"NGOs, they cannot kill people": Cholera Vaccination in the Context of Humanitarian Crises in South Sudan

Cholera is endemic and remains a significant public health problem in places like South Sudan where decades of war have devastated basic infrastructures and left people vulnerable to diseases mostly forgotten in other places. In 2010, the World Health Organization (WHO) recommended that oral cholera vaccination (OCV) be used in conjunction with other cholera prevention and control measures and an OCV stockpile was created to improve access to the vaccines in situations of outbreaks, humanitarian emergencies and other high risk settings. Four years later, following the eruption of a violent political crisis that has left more than 50,000 people dead and another 2.5million displaced, OCV campaigns were conducted in PoCs (Protection of Civilian areas) across South Sudan with vaccines provided from the stockpile. This was the first use of the OCV stockpile in a humanitarian crisis. The potential social and health systems effects of the vaccine have so far been unexplored. This thesis uses qualitative methods to examine the socio-cultural and political dimensions of cholera and OCV campaigns among internally displaced Nuer people living in PoC areas in Juba, South Sudan, and their relation to perceptions of health, cholera risk and vaccination decisions. Interviews were conducted with humanitarian health professionals involved in the cholera response as well as with Nuer residents in the two PoCs where the OCV campaigns were conducted. Their narratives were interpreted with attention to the political and humanitarian crises in South Sudan as well as the humanitarian response by domestic and international actors. This thesis argues that the violent conflict, which led to the displacement of Nuers in Juba into UN-protected areas also led to changes in their conceptualization of risk and health. Both became intertwined in a socio-political narrative, framing the Dinka dominated SPLM government as a source of disease and UN/NGOs as a source of health. Cholera risk and vaccination decisions were described in non-political and political terms. Vaccination decisions were one of few means Nuers had of exercising political autonomy and control. Similarly, for humanitarian health professionals, the provision of OCVs was an essential aspect of building credibility and trust among Nuers in the PoCs. In this context, trust in institutions emerged as the most significant influence in vaccine decision making. The significance of trust, which is not encompassed in a typical “exposure-outcome” framework of epidemiology, also explains why vaccine recipients neither perceived their risk of cholera as diminishing nor perceived a reduced need for preventative practices, such as hand-washing, five months after vaccination. The thesis concludes that vaccination in a humanitarian crisis context warrants re-conceptualization not simply in an equation weighing epidemiological risk and disease perception on the part of the target population, nor a simple decision of doing what is best from the perspective of humanitarian actors, but as part of a complex process also considering the political and social dynamics surrounding health interventions and their influence on public willingness to accept them

Mycorrhizal Association and its Benefits to Allanblackia parviflora Tree Seedlings in the Nursery

Allanblackia species are high value multipurpose indigenous fruit trees whose seeds contain edible oil that has become a foreign exchange earner for rural-based enterprises. Wild harvesting could not sustain the supply to industry and therefore domestication was focused on developing propagation techniques, selecting and collecting elite planting materials. Little emphasis was placed on the soil nutrient requirements where preliminary results showed seedlings grown in rhizosphere soil of wild trees had good growth performance. A study was undertaken to examine microbial-Allanblackia parviflora plant interactions and determine their benefits to nursery seedlings. Roots of wildlings and rhizosphere soil from A. parviflora trees were collected from three forest reserves and the roots assessed for mycorrhizal colonization. Allanblackia parviflora seedlings were raised in different potting media with different ratios and their height and diameter determined. Soil treatments were also analyzed for nutrient and chemical contents. Vesicles, arbuscular structures, hyphal coils and intercellular hyphae were found on root tips of wildlings collected from rhizosphere soil of Allanblackia (AB) trees and seedlings grown in soil treatments containing AB soil. Root colonization of A. parviflora was largely in the form of extensive cell-to-cell growth of hyphal coils characteristic of Paris-type morphology. Addition of Agricultural field soil (Ferric Acrisol, Afs) or Humus (H)+Afs to AB improved height of seedlings. Seedlings grown in AB soil alone increased best in height with age followed by those grown in combination of 75% AB soil and 25% Afs. Available P was highest in Afs (220.84 mgP/kg) and low in AB soil (6.54 mgP/kg) while combination of H + Afs to AB increased K level to 341.34 mgK/kg. The improvement in growth must be due to both vesicular-arbuscular mycorrhizal fungi and soil chemical content of AB soil

The mental health outcomes of food insecurity and insufficiency in west Africa: A systematic narrative review

