Dendritic cell targeted HIV gag protein vaccine provides help to a DNA vaccine including mobilization of protective CD8+ T cells

To improve the efficacy of T cell-based vaccination, we pursued the principle that CD4+ T cells provide help for functional CD8 + T cell immunity. To do so, we administered HIV gag to mice successively as protein and DNA vaccines. To achieve strong CD4+ T cell immunity, the protein vaccine was targeted selectively to DEC-205, a receptor for antigen presentation on dendritic cells. This targeting helped CD8+ T cell immunity develop to a subsequent DNA vaccine and improved protection to intranasal challenge with recombinant vaccinia gag virus, including more rapid accumulation of CD8+ T cells in the lung. The helper effect of dendritic cell-targeted protein vaccine wasmimicked by immunization with specificMHCII binding HIV gag peptides but not peptides from a disparate Yersinia pestis microbe. CD4+ helper cells upon adoptive transfer allowed wild-type, but not CD40-/-, recipient mice to respond better to the DNA vaccine. The transfer also enabled recipients to more rapidly accumulate gagspecific CD8+ T cells in the lung following challenge with vaccinia gag virus. Thus, complementary prime boost vaccination, in which prime and boost favor distinct types of T cell immunity, improves plasmid DNA immunization, including mobilization of CD8+ T cells to sites of infection

Torture and the UK’s “war on asylum”: medical power and the culture of disbelief

When the now ‘iconic’ images of shackled, humiliated and dehumanised detainees in the Abu Ghraib prison complex in Iraq were broadcast globally, in the mid-2000s, the relationship between medical power and torture in the “war on terror” was also thrust sharply into focus. Graphic images of coalition troops photographing and posing in front of hooded, naked prisoners forced into a “human pyramid”, and of people made to wear animal collars, indicated a regime in which degradation had a defining role. The photograph of a soldier gloating over the corpse of a man who had died as a result of torture was just one picture of a network of interrogation camps in which detention by coalition forces could be fatal. Yet if there were any expectations that the presence of medical personnel may have checked this violence, these were shattered by the fact that clinicians – in some cases at least – were integral to its practice. «It is now beyond doubt that Armed Forces physicians, psychologists, and medics were active and passive partners in the systematic neglect and abuse of war on terror prisoners», wrote Steven Miles in 2009 (Miles 2009, X). And as he continued, this involved providing interrogators «with medical information to use in setting the nature and degree of physical and psychological abuse during interrogations». It involved monitoring «interrogations to devise ways to break prisoners down or to keep them alive». It involved pathologists holding back death certificates and autopsy reports in order to minimise the number of fatalities or cover up torture-related deaths as deaths by natural causes (Ibid). Procedures including «cramped confinement, dietary manipulation, sleep deprivation, and waterboarding» were among the practices that were «at times (…) legally sanctioned due to medical supervision» in the context of the “war on terror”, according to Hoffman (2011, 1535). He continued to suggest that doctors are not just important to «modern torture methods», they are «irreplaceable». In this context, the “war on terror” is no aberration. As the revolutionary psychoanalyst and philosopher Frantz Fanon documented in 1959, for example, certain medical practitioners had an integral role in the military occupation of Algeria, and «There are, for instance, psychiatrists … known to numerous prisoners», he suggested, «who have given electric shock treatments to the accused and have questioned them during the waking phase, which is characterized by a certain confusion, a relaxation of resistance, a disappearance of the person's defences.» (Fanon 1959/1965, 138). Indeed, in his analysis of the Algerian revolution, he discussed how resistance to and struggles over the meanings of medical power were integral to the revolution itself. However, while the role of medical power in the practice of torture has been subjected to sustained critique in the context of the “war on terror”, what follows examines the relationship between medical power and torture in the context of what has been depicted – metaphorically – as another (although to some extents related) “war”: the “war” on asylum. According to the UNHCR (2017, 3), between 5 and 35 per cent of those asylum seekers who have been granted refugee status have survived torture. And focusing on the UK as a case study, this chapter examines the institutional and legal structures prohibiting torture and inhuman and degrading treatment, particularly as they apply to those subject to immigration control in this context. But further, it also examines the ideological and political conditions within which claims by those seeking asylum that they have been subjected to torture prior to arrival can be (and have been) ignored, downplayed and denied. It examines how medical expertise has frequently been undermined in the asylum process when this expertise is utilised to add weight to asylum seekers’ claims to have experienced torture. It examines how there have been attempts to narrow the definition of torture in ways which exclude people from the protections to which torture survivors are entitled. But it also explores the ways in which segments of the medical profession have been complicit in riding roughshod over existing safeguards to prevent further harm to those who have experienced torture, thus potentially compounding its effects. In particular, it examines claims that in certain contexts clinicians have administered dangerous “care” in order to ensure the removal of people from the UK, despite them claiming that they – or their family members – face serious harm and persecution on arrival as a result of this. In a historical discussion of medical involvement in torture, Giovanni Maio (2001, 1609) has noted that from its earliest incarnations one of the features of torture has been its use as an «oppressive instrument used in the preservation of power». Furthermore, whilst methods of torture have certainly «developed», and continue to do so, he argues, this «function» of torture is «especially relevant today». This chapter argues that the (mis)treatment of those in the UK who say they have been tortured, preserves and is bound up with a particular manifestation of state power: the aims, rationale and dictates of immigration control. Its claims are perhaps much more mundane than the forms of direct medical complicity in torture alluded to above. But they are nonetheless important. For it is argued that the acts of omission and commission documented in this chapter expose the tensions between the rights of certain “categories” of migrants to be afforded adequate clinical care on the one hand, and the goals and aims of immigration control itself on the other. This poses profound questions about the functions of clinical care and the ethical duties, responsibilities and obligations of clinicians, it is suggested. But as this chapter also crucially explores, this is a form of power that many within the medical profession have historically challenged, and continue to do so

An Update on the Surveillance of Livestock Diseases and Antimicrobial Use in Sierra Leone in 2021-An Operational Research Study.

In Sierra Leone, in 2020, a study by the Livestock and Veterinary Services Division (Ministry of Agriculture and Forestry) on the surveillance system of animal diseases and antimicrobial use found poor reporting. Of the expected weekly districts reports, <1% were received and only three of the 15 districts had submitted reports occasionally between 2016 and 2019. Following this, staff-capacity-building on reporting was undertaken. In 2021, we reassessed the improvement in reporting and used the reports to describe livestock diseases and antimicrobials utilized in their treatment. Between March and October 2021, 88% of expected weekly reports from all 15 districts were received. There were minor deficiencies in completeness and consistency in the terminology used for reporting animal disease and antimicrobials. Available reports showed that 25% of the livestock had an infectious disease, and a quarter of the sick animals had received an antimicrobial drug. Most animals received antimicrobials belonging to World Organization for Animal Health's "veterinary critically important" category (77%) and World Health Organization's "critically" (17%) and "highly important" (60%) categories for human health. These indicate a significant improvement in the animal health surveillance system and highlight the need for enhanced antimicrobial stewardship to prevent misuse of antimicrobials that are significant in animal and human health

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

Improvement in the Surveillance System for Livestock Diseases and Antimicrobial Use Following Operational Research Studies in Sierra Leone January–March 2023

In Sierra Leone, two operational research (OR) studies in 2019 and 2021 showed deficiencies in the data being captured by the Integrated Animal Disease Surveillance and Reporting (IADSR) system. This third OR study was conducted in 2023 to assess whether the second OR study’s results and recommendations were disseminated with the key stakeholders, the uptake of the recommendations, improvements in data capture in the IADSR system, and to describe the data on livestock disease and antimicrobial use. In 2022, on seven occasions, the authors of the second OR study disseminated the study’s findings. Of the four recommendations, the one on improving laboratory infrastructure for confirmation of animal disease was not implemented. The district animal health weekly surveillance reports received through the IADSR system were sustained at 88% between the second (2021) and third (2023) studies. In both studies, the proportion of sick animals receiving antibiotics (25%) remained the same, but the use of “critically important antimicrobials for veterinary use” declined from 77% (in 2021) to 69% (in 2023). The IADSR system has improved considerably in providing information on animal health and antibiotic use, and sequential OR studies have played a key role in its improvement