MEASURING CAPACITY AND WILLINGNESS FOR POVERTY REDUCTION IN FRAGILE STATES

Food Security and Poverty,

Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles

Background: There is renewed interest in the development of poxvirus vector-based HIV vaccines due to the protective effect observed with repeated recombinant canarypox priming with gp120 boosting in the recent Thai placebo-controlled trial. This study sought to investigate whether a heterologous prime-boost-boost vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant poxviral vectors expressing HIV virus-like particles bearing envelopes derived from the most prevalent clades circulating in sub-Saharan Africa, focused the antibody response to shared neutralising epitopes. Methods: Three Chinese cynomolgus macaques were immunised via intramuscular injections using a regimen composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag, Env and cholera toxin B subunit followed by the final boost with recombinant modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human complement protein C3d. We measured the macaque serum antibody responses by ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with primary isolates of HIV-1. Results: This study shows that large and complex synthetic DNA sequences can be successfully cloned in a single step into two poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to high titres. The vaccine candidates showed appropriate expression of recombinant proteins with the formation of authentic HIV virus-like particles seen on transmission electron microscopy. In addition the b12 epitope was shown to be held in common by the vaccine candidates using confocal immunofluorescent microscopy. The vaccine candidates were safely administered to Chinese cynomolgus macaques which elicited modest T cell responses at the end of the study but only one out of the three macaques elicited an HIV-specific antibody response. However, the antibodies did not neutralise primary isolates of HIV-1 or the V3-sensitive isolate SF162 using the TZM-bl b-galactosidase assay. Conclusions: MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due to their excellent safety profile for use in humans. This study shows this novel prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques

Protection of pigs against challenge with virulent <i>Streptococcus suis</i> serotype 2 strains by a muramidase-released protein and extracellular factor vaccine

The efficacy of a muramidase-released protein (MRP) and extracellular factor (EF) vaccine in preventing infection and disease in pigs challenged either with a homologous or a heterologous Streptococcus suis serotype 2 strain (MRP EF ) was compared with the efficacy of a vaccine containing formalin-killed bacterin of S suis serotype 2 (MRP EF ). The enhancement of the immune response by different adjuvants (a water-in-oil emulsion [wo] and an aluminium hydroxide-based adjuvant [AH]) and their side effects were also studied. The MRP and EF were purified by affinity chromatography. Pigs were vaccinated twice at three weeks and six weeks of age and challenged intravenously with virulent S suis serotype 2 strains (MRP EF ) at eight weeks of age. At challenge, the pigs vaccinated with MRP EF/WO had high anti-MRP and anti-EF titres and were protected as effectively as pigs vaccinated with wo-formulated vaccines with bacterin. Eight of the nine pigs survived the challenge and almost no clinical signs of disease were observed. The titres obtained with the MRP EF/AH vaccine were low and only two of the five pigs were protected. Pigs vaccinated with either MRP or EF were less well protected; three of the four pigs died after challenge but the clinical signs of disease were significantly less severe than those observed in the placebo-vaccinated pigs. The protective capacity of the bacterin/AH vaccine was very low, and the mortality among these pigs was as high as in the placebo-vaccinated pigs (80 per cent). Postmortem histological examination revealed meningitis, polyserositis and arthritis in the clinically affected pigs. The results demonstrate that a subunit vaccine containing both MRP and EF, formulated with the wo adjuvant, protected pigs against challenge with virulent S suis type 2 strains

Timing impact assessment for COAG Closing the Gap targets: child mortality

This report outlines the main drivers impacting on the Council of Australian Governments target to halve the gap in child mortality within a decade. Summary In 2008, one of the 6 Closing the Gap targets agreed by the Council of Australian Governments (COAG) was to halve the gap in mortality rates for Indigenous children under 5 by 2018. This report looks at current patterns and trends in Indigenous child mortality and associated risk factors. It examines interventions aimed at reducing child mortality; the time frames between program implementation and expected reductions in risk factors; child health outcomes; and data availability to measure outcomes achieved. Indigenous child mortality Mortality rates for Indigenous children aged under 5 have declined over the past decade, largely driven by decreases in infant mortality. In particular, there were significant declines in deaths from sudden infant death syndrome and deaths from certain conditions originating in the perinatal period. These contributed 42% and 25% respectively to the fall in Indigenous infant mortality between 2001 and 2011. Conditions originating in the perinatal period and congenital malformations have continued to dominate infant mortality rates in recent years, while external causes (injury and poisoning) still account for just over one half of all deaths of Indigenous children aged 1-4. Further declines in these three causes of death will likely have the greatest impact on achieving the COAG child mortality target. Risk factors and interventions A number of risk factors are associated with infant and child mortality, including low birthweight and pre-term births, maternal health and behaviours (smoking and alcohol use during pregnancy; STIs; breastfeeding) and access to health services (antenatal care and immunisation). The literature suggests that one way to improve outcomes for Indigenous mothers and babies is through improved access to, and take up of, antenatal care services, as studies have shown an association between inadequate antenatal care and increased risk of stillbirths, perinatal deaths, fetal growth retardation, low birthweight and pre-term births (Taylor et al. 2013). Culturally secure and comprehensive antenatal care services also address a number of risk factors including maternal smoking and alcohol use during pregnancy. Time frames Time frames from program implementation to improved health outcomes vary. For example, the impact of antenatal care, immunisation and health check initiatives can be seen fairly quickly after program implementation (for example, recent data show increases in immunisation rates and health checks for Indigenous children following the first year of funding of relevant COAG health initiatives). However, it may take several years to see the impact of population health initiatives on reductions in risk factors and child health outcomes. There is also a time lag between when improvements occur and when data are available to measure those changes. Given these timing issues, 2014 is the earliest year that data are expected to be available to measure initial changes in Indigenous child mortality resulting from the COAG maternal and child health initiatives, and the full effect of these initiatives may not be evident for a number of years to come

A study of some blood cellular antigenic factors and iso-immunisation in the pig

It has "been shown for the first time that isoimmunisation of sows by foetal red cell antigens can occur. By studies on two sows in a minimal disease pig unit, it was demonstrated that iso-antibodies were produced to the blood group factor, Ea, after giving birth to Ea positive piglets but not after giving birth to Ea negative piglets alone. Complete and reliable life histories of both sows were available and the possibility of previous injections of pig red cells in any form was precluded.Further studies were carried out on two Ea negative, Kb negative sows which were mated to an Sa positive, Kb positive boar. In one of these, anti Ea was boosted after farrowing as in the previous two cases, while in the other the anti-Ea titre rose about six weeks before parturition. In addition anti-Kb was produced in both at the same time as anti-Ea. A subsequent mating of the first of these to an Ea negative, Kb positive boar resulted in the boosting of the anti-Kb titre but not the anti-Ea titre, again after parturition. Likewise on mating the second sow to an Ea negative, Kb negative boar, there was little effect on the anti-Ea and anti-Kb titres either throughout pregnancy or after parturition.Two Ea negative gilts and a further Ea negative sow, all of which had no evidence of red cell iso-antibodies in their sera were mated to an Ea positive boar. Anti-Sa was detected in the sera of two of them for the first time after the subsequent parturition; the third remained negative.On examining the sera from eighty sows and sixty-seven boars in the routine typing service carried out by the Blood Group Research Unit, no antibodies other than anti-A were found in the boars' sera while, in twenty-six per cent of the sows' sera, red cell iso-antibodies were found as well as anti-A. All these sows were bred to boars of the same breed as themselves. Similarly, the sera of fifty per cent of twenty-four sows which had produced litters affected with thrombocytopenic purpura and which were mainly bred to boars of different breeds than themselves, had iso-antibodies presentOf these iso-antibodies, anti-Ea and anti-Eb were the most prevalent and also present at the highest titres. Anti-Ee, anti-Pa, anti-Ka, anti-Kb, anti-Kd, anti-La and anti-Lg were also found but usually at only low titres.The effect of anti-Ea on the red cells of piglets in four litters was studied. Although the antibody was absorbed from the colostrum by all the piglets, it had little effect on their haematological pictures and no differences were noted between Ea positive and Ea negative piglets in the same litter.All these results support further the hypothesis that iso-immunisation of sows by incompatible foetal antigens does occur. In support of this hypothesis a condition of piglets known as thrombocytopenic purpura has been reported in several Scandinavian countries as well as in the United Kingdom. It is considered that iso-immunisation of the sow by thrombocytes of the foetuses takes place in vitro or at parturition resulting in the destruction of thrombocytes in the neonatal piglets after absorption of antibodies from their dam's colostrum. Four litters affected "by this condition were studied in detail and clinical symptoms similar to that described by the other workers were noted.Two gilts, non-affected members of a litter which suffered from the condition, were mated to a boar, an affected survivor of a similar litter. During pregnancy the gilts were injected with pure thrombocyte suspensions from the boar. The piglets produced from these matings had normal thrombocyte counts at birth but a proportion of them developed thrombocytopenia and purpura similar to that seen in natural cases within a few hours of receiving colostrum. However, despite the fact that this condition was observed in three litters from each of these gilts, a secondary thrombocytopenia at ten to fourteen days of age, characteristic of the naturally occurring condition, was only observed in two piglets in one litter.Of all techniques investigated the antiglobulin consumption test was found to be the most satisfactory for the detection of thrombocyte antigen/iso-antibody reactions. Using this, the thrombocytes of affected and non-affected piglets in the litters experimentally affected with thrombocytopenic purpura, were tested against their dam's serum. A correlation was demonstrated between the serological reactions of the piglets' thrombocytes and the clinical signs of purpura and thrombocytopenia

Observations on the role of the Rh factor in human disease, with particular reference to mental deficiency

The study of the Rh Factor in all its ramifications is an extraordinarily fascinating one, and the discovery of its presence in human blood has lead to far -reaching consequences. Many workers on both sides of the Atlantic have done intensive research work on this subject since the discovery of the factor was first published in 1940. The great majority of these workers have been concerned essentially with its influence on physical disease, the mental aspects being either ignored entirely or only lightly touched upon.Recent work in America, however, has suggested that possibly the Rh factor may play an important part in the aetiology of some cases of mental deficiency, at present of unknown aetiology. The number of cases of mental deficiency in our institutions, apart from the large number cared for at home, both in this country and in America, as well as in other countries, lends urgency to any research which will throw light on the cause of this distressing condition; as prophylaxis is even more essential in mental deficiency than in most other forms of disease owing to the fact that there is no possible cure. If a means of preventing even a small proportion of the present number of defectives from being born could be found, the result would be well worth while from an economic and social point of view, apart altogether from the avoidance of the distress caused to parents who have the misfortune to produce a :mentally defective child.The object of the present work is two-fold. In the first place, a review of the literature will be given, showing on the one hand how the Rh factor came to be associated with the condition known as E rythroblastos is Foetalis, and on the other how this condition was associated with Kernicterus and its consequences. An attempt will be made to correlate these two lines of research and to show how the idea developed that the Rh factor may cause certain cases of mental deficiency other than those obviously associated with Kernicterus. In the second place, my own investigations will be described, and my results compared with those already in the literature. Certain case histories will be described and commented on, and finally, attention will be drawn to any inference and conclusions that can be made

Importance de la recherche des Agglutinines Irrégulières (RAI) avant toute transfusion sanguine en Afrique subsaharienne : une mini -revue: Utility of irregular agglutinin test before blood Transfusion in sub-Saharan Africa: a mini-review

Irregular agglutinins are antierythrocyte antibodies directed against certain molecules at the surface of red cells. Testing for irregular agglutinins (IAT) is very meaningful to strictly select for red cells to transfuse. Irregular agglutinins appear in the blood only after a blood transfusion, or in the women, after a pregnancy. Unfortunately, in many sub-Saharan Africa countries, irregular agglutinins are not usually searched before blood transfusion. Yet, this mandatory and fundamental pre-blood transfusion test is essential to prevent immune-induced blood transfusion accidents. Les agglutinines irrégulières sont des anticorps anti-érythrocytaires qui attaquent certaines molécules (les antigènes) présentes à la surface des globules rouges. Elles n’apparaissent dans le sang qu’après une immunisation, soit après, une transfusion sanguine, soit, chez la femme, après une grossesse. La recherche d’agglutinines irrégulières s’avère donc être un examen important pour sélectionner de façon plus stricte les globules rouges à transfuser. Malheureusement, la majorité d’institutions sanitaires dans les pays d’Afrique subsaharienne ne recourent pas à cet examen. Pourtant, cet examen pré-transfusionnel devra être rendu obligatoire et fondamental pour la prévention des accidents immuno- hémolytiques de la transfusion sanguine souvent méconnus dans ces contrées

Proteomic variation and diversity in clinical Streptococcus pneumoniae isolates from invasive and non-invasive sites

Mustapha Bittaye is a PhD student funded by the Medical Research Council Unit, The Gambia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Transmission of toxigenic Corynebacterium diphtheriae by a fully immunised resident returning from a visit to West Africa, United Kingdom, 2017.

In early 2017, a United Kingdom (UK)-born person in their 20s presented with a skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last received a diphtheria-containing vaccine in 2013, completing the recommended course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae. Real-time PCR ascertained the species and presence of the diphtheria toxin gene. An Elek test confirmed toxigenicity. The isolate was macrolide sensitive and penicillin resistant. The local Public Health England (PHE) Health Protection Team obtained the patient's clinical history and traced contacts to inform appropriate public health action. One close contact (in their early 80s with uncertain immunisation status who had not recently travelled) had a positive throat swab for toxigenic C. diphtheriae and reported a history of mild coryzal symptoms. Multilocus sequence typing revealed that strains from the index case and contact had Sequence Type 463. Diphtheria is extremely rare in the UK due to high vaccine coverage and this is the first documented transmission in 30 years. Clinicians and laboratory staff should remain highly suspicious of lesions in overseas travellers, even when patients are fully vaccinated. Older individuals who might not have completed a full immunisation course may have higher diphtheria susceptibility

Transmission of toxigenic Corynebacterium diphtheriae by a fully immunised resident returning from a visit to West Africa, United Kingdom, 2017

In early 2017, a United Kingdom (UK)-born person in their 20s presented with a skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last received a diphtheria-containing vaccine in 2013, completing the recommended course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae. Real-time PCR ascertained the species and presence of the diphtheria toxin gene. An Elek test confirmed toxigenicity. The isolate was macrolide sensitive and penicillin resistant. The local Public Health England (PHE) Health Protection Team obtained the patient’s clinical history and traced contacts to inform appropriate public health action. One close contact (in their early 80s with uncertain immunisation status who had not recently travelled) had a positive throat swab for toxigenic C. diphtheriae and reported a history of mild coryzal symptoms. Multilocus sequence typing revealed that strains from the index case and contact had Sequence Type 493*. Diphtheria is extremely rare in the UK due to high vaccine coverage and this is the first documented transmission in 30 years. Clinicians and laboratory staff should remain highly suspicious of lesions in overseas travellers, even when patients are fully vaccinated. Older individuals who might not have completed a full immunisation course may have higher diphtheria susceptibility