(1) Background: Food insufficiency is a global pandemic affecting many people, especially those residing in developing countries. African countries have been affected by food insufficiency, which is mostly caused by drought or wars. Famine or food insufficiency has been reported to have an impact on the psychological health and quality of life of people affected. This review assessed the mental health outcomes of famine and food insufficiency in West Africa. (2) Methods: A search of the published literature was conducted using PubMed, PsycExtra, Medline, and PsycINFO databases. The search was limited to papers published in English between the years 2010 and 2020. Two reviewers independently screened the titles and abstracts of the retrieved papers using pre-defined inclusion and exclusion criteria and a third reviewer resolved conflicts. Data were extracted and appraised using a data extraction form and an appraisal checklist. (3) Results: A total of 81 papers were identified through the journal databases search. Out of the seven papers that met the inclusion criteria, six papers used cross-sectional designs and one paper used an experimental design. The six papers used quantitative approach for data collection, while the one paper used a qualitative technique. The evidence synthesized from this review indicated that exposure to food insecurity or insufficiency is associated with increased psychological distress including anxiety, sleeplessness, intellectual disability, general mental, and emotional instability. (4) Conclusions: This review strongly highlights the need for further research across the sub-region. It further suggests that famine and food insufficiency are associated with significant mental health problems in adults and impacts the cognitive and intellectual development of children. Although there is paucity of literature about famine and its impact on mental health in West Africa, these findings are important for developing social policy initiatives for increasing food supply and mental health interventions for all ages

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

Histone deacetylases suppress cgg repeat-induced neurodegeneration via transcriptional silencing in models of Fragile X Tremor Ataxia Syndrome

Fragile X Tremor Ataxia Syndrome (FXTAS) is a common inherited neurodegenerative disorder caused by expansion of a CGG trinucleotide repeat in the 59UTR of the fragile X syndrome (FXS) gene, FMR1. The expanded CGG repeat is thought to induce toxicity as RNA, and in FXTAS patients mRNA levels for FMR1 are markedly increased. Despite the critical role of FMR1 mRNA in disease pathogenesis, the basis for the increase in FMR1 mRNA expression is unknown. Here we show that overexpressing any of three histone deacetylases (HDACs 3, 6, or 11) suppresses CGG repeat-induced neurodegeneration in a Drosophila model of FXTAS. This suppression results from selective transcriptional repression of the CGG repeat-containing transgene. These findings led us to evaluate the acetylation state of histones at the human FMR1 locus. In patient-derived lymphoblasts and fibroblasts, we determined by chromatin immunoprecipitation that there is increased acetylation of histones at the FMR1 locus in pre-mutation carriers compared to control or FXS derived cell lines. These epigenetic changes correlate with elevated FMR1 mRNA expression in pre-mutation cell lines. Consistent with this finding, histone acetyltransferase (HAT) inhibitors repress FMR1 mRNA expression to control levels in pre-mutation carrier cell lines and extend lifespan in CGG repeat-expressing Drosophila. These findings support a disease model whereby the CGG repeat expansion in FXTAS promotes chromatin remodeling in cis, which in turn increases expression of the toxic FMR1 mRNA. Moreover, these results provide proof of principle that HAT inhibitors or HDAC activators might be used to selectively repress transcription at the FMR1 locus.open293

Perceptions of oral cholera vaccine and reasons for full, partial and non-acceptance during a humanitarian crisis in South Sudan.

: Oral cholera vaccination (OCV) campaigns were conducted from February to April 2014 among internally displaced persons (IDPs) in the midst of a humanitarian crisis in Juba, South Sudan. IDPs were predominantly members of the Nuer ethnic group who had taken refuge in United Nations bases following the eruption of violence in December 2013. The OCV campaigns, which were conducted by United Nations and non-governmental organizations (NGOs) at the request of the Ministry of Health, reached an estimated 85-96% of the target population. As no previous studies on OCV acceptance have been conducted in the context of an on-going humanitarian crisis, semi-structured interviews were completed with 49 IDPs in the months after the campaigns to better understand perceptions of cholera and reasons for full, partial or non-acceptance of the OCV. Heightened fears of disease and political danger contributed to camp residents' perception of cholera as a serious illness and increased trust in United Nations and NGOs providing the vaccine to IDPs. Reasons for partial and non-acceptance of the vaccination included lack of time and fear of side effects, similar to reasons found in OCV campaigns in non-crisis settings. In addition, distrust in national institutions in a context of fears of ethnic persecution was an important reason for hesitancy and refusal. Other reasons included fear of taking the vaccine alongside other medication or with alcohol. The findings highlight the importance of considering the target populations' perceptions of institutions in the delivery of OCV interventions in humanitarian contexts. They also suggest a need for better communication about the vaccine, its side effects and interactions with other substances.<br/

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning