was developed for characterising differences in isooenzyme banding patterns in aphids. In this study, 18 enzyme systems namely adenylate kinase (AK); alkaline phosphatase (ALK-P) and acid phosphatase (ACID-P); -amylase ( -AMY); esterase's (EST); glucose-6-phosphate dehydrogenase (G-6-P-DeH); glutamate oxaloacetate transaminase (GOT); -glycerophosphate dehydrogenase ( -GPD); hexokinase (HK); leucine-alanine peptidase (LeAP); malate dehydrogenase (MTDH); malic enzyme (ME); malic enzyme dehydrogenase (MDH); peptidase P (PEP-P); peroxidase (POD); phosphoglucomutase (PGM); sorbitol dehydrogenase (SOD) and tetrazolium oxidase (TOD) were screened in an attempt to identify isoenzymes that might be useful in distinguishing between various aphid taxa at or above the species level or within the populations of single species. In this study the enzymes found to be most effective in distinguishing three morphologically distinct (but not critically identified) species of aphids collected from tobacco, cabbage and lemon plants were ACID-P, EST and GOT, while the remaining enzymes found to have limited discriminating power. The method developed in this study offers a cheap, sensitive and rapid technique for detecting expresed genmetic differences between single aphic individuals. Transactions of the Zimbabwe Scientific Association Vol.74 2000: 1